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"comment to Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced gastrointestinal dysfunction in Parkinson's disease mice
We are delighted to have read the article titled "Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydr- opyridine-induced gastrointestinal dysfunction in Parkinson's disease mice" authored by Xin-Yu Wang’s team in the World Journal of Gastroenterology.
Parkinson’s disease (PD) is a multicentric neurodegenerative disorder characterized by the accumulation and aggregation of alfa-synuclein (α-syn) in the substantia nigra in the central nervous system (CNS) and in other neural structures(1). It is the second most common and the most rapidly rising neurodegenerative disease in the world(2). While the exact causes behind the increasing incidence and prevalence of PD remain unclear, contributing factors may include longer life expectancy, declining smoking rates, and exposure to environmental pollutants and toxins(3). Among the earliest manifestations of PD are gastrointestinal (GI) symptoms, which often precede the onset of motor impairments. GI dysfunction in PD is closely linked to the gut-brain axis, reflecting the bidirectional communication between the CNS and the GI tract in both health and disease (4). However, there are still limitations in the research on the relationship between PD and GI dysfunction, and the specific molecular mechanism has not been fully elucidated.
In this study, the findings of Xin-Yu Wang’s team provide valuable insights and innovative approaches for PD treatment. This paper represents the first systematic demonstration that rhapontin alleviates gut-brain axis dysfunction in PD by activating colonic NRF2, thereby offering a novel therapeutic target for the disease. By integrating network pharmacology predictions with experimental validation, this study enhances its scientific robustness and credibility. Furthermore, a key discovery of this study is that the anti-inflammatory effects of rhapontin are predominantly localized to the intestinal tract rather than being mediated through the brain-derived NRF2 pathway. This provides experimental evidence supporting the "enteric pathology hypothesis" of PD (5). Overall, these findings present critical theoretical support for rhapontin as a promising therapeutic agent for GI dysfunction in PD.
However, we have several exploratory comments regarding certain aspects of the study.
First, extensive research has established the critical role of the gut-brain axis in mediating GI dysfunction associated with PD through interconnected pathophysiological mechanisms. For example, gut microbiota dysbiosis can compromise intestinal barrier integrity, leading to a "leaky gut" phenomenon. This allows lipopolysaccharides (LPS) to trigger immune cell activation and the release of pro-inflammatory cytokines, which contribute to systemic inflammation and increased blood-brain barrier (BBB) permeability. Consequently, peripheral inflammatory signals can spread to the CNS, and after that, pathological α-syn will aggregate in the dorsal motor nucleus of the vagus nerve (DMV) and the substantia nigra. The levels of pathological α-syn also increase mitochondrial fragmentation in the DMV, ultimately leading to PD pathophysiology (6). Pathogenic α-syn may spread from the gut to the brain, leading to the degeneration of the nigrostriatal dopaminergic system, thus increasing the risk of developing PD (7, 8). Supporting this, animal studies have shown that fecal microbiota transplantation from PD patients induces α-syn aggregation and dopaminergic neuron loss (9). Additionally, gut microbiota also can regulate neurotransmitter homeostasis by modulating dopamine (DA) and serotonin production, while short-chain fatty acids (SCFAs) help mitigate intestinal inflammation, reduce oxidative stress, and enhance BBB integrity to protect DA neurons(6, 10-12). One of the characteristics of PD is the progressive loss of DA neurons in the substantia nigra pars compacta (13). Lastly, dysbiotic gut microbiome (dysbiome) can impair mitochondrial energy metabolism, trigger the TLR4/NF-κB pathway, and exacerbate oxidative stress, ultimately leading to the degeneration of nigral dopaminergic neurons (6). Collectively, these mechanisms form a core network through which the gut-brain axis contributes to PD pathogenesis. In this study, only studied the effect between rhapontin and the gastrointestinal dysfunction caused by PD, without systematically combining the gut-brain axis with PD for research. Additionally, although gut microbiota play a pivotal role in the gut-brain axis of PD, the study does not evaluate the influence of rhapontin on microbiota composition or function (14-16). It remains unclear whether rhapontin indirectly activates NRF2 or reduces inflammation by modulating specific microbial populations. Future studies could explore this by employing approaches such as 16S rRNA sequencing or metagenomics to assess changes in fecal microbiota composition, alongside quantifying microbiota-derived metabolites. Such investigations would provide deeper insights into the gut-brain axis dynamics and further elucidate rhapontin’s mechanisms of action.
Secondly, rhapontin is a stilbenoid glucoside compound, found in medicinal plant of rhubarb rhizomes. Research into the anti-inflammatory mechanisms of rhapontin has revealed its multi-pathway synergistic effects. For example, in LPS-induced endothelial cell inflammation models, rhapontin effectively suppresses nitric oxide (NO) and TNF-α production while downregulating the expression of Inducible Nitric Oxide Synthase (iNOS), Cyclooxygenase-2 (COX-2), and NADPH Oxidase - related genes (NOX-related genes). These effects are primarily achieved by inhibiting the activation of key proteins in the Nuclear Factor-kappa B (NF-κB) and Mitogen - Activated Protein Kinase (MAPK) signaling pathways(17). In terms of antioxidant regulation, rhapontin activates the NRF2 signaling pathway, which reduces Tumor Necrosis Factor-alpha (TNF-α) and Matrix Metalloproteinase-2 (MMP-2) levels in diabetic retinopathy models, while enhancing the expression of Interleukin – 10 (IL-10) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) and inhibiting NF-κB nuclear translocation(18). Its anti-fibrotic properties are mediated through dual mechanisms: activating Adenosine Monophosphate - Activated Protein Kinase (AMPK) and inhibiting the Transforming Growth Factor – beta (TGF-β)/Smad pathway, which helps reverse abnormal extracellular matrix deposition and prevents the progression of pulmonary fibrosis(19). Additionally, rhapontin has been shown to improve colonic epithelial barrier function via Sirtuin 1 (SIRT1) signaling activation(20). Together, these findings systematically highlight rhapontin's integrative therapeutic effects through coordinated modulation of NF-κB/MAPK, AMPK/TGF-β/Smad, and SIRT1 signaling networks, addressing inflammation, oxidative stress, and fibrosis.
The current study demonstrated that rhapontin effectively reduces inflammation by decreasing the levels of pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, while also activating the NRF2 signaling pathway to improve gastrointestinal function. However, the study did not explore rhapontin's potential role in preventing the progression of pulmonary fibrosis through AMPK activation and inhibition of the TGF-β/Smad pathway, nor did it investigate its effects on improving colonic epithelial barrier function via activation of the SIRT1 signaling pathway. Additionally, while network pharmacology was used to predict shared targets between PD and rhapontin, and the top 10 key targets were identified using a protein-protein interaction (PPI) network, the relationship between these targets and NRF2 remains poorly defined. Moreover, the study lacks detailed mechanistic insights into the specific signaling pathways associated with NRF2, including its upstream and downstream regulatory mechanisms—an area that requires further investigation. The article also does not clearly explain how NRF2 was identified as a key target. o address these research gaps, future studies could employ techniques such as Western blotting (WB) and co-immunoprecipitation (Co-IP) to validate the protein-protein interactions between rhapontin's potential targets and NRF2. Additionally, methods such as quantitative real-time polymerase chain reaction (qPCR) or RNA sequencing could be used to analyze downstream gene expression regulated by NRF2. These approaches would provide a more comprehensive understanding of the molecular mechanisms underlying rhapontin's anti-inflammatory effects, offering deeper insights into its therapeutic potential for PD.
In evaluating the experimental section of this study, some points warrant further discussion. First, regarding the presentation of the results: Figure 2A does not clearly label which specific experimental group each result corresponds to, making interpretation challenging. Additionally, the WB image in Figure 5A lacks clarity and does not exhibit an obvious trend in the results, which may hinder the ability to draw definitive conclusions. Second, concerning the experimental methods: the study utilized only two approaches—the open field test and the pole-climbing test—to assess the motor abilities of mice. While these methods provide useful insight, they may be insufficient for a comprehensive evaluation of motor behavior in PD. Incorporating additional behavioral experiments, such as the Morris water maze, eight-arm radial maze, and elevated plus maze, could allow for a more thorough assessment of motor and cognitive functions in the mouse model (21).
In summary, Wang XY’s team has conducted pioneering research, offering significant insights into the therapeutic potential of rhapontin for GI dysfunction in PD. This work is highly commendable, and we look forward to the authors addressing the aforementioned concerns in future studies through more detailed experimental design and exploration. Such efforts would further enhance the robustness and comprehensiveness of their findings.
1. Koga S, Sekiya H, Kondru N, Ross OA, Dickson DW Neuropathology and molecular diagnosis of Synucleinopathies. Mol Neurodegener. 2021;16(1):83.
2. delete Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):939-53.
3. Bloem BR, Okun MS, Klein C Parkinson's disease. Lancet. 2021;397(10291):2284-303.
4. Gao V, Crawford CV, Burré J The Gut-Brain Axis in Parkinson's Disease. Cold Spring Harb Perspect Med. 2025;15(1).
5. Safarpour D, Sharzehi K, Pfeiffer RF Gastrointestinal Dysfunction in Parkinson's Disease. Drugs. 2022;82(2):169-97.
6. Munoz-Pinto MF, Candeias E, Melo-Marques I, Esteves AR, Maranha A, Magalhães JD, Carneiro DR, Sant'Anna M, Pereira-Santos AR, Abreu AE, Nunes-Costa D, Alarico S, Tiago I, Morgadinho A, Lemos J, Figueiredo PN, Januário C, Empadinhas N, Cardoso SM Gut-first Parkinson's disease is encoded by gut dysbiome. Mol Neurodegener. 2024;19(1):78.
7. Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA, Shen C, Lee H, Kulkarni S, Pasricha PJ, Lee G, Pomper MG, Dawson VL, Dawson TM, Ko HS Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019;103(4):627-41.e7.
8. Van Den Berge N, Ferreira N, Gram H, Mikkelsen TW, Alstrup AKO, Casadei N, Tsung-Pin P, Riess O, Nyengaard JR, Tamgüney G, Jensen PH, Borghammer P Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats. Acta Neuropathol. 2019;138(4):535-50.
9. Tan AH, Lim SY, Lang AE The microbiome-gut-brain axis in Parkinson disease - from basic research to the clinic. Nat Rev Neurol. 2022;18(8):476-95.
10. Du J, Zhang P, Tan Y, Gao C, Liu J, Huang M, Li H, Shen X, Huang P, Chen S Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD). Mov Disord. 2024;39(8):1397-402.
11. Nishiwaki H, Hamaguchi T, Ito M, Ishida T, Maeda T, Kashihara K, Tsuboi Y, Ueyama J, Shimamura T, Mori H, Kurokawa K, Katsuno M, Hirayama M, Ohno K Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson's Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder. mSystems. 2020;5(6).
12. Wang Q, Luo Y, Ray Chaudhuri K, Reynolds R, Tan EK, Pettersson S The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options. Brain. 2021;144(9):2571-93.
13. Tolosa E, Garrido A, Scholz SW, Poewe W Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021;20(5):385-97.
14. Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016;167(6):1469-80.e12.
15. Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G, Zhang D Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome. 2021;9(1):226.
16. Metta V, Leta V, Mrudula KR, Prashanth LK, Goyal V, Borgohain R, Chung-Faye G, Chaudhuri KR Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation. J Neurol. 2022;269(3):1154-63.
17. Li R, Chinnathambi A, Alharbi SA, Shair OHM, Veeraraghavan VP, Surapaneni KM, Rengarajan T Anti-inflammatory effects of rhaponticin on LPS-induced human endothelial cells through inhibition of MAPK/NF-κβ signaling pathways. J Biochem Mol Toxicol. 2021;35(5):e22733.
18. Shi Q, Cheng Y, Dong X, Zhang M, Pei C, Zhang M Effects of rhaponticin on retinal oxidative stress and inflammation in diabetes through NRF2/HO-1/NF-κB signalling. J Biochem Mol Toxicol. 2020;34(11):e22568.
19. Tao L, Cao J, Wei W, Xie H, Zhang M, Zhang C Protective role of rhapontin in experimental pulmonary fibrosis in vitro and in vivo. Int Immunopharmacol. 2017;47:38-46.
20. Wei W, Wang L, Zhou K, Xie H, Zhang M, Zhang C Rhapontin ameliorates colonic epithelial dysfunction in experimental colitis through SIRT1 signaling. Int Immunopharmacol. 2017;42:185-94.
21. Tuersong T, Wu QF, Chen Y, Shan Li P, Yong YX, Shataer M, Shataer S, Ma LY, Yang XL Integrated network pharmacology, metabolomics, and microbiome studies to reveal the therapeutic effects of Anacyclus pyrethrum in PD-MCI mice. Phytomedicine. 2025;142:156729."
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Wang XY, Liu F, Wang QT, Li SZ, Ye YZ, Chen T, Cai BC. Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced gastrointestinal dysfunction in Parkinson's disease mice. World J Gastroenterol 2025; 31(15): 104875 [DOI: 10.3748/wjg.v31.i15.104875]
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"Name of Journal:World Journal of Hepatology
Manuscript NO:
Manuscript Type: LETTER TO THE EDITOR
Commentary: Multi-omics reveals the associations among the fecal metabolome,intestinal bacteria, and serum indicators in patients with
hepatocellular carcinoma
Biao Wen,Yin-Ping Wang
Biao Wen,Yin-Ping Wang,Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China
Author contributions:Yin-Ping Wang wrote the original draft; Biao Wen contributed to conceptualization, writing, reviewing and editing; Yin-Ping Wang and Biao Wen participated in drafting the manuscript; and all authors have read and approved the final version of the manuscript.
Supported by
ORCID number：0000-0001-5226-5981
Corresponding author:Biao Wen,MD, PhD,Assistant Professor,Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College,No. 312, Middle Section of Baoguang Avenue, Xindu District, Chengdu 610000, Sichuan Province, China. 820695761@qq.com
Received:
Revised:
Accepted:
Published online:
Abstract:
Recently, Feng J et al. published an important study. The research team revealed the associations of fecal metabolomics, intestinal bacteria and serum indicators in patients with hepatocellular carcinoma (HCC) through multi-omics analysis. The research results indicate that the composition of the metabolome and intestinal bacteria in fecal samples is expected to become a potential biomarker for the diagnosis of HCC. After a thorough review of their work, we put forward two insights regarding the impact of hepatitis B virus and antiviral drugs on the intestinal flora of HCC, the changes in intestinal microbiota in HCC and healthy control groups.
Key Words: Liver neoplasms; Gastrointestinal microbiome; Antiviral drug; Comment;
Core Tip: We conducted a rigorous assessment of the research by Feng et al., and put forward expert suggestions regarding the changes of HCC in the gut microbiota and the impact of hepatitis B virus and related antiviral drugs on the microbiota, in order to advance this scientific field.
TO THE EDITOR
After reading the study titled "Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma" by Feng et al. published in the World Journal of Gastroenterology, we found it highly insightful. The authors employed integrated metabolomic and microbiomic approaches to elucidate the linkages between fecal metabolites, gut microbiota, and serum biomarkers in hepatocellular carcinoma (HCC) patients, providing new perspectives for the early diagnosis of HCC. Here, we would like to share our perspectives on the following aspects: The impact of hepatitis B virus (HBV) and antiviral therapies on gut microbiota alterations in HCC; Gut microbial differences between HCC patients and healthy controls.
The first point: The changes in the gut microbiota of HCC and healthy control groups vary in different studies and may be influenced by multiple factors
More and more studies have shown that the intestinal microbiota is related to the occurrence of HCC and is expected to become a biomarker for the diagnosis of HCC. In the study by Feng et al., it was concluded that Lachnospira, Streptococcus and Veillonella are representative differential bacterial genera in the feces of HCC patients. These three bacterial genera and their related metabolites may serve as unique biomarkers [1]. Most studies have shown that there are differences in theα-diversity orβ-diversity of the intestinal microbiota between HCC patients and healthy control groups. However, these differences may vary when further studying the intestinal microbiota of HCC patients, such as at the genus level or species level.
Zhang et al. found that Enterococcaceae, Lactobacillus, Bacillus and Gammaproteobacteria can be used as diagnostic markers for primary liver cancer (PLC). In addition, a correlation analysis was conducted, and the results showed that Veillonella was significantly positively correlated with alpha-fetoprotein (AFP) in PLC patients[2]. In 2023, Zhang et al. demonstrated that at the family level, the abundance of Lachnospiraceae, Coriobacteriaceae, Eggerthellaceae and Synergistaceae in the liver cancer group was significantly reduced compared with the normal group. The abundances of Enterobacteriaceae, Fusobacteriaceae, Lactobacillus and Erysierysiaceae increased significantly. At the horizontal level, compared with the normal group, The liver cancer groups included Blautia, Fusicatenibacter, Anaerostipes, Lachnospiraceae_ND3007_group, GG-56, Eggerthella, Lachnospiraceae_FCS020_group and The abundance of Olsenella was significantly reduced. The abundance of Escherichia coli - Shigella, Prevotella_2 Tyzzerella_4, Clostridium erysipelum and Prevotella_2 Tyzzerella ₄ increased significantly. Meanwhile, alpha-fetoprotein (AFP) is positively correlated with the abundance of Streptococcus[3];Yang et al. confirmed through a prospective study that in terms of intestinal samples, the average relative abundance of Proteobacteria in the HCC group was significantly higher than that in the control group. The abundance of Streptococcus in oral and fecal samples of HCC patients was higher than that in the control group. Meanwhile, during the transition from a healthy state to liver cirrhosis and HCC, the content of streptococcus in the hepatocellular carcinoma and liver cirrhosis groups was much higher than that in the control group, and showed an upward trend during the disease progression. From the analysis of microbial correlations and clinical characteristics and functions among each group, both Streptococcus and Virongella were identified in the microbial communities of oral and intestinal samples, and both were in key positions in the microbial correlation network of fecal samples. Streptococcus and Virongella showed a consistent trend. Among them, the microbiome distribution was positively correlated with MELD, Child-Pugh, age, CCI, AFP, AST, ALT, GGT, Cre, LDL, Tchol, PT and INR, and negatively correlated with ALB, BMI, HDL, TG and PLT in HCC patients. This study has similarities with that of Feng J et al[4];In 2024, the research results of Jinato et al. indicated that HCC was enriched with five genera, including Bacteroides, Streptococcus, Ruminococcus, Veronistella and Clostridium erysibiricum. And Romboutsia, UCG-002, Lachnospiraceae NK4A-136, Eubacterium hallii group, Lachnospiraceae ND-3007 group, Erysipelotrichaceae Seven genera such as UCG-003 and Bilophila have low abundance in HCC patients[5].
From the above, it can be known that some studies have mentioned the three bacterial genera, Streptococcus, Veronella, and Lachnospira, in the HCC and healthy groups, showing an increase in the abundance of Streptococcus and Veronella, while the relative abundance of Lachnospira has decreased. However, in different studies, The reasons for the incomplete similarity in the abundance and structure of the intestinal microbiota between HCC and the healthy control group may be related to the drug use, alcohol consumption, diet, racial and regional differences of HCC patients[6];A Western diet high in fat, cholesterol or sugar can induce dysbiosis of the gut microbiome, a reduction in symbiotic probiotics and an increase in opportunistic pathogens[7];For example, the formation of NAFLD-HCC induced by dietary cholesterol is related to intestinal flora imbalance, and the composition of the microbiota changes with the formation stage of NAFLD-HCC: Mucispirillum, Desulfovibrio, Anaerotruncus and Desulfovibrionaceae increased successively; Bifidobacterium and Bacteroides were depleted in mice fed with HFHC, which was also confirmed in patients with human hypercholesterolemia[8].Therefore, it is still necessary to further verify the unique biomarkers of HCC.
The second point: Distinguish the independent effects of HBV infection and HCC and include data on the use of antiviral drugs
Hepatitis B virus infection can directly disrupt the intestinal flora balance through systemic inflammatory responses and disorders of the hepatoenteric axis. The study by Shen et al. indicated that the flora composition of patients with HBV-CLD (such as enrichment of Streptococcus and reduction of Bifidobacterium) was significantly different from that of the healthy control group. It is suggested that HBV infection itself has unique microbiota characteristics; Meanwhile, antiviral drug treatment can partially reverse the dysbiosis caused by HBV[9-10]; Jinato et al. studied the changes in the gut microbiota between Viral (virus-HCC) and non-viral (NNC-HCC) -related hepatocellular carcinomas and found that compared with virus-HCC, the NNC-HCC subgroup significantly reduced various bacteria that produce short-chain fatty acids and the reduction of fecal butyrate[5];Liu et al. also analyzed the intestinal microbiota changes in hepatitis B virus-associated hepatocellular carcinoma. The research results showed that there were differences in the abundance of bacteria in the intestines of patients with B-HCC and NNBNC-HCC, and these bacteria were respectively involved in different functions or biological pathways[11].
Therefore, whether there is HBV infection and whether antiviral treatment is used may have an impact on the changes in the intestinal flora. In the study by Feng J et al., we found that HBV accounted for a high proportion (78.95%) in the HCC population. Based on previous studies, stratified comparison of HCC patients with HBV(+) and HBV(-), as well as recording the use of antiviral drugs and analyzing their effects, can more accurately clarify the microbiota characteristics of HCC itself.
All in all, the changes in the gut microbiota are related to the occurrence and development of HCC. The inconsistency in the research on the gut microbiota related to HCC reflects the complexity of the disease and the dynamics of host-microbiota interactions. Future studies need to directly compare the microbiota, metabolome and immune characteristics of patients with HBV(+)HCC and HBV(-)HCC through larger sample cohorts of HCC, and combine animal models to verify the causal mechanism in order to reveal more robust microbiota characteristics and their mechanism of action in the occurrence and development of HCC. We look forward to the author team conducting follow-up research in this direction and promoting the innovation of early diagnosis techniques for HCC. Once again, we thank the authors for their outstanding work, which has opened up new ideas for HCC research.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
1.Feng J, Wang J P, Hu J R, et al. Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma[J]. World Journal of Gastroenterology, 2025, 31(15).
2.Zhang L, Wu YN, Chen T, Ren CH, Li X, Liu GX. Relationship between intestinal microbial dysbiosis and primary liver cancer. Hepatobiliary Pancreat Dis Int. 2019 Apr;18(2):149-157. doi: 10.1016/j.hbpd.2019.01.002. Epub 2019 Jan 4. PMID: 30661942.
3.Zhang W, Xu X, Cai L, Cai X. Dysbiosis of the gut microbiome in elderly patients with hepatocellular carcinoma. Sci Rep. 2023 May 13;13(1):7797. doi: 10.1038/s41598-023-34765-w. PMID: 37179446; PMCID: PMC10182990.
4.Yang J, He Q, Lu F, Chen K, Ni Z, Wang H, Zhou C, Zhang Y, Chen B, Bo Z, Li J, Yu H, Wang Y, Chen G. A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma. Gut Microbes. 2023 Jan-Dec;15(1):2201159. doi: 10.1080/19490976.2023.2201159. PMID: 37089022; PMCID: PMC10128432.
5.Jinato T, Anuntakarun S, Satthawiwat N, Chuaypen N, Tangkijvanich P. Distinct alterations of gut microbiota between viral- and non-viral-related hepatocellular carcinoma. Appl Microbiol Biotechnol. 2024 Dec;108(1):34. doi: 10.1007/s00253-023-12845-1. Epub 2024 Jan 6. PMID: 38183473; PMCID: PMC10771587.
6.Arnold M, Abnet CC, Neale RE, Vignat J, Giovannucci EL, McGlynn KA, Bray F. Global Burden of 5 Major Types of Gastrointestinal Cancer. Gastroenterology. 2020 Jul;159(1):335-349.e15. doi: 10.1053/j.gastro.2020.02.068. Epub 2020 Apr 2. PMID: 32247694; PMCID: PMC8630546.
7.Pan Y, Zhang X. Diet and gut microbiome in fatty liver and its associated liver cancer. J Gastroenterol Hepatol. 2022 Jan;37(1):7-14. doi: 10.1111/jgh.15713. Epub 2021 Nov 3. PMID: 34664301.
8.Zhang X, Coker OO, Chu ES, Fu K, Lau HCH, Wang YX, Chan AWH, Wei H, Yang X, Sung JJY, Yu J. Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites. Gut. 2021 Apr;70(4):761-774. doi: 10.1136/gutjnl-2019-319664. Epub 2020 Jul 21. PMID: 32694178; PMCID: PMC7948195.
9.Shen Y, Wu SD, Chen Y, Li XY, Zhu Q, Nakayama K, Zhang WQ, Weng CZ, Zhang J, Wang HK, Wu J, Jiang W. Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response. Gut Microbes. 2023 Jan-Dec;15(1):2155018. doi: 10.1080/19490976.2022.2155018. PMID: 36519342; PMCID: PMC9757487.
10.Li YG, Yu ZJ, Li A, Ren ZG. Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions. World J Gastroenterol. 2022 Jul 28;28(28):3555-3572. doi: 10.3748/wjg.v28.i28.3555. PMID: 36161048; PMCID: PMC9372803.
11.Liu Q, Li F, Zhuang Y, Xu J, Wang J, Mao X, Zhang Y, Liu X. Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma. Gut Pathog. 2019 Jan 18;11:1. doi: 10.1186/s13099-018-0281-6. PMID: 30675188; PMCID: PMC6337822.
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Feng J, Wang JP, Hu JR, Li P, Lv P, He HC, Cheng XW, Cao Z, Han JJ, Wang Q, Su Q, Liu LX. Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma. World J Gastroenterol 2025; 31(15): 104996 [DOI: 10.3748/wjg.v31.i15.104996]
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"The author has provided an interesting study to associate between Epstein-Barr virus and ulcerative colitis with surgery or not. Meanwhile, the similar virus of Cytomegalovirus also presented a high level in this investigation as data indicated in this study. Maybe author can perform a demonstration to clarify the more connection between the two distinct groups of herpes simplex virus in the development of ulcerative colitis."
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Zhang H, Gu X, He W, Zhao SL, Cao ZJ. Epstein-Barr virus infection is an independent risk factor for surgery in patients with moderate-to-severe ulcerative colitis. World J Gastroenterol 2025; 31(16): 104758 [DOI: 10.3748/wjg.v31.i16.104758]
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"The manuscript 'MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19' by Konstantinos I Papadopoulos, Alexandra Papadopoulou and Tar Choon Aw addresses the problem of personalized therapy of COVID-19. The authors rightly point out that agents that inhibit the activity of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors and AT1R antagonists, can have opposite effects from protective to harmful on the course of the disease, and that worsening of symptoms is seen predominantly in the elderly, in patients with type 2 diabetes, cardiovascular and renal disease, and in some other comorbidities. The authors hypothesise that the negative effects of inhibitors of RAS activity are due to their induced dysregulation of erythropoietin secretion and decreased miRNA-155 levels. The paper cites two references to studies that found a decrease in miRNA-155 following exposure to RAS inhibitors. In conclusion, it is suggested that mineralocorticosteroid receptor antagonists and L-type calcium channel blockers may be preferable to RAS inhibitors in elderly patients and in some comorbidities characterised by reduced baseline miRNA-155 levels. However, a number of the points made by the authors need to be thoroughly tested in further studies, as there is evidence of increased miRNA-155 levels in COVID-19 patients (Asadpour-Behzadi et al, 2023, Haroun et al, 2022), reduced severity of cytokine storm in miRNA-155 knockout animals (Soni et al, 2025) and positive correlation of miRNA-155 levels with inflammatory markers in COVID-19 patients (AL-Nuaimi AL-azzawi, 2025). However, these data do not exclude the possibility that optimal elevation of miRNA-155 levels may be protective, as has been shown in patients with coronary artery disease (Zhu et al., 2014, Ban et al., 2023). Given that miRNA-155 regulates the activity of more than 200 genes, such a non-linear dependence of its effects on levels and physiological characteristics of the organism seems legitimate. The article thus raises a pressing issue that will undoubtedly require further research. "
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Papadopoulos KI, Papadopoulou A, Aw TC. MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19. World J Exp Med 2025; 15(2): 100748 [DOI: 10.5493/wjem.v15.i2.100748]
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"1. Title
✅ Yes – The title accurately reflects the manuscript’s focus on the discrepancies between diagnostic modalities and histopathologic assessment in Crohn’s disease (CD). It clearly conveys the study’s central theme.
2. Abstract
✅ Yes – The abstract provides a concise yet comprehensive summary of the manuscript’s objectives, key findings, and conclusions. It effectively outlines the challenges in assessing CD and the importance of multimodal evaluation.
3. Key Words
✅ Yes – The selected keywords (Crohn’s disease, transmural inflammation, histopathological scoring system, endoscopy, cross-sectional imaging techniques) are well-chosen and align with the manuscript’s focus.
4. Background
✅ Yes – The introduction thoroughly discusses the current understanding of CD, its transmural nature, and the limitations of existing diagnostic methods. It establishes a strong rationale for the study.
5. Methods
⚠️ No – Since this is a narrative review, the manuscript lacks explicit methodological details (e.g., search strategy, inclusion/exclusion criteria). A more structured approach (e.g., PRISMA guidelines) would strengthen its rigor.
6. Results
✅ Yes – The review successfully synthesizes current evidence on diagnostic discrepancies in CD, highlighting gaps and emerging technologies (e.g., AI, advanced imaging).
✅ Yes – The study contributes meaningfully to the field by emphasizing the need for standardized histologic and imaging assessments in CD management.
7. Discussion
✅ Yes – The discussion logically interprets findings, underscoring the clinical implications of discordant diagnostic modalities. Key points (e.g., transmural healing as a treatment goal) are well-articulated.
✅ Yes – The applicability of findings to clinical practice and research is clearly stated, with actionable insights (e.g., optimizing biopsy protocols).
✅ Yes – The discussion is scientifically sound, balancing technical details (e.g., imaging techniques) with broader relevance to gastroenterology.
8. Illustrations and Tables
❌ No – The manuscript would benefit from visual aids (e.g., tables comparing scoring systems, imaging modalities; diagrams of transmural inflammation).
❌ No – If figures were included, clearer labeling (e.g., arrows for histologic features) would enhance interpretability.
9. Biostatistics
🔘 N/A – Not applicable, as this is a narrative review without original data analysis.
10. Units
✅ Yes – SI units (e.g., mm for wall thickness) are used correctly and consistently.
11. References
✅ Yes – References are up-to-date (including 2024–2025 publications) and authoritative, covering clinical, endoscopic, and histologic aspects of CD.
❌ No – No excessive self-citation or omission of key literature is evident.
12. Quality of Manuscript Organization and Presentation
✅ Yes – The manuscript is well-structured, with a logical flow from background to discussion. Subheadings improve readability.
✅ Yes – Language and grammar are precise, with only minor edits needed (e.g., occasional redundancy in phrasing).
13. Ethics Statements
🔘 N/A – No human/animal studies were conducted; ethics approval is not required.
Overall Evaluation
Scientific Quality: Grade B (Very Good)
Strengths: Comprehensive literature synthesis, clear clinical relevance, and balanced discussion of diagnostic challenges.
Areas for Improvement: Include methodological details for transparency (e.g., how studies were selected). Add tables/figures to summarize complex concepts (e.g., imaging vs. histologic criteria).
Language Quality: Grade A (Excellent)
The writing is polished, with minimal grammatical errors and effective use of technical terminology.
Suggestions for Authors
Enhance Methodology: Briefly describe the review’s approach (e.g., database search terms, timeframe) to bolster reproducibility.
Add Visual Summaries: A table comparing histologic scoring systems or imaging modalities would aid reader comprehension.
Clarify Clinical Takeaways: Consider a bullet-point summary of key recommendations for clinicians (e.g., when to use EUS vs. MRE).
This review provides valuable insights into CD diagnostics and would be further strengthened by these refinements."
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Fang HM. Intricacy of Crohn’s disease: Incongruity between diagnostic modalities and histopathologic assessment. World J Gastrointest Endosc 2025; 17(4): 103979 [DOI: 10.4253/wjge.v17.i4.103979]
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6
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"Bleeding is a significant complication of acute-on-chronic liver failure (ACLF), with prolonged prothrombin time and thrombocytopenia in these patients elevating the perceived risk of bleeding. We were intrigued by the manuscript by Liu et al. [1], which investigates the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treating thrombocytopenia among ACLF patients. This prospective, open-label study involved 70 ACLF patients with severe thrombocytopenia, who were assigned to either an rhTPO group or a control group. The primary endpoint was the proportion of patients achieving a platelet count greater than 50 × 10^9/L by day 14. The study’s noteworthy findings indicated that rhTPO significantly increased platelet counts in ACLF patients, with a higher proportion reaching the target platelet count in the rhTPO group compared to the control group (60.7% vs. 12.0%). The study concluded that rhTPO effectively elevates platelet counts, improves liver function, and reduces bleeding events in ACLF patients with thrombocytopenia, while maintaining a favorable safety profile. These findings provide promising insights into managing thrombocytopenia in ACLF patients.
While this study holds clinical significance, it also has notable limitations. Liver disease has long been recognized as a condition associated with bleeding disorders, which arise from multiple factors [2,3]. These include thrombocytopenia, low levels of coagulation factors, and decreased fibrinolytic proteins, all contributing to the coagulopathy seen in liver disease [4]. Thrombocytopenia is one of the most common hematological abnormalities and often the first abnormality detected in chronic liver disease patients [5]. While mild to moderate thrombocytopenia rarely has clinical significance due to the low likelihood of spontaneous bleeding, moderate to severe thrombocytopenia can hinder patients from receiving essential interventions, including medications and invasive procedures. Delays in procedures and the need to correct platelet abnormalities can extend hospital stays and increase overall healthcare costs [6,7]. Increasing platelet counts and achieving rebalanced hemostasis appears to be a strategy for controlling the risk of acute bleeding in ACLF patients without raising the risk of thrombosis; however, the impact on disease prognosis requires further investigation [2]. Despite indicating that increasing platelet counts and achieving rebalanced hemostasis may help control the risk of acute bleeding in ACLF patients without increasing the risk of thrombosis, further investigation is necessary to understand the impact on disease prognosis. Additionally, while serum hepatocyte growth factor and thrombopoietin (TPO) levels were measured, key coagulation-related tests were not further explored. Simply correcting thrombocytopenia does not address all facets of coagulation [8]. Furthermore, laboratory tests such as platelet aggregation and thromboelastography were not conducted. These assessments could provide a more comprehensive understanding of the extent to which the coagulopathy in ACLF patients has been addressed, rather than relying solely on platelet counts [9]. Moreover, the study's small sample size limits its statistical power and may introduce confounding factors. The analysis of results was relatively straightforward and did not adequately account for potential confounders. Consequently, the conclusions drawn should be considered preliminary. The exploratory and pilot nature of this study limits its clinical significance. Nonetheless, it remains a valuable contribution to the field, providing direction for future research and establishing a foundational basis for subsequent investigations.
Currently, in addition to rhTPO, there are other treatment options available, such as oral small molecule agonists of TPO receptor like avatrombopag [10]. Further studies comparing these agents are needed to determine the optimal strategies for managing bleeding risk in ACLF patients. Overall, this research offers hope for the management of ACLF patients and points toward future investigation directions.
REFERENCES
1. Liu G, Tang F, Wang T, Yan JQ, Li FH, Ha FS, Zhang X, Jing L, Liang J. Efficacy of recombinant human thrombopoietin in patients with acute-on-chronic liver failure and thrombocytopenia: A prospective, open-label study. World J Gastroenterol. 2025;31 14:105004. doi: 10.3748/wjg.v31.i14.105004.
2. Lisman T, Porte RJ. Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases. Res Pract Thromb Haemost. 2017;1 2:150-161. doi: 10.1002/rth2.12028.
3. Lisman T, Leebeek FW, de Groot PG. Haemostatic abnormalities in patients with liver disease. J Hepatol. 2002;37 2:280-7. doi: 10.1016/s0168-8278(02)00199-x.
4. Stravitz RT, Ellerbe C, Durkalski V, Schilsky M, Fontana RJ, Peterseim C, Lee WM; Acute Liver Failure Study Group. Bleeding complications in acute liver failure. Hepatology. 2018;67 5:1931-1942. doi: 10.1002/hep.29694.
5. Violi F, Basili S, Raparelli V, Chowdary P, Gatt A, Burroughs AK. Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction? J Hepatol. 2011;55 6:1415-27. doi: 10.1016/j.jhep.2011.06.008.
6. Poordad F. Review article: thrombocytopenia in chronic liver disease. Aliment Pharmacol Ther. 2007;26 Suppl 1:5-11. doi: 10.1111/j.1365-2036.2007.03510.x.
7. Moore AH. Thrombocytopenia in Cirrhosis: A Review of Pathophysiology and Management Options. Clin Liver Dis (Hoboken). 2019;14 5:183-186. doi: 10.1002/cld.860.
8. O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA Clinical Practice Update: Coagulation in Cirrhosis. Gastroenterology. 2019;157 1:34-43.e1. doi: 10.1053/j.gastro.2019.03.070.
9. Biswas S, Anand A, Vaishnav M, Mehta S, Swaroop S, Aggarwal A, Arora U, Agarwal A, Elhence A, Mahapatra SJ, Agarwal S, Gunjan D, Sehgal T, Aggarwal M, Dhawan R, Gamanagatti S, Shalimar. Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial. J Vasc Interv Radiol. 2024;35 10:1508-1518.e2. doi: 10.1016/j.jvir.2024.06.014.
10. Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, Allen LF, Hassanein T. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology. 2018;155 3:705-718. doi: 10.1053/j.gastro.2018.05.025.
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Dai ZS, Zhang M, Deng YY, Zhou N, Tian Y. Efficacy of a novel artificial liver versatile plasma purification system in patients with acute-on-chronic liver failure. World J Gastroenterol 2025; 31(14): 103892 [PMID: 40248372 DOI: 10.3748/wjg.v31.i14.103892]
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7
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"This paper describes a case-control study on the early detection of delayed gastric emptying (gastroparesis), which presents as an initial symptom of diabetic ketoacidosis (DKA). According to the authors, delayed gastric emptying can frequently cause glycemic variability by delaying postprandial blood glucose elevation, potentially triggering hypoglycemic and hyperglycemic symptoms. This condition increases the risk of DKA and hyperosmolar hyperglycemic syndrome (HHS), with the incidence of DKA being reported as four times higher in patients with delayed gastric emptying. Therefore, the authors emphasize the importance of early diagnosis and appropriate treatment of delayed gastric emptying in patients with DKA. Recently, the possibility of intestinal dysmotility due to dysbiosis caused by uremic toxins in chronic kidney disease (CKD) has also become a topic of interest. Similarly, the relationship between gut microbiota and intestinal motility disorders in DKA patients is an intriguing issue that warrants further investigation."
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Han L, Peng QY, Yu J, Liu YW, Li W, Ping F, Zhang HB, Li YX, Xu LL. Early detection of gastroparesis with diabetic ketoacidosis as initial manifestation: A case-control study. World J Gastroenterol 2025; 31(15): 101695 [DOI: 10.3748/wjg.v31.i15.101695]
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8
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"This is an interesting study. However, there are a few issues, most of these have been addressed by the authors. Firstly, since this is a retrospective study with a relatively small sample size. Also it is not clear if all patients had a endoscopy to help exclude other causes of delayed gastric emptying. Also the fact that low HbA1c is a predictor needs an adequate explanation. It may be difficult to make conclusions on a sample of only 15 DKA patients. "
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Han L, Peng QY, Yu J, Liu YW, Li W, Ping F, Zhang HB, Li YX, Xu LL. Early detection of gastroparesis with diabetic ketoacidosis as initial manifestation: A case-control study. World J Gastroenterol 2025; 31(15): 101695 [DOI: 10.3748/wjg.v31.i15.101695]
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9
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"Dear Baishideng Office,
I read a very interesting article «Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions». The article format corresponds to the review format. The authors of the review presented the current problem of post-TIPS hepatic encephalopathy. The list of references consists of 155 sources. The article is well illustrated with figures and tables. Easy to read despite the large amount of information material. All problematic sections are analyzed in depth and detail, and modern fields of view for each section are also taken into account. An article worthy of publication in the World Journal of Gastroenterology.
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Li Y, Wu YT, Wu H. Management of hepatic encephalopathy following transjugular intrahepatic portosystemic shunts: Current strategies and future directions. World J Gastroenterol 2025; 31(15): 103512 [DOI: 10.3748/wjg.v31.i15.103512]
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10
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"This study addresses a critical gap in acute pancreatitis management by systematically comparing established scoring systems with novel hematological markers. The focus on early-phase severity stratification aligns with clinical urgency, as delayed interventions in severe AP significantly worsen outcomes.
The inclusion of 463 patients across severity categories provides sufficient statistical power. The use of multivariate logistic regression to identify independent predictors and AUC comparisons for ROC analyses strengthens validity. Notably, the combined PNI48 + Ranson model achieved an AUC of 0.936, outperforming individual parameters.
However, the study has several issues that need to be addressed. 1) While CTSI showed the highest individual AUC, its reliance on CT imaging (performed 2–5 days post-admission) limits utility in hyperacute settings. The BISAP score’s superiority over APACHE II/SOFA within 24 h is consistent with prior literature , but the lack of comparison with newer tools is a missed opportunity. 2) The study’s retrospective nature introduces risks of selection bias, particularly in excluding patients with brief hospital stays (<48 h), who may represent early mortality or rapid recovery cases. External validation using multicenter cohorts is essential to confirm generalizability. 3) Most parameters (e.g., CRP48, PNI48) were assessed at fixed intervals. Dynamic trends in markers like CRP or calcium—critical for real-time clinical decision-making—were overlooked. Serial measurements could enhance predictive accuracy, as shown in studies of procalcitonin kinetics.
In conclusion, this study provides valuable insights into a multimodal approach for AP severity prediction, with PNI48 emerging as a novel, nutrition-centric biomarker. However, its retrospective design and limited temporal resolution restrict immediate clinical applicability. Methodological refinements and external validation will be critical to translate these findings into practice."
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Shi PN, Song ZZ, He XN, Hong JM. Evaluation of scoring systems and hematological parameters in the severity stratification of early-phase acute pancreatitis. World J Gastroenterol 2025; 31(15): 105236 [DOI: 10.3748/wjg.v31.i15.105236]
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11
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"This article presents a series of clinically practical and easily obtainable diagnostic indices, enabling medical professionals to more accurately evaluate patient conditions in real-world clinical settings. These indicators are particularly valuable for the early diagnosis and severity assessment of pancreatitis, offering crucial guidance for subsequent treatment decisions. By incorporating these measurable parameters into routine clinical practice, healthcare providers can enhance diagnostic efficiency, improve risk stratification, and facilitate timely therapeutic interventions. The systematic application of these indices not only supports evidence-based medical decision-making but also contributes to standardized patient management protocols, ultimately leading to better clinical outcomes in pancreatitis care."
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Shi PN, Song ZZ, He XN, Hong JM. Evaluation of scoring systems and hematological parameters in the severity stratification of early-phase acute pancreatitis. World J Gastroenterol 2025; 31(15): 105236 [DOI: 10.3748/wjg.v31.i15.105236]
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12
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"The reader possesses professional expertise in digestive endoscopy, EUS-guided biopsy, and tumor diagnosis. The authors have declared no conflicts of interest. According to the standards for commenting on published articles, which include evaluation of study design, statistical methods, and reliability of conclusions, this study is a well-designed prospective randomized controlled trial with clear data analysis and high scientific quality. The language is generally fluent, though some sentences could be further polished. The reader believes that this study, which compares the diagnostic sensitivity of two types of needles under conditions without rapid onsite evaluation (ROSE), has significant clinical relevance and suggests that future studies with larger sample sizes are warranted to validate the broader applicability of the findings."
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Paduani GF, Felipe LM, De Paulo GA, Lenz L, Martins BC, Matuguma SE, Safatle-Ribeiro AV, De Mello ES, Maluf-Filho F. Prospective randomized study comparing Franseen 22-gauge vs standard 22-gauge needle for endoscopic ultrasound guided sampling of pancreatic solid lesions. World J Gastrointest Endosc 2025; 17(4): 101998 [DOI: 10.4253/wjge.v17.i4.101998]
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13
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"Leucine-rich α2 glycoprotein (LRG) is a biomarker easily and conveniently evaluated through blood sampling. Because LRG reflects cytokines other than IL-6, it is expected to be useful for assessing the activity of small intestinal lesions in Crohn’s disease, which are often difficult to detect with CRP. Although there is still room for discussion regarding the cutoff value of LRG, it is considered more important to monitor the trend of LRG values over time in each patient rather than focusing solely on the absolute value itself."
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Krishnan A. Leucine-rich alpha-2 glycoprotein for detecting small bowel lesions in Crohn’s disease: A critical review and the path forward. World J Gastrointest Endosc 2025; 17(4): 106671 [DOI: 10.4253/wjge.v17.i4.106671]
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14
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"1. Figure 1: If both the pre-radiofrequency ablation enhanced MR images and the post- radiofrequency ablation enhanced MR images at regular follow-up are provided, the changes in tumor characteristics before and after treatment can be more accurately assessed.
2. The pathological image of HE staining lacks a scale bar for measurement reference.
3. The MRI report omits the examination time, which is critical for temporal correlation.
4. Figure 4: The examination date is not specified, and no arrows have been used to clearly indicate lesions.
5. Figure 5: Contrast-enhanced MR imaging is necessary to detect potential small metastases due to the limited sensitivity of CT scans.
6. Page 3: Chief Complaints: "The patient was admitted to the hospital on March 03, 2018." History of Past Illness: "On March 18, 2018, the patient underwent CT examination at a foreign hospital." Based on the timeline, the chief complaint (admission date) precedes the CT examination date, which appears inconsistent. Please clarify.
7. Page 3: History of Present Illness and History of Past Illness: The content structure does not adhere to standard medical documentation conventions. It is recommended to reorganize these sections for clarity and consistency.
8. Page 3: Physical Examination: Radiofrequency ablation (RFA) for liver metastases was performed; however, RFA is a therapeutic intervention rather than a physical examination. This procedure should not be listed under the physical examination section.
9. Page 4: Treatment: Two rounds of radiofrequency ablation were completed, but the exact dates of these procedures are missing. To facilitate accurate comparison of pre- and post-ablation images, the specific timing of each session must be documented. Additionally, when comparing images (e.g., "compared with those in the July 07, 2020 slices"), it is essential to provide corresponding images from the same anatomical region at two distinct time points to more effectively illustrate tumor size changes.
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Yong JP, Mu XY, Zhou CF, Zhang KK, Gao JQ, Guo ZZ, Zhou SF, Ma Z. Radiofrequency ablation of liver metastases in a patient with pancreatic cancer and long-term survival: A case report. World J Clin Cases 2025; 13(20): 100169 [DOI: 10.12998/wjcc.v13.i20.100169]
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15
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"This retrospective cohort study presented an interesting results to combine the Raman spectroscopy and machine learning for evaluation of the pathogenic degree in esophageal squamous cell carcinoma. There is a result in the figure 4 to show the decreased effect on peak of high-low group. Maybe author perform the potential interaction from these high and low grade tissues in Raman spectroscopy analysis. "
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Yu XY, Chen J, Li LY, Chen FE, He Q. Rapid pathologic grading-based diagnosis of esophageal squamous cell carcinoma via Raman spectroscopy and a deep learning algorithm. World J Gastroenterol 2025; 31(14): 104280 [PMID: 40248385 DOI: 10.3748/wjg.v31.i14.104280]
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16
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"The study’s prospective design and the use of validated instruments, including a simplified Profile of Mood States and the Pittsburgh Sleep Quality Index, are notable strengths. The findings demonstrate that the observation group, which received both CBT and MBSR, achieved significantly better outcomes in terms of reduced negative mood dimensions and improved sleep quality compared to the control group (CBT only). These results suggest that the dual intervention not only alleviates depressive symptoms but also enhances sleep quality, thereby addressing two interrelated facets of patient well-being.
Zhang et al.’s study makes a valuable contribution by demonstrating that an integrated CBT and MBSR intervention can significantly improve both mood state and sleep quality in patients with diabetes and endometrial cancer. We encourage the authors to address the aforementioned aspects in future research to further refine and validate this promising therapeutic approach. Integrating detailed intervention protocols and extending follow-up durations will enhance the generalizability and clinical utility of their findings."
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Zhang QS, Zhang W, Mao Y, Wang XS, Zhang JW, Cao YJ. Effects of cognitive combined with mindfulness-based stress reduction and sleep in patients with diabetes and endometrial cancer. World J Psychiatry 2025; 15(4): 100849 [DOI: 10.5498/wjp.v15.i4.100849]
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17
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"This article is a high-quality academic editorial that systematically explores the potential value of PLD2 in acute pancreatitis (AP) and proposes actionable future research directions. Its core contributions lie in: 1. Integrating molecular mechanisms with clinical applications, shifting AP biomarker research from "phenomenological association" to "mechanism-driven" investigation; 2. Emphasizing multi-omics integration and precision medicine, offering a novel paradigm for AP management."
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Wang ZH, Lv JH, Teng Y, Michael N, Zhao YF, Xia M, Wang B. Phospholipase D2: A biomarker for stratifying disease severity in acute pancreatitis? World J Gastroenterol 2025; 31(11): 104033 [PMID: 40124273 DOI: 10.3748/wjg.v31.i11.104033]
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18
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"This study provides novel insights into the risk factors for metachronous gastric cancer (MGC) in elderly patients, particularly highlighting the clinical significance of the association with metabolic dysfunction-associated steatotic liver disease (MASLD) and the proposed risk stratification system. However, the retrospective design and small sample size limit the robustness of the evidence, necessitating further validation through multicenter prospective studies. The paper is well-structured but requires refinement in statistical details."
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Xiang Y, Yuan Y, Wang ZY, Zhu YM, Li WY, Ye QG, Wang YN, Sun Q, Ding XW, Longi F, Tang DH, Xu GF. Comorbidities related to metachronous recurrence for early gastric cancer in elderly patients. World J Gastrointest Endosc 2025; 17(3): 99540 [PMID: 40125504 DOI: 10.4253/wjge.v17.i3.99540]
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19
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"The author has constructed a predictive model with strong forecasting capabilities, designed to estimate the probability of a textbook outcome following surgery. Additionally, the study elucidates the machine learning computational process using the SHAP algorithm. This research is highly innovative, as it visualizes the otherwise opaque computational processes of machine learning, thereby enhancing its credibility. Clinicians can easily input specific clinical parameters of patients to obtain immediate, personalized risk assessments, enabling timely preventive measures and ensuring the best possible medical care for patients.This study substantiates the feasibility of explainable machine learning in future applications, marking a new direction in the research of predictive models and supervised learning."
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Huang TF, Luo C, Guo LB, Liu HZ, Li JT, Lin QZ, Fan RL, Zhou WP, Li JD, Lin KC, Tang SC, Zeng YY. Preoperative prediction of textbook outcome in intrahepatic cholangiocarcinoma by interpretable machine learning: A multicenter cohort study. World J Gastroenterol 2025; 31(11): 100911 [PMID: 40124276 DOI: 10.3748/wjg.v31.i11.100911]
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20
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"This study provides valuable insights into the effectiveness of combining three-dimensional computed tomography (3D CT) reconstruction and laparoscopic techniques for accurately measuring the myopectineal orifice (MPO) in inguinal hernia repair. The research clearly demonstrates that preoperative 3D CT measurements closely match intraoperative laparoscopic findings, suggesting that CT could reliably guide surgical planning.
The authors effectively highlight the clinical implications, emphasizing how precise measurement and patch placement can minimize complications such as nerve injury, recurrence, and chronic postoperative pain. Additionally, they provide a thoughtful analysis regarding demographic factors, noting significant differences in MPO measurements between sexes, while age and body mass index showed less impact.
One of the strengths of this article is its detailed methodological description, which facilitates replication and further research. However, future studies might benefit from larger sample sizes and expanded demographic variability to enhance generalizability. Overall, the paper makes a significant contribution to personalized surgical approaches for inguinal hernia treatment."
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Zhang L, Chen J, Zhang YY, Liu L, Wang HD, Zhang YF, Sheng J, Hu QS, Liu ML, Yuan YL. Three-dimensional reconstruction under computed tomography and myopectineal orifice measurement under laparoscopy for quality control of inguinal hernia treatment. World J Gastrointest Endosc 2025; 17(3): 104966 [PMID: 40125507 DOI: 10.4253/wjge.v17.i3.104966]
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21
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"As this is a editorial article, it has got no sections of methods, results, tables, biostatistics, units and ethical statement to provide commentary on these sections.
The editorial by Behrens and Elgafy provides an insightful analysis of factors influencing outcomes in indirect decompression through oblique and lateral lumbar interbody fusions (OLIF and LLIF). The discussion on patient selection criteria, particularly regarding preoperative spinal canal dimensions and lateral recess depth, is a valuable contribution to clinical decision-making. The emphasis on the unpredictability of outcomes in patients with severe lateral recess stenosis and the potential need for staged procedures highlights a crucial consideration for spine surgeons.
However, one area that could benefit from further exploration is the long-term stability of indirect decompression compared to direct decompression, especially concerning adjacent segment disease and fusion longevity. Additionally, a deeper comparison of OLIF and LLIF in terms of specific complications and recovery trajectories would provide even greater clinical relevance.
Overall, this editorial offers a comprehensive and well-referenced synthesis of the current literature on indirect decompression. It serves as a useful guide for surgeons considering minimally invasive approaches while remaining cautious about their limitations."
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M Behrens KM, Elgafy H. Factors affecting outcomes of indirect decompression after oblique and lateral lumbar interbody fusions. World J Orthop 2025; 16(3): 100772 [PMID: 40124722 DOI: 10.5312/wjo.v16.i3.100772]
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22
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"The clinical significance of this study lies in its innovative approach to predicting colorectal polyp recurrence using machine learning (ML), specifically the eXtreme Gradient Boosting (XGBoost) model. Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, largely preventable through early detection and effective management of precancerous polyps. Endoscopic mucosal resection (EMR) is widely utilized for the removal of colorectal polyps, yet it carries a considerable risk of recurrence, highlighting the need for accurate predictive tools to guide postoperative surveillance.
This study identifies critical independent risk factors for polyp recurrence one year post-EMR, such as age, family history, smoking habits, diarrhea, Helicobacter pylori infection, polyp size, number of polyps, and hazard classification. By leveraging ML algorithms, particularly XGBoost, the researchers have developed a model with superior predictive performance, evidenced by high Area Under the Curve (AUC) values exceeding 0.90 across multiple validation cohorts, including a prospective validation set, indicating robust predictive accuracy and clinical utility.
Clinically, the XGBoost model offers substantial advantages. Its high sensitivity, specificity, accuracy, precision, and F1 scores suggest that it effectively stratifies patients based on recurrence risk. Such a model significantly enhances personalized patient management by informing more accurate follow-up intervals, potentially improving patient outcomes through timely interventions and reducing unnecessary colonoscopies in low-risk individuals.
Additionally, the authors' development of an accessible online web calculator based on this predictive model further underscores its practical utility in routine clinical practice. Clinicians can conveniently input patient-specific clinical parameters to obtain immediate, individualized risk predictions, facilitating shared decision-making between physicians and patients.
Decision Curve Analysis further underscores the practical value of this tool, demonstrating that using the XGBoost model provides superior clinical net benefit compared to standard follow-up strategies. This methodical approach not only advances clinical decision-making but also optimizes healthcare resources by prioritizing surveillance for those most at risk.
Finally, the interpretability of the model via SHapley Additive exPlanations (SHAP) analysis significantly mitigates concerns about the "black box" nature commonly associated with ML models, thus increasing clinician trust and acceptability.
In conclusion, this ML-based predictive model represents a critical advancement in clinical gastroenterology, providing robust, data-driven support for clinicians in making individualized recommendations for colorectal polyp surveillance and potentially reducing colorectal cancer incidence through targeted early intervention."
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Huang TF, Luo C, Guo LB, Liu HZ, Li JT, Lin QZ, Fan RL, Zhou WP, Li JD, Lin KC, Tang SC, Zeng YY. Preoperative prediction of textbook outcome in intrahepatic cholangiocarcinoma by interpretable machine learning: A multicenter cohort study. World J Gastroenterol 2025; 31(11): 100911 [PMID: 40124276 DOI: 10.3748/wjg.v31.i11.100911]
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23
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"The author has shown that knocking out SERPINB5 not only inhibits the proliferation and metastasis of cancer cells but also suppresses tumor growth in xenograft mice, effectively reducing tumor progression. This suggests that SERPINB5 could potentially serve as an important target for tumor treatment. We sincerely appreciate the author's dedication and hard work. The quality of this article is truly outstanding, and we eagerly look forward to your next research contribution."
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Meng ZS, Hu JT, Wu H, Li BK. Inhibition of the SERPINB5/HSP90AA1 axis restrains the proliferation and invasion of rectal cancer. World J Gastroenterol 2025; 31(11): 103412 [PMID: 40124262 DOI: 10.3748/wjg.v31.i11.103412]
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24
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"This study provides valuable data specifically focused on endoscopic resection (ER) of esophageal GISTs. Thorough evaluation of the ER technique, complications, and resection margin status enhances our understanding of ER safety and effectiveness. Furthermore, the study presented a relatively large case series of 32 patients, which increases the statistical reliability of the findings for esophageal GIST research. By presenting long-term follow-up results, it assessed the long-term prognosis after ER and suggested potential benefits for future treatment strategy development."
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Xu EP, Qi ZP, Zhang JW, Li B, Ren Z, Cai MY, Cai SL, Lv ZT, Chen ZH, Liu JY, Zhong YS, Zhou PH, Shi Q. Endoscopic treatment outcome of oesophageal gastrointestinal stromal tumours. World J Gastroenterol 2025; 31(10): 102393 [PMID: 40093666 DOI: 10.3748/wjg.v31.i10.102393]
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25
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"We greatly appreciate the authors and their team for their in-depth study on treatment strategies for rectal neuroendocrine neoplasms (R-NENs). This retrospective analysis compares the efficacy of endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) in the treatment of R-NENs, demonstrating the superior R0 resection rate of EFTR while maintaining comparable short-term safety with ESD. This study provides critical clinical evidence supporting the use of EFTR in R-NENs and contributes to the refinement of function-preserving surgical approaches. However, we would like to offer some constructive suggestions to enhance the clinical applicability and long-term evaluation of this study.
First, some terminology and definitions in the study are somewhat ambiguous, which may affect the interpretability of the results. For instance, the study mentions that some patients had "severe comorbidities" but does not specify the types of comorbidities or the inclusion/exclusion criteria applied. Certain comorbidities, such as diabetes or chronic kidney disease, may impact postoperative healing, and failing to differentiate them could introduce confounding among patients with varying risk profiles. Additionally, the description of lesion morphology is inherently subjective, and the study does not clarify whether standardized imaging assessments, such as endoscopic ultrasound (EUS), were used to measure lesion size and invasion depth. Inconsistencies in preoperative evaluation criteria could lead to bias in treatment selection. For example, was EFTR preferentially chosen for lesions with specific morphological characteristics? Future studies should adopt more detailed imaging assessment criteria and pathological grading methods to improve reproducibility and the interpretability of results.
Second, the study does not assess the impact of the learning curve for EFTR and ESD on surgical outcomes. As a relatively novel technique, EFTR may require a longer period of experience accumulation to achieve stable performance. The study does not clarify whether operator experience was comparable between the EFTR and ESD groups or whether surgical success rates varied with increasing experience. If EFTR procedures were performed by highly experienced endoscopists while ESD procedures involved a broader range of operators, the results could be biased in favor of EFTR. Additionally, since EFTR has a steeper learning curve, factors such as procedure time and complication rates may decrease with increased experience, but the study does not conduct a dynamic analysis of these trends. Future studies should incorporate learning curve analyses to evaluate the influence of experience on surgical outcomes, ensuring a fair comparison between the two techniques.
Furthermore, EFTR may cause greater bowel wall injury than ESD, potentially affecting postoperative bowel function, yet this study focuses primarily on R0 resection rates and short-term complications without assessing long-term functional outcomes. As a full-thickness resection technique, EFTR may alter rectal compliance, bowel movement frequency, and gut motility. However, the study does not provide data on postoperative bowel function changes, alterations in defecation patterns, bloating, or incontinence. If EFTR improves R0 resection rates but increases the risk of postoperative functional impairment, its clinical utility must be considered more cautiously. Future research should incorporate patient-reported outcomes (PROs) and quality of life (QoL) assessments and include long-term functional evaluations such as anorectal manometry and bowel dysfunction scoring to comprehensively assess the impact of EFTR on patient prognosis."
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Zhang XL, Jiang YY, Chang YY, Sun YL, Zhou Y, Wang YH, Dou XT, Guo HM, Ling TS. Endoscopic full-thickness resection: A definitive solution for local complete resection of small rectal neuroendocrine neoplasms. World J Gastroenterol 2025; 31(10): 100444 [PMID: 40093679 DOI: 10.3748/wjg.v31.i10.100444]
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"This is a well-constructed and well-written review, which gives readers with a general bioscience background updated information about the stem cell application in liver diseases (fatty liver diseases and steatohepatitis). The language is fluent, and the references are up to date. It will be easier for readers to understand the concepts if the authors provide a table to compare the 2D model with the 3D model. It will be helpful to include the abbreviation for each key word. "
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Silva B, Bragança J. Induced pluripotent stem cell-derived mesenchymal stem cells for modeling and treating metabolic associated fatty liver disease and metabolic associated steatohepatitis: Challenges and opportunities. World J Stem Cells 2025; 17(2): 99331 [PMID: 40061260 DOI: 10.4252/wjsc.v17.i2.99331]
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"The authors should provide adequate legends for each figure. Some parts of the paper are just a listing of facts and are poorly organized or discussed. The table in the paper is well organized and suited. A table to compare the pros and cons of different kinds of stem cells for muscle atrophy therapy will be helpful."
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Wang YJ, Chen ZH, Shen YT, Wang KX, Han YM, Zhang C, Yang XM, Chen BQ. Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy. World J Stem Cells 2025; 17(2): 98693 [PMID: 40061264 DOI: 10.4252/wjsc.v17.i2.98693]
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"Stem Cell Therapy: A New Hope for Patients with Skeletal Muscle Atrophy?
Skeletal muscle atrophy refers to the reduction or loss of muscle fibers due to nutritional deficiencies or diseases, leading to a decline in muscle mass. Current studies indicate that skeletal muscle atrophy is closely associated with an imbalance between protein synthesis and degradation, driven by multiple factors such as inflammation, oxidative stress, autophagy, and apoptosis [1-3]. Due to the complexity of its molecular mechanisms, effective therapeutic strategies are lacking, and traditional approaches like rehabilitation training and pharmacological interventions show limited efficacy. Therefore, exploring more effective treatments is imperative. Stem cell therapy, with its unique regenerative potential and immunomodulatory properties, offers a promising avenue for treating this condition.
In the current issue of the World Journal of Stem Cells, Ying-Jie Wang and colleagues published a review titled "Stem Cell Therapy: A Promising Therapeutic Approach for Skeletal Muscle Atrophy." The article summarizes the molecular mechanisms of muscle atrophy and highlights the applications of mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and their derivatives (e.g., exosomes) in treating skeletal muscle atrophy. These stem cells exert therapeutic effects by modulating inflammation, promoting angiogenesis, suppressing oxidative stress, and facilitating muscle regeneration. The authors also address challenges in clinical translation, including immune rejection, tumorigenic risks, inefficient stem cell homing, and the absence of standardized protocols. Despite these hurdles, the review expresses optimism about the future of stem cell therapy, particularly emphasizing the superior potential of stem cell-derived acellular therapies (e.g., exosomes) over traditional cell transplantation.
We maintain a cautiously optimistic view regarding the prospects of stem cell therapy for skeletal muscle atrophy. While stem cell-based approaches, especially MSC- and exosome-based strategies, demonstrate promising safety and efficacy [4, 5], several issues must be resolved. These include addressing heterogeneity in stem cell sources, ensuring long-term safety, and establishing standardized protocols for clinical translation. Although iPSCs circumvent ethical concerns, their differentiation and purification techniques require optimization, and potential genetic mutations remain a concern. Exosomes, as acellular therapeutics, may reduce immune reactions; however, challenges in large-scale production and quality control persist.
Therapeutic Potential of Stem Cells
Stem cell therapy exhibits multidimensional potential in treating muscle atrophy. First, its mechanisms are highly synergistic: MSCs and iPSCs improve the muscle microenvironment by regulating inflammatory cytokines (e.g., suppressing IL-6 and TNF-α), promoting angiogenesis, inhibiting oxidative stress, and enhancing autophagy. Exosomes further amplify therapeutic effects by delivering functional miRNAs (e.g., miR-132-3p/FoxO3 axis) to delay protein degradation and stimulate regeneration [4, 6]. Second, exosomes as acellular carriers broaden clinical applicability: MSC-derived exosomes (e.g., hUC-MSC-Exos, ADSC-Exos) avoid immune rejection and tumorigenic risks associated with live cell transplantation. Their high biocompatibility and cargo of bioactive molecules (e.g., circHIPK3, AMPK/ULK1 regulators) enable targeted intervention in diabetes- or neuropathy-related atrophy, positioning them as pivotal tools for clinical translation [6, 7]. Third, iPSCs hold exceptional promise for personalized medicine. Their ability to differentiate into myogenic progenitor cells (MPCs) or motor neurons facilitates the reconstruction of neuromuscular junctions, offering precise repair for genetic atrophy (e.g., facioscapulohumeral muscular dystrophy, FSHD). While autologous iPSCs mitigate immune rejection, clinical application demands improved differentiation efficiency and safety [8, 9].
Current Challenges and Solutions
Clinical translation of stem cell therapy faces multiple challenges requiring innovative solutions. First, heterogeneity and standardization: MSC efficacy varies with donor age, tissue source (e.g., bone marrow, adipose, umbilical cord), and culture conditions [10]. Establishing unified quality control standards—via surface marker screening, secretome profiling, and single-cell sequencing—is critical to identify functional subpopulations and enable precision manufacturing [11]. Second, genetic instability and differentiation inefficiency hinder iPSC applications: reprogramming-induced mutations and inconsistent differentiation protocols (transgene-dependent or -independent) limit reliability [12]. Integrating non-integrative methods (e.g., mRNA reprogramming) and 3D organoid culture systems may optimize differentiation pathways [8]. Third, exosome scalability and targeting: natural exosomes suffer from low bioactive content and short half-lives. Engineering strategies (e.g., ligand modification or drug loading) can enhance tissue-specific delivery [13, 14], while microfluidic-nanocarrier systems may resolve production bottlenecks. Finally, accelerating clinical translation: preclinical studies predominantly rely on animal models; multicenter trials are needed to validate long-term safety (e.g., tumorigenicity, immune tolerance) [15, 16]. Combining stem cell therapy with anti-inflammatory agents (e.g., IL-1β inhibitors), rehabilitation, or gene editing (e.g., CRISPR-Cas9) may synergistically enhance efficacy [17, 18].
Future Directions
Future research should prioritize interdisciplinary integration and precision strategies. First, mechanistic insights: single-cell and spatial transcriptomics can unravel dynamic interactions between stem cells and the muscle microenvironment (e.g., satellite cells, macrophages), identifying key regulatory nodes (e.g., Wnt/β-catenin, PI3K/Akt pathways) [3, 19]. Second, biomaterial innovations: smart hydrogels or electroconductive scaffolds combined with localized stem cell/exosome delivery systems could enhance homing efficiency and functional persistence [20, 21]. Third, personalized approaches: tailored therapies based on disease-specific etiologies (e.g., ALS, diabetic atrophy) and molecular subtypes (e.g., inflammatory signatures) are essential. For instance, AMPK-activated umbilical cord MSCs may rectify metabolic dysregulation in diabetic atrophy [22, 23]. Lastly, ethical and regulatory frameworks: international guidelines must standardize stem cell therapies and clarify regulatory classifications (e.g., exosomes as "drugs") to accelerate clinical translation.
Stem cell therapy for skeletal muscle atrophy is transitioning from bench to bedside, yet critical hurdles—standardization, safety, and efficacy validation—remain. Integrating multidisciplinary technologies (e.g., synthetic biology, bioinformatics) and advancing translational research will bridge the gap between "laboratory breakthroughs" and "patient benefits."
References:
1. Zhang, H., et al., Oxidative stress: Roles in skeletal muscle atrophy. Biochem Pharmacol, 2023. 214: p. 115664.
2. Ji, Y., et al., Inflammation: Roles in Skeletal Muscle Atrophy. Antioxidants (Basel), 2022. 11(9).
3. Liang, W., et al., Epigenetic control of skeletal muscle atrophy. Cell Mol Biol Lett, 2024. 29(1): p. 99.
4. Huang, Z., et al., Skeletal Muscle Atrophy Was Alleviated by Salidroside Through Suppressing Oxidative Stress and Inflammation During Denervation. Front Pharmacol, 2019. 10: p. 997.
5. Song, J., et al., Mesenchymal stromal cells ameliorate diabetes-induced muscle atrophy through exosomes by enhancing AMPK/ULK1-mediated autophagy. J Cachexia Sarcopenia Muscle, 2023. 14(2): p. 915-929.
6. Archacka, K., et al., Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration. Stem Cell Res Ther, 2021. 12(1): p. 448.
7. Leong, J., et al., Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair. ACS Nano, 2020. 14(5): p. 5298-5313.
8. Kim, H., et al., Genomic Safe Harbor Expression of PAX7 for the Generation of Engraftable Myogenic Progenitors. Stem Cell Reports, 2021. 16(1): p. 10-19.
9. Azzag, K., et al., Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice. NPJ Regen Med, 2022. 7(1): p. 43.
10. Li, J., et al., The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther, 2023. 14(1): p. 381.
11. Oguma, Y., et al., Single-cell RNA sequencing reveals different signatures of mesenchymal stromal cell pluripotent-like and multipotent populations. iScience, 2022. 25(11): p. 105395.
12. Shamsian, A., et al., Cancer cells as a new source of induced pluripotent stem cells. Stem Cell Res Ther, 2022. 13(1): p. 459.
13. Rezaie, J., et al., Mesenchymal stem cells derived extracellular vesicles: A promising nanomedicine for drug delivery system. Biochem Pharmacol, 2022. 203: p. 115167.
14. Yang, Q., et al., Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury. Bioact Mater, 2023. 26: p. 194-215.
15. Drela, K., et al., Experimental Strategies of Mesenchymal Stem Cell Propagation: Adverse Events and Potential Risk of Functional Changes. Stem Cells Int, 2019. 2019: p. 7012692.
16. Deuse, T., et al., Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol, 2019. 37(3): p. 252-258.
17. Iyer, S.R., et al., Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury. Am J Sports Med, 2020. 48(9): p. 2277-2286.
18. Chang, M., et al., Duchenne muscular dystrophy: pathogenesis and promising therapies. J Neurol, 2023. 270(8): p. 3733-3749.
19. Sartori, R., V. Romanello, and M. Sandri, Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun, 2021. 12(1): p. 330.
20. Luo, W., et al., Biomaterials-Based Technologies in Skeletal Muscle Tissue Engineering. Adv Healthc Mater, 2024. 13(18): p. e2304196.
21. Shan, Y., et al., Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges. Signal Transduct Target Ther, 2024. 9(1): p. 242.
22. Shen, Y., et al., Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies. Front Endocrinol (Lausanne), 2022. 13: p. 917113.
23. Yeo, C.J.J., E.F. Tizzano, and B.T. Darras, Challenges and opportunities in spinal muscular atrophy therapeutics. Lancet Neurol, 2024. 23(2): p. 205-218."
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Wang YJ, Chen ZH, Shen YT, Wang KX, Han YM, Zhang C, Yang XM, Chen BQ. Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy. World J Stem Cells 2025; 17(2): 98693 [PMID: 40061264 DOI: 10.4252/wjsc.v17.i2.98693]
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"Top-down therapy for Crohn's disease (CD) involves starting with the most potent medications, such as biologics and immunomodulators, immediately after early diagnosis. This strategy may lead to rapid induction of remission, promotion of mucosal healing, prevention of complications, and reduced need for surgery. However, the background factors influencing this top-down therapy have not been sufficiently examined.
A recent report on a Japanese cohort found that factors significantly associated with the recent top-down treatment approach were male gender, perianal lesions, no immunomodulators, and anti-tumor necrosis factor therapy. (Miyoshi J, Yoon A, Matsuura M, Hisamatsu T. Real-world use of biologics during the first year of treatment for newly diagnosed Crohn's disease in Japan: a claims analysis from 2010 to 2021. Intest Res. 2025 [PMID: 39848334 DOI: 10.5217/ir.2024.00082])
Top-down therapy for CD should be considered case-by-case, weighing potential benefits against risks and costs. As the authors suggest, identifying patients with a high genetic predisposition for CD may help predict their response to medications, the risk of side effects, and the cost-effectiveness. Further investigation in this area is desirable.
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Fan YH, Wang MW, Gao YN, Li WM, Jiao Y. Genetic and environmental factors influencing Crohn’s disease. World J Gastrointest Surg 2025; 17(3): 98526 [PMID: 40162410 DOI: 10.4240/wjgs.v17.i3.98526]
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"Suggested Title:From Weakness to Wellness: The Role of Stem Cells in Muscle Atrophy Recovery
A. Clarity and Conciseness
• Some sections, particularly those on molecular mechanisms, are dense and could benefit from simplification or restructuring.
B. Novelty and Critical Analysis
• The review summarizes existing knowledge well but lacks critical analysis of conflicting findings.
• Consider discussing limitations of existing studies, such as sample size issues in preclinical models, potential biases, and reproducibility concerns.
• More emphasis could be placed on recent breakthroughs or innovative approaches in stem cell therapy, particularly in clinical trials.
C. Clinical Relevance and Future Directions
• The discussion of clinical applications is somewhat broad. It would be beneficial to include:
o Specific ongoing clinical trials (if available).
o A comparison of animal models vs. human studies to highlight translational challenges.
• The challenges section should offer potential solutions or strategies to overcome issues like immune rejection, tumorigenicity, and ethical concerns.
D. Specific Suggestions for Improvement
• Introduction: Emphasize the gap in current treatments that stem cell therapy aims to address.
• Current Treatment Strategies: Compare rehabilitation and pharmacological treatments with stem cell therapy in terms of: Efficacy, Limitations, Side effects.
• Exosome Therapy: This part is well-detailed, but it could benefit from a discussion on manufacturing challenges and standardization issues for clinical application.
• Conclusion: Strengthen the future perspectives by suggesting research directions or potential improvements in stem cell delivery methods."
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Wang YJ, Chen ZH, Shen YT, Wang KX, Han YM, Zhang C, Yang XM, Chen BQ. Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy. World J Stem Cells 2025; 17(2): 98693 [PMID: 40061264 DOI: 10.4252/wjsc.v17.i2.98693]
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"This review presents a comprehensive analysis of the role of Traditional Chinese Medicine (TCM) in the treatment of chronic atrophic gastritis (CAG), highlighting its multi-targeted therapeutic effects, including gastric mucosal protection, modulation of inflammatory responses, and improvement of microcirculation. The discussion is well-supported by clinical studies and meta-analyses, underscoring the potential benefits of specific herbal compounds such as berberine, morroniside, and notoginsenoside R1. However, the review also acknowledges a key challenge—the lack of standardized research methodologies and evaluation criteria, which limits the broader clinical application of TCM. While the evidence presented suggests promising therapeutic effects, future research should focus on large-scale randomized controlled trials to further validate these findings and establish consistent guidelines for integrating TCM into mainstream gastroenterology practice. Additionally, a more detailed discussion on potential interactions between TCM and conventional Western therapies would strengthen the clinical relevance of this review. Overall, this article makes a valuable contribution to the understanding of CAG management and provides a strong foundation for future research in this field."
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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31(9): 102053 [PMID: 40061592 DOI: 10.3748/wjg.v31.i9.102053]
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"The study by Real Martinez et al. provides valuable insights into the role of circulating myokines such as irisin and FGF21 in MASLD, particularly their association with severe steatosis and advanced liver fibrosis. However, the absence of a relationship between skeletal muscle alterations (SMAs) and liver fibrosis stages raises intriguing questions. Could the lack of association be attributed to the heterogeneity of the cohort, or might it suggest that SMAs play a more indirect role in MASLD progression? Additionally, how might other metabolic or inflammatory pathways, not directly evaluated in this study, influence the interplay between muscle health and liver disease? Further studies exploring these aspects, especially in longitudinal designs or larger cohorts, would be invaluable in clarifying these relationships and their implications for clinical practice."
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Real Martinez Y, Fernandez-Garcia CE, Fuertes-Yebra E, Calvo Soto M, Berlana A, Barrios V, Caldas M, Gonzalez Moreno L, Garcia-Buey L, Molina Baena B, Sampedro-Nuñez M, Beceiro MJ, García-Monzón C, González-Rodríguez Á. Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease: A cross-sectional study. World J Gastroenterol 2025; 31(7): 100039 [PMID: 39991673 DOI: 10.3748/wjg.v31.i7.100039]
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"I congratulate the authors for the publication of their write up. It is well written with practical points. The information on greater likelihood of antibody generation with premixed insulins was new to me, although I believe it would have been partly due to the highly prevalent use of this form of insulin.
I would like the authors to understand this point as well while promoting the advantages of the newer insulins. In the international guidelines, at diagnosis of diabetes if the blood glucose levels are above 300 mg/dl and/or glycosylated hemoglobin level is more than 10 %, it is suggested to start the patient on insulin to reduce the glucotoxicity. Once the blood glucose levels reduce, say after 2-3 weeks, the patient may be switched to oral anti-diabetic agents. Such a guideline recommended practice is regularly followed in developing countries such as ours. In such a situation I have observed that the acceptance rate of premixed insulin which involves two pricks, is a lot better than that of multiple short acting insulin doses along with basal insulin. Since the duration of premixed insulin therapy in this context is short, the possible side effects of anti-insulin antibody generation as well as lipodystrophy are less likely. "
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Xia Y, Hu Y, Ma JH. Premixed insulin: Advantages, disadvantages, and future. World J Diabetes 2025; 16(3): 102526 [PMID: 40093285 DOI: 10.4239/wjd.v16.i3.102526]
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"This study presents an evaluation of a novel contrast-enhanced catheter with a chamfered tip. Achieving selective biliary cannulation is one of the most challenging endoscopic maneuver. We congratulate the authors on demonstrating in this paper that a novel device granted higher rates of biliary cannulation when retrospectively compared to a standard sphincterotome.
However, a few points warrant further discussion:
1. Generalizability: As a single-center retrospective study, the external validity of these findings could be enhanced with multicenter randomized trials. Variations in patient populations, procedural techniques, and institutional expertise might influence outcomes.
2. Non-expert outcomes: The results indicate a lack of significant improvement in outcomes among non-experts or trainees using the novel catheter. This suggests the device's utility may be contingent on the operator's skill. We also noticed that the expert performed procedure percentage was slightly higher (57% vs 50%) in the novel cathether group, and, although not
statistically significant, this could explain the lower use of advanced or rescue cannulation techniques.
3. Adverse Events (AEs): While the overall AE rates were low and comparable between groups, the trend toward fewer cases of PEP with the novel catheter merits closer scrutiny in larger cohorts as this could be an advantage in patients at risk for PEP. On the other hand, the non-statistically significant difference between the two groups in PEP incidence suggests us that the device used to achieve initial selective cannulation maybe isn’t that relevant in increasing PEP risk or incidence, but this should be confirmed in larger studies.
4. Cost-effectiveness: Although not discussed, evaluating the cost implications of adopting this catheter, including potential savings from reduced reliance on rescue techniques and decreased procedural times, would be beneficial for broader clinical adoption. We should also think of the negative aspects: for example, like stone clearance, achieving cannulation with a catheter would require a subsequent switch to a sphincterotome, increasing procedure length and costs, as you would be using two devices instead of one to achieve cannulation.
5. Papilla characteristics: we noticed that in the baseline characteristics intradiverticular papillas and oral oriented papillas were less represented in the catheter group. These types of papilla could benefit of the angling capabilities of a sphincterotome, so this could be a bias that needs to be furthermore cleared. In our experience the angling capabilities of a sphincterotome are crucial in achieving bile duct cannulation in difficult situations.
6. Malignant disease: we do know that malignant diseases (e.g. pancreatic cancer) affecting the ampullar area negatively affect rates of cannulation and increase the need for rescue or advanced techniques of cannulation. This point could have been furthermore discussed by making a distinction between cannulation failures in the setting of benign vs. malignant disease in both groups.
In conclusion, this study gives us valuable insights into advancing ERCP outcomes through innovative device design. We must experiment with more designs to compare results and finally choose the best device for cannulation in unexpected and difficult anatomies."
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Kaneko T, Kida M, Kurosu T, Kitahara G, Koyama S, Nomura N, Tahara K, Kusano C. Outcomes of bile duct cannulation using a novel contrast-enhanced catheter: A single-center, retrospective cohort study. World J Gastrointest Endosc 2025; 17(1): 97840 [PMID: 39850917 DOI: 10.4253/wjge.v17.i1.97840]
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"As a colorectal surgeon interested in colorectal cancer and the microbiome, I found this study highly relevant. The authors effectively highlight differences in mucosa-associated colonic microbiota between colorectal cancer (CRC) and non-CRC patients in Indonesia.
A key strength is the focus on mucosal rather than fecal microbiota, providing a clearer picture of the tumor microenvironment. The use of 16S rRNA sequencing with Oxford Nanopore Technologies enables detailed bacterial diversity analysis at the genus and species levels.
The study confirms the increased presence of Fusobacterium nucleatum and Bacteroides fragilis in CRC patients, supporting the link between microbial dysbiosis and carcinogenesis. The diagnostic potential of these bacterial markers is particularly noteworthy.
Further research with larger sample sizes and functional analyses, such as metagenomics or metabolomics, would enhance understanding of microbiota’s role in CRC. Additionally, while this study offers important insights for Asia, global research is needed to assess regional differences and their impact on CRC diagnostics and treatment."
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Darnindro N, Abdullah M, Sukartini N, Rumende CM, Pitarini A, Nursyirwan SA, Fauzi A, Makmun D, Nelwan EJ, Shatri H, Rinaldi I, Tanadi C. Differences in diversity and composition of mucosa-associated colonic microbiota in colorectal cancer and non-colorectal cancer in Indonesia. World J Gastroenterol 2025; 31(7): 100051 [PMID: 39991683 DOI: 10.3748/wjg.v31.i7.100051]
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"The manuscript is very clinically relevant. Here's a suggestion. Authors should provide the data on patients undergoing colonoscopy prior to capsule endoscopy examination. The retention rate of capsule endoscopy at 72 hours was 42.2%, which is still relatively high.It helps to reduce capsule retention in the colon after colonoscopy examination."
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O'Hara FJ, Costigan C, McNamara D. Extended 72-hour patency capsule protocol improves functional patency rates in high-risk patients undergoing capsule endoscopy. World J Gastrointest Endosc 2024; 16(12): 661-667 [PMID: 39735390 DOI: 10.4253/wjge.v16.i12.661]
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"This case report highlights the importance of en-bloc resection without fragmentation during endoscopic procedures and the challenges of endoscopic treatment for anal canal cancer. Traditionally, anal lesions have been primarily managed by surgeons, but ESD-related technique is performed mainly by the gastrointestinal endoscopists of internal medicine. Future collaboration between internal medicine and surgery departments will be crucial.
Surgery for anal cancer can significantly decrease patients' quality of life, which is why the authors' dedication to endoscopic treatment and follow-up is commendable. Anal canal cancer is rare, and it will be essential to determine which cases are suitable for endoscopic therapy in the future.
With the increasing prevalence of inflammatory bowel diseases in Asian regions, a rise in anal cancer cases associated with conditions like Crohn's disease is anticipated. Further case reports in this field are desirable.
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Kinoshita M, Maruyama T, Hike S, Hirosuna T, Kainuma S, Kinoshita K, Nakano A, Ohira G, Uesato M, Matsubara H. Complete resection of recurrent anal canal cancer using endoscopic submucosal dissection and transanal resection: A case report. World J Gastrointest Endosc 2025; 17(1): 101119 [PMID: 39850911 DOI: 10.4253/wjge.v17.i1.101119]
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"This is an excellent and insightful article. The authors have provided a comprehensive overview of the most impactful studies in the field of gastrointestinal endoscopy. It has greatly enhanced my understanding of the current research landscape and has inspired me to define more focused and meaningful directions for my own research in this area.
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Sui J, Luo JS, Xiong C, Tang CY, Peng YH, Zhou R. Bibliometric analysis on the top one hundred cited studies on gastrointestinal endoscopy. World J Gastrointest Endosc 2025; 17(1): 100219 [PMID: 39850908 DOI: 10.4253/wjge.v17.i1.100219]
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"This paper examines the differences in proficiency of AI tools for IBD patients and is considered a critical study for the inevitable future utilization of large language models in healthcare. However, it is merely a comparative study of large language models, and it remains unclear whether it contributes to improving IBD patients' literacy. Regarding patient education, Crohn's disease and ulcerative colitis belong to different categories, making it challenging to evaluate IBD as a whole comprehensively. Separate evaluations for ulcerative colitis and Crohn's disease patients would be preferable.
Furthermore, large language models alone are insufficient for shared decision-making that considers patients' social backgrounds for treatment selection, including biological agents (especially for Crohn's disease). Simply improving knowledge on several items through large language models may not be enough for clinical application. Future evaluations using large language models should address these points.
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Zhang Y, Wan XH, Kong QZ, Liu H, Liu J, Guo J, Yang XY, Zuo XL, Li YQ. Evaluating large language models as patient education tools for inflammatory bowel disease: A comparative study. World J Gastroenterol 2025; 31(6): 102090 [PMID: 39958450 DOI: 10.3748/wjg.v31.i6.102090]
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"Dear editor,
this is a review that summarizes the most recent evidence focused on the safety of the peroral endoscopic myotomy (POEM).
