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"This article is a high-quality academic editorial that systematically explores the potential value of PLD2 in acute pancreatitis (AP) and proposes actionable future research directions. Its core contributions lie in: 1. Integrating molecular mechanisms with clinical applications, shifting AP biomarker research from "phenomenological association" to "mechanism-driven" investigation; 2. Emphasizing multi-omics integration and precision medicine, offering a novel paradigm for AP management."
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Wang ZH, Lv JH, Teng Y, Michael N, Zhao YF, Xia M, Wang B. Phospholipase D2: A biomarker for stratifying disease severity in acute pancreatitis? World J Gastroenterol 2025; 31(11): 104033 [PMID: 40124273 DOI: 10.3748/wjg.v31.i11.104033]
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"This study provides novel insights into the risk factors for metachronous gastric cancer (MGC) in elderly patients, particularly highlighting the clinical significance of the association with metabolic dysfunction-associated steatotic liver disease (MASLD) and the proposed risk stratification system. However, the retrospective design and small sample size limit the robustness of the evidence, necessitating further validation through multicenter prospective studies. The paper is well-structured but requires refinement in statistical details."
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Xiang Y, Yuan Y, Wang ZY, Zhu YM, Li WY, Ye QG, Wang YN, Sun Q, Ding XW, Longi F, Tang DH, Xu GF. Comorbidities related to metachronous recurrence for early gastric cancer in elderly patients. World J Gastrointest Endosc 2025; 17(3): 99540 [PMID: 40125504 DOI: 10.4253/wjge.v17.i3.99540]
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"The author has constructed a predictive model with strong forecasting capabilities, designed to estimate the probability of a textbook outcome following surgery. Additionally, the study elucidates the machine learning computational process using the SHAP algorithm. This research is highly innovative, as it visualizes the otherwise opaque computational processes of machine learning, thereby enhancing its credibility. Clinicians can easily input specific clinical parameters of patients to obtain immediate, personalized risk assessments, enabling timely preventive measures and ensuring the best possible medical care for patients.This study substantiates the feasibility of explainable machine learning in future applications, marking a new direction in the research of predictive models and supervised learning."
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Huang TF, Luo C, Guo LB, Liu HZ, Li JT, Lin QZ, Fan RL, Zhou WP, Li JD, Lin KC, Tang SC, Zeng YY. Preoperative prediction of textbook outcome in intrahepatic cholangiocarcinoma by interpretable machine learning: A multicenter cohort study. World J Gastroenterol 2025; 31(11): 100911 [PMID: 40124276 DOI: 10.3748/wjg.v31.i11.100911]
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"This study provides valuable insights into the effectiveness of combining three-dimensional computed tomography (3D CT) reconstruction and laparoscopic techniques for accurately measuring the myopectineal orifice (MPO) in inguinal hernia repair. The research clearly demonstrates that preoperative 3D CT measurements closely match intraoperative laparoscopic findings, suggesting that CT could reliably guide surgical planning.
The authors effectively highlight the clinical implications, emphasizing how precise measurement and patch placement can minimize complications such as nerve injury, recurrence, and chronic postoperative pain. Additionally, they provide a thoughtful analysis regarding demographic factors, noting significant differences in MPO measurements between sexes, while age and body mass index showed less impact.
One of the strengths of this article is its detailed methodological description, which facilitates replication and further research. However, future studies might benefit from larger sample sizes and expanded demographic variability to enhance generalizability. Overall, the paper makes a significant contribution to personalized surgical approaches for inguinal hernia treatment."
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Zhang L, Chen J, Zhang YY, Liu L, Wang HD, Zhang YF, Sheng J, Hu QS, Liu ML, Yuan YL. Three-dimensional reconstruction under computed tomography and myopectineal orifice measurement under laparoscopy for quality control of inguinal hernia treatment. World J Gastrointest Endosc 2025; 17(3): 104966 [PMID: 40125507 DOI: 10.4253/wjge.v17.i3.104966]
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"As this is a editorial article, it has got no sections of methods, results, tables, biostatistics, units and ethical statement to provide commentary on these sections.
The editorial by Behrens and Elgafy provides an insightful analysis of factors influencing outcomes in indirect decompression through oblique and lateral lumbar interbody fusions (OLIF and LLIF). The discussion on patient selection criteria, particularly regarding preoperative spinal canal dimensions and lateral recess depth, is a valuable contribution to clinical decision-making. The emphasis on the unpredictability of outcomes in patients with severe lateral recess stenosis and the potential need for staged procedures highlights a crucial consideration for spine surgeons.
However, one area that could benefit from further exploration is the long-term stability of indirect decompression compared to direct decompression, especially concerning adjacent segment disease and fusion longevity. Additionally, a deeper comparison of OLIF and LLIF in terms of specific complications and recovery trajectories would provide even greater clinical relevance.
Overall, this editorial offers a comprehensive and well-referenced synthesis of the current literature on indirect decompression. It serves as a useful guide for surgeons considering minimally invasive approaches while remaining cautious about their limitations."
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M Behrens KM, Elgafy H. Factors affecting outcomes of indirect decompression after oblique and lateral lumbar interbody fusions. World J Orthop 2025; 16(3): 100772 [PMID: 40124722 DOI: 10.5312/wjo.v16.i3.100772]
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"The clinical significance of this study lies in its innovative approach to predicting colorectal polyp recurrence using machine learning (ML), specifically the eXtreme Gradient Boosting (XGBoost) model. Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, largely preventable through early detection and effective management of precancerous polyps. Endoscopic mucosal resection (EMR) is widely utilized for the removal of colorectal polyps, yet it carries a considerable risk of recurrence, highlighting the need for accurate predictive tools to guide postoperative surveillance.
This study identifies critical independent risk factors for polyp recurrence one year post-EMR, such as age, family history, smoking habits, diarrhea, Helicobacter pylori infection, polyp size, number of polyps, and hazard classification. By leveraging ML algorithms, particularly XGBoost, the researchers have developed a model with superior predictive performance, evidenced by high Area Under the Curve (AUC) values exceeding 0.90 across multiple validation cohorts, including a prospective validation set, indicating robust predictive accuracy and clinical utility.
Clinically, the XGBoost model offers substantial advantages. Its high sensitivity, specificity, accuracy, precision, and F1 scores suggest that it effectively stratifies patients based on recurrence risk. Such a model significantly enhances personalized patient management by informing more accurate follow-up intervals, potentially improving patient outcomes through timely interventions and reducing unnecessary colonoscopies in low-risk individuals.
Additionally, the authors' development of an accessible online web calculator based on this predictive model further underscores its practical utility in routine clinical practice. Clinicians can conveniently input patient-specific clinical parameters to obtain immediate, individualized risk predictions, facilitating shared decision-making between physicians and patients.
Decision Curve Analysis further underscores the practical value of this tool, demonstrating that using the XGBoost model provides superior clinical net benefit compared to standard follow-up strategies. This methodical approach not only advances clinical decision-making but also optimizes healthcare resources by prioritizing surveillance for those most at risk.
Finally, the interpretability of the model via SHapley Additive exPlanations (SHAP) analysis significantly mitigates concerns about the "black box" nature commonly associated with ML models, thus increasing clinician trust and acceptability.
In conclusion, this ML-based predictive model represents a critical advancement in clinical gastroenterology, providing robust, data-driven support for clinicians in making individualized recommendations for colorectal polyp surveillance and potentially reducing colorectal cancer incidence through targeted early intervention."
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Huang TF, Luo C, Guo LB, Liu HZ, Li JT, Lin QZ, Fan RL, Zhou WP, Li JD, Lin KC, Tang SC, Zeng YY. Preoperative prediction of textbook outcome in intrahepatic cholangiocarcinoma by interpretable machine learning: A multicenter cohort study. World J Gastroenterol 2025; 31(11): 100911 [PMID: 40124276 DOI: 10.3748/wjg.v31.i11.100911]
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"The author has shown that knocking out SERPINB5 not only inhibits the proliferation and metastasis of cancer cells but also suppresses tumor growth in xenograft mice, effectively reducing tumor progression. This suggests that SERPINB5 could potentially serve as an important target for tumor treatment. We sincerely appreciate the author's dedication and hard work. The quality of this article is truly outstanding, and we eagerly look forward to your next research contribution."
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Meng ZS, Hu JT, Wu H, Li BK. Inhibition of the SERPINB5/HSP90AA1 axis restrains the proliferation and invasion of rectal cancer. World J Gastroenterol 2025; 31(11): 103412 [PMID: 40124262 DOI: 10.3748/wjg.v31.i11.103412]
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"This study provides valuable data specifically focused on endoscopic resection (ER) of esophageal GISTs. Thorough evaluation of the ER technique, complications, and resection margin status enhances our understanding of ER safety and effectiveness. Furthermore, the study presented a relatively large case series of 32 patients, which increases the statistical reliability of the findings for esophageal GIST research. By presenting long-term follow-up results, it assessed the long-term prognosis after ER and suggested potential benefits for future treatment strategy development."
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Xu EP, Qi ZP, Zhang JW, Li B, Ren Z, Cai MY, Cai SL, Lv ZT, Chen ZH, Liu JY, Zhong YS, Zhou PH, Shi Q. Endoscopic treatment outcome of oesophageal gastrointestinal stromal tumours. World J Gastroenterol 2025; 31(10): 102393 [PMID: 40093666 DOI: 10.3748/wjg.v31.i10.102393]
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"We greatly appreciate the authors and their team for their in-depth study on treatment strategies for rectal neuroendocrine neoplasms (R-NENs). This retrospective analysis compares the efficacy of endoscopic full-thickness resection (EFTR) and endoscopic submucosal dissection (ESD) in the treatment of R-NENs, demonstrating the superior R0 resection rate of EFTR while maintaining comparable short-term safety with ESD. This study provides critical clinical evidence supporting the use of EFTR in R-NENs and contributes to the refinement of function-preserving surgical approaches. However, we would like to offer some constructive suggestions to enhance the clinical applicability and long-term evaluation of this study.
First, some terminology and definitions in the study are somewhat ambiguous, which may affect the interpretability of the results. For instance, the study mentions that some patients had "severe comorbidities" but does not specify the types of comorbidities or the inclusion/exclusion criteria applied. Certain comorbidities, such as diabetes or chronic kidney disease, may impact postoperative healing, and failing to differentiate them could introduce confounding among patients with varying risk profiles. Additionally, the description of lesion morphology is inherently subjective, and the study does not clarify whether standardized imaging assessments, such as endoscopic ultrasound (EUS), were used to measure lesion size and invasion depth. Inconsistencies in preoperative evaluation criteria could lead to bias in treatment selection. For example, was EFTR preferentially chosen for lesions with specific morphological characteristics? Future studies should adopt more detailed imaging assessment criteria and pathological grading methods to improve reproducibility and the interpretability of results.
Second, the study does not assess the impact of the learning curve for EFTR and ESD on surgical outcomes. As a relatively novel technique, EFTR may require a longer period of experience accumulation to achieve stable performance. The study does not clarify whether operator experience was comparable between the EFTR and ESD groups or whether surgical success rates varied with increasing experience. If EFTR procedures were performed by highly experienced endoscopists while ESD procedures involved a broader range of operators, the results could be biased in favor of EFTR. Additionally, since EFTR has a steeper learning curve, factors such as procedure time and complication rates may decrease with increased experience, but the study does not conduct a dynamic analysis of these trends. Future studies should incorporate learning curve analyses to evaluate the influence of experience on surgical outcomes, ensuring a fair comparison between the two techniques.
Furthermore, EFTR may cause greater bowel wall injury than ESD, potentially affecting postoperative bowel function, yet this study focuses primarily on R0 resection rates and short-term complications without assessing long-term functional outcomes. As a full-thickness resection technique, EFTR may alter rectal compliance, bowel movement frequency, and gut motility. However, the study does not provide data on postoperative bowel function changes, alterations in defecation patterns, bloating, or incontinence. If EFTR improves R0 resection rates but increases the risk of postoperative functional impairment, its clinical utility must be considered more cautiously. Future research should incorporate patient-reported outcomes (PROs) and quality of life (QoL) assessments and include long-term functional evaluations such as anorectal manometry and bowel dysfunction scoring to comprehensively assess the impact of EFTR on patient prognosis."
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Zhang XL, Jiang YY, Chang YY, Sun YL, Zhou Y, Wang YH, Dou XT, Guo HM, Ling TS. Endoscopic full-thickness resection: A definitive solution for local complete resection of small rectal neuroendocrine neoplasms. World J Gastroenterol 2025; 31(10): 100444 [PMID: 40093679 DOI: 10.3748/wjg.v31.i10.100444]
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"This is a well-constructed and well-written review, which gives readers with a general bioscience background updated information about the stem cell application in liver diseases (fatty liver diseases and steatohepatitis). The language is fluent, and the references are up to date. It will be easier for readers to understand the concepts if the authors provide a table to compare the 2D model with the 3D model. It will be helpful to include the abbreviation for each key word. "
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Silva B, Bragança J. Induced pluripotent stem cell-derived mesenchymal stem cells for modeling and treating metabolic associated fatty liver disease and metabolic associated steatohepatitis: Challenges and opportunities. World J Stem Cells 2025; 17(2): 99331 [PMID: 40061260 DOI: 10.4252/wjsc.v17.i2.99331]
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"The authors should provide adequate legends for each figure. Some parts of the paper are just a listing of facts and are poorly organized or discussed. The table in the paper is well organized and suited. A table to compare the pros and cons of different kinds of stem cells for muscle atrophy therapy will be helpful."
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Wang YJ, Chen ZH, Shen YT, Wang KX, Han YM, Zhang C, Yang XM, Chen BQ. Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy. World J Stem Cells 2025; 17(2): 98693 [PMID: 40061264 DOI: 10.4252/wjsc.v17.i2.98693]
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"Stem Cell Therapy: A New Hope for Patients with Skeletal Muscle Atrophy?
Skeletal muscle atrophy refers to the reduction or loss of muscle fibers due to nutritional deficiencies or diseases, leading to a decline in muscle mass. Current studies indicate that skeletal muscle atrophy is closely associated with an imbalance between protein synthesis and degradation, driven by multiple factors such as inflammation, oxidative stress, autophagy, and apoptosis [1-3]. Due to the complexity of its molecular mechanisms, effective therapeutic strategies are lacking, and traditional approaches like rehabilitation training and pharmacological interventions show limited efficacy. Therefore, exploring more effective treatments is imperative. Stem cell therapy, with its unique regenerative potential and immunomodulatory properties, offers a promising avenue for treating this condition.
In the current issue of the World Journal of Stem Cells, Ying-Jie Wang and colleagues published a review titled "Stem Cell Therapy: A Promising Therapeutic Approach for Skeletal Muscle Atrophy." The article summarizes the molecular mechanisms of muscle atrophy and highlights the applications of mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), and their derivatives (e.g., exosomes) in treating skeletal muscle atrophy. These stem cells exert therapeutic effects by modulating inflammation, promoting angiogenesis, suppressing oxidative stress, and facilitating muscle regeneration. The authors also address challenges in clinical translation, including immune rejection, tumorigenic risks, inefficient stem cell homing, and the absence of standardized protocols. Despite these hurdles, the review expresses optimism about the future of stem cell therapy, particularly emphasizing the superior potential of stem cell-derived acellular therapies (e.g., exosomes) over traditional cell transplantation.
We maintain a cautiously optimistic view regarding the prospects of stem cell therapy for skeletal muscle atrophy. While stem cell-based approaches, especially MSC- and exosome-based strategies, demonstrate promising safety and efficacy [4, 5], several issues must be resolved. These include addressing heterogeneity in stem cell sources, ensuring long-term safety, and establishing standardized protocols for clinical translation. Although iPSCs circumvent ethical concerns, their differentiation and purification techniques require optimization, and potential genetic mutations remain a concern. Exosomes, as acellular therapeutics, may reduce immune reactions; however, challenges in large-scale production and quality control persist.
Therapeutic Potential of Stem Cells
Stem cell therapy exhibits multidimensional potential in treating muscle atrophy. First, its mechanisms are highly synergistic: MSCs and iPSCs improve the muscle microenvironment by regulating inflammatory cytokines (e.g., suppressing IL-6 and TNF-α), promoting angiogenesis, inhibiting oxidative stress, and enhancing autophagy. Exosomes further amplify therapeutic effects by delivering functional miRNAs (e.g., miR-132-3p/FoxO3 axis) to delay protein degradation and stimulate regeneration [4, 6]. Second, exosomes as acellular carriers broaden clinical applicability: MSC-derived exosomes (e.g., hUC-MSC-Exos, ADSC-Exos) avoid immune rejection and tumorigenic risks associated with live cell transplantation. Their high biocompatibility and cargo of bioactive molecules (e.g., circHIPK3, AMPK/ULK1 regulators) enable targeted intervention in diabetes- or neuropathy-related atrophy, positioning them as pivotal tools for clinical translation [6, 7]. Third, iPSCs hold exceptional promise for personalized medicine. Their ability to differentiate into myogenic progenitor cells (MPCs) or motor neurons facilitates the reconstruction of neuromuscular junctions, offering precise repair for genetic atrophy (e.g., facioscapulohumeral muscular dystrophy, FSHD). While autologous iPSCs mitigate immune rejection, clinical application demands improved differentiation efficiency and safety [8, 9].
Current Challenges and Solutions
Clinical translation of stem cell therapy faces multiple challenges requiring innovative solutions. First, heterogeneity and standardization: MSC efficacy varies with donor age, tissue source (e.g., bone marrow, adipose, umbilical cord), and culture conditions [10]. Establishing unified quality control standards—via surface marker screening, secretome profiling, and single-cell sequencing—is critical to identify functional subpopulations and enable precision manufacturing [11]. Second, genetic instability and differentiation inefficiency hinder iPSC applications: reprogramming-induced mutations and inconsistent differentiation protocols (transgene-dependent or -independent) limit reliability [12]. Integrating non-integrative methods (e.g., mRNA reprogramming) and 3D organoid culture systems may optimize differentiation pathways [8]. Third, exosome scalability and targeting: natural exosomes suffer from low bioactive content and short half-lives. Engineering strategies (e.g., ligand modification or drug loading) can enhance tissue-specific delivery [13, 14], while microfluidic-nanocarrier systems may resolve production bottlenecks. Finally, accelerating clinical translation: preclinical studies predominantly rely on animal models; multicenter trials are needed to validate long-term safety (e.g., tumorigenicity, immune tolerance) [15, 16]. Combining stem cell therapy with anti-inflammatory agents (e.g., IL-1β inhibitors), rehabilitation, or gene editing (e.g., CRISPR-Cas9) may synergistically enhance efficacy [17, 18].
Future Directions
Future research should prioritize interdisciplinary integration and precision strategies. First, mechanistic insights: single-cell and spatial transcriptomics can unravel dynamic interactions between stem cells and the muscle microenvironment (e.g., satellite cells, macrophages), identifying key regulatory nodes (e.g., Wnt/β-catenin, PI3K/Akt pathways) [3, 19]. Second, biomaterial innovations: smart hydrogels or electroconductive scaffolds combined with localized stem cell/exosome delivery systems could enhance homing efficiency and functional persistence [20, 21]. Third, personalized approaches: tailored therapies based on disease-specific etiologies (e.g., ALS, diabetic atrophy) and molecular subtypes (e.g., inflammatory signatures) are essential. For instance, AMPK-activated umbilical cord MSCs may rectify metabolic dysregulation in diabetic atrophy [22, 23]. Lastly, ethical and regulatory frameworks: international guidelines must standardize stem cell therapies and clarify regulatory classifications (e.g., exosomes as "drugs") to accelerate clinical translation.
Stem cell therapy for skeletal muscle atrophy is transitioning from bench to bedside, yet critical hurdles—standardization, safety, and efficacy validation—remain. Integrating multidisciplinary technologies (e.g., synthetic biology, bioinformatics) and advancing translational research will bridge the gap between "laboratory breakthroughs" and "patient benefits."
References:
1. Zhang, H., et al., Oxidative stress: Roles in skeletal muscle atrophy. Biochem Pharmacol, 2023. 214: p. 115664.
2. Ji, Y., et al., Inflammation: Roles in Skeletal Muscle Atrophy. Antioxidants (Basel), 2022. 11(9).
3. Liang, W., et al., Epigenetic control of skeletal muscle atrophy. Cell Mol Biol Lett, 2024. 29(1): p. 99.
4. Huang, Z., et al., Skeletal Muscle Atrophy Was Alleviated by Salidroside Through Suppressing Oxidative Stress and Inflammation During Denervation. Front Pharmacol, 2019. 10: p. 997.
5. Song, J., et al., Mesenchymal stromal cells ameliorate diabetes-induced muscle atrophy through exosomes by enhancing AMPK/ULK1-mediated autophagy. J Cachexia Sarcopenia Muscle, 2023. 14(2): p. 915-929.
6. Archacka, K., et al., Hypoxia preconditioned bone marrow-derived mesenchymal stromal/stem cells enhance myoblast fusion and skeletal muscle regeneration. Stem Cell Res Ther, 2021. 12(1): p. 448.
7. Leong, J., et al., Surface Tethering of Inflammation-Modulatory Nanostimulators to Stem Cells for Ischemic Muscle Repair. ACS Nano, 2020. 14(5): p. 5298-5313.
8. Kim, H., et al., Genomic Safe Harbor Expression of PAX7 for the Generation of Engraftable Myogenic Progenitors. Stem Cell Reports, 2021. 16(1): p. 10-19.
9. Azzag, K., et al., Transplantation of PSC-derived myogenic progenitors counteracts disease phenotypes in FSHD mice. NPJ Regen Med, 2022. 7(1): p. 43.
10. Li, J., et al., The heterogeneity of mesenchymal stem cells: an important issue to be addressed in cell therapy. Stem Cell Res Ther, 2023. 14(1): p. 381.
11. Oguma, Y., et al., Single-cell RNA sequencing reveals different signatures of mesenchymal stromal cell pluripotent-like and multipotent populations. iScience, 2022. 25(11): p. 105395.
12. Shamsian, A., et al., Cancer cells as a new source of induced pluripotent stem cells. Stem Cell Res Ther, 2022. 13(1): p. 459.
13. Rezaie, J., et al., Mesenchymal stem cells derived extracellular vesicles: A promising nanomedicine for drug delivery system. Biochem Pharmacol, 2022. 203: p. 115167.
14. Yang, Q., et al., Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury. Bioact Mater, 2023. 26: p. 194-215.
15. Drela, K., et al., Experimental Strategies of Mesenchymal Stem Cell Propagation: Adverse Events and Potential Risk of Functional Changes. Stem Cells Int, 2019. 2019: p. 7012692.
16. Deuse, T., et al., Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol, 2019. 37(3): p. 252-258.
17. Iyer, S.R., et al., Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury. Am J Sports Med, 2020. 48(9): p. 2277-2286.
18. Chang, M., et al., Duchenne muscular dystrophy: pathogenesis and promising therapies. J Neurol, 2023. 270(8): p. 3733-3749.
19. Sartori, R., V. Romanello, and M. Sandri, Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun, 2021. 12(1): p. 330.
20. Luo, W., et al., Biomaterials-Based Technologies in Skeletal Muscle Tissue Engineering. Adv Healthc Mater, 2024. 13(18): p. e2304196.
21. Shan, Y., et al., Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges. Signal Transduct Target Ther, 2024. 9(1): p. 242.
22. Shen, Y., et al., Diabetic Muscular Atrophy: Molecular Mechanisms and Promising Therapies. Front Endocrinol (Lausanne), 2022. 13: p. 917113.
23. Yeo, C.J.J., E.F. Tizzano, and B.T. Darras, Challenges and opportunities in spinal muscular atrophy therapeutics. Lancet Neurol, 2024. 23(2): p. 205-218."
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Wang YJ, Chen ZH, Shen YT, Wang KX, Han YM, Zhang C, Yang XM, Chen BQ. Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy. World J Stem Cells 2025; 17(2): 98693 [PMID: 40061264 DOI: 10.4252/wjsc.v17.i2.98693]
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"Top-down therapy for Crohn's disease (CD) involves starting with the most potent medications, such as biologics and immunomodulators, immediately after early diagnosis. This strategy may lead to rapid induction of remission, promotion of mucosal healing, prevention of complications, and reduced need for surgery. However, the background factors influencing this top-down therapy have not been sufficiently examined.
A recent report on a Japanese cohort found that factors significantly associated with the recent top-down treatment approach were male gender, perianal lesions, no immunomodulators, and anti-tumor necrosis factor therapy. (Miyoshi J, Yoon A, Matsuura M, Hisamatsu T. Real-world use of biologics during the first year of treatment for newly diagnosed Crohn's disease in Japan: a claims analysis from 2010 to 2021. Intest Res. 2025 [PMID: 39848334 DOI: 10.5217/ir.2024.00082])
Top-down therapy for CD should be considered case-by-case, weighing potential benefits against risks and costs. As the authors suggest, identifying patients with a high genetic predisposition for CD may help predict their response to medications, the risk of side effects, and the cost-effectiveness. Further investigation in this area is desirable.
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Fan YH, Wang MW, Gao YN, Li WM, Jiao Y. Genetic and environmental factors influencing Crohn’s disease. World J Gastrointest Surg 2025; 17(3): 98526 [DOI: 10.4240/wjgs.v17.i3.98526]
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"Suggested Title:From Weakness to Wellness: The Role of Stem Cells in Muscle Atrophy Recovery
A. Clarity and Conciseness
• Some sections, particularly those on molecular mechanisms, are dense and could benefit from simplification or restructuring.
B. Novelty and Critical Analysis
• The review summarizes existing knowledge well but lacks critical analysis of conflicting findings.
• Consider discussing limitations of existing studies, such as sample size issues in preclinical models, potential biases, and reproducibility concerns.
• More emphasis could be placed on recent breakthroughs or innovative approaches in stem cell therapy, particularly in clinical trials.
C. Clinical Relevance and Future Directions
• The discussion of clinical applications is somewhat broad. It would be beneficial to include:
o Specific ongoing clinical trials (if available).
o A comparison of animal models vs. human studies to highlight translational challenges.
• The challenges section should offer potential solutions or strategies to overcome issues like immune rejection, tumorigenicity, and ethical concerns.
D. Specific Suggestions for Improvement
• Introduction: Emphasize the gap in current treatments that stem cell therapy aims to address.
• Current Treatment Strategies: Compare rehabilitation and pharmacological treatments with stem cell therapy in terms of: Efficacy, Limitations, Side effects.
• Exosome Therapy: This part is well-detailed, but it could benefit from a discussion on manufacturing challenges and standardization issues for clinical application.
• Conclusion: Strengthen the future perspectives by suggesting research directions or potential improvements in stem cell delivery methods."
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Wang YJ, Chen ZH, Shen YT, Wang KX, Han YM, Zhang C, Yang XM, Chen BQ. Stem cell therapy: A promising therapeutic approach for skeletal muscle atrophy. World J Stem Cells 2025; 17(2): 98693 [PMID: 40061264 DOI: 10.4252/wjsc.v17.i2.98693]
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"This review presents a comprehensive analysis of the role of Traditional Chinese Medicine (TCM) in the treatment of chronic atrophic gastritis (CAG), highlighting its multi-targeted therapeutic effects, including gastric mucosal protection, modulation of inflammatory responses, and improvement of microcirculation. The discussion is well-supported by clinical studies and meta-analyses, underscoring the potential benefits of specific herbal compounds such as berberine, morroniside, and notoginsenoside R1. However, the review also acknowledges a key challenge—the lack of standardized research methodologies and evaluation criteria, which limits the broader clinical application of TCM. While the evidence presented suggests promising therapeutic effects, future research should focus on large-scale randomized controlled trials to further validate these findings and establish consistent guidelines for integrating TCM into mainstream gastroenterology practice. Additionally, a more detailed discussion on potential interactions between TCM and conventional Western therapies would strengthen the clinical relevance of this review. Overall, this article makes a valuable contribution to the understanding of CAG management and provides a strong foundation for future research in this field."
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Wang L, Lian YJ, Dong JS, Liu MK, Liu HL, Cao ZM, Wang QN, Lyu WL, Bai YN. Traditional Chinese medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets. World J Gastroenterol 2025; 31(9): 102053 [PMID: 40061592 DOI: 10.3748/wjg.v31.i9.102053]
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"The study by Real Martinez et al. provides valuable insights into the role of circulating myokines such as irisin and FGF21 in MASLD, particularly their association with severe steatosis and advanced liver fibrosis. However, the absence of a relationship between skeletal muscle alterations (SMAs) and liver fibrosis stages raises intriguing questions. Could the lack of association be attributed to the heterogeneity of the cohort, or might it suggest that SMAs play a more indirect role in MASLD progression? Additionally, how might other metabolic or inflammatory pathways, not directly evaluated in this study, influence the interplay between muscle health and liver disease? Further studies exploring these aspects, especially in longitudinal designs or larger cohorts, would be invaluable in clarifying these relationships and their implications for clinical practice."
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Real Martinez Y, Fernandez-Garcia CE, Fuertes-Yebra E, Calvo Soto M, Berlana A, Barrios V, Caldas M, Gonzalez Moreno L, Garcia-Buey L, Molina Baena B, Sampedro-Nuñez M, Beceiro MJ, García-Monzón C, González-Rodríguez Á. Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease: A cross-sectional study. World J Gastroenterol 2025; 31(7): 100039 [PMID: 39991673 DOI: 10.3748/wjg.v31.i7.100039]
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"I congratulate the authors for the publication of their write up. It is well written with practical points. The information on greater likelihood of antibody generation with premixed insulins was new to me, although I believe it would have been partly due to the highly prevalent use of this form of insulin.
I would like the authors to understand this point as well while promoting the advantages of the newer insulins. In the international guidelines, at diagnosis of diabetes if the blood glucose levels are above 300 mg/dl and/or glycosylated hemoglobin level is more than 10 %, it is suggested to start the patient on insulin to reduce the glucotoxicity. Once the blood glucose levels reduce, say after 2-3 weeks, the patient may be switched to oral anti-diabetic agents. Such a guideline recommended practice is regularly followed in developing countries such as ours. In such a situation I have observed that the acceptance rate of premixed insulin which involves two pricks, is a lot better than that of multiple short acting insulin doses along with basal insulin. Since the duration of premixed insulin therapy in this context is short, the possible side effects of anti-insulin antibody generation as well as lipodystrophy are less likely. "
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Xia Y, Hu Y, Ma JH. Premixed insulin: Advantages, disadvantages, and future. World J Diabetes 2025; 16(3): 102526 [PMID: 40093285 DOI: 10.4239/wjd.v16.i3.102526]
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"This study presents an evaluation of a novel contrast-enhanced catheter with a chamfered tip. Achieving selective biliary cannulation is one of the most challenging endoscopic maneuver. We congratulate the authors on demonstrating in this paper that a novel device granted higher rates of biliary cannulation when retrospectively compared to a standard sphincterotome.
However, a few points warrant further discussion:
1. Generalizability: As a single-center retrospective study, the external validity of these findings could be enhanced with multicenter randomized trials. Variations in patient populations, procedural techniques, and institutional expertise might influence outcomes.
2. Non-expert outcomes: The results indicate a lack of significant improvement in outcomes among non-experts or trainees using the novel catheter. This suggests the device's utility may be contingent on the operator's skill. We also noticed that the expert performed procedure percentage was slightly higher (57% vs 50%) in the novel cathether group, and, although not
statistically significant, this could explain the lower use of advanced or rescue cannulation techniques.
3. Adverse Events (AEs): While the overall AE rates were low and comparable between groups, the trend toward fewer cases of PEP with the novel catheter merits closer scrutiny in larger cohorts as this could be an advantage in patients at risk for PEP. On the other hand, the non-statistically significant difference between the two groups in PEP incidence suggests us that the device used to achieve initial selective cannulation maybe isn’t that relevant in increasing PEP risk or incidence, but this should be confirmed in larger studies.
4. Cost-effectiveness: Although not discussed, evaluating the cost implications of adopting this catheter, including potential savings from reduced reliance on rescue techniques and decreased procedural times, would be beneficial for broader clinical adoption. We should also think of the negative aspects: for example, like stone clearance, achieving cannulation with a catheter would require a subsequent switch to a sphincterotome, increasing procedure length and costs, as you would be using two devices instead of one to achieve cannulation.
5. Papilla characteristics: we noticed that in the baseline characteristics intradiverticular papillas and oral oriented papillas were less represented in the catheter group. These types of papilla could benefit of the angling capabilities of a sphincterotome, so this could be a bias that needs to be furthermore cleared. In our experience the angling capabilities of a sphincterotome are crucial in achieving bile duct cannulation in difficult situations.
6. Malignant disease: we do know that malignant diseases (e.g. pancreatic cancer) affecting the ampullar area negatively affect rates of cannulation and increase the need for rescue or advanced techniques of cannulation. This point could have been furthermore discussed by making a distinction between cannulation failures in the setting of benign vs. malignant disease in both groups.
In conclusion, this study gives us valuable insights into advancing ERCP outcomes through innovative device design. We must experiment with more designs to compare results and finally choose the best device for cannulation in unexpected and difficult anatomies."
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Kaneko T, Kida M, Kurosu T, Kitahara G, Koyama S, Nomura N, Tahara K, Kusano C. Outcomes of bile duct cannulation using a novel contrast-enhanced catheter: A single-center, retrospective cohort study. World J Gastrointest Endosc 2025; 17(1): 97840 [PMID: 39850917 DOI: 10.4253/wjge.v17.i1.97840]
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"As a colorectal surgeon interested in colorectal cancer and the microbiome, I found this study highly relevant. The authors effectively highlight differences in mucosa-associated colonic microbiota between colorectal cancer (CRC) and non-CRC patients in Indonesia.
A key strength is the focus on mucosal rather than fecal microbiota, providing a clearer picture of the tumor microenvironment. The use of 16S rRNA sequencing with Oxford Nanopore Technologies enables detailed bacterial diversity analysis at the genus and species levels.
The study confirms the increased presence of Fusobacterium nucleatum and Bacteroides fragilis in CRC patients, supporting the link between microbial dysbiosis and carcinogenesis. The diagnostic potential of these bacterial markers is particularly noteworthy.
Further research with larger sample sizes and functional analyses, such as metagenomics or metabolomics, would enhance understanding of microbiota’s role in CRC. Additionally, while this study offers important insights for Asia, global research is needed to assess regional differences and their impact on CRC diagnostics and treatment."
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Darnindro N, Abdullah M, Sukartini N, Rumende CM, Pitarini A, Nursyirwan SA, Fauzi A, Makmun D, Nelwan EJ, Shatri H, Rinaldi I, Tanadi C. Differences in diversity and composition of mucosa-associated colonic microbiota in colorectal cancer and non-colorectal cancer in Indonesia. World J Gastroenterol 2025; 31(7): 100051 [PMID: 39991683 DOI: 10.3748/wjg.v31.i7.100051]
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"The manuscript is very clinically relevant. Here's a suggestion. Authors should provide the data on patients undergoing colonoscopy prior to capsule endoscopy examination. The retention rate of capsule endoscopy at 72 hours was 42.2%, which is still relatively high.It helps to reduce capsule retention in the colon after colonoscopy examination."
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O'Hara FJ, Costigan C, McNamara D. Extended 72-hour patency capsule protocol improves functional patency rates in high-risk patients undergoing capsule endoscopy. World J Gastrointest Endosc 2024; 16(12): 661-667 [PMID: 39735390 DOI: 10.4253/wjge.v16.i12.661]
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"This case report highlights the importance of en-bloc resection without fragmentation during endoscopic procedures and the challenges of endoscopic treatment for anal canal cancer. Traditionally, anal lesions have been primarily managed by surgeons, but ESD-related technique is performed mainly by the gastrointestinal endoscopists of internal medicine. Future collaboration between internal medicine and surgery departments will be crucial.
Surgery for anal cancer can significantly decrease patients' quality of life, which is why the authors' dedication to endoscopic treatment and follow-up is commendable. Anal canal cancer is rare, and it will be essential to determine which cases are suitable for endoscopic therapy in the future.
With the increasing prevalence of inflammatory bowel diseases in Asian regions, a rise in anal cancer cases associated with conditions like Crohn's disease is anticipated. Further case reports in this field are desirable.
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Kinoshita M, Maruyama T, Hike S, Hirosuna T, Kainuma S, Kinoshita K, Nakano A, Ohira G, Uesato M, Matsubara H. Complete resection of recurrent anal canal cancer using endoscopic submucosal dissection and transanal resection: A case report. World J Gastrointest Endosc 2025; 17(1): 101119 [PMID: 39850911 DOI: 10.4253/wjge.v17.i1.101119]
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"This is an excellent and insightful article. The authors have provided a comprehensive overview of the most impactful studies in the field of gastrointestinal endoscopy. It has greatly enhanced my understanding of the current research landscape and has inspired me to define more focused and meaningful directions for my own research in this area.
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Sui J, Luo JS, Xiong C, Tang CY, Peng YH, Zhou R. Bibliometric analysis on the top one hundred cited studies on gastrointestinal endoscopy. World J Gastrointest Endosc 2025; 17(1): 100219 [PMID: 39850908 DOI: 10.4253/wjge.v17.i1.100219]
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"This paper examines the differences in proficiency of AI tools for IBD patients and is considered a critical study for the inevitable future utilization of large language models in healthcare. However, it is merely a comparative study of large language models, and it remains unclear whether it contributes to improving IBD patients' literacy. Regarding patient education, Crohn's disease and ulcerative colitis belong to different categories, making it challenging to evaluate IBD as a whole comprehensively. Separate evaluations for ulcerative colitis and Crohn's disease patients would be preferable.
Furthermore, large language models alone are insufficient for shared decision-making that considers patients' social backgrounds for treatment selection, including biological agents (especially for Crohn's disease). Simply improving knowledge on several items through large language models may not be enough for clinical application. Future evaluations using large language models should address these points.
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Zhang Y, Wan XH, Kong QZ, Liu H, Liu J, Guo J, Yang XY, Zuo XL, Li YQ. Evaluating large language models as patient education tools for inflammatory bowel disease: A comparative study. World J Gastroenterol 2025; 31(6): 102090 [PMID: 39958450 DOI: 10.3748/wjg.v31.i6.102090]
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"Dear editor,
this is a review that summarizes the most recent evidence focused on the safety of the peroral endoscopic myotomy (POEM).
The manuscript is well written. However, I found some inaccuracies in the background.
The style, language and grammar are appropriate.
Since there are no figures or tables in the paper I answered no to the dedicated questions.
Although the safety of POEM is well explained, superficial informations were provided on the precision and the post-procedural management. Therefore, I would focus the article mainly on the safety, explaining better the post-procedural management."
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Christodoulidis G, Tsagkidou K, Koumarelas KE, Kouliou MN. Advances and challenges in peroral endoscopic myotomy: Safety, precision, and post-procedure management. World J Gastroenterol 2025; 31(5): 97574 [PMID: 39926218 DOI: 10.3748/wjg.v31.i5.97574]
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"This case is an extensively worked-up and well-written report. Best regards to the team. Stroke is not a clear-cut biophysics in neurology, with challenges in the clinical-radiological correlation encountered so often in clinical practice. As in this case, the work-up in SPECT could not convincingly determine theexact biomechanism of the clinical phenomena. However, it opened up information for future scopes of research into lacunar strokes. DSA, functional MRI, and Perfusion mismatch studies can also help in this type of situations. In contrast, the treatment is fairly less complicated in lacunar stroke.
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Tsai YH, Chen YH, Chao TC, Lin LF, Chang ST. New type of lacunar stroke presenting in brain perfusion images: A case report. World J Neurol 2024; 10(1): 98672 [DOI: 10.5316/wjn.v10.i1.98672]
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"Fu et al.'s recent study published in the World Journal of Psychiatry examines a complex connection between parenting stress, various family parenting styles, and the behavioral and emotional challenges that children experience. This study highlights the need for appropriate emotional management during the preschool years, demonstrating how differences in parental stress may have a significant impact on children's early emotional health. The analytical strength of this study is really impressive. The authors use structural equation modeling (SEM) to give a detailed examination of how different parenting styles mediate the relationships between these factors. Moreover, comprehensive questionnaire data collection contributes to a better understanding of family dynamics in a variety of environments.
According to the findings, parents report high levels of stress, which suggests that they face constant challenges. The study discovers a link between "hostile/coercive" parenting and problem behaviors in children, revealing the deleterious effects of negative strategies for parenting. This conclusion is consistent with previous research, which emphasizes the importance of understanding how inadequate parenting may lead to behavioral problems in children. Conversely, the negative connection with "supportive/engaged" parenting implies that positive approaches might provide large protective benefits, emphasizing the importance of specific treatments.
Besides, this study emphasizes how parenting styles serve as mediators in the relationship between parental stress and children's emotional health. The data show a 28.99% mediation impact, indicating that how parents handle stress influences the behaviors of their kids through their strategies for parenting. This finding not only strengthens the foundation for designing personalized therapies, but it also emphasizes the important need to improve parental practices. Also, the study points out the importance of providing parents with evidence-based strategies for managing their emotional health, with a focus on both parental and child well-being.
The study aims to establish a caring environment for preschoolers by giving practical ways to reduce stress and promoting positive parenting behaviors. It focuses on the broader impacts of various parenting styles, implying that investing in parental support systems is important for enhancing children's mental health and promoting total family happiness. This perspective is consistent with current trends in mental health initiatives and requires a comprehensive effort to address families' emotional needs, supplying the framework for future research in this important area.
Although Fu et al.'s work contributes significantly to our understanding of the link between parental stress and children's behavior, future research might profit from using a longitudinal strategy. Such an approach might allow researchers to investigate the changing dynamics of parental stress and child behavior over time, leading to a more comprehensive explanation of their causal relationships. Longitudinal studies may track how changes in parental stress affect the growth path of children's behavior by following the same set of participants at different points in time. This method not only gives a more in-depth understanding of these dynamics, but it also identifies potential mediators and moderators, offering light on the underlying reasons of the connections. Finally, this strategy may help us understand how the family environment affects children's developmental achievement.
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Fu ZW, Li YJ, Yu R, Guo RQ, Gao LX, Zhao SX. Relationship between parenting stress and behavioral and emotional problems in preschool children: A mediation effect analysis. World J Psychiatry 2025; 15(1): 100068 [PMID: 39831023 DOI: 10.5498/wjp.v15.i1.100068]
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"There is a need for non-invasive methods of evaluating mucosal healing in the small bowel. This study applies the principles of radiomics using small bowel CTE to develop a predictive normogram capable of predicting mucosal healing. Despite the study's stated limitations, it adds to the current literature, and extends the emerging field of radiomics in Crohn's disease."
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Ding H, Fang YY, Fan WJ, Zhang CY, Wang SF, Hu J, Han W, Mei Q. Computed tomography enterography-based radiomics for assessing mucosal healing in patients with small bowel Crohn's disease. World J Gastroenterol 2025; 31(3): 102283 [PMID: 39839900 DOI: 10.3748/wjg.v31.i3.102283]
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"The article presents a strong case for the use of endoscopic ultrasound-guided gastroenterostomy (EUS-GE) in managing gastric outlet obstruction (GOO). However, a few points could be clarified to strengthen its conclusions. Specifically, it would be helpful to elaborate on the inclusion or exclusion criteria for patient selection, as well as provide data on long-term outcomes like stent patency and recurrence rates. Additionally, discussing the learning curve associated with EUS-GE and the level of expertise required for its successful implementation would offer valuable insight for broader clinical adoption."
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Jagielski M. Endoscopic ultrasound guided-gastroenterostomy is the best choice in the treatment of gastric outlet obstruction. World J Gastrointest Endosc 2024; 16(12): 691-693 [PMID: 39735392 DOI: 10.4253/wjge.v16.i12.691]
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"The manuscript is very interesting. Global burden of human disorders caused by parasites is high. The topic is hot in selected areas. Those areas include not only Asia or Africa, but some parts of Eastern and Central Europe. I recommend to read the article for specialists in Hepatology, Liver surgery, including liver transplantation, Epademiology and Infectious Diuseases."
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Shahid Y, Emman B, Abid S. Liver parasites: A global endemic and journey from infestation to intervention. World J Gastroenterol 2025; 31(1): 101360 [PMID: 39777245 DOI: 10.3748/wjg.v31.i1.101360]
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"This editorial pointed out the connection between adipose tissue and intestinal bacteria in Crohn's disease (CD). It is an interesting paper. The authors found that Clostridium innocuum migrates to adjacent adipose tissue and remains "trapped" in the fat. As a result, immune cell migration and macrophage differentiation increase, leading to fibrosis, narrowing, and, eventually, the formation of creeping fat. Although the main cytokine release is mainly TNFα and IL-6 in adipocytes, the cytokine profile changes over time, especially in fibrosis, may be related to IL-17, and the dominant cytokines will change from IL-12 to IL-23, as previously pointed out. It is interesting to evaluate the aging adipose tissue in CD. However, it is difficult to determine the actual time of onset in patients with CD, and it is challenging to evaluate this issue. "
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Quaglio AE, Magro DO, Imbrizi M, De Oliveira EC, Di Stasi LC, Sassaki LY. Creeping fat and gut microbiota in Crohn’s disease. World J Gastroenterol 2025; 31(1): 102042 [PMID: 39777251 DOI: 10.3748/wjg.v31.i1.102042]
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"The authors provide evidence supporting the efficacy of serum-free cultured human umbilical cord mesenchymal stem cells (N-hUCMSCs) in treating knee osteoarthritis (OA). However, as the results indicate that the therapeutic effects of N-hUCMSCs, serum-cultured hUCMSCs (S-hUCMSCs), and hyaluronic acid (HA) are comparable, the rationale for prioritizing N-hUCMSCs warrants further exploration, particularly in comparison to the well-established use of HA.
There are also issues with data quality and clarity
1.The study administered three injections (at 2, 4, and 6 weeks after model establishment). However, the rationale for this dosing schedule is not provided. HA dosing is not described in the manuscript.
2.The source of the N-hUCMSCs and S-hUCMSCs should be disclosed. Were these cells derived from the same donor? If not, what were the baseline characteristics of each donor (e.g., age, health status)? Such details are critical, as MSC functionality can vary significantly based on donor conditions.
3.Some results, such as those described in Figure 1 and the observation that “Uneven chondrocyte thickness, disorganized cartilage structure, and increased clefts were more pronounced in the model control group than in the blank control group,” are inappropriately placed in the methods section. These descriptions should be moved to the results section.
4. Figure 3c and 3d: Both graphs have the same y-axis label, but according to the results section, one should represent IL-6 and the other IL-1β.
Figure 4a and 4b: These panels illustrate hematoxylin-eosin (HE) staining for the model and control groups. However, the HE results for the treatment groups (N-hUCMSCs, S-hUCMSCs, and HA) are missing. Including these results would provide a clearer comparison of treatment effects.
5.Figure 4d: The manuscript mentions that “The Mankin scores were significantly lower in the experimental group than in the model control group (P < 0.05),” but this result is not adequately represented in the figure.
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Xiao KZ, Liao G, Huang GY, Huang YL, Gu RH. Efficacy of serum-free cultured human umbilical cord mesenchymal stem cells in the treatment of knee osteoarthritis in mice. World J Stem Cells 2024; 16(11): 944-955 [PMID: 39619871 DOI: 10.4252/wjsc.v16.i11.944]
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"he significant impact of surgical approaches on male sexual dysfunction after rectal cancer surgery is highlighted by both this letter to the editor and the latest study by Numata et al. published in Annals of Surgery1). Damage to the autonomic nervous system during rectal cancer surgery is a major cause of sexual dysfunction, with problems such as ejaculatory dysfunction, erectile dysfunction, and sexual dysfunction commonly reported. These complications are particularly common with open surgery, and previous research has also shown that the incidence of sexual dysfunction following surgery is high.
However, advances in surgical techniques such as robotic surgery are expected to reduce these complications. The LANDMARC Study provided convincing evidence that robotic surgery significantly reduces the incidence of postoperative sexual dysfunction compared to laparoscopic surgery. The incidence of ejaculatory dysfunction at 12 months postoperatively was 25% in robotic surgery patients compared to 40.9% in laparoscopic surgery patients. The incidence of sexual dysfunction was 17.8% and 29%, respectively.
This letter to editor alos emphasized the importance of accurate surgical technique and knowledge of pelvic nerve anatomy. It also discussed the benefits of new techniques such as robotic surgery and transanal total mesorectal excision (Ta-TME), as well as the use of intraoperative pelvic nerve monitoring. These advances enhance nerve preservation, reduce complications, and improve patients' postoperative quality of life.
These findings highlight the need to adapt innovative surgical techniques in rectal cancer treatment to minimize adverse effects on sexual health while maintaining oncologic effectiveness.
1) Numata, Masakatsu, et al. "Prospective Multicenter Comprehensive Survey on Male Sexual Dysfunction following Laparoscopic, Robotic, and Transanal Approaches for Rectal Cancer (the LANDMARC Study)." Annals of Surgery: 10-1097"
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Kolokotronis T, Pantelis D. Urinary and sexual dysfunction after rectal cancer surgery: A surgical challenge. World J Gastroenterol 2024; 30(47): 5081-5085 [PMID: 39713160 DOI: 10.3748/wjg.v30.i47.5081]
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"since the patient also had general anesthesia, it should be clairifed to whihc degree analgesics given for the procedure prevented the patient from experienceing severe pain
xxxx xx x x x x x x x x x x x x x x x x x x x x x x xx x x x x x xx "
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Chen KH, Kang MY, Chang YT, Huang SY, Wu YS. Enhancing postoperative pain control by surgically-initiated rectus sheath block in abdominal aortic aneurysm open repair: A case report. World J Clin Cases 2025; 13(6): 100673 [PMID: 40012827 DOI: 10.12998/wjcc.v13.i6.100673]
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"The novelty of the topic is very important, suitable for fine rather than too broad content. The interpretation of statistical results needs to be rigorous, correlation does not mean causation, and the HR presented may be inaccurate. The discussion needs to be tightly focused on the results and not extend to other unwarranted conclusions."
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Chen DQ, Wu YX, Zhang YX, Yang HL, Huang HH, Lv JY, Xiao Q. Sarcopenia-associated factors and their bone mineral density levels in middle-aged and elderly male type 2 diabetes patients. World J Diabetes 2024; 15(12): 2285-2292 [PMID: 39676813 DOI: 10.4239/wjd.v15.i12.2285]
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"I would like to commend the authors for their comprehensive analysis of the complex interplay between gut microbiota, mesenteric adipose tissue (MAT), and creeping fat (CF) in the context of Crohn’s disease (CD). The manuscript provides a valuable contribution to the field.
The article meticulously elucidates the profound clinical significance of the interplay between the gut microbiota and MAT/CF. The authors have not only reviewed the current body of knowledge but have also contributed novel insights into the role of MAT and CF in shaping CD phenotypes and treatment strategies.The structure of the letter is well-organized, making it easy to follow the authors' line of reasoning. The abstract succinctly captures the essence of the study, and the core tip effectively highlights the main takeaways for the reader.The exploration of fecal microbiota transplantation (FMT) as a therapeutic strategy is both timely and relevant. The authors have successfully linked the current understanding of microbial imbalances to potential clinical applications, which could influence future treatment protocols for CD.
In conclusion, Hasnaoui et al. have provided a thought-provoking analysis of the role of gut microbiota and MAT/CF in CD. Their work not only advances our understanding of the disease but also offers promising avenues for therapeutic intervention."
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Hasnaoui A, Trigui R, Giuffrida M. Gut microbiota and mesenteric adipose tissue interactions in shaping phenotypes and treatment strategies for Crohn’s disease. World J Gastroenterol 2024; 30(46): 4969-4976 [PMID: 39679306 DOI: 10.3748/wjg.v30.i46.4969]
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"The author suggests to use in all diabetic patients an interesting technique, the” body surface gastric mapping” (BSGM), to detect the onset of gastric dysmotility precursor of gastroparesis, instead of invasive procedures, as gastroscopy, manometry, emptying of radiopaque markers or radioactive bolus and breath tests .
The idea is interesting , but there are some observations to make.
First of all the author forgot a simple, not invasive, physiologic and reliable method to measure gastric emptying, that is real-time ultrasonography, which allows the use of a normal solid–liquid meal and gives an immediate result (1).
Furthermore the author did not take into account the fact that, as indicated in figure 1 of ref. 4, the cause of delayed gastric emptying in gastroparesis may be also due, not only to antral dysmotility detectable with BSGM, but also to impaired pyloric relaxation upon arrival of antral peristalsis (pylorospasm) and, sometimes, to dysmotility of duodenum, which does not accept the bolus coming from the stomach.
The pylorospasm, which was observed in 14 of 24 diabetics, by Mearin et al (2) forms part of the widespread disruption of gut motility that affects some patients with diabetes.
Unfortunately these pyloric and duodenal motor abnormalities are not detected by the technique of BSGM, which could find a normal antral motility, giving the impression that everything is OK, while the gastric emptying is already delayed.
Therefore I would suggest to monitor the diabetic patients with the real-time ultrasonography, which is able to detect also a minimal delay in gastric emptying harbinger of gastroparesis, and, if the gastric emptying is delayed, then perform the BSGM, to see if the cause of the slowing is due to antral dysmotility. If the latter examination is negative, then the cause of delayed gastric emptying shoul be pylorospasm or duodenal dysmotility.
REFERENCES
1) Bolondi L, Bortolotti M, Santi V, Calletti T, Gaiani S, Labò G. Measurement of gastric emptying time by real-time ultrasonography. Gastroenterology. 1985 Oct; 89(4):752-9.PMID:3896910.
2) Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology. 1986 Jun;90(6):1919-25. doi: 10.1016/0016-5085(86)90262-3. PMID: 3699409
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Mori H. Early detection and intervention in diabetic gastroparesis: Role of body surface gastric mapping. World J Gastroenterol 2024; 30(45): 4836-4838 [PMID: 39649543 DOI: 10.3748/wjg.v30.i45.4836]
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"This article presents a case report of air embolism occurring during endoscopic retrograde cholangiopancreatography (ERCP), emphasizing the necessity for gastroenterologists to maintain a high level of vigilance regarding this potential complication during such procedures. While ERCP is a widely used and effective diagnostic and therapeutic technique, air embolism represents a serious complication that can significantly jeopardize patient health. Consequently, this article not only reviews pertinent cases and analyzes the mechanisms, clinical manifestations, and countermeasures associated with air embolism but also underscores the importance of preventive measures that medical staff should implement to minimize the incidence of such complications during ERCP. The aim of this article is to provide a comprehensive overview of relevant knowledge, thereby enabling medical professionals to better understand and address this issue, ultimately enhancing the safety and effectiveness of clinical operations."
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Li JH, Luo ZK, Zhang Y, Lu TT, Deng Y, Shu RT, Yu H. Systemic air embolism associated with endoscopic retrograde cholangiopancreatography: A case report. World J Gastrointest Endosc 2024; 16(11): 617-622 [PMID: 39600553 DOI: 10.4253/wjge.v16.i11.617]
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"Exercise during pregnancy improve organ development in offspring with gestational diabetes mellitus
Shengju Chen, Hangming Fan, Yu Chen
Abstract
In this commentary, we discuss the study by Tang et al., “Effect of exercise during pregnancy on offspring development through ameliorating high glucose and hypoxia in gestational diabetes mellitus”. Gestational diabetes mellitus (GDM), defined as ‘glucose intolerance with onset or first recognition during pregnancy’, impacts millions of women worldwide and poses significant health risks. Exercise during pregnancy has been shown to improve offspring health outcomes in obese mothers, potentially reducing epigenetic changes associated with maternal high-fat diets and minimizing abnormalities in lipid and glucose metabolism. However, while prenatal exercise’s impact on metabolic disorders in GDM offspring has been explored, its effects on organ growth remain insufficiently understood. Tang et al. identified GLUT1 and HIF1 as key regulators influencing the development of the heart, liver, and kidney in GDM offspring. Their study demonstrates that exercise during pregnancy supports organ development by inhibiting placental GLUT1 and HIF1 expression in GDM. This work contributes to understanding the role of GLUT1 and HIF1 in moderating the effects of prenatal exercise on organ development in GDM-affected offspring, supporting the idea that maternal exercise is an important intervention for improving offspring outcomes in GDM pregnancies and warrants further investigation in future epigenetic research.
Introduction
Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications, affecting approximately 20.9 million pregnant women and their newborns worldwide as of 2020. GDM is associated with a range of adverse pregnancy outcomes, including preeclampsia, polyhydramnios, and fetal organomegaly (Pettitt et al., 1980). Additionally, GDM poses several short-term risks to offspring, such as neonatal respiratory distress, metabolic complications (Ferrara et al., 2007), and increased perinatal mortality rates. The GDM quintet management model recommends five core interventions to mitigate these risks, exercise, dietary regulation, maternal education, pharmacological treatment, and fetal health evaluation (Association, 2003). Pathophysiologically, GDM is characterized by hyperglycemia, glucose intolerance, and insulin resistance, typically manifesting in the late second to early third trimester of pregnancy (Buchanan et al., 2012, Jovanovic and Pettitt, 2001, Pereira et al., 2015). Several mechanisms have been proposed to explain these outcomes, including chronic fetal hyperinsulinemia, impaired oxygenation due to elevated metabolic rates, and metabolic acidosis (Freinkel, 1980). In this commentary, we discuss the article by Tang et al., recently published in the recent issue of the World Journal of Diabetes, which explores the impact of maternal exercise during pregnancy on organ development in offspring of mothers with GDM.
Risks and complications associated with GDM
In a healthy pregnancy, insulin sensitivity decreases to allow more glucose availability for the fetus; however, normoglycemia is typically maintained through increased insulin production by pancreatic β-cells. In cases of GDM, the pancreas may fail to produce sufficient insulin, resulting in elevated blood glucose levels and the onset of GDM (Freinkel, 1980). GDM pregnancies can lead to additional complications that negatively impact maternal and fetal health (Poston et al., 2011). Immediate complications in offspring of overweight women with GDM include macrosomia, the most severe of which is shoulder dystocia; other neonatal complications such as hypoglycemia and hyperbilirubinemia have also been reported (Kaaja and Rönnemaa, 2008, Lecomte et al., 2017). Long-term exposure to GDM increases the risk of obesity, type 2 diabetes, and cardiovascular diseases (CVD) as offspring age (Capobianco et al., 2016). Epigenetic studies indicate that the intrauterine environment significantly influences offspring organ development, and exposure to elevated maternal blood levels can impair fetal health. Maintaining a healthy uterine environment is thus essential to promoting favorable health outcomes in offspring. Exercise, as a non-pharmacological intervention without side effects, is widely used in diabetes prevention and management. Given that pregnancy is a period when non-pharmacological interventions are especially favored by medical staff and patients, exercise is particularly promising for managing GDM.
Benefits of exercise during pregnancy
Eight national guidelines on exercise during pregnancy recommend 60-150 minutes of aerobic exercise per week for healthy pregnant women (Savvaki et al., 2018). The benefits of exercise for pregnant women include improved overall health, better weight management, reduced risk of GDM and gestational hypertension (Davenport et al., 2018, Yu et al., 2018). For women with GDM, moderate aerobic or combined exercise has been shown to enhance postprandial blood glucose control (Walter and Klaus, 2014), although the optimal duration and intensity remain unclear. Moderate exercise during pregnancy can improve maternal insulin sensitivity, reduce placental lipid accumulation in both male and female fetuses, and alleviate hypoxia, positively influencing the intrauterine environment and fetal growth (Laker et al., 2014). Exercise during pregnancy also promotes healthier liver glucose production, helps maintain liver triglycerides levels, and prevents the expression of liver enzymes and genes in offspring caused by maternal high-fat diet, thereby improving the offspring’s metabolic profile. These findings suggest that maternal exercise can mitigate modifications linked to a high-fat diet, protecting offspring from future metabolic diseases.
Regulation of GLUT1 by maternal exercise and offspring health outcomes in GDM
The placenta is responsible for transporting essential nutrients and oxygen from maternal to fetal circulation, as fetal gluconeogenesis is minimal (Kalhan and Parimi, 2000). GDM disrupts placental function, leading to various morphological (Treesh and Khair, 2015) and vascular changes (Aldahmash et al., 2022, El Sawy et al., 2018) and including fetal vascular changes and DNA methylation (Song et al., 2022). Placental transport proteins, such as glucose transporters, facilitate nutrient transfer from the mother to the fetus. Glucose is the primary energy source for both placental and fetal growth (Stanirowski et al., 2017), with GLUT1 and GLUT3 serving as the main placental glucose transport proteins in humans. GLUT1 is expressed in syncytiotrophoblast microvilli and the basal membrane, as well as in vascular endothelium and cell layers (Brown et al., 2011, Jansson et al., 1993). Research on GDM in humans and mice shows increased placental GLUT1 expression, likely due to increased glucose availability in maternal circulation, which enhances placental glucose consumption (Muralimanoharan et al., 2016). This increase in GLUT1 may contribute to the higher rates of macrosomia observed in GDM pregnancies (Stanirowski et al., 2022). Moreover, GDM leads to placental hypoxia, elevated hypoxia-inducible (HIF) levels, and glial cell missing 1 degradation, inhibiting trophoblast migration and invasion. Exercise during pregnancy can significantly reduce placental GLUT1 expression and alleviate hypoxia. Silencing GLUT1 can partially counteract the reduced trophoblast migration caused by hyperglycemia and hypoxia. Beyond energy metabolism, GLUT1 is also related to the development of the heart, liver, and kidneys. Zhang et al. investigated the relationship between GLUT1 expression in these organs and their structural and pathological changes, examining how exercise influences growth and development in offspring with GDM. In a neonatal GLUT1 transgenic heart model, increased glucose metabolism can stimulate hyperplastic growth after cardiac injury (Fajardo et al., 2021). Maternal exercise during pregnancy has been shown to lower hepatic GLUT1 expression, reduce inflammatory infiltration, and decrease the risk of liver disease in adult offspring (Baker and Friedman, 2018). In the kidney, GLUT1 functions vary by cell type; elevated GLUT1 in mesangial cells can impair kidney structure, while in podocytes, it may reduce mesangial expansion and fibronectin accumulation (Chen et al., 2024). Future research is recommended to clarify the specific mechanisms by which exercise benefits renal structure and function in GDM offspring.
Directions for future studies
The specific mechanisms by which maternal exercise during pregnancy improves health outcomes in diabetic offspring remain under investigation, with multiple synergistic pathways likely involved. Given its role in glucose metabolism, GLUT1 is of particular interest as a regulatory factor in mitigating adverse outcomes in offspring of mothers with GDM through exercise. This underscores the significant influence of exercise on glucose metabolism, which enhances the intrauterine environment and supports offspring health. Improved placental GLUT1 expression appears to regulate the GLUT1 levels in offspring organs, positively impacting organ development. These findings extend our understanding of exercise-related epigenetics modifications, yet further research is essential to clarify the pathways through which maternal exercise regulates placental GLUT1, thereby promoting healthy organ development in offspring and underscoring the benefits of prenatal exercise.
Conclusion
GDM can lead to adverse outcomes for both the mother and their offspring. Maternal exercise during pregnancy improves the intrauterine environment and enhances offspring health. Elevated maternal blood glucose can cause fetal hyperinsulinemia, hypoxia, and metabolic acidosis. Exercise enhances glucose metabolism, reduces high blood sugar levels, and supports a healthier intrauterine environment, thereby decreasing the risk of metabolic diseases in offspring. The study by Tang et al. confirms the association between elevated placental GLUT1 expression in GDM and abnormal offspring organ development related to hypoxia. Their research demonstrates that exercise during pregnancy can improve placental glucose transport and reduce hypoxia, mitigating adverse developmental outcomes in offspring organs at various stages. These findings validate, across human, animal, and cellular models, the molecular mechanisms through which maternal exercise enhances organ development in offspring affected by GDM. This contributes to clinical application and emphasizes the role of epigenetics in promoting offspring health. As research in epigenetic progresses, the pathways through exercise benefits GDM-affected offspring will become clearer, with GLUT1 as a central regulator of glucose metabolism. Further investigation into these mechanisms will advance our understanding of how maternal exercise supports healthier outcomes for GDM offspring.
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Baker, P.R., 2nd, Friedman, J.E., 2018. Mitochondrial role in the neonatal predisposition to developing nonalcoholic fatty liver disease. J Clin Invest 128 (9), 3692-3703.
Brown, K., Heller, D.S., Zamudio, S., Illsley, N.P., 2011. Glucose transporter 3 (GLUT3) protein expression in human placenta across gestation. Placenta 32 (12), 1041-1049.
Buchanan, T.A., Xiang, A.H., Page, K.A., 2012. Gestational diabetes mellitus: risks and management during and after pregnancy. Nat Rev Endocrinol 8 (11), 639-649.
Capobianco, E., Fornes, D., Linenberg, I., Powell, T.L., Jansson, T., Jawerbaum, A., 2016. A novel rat model of gestational diabetes induced by intrauterine programming is associated with alterations in placental signaling and fetal overgrowth. Mol Cell Endocrinol 422, 221-232.
Chen, Y., Bai, X., Chen, J., Huang, M., Hong, Q., Ouyang, Q., Sun, X., Zhang, Y., Liu, J., Wang, X., Wu, L., Chen, X., 2024. Pyruvate kinase M2 regulates kidney fibrosis through pericyte glycolysis during the progression from acute kidney injury to chronic kidney disease. Cell Prolif 57 (2), e13548.
Davenport, M.H., Ruchat, S.M., Poitras, V.J., Jaramillo Garcia, A., Gray, C.E., Barrowman, N., Skow, R.J., Meah, V.L., Riske, L., Sobierajski, F., James, M., Kathol, A.J., Nuspl, M., Marchand, A.A., Nagpal, T.S., Slater, L.G., Weeks, A., Adamo, K.B., Davies, G.A., Barakat, R., Mottola, M.F., 2018. Prenatal exercise for the prevention of gestational diabetes mellitus and hypertensive disorders of pregnancy: a systematic review and meta-analysis. Br J Sports Med 52 (21), 1367-1375.
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Fajardo, V.M., Feng, I., Chen, B.Y., Perez-Ramirez, C.A., Shi, B., Clark, P., Tian, R., Lien, C.L., Pellegrini, M., Christofk, H., Nakano, H., Nakano, A., 2021. GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration. Sci Rep 11 (1), 8669.
Ferrara, A., Weiss, N.S., Hedderson, M.M., Quesenberry, C.P., Jr., Selby, J.V., Ergas, I.J., Peng, T., Escobar, G.J., Pettitt, D.J., Sacks, D.A., 2007. Pregnancy plasma glucose levels exceeding the American Diabetes Association thresholds, but below the National Diabetes Data Group thresholds for gestational diabetes mellitus, are related to the risk of neonatal macrosomia, hypoglycaemia and hyperbilirubinaemia. Diabetologia 50 (2), 298-306.
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Kaaja, R., Rönnemaa, T., 2008. Gestational diabetes: pathogenesis and consequences to mother and offspring. Rev Diabet Stud 5 (4), 194-202.
Kalhan, S., Parimi, P., 2000. Gluconeogenesis in the fetus and neonate. Semin Perinatol 24 (2), 94-106.
Laker, R.C., Lillard, T.S., Okutsu, M., Zhang, M., Hoehn, K.L., Connelly, J.J., Yan, Z., 2014. Exercise prevents maternal high-fat diet-induced hypermethylation of the Pgc-1α gene and age-dependent metabolic dysfunction in the offspring. Diabetes 63 (5), 1605-1611.
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Muralimanoharan, S., Maloyan, A., Myatt, L., 2016. Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: role of miR-143. Clin Sci (Lond) 130 (11), 931-941.
Pereira, T.J., Moyce, B.L., Kereliuk, S.M., Dolinsky, V.W., 2015. Influence of maternal overnutrition and gestational diabetes on the programming of metabolic health outcomes in the offspring: experimental evidence. Biochem Cell Biol 93 (5), 438-451.
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Savvaki, D., Taousani, E., Goulis, D.G., Tsirou, E., Voziki, E., Douda, H., Nikolettos, N., Tokmakidis, S.P., 2018. Guidelines for exercise during normal pregnancy and gestational diabetes: a review of international recommendations. Hormones (Athens) 17 (4), 521-529.
Song, J.Y., Lee, K.E., Byeon, E.J., Choi, J., Kim, S.J., Shin, J.E., 2022. Maternal Gestational Diabetes Influences DNA Methylation in the Serotonin System in the Human Placenta. Life (Basel) 12 (11).
Stanirowski, P.J., Szukiewicz, D., Majewska, A., Wątroba, M., Pyzlak, M., Bomba-Opoń, D., Wielgoś, M., 2022. Placental expression of glucose transporters GLUT-1, GLUT-3, GLUT-8 and GLUT-12 in pregnancies complicated by gestational and type 1 diabetes mellitus. J Diabetes Investig 13 (3), 560-570.
Stanirowski, P.J., Szukiewicz, D., Pyzlak, M., Abdalla, N., Sawicki, W., Cendrowski, K., 2017. Impact of pre-gestational and gestational diabetes mellitus on the expression of glucose transporters GLUT-1, GLUT-4 and GLUT-9 in human term placenta. Endocrine 55 (3), 799-808.
Treesh, S.A., Khair, N.S.B., 2015. Histological Changes of the Human Placenta in Pregnancies Complicated with Diabetes. Journal of Cytology and Histology 6, 1-7.
Walter, I., Klaus, S., 2014. Maternal high-fat diet consumption impairs exercise performance in offspring. J Nutr Sci 3, e61.
Yu, Y., Xie, R., Shen, C., Shu, L., 2018. Effect of exercise during pregnancy to prevent gestational diabetes mellitus: a systematic review and meta-analysis. J Matern Fetal Neonatal Med 31 (12), 1632-1637.
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Tang YB, Wang LS, Wu YH, Zhang LX, Hu LY, Wu Q, Zhou ML, Liang ZX. Effect of exercise during pregnancy on offspring development through ameliorating high glucose and hypoxia in gestational diabetes mellitus. World J Diabetes 2024; 15(11): 2203-2219 [PMID: 39582571 DOI: 10.4239/wjd.v15.i11.2203]
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"I would love to congratulate the authors for writing this excellent editorial about malignant gastric outlet obstruction. The authors have given an overview of the changing spectrum of therapeutic modalities from surgery to endoscopic stenting to the latest EUS-guided interventions. There was an enlightening discussion about the potential benefit of stomach-partitioning gastrojejunostomy to reduce the rate of delayed gastric emptying. The authors have rightly advocated the need for a holistic approach to treat patients with malignant gastric outlet obstructions, keeping in mind their nutritional and clinical status.
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Jiang L, Chen XP. Treatment of choice for malignant gastric outlet obstruction: More than clearing the road. World J Gastrointest Endosc 2024; 16(11): 587-594 [PMID: 39600555 DOI: 10.4253/wjge.v16.i11.587]
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"I would like to congratulate the authors for reporting a rare but potentially treatable complication of ERCP. The authors have clearly stated the scenarios when air embolism should be suspected in a patient undergoing ERCP. The authors have beautifully shown the relevant images showing air embolism. They have also discussed in detail about the timing and efficacy of hyperbaric oxygen therapy for such patients. As GI endoscopists doing regular ERCP, we should be aware of all the potential complications of ERCP, their manifestations, how to diagnose them early and the readily available treatment modalities and availability. "
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Li JH, Luo ZK, Zhang Y, Lu TT, Deng Y, Shu RT, Yu H. Systemic air embolism associated with endoscopic retrograde cholangiopancreatography: A case report. World J Gastrointest Endosc 2024; 16(11): 617-622 [PMID: 39600553 DOI: 10.4253/wjge.v16.i11.617]
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"Re-evaluating the clinical impact of functional regulatory variants
Ying Ming, Yun-Ling Du, Meng-Na Zhang
Ying Ming, Molecular Diagnosis Center,The Affiliated Hospital of Chengde Medical University, Chengde, 067000, China
Yun-Ling Du, Molecular Diagnosis Center,The Affiliated Hospital of Chengde Medical University, Chengde, 067000, China
Meng-Na Zhang, Molecular Diagnosis Center,The Affiliated Hospital of Chengde Medical University, Chengde, 067000, China
Meng-Na Zhang, Hebei Key Laboratory of Panvascular Diseases, Chengde, 067000, China
ORCID number: Ying Ming (0009-0006-2161-8207) , Yun-Ling Du (0000-0001-7624-3226) , Meng-Na Zhang (0000-0001-7624-3226)
Author contributions: Ying Ming contributed to the initial drafting of the work; Yun-Ling Du contributed to the drafting process; Meng-Na Zhang contributed to the initial drafting and provided overall supervision to the drafting process; All authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Corresponding author: Meng-Na Zhang, Molecular Diagnosis Center,The Affiliated Hospital of Chengde Medical University, Chengde, China zhangmengna2014@sina.com
Abstract
Serotonin 1A receptor polymorphism (5-HTR1A) C-1019G polymorphism (rs6295) is a functional regulatory variants reported to be related with multiple phenotypes including major depression, suicidal behavior and antidepressant response. However, clinical studies investigating this variant and its potential phenotypes had incongruous findings. Molecular studies on this variant showed it does regulate HTR1A expression but meta-analysis showed it had negative relationship with antidepressant drug response in major depressive disorder (MDD), as reported by Wu et al. in the lasted issue of the World Journal of Psychiatry. This suggested the importance of re-evaluating the clinical impact of functional regulatory variants.
Key words: regulatory variants, snp-meta, snp-phenotype association
Core Tip: Functional regulatory variants might have negative relationship with putative phenotypes even it do regulate gene expression. Single nucleotide polymorphism (SNP) meta analysis helps to identify a more robust SNP-phenotype relationship.
We carefully read the article titled “Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder: A meta-analysis” published in the World Journal of Psychiatry by Wu et al.[1]. In this study the authors reviewed 11 clinical studies about serotonin 1A receptor polymorphism (5-HTR1A) C-1019G polymorphism (rs6295) and antidepressant response. Though reported to be related with major depression[2], suicidal behavior[3] and antidepressant response[4], rs6295 did not show significant association with antidepressant drug response in major depressive disorder (MDD) in this meta-analysis.
Genome-wide association studies (GWAS) show to be a useful tool to investigate the effect of polymorphism on clinical phenotypes. Most disease-associated variants are non-coding variants. Researchers have developed multiple methods to identify functional regulatory variants from putative regulatory regions and their cis-regulated genes, like massively parallel reporter assays (MPRAs) and expression quantitative trait loci (eQTL)[5,6]. The 5-HTR1A C-1019G polymorphism (rs6295) reviewed by Wu et al. [1] is a functional upstream variant that affects HTR1A expression but not associates with antidepressant response in patients with MDD, though the 5-HT1A receptor is a primary target for most antidepressant drugs.
This variant has been reported to influence HTR1A expression in numerous molecular studies. The C-allele of this variant is capable of interacting with transcription factors (TFs) such as Hes1, Hes5, and Deaf1, whereas the G-allele fails to bind these TFs [7]. Although these three TFs are typically regarded as repressors, the activity of Deaf1 at the 5-HT1A promoter exhibits opposing effects in presynaptic versus postsynaptic neuronal cells [7]. In the human prefrontal cortex, the G-allele demonstrates a lower expression level compared to the C-allele; however, this pattern does not hold true for the midbrain and hippocampus [8]. In a humanized mouse model, subjects with GG genotype exhibited higher levels of HTR1A mRNA and protein than those with CC genotype in a line-dependent manner [9]. Furthermore, in 5-HT1A-expressing neuronal cells, the G-allele was found to downregulate 5-HT1A expression [10]. These showed the complexity of regulatory variant function.
Clinical researches on rs6295 had incongruous findings, raising the need for a SNP-based meta analysis. A single variant approach is a classical method to ascertain the relationship between a variant and putative phenotypes. Selective serotonin re-uptake Inhibitors (SSRIs) like fluoxetine, paroxetine, sertraline, citalopram, and fluvoxamine were included in this meta analysis, however, the result showed no significant correlation between this variation and antidepressant drug efficacy in MDD in the dominant model (CG vs CC), recessive model (GG vs CC), and combined dominant model (CG+GG vs CC). The 11 clinical studies collected in their meta analysis included multiple populations from over 10 countries with low to moderate heterogeneity and were scored 7-9 according to the Newcastle-Ottawa Scale (NOS), suggesting a result with higher confidence.
The negative correlation might due to gene-gene interactions or gene-environment interactions in MDD and its treatment. A genome-wide linkage analysis for MDD showed that association of LHPP SNPs to MDD were depended on HTR1A -1019G allele [11]. Single variant approaches are limited by lower statistical detection power because most phenotypes result from the influence of many genetic variants in many genes and pathways[12]. This limitation is particularly pronounced in pharmacogenetics and multigenic diseases like MDD. Large-scale meta-analysis of GWAS might overcome this disadvantage. However, phenotype analysis involving rs6295 through GWAS is inherently limited due to its ambiguous nature (C/G). It is challenging to distinguish which complementary allele serves as the effect allele. Furthermore, the minor allele frequency (MAF) of rs6295 is G=0.483 in gnomAD and C=0.458 in 1000G, making it impossible to solve the problem by allele frequency. Ambiguous SNPs with allele frequencies close to 0.5 are usually removed in GWAS [13]. Therefore, a SNP meta-analysis remains a viable option for investigating rs6295.
The clinical impacts of regulatory variants in monogenic Mendelian diseases have also been noticed. Many bioinformatic tools were developed to predict TF binding of regulatory variants like SNEEP [14]. Many of them use eQTL datasets as training and validation sets. In rs6295’s case, the variant had different functions in different brain regions, and showed negative significance to putative related phenotype. This suggested a limitation of using these tools to predict clinical candidate variants. However, there are few clinical curated regulatory variants databases available. There are only hundreds of regulatory variants in Clinvar database classified as pathogenic/likely pathogenic/benign/likely benign (data not shown). That’s not enough to feed a complex model.
Overall, the negative relationship between the functional regulatory variant rs6295 and antidepressant response underscores the importance of re-evaluating the clinical significance of functional regulatory variants. Both positive and negative meta-analyses are essential for establishing robust relationships between polymorphisms and phenotypes.
References
[1] Wu HN, Zhu SY, Zhang LN, Shen BH, Xu LL. Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder: A meta-analysis. World J Psychiatry 2024; 14(10): 1573-1582
[2]Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, Sequeira A, Kushwaha N, Morris SJ, Basak A, Ou XM, Albert PR. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci. 2003 Sep 24;23(25):8788-99
[3]Hernández-Díaz, Y., Tovilla-Zárate, C. A., Castillo-Avila, R. G., Juárez-Rojop, I. E., Genis-Mendoza, A. D., López-Narváez, M. L., Villar-Juárez, G. E., & González-Castro, T. B. (2023). Association between the HTR1A rs6295 gene polymorphism and suicidal behavior: an updated meta-analysis. European archives of psychiatry and clinical neuroscience, 273(1), 5–14
[4]Lemonde S, Du L, Bakish D, Hrdina P, Albert PR. Association of the C(-1019)G 5-HT1A functional promoter polymorphism with antidepressant response. Int J Neuropsychopharmacol. 2004 Dec;7(4):501-6
[5]Abell NS, DeGorter MK, Gloudemans MJ, Greenwald E, Smith KS, He Z, Montgomery SB. Multiple causal variants underlie genetic associations in humans. Science. 2022 Mar 18;375(6586):1247-1254
[6]Umans BD, Battle A, Gilad Y. Where Are the Disease-Associated eQTLs? Trends Genet. 2021 Feb;37(2):109-124
[7]Czesak M, Lemonde S, Peterson EA, Rogaeva A, Albert PR. Cell-specific repressor or enhancer activities of Deaf-1 at a serotonin 1A receptor gene polymorphism. J Neurosci. 2006 Feb 8;26(6):1864-71
[8]Donaldson ZR, le Francois B, Santos TL, Almli LM, Boldrini M, Champagne FA, Arango V, Mann JJ, Stockmeier CA, Galfalvy H, Albert PR, Ressler KJ, Hen R. The functional serotonin 1a receptor promoter polymorphism, rs6295, is associated with psychiatric illness and differences in transcription. Transl Psychiatry. 2016 Mar 1;6(3):e746
[9]Cunningham AM, Santos TL, Gutzeit VA, Hamilton H, Hen R, Donaldson ZR. Functional Interrogation of a Depression-Related Serotonergic Single Nucleotide Polymorphism, rs6295, Using a Humanized Mouse Model. ACS Chem Neurosci. 2019 Jul 17;10(7):3197-3206
[10]Czesak M, Lemonde S, Peterson EA, Rogaeva A, Albert PR. Cell-specific repressor or enhancer activities of Deaf-1 at a serotonin 1A receptor gene polymorphism. J Neurosci. 2006 Feb 8;26(6):1864-71
[11]Neff CD, Abkevich V, Packer JC, Chen Y, Potter J, Riley R, Davenport C, DeGrado Warren J, Jammulapati S, Bhathena A, Choi WS, Kroeger PE, Metzger RE, Gutin A, Skolnick MH, Shattuck D, Katz DA. Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression. Mol Psychiatry. 2009 Jun;14(6):621-30
[12]Defo J, Awany D, Ramesar R. From SNP to pathway-based GWAS meta-analysis: do current meta-analysis approaches resolve power and replication in genetic association studies? Brief Bioinform. 2023 Jan 19;24(1):bbac600
[13]Ndong Sima, C.A.A., Step, K., Swart, Y. et al. Methodologies underpinning polygenic risk scores estimation: a comprehensive overview. Hum. Genet. 143, 1265–1280 (2024)
[14]Baumgarten N, Rumpf L, Kessler T, Schulz MH. A statistical approach for identifying single nucleotide variants that affect transcription factor binding. iScience. 2024 Apr 18;27(5):109765"
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Wu HN, Zhu SY, Zhang LN, Shen BH, Xu LL. Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder: A meta-analysis. World J Psychiatry 2024; 14(10): 1573-1582 [PMID: 39474388 DOI: 10.5498/wjp.v14.i10.1573]
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"This study provides valuable insights into the treatment of Helicobacter pylori infection. The comparison between low - dose and standard - dose tetracycline in combination with amoxicillin quadruple therapy is well - designed and the results are significant.The research is comprehensive, considering factors such as eradication rates and adverse events. It offers a potential alternative treatment option with better safety profiles, which is beneficial for patients.
Also, there still exist some questions to be considered.
1. Regarding the article structure
• When introducing the research background, various antibiotic resistance rates against Helicobacter pylori are listed in detail. However, could this part be presented more concisely and focused more on the resistance situations of tetracycline and amoxicillin directly related to this study?
• In the research methods section, could the description of the patient inclusion and exclusion criteria be more focused on the key points and avoid being interfered by too many irrelevant details? For example, the emphasis could be placed on those factors that may have a crucial impact on the research results.
• In the results presentation part, could the comparison results of different groups be shown in a clearer structure? For example, the main results of all groups could be presented first, and then the situations of each subgroup (such as the primary treatment group and the rescue treatment group) could be elaborated in detail respectively, which would make it easier for readers to grasp the overall logic.
2. Regarding the article content
• When discussing the advantages of low - dose tetracycline, besides comparing the eradication rates and adverse events with the standard - dose tetracycline, could the possible mechanism of action be further explored? This would help readers understand the research results more in - depth.
• Some factors affecting the Helicobacter pylori eradication rate are mentioned in the article, such as patient compliance, smoking history, etc. However, could a more in - depth analysis of the interactions between these factors be carried out? For example, does smoking affect the eradication rate by influencing compliance?
• Regarding the content of the gut microbiota, although it is mentioned in the limitations that the impact of the low - dose tetracycline regimen on the gut microbiota has not been studied, could the future research directions be more specifically elaborated on how to design relevant studies to explore this issue?
3. Regarding the charts
• There is a lot of data in the tables in the article, and some abbreviations in the tables may confuse readers. Could more detailed explanations be given below the tables or where the abbreviations first appear?
• Could the titles of the charts more clearly reflect the core content of the charts? For example, some chart titles only simply describe the variables involved in the charts without highlighting the main conclusions or trends.
• Could some more charts be considered to present the key information in the research more intuitively? For example, charts could be used to show the occurrence trends of adverse events in different tetracycline dose groups during the treatment process, or to present the relative magnitudes of the impacts of different factors on the eradication rate.
4.Further study
• It would be interesting to see if the results hold true in different populations and geographical regions.
• The study could have included a more detailed analysis of the long - term effectiveness and potential recurrence of H. pylori infection after treatment.
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Zhao YR, Wang XJ, Zhu MJ, Chen AL, Zhang D, Du Q, Kim JJ, Hu WL. Efficacy and safety of low-dose tetracycline, amoxicillin quadruple therapy in Helicobacter pylori infection: A retrospective single center study. World J Gastroenterol 2024; 30(39): 4295-4304 [PMID: 39492823 DOI: 10.3748/wjg.v30.i39.4295]
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"This paper conducts an in-depth study on the effects of invigorating-spleen and anticancer prescription (ISAP) in a mice model of colon cancer, providing valuable experimental data and analysis. Here are some of my comments on the paper:
1. Clear research background: The paper begins with a detailed introduction to the epidemiological data of colon cancer, emphasizing the severity of the disease and the limitations of existing treatment methods, providing a good background for the necessity of the study.
2. Reasonable experimental design: The study established a mice model of colon cancer and divided it into several experimental groups (including a control group and groups with different doses of ISAP), a design that effectively compares the effects of different doses of ISAP on tumor suppression.
3. Detailed data analysis: The paper provides detailed data on the measurement of mice weight, tumor inhibition rate, and related protein expression levels, with clear and understandable results. These data provide empirical support for the anti-tumor mechanism of ISAP.
4. In-depth mechanism exploration: By analyzing key proteins in the ERK/MAPK signaling pathway, the paper explores the potential mechanism of action of ISAP, providing new ideas for subsequent research.
5. Clinical significance: Although the study has achieved positive results in the mice model, the effectiveness and safety of ISAP still need to be verified in clinical trials. This point can be further emphasized in the discussion section.
6. Language and structure: The language of the paper is relatively fluent, with a clear structure, making it easy for readers to understand. However, the explanation of some professional terms could be more detailed, for the understanding of non-professional readers.
Overall, this paper provides strong support for the potential of ISAP in the treatment of colon cancer, looking forward to seeing more clinical research results in the future."
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Wang W, Wang J, Ren XX, Yue HL, Li Z. Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model. World J Gastrointest Oncol 2024; 16(11): 4468-4476 [PMID: 39554742 DOI: 10.4251/wjgo.v16.i11.4468]
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"The original article by Wang FD et al., "Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischaemia-reperfusion injury via TXNIP regulation," is very good.
GABA-induced miR-21-5p-loaded EVs utilise a unique mechanism to lessen myocardial ischaemia-reperfusion injury (MIRI) and present a novel method for managing MIRI through oxidative stress modulation. The study reported that miR-21-5p exerts its effects through a direct interaction with TXNIP in cardiomyocytes, thereby triggering oxidative stress and elucidating related molecular mechanisms. Furthermore, this work systematically employs in vivo, in vitro, and a variety of imaging methods with gene knockout models to provide comprehensive methodological proofs.
Considering myocardial ischaemia is a common clinical condition, this study has high translational relevance.
But there are few queries:
The experiment only evaluates its EV source in inguinal ADSCs and could miss other potential beneficial configurations of EV.
It is still unclear whether these short-term therapeutic effects are sustainable or if they interfere with repeated dosing against MIRI, despite the study's lack of a long-term assessment.
The process of producing, standardizing, and ensuring the safety of EVs for human use could potentially complicate the clinical translation of the latter strategy."
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Wang FD, Ding Y, Zhou JH, Zhou E, Zhang TT, Fan YQ, He Q, Zhang ZQ, Mao CY, Zhang JF, Zhou J. Gamma-aminobutyric acid enhances miR-21-5p loading into adipose-derived stem cell extracellular vesicles to alleviate myocardial ischemia-reperfusion injury via TXNIP regulation. World J Stem Cells 2024; 16(10): 873-895 [PMID: 39493825 DOI: 10.4252/wjsc.v16.i10.873]
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"The theme of this article is very practical and a common problem that troubles elderly women, and the conclusion is very meaningful. It can help alleviate the pain of many women. The abundant scientific data and clear images fully demonstrate the role of exercise therapy, providing methods and ideas for further research.As a reader, I really enjoy this article as it allows me to quickly gain knowledge about this topic."
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Dai ZQ, Gong XY, Zhang R, Jin MQ, Lu W, Wen W, Chen J, Lu FJ, Yang YF, Wang L, He XJ. Research trends in exercise therapy for the treatment of pain in postmenopausal osteoporosis over the past decade: A bibliometric analysis. World J Orthop 2024; 15(10): 950-964 [PMID: 39473512 DOI: 10.5312/wjo.v15.i10.950]
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"This article is interesting, but does not provide any novelties nor scientific approaches in diagnostics of IBD, it is based on "defending" physicians and minorizing their role in detecting Crohn's disease.
I could agree with main conclusion of this article, that providing a diagnose of Crohn's disease is multifactorial, and it depends not only on physicians but on patients itself, time frame, diagnostic abilities.
"
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Zeng Y, Zhang JW, Yang J. Physician-dependent diagnosis delay in Crohn's disease: A pseudo-proposition or not? World J Gastroenterol 2024; 30(38): 4242-4245 [PMID: 39493331 DOI: 10.3748/wjg.v30.i38.4242]
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"1. This study lacks an ethics statement. It is advisable to include an ethics statement within the methods section. 2. The ROC curve presented in the results suggests that the sample size may be relatively insufficient. It is recommended that researchers increase the sample size in further studies and conduct prospective investigations to validate these findings."
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Lin BS, Liu ZG, Chen DR, Yang YL, Yang DZ, Yan JH, Zeng LY, Yang XB, Xu W. Relationship between hemoglobin glycation index and risk of hypoglycemia in type 2 diabetes with time-in-range in target. World J Diabetes 2024; 15(10): 2058-2069 [PMID: 39493564 DOI: 10.4239/wjd.v15.i10.2058]
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"Title: A Study on the Deterioration of Intracranial Epidermoid Cysts through Whole Exome Sequencing
Dear Editors and Authors,
First and foremost, I would like to congratulate the authors on the publication of this high-quality case report on the malignant transformation of intracranial epidermoid cysts (IEC) into squamous cell carcinoma (SCC) in the "World Journal of Clinical Oncology." This study not only provides valuable insights into the molecular mechanisms underlying the transformation of IEC to SCC but also reveals two potential disease-related gene mutations: GJB2 (c.257C>T) and TLR2 (c.1039A>G) through whole exome sequencing (WES).
Comment Content:
Innovation and Importance of the Study:
The innovation of this study lies in providing the first clinical evidence for the potential role of GJB2 and TLR2 in the development and treatment of IEC. This is significant for guiding future research directions and potential therapeutic targets.
Rigorous Study Design:
The authors have employed WES technology, which is efficient and cost-effective for processing large amounts of data quickly. This method is highly applicable for screening genetic variants related to rare and complex diseases, demonstrating the rigor and forward-thinking of the study design.
Detailed Case Report:
The article provides a very detailed description of the case, including the patient's clinical symptoms, medical history, laboratory test results, and imaging examination results. These details help readers to fully understand the case and provide valuable data for future research.
In-Depth Analysis of Genetic Variants:
The authors not only identified two risk variants but also conducted an in-depth analysis of their impact on protein structure and function. This in-depth analysis helps to understand how these variants affect the occurrence and development of the disease.
Comprehensive Treatment and Follow-Up:
The article describes the patient's treatment process and follow-up results in detail, providing valuable references for clinical doctors and demonstrating the effectiveness of comprehensive treatment in controlling the condition.
Suggestions for Improvement:
Increase the Sample Size:
Although this is a report on a rare case, increasing the sample size will help to verify the association between these gene mutations and the deterioration of IEC and improve the generalizability and reliability of the study's results.
Functional Validation Experiments:
The authors mentioned plans for functional validation experiments in future studies. These experiments will help further confirm the role of GJB2 and TLR2 in the development of IEC and how these mutations affect protein function.
Long-Term Follow-Up Data:
Long-term follow-up data will help assess the long-term effects of treatment and the patient's quality of life, which is crucial for evaluating treatment outcomes and formulating treatment guidelines.
Conclusion:
This article is an important contribution to the study of the mechanisms underlying the malignant transformation of IEC. It not only enhances our understanding of the genetic basis of this rare disease but also provides new ideas for future treatments. The authors' work is commendable, and I look forward to their future research bringing more breakthrough"
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Song ZN, Cheng Y, Wang DD, Li MJ, Zhao XR, Li FW, Liu Z, Zhu XR, Jia XD, Wang YF, Liang FF. Whole exome sequencing identifies risk variants associated with intracranial epidermoid cyst deterioration: A case report. World J Clin Oncol 2024; 15(11): 1428-1434 [PMID: 39582614 DOI: 10.5306/wjco.v15.i11.1428]
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"The combination of Astragalus polysaccharide and gimeracil oteracil potassium capsule (S-1) in the treatment of pancreatic cancer can effectively improve the efficacy, reduce side effects, and increase long-term survival rates, which has significant clinical value.In the future, we can further validate its efficacy by conducting prospective, large-scale, multi-center studies and provide more guiding recommendations for clinical practice."
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Li GY, Jiang J. Recent efficacy and long-term survival of Astragalus polysaccharide combined with gemcitabine and S-1 in pancreatic cancer. World J Clin Oncol 2024; 15(11): 1404-1411 [PMID: 39582615 DOI: 10.5306/wjco.v15.i11.1404]
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" Commentary: Predictors of survival in autoimmune liver disease overlap syndromes
Jian-Guo Zhang,Biao Wen
Jian-Guo Zhang,Biao Wen,Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China
Author contributions:Jian-Guo Zhang wrote the original draft; Biao Wen contributed to conceptualization, writing, reviewing and editing; Jian-Guo Zhang and Biao Wen participated in drafting the manuscript; and all authors have read and approved the final version of the manuscript.
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
We perused the article authored by Jayabalan et al[1]with considerable interest and extend our congratulations to the authors for their commendable endeavor. The authors have reported a prospective investigation into the predictors of survival in patients with autoimmune liver disease overlap syndromes (AILDOS)[1]. The study's conclusion suggests that the LOS holds potential as a predictive tool for liver-related mortality in individuals with autoimmune hepatitis and primary biliary cholangitis overlap (AIH-PBC)[1]. However, several aspects of this study merit further scrutiny and discussion.
Firstly, a critical exclusion criterion for the study was the prior performance of a liver transplant prior to enrollment[1]. Upon consideration, we postulated the possibility that a portion of the enrolled patients might harbor coexisting liver pathology stemming from disparate causes (including, but not limited to, alcoholic liver disease or viral hepatitis), which could introduce bias and complicate the interpretation of our results. Therefore, we advised the authors to implement rigorous exclusion criteria for such patients to uphold the accuracy and reliability of our findings.
Secondly, the diagnoses of autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC) were established in accordance with the criteria stipulated by the International Autoimmune Hepatitis Group, the European Association for the Study of the Liver Clinical Practice Guidelines, and the American College of Gastroenterology Clinical Guidelines, respectively[1-4]. It is noteworthy that these diagnostic criteria originate from disparate geographical regions, and the progression of research concerning each disease varies across these regions. Consequently, such variability may potentially impact the precision of the study's findings. In light of this, we propose that the authors consider adopting diagnostic criteria from a uniform geographical region. Therefore, we recommend the uniform application of diagnostic guidelines or consensus recommendations established by reputable institutions in the United States for the purposes of disease ascertainment. Such standardization is poised to substantially elevate the reliability and validity of the research findings, thereby reinforcing the scientific rigor and credibility of the conducted studies.[4-6].
Thirdly, the authors confined their analysis solely to the occurrence or absence of liver-related mortality, while neglecting to account for the medical interventions undergone by the patients during the follow-up period[1]. It is imperative to elucidate the potential impact of these interventions on the study's findings. A comprehensive assessment of the medical interventions received by the patients is crucial for ensuring the accuracy and robustness of the study's conclusions.
Ultimately, as highlighted by the authors, the primary limitation of this study is the relatively modest sample size[1]. Consequently, it is imperative that future research endeavors incorporate larger sample populations and adopt a multicenter design to validate the findings of the present study and further elucidate the pertinence to patients with AIH-PSC.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
REFERENCES
1 Jayabalan D, Huang Y, Calzadilla-Bertot L, Janjua M, de Boer B, Joseph J, Cheng W, Hazeldine S, Smith BW, MacQuillan GC, Wallace MC, Garas G, Adams LA, Jeffrey GP. Predictors of survival in autoimmune liver disease overlap syndromes. World J Hepatol 2024; 16: 1269-1277. [PMID:39351512 DOI: 10.4254/wjh.v16.i9.1269]
2 European Association for the Study of the Liver. EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J Hepatol 2017; 67: 145-172. [PMID: 28427765 DOI: 10.1016/j.jhep.2017.03.022]
3 Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions. Gut Liver 2016; 10: 177-203. [PMID:26934884 DOI: 10.5009/gnl15352]
4 Lindor KD, Kowdley KV, Harrison ME. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol 2015; 110: 646-659, 660. [PMID: 25869391 DOI: 10.1038/ajg.2015.112]
5 Mack CL, Adams D, Assis DN, Kerkar N, Manns MP, Mayo MJ, Vierling JM, Alsawas M, Murad MH, Czaja AJ. Diagnosis and Management of Autoimmune Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American Association for the Study of Liver Diseases. Hepatology 2020; 72: 671-722. [PMID: 31863477 DOI: 10.1002/hep.31065]
6 Lindor KD, Bowlus CL, Boyer J, Levy C, Mayo M. Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases. Hepatology 2019; 69: 394-419. [PMID:30070375 DOI: 10.1002/hep.30145]"
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Jayabalan D, Huang Y, Calzadilla-Bertot L, Janjua M, de Boer B, Joseph J, Cheng W, Hazeldine S, Smith BW, MacQuillan GC, Wallace MC, Garas G, Adams LA, Jeffrey GP. Predictors of survival in autoimmune liver disease overlap syndromes. World J Hepatol 2024; 16(9): 1269-1277 [PMID: 39351512 DOI: 10.4254/wjh.v16.i9.1269]
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