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1
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"The title of this article is not only novel but also accurately reflects the scope and focus of the content presented. It captures the reader’s attention while maintaining consistency with the study’s objectives and findings. Additionally, the references are cited appropriately, demonstrating thorough literature review and academic rigor throughout the manuscript.
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Wang WX, Dang FL, Li TT, Yu Y. Nalbuphine vs sufentanil as effective analgesics for postoperative pain management in gastric cancer resection. World J Gastrointest Pharmacol Ther 2025; 16(2): 103232 [DOI: 10.4292/wjgpt.v16.i2.103232]
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2
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"This article discusses the importance of perioperative nutritional support and prehabilitation in patients undergoing gastrointestinal surgery. Perioperative nutritional support includes care before, during, and after surgery. Comprehensive nutritional support programs improve immune function and wound healing, and shorten the length of hospital stay. Prehabilitation enhances the patient's condition before surgery and reduces the risk of complications. Future research needs to identify the optimal combination and amount of nutritional components. However, the paper does not specifically mention GLIM (Global Leadership Initiative on Malnutrition). Nevertheless, the importance of nutritional support throughout the document, as well as the evaluation and improvement of nutritional status before and after surgery, may align with the improvement goals of GLIM. Further investigation is warranted."
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Triantafillidis JK. Perioperative nutritional support in patients undergoing gastrointestinal surgery: Current views with an emphasis on prehabilitation efforts. World J Gastrointest Surg 2025; 17(6): 101244 [DOI: 10.4240/wjgs.v17.i6.101244]
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3
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"This study presents significant findings regarding the metabolic effects of esophagectomy with gastric conduit reconstruction, particularly in T2D patients. Although the observed remission rate is modest compared to bariatric surgery outcomes, it opens up a new avenue for exploring the potential benefits of esophagectomy on metabolic health, especially in patients with comorbid diabetes. The study provides evidence that the use of a narrow gastric tube during esophagectomy might contribute to better diabetes outcomes, offering a potential modification to surgical practice that could improve patient care and prognosis."
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Xing HJ, Hu MY, Jiang YQ, Li XH, Zhu B, Wang ZQ. Remission of type 2 diabetes one year after esophagectomy with gastric conduit reconstruction: A prospective cohort study. World J Gastrointest Surg 2025; 17(6): 105514 [DOI: 10.4240/wjgs.v17.i6.105514]
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4
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"The topic of perioperative nutritional support is highly relevant, particularly in the context of enhancing patient recovery and reducing postoperative complications. Given the increasing focus on improving surgical outcomes through preoperative interventions, this manuscript addresses a critical aspect of patient care. This paper underscores the importance of perioperative nutritional interventions and their potential to significantly improve postoperative outcomes, including reduced complications, shorter hospital stays, and faster recovery. Given the high rates of malnutrition and postoperative complications in gastrointestinal surgery patients, this review is highly significant for improving clinical practice. While the article touches on prehabilitation, the section could delve deeper into the specific methods of implementation and the practical challenges faced in clinical settings. A more detailed discussion of how to integrate prehabilitation into routine clinical practice, especially in less resource-rich environments, would add value for practitioners looking to apply these strategies."
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Triantafillidis JK. Perioperative nutritional support in patients undergoing gastrointestinal surgery: Current views with an emphasis on prehabilitation efforts. World J Gastrointest Surg 2025; 17(6): 101244 [DOI: 10.4240/wjgs.v17.i6.101244]
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5
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"This review article is a really helpful and up-to-date look at how PET/CT scans using FDG are used for bile duct cancer (BTC). The authors do a great job pulling together the latest research, especially focusing on the past three years. They carefully examine how well PET/CT works for the different types of BTC – like cancers inside the liver (ICC), near the liver's exit (PCC), further down the bile duct (DCC), and gallbladder cancer (GBC). This breakdown is important because each type behaves differently.
A key point the review makes is comparing PET/CT to standard scans like CT or MRI. PET/CT is generally better at finding cancer spread to lymph nodes, even if they aren't enlarged, and at spotting distant cancer spread elsewhere in the body. This can be crucial for planning treatment and avoiding unnecessary surgeries. However, the review honestly points out that PET/CT isn't perfect. It can sometimes miss smaller bile duct cancers (especially PCC) or cancers that produce a lot of mucus. It can also give "false alarms" due to inflammation, infection, or the presence of stents.
The article highlights a significant shift happening: moving beyond just looking at the pictures to actually measuring things from the scan. Measurements like how "hot" the cancer appears (SUVmax) or the total amount of active cancer (MTV, TLG) can help doctors predict how aggressive the cancer might be and how long patients might live. Even more exciting is brand new research showing these PET/CT measurements might give clues about the cancer's genetics (like KRAS mutations in ICC) without needing a new biopsy. The review also covers advanced computer analysis of the scans (radiomics and AI), which shows promise in predicting things like how likely the cancer is to invade blood vessels or come back after surgery, especially for ICC.
The authors also touch on the potential of combining PET with MRI (PET/MRI). This newer technology might offer better pictures of the soft tissues around the bile ducts and gallbladder, which could be useful for seeing exactly where the cancer is locally or if it has come back. However, more studies are needed, particularly for gallbladder cancer.
Overall, this is a very valuable summary. It clearly explains where PET/CT is most useful right now for BTC patients – mainly in accurate staging to find hidden spread and guide treatment choices. It also effectively shows where the field is heading: using the scan data more precisely to understand the cancer's biology and predict outcomes, paving the way for more personalized care. The balanced view of both the strengths and weaknesses of PET/CT makes this review practical for doctors and informative for researchers looking at the future of imaging for these difficult cancers.
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Yin JX, Fan X, Chen QL, Chen J, He J. Progress in the application of fludeoxyglucose positron emission tomography computed tomography in biliary tract cancer. World J Hepatol 2025; 17(5): 105446 [DOI: 10.4254/wjh.v17.i5.105446]
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6
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"This bibliometric study systematically examines artificial intelligence applications in hepatobiliary surgery from 2014-2024, offering a quantitative perspective on this evolving field. The research effectively maps global publication patterns, collaborative networks, and research priorities. The title accurately defines the scope, while the abstract concisely summarizes objectives, methodology, and key findings. Keywords demonstrate appropriate thematic alignment, and the background section adequately contextualizes AI's integration into hepatobiliary practice, noting its clinical relevance for diagnostic and therapeutic applications.
Methodologically, the study employs Web of Science data with visualization tools (CiteSpace/VOSviewer) to analyze authorship, institutional contributions, national productivity, and keyword evolution. However, the search strategy shows limitations through its predominant focus on "CNN" (Convolutional Neural Networks), overlooking emerging architectures like Transformer models that are gaining prominence in medical AI research. Results clearly demonstrate China's leadership in publication volume alongside the United States' influence in citation impact, with network visualizations effectively illustrating these geographical patterns. The discussion reasonably outlines AI's role in imaging diagnostics and tumor segmentation, though greater analytical depth regarding clinical implementation challenges - such as model validation requirements and integration with surgical workflows - would strengthen its practical relevance.
Presentation issues require attention as Figure 3 suffers from resolution limitations affecting text legibility, while Figures 10-11 contain non-essential graphical elements that reduce interpretive clarity. Strategic labeling could enhance data communication in these visualizations. Statistical approaches are appropriately applied for bibliometric analysis, and referenced literature shows generally authoritative coverage. Minor language issues exist, including inconsistent quotation usage in the abstract (e.g., "classification", "CT and "diagnosis") and occasional terminology variations, though these do not substantially hinder comprehension.
Collectively, this work provides a structured, data-informed overview of AI research in hepatobiliary surgery during the specified decade. It documents the field's development trajectory, identifies primary research themes and key contributors, and establishes baseline patterns of international collaboration. The analysis offers researchers a useful reference point for understanding current research landscapes and potential partnership opportunities. With refinements addressing methodological scope, analytical depth, and visual presentation, the study could serve as a more comprehensive benchmark for future investigations in this domain.
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Zheng RJ, Li DL, Lin HM, Wang JF, Luo YM, Tang Y, Li F, Hu Y, Su S. Bibliometrics of artificial intelligence applications in hepatobiliary surgery from 2014 to 2024. World J Gastrointest Surg 2025; 17(5): 104728 [DOI: 10.4240/wjgs.v17.i5.104728]
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7
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"The he article is well-written, and the research methodology is scientifically rigorous. The article holds significant scientific value and clinical relevance in the research of stem cell therapies for retinal pigment epithelium (RPE) cells. I hope the authors will address the current challenges in future studies, advancing the application of stem cell therapies in the treatment of RPE-related diseases. Thank you once again for your outstanding contributions to this field."
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Sorrentino FS, Parmeggiani F, Gardini L, Fontana L, Musa M, Gagliano C, Zeppieri M. Stem cell therapy for retinal pigment epithelium disorders. World J Stem Cells 2025; 17(5): 103100 [DOI: 10.4252/wjsc.v17.i5.103100]
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8
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"Title: A Critical Appraisal of Dissociative Psychosis and Dissociative Schizophrenia as Distinct Entities
Body:
Having reviewed the article titled "Are dissociative psychosis and dissociative schizophrenia reality?" by H. Belli, I am compelled to offer a commentary that reflects on the conceptualization and clinical significance of these conditions. The article presents a comprehensive analysis of dissociative phenomena within the context of psychotic disorders, challenging readers to reconsider the boundaries between dissociative and schizophrenic experiences.
Belli's work prompts a reevaluation of the diagnostic criteria and the potential overlap between dissociative symptoms and schizophrenia. The discussion on the role of childhood trauma as a precipitating factor for dissociative experiences that may manifest as psychotic symptoms is particularly noteworthy. It suggests a bio-psycho-social model that could enhance our understanding of the etiology and comorbidity of these disorders.
The article also underscores the importance of psychometric testing in identifying dissociative features in individuals with psychotic disorders. This approach could potentially lead to more personalized and effective treatment strategies, emphasizing the need for a trauma-informed care framework.
In conclusion, Belli's article contributes to a growing body of research that questions the traditional dichotomy between dissociative and psychotic disorders. It advocates for a more integrated view that recognizes the complexity of mental health conditions and the impact of early life experiences on later psychiatric outcomes. I look forward to future studies that build on these insights and further explore the implications for clinical practice and mental health policy.
Reviewer: Lu Hou"
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Belli H. Are dissociative psychosis and dissociative schizophrenia reality? World J Psychiatry 2025; 15(4): 102008 [PMID: 40309595 DOI: 10.5498/wjp.v15.i4.102008]
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9
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"This study by Wang et al. presents a compelling advancement in the noninvasive prediction of variceal bleeding risk in Budd-Chiari syndrome (BCS) patients using a combined radiomics and clinical model (R+C model). The integration of high-dimensional radiomics features with clinical parameters to stratify bleeding risk is both innovative and clinically relevant. The authors should be commended for conducting a multicenter study with an external validation cohort, which strengthens the generalizability of their findings.
Strengths of the Study:
Innovative Use of Radiomics: The application of radiomics in BCS—a relatively rare and under-studied condition—represents a novel contribution. The extraction of hepatic and splenic texture features from CT images enhances the predictive capability beyond conventional clinical models.
Robust Methodology: The use of LASSO Cox regression for feature selection and validation of the model using an external cohort adds credibility. The model’s performance metrics, such as the C-index (0.906 for training and 0.859 for validation), demonstrate excellent discriminative ability.
Clinical Utility: The development of an accessible online tool for individualized risk prediction (https://bcsvh.shinyapps.io/BCS_Variceal_Bleeding_Risk_Tool/) is a practical step towards clinical translation, potentially aiding in decision-making for prophylactic interventions.
Risk Stratification: The ability to categorize patients into low-, medium-, and high-risk groups offers a framework for personalized management strategies, which could reduce unnecessary interventions in low-risk patients and prioritize high-risk individuals for aggressive preventive therapies.
Limitations and Areas for Improvement:
Retrospective Design: As with all retrospective studies, the potential for selection bias and unmeasured confounding exists. Prospective validation in diverse populations, including Western cohorts where thrombophilic etiologies of BCS predominate, is necessary.
Limited Radiomics Scope: The use of single-slice regions of interest (ROIs) for liver and spleen may not capture the full heterogeneity of these organs. A volumetric or multi-slice approach could improve robustness.
Generalizability: The study population is entirely Chinese, with BCS cases predominantly due to membranous obstruction—an etiology not common in other geographic regions. Thus, external validation in populations with differing BCS etiologies is crucial.
Anticoagulation Risk Interpretation: While anticoagulation was found to be an independent risk factor for bleeding, the model does not differentiate between anticoagulant types or dosing strategies. Given the importance of anticoagulation in BCS, further work is needed to clarify safe therapeutic windows.
Manual Segmentation: The reliance on manual ROI delineation is resource-intensive and may limit scalability. Incorporating semi-automated or AI-driven segmentation could enhance reproducibility and feasibility in routine clinical settings"
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Wang ZD, Nan HJ, Li SX, Li LH, Liu ZC, Guo HH, Li L, Liu SY, Li H, Bai YL, Dang XW. Development and validation of a radiomics-based prediction model for variceal bleeding in patients with Budd-Chiari syndrome-related gastroesophageal varices. World J Gastroenterol 2025; 31(19): 104563 [DOI: 10.3748/wjg.v31.i19.104563]
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10
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"I read a very interesting manuscript. The authors propose to use Hericium erinaceus to regress gastric mucosal atrophy. The authors present convincing evidence of the effectiveness of this medicine. Prevention of gastric cancer has several successive stages of implementation (detection of precancerous diseases and precancerous changes in the gastric mucosa, implementation of screening, diagnostics, verification of diagnosis by morphological methods and treatment). Preventive treatment of precancerous lesions has a very limited number of means and methods. I believe that it is necessary to continue studying and using Hericium erinaceus. Perhaps Hericium erinaceus will be an effective drug for the prevention of gastric cancer."
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Pellegrino R, Gravina AG. Potential of traditional Chinese medicine in gastrointestinal disorders: Hericium erinaceus in chronic atrophic gastritis. World J Gastroenterol 2025; 31(20): 106615 [DOI: 10.3748/wjg.v31.i20.106615]
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11
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"This paper systematically analyzes the etiology of the two major subtypes of inflammatory bowel disease (IBD): Crohn’s disease and ulcerative colitis. It is highly comprehensive and commendable. It examines the etiology broadly, focusing on immune responses and considering genetic changes, gut microbiota, and social and environmental factors. On the other hand, further discussion is needed regarding how concretely these theoretical insights into etiology are linked to the development of therapeutic approaches. Additionally, genetic factors and changes in gut microbiota can vary by region, making universal evaluation difficult.
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Yang QH, Zhang CN. Comparative study on the pathogenesis of Crohn’s disease and ulcerative colitis. World J Gastroenterol 2025; 31(19): 106406 [DOI: 10.3748/wjg.v31.i19.106406]
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12
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"This minireview article provides a systematic comparison of the pathogenic mechanisms of Crohn’s disease and ulcerative colitis. It outlines six shared mechanisms—including immune dysregulation, genetics, microbiota imbalance, and infections—and identifies 14 key differences between the two diseases. The article is well-structured, comprehensive in scope, and supported by clear diagrams, offering strong academic value and clinical relevance. While its originality and depth of mechanistic insight could be further improved and the discussion on clinical translation is somewhat limited, it remains a well-organized and information-rich review suitable for researchers and clinicians alike."
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Yang QH, Zhang CN. Comparative study on the pathogenesis of Crohn’s disease and ulcerative colitis. World J Gastroenterol 2025; 31(19): 106406 [DOI: 10.3748/wjg.v31.i19.106406]
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13
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"This article explores the role of the "obesity paradox" in immunotherapy for hepatocellular carcinoma (HCC), suggesting that obese patients may experience better survival outcomes when treated with immune checkpoint inhibitors such as lenvatinib and camrelizumab. Based on recent clinical findings, the authors discuss leptin-mediated immune modulation as a possible mechanism, noting that obesity may enhance the efficacy of anti-PD-1 therapies but potentially reduce the effectiveness of anti-VEGF treatments. While the topic is novel and clinically relevant, the current evidence remains limited and the mechanistic explanation could be more detailed. Overall, the article provides a valuable perspective on the dual role of obesity in HCC immunotherapy and highlights the need for further research in this area."
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Sierra L, Abu-Hammour MN, Chatterjee A, Simons-Linares CR. Obesity paradox role in the immunosuppressive treatment of hepatocellular carcinoma. World J Gastroenterol 2025; 31(19): 105617 [DOI: 10.3748/wjg.v31.i19.105617]
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14
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"Reader′s comments:
We are delighted to read the interesting article by Hu et al entitled: "Pescadillo ribosomal biogenesis factor 1 and programmed death-ligand 1 in gastric and head and neck squamous cell carcinoma"it is an interesting study, but we have some comments:
In section of patients selection: exclusion criteria: it is not clear what was meant by pathological condition?????
I think it is better to represent demographic , clinical data of enrolled patients.
Result section: it is better to clear if difference between positive and negative patients is significant or not.
What about expression of the studied markers in adjacent non tumor tissues????????
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Hu XN, Li CF, Huang SM, Nie CL, Pang R. Pescadillo ribosomal biogenesis factor 1 and programmed death-ligand 1 in gastric and head and neck squamous cell carcinoma. World J Gastroenterol 2025; 31(19): 106644 [DOI: 10.3748/wjg.v31.i19.106644]
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15
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"Shukla et al.'s comprehensive review on remnant pancreatic carcinoma (RPC) brings much-needed attention to a rare but clinically formidable entity increasingly recognized in the era of improved surgical outcomes and long-term survival following partial pancreatectomy. Their work, titled "Remnant Pancreatic Carcinoma: The Current Status", outlines the epidemiology, risk factors, surveillance strategies, and therapeutic challenges of RPC, providing a valuable clinical framework for a condition historically relegated to case reports and small series.
The authors astutely emphasize the evolving landscape of RPC, shaped by the growing volume of patients undergoing distal or proximal pancreatectomy for benign or malignant lesions. The incidence of RPC is likely underestimated, given limited long-term follow-up in most cohorts. As such, the article's call for structured postoperative surveillance protocols is particularly timely. Importantly, Shukla et al. underscore that remnant pancreatic malignancies may arise de novo or as recurrences, and often present with more aggressive histological and molecular profiles, reinforcing the need for tailored risk stratification.
A notable strength of this review is its discussion on the putative mechanisms underlying RPC, including genetic predisposition, field cancerization, and chronic inflammation of the residual gland. These insights are crucial for identifying high-risk patients who may benefit from enhanced surveillance or prophylactic strategies. However, while the authors reference KRAS and TP53 mutations, a more extensive exploration of genomic drivers and their potential as surveillance biomarkers would have added translational depth.
Surgically, re-resection remains the mainstay of curative intent in selected patients with adequate functional reserve. The article appropriately highlights the technical and oncological complexities of completion pancreatectomy. Nonetheless, future perspectives might benefit from the integration of evolving minimally invasive approaches and neoadjuvant strategies tailored to RPC biology.
One of the article’s understated yet significant contributions is its implication that RPC represents a failure of current surveillance paradigms. Given the shift towards parenchyma-sparing resections and increased survivorship, integrating longitudinal imaging and biomarker monitoring—such as circulating tumor DNA (ctDNA) or CA 19-9 kinetics—may optimize early detection. Moreover, data on long-term outcomes post-remnant resection remain sparse, and prospective registries are needed to define survival benchmarks and refine selection criteria.
In conclusion, Shukla et al. succeed in framing RPC not merely as a post-surgical curiosity, but as a distinct oncological entity warranting multidisciplinary attention. Their review lays the foundation for future clinical and translational studies in a domain poised to grow in relevance. Establishing consensus on definitions, risk stratification algorithms, and surveillance protocols will be essential to improving outcomes in this uniquely challenging subset of pancreatic cancer."
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Shukla A, Kalayarasan R, Sai Krishna P, Pottakkat B. Remnant pancreatic carcinoma: The current status. World J Clin Oncol 2025; 16(5): 107039 [DOI: 10.5306/wjco.v16.i5.107039]
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16
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"The “obesity paradox” in hepatocellular carcinoma suggests better outcomes in patients with obesity undergoing immunotherapy, potentially due to leptin-driven immune modulation and enhanced nutritional reserves. While promising, these findings have only been demonstrated with lenvatinib and camrelizumab, and have not yet been observed with more commonly used immunotherapy treatments for hepatocellular carcinoma, such as nivolumab, pembrolizumab, or bevacizumab. Although intriguing, this phenomenon remains limited by the scope of current studies"
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Sierra L, Abu-Hammour MN, Chatterjee A, Simons-Linares CR. Obesity paradox role in the immunosuppressive treatment of hepatocellular carcinoma. World J Gastroenterol 2025; 31(19): 105617 [DOI: 10.3748/wjg.v31.i19.105617]
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17
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"Six common and fourteen unique aspects of the pathogenesis of inflammatory bowel disease, primarily Crohn’s disease and ulcerative colitis, illustrate the causes and beneficial factors of resistance to inflammatory bowel disease, providing critical insights for the targeted treatment of Crohn’s disease and ulcerative colitis. Utilizing the main contents of this paper allows for the development of comprehensive interventions that reduce harmful influences, enhance protective factors and use an integrative approach to address the diseases for the benefit of the human being"
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Yang QH, Zhang CN. Comparative study on the pathogenesis of Crohn’s disease and ulcerative colitis. World J Gastroenterol 2025; 31(19): 106406 [DOI: 10.3748/wjg.v31.i19.106406]
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18
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"The article is devoted to the problem of introducing narrative medicine into primary health care systems. This process is part of the enriching the humanistic dimensions of medical care and, in general, of a systemic approach to maintaining public health. The relevance of this problem has significantly increased recently due to the increasing role of instrumental component of the medical industry and some dehumanization associated primarily with the crisis of individualizing clinical approach and increasing standardization in the provision of medical services. It is expected that the development of narrative medicine can improve the comfort of doctor-patient interaction, provide a personalized approach with improved diagnostic efficiency and quality of treatment.
The authors analyze the main problems of the widespread introduction of narrative medicine in primary health care, namely, the strengthening of the humanitarian component in the educational programs of medical professionals, increasing the burden on the staff, the need to allocate additional funds, the peculiarities of the national health care system of China.
The article discusses possible solutions to some of these problems, such as the involvement of volunteers, application of artificial intelligence, optimization of equipment operation mode in order to save money. Feedback mechanisms, telemedicine methods, etc. are built into the implementation system proposed by the authors.
However, it seems that the proposed schemes need experimental validation, which requires the creation of interdisciplinary research groups in which doctors and humanities can interact.
Given the peculiarities of the humanitarian environment of Chinese society, it would be appropriate to include representatives of different schools of psychology and even philosophy in such groups.
In general, given the novelty of the problem and its relevance, the quality of the article is quite high.
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Lei NJ, Vaishnani DK, Shaheen M, Pisheh H, Zeng J, Ying FR, Yang QQ, Wang CY, Ma J, Pan JY, Hou NJ. Embedding narrative medicine in primary healthcare: Exploration and practice from a medical humanities perspective. World J Clin Cases 2025; 13(22): 105684 [DOI: 10.12998/wjcc.v13.i22.105684]
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19
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"The studied groups were not homogeneous by age and gender proportion. Research does not achieve the objectives of the experiment.
The results are unreliable and cannot be considered to be a meaningful contribution to research progress in this field.
Furthermore, the comorbidity was not reported: this represents a further limit that could affect the results.
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Buterin A, Vuckovic M, Spanja Prpic S, Zaharija V, Nonkovic M, Prpic T. Comparison of functional recovery of the knee following total knee arthroplasty in patients with and without ankle symptoms. World J Orthop 2025; 16(5): 106004 [DOI: 10.5312/wjo.v16.i5.106004]
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20
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"This prospective study rightly identifies a significant problem i.e.,preoperative ankle pain might effect the early functional outcome in patients undergoing total knee arthroplasty for primary Osteoarthritis knee.It is often overlooked but the deformity at the level of knee definitely impacts the biomechanics alignment of the entire lower limb and also at the ankle. The key finding was patients exhibited significantly lower KOOS scores and extension recovery at 3 months postoperatively, even after adjusting for demographic confounders. This reiterates the necessity for a complete lower limb assessment and managing preoperatively any hip/ankle symptoms preoperatively to optimize TKA outcomes. The methodology, protocol, grouping of patients was all good.
The authors could have given a detailed radiographic alignment of the patient's lowerliimbs that were operated to substantiate the preoperative status and the results postoperatively. Even though AOFAS score, is an appropriate tool for assessing the ankle symptoms and pathologies, a detailed radiographic assessment of the ankle including ankle hind foot assessment, weight bearing alignment could have been added/ mentioned. Incorporating pre- and postoperative radiographs would have allowed the authors to better delineate whether the observed differences in KOOS and knee extension were attributable to underlying mechanical misalignment or simply symptomatic variation.
A gait analysis of the patients can also be included to add objective assessment to the data. That would tell us whether the results are an outcome of any malalignment or just symptomatic variation.
A longer followup would also suggest us whether the symptoms are resolving over time or still persisting."
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Buterin A, Vuckovic M, Spanja Prpic S, Zaharija V, Nonkovic M, Prpic T. Comparison of functional recovery of the knee following total knee arthroplasty in patients with and without ankle symptoms. World J Orthop 2025; 16(5): 106004 [DOI: 10.5312/wjo.v16.i5.106004]
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21
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"This study addresses the deficit of medical humanities in China’s resource-limited primary healthcare (PHC) system by systematically exploring pathways to integrate narrative medicine (NM) into grassroots care. Situated within the Healthy China 2030 policy framework, the research proposes actionable strategies for humanizing PHC through theoretical analysis and practical innovations, such as the One-Minute Patient Narrative and 11253 Family Doctor Service Model. Key contributions include: (1) revealing tensions between policy mandates and on-the-ground realities, emphasizing NM’s localization to regional disparities; (2) enhancing care efficiency via AI-mediated narrative analysis (e.g., a 25% increase in treatment adherence); and (3) offering scalable models to ensure PHC sustainability.
However, three critical gaps require further exploration. First, cultural dynamics—such as patients’ traditional deference to medical authority and healthcare commercialization—demand culturally adaptive interventions (e.g., competency training for clinicians, redefining relational medicine values). Current analyses lack actionable steps to operationalize these strategies across diverse contexts. Second, sustainability challenges—including the feasibility of urban NM models in high-demand rural settings and volunteer system stability in under-resourced areas—are underexamined. Systemic inequities (e.g., funding gaps, workforce shortages) further constrain implementation. Third, while short-term metrics like patient satisfaction are prioritized, long-term systemic issues—health equity, clinician burnout, and bureaucratic barriers to PDCA (Plan-Do-Check-Act) cycles—remain unaddressed. Future studies must adopt mixed-method evaluations to bridge these gaps and enable NM’s transition from pilot projects to systemic reform.
To further this agenda, this study presents a three-pillar framework. Firstly, by fostering interdisciplinary collaboration, we aim to integrate public health experts, community advocates, and policymakers. Together, they will devise NM interventions, such as narrative-driven public health campaigns. This approach will transform patient stories into effective social governance tools, thereby enhancing the inclusivity of medical decision-making. Secondly, we propose establishing an ethical AI governance system. This system will ensure that AI-driven narrative data processing aligns with China's data security regulations. We plan to adopt encryption technology and an informed consent mechanism to bolster privacy protections. Additionally, we will systematically mitigate technical biases through algorithm fairness audits and transparent training protocols, including the use of open dataset sources. Finally, we advocate for a global localization adaptation strategy, drawing inspiration from international practices like the Indian Asha worker model. While respecting the universal principle of patient autonomy, we intend to devise localized solutions, such as a health narrative literacy improvement project tailored for rural areas. This will facilitate the effective integration of medical humanistic values within diverse social and cultural contexts.
Ultimately, this framework aims to shift healthcare paradigms from fragmented, biomarker-centric models to holistic, humanistic systems. By empowering patients and frontline workers as NM co-designers through participatory research, localized innovations can catalyze structural reforms, ensuring medical services prioritize humanistic care over purely biomedical metrics. "
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Lei NJ, Vaishnani DK, Shaheen M, Pisheh H, Zeng J, Ying FR, Yang QQ, Wang CY, Ma J, Pan JY, Hou NJ. Embedding narrative medicine in primary healthcare: Exploration and practice from a medical humanities perspective. World J Clin Cases 2025; 13(22): 105684 [DOI: 10.12998/wjcc.v13.i22.105684]
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22
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" Endoscopic gastroplasty treatments were significantly better in reducing total body weight, excessive weight, and average weight among obese population. No significant difference between endoscopic transoral outlet reduction and full-thickness suturing plus argon plasma mucosal coagulation. Lack of comparative, long-term follow-up and randomized studies, reporting and selection bias, high level of heterogeneity were the major limitations in the currently available meta-analyses."
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Abdulla M, Mohammed N, AlQamish J, Arau RT. Efficacy and safety of endoscopic gastroplasty for treatment of obesity: An overview of comparative meta-analyses. World J Gastrointest Endosc 2025; 17(5): 105158 [PMID: 40438714 DOI: 10.4253/wjge.v17.i5.105158]
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23
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"This review comprehensively explores the latest advancements in gastrointestinal (GI) endoscopy, highlighting innovations in diagnostic and therapeutic techniques for GI cancers. Cutting-edge technologies such as magnification endoscopy, narrow-band imaging, endoscopic ultrasound with fine-needle biopsy, and artificial intelligence-enhanced methods are transforming cancer detection, staging, and management. Endoscopic approaches like submucosal dissection and mucosal resection are improving outcomes for premalignant and malignant lesions. These developments underscore the pivotal role of endoscopy in reducing morbidity, mortality, and healthcare costs associated with GI cancers."
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Abusuliman M, Jamali T, Zuchelli TE. Advances in gastrointestinal endoscopy: A comprehensive review of innovations in cancer diagnosis and management. World J Gastrointest Endosc 2025; 17(5): 105468 [PMID: 40438719 DOI: 10.4253/wjge.v17.i5.105468]
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24
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"Gastric polyps (GPs) are a common clinical disease. In recent years, with the change in dietary habits, the incidence of GPs is increasing in China. GPs are usually found by gastroscopy. Some GPs may have malignant potential and are associated with hereditary diseases. Therefore, early detection and biopsy examination are important in clinical practice to better reduce the rate of cancer。It is an interesting manuscript. Authors can succeed to present their idea in a clear way adding information to the existing literature."
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Zheng L, Shi YQ, Xue T, Duan SL. Evaluating the detection rate and pathological features of polyps in patients with upper gastrointestinal endoscopy. World J Gastrointest Endosc 2025; 17(5): 105471 [PMID: 40438721 DOI: 10.4253/wjge.v17.i5.105471]
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25
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"This Letter to Editor does a great job of highlighting an important issue that many of us face in real-world clinical practice—when to perform cholecystectomy in patients with gallstone-related acute cholangitis.
The authors point out the growing evidence in favor of same-admission surgery rather than waiting, and they support this with data from a large national database, which adds weight to their argument.
What I appreciated most was how clearly the authors outlined the benefits of early surgery—not just in terms of clinical outcomes like reduced readmission and mortality, but also from a healthcare system perspective. These are the kinds of practical, patient-centered decisions we need to think more carefully about.
That said, I would have liked to see a little more discussion on what makes early surgery difficult to implement in some hospitals. For example, resource limitations, operating room availability, or patient comorbidities could be relevant factors. A few thoughts on how to overcome those barriers would make the piece even more helpful.
In summary, this is a well-written and very relevant commentary that reminds us of the gap that often exists between evidence and practice. I think it will be helpful not only for clinicians but also for institutions looking to improve care pathways for biliary emergencies.
Reviewer Name: Bum-Soo Kim
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Paramythiotis D, Tsavdaris D, Karlafti E. Reassessing cholecystectomy timing in gallstone-related acute cholangitis. World J Gastrointest Endosc 2025; 17(5): 106473 [PMID: 40438711 DOI: 10.4253/wjge.v17.i5.106473]
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"This article is very innovative and has great reference value for clinical medical treatment, the language has no obvious errors, the quality of charts and graphs is clear, it is worthy of publication, the level of publication meets the requirements of journals, and for the insufficiency of the research hopefully further in-depth discussion."
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Singeap AM, Minea H, Stafie R, Stanciu C, Trifan A. Towards precision care: Fluctuations in albumin and fibrinogen as noninvasive predictors of endoscopic outcomes in Crohn’s disease. World J Gastrointest Endosc 2025; 17(5): 105365 [PMID: 40438718 DOI: 10.4253/wjge.v17.i5.105365]
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"I read an interesting article "Efficacy and safety of endoscopic gastroplasty for the treatment of obesity: An overview of comparative meta-analyses". The authors very accurately analyzed a large list of available publications on the topic of endoscopic gastroplasty in accordance with the PRISMA method. The authors also compared various strategies, including interventional ones for the treatment of obesity. They made interesting conclusions about the effectiveness of endoscopic gastroplasty for the treatment of obesity. "
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Abdulla M, Mohammed N, AlQamish J, Arau RT. Efficacy and safety of endoscopic gastroplasty for treatment of obesity: An overview of comparative meta-analyses. World J Gastrointest Endosc 2025; 17(5): 105158 [PMID: 40438714 DOI: 10.4253/wjge.v17.i5.105158]
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"This article describes a prospective study evaluating the efficacy of colon capsule endoscopy (CCE) for surveillance of colonic polyps. Although the study was conducted at a single institution and may lack diversity in its patient population, it is a prospective study that provides essential data demonstrating the utility of CCE. Currently, CCE is also used in routine clinical practice, such as for assessing the effectiveness of medications in ulcerative colitis. There are challenges to overcome, such as the volume of laxatives required for bowel preparation being greater than that for conventional colonoscopy (CS) and the higher examination cost. However, CCE can potentially reduce the number of unnecessary CS, suppress carbon dioxide emissions associated with endoscopic procedures, and significantly contribute to green endoscopy. For these reasons, determining how to promote the use of CCE further in daily clinical practice is considered an important issue for the future."
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Semenov S, Ismail MS, Sihag S, Manoharan T, Reilly P, Boran G, Ryan B, Breslin N, O’Connor A, O’Donnell S, McNamara D. Colon capsule endoscopy is an effective filter test for colonic polyp surveillance. World J Gastrointest Endosc 2025; 17(5): 101322 [PMID: 40438717 DOI: 10.4253/wjge.v17.i5.101322]
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"This review article presents a comprehensive synthesis of recent developments in conversion therapy for intrahepatic cholangiocarcinoma (ICC), specifically focusing on strategies to render initially unresectable disease amenable to surgical resection. The authors have successfully compiled and analyzed a broad range of relevant studies, providing a balanced overview of multimodal treatment approaches, including systemic chemotherapy, targeted therapy, immunotherapy, and locoregional interventions such as TACE, TARE, and HAIC.
The manuscript is commendable for its integration of recent clinical data and its emphasis on multidisciplinary management, which aligns with current oncologic practice. The inclusion of well-organized tables and illustrative figures contributes to the accessibility and clarity of the content. Furthermore, the discussion of strategies aimed at optimizing the future liver remnant—such as portal vein embolization (PVE) and ALPPS—offers valuable clinical insights for hepatobiliary surgeons and oncologists alike.
To further strengthen the manuscript, the following suggestions are offered:
1. A more explicit and operational definition of “conversion therapy” would improve conceptual clarity, particularly if contrasted with related terms such as “bridging therapy” and “downstaging.”
2. While Figure 1 is informative, reformatting it into a structured algorithm or decision-making flowchart could enhance its clinical utility and instructional value.
3. The generalizability of findings from small-scale or non-standardized studies should be addressed, as this would add depth to the critical appraisal and enhance the scholarly rigor of the discussion.
In conclusion, this review represents a timely and academically significant contribution to the evolving field of hepatobiliary oncology. With modest revisions, it has the potential to serve as both an educational reference and a practical guide for clinicians managing advanced ICC.
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Liu JJ, Zhou M, Yuan T, Huang ZY, Zhang ZY. Conversion treatment for advanced intrahepatic cholangiocarcinoma: Opportunities and challenges. World J Gastroenterol 2025; 31(15): 104901 [PMID: 40309227 DOI: 10.3748/wjg.v31.i15.104901]
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"The title of this paper should condense the main idea of the article and clearly indicate that it is a retrospective study. The description of research methods is not specific and clear enough. The citation of literature should include more recent references, which will increase the novelty and scientific value of the paper."
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Wu YP, Zhou JX, Wu HB, Wu DP, Qin LZ, Qin B, Xu XY, Yehya SAA, Cheng Y. Clinical characteristics and risk factors of esophageal reflux hypersensitivity: A multicenter study. World J Gastroenterol 2025; 31(17): 105281 [DOI: 10.3748/wjg.v31.i17.105281]
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"The retrospective study by Zhao et al. offers critical insights into sex-based differences in achalasia symptomatology and outcomes following peroral endoscopic myotomy (POEM). By analyzing 526 cases over a decade, the authors address a significant gap in understanding how sex influences preoperative presentation, manometric parameters, and postoperative recovery. While the study reaffirms POEM’s efficacy and highlights sex-specific nuances, two methodological limitations warrant attention: the absence of normality testing for data distribution and incomplete reporting of statistical metrics in tables. These omissions slightly undermine the robustness of the statistical analysis but do not negate the study’s overall contributions."
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Zhao CY, Xu N, Dong H, Chai NL, Linghu EQ. Effect of sex on the outcomes of peroral endoscopic myotomy for the treatment of achalasia. World J Gastroenterol 2025; 31(17): 104579 [DOI: 10.3748/wjg.v31.i17.104579]
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"This review by Liu and He provides a comprehensive exploration of intelligent hydrogel-based dressings for diabetic wound management. Chronic diabetic wounds, characterized by impaired or delayed healing due to multiple physiological disruptions, demand innovative solutions. The authors systematically categorize hydrogels into natural, synthetic, and composite types, dissecting their structural and functional mechanisms while highlighting their clinical potential. Below is a critical analysis of the article’s strengths, limitations, and future implications.
The article is well-organized, progressing logically from the pathophysiology of diabetic wounds to hydrogel design, responsiveness mechanisms, applications, and future challenges. This structure helps readers understand the progression from fundamental biological science to clinical findings in translational studies. The integration of materials science, nanotechnology, and biotechnology is a highlight. For instance, the discussion on composite hydrogels incorporating silver nanoparticles or conductive polymers demonstrates how hybrid materials enhance antibacterial efficacy and mimic bioelectrical environments. The inclusion of emerging technologies like 3D printing and real-time monitoring systems reflects a forward-thinking approach.
The authors bolster their claims with recent preclinical and clinical studies (e.g., phase 4 trials of Fitostimoline and SANTYL hydrogels). References to advanced functionalities, such as glucose-responsive insulin release or photothermal antibacterial activity, are supported by robust experimental data, lending credibility to the proposed applications. The emphasis on personalized precision medicine aligns with current trends in healthcare. The concept of hydrogels adapting to wound microenvironment changes (pH, temperature, biomarkers) for tailored drug delivery represents a paradigm shift from traditional "one-size-fits-all" therapies.
The article does have some limitations. In terms of clinical translation challenges, while the article acknowledges barriers like high costs and biocompatibility concerns, it lacks actionable strategies for overcoming these hurdles. For example, cost reduction could be addressed through scalable manufacturing techniques or public-private partnerships, yet these solutions are only briefly mentioned. Certain sections, particularly those detailing chemical cross-linking mechanisms or nanomaterial interactions, may alienate non-specialist readers. Simplifying jargon or incorporating analogies (e.g., comparing hydrogel networks to "smart sponges") could improve accessibility. In addition, long-term biocompatibility and potential side effects of nanomaterials (e.g., silver nanoparticle toxicity) are underexplored. A discussion on regulatory pathways or post-market surveillance would strengthen the clinical relevance of the review.
For future direction of dressings development, combining hydrogel dressings with wearable sensors or AI-driven diagnostics could enable closed-loop systems for real-time wound management. For instance, hydrogels equipped with IoT-enabled sensors might autonomously adjust drug release based on cloud-analyzed biomarker data. Exploring eco-friendly materials (e.g., biodegradable polymers) and energy-efficient production methods would address environmental concerns. Additionally, cost-benefit analyses comparing hydrogel dressings to standard care could incentivize healthcare adoption. Future studies should prioritize patient feedback to improve usability, such as optimizing hydrogel adhesion for mobility or reducing dressing change frequency. Ethnographic studies on patient adherence could inform design modifications.
In conclusion, Liu and He’s review underscores the transformative potential of intelligent hydrogels in diabetic wound care, bridging scientific innovation with clinical needs. By addressing microenvironmental challenges through responsive drug delivery, antibacterial action, and tissue regeneration, these materials represent a leap toward personalized medicine. However, translating laboratory success to bedside application requires tackling economic, technical, and regulatory barriers. Future efforts must prioritize interdisciplinary collaboration, patient-centric design, and sustainable scaling to unlock the full promise of intelligent hydrogels. This article serves as both a foundational reference and a call to action for researchers, clinicians, and policymakers to reimagine diabetic wound management."
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Liu H, He L. Intelligent hydrogel-based dressings for treatment of chronic diabetic wounds. World J Diabetes 2025; 16(5): 104937 [DOI: 10.4239/wjd.v16.i5.104937]
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" This article provides important data and insights for the study of reflux hypersensitivity (RH). The study is well-designed as a multicenter, large-sample, retrospective investigation, comprehensively analyzing the clinical characteristics and risk factors of patients with reflux hypersensitivity (RH). The assessment is extensive, covering symptoms, esophageal motility, impedance-pH monitoring, and psychological factors, revealing the significance of weakly acidic reflux (WAR) and non-acid reflux (NAR) in RH. The use of multiple statistical methods ensures the scientific reliability of the results. However, there are some limitations. Despite involving three medical centers, the sample size is still relatively small, with only 109 cases. The follow-up period is short, from January 2022 to December 2023, which may limit the generalizability of the study results and the assessment of long-term effects. The study mainly focuses on the clinical characteristics and risk factors of RH, but there is relatively little analysis of treatment response and prognosis in patients. The article uses the Hamilton Anxiety Scale and the Hamilton Depression Scale to assess the psychological status of patients, but it does not evaluate the effectiveness of psychological interventions in RH patients."
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Wu YP, Zhou JX, Wu HB, Wu DP, Qin LZ, Qin B, Xu XY, Yehya SAA, Cheng Y. Clinical characteristics and risk factors of esophageal reflux hypersensitivity: A multicenter study. World J Gastroenterol 2025; 31(17): 105281 [DOI: 10.3748/wjg.v31.i17.105281]
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"This article investigates the therapeutic potential of BIC in the context of MASLD, with a particular focus on its effects on lipid metabolism and inflammation. BIC, an alkaloid traditionally recognized as a GABA receptor antagonist, is presented as a novel therapeutic candidate for MASLD. This exploration is particularly intriguing, as the GABAergic pathways are well-documented for their roles within the nervous system; however, the investigation into BIC’s impact on hepatic lipid metabolism and inflammatory processes remains relatively novel and promising. The utilization of zebrafish, HepG2, and AML12 cellular models, alongside mouse models induced by a MCD diet, significantly enhances the validity of the findings. By employing multiple experimental models, the researchers provide robust evidence supporting the efficacy of BIC in alleviating MASLD, which is essential for the translation of these findings into clinical practice. Furthermore, the absence of significant toxicity observed in zebrafish embryos and cellular models, even at relatively high concentrations of BIC, suggests a favorable safety profile for this compound. This aspect is critical, as it bolsters the notion that BIC could potentially be developed into a therapeutic agent devoid of the toxic effects commonly associated with alternative treatments. However, while the study offers compelling evidence from preclinical models, it is imperative to investigate the long-term effects of BIC. Given that MASLD can progress to more severe forms, such as steatohepatitis and fibrosis, long-term studies are necessary to ascertain whether BIC can effectively prevent such progression. Moreover, although the results of the study confirm the absence of significant toxicity associated with the drug, the relationship between its pharmacological mechanisms and GABA warrants further discussion, or at the very least, should be acknowledged in the limitations section."
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Wang XM, Dai Z, Lu DJ, Bao CQ, Yang NB, Zhou YP. Bicuculline ameliorates metabolic dysfunction-associated steatotic liver disease by inhibiting the nuclear factor-kappa B pathway and reducing lipid accumulation. World J Gastroenterol 2025; 31(17): 105438 [DOI: 10.3748/wjg.v31.i17.105438]
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"Title: Interventional effect of hesperetin on N-methyl-N’-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis.
The study proved that hesperetin aleviated the gastric carcinogenesis by mediating exosome-derived circ0008274 targeting miR-526b-5p. The hesperidin-mediated exosomes circ0008274/miR-526b-5p axis and it can serve as a potential target for slowing the onset of gastric cancer. These findings play an important role in the management of gastric precancerous lesions.
The overall study is good but this research used bioinformatics technique and future researches are need to used the integration of bioinformatics, genomics, and proteomics to give more explanation for the protective effect of hesperetin on the gastric cancer. "
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Liang ZF, Xu YM, Song JJ, Gao ZH, Qian H, Xu XZ. Interventional effect of hesperetin on N-methyl-N’-nitro-N-nitrosoguanidine-induced exosomal circ008274 in affecting normal cells to promote gastric carcinogenesis. World J Gastroenterol 2025; 31(16): 104920 [PMID: 40308800 DOI: 10.3748/wjg.v31.i16.104920]
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"The current study is very interesting as the authors addressed the role of gut micro biota in pathogenesis of chronic hepatitis B infection. They reported that the abundance of Dorea varies significantly across various stages of liver fibrosis, making it a potential microbial marker for identifying the onset and progression of liver fibrosis. This useful conclusion will pave the way for modification of treatment strategy of chronic hepatitis B infection
However, I have two comments:
1-The selection of patients with a wide range of age : 18-80 may have an impact on the results. Previous studies have sown as individuals age, the gut microbiota undergoes significant changes in composition, diversity, and functionality , which have been linked to various health conditions, including cognitive decline and inflammatory diseases.
2-It would have been better to select two equal groups of patients from the start: one group with hepatic fibrosis and the other without fibrosis .Having the equal or nearly equal groups would make statistical analysis more fair as the groups already studied had one with 35 patients and the other with 102 patients.
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Zhu Y, Geng SY, Chen Y, Ru QJ, Zheng Y, Jiang N, Zhu FY, Zhang YS. Machine learning algorithms reveal gut microbiota signatures associated with chronic hepatitis B-related hepatic fibrosis. World J Gastroenterol 2025; 31(16): 105985 [PMID: 40308807 DOI: 10.3748/wjg.v31.i16.105985]
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"The authors have made a significant contribution by uncovering the role of the Interleukin-36 (IL-36) subfamily in liver cirrhosis, particularly highlighting the relationship between these cytokines and gut microbiota. This work provides a fresh perspective on the gut-liver axis, demonstrating how an imbalance in the gut microbiome might contribute to liver disease progression through inflammatory cytokine signaling.
The innovation of the study lies in its identification of IL-36 cytokines, such as IL-36α, IL-36γ, IL-36Ra, and IL-38, as crucial players in the inflammatory processes associated with liver cirrhosis. By correlating these cytokines with gut microbiota alterations, the authors open new avenues for potential biomarkers and therapeutic targets in liver disease management. Their findings suggest that the IL-36 subfamily could help us better understand the pathophysiological mechanisms underlying liver cirrhosis and its association with dysbiosis in the gut microbiome.
However, a notable limitation of the study is the lack of mechanistic exploration of how IL-36 cytokines mediate these effects in the liver. While the paper discusses correlations between IL-36 subfamily levels and gut microbiota, the underlying mechanisms linking these factors to liver cirrhosis progression are not fully explored. Further research into how IL-36 cytokines influence microbiota composition and how they interact with liver disease would enhance the understanding of the gut-liver axis."
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Pan YZ, Chen WT, Jin HR, Liu Z, Gu YY, Wang XR, Wang J, Lin JJ, Zhou Y, Xu LM. Correlation between the interleukin-36 subfamily and gut microbiota in patients with liver cirrhosis: Implications for gut-liver axis imbalance. World J Hepatol 2025; 17(4): 105660 [PMID: 40308824 DOI: 10.4254/wjh.v17.i4.105660]
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"This paper evaluates the impact of sex on the outcomes of peroral endoscopic myotomy (POEM) in the treatment of esophageal achalasia. POEM is concluded to be a safe and effective treatment for both men and women, with women potentially deriving greater benefit than men. The study further suggests that sex may influence the therapeutic effect and symptom improvement after POEM, with hormonal factors being particularly important in women. The short-term success rate of POEM surgery is 96.52%. Success is improving the Eckardt score to 3 or less without additional treatment. These results indicate that POEM is a highly effective first-line option for achalasia treatment. However, the technical difficulty of POEM is high, and even in Japan, where endoscopic therapy is widespread, the procedure is limited to a small number of high-volume centers. Addressing expanding access to this effective technique is a significant future challenge.
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Zhao CY, Xu N, Dong H, Chai NL, Linghu EQ. Effect of sex on the outcomes of peroral endoscopic myotomy for the treatment of achalasia. World J Gastroenterol 2025; 31(17): 104579 [DOI: 10.3748/wjg.v31.i17.104579]
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"The manuscript addresses the role of exosomal miR-137-3p derived from hypoxia-injured endometrial epithelial cells (EECDs) in regulating hucMSC behavior, which is of potential interest in the context of endometrial regeneration. However, several critical issues limit the scientific clarity and integrity of the current work:
In the first part of the results, the authors performed RNA sequencing to compare miRNA expression profiles in hucMSCs treated with EECD-ex versus EEC-ex. However, Figure 7 implies that the differential expression of miR-137-3p originates from differences in the exosomal content of EECD-ex versus EEC-ex. This is a fundamental inconsistency. Changes in miRNA expression within recipient hucMSCs do not directly reflect the cargo of the exosomes unless validated by exosome profiling. Such discrepancy may mislead the interpretation regarding the source and function of miR-137-3p.
The manuscript does not provide essential data on the characterization of exosomes (e.g., TEM, NTA, exosomal markers such as CD63, CD81, or TSG101). Moreover, it is unclear whether there is a difference in exosome yield (i.e., production efficiency or protein content) between EEC-ex and EECD-ex.
The manuscript lacks transparency on how miR-137-3p was selected from the pool of 53 differentially expressed miRNAs.
While functional assays were performed on hucMSCs, the study does not include gain- or loss-of-function experiments at the exosomal level (e.g., using miR-137-3p inhibitors/mimics in donor EECs before exosome collection). Such experiments are critical to directly establish causality between EECD-exosomal miR-137-3p and the observed hucMSC behavior."
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Zhang WY, Liu SM, Wang HB, Deng CY. Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia. World J Stem Cells 2025; 17(4): 100359 [PMID: 40308888 DOI: 10.4252/wjsc.v17.i4.100359]
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"A letter to the Editor entitled Hypoxic endometrial epithelial cell-derived microRNAs effectively regulate the regenerative properties of mesenchymal stromal cells by Dr Mallis elegantly comments on the significance of the study published by Dr Zhang. The author highlights the clinical significance of the data obtained from in vitro experiments and, at the same time, provides mechanistic insight into the role of mir-214-5p and 21-5p in mesenchymal stem cells’ functionality and reparability of endometrial endothelial cells. The author has rightfully suggested that the published data by Zhang et al. has been derived from in vitro experimentation and there is a need for supporting this data by in vivo experiments. The letter is fluently written and supplements the findings of Zhang et al."
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Mallis P. Hypoxic endometrial epithelial cell-derived microRNAs effectively regulate the regenerative properties of mesenchymal stromal cells. World J Stem Cells 2025; 17(4): 102482 [PMID: 40308881 DOI: 10.4252/wjsc.v17.i4.102482]
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"Mubin Ozercan et al. presented an interesting article "Vonoprazan and proton pump inhibitors: Which is superior for Helicobacter pylori eradication?" The authors' decision to summarize current information on the effectiveness of anti-Helicobacter therