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1	"This prospective study rightly identifies a significant problem i.e.,preoperative ankle pain might effect the early functional outcome in patients undergoing total knee arthroplasty for primary Osteoarthritis knee.It is often overlooked but the deformity at the level of knee definitely impacts the biomechanics alignment of the entire lower limb and also at the ankle. The key finding was patients exhibited significantly lower KOOS scores and extension recovery at 3 months postoperatively, even after adjusting for demographic confounders. This reiterates the necessity for a complete lower limb assessment and managing preoperatively any hip/ankle symptoms preoperatively to optimize TKA outcomes. The methodology, protocol, grouping of patients was all good. The authors could have given a detailed radiographic alignment of the patient's lowerliimbs that were operated to substantiate the preoperative status and the results postoperatively. Even though AOFAS score, is an appropriate tool for assessing the ankle symptoms and pathologies, a detailed radiographic assessment of the ankle including ankle hind foot assessment, weight bearing alignment could have been added/ mentioned. Incorporating pre- and postoperative radiographs would have allowed the authors to better delineate whether the observed differences in KOOS and knee extension were attributable to underlying mechanical misalignment or simply symptomatic variation. A gait analysis of the patients can also be included to add objective assessment to the data. That would tell us whether the results are an outcome of any malalignment or just symptomatic variation. A longer followup would also suggest us whether the symptoms are resolving over time or still persisting." Buterin A, Vuckovic M, Spanja Prpic S, Zaharija V, Nonkovic M, Prpic T. Comparison of functional recovery of the knee following total knee arthroplasty in patients with and without ankle symptoms. World J Orthop 2025; 16(5): 106004 [DOI: 10.5312/wjo.v16.i5.106004]
2	"This study addresses the deficit of medical humanities in China’s resource-limited primary healthcare (PHC) system by systematically exploring pathways to integrate narrative medicine (NM) into grassroots care. Situated within the Healthy China 2030 policy framework, the research proposes actionable strategies for humanizing PHC through theoretical analysis and practical innovations, such as the One-Minute Patient Narrative and 11253 Family Doctor Service Model. Key contributions include: (1) revealing tensions between policy mandates and on-the-ground realities, emphasizing NM’s localization to regional disparities; (2) enhancing care efficiency via AI-mediated narrative analysis (e.g., a 25% increase in treatment adherence); and (3) offering scalable models to ensure PHC sustainability. However, three critical gaps require further exploration. First, cultural dynamics—such as patients’ traditional deference to medical authority and healthcare commercialization—demand culturally adaptive interventions (e.g., competency training for clinicians, redefining relational medicine values). Current analyses lack actionable steps to operationalize these strategies across diverse contexts. Second, sustainability challenges—including the feasibility of urban NM models in high-demand rural settings and volunteer system stability in under-resourced areas—are underexamined. Systemic inequities (e.g., funding gaps, workforce shortages) further constrain implementation. Third, while short-term metrics like patient satisfaction are prioritized, long-term systemic issues—health equity, clinician burnout, and bureaucratic barriers to PDCA (Plan-Do-Check-Act) cycles—remain unaddressed. Future studies must adopt mixed-method evaluations to bridge these gaps and enable NM’s transition from pilot projects to systemic reform. To further this agenda, this study presents a three-pillar framework. Firstly, by fostering interdisciplinary collaboration, we aim to integrate public health experts, community advocates, and policymakers. Together, they will devise NM interventions, such as narrative-driven public health campaigns. This approach will transform patient stories into effective social governance tools, thereby enhancing the inclusivity of medical decision-making. Secondly, we propose establishing an ethical AI governance system. This system will ensure that AI-driven narrative data processing aligns with China's data security regulations. We plan to adopt encryption technology and an informed consent mechanism to bolster privacy protections. Additionally, we will systematically mitigate technical biases through algorithm fairness audits and transparent training protocols, including the use of open dataset sources. Finally, we advocate for a global localization adaptation strategy, drawing inspiration from international practices like the Indian Asha worker model. While respecting the universal principle of patient autonomy, we intend to devise localized solutions, such as a health narrative literacy improvement project tailored for rural areas. This will facilitate the effective integration of medical humanistic values within diverse social and cultural contexts. Ultimately, this framework aims to shift healthcare paradigms from fragmented, biomarker-centric models to holistic, humanistic systems. By empowering patients and frontline workers as NM co-designers through participatory research, localized innovations can catalyze structural reforms, ensuring medical services prioritize humanistic care over purely biomedical metrics. " Lei NJ, Vaishnani DK, Shaheen M, Pisheh H, Zeng J, Ying FR, Yang QQ, Wang CY, Ma J, Pan JY, Hou NJ. Embedding narrative medicine in primary healthcare: Exploration and practice from a medical humanities perspective. World J Clin Cases 2025; 13(22): 105684 [DOI: 10.12998/wjcc.v13.i22.105684]
3	" Endoscopic gastroplasty treatments were significantly better in reducing total body weight, excessive weight, and average weight among obese population. No significant difference between endoscopic transoral outlet reduction and full-thickness suturing plus argon plasma mucosal coagulation. Lack of comparative, long-term follow-up and randomized studies, reporting and selection bias, high level of heterogeneity were the major limitations in the currently available meta-analyses." Abdulla M, Mohammed N, AlQamish J, Arau RT. Efficacy and safety of endoscopic gastroplasty for treatment of obesity: An overview of comparative meta-analyses. World J Gastrointest Endosc 2025; 17(5): 105158 [DOI: 10.4253/wjge.v17.i5.105158]
4	"This review comprehensively explores the latest advancements in gastrointestinal (GI) endoscopy, highlighting innovations in diagnostic and therapeutic techniques for GI cancers. Cutting-edge technologies such as magnification endoscopy, narrow-band imaging, endoscopic ultrasound with fine-needle biopsy, and artificial intelligence-enhanced methods are transforming cancer detection, staging, and management. Endoscopic approaches like submucosal dissection and mucosal resection are improving outcomes for premalignant and malignant lesions. These developments underscore the pivotal role of endoscopy in reducing morbidity, mortality, and healthcare costs associated with GI cancers." Abusuliman M, Jamali T, Zuchelli TE. Advances in gastrointestinal endoscopy: A comprehensive review of innovations in cancer diagnosis and management. World J Gastrointest Endosc 2025; 17(5): 105468 [DOI: 10.4253/wjge.v17.i5.105468]
5	"Gastric polyps (GPs) are a common clinical disease. In recent years, with the change in dietary habits, the incidence of GPs is increasing in China. GPs are usually found by gastroscopy. Some GPs may have malignant potential and are associated with hereditary diseases. Therefore, early detection and biopsy examination are important in clinical practice to better reduce the rate of cancer。It is an interesting manuscript. Authors can succeed to present their idea in a clear way adding information to the existing literature." Zheng L, Shi YQ, Xue T, Duan SL. Evaluating the detection rate and pathological features of polyps in patients with upper gastrointestinal endoscopy. World J Gastrointest Endosc 2025; 17(5): 105471 [DOI: 10.4253/wjge.v17.i5.105471]
6	"This Letter to Editor does a great job of highlighting an important issue that many of us face in real-world clinical practice—when to perform cholecystectomy in patients with gallstone-related acute cholangitis. The authors point out the growing evidence in favor of same-admission surgery rather than waiting, and they support this with data from a large national database, which adds weight to their argument. What I appreciated most was how clearly the authors outlined the benefits of early surgery—not just in terms of clinical outcomes like reduced readmission and mortality, but also from a healthcare system perspective. These are the kinds of practical, patient-centered decisions we need to think more carefully about. That said, I would have liked to see a little more discussion on what makes early surgery difficult to implement in some hospitals. For example, resource limitations, operating room availability, or patient comorbidities could be relevant factors. A few thoughts on how to overcome those barriers would make the piece even more helpful. In summary, this is a well-written and very relevant commentary that reminds us of the gap that often exists between evidence and practice. I think it will be helpful not only for clinicians but also for institutions looking to improve care pathways for biliary emergencies. Reviewer Name: Bum-Soo Kim " Paramythiotis D, Tsavdaris D, Karlafti E. Reassessing cholecystectomy timing in gallstone-related acute cholangitis. World J Gastrointest Endosc 2025; 17(5): 106473 [DOI: 10.4253/wjge.v17.i5.106473]
7	"This article is very innovative and has great reference value for clinical medical treatment, the language has no obvious errors, the quality of charts and graphs is clear, it is worthy of publication, the level of publication meets the requirements of journals, and for the insufficiency of the research hopefully further in-depth discussion." Singeap AM, Minea H, Stafie R, Stanciu C, Trifan A. Towards precision care: Fluctuations in albumin and fibrinogen as noninvasive predictors of endoscopic outcomes in Crohn’s disease. World J Gastrointest Endosc 2025; 17(5): 105365 [DOI: 10.4253/wjge.v17.i5.105365]
8	"I read an interesting article "Efficacy and safety of endoscopic gastroplasty for the treatment of obesity: An overview of comparative meta-analyses". The authors very accurately analyzed a large list of available publications on the topic of endoscopic gastroplasty in accordance with the PRISMA method. The authors also compared various strategies, including interventional ones for the treatment of obesity. They made interesting conclusions about the effectiveness of endoscopic gastroplasty for the treatment of obesity. " Abdulla M, Mohammed N, AlQamish J, Arau RT. Efficacy and safety of endoscopic gastroplasty for treatment of obesity: An overview of comparative meta-analyses. World J Gastrointest Endosc 2025; 17(5): 105158 [DOI: 10.4253/wjge.v17.i5.105158]
9	"This article describes a prospective study evaluating the efficacy of colon capsule endoscopy (CCE) for surveillance of colonic polyps. Although the study was conducted at a single institution and may lack diversity in its patient population, it is a prospective study that provides essential data demonstrating the utility of CCE. Currently, CCE is also used in routine clinical practice, such as for assessing the effectiveness of medications in ulcerative colitis. There are challenges to overcome, such as the volume of laxatives required for bowel preparation being greater than that for conventional colonoscopy (CS) and the higher examination cost. However, CCE can potentially reduce the number of unnecessary CS, suppress carbon dioxide emissions associated with endoscopic procedures, and significantly contribute to green endoscopy. For these reasons, determining how to promote the use of CCE further in daily clinical practice is considered an important issue for the future." Semenov S, Ismail MS, Sihag S, Manoharan T, Reilly P, Boran G, Ryan B, Breslin N, O’Connor A, O’Donnell S, McNamara D. Colon capsule endoscopy is an effective filter test for colonic polyp surveillance. World J Gastrointest Endosc 2025; 17(5): 101322 [DOI: 10.4253/wjge.v17.i5.101322]
10	"This review article presents a comprehensive synthesis of recent developments in conversion therapy for intrahepatic cholangiocarcinoma (ICC), specifically focusing on strategies to render initially unresectable disease amenable to surgical resection. The authors have successfully compiled and analyzed a broad range of relevant studies, providing a balanced overview of multimodal treatment approaches, including systemic chemotherapy, targeted therapy, immunotherapy, and locoregional interventions such as TACE, TARE, and HAIC. The manuscript is commendable for its integration of recent clinical data and its emphasis on multidisciplinary management, which aligns with current oncologic practice. The inclusion of well-organized tables and illustrative figures contributes to the accessibility and clarity of the content. Furthermore, the discussion of strategies aimed at optimizing the future liver remnant—such as portal vein embolization (PVE) and ALPPS—offers valuable clinical insights for hepatobiliary surgeons and oncologists alike. To further strengthen the manuscript, the following suggestions are offered: 1. A more explicit and operational definition of “conversion therapy” would improve conceptual clarity, particularly if contrasted with related terms such as “bridging therapy” and “downstaging.” 2. While Figure 1 is informative, reformatting it into a structured algorithm or decision-making flowchart could enhance its clinical utility and instructional value. 3. The generalizability of findings from small-scale or non-standardized studies should be addressed, as this would add depth to the critical appraisal and enhance the scholarly rigor of the discussion. In conclusion, this review represents a timely and academically significant contribution to the evolving field of hepatobiliary oncology. With modest revisions, it has the potential to serve as both an educational reference and a practical guide for clinicians managing advanced ICC. " Liu JJ, Zhou M, Yuan T, Huang ZY, Zhang ZY. Conversion treatment for advanced intrahepatic cholangiocarcinoma: Opportunities and challenges. World J Gastroenterol 2025; 31(15): 104901 [PMID: 40309227 DOI: 10.3748/wjg.v31.i15.104901]
11	"The title of this paper should condense the main idea of the article and clearly indicate that it is a retrospective study. The description of research methods is not specific and clear enough. The citation of literature should include more recent references, which will increase the novelty and scientific value of the paper." Wu YP, Zhou JX, Wu HB, Wu DP, Qin LZ, Qin B, Xu XY, Yehya SAA, Cheng Y. Clinical characteristics and risk factors of esophageal reflux hypersensitivity: A multicenter study. World J Gastroenterol 2025; 31(17): 105281 [DOI: 10.3748/wjg.v31.i17.105281]
12	"The retrospective study by Zhao et al. offers critical insights into sex-based differences in achalasia symptomatology and outcomes following peroral endoscopic myotomy (POEM). By analyzing 526 cases over a decade, the authors address a significant gap in understanding how sex influences preoperative presentation, manometric parameters, and postoperative recovery. While the study reaffirms POEM’s efficacy and highlights sex-specific nuances, two methodological limitations warrant attention: the absence of normality testing for data distribution and incomplete reporting of statistical metrics in tables. These omissions slightly undermine the robustness of the statistical analysis but do not negate the study’s overall contributions." Zhao CY, Xu N, Dong H, Chai NL, Linghu EQ. Effect of sex on the outcomes of peroral endoscopic myotomy for the treatment of achalasia. World J Gastroenterol 2025; 31(17): 104579 [DOI: 10.3748/wjg.v31.i17.104579]
13	"This review by Liu and He provides a comprehensive exploration of intelligent hydrogel-based dressings for diabetic wound management. Chronic diabetic wounds, characterized by impaired or delayed healing due to multiple physiological disruptions, demand innovative solutions. The authors systematically categorize hydrogels into natural, synthetic, and composite types, dissecting their structural and functional mechanisms while highlighting their clinical potential. Below is a critical analysis of the article’s strengths, limitations, and future implications. The article is well-organized, progressing logically from the pathophysiology of diabetic wounds to hydrogel design, responsiveness mechanisms, applications, and future challenges. This structure helps readers understand the progression from fundamental biological science to clinical findings in translational studies. The integration of materials science, nanotechnology, and biotechnology is a highlight. For instance, the discussion on composite hydrogels incorporating silver nanoparticles or conductive polymers demonstrates how hybrid materials enhance antibacterial efficacy and mimic bioelectrical environments. The inclusion of emerging technologies like 3D printing and real-time monitoring systems reflects a forward-thinking approach. The authors bolster their claims with recent preclinical and clinical studies (e.g., phase 4 trials of Fitostimoline and SANTYL hydrogels). References to advanced functionalities, such as glucose-responsive insulin release or photothermal antibacterial activity, are supported by robust experimental data, lending credibility to the proposed applications. The emphasis on personalized precision medicine aligns with current trends in healthcare. The concept of hydrogels adapting to wound microenvironment changes (pH, temperature, biomarkers) for tailored drug delivery represents a paradigm shift from traditional "one-size-fits-all" therapies. The article does have some limitations. In terms of clinical translation challenges, while the article acknowledges barriers like high costs and biocompatibility concerns, it lacks actionable strategies for overcoming these hurdles. For example, cost reduction could be addressed through scalable manufacturing techniques or public-private partnerships, yet these solutions are only briefly mentioned. Certain sections, particularly those detailing chemical cross-linking mechanisms or nanomaterial interactions, may alienate non-specialist readers. Simplifying jargon or incorporating analogies (e.g., comparing hydrogel networks to "smart sponges") could improve accessibility. In addition, long-term biocompatibility and potential side effects of nanomaterials (e.g., silver nanoparticle toxicity) are underexplored. A discussion on regulatory pathways or post-market surveillance would strengthen the clinical relevance of the review. For future direction of dressings development, combining hydrogel dressings with wearable sensors or AI-driven diagnostics could enable closed-loop systems for real-time wound management. For instance, hydrogels equipped with IoT-enabled sensors might autonomously adjust drug release based on cloud-analyzed biomarker data. Exploring eco-friendly materials (e.g., biodegradable polymers) and energy-efficient production methods would address environmental concerns. Additionally, cost-benefit analyses comparing hydrogel dressings to standard care could incentivize healthcare adoption. Future studies should prioritize patient feedback to improve usability, such as optimizing hydrogel adhesion for mobility or reducing dressing change frequency. Ethnographic studies on patient adherence could inform design modifications. In conclusion, Liu and He’s review underscores the transformative potential of intelligent hydrogels in diabetic wound care, bridging scientific innovation with clinical needs. By addressing microenvironmental challenges through responsive drug delivery, antibacterial action, and tissue regeneration, these materials represent a leap toward personalized medicine. However, translating laboratory success to bedside application requires tackling economic, technical, and regulatory barriers. Future efforts must prioritize interdisciplinary collaboration, patient-centric design, and sustainable scaling to unlock the full promise of intelligent hydrogels. This article serves as both a foundational reference and a call to action for researchers, clinicians, and policymakers to reimagine diabetic wound management." Liu H, He L. Intelligent hydrogel-based dressings for treatment of chronic diabetic wounds. World J Diabetes 2025; 16(5): 104937 [DOI: 10.4239/wjd.v16.i5.104937]
14	" This article provides important data and insights for the study of reflux hypersensitivity (RH). The study is well-designed as a multicenter, large-sample, retrospective investigation, comprehensively analyzing the clinical characteristics and risk factors of patients with reflux hypersensitivity (RH). The assessment is extensive, covering symptoms, esophageal motility, impedance-pH monitoring, and psychological factors, revealing the significance of weakly acidic reflux (WAR) and non-acid reflux (NAR) in RH. The use of multiple statistical methods ensures the scientific reliability of the results. However, there are some limitations. Despite involving three medical centers, the sample size is still relatively small, with only 109 cases. The follow-up period is short, from January 2022 to December 2023, which may limit the generalizability of the study results and the assessment of long-term effects. The study mainly focuses on the clinical characteristics and risk factors of RH, but there is relatively little analysis of treatment response and prognosis in patients. The article uses the Hamilton Anxiety Scale and the Hamilton Depression Scale to assess the psychological status of patients, but it does not evaluate the effectiveness of psychological interventions in RH patients." Wu YP, Zhou JX, Wu HB, Wu DP, Qin LZ, Qin B, Xu XY, Yehya SAA, Cheng Y. Clinical characteristics and risk factors of esophageal reflux hypersensitivity: A multicenter study. World J Gastroenterol 2025; 31(17): 105281 [DOI: 10.3748/wjg.v31.i17.105281]
15	"This article investigates the therapeutic potential of BIC in the context of MASLD, with a particular focus on its effects on lipid metabolism and inflammation. BIC, an alkaloid traditionally recognized as a GABA receptor antagonist, is presented as a novel therapeutic candidate for MASLD. This exploration is particularly intriguing, as the GABAergic pathways are well-documented for their roles within the nervous system; however, the investigation into BIC’s impact on hepatic lipid metabolism and inflammatory processes remains relatively novel and promising. The utilization of zebrafish, HepG2, and AML12 cellular models, alongside mouse models induced by a MCD diet, significantly enhances the validity of the findings. By employing multiple experimental models, the researchers provide robust evidence supporting the efficacy of BIC in alleviating MASLD, which is essential for the translation of these findings into clinical practice. Furthermore, the absence of significant toxicity observed in zebrafish embryos and cellular models, even at relatively high concentrations of BIC, suggests a favorable safety profile for this compound. This aspect is critical, as it bolsters the notion that BIC could potentially be developed into a therapeutic agent devoid of the toxic effects commonly associated with alternative treatments. However, while the study offers compelling evidence from preclinical models, it is imperative to investigate the long-term effects of BIC. Given that MASLD can progress to more severe forms, such as steatohepatitis and fibrosis, long-term studies are necessary to ascertain whether BIC can effectively prevent such progression. Moreover, although the results of the study confirm the absence of significant toxicity associated with the drug, the relationship between its pharmacological mechanisms and GABA warrants further discussion, or at the very least, should be acknowledged in the limitations section." Wang XM, Dai Z, Lu DJ, Bao CQ, Yang NB, Zhou YP. Bicuculline ameliorates metabolic dysfunction-associated steatotic liver disease by inhibiting the nuclear factor-kappa B pathway and reducing lipid accumulation. World J Gastroenterol 2025; 31(17): 105438 [DOI: 10.3748/wjg.v31.i17.105438]
16	"Title: Interventional effect of hesperetin on N-methyl-N’-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis. The study proved that hesperetin aleviated the gastric carcinogenesis by mediating exosome-derived circ0008274 targeting miR-526b-5p. The hesperidin-mediated exosomes circ0008274/miR-526b-5p axis and it can serve as a potential target for slowing the onset of gastric cancer. These findings play an important role in the management of gastric precancerous lesions. The overall study is good but this research used bioinformatics technique and future researches are need to used the integration of bioinformatics, genomics, and proteomics to give more explanation for the protective effect of hesperetin on the gastric cancer. " Liang ZF, Xu YM, Song JJ, Gao ZH, Qian H, Xu XZ. Interventional effect of hesperetin on N-methyl-N’-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis. World J Gastroenterol 2025; 31(16): 104920 [PMID: 40308800 DOI: 10.3748/wjg.v31.i16.104920]
17	"The current study is very interesting as the authors addressed the role of gut micro biota in pathogenesis of chronic hepatitis B infection. They reported that the abundance of Dorea varies significantly across various stages of liver fibrosis, making it a potential microbial marker for identifying the onset and progression of liver fibrosis. This useful conclusion will pave the way for modification of treatment strategy of chronic hepatitis B infection However, I have two comments: 1-The selection of patients with a wide range of age : 18-80 may have an impact on the results. Previous studies have sown as individuals age, the gut microbiota undergoes significant changes in composition, diversity, and functionality , which have been linked to various health conditions, including cognitive decline and inflammatory diseases. 2-It would have been better to select two equal groups of patients from the start: one group with hepatic fibrosis and the other without fibrosis .Having the equal or nearly equal groups would make statistical analysis more fair as the groups already studied had one with 35 patients and the other with 102 patients. " Zhu Y, Geng SY, Chen Y, Ru QJ, Zheng Y, Jiang N, Zhu FY, Zhang YS. Machine learning algorithms reveal gut microbiota signatures associated with chronic hepatitis B-related hepatic fibrosis. World J Gastroenterol 2025; 31(16): 105985 [PMID: 40308807 DOI: 10.3748/wjg.v31.i16.105985]
18	"The authors have made a significant contribution by uncovering the role of the Interleukin-36 (IL-36) subfamily in liver cirrhosis, particularly highlighting the relationship between these cytokines and gut microbiota. This work provides a fresh perspective on the gut-liver axis, demonstrating how an imbalance in the gut microbiome might contribute to liver disease progression through inflammatory cytokine signaling. The innovation of the study lies in its identification of IL-36 cytokines, such as IL-36α, IL-36γ, IL-36Ra, and IL-38, as crucial players in the inflammatory processes associated with liver cirrhosis. By correlating these cytokines with gut microbiota alterations, the authors open new avenues for potential biomarkers and therapeutic targets in liver disease management. Their findings suggest that the IL-36 subfamily could help us better understand the pathophysiological mechanisms underlying liver cirrhosis and its association with dysbiosis in the gut microbiome. However, a notable limitation of the study is the lack of mechanistic exploration of how IL-36 cytokines mediate these effects in the liver. While the paper discusses correlations between IL-36 subfamily levels and gut microbiota, the underlying mechanisms linking these factors to liver cirrhosis progression are not fully explored. Further research into how IL-36 cytokines influence microbiota composition and how they interact with liver disease would enhance the understanding of the gut-liver axis." Pan YZ, Chen WT, Jin HR, Liu Z, Gu YY, Wang XR, Wang J, Lin JJ, Zhou Y, Xu LM. Correlation between the interleukin-36 subfamily and gut microbiota in patients with liver cirrhosis: Implications for gut-liver axis imbalance. World J Hepatol 2025; 17(4): 105660 [PMID: 40308824 DOI: 10.4254/wjh.v17.i4.105660]
19	"This paper evaluates the impact of sex on the outcomes of peroral endoscopic myotomy (POEM) in the treatment of esophageal achalasia. POEM is concluded to be a safe and effective treatment for both men and women, with women potentially deriving greater benefit than men. The study further suggests that sex may influence the therapeutic effect and symptom improvement after POEM, with hormonal factors being particularly important in women. The short-term success rate of POEM surgery is 96.52%. Success is improving the Eckardt score to 3 or less without additional treatment. These results indicate that POEM is a highly effective first-line option for achalasia treatment. However, the technical difficulty of POEM is high, and even in Japan, where endoscopic therapy is widespread, the procedure is limited to a small number of high-volume centers. Addressing expanding access to this effective technique is a significant future challenge. " Zhao CY, Xu N, Dong H, Chai NL, Linghu EQ. Effect of sex on the outcomes of peroral endoscopic myotomy for the treatment of achalasia. World J Gastroenterol 2025; 31(17): 104579 [DOI: 10.3748/wjg.v31.i17.104579]
20	"The manuscript addresses the role of exosomal miR-137-3p derived from hypoxia-injured endometrial epithelial cells (EECDs) in regulating hucMSC behavior, which is of potential interest in the context of endometrial regeneration. However, several critical issues limit the scientific clarity and integrity of the current work: In the first part of the results, the authors performed RNA sequencing to compare miRNA expression profiles in hucMSCs treated with EECD-ex versus EEC-ex. However, Figure 7 implies that the differential expression of miR-137-3p originates from differences in the exosomal content of EECD-ex versus EEC-ex. This is a fundamental inconsistency. Changes in miRNA expression within recipient hucMSCs do not directly reflect the cargo of the exosomes unless validated by exosome profiling. Such discrepancy may mislead the interpretation regarding the source and function of miR-137-3p. The manuscript does not provide essential data on the characterization of exosomes (e.g., TEM, NTA, exosomal markers such as CD63, CD81, or TSG101). Moreover, it is unclear whether there is a difference in exosome yield (i.e., production efficiency or protein content) between EEC-ex and EECD-ex. The manuscript lacks transparency on how miR-137-3p was selected from the pool of 53 differentially expressed miRNAs. While functional assays were performed on hucMSCs, the study does not include gain- or loss-of-function experiments at the exosomal level (e.g., using miR-137-3p inhibitors/mimics in donor EECs before exosome collection). Such experiments are critical to directly establish causality between EECD-exosomal miR-137-3p and the observed hucMSC behavior." Zhang WY, Liu SM, Wang HB, Deng CY. Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia. World J Stem Cells 2025; 17(4): 100359 [PMID: 40308888 DOI: 10.4252/wjsc.v17.i4.100359]
21	"A letter to the Editor entitled Hypoxic endometrial epithelial cell-derived microRNAs effectively regulate the regenerative properties of mesenchymal stromal cells by Dr Mallis elegantly comments on the significance of the study published by Dr Zhang. The author highlights the clinical significance of the data obtained from in vitro experiments and, at the same time, provides mechanistic insight into the role of mir-214-5p and 21-5p in mesenchymal stem cells’ functionality and reparability of endometrial endothelial cells. The author has rightfully suggested that the published data by Zhang et al. has been derived from in vitro experimentation and there is a need for supporting this data by in vivo experiments. The letter is fluently written and supplements the findings of Zhang et al." Mallis P. Hypoxic endometrial epithelial cell-derived microRNAs effectively regulate the regenerative properties of mesenchymal stromal cells. World J Stem Cells 2025; 17(4): 102482 [PMID: 40308881 DOI: 10.4252/wjsc.v17.i4.102482]
22	"Mubin Ozercan et al. presented an interesting article "Vonoprazan and proton pump inhibitors: Which is superior for Helicobacter pylori eradication?" The authors' decision to summarize current information on the effectiveness of anti-Helicobacter therapy based on the use of proton pump inhibitors and based on the use of potassium-competing acid blockers(P-CAB) was absolutely correct and timely. A large number of comparative studies are available in scientific medical databases. Confirmation of the high level of effectiveness of potassium-competing acid blockers has practical significance for use in various eradication treatment regimens." Ozercan M, Tawheed A, Ismail A, Amer MS, El-Kassas M. Vonoprazan and proton pump inhibitors: Which is superior for Helicobacter pylori eradication? World J Gastroenterol 2025; 31(17): 103156 [DOI: 10.3748/wjg.v31.i17.103156]
23	"Title: Cardiac Metastatic Tumors: Revisiting Mechanisms and Future Perspectives To the Editor We read with great interest the article by Luo et al.[1] titled "Comprehensive understanding of a rare disease: Cardiac metastatic tumor, a double-center 10-year case review," recently published in World Journal of Cardiology. We congratulate the authors for providing valuable clinical insights into the rare and underrecognized entity of cardiac metastatic tumors (CMTs). The study's finding that intracardiac metastases are associated with a poorer prognosis compared to pericardial involvement aligns with prior autopsy-based observations[2,3], emphasizing the prognostic importance of metastatic localization within the cardiac structure. The authors' inclusion of cardiac biomarkers, such as BNP and troponin, as predictors of adverse outcomes is particularly commendable and may represent a step toward more precise risk stratification. Building upon these important findings, we wish to highlight several emerging directions that could deepen our understanding of CMTs: First, organotropism and pre-metastatic niche formation are increasingly recognized as critical determinants of metastatic dissemination[4,5]. Experimental studies have demonstrated that cardiac tissue exhibits a unique extracellular matrix composition and a dynamic immunological environment, which may preferentially attract circulating tumor cells[6]. Investigating the role of cardiac-specific chemokine axes, such as CXCL12-CXCR4 signaling, may provide new insights into the molecular determinants of cardiac colonization. Second, advanced imaging modalities warrant greater emphasis in the diagnostic pathway. While echocardiography remains the first-line modality, cardiac magnetic resonance (CMR) imaging and ^18F-FDG PET-CT possess superior tissue characterization capabilities, enabling differentiation between malignant and benign cardiac masses with higher sensitivity and specificity[7,8]. Early integration of these modalities could significantly alter the therapeutic trajectory for patients with occult cardiac involvement. Third, therapeutic approaches for CMTs remain largely individualized and empirical. Although palliative strategies predominate, isolated reports suggest that surgical resection or stereotactic radiotherapy may improve quality of life and survival in carefully selected patients[9]. Prospective studies incorporating molecular tumor profiling—such as HER2, EGFR, or ALK status—may refine patient selection and therapeutic planning[10]. Moreover, given the rising incidence of CMTs in the era of improved oncological survival, it is imperative to establish multicenter registries and collaborative research networks focusing specifically on cardiac oncology. Standardizing diagnostic criteria, staging systems, and treatment algorithms would provide an urgently needed framework for evidence-based clinical decision-making. In conclusion, Luo et al. have made a valuable contribution by elucidating the clinical and prognostic characteristics of CMTs. Future investigations integrating molecular oncology, advanced imaging, and standardized therapeutic strategies will be pivotal to improving the outcomes of patients with this rare but increasingly encountered condition. References 1.Luo LY, Yang TS, He Z, Lin L, Luo XL. Comprehensive understanding of a rare disease: Cardiac metastatic tumor, a double-center 10-year case review. World J Cardiol. 2025;17(2):101851. doi:10.4330/wjc.v17.i2.101851 2.Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol. 2007;60(1):27-34. doi:10.1136/jcp.2005.035105 3.Lam KY, Dickens P, Chan AC. Tumors of the heart: a 20-year experience with a review of 12,485 consecutive autopsies. Arch Pathol Lab Med. 1993;117(10):1027-1031. 4.Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer. 2017;17(5):302-317. doi:10.1038/nrc.2017.6 5.Labelle M, Hynes RO. The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discov. 2012;2(12):1091-1099. doi:10.1158/2159-8290.CD-12-0329 6.Shinde AV, Frangogiannis NG. Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol. 2014;70:74-82. doi:10.1016/j.yjmcc.2013.12.011 7.Bogaert J, Francone M. Cardiac tumors and masses: the role of cardiovascular magnetic resonance imaging. Eur Radiol. 2009;19(1):14-27. doi:10.1007/s00330-008-1161-0 8.Rahbar K, Seifarth H, Schäfers M, et al. Differentiation of malignant and benign cardiac tumors using 18F-FDG PET/CT. J Nucl Med. 2012;53(6):856-863. doi:10.2967/jnumed.111.099028 9.Yusuf SW, Bathina JD, Qureshi S, et al. Cardiac tumors in cancer patients: diagnosis, management, and prognosis. Oncologist. 2007;12(4):443-450. doi:10.1634/theoncologist.12-4-443 10.Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-284. doi:10.1038/nrc2622" Luo LY, Yang TS, He Z, Lin L, Luo XL. Comprehensive understanding of a rare disease: Cardiac metastatic tumor, a double-center 10-year case review. World J Cardiol 2025; 17(2): 101851 [PMID: 40061273 DOI: 10.4330/wjc.v17.i2.101851]
24	"The low-cost and easy-to-obtain characteristics of the TyG index introduced in this article make it feasible for clinical translation, especially in resource-limited settings. However, the universality of the TyG index threshold is questionable, and the influence of metabolic characteristics (e.g., diet and genetics) in different populations needs to be considered. In addition, the role of TyG index in early gastric cancer and its relationship with the dynamic changes of tumor microenvironment have not been elucidated. It is worth noting that high TyG index may reflect enhanced metabolic reserve in advanced patients, while may promote malignant transformation in precancerous lesions, and this "double-edged sword" effect needs to be further explored." Zhao CF, Liu XL, Wu NB, Xu ZF. Triglyceride-glucose index as a prognostic indicator in advanced gastric cancer: Insights and future research. World J Gastroenterol 2025; 31(17): 104794 [DOI: 10.3748/wjg.v31.i17.104794]
25	"1、The study would be further strengthened if the authors could elaborate in greater detail on how STAT3 was identified and the specific mechanisms by which miR-137-3p regulates STAT3. 2、Frankly, the impact of miR-137-3p on p-STAT3 appears minimal, as shown in Figure 3B. 3、A more in-depth exploration of UBE3C’s role in modulating the STAT3 signaling pathway and its mechanistic underpinnings would enhance the study. For instance, investigating whether miR-137-3p influences STAT3 signaling following UBE3C knockdown could yield valuable insights." Zhang WY, Liu SM, Wang HB, Deng CY. Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia. World J Stem Cells 2025; 17(4): 100359 [PMID: 40308888 DOI: 10.4252/wjsc.v17.i4.100359]
26	"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." 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 [PMID: 40309229 DOI: 10.3748/wjg.v31.i15.104875]
27	"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. " 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 [PMID: 40309232 DOI: 10.3748/wjg.v31.i15.104996]
28	"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." 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 [PMID: 40308799 DOI: 10.3748/wjg.v31.i16.104758]
29	"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. " 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]
30	"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." Fang HM. Intricacy of Crohn’s disease: Incongruity between diagnostic modalities and histopathologic assessment. World J Gastrointest Endosc 2025; 17(4): 103979 [PMID: 40291133 DOI: 10.4253/wjge.v17.i4.103979]
31	"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. " 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]
32	"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." 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 [PMID: 40309231 DOI: 10.3748/wjg.v31.i15.101695]
33	"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. " 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 [PMID: 40309231 DOI: 10.3748/wjg.v31.i15.101695]
34	"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. " 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 [PMID: 40309228 DOI: 10.3748/wjg.v31.i15.103512]
35	"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." 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 [PMID: 40309234 DOI: 10.3748/wjg.v31.i15.105236]
36	"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." 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 [PMID: 40309234 DOI: 10.3748/wjg.v31.i15.105236]
37	"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." 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 [PMID: 40291131 DOI: 10.4253/wjge.v17.i4.101998]
38	"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." 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 [PMID: 40291129 DOI: 10.4253/wjge.v17.i4.106671]
39	"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. " 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]
40	"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. " 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]
41	"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." 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 [PMID: 40309606 DOI: 10.5498/wjp.v15.i4.100849]
42	"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." 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]
43	"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." 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]
44	"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." 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]
45	"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." 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]
46	"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." 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]
47	"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." 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]
48	"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." 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]
49	"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." 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]
50	"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." 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]