The manuscript is well written. However, I found some inaccuracies in the background.
The style, language and grammar are appropriate.
Since there are no figures or tables in the paper I answered no to the dedicated questions.
Although the safety of POEM is well explained, superficial informations were provided on the precision and the post-procedural management. Therefore, I would focus the article mainly on the safety, explaining better the post-procedural management."
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Christodoulidis G, Tsagkidou K, Koumarelas KE, Kouliou MN. Advances and challenges in peroral endoscopic myotomy: Safety, precision, and post-procedure management. World J Gastroenterol 2025; 31(5): 97574 [PMID: 39926218 DOI: 10.3748/wjg.v31.i5.97574]
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"This case is an extensively worked-up and well-written report. Best regards to the team. Stroke is not a clear-cut biophysics in neurology, with challenges in the clinical-radiological correlation encountered so often in clinical practice. As in this case, the work-up in SPECT could not convincingly determine theexact biomechanism of the clinical phenomena. However, it opened up information for future scopes of research into lacunar strokes. DSA, functional MRI, and Perfusion mismatch studies can also help in this type of situations. In contrast, the treatment is fairly less complicated in lacunar stroke.
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Tsai YH, Chen YH, Chao TC, Lin LF, Chang ST. New type of lacunar stroke presenting in brain perfusion images: A case report. World J Neurol 2024; 10(1): 98672 [DOI: 10.5316/wjn.v10.i1.98672]
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"Fu et al.'s recent study published in the World Journal of Psychiatry examines a complex connection between parenting stress, various family parenting styles, and the behavioral and emotional challenges that children experience. This study highlights the need for appropriate emotional management during the preschool years, demonstrating how differences in parental stress may have a significant impact on children's early emotional health. The analytical strength of this study is really impressive. The authors use structural equation modeling (SEM) to give a detailed examination of how different parenting styles mediate the relationships between these factors. Moreover, comprehensive questionnaire data collection contributes to a better understanding of family dynamics in a variety of environments.
According to the findings, parents report high levels of stress, which suggests that they face constant challenges. The study discovers a link between "hostile/coercive" parenting and problem behaviors in children, revealing the deleterious effects of negative strategies for parenting. This conclusion is consistent with previous research, which emphasizes the importance of understanding how inadequate parenting may lead to behavioral problems in children. Conversely, the negative connection with "supportive/engaged" parenting implies that positive approaches might provide large protective benefits, emphasizing the importance of specific treatments.
Besides, this study emphasizes how parenting styles serve as mediators in the relationship between parental stress and children's emotional health. The data show a 28.99% mediation impact, indicating that how parents handle stress influences the behaviors of their kids through their strategies for parenting. This finding not only strengthens the foundation for designing personalized therapies, but it also emphasizes the important need to improve parental practices. Also, the study points out the importance of providing parents with evidence-based strategies for managing their emotional health, with a focus on both parental and child well-being.
The study aims to establish a caring environment for preschoolers by giving practical ways to reduce stress and promoting positive parenting behaviors. It focuses on the broader impacts of various parenting styles, implying that investing in parental support systems is important for enhancing children's mental health and promoting total family happiness. This perspective is consistent with current trends in mental health initiatives and requires a comprehensive effort to address families' emotional needs, supplying the framework for future research in this important area.
Although Fu et al.'s work contributes significantly to our understanding of the link between parental stress and children's behavior, future research might profit from using a longitudinal strategy. Such an approach might allow researchers to investigate the changing dynamics of parental stress and child behavior over time, leading to a more comprehensive explanation of their causal relationships. Longitudinal studies may track how changes in parental stress affect the growth path of children's behavior by following the same set of participants at different points in time. This method not only gives a more in-depth understanding of these dynamics, but it also identifies potential mediators and moderators, offering light on the underlying reasons of the connections. Finally, this strategy may help us understand how the family environment affects children's developmental achievement.
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Fu ZW, Li YJ, Yu R, Guo RQ, Gao LX, Zhao SX. Relationship between parenting stress and behavioral and emotional problems in preschool children: A mediation effect analysis. World J Psychiatry 2025; 15(1): 100068 [PMID: 39831023 DOI: 10.5498/wjp.v15.i1.100068]
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43
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"There is a need for non-invasive methods of evaluating mucosal healing in the small bowel. This study applies the principles of radiomics using small bowel CTE to develop a predictive normogram capable of predicting mucosal healing. Despite the study's stated limitations, it adds to the current literature, and extends the emerging field of radiomics in Crohn's disease."
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Ding H, Fang YY, Fan WJ, Zhang CY, Wang SF, Hu J, Han W, Mei Q. Computed tomography enterography-based radiomics for assessing mucosal healing in patients with small bowel Crohn's disease. World J Gastroenterol 2025; 31(3): 102283 [PMID: 39839900 DOI: 10.3748/wjg.v31.i3.102283]
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44
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"The article presents a strong case for the use of endoscopic ultrasound-guided gastroenterostomy (EUS-GE) in managing gastric outlet obstruction (GOO). However, a few points could be clarified to strengthen its conclusions. Specifically, it would be helpful to elaborate on the inclusion or exclusion criteria for patient selection, as well as provide data on long-term outcomes like stent patency and recurrence rates. Additionally, discussing the learning curve associated with EUS-GE and the level of expertise required for its successful implementation would offer valuable insight for broader clinical adoption."
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Jagielski M. Endoscopic ultrasound guided-gastroenterostomy is the best choice in the treatment of gastric outlet obstruction. World J Gastrointest Endosc 2024; 16(12): 691-693 [PMID: 39735392 DOI: 10.4253/wjge.v16.i12.691]
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45
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"The manuscript is very interesting. Global burden of human disorders caused by parasites is high. The topic is hot in selected areas. Those areas include not only Asia or Africa, but some parts of Eastern and Central Europe. I recommend to read the article for specialists in Hepatology, Liver surgery, including liver transplantation, Epademiology and Infectious Diuseases."
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Shahid Y, Emman B, Abid S. Liver parasites: A global endemic and journey from infestation to intervention. World J Gastroenterol 2025; 31(1): 101360 [PMID: 39777245 DOI: 10.3748/wjg.v31.i1.101360]
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46
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"This editorial pointed out the connection between adipose tissue and intestinal bacteria in Crohn's disease (CD). It is an interesting paper. The authors found that Clostridium innocuum migrates to adjacent adipose tissue and remains "trapped" in the fat. As a result, immune cell migration and macrophage differentiation increase, leading to fibrosis, narrowing, and, eventually, the formation of creeping fat. Although the main cytokine release is mainly TNFα and IL-6 in adipocytes, the cytokine profile changes over time, especially in fibrosis, may be related to IL-17, and the dominant cytokines will change from IL-12 to IL-23, as previously pointed out. It is interesting to evaluate the aging adipose tissue in CD. However, it is difficult to determine the actual time of onset in patients with CD, and it is challenging to evaluate this issue. "
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Quaglio AE, Magro DO, Imbrizi M, De Oliveira EC, Di Stasi LC, Sassaki LY. Creeping fat and gut microbiota in Crohn’s disease. World J Gastroenterol 2025; 31(1): 102042 [PMID: 39777251 DOI: 10.3748/wjg.v31.i1.102042]
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47
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"The authors provide evidence supporting the efficacy of serum-free cultured human umbilical cord mesenchymal stem cells (N-hUCMSCs) in treating knee osteoarthritis (OA). However, as the results indicate that the therapeutic effects of N-hUCMSCs, serum-cultured hUCMSCs (S-hUCMSCs), and hyaluronic acid (HA) are comparable, the rationale for prioritizing N-hUCMSCs warrants further exploration, particularly in comparison to the well-established use of HA.
There are also issues with data quality and clarity
1.The study administered three injections (at 2, 4, and 6 weeks after model establishment). However, the rationale for this dosing schedule is not provided. HA dosing is not described in the manuscript.
2.The source of the N-hUCMSCs and S-hUCMSCs should be disclosed. Were these cells derived from the same donor? If not, what were the baseline characteristics of each donor (e.g., age, health status)? Such details are critical, as MSC functionality can vary significantly based on donor conditions.
3.Some results, such as those described in Figure 1 and the observation that “Uneven chondrocyte thickness, disorganized cartilage structure, and increased clefts were more pronounced in the model control group than in the blank control group,” are inappropriately placed in the methods section. These descriptions should be moved to the results section.
4. Figure 3c and 3d: Both graphs have the same y-axis label, but according to the results section, one should represent IL-6 and the other IL-1β.
Figure 4a and 4b: These panels illustrate hematoxylin-eosin (HE) staining for the model and control groups. However, the HE results for the treatment groups (N-hUCMSCs, S-hUCMSCs, and HA) are missing. Including these results would provide a clearer comparison of treatment effects.
5.Figure 4d: The manuscript mentions that “The Mankin scores were significantly lower in the experimental group than in the model control group (P < 0.05),” but this result is not adequately represented in the figure.
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Xiao KZ, Liao G, Huang GY, Huang YL, Gu RH. Efficacy of serum-free cultured human umbilical cord mesenchymal stem cells in the treatment of knee osteoarthritis in mice. World J Stem Cells 2024; 16(11): 944-955 [PMID: 39619871 DOI: 10.4252/wjsc.v16.i11.944]
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48
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"he significant impact of surgical approaches on male sexual dysfunction after rectal cancer surgery is highlighted by both this letter to the editor and the latest study by Numata et al. published in Annals of Surgery1). Damage to the autonomic nervous system during rectal cancer surgery is a major cause of sexual dysfunction, with problems such as ejaculatory dysfunction, erectile dysfunction, and sexual dysfunction commonly reported. These complications are particularly common with open surgery, and previous research has also shown that the incidence of sexual dysfunction following surgery is high.
However, advances in surgical techniques such as robotic surgery are expected to reduce these complications. The LANDMARC Study provided convincing evidence that robotic surgery significantly reduces the incidence of postoperative sexual dysfunction compared to laparoscopic surgery. The incidence of ejaculatory dysfunction at 12 months postoperatively was 25% in robotic surgery patients compared to 40.9% in laparoscopic surgery patients. The incidence of sexual dysfunction was 17.8% and 29%, respectively.
This letter to editor alos emphasized the importance of accurate surgical technique and knowledge of pelvic nerve anatomy. It also discussed the benefits of new techniques such as robotic surgery and transanal total mesorectal excision (Ta-TME), as well as the use of intraoperative pelvic nerve monitoring. These advances enhance nerve preservation, reduce complications, and improve patients' postoperative quality of life.
These findings highlight the need to adapt innovative surgical techniques in rectal cancer treatment to minimize adverse effects on sexual health while maintaining oncologic effectiveness.
1) Numata, Masakatsu, et al. "Prospective Multicenter Comprehensive Survey on Male Sexual Dysfunction following Laparoscopic, Robotic, and Transanal Approaches for Rectal Cancer (the LANDMARC Study)." Annals of Surgery: 10-1097"
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Kolokotronis T, Pantelis D. Urinary and sexual dysfunction after rectal cancer surgery: A surgical challenge. World J Gastroenterol 2024; 30(47): 5081-5085 [PMID: 39713160 DOI: 10.3748/wjg.v30.i47.5081]
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49
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"since the patient also had general anesthesia, it should be clairifed to whihc degree analgesics given for the procedure prevented the patient from experienceing severe pain
xxxx xx x x x x x x x x x x x x x x x x x x x x x x xx x x x x x xx "
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Chen KH, Kang MY, Chang YT, Huang SY, Wu YS. Enhancing postoperative pain control by surgically-initiated rectus sheath block in abdominal aortic aneurysm open repair: A case report. World J Clin Cases 2025; 13(6): 100673 [PMID: 40012827 DOI: 10.12998/wjcc.v13.i6.100673]
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50
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"The novelty of the topic is very important, suitable for fine rather than too broad content. The interpretation of statistical results needs to be rigorous, correlation does not mean causation, and the HR presented may be inaccurate. The discussion needs to be tightly focused on the results and not extend to other unwarranted conclusions."
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Chen DQ, Wu YX, Zhang YX, Yang HL, Huang HH, Lv JY, Xiao Q. Sarcopenia-associated factors and their bone mineral density levels in middle-aged and elderly male type 2 diabetes patients. World J Diabetes 2024; 15(12): 2285-2292 [PMID: 39676813 DOI: 10.4239/wjd.v15.i12.2285]
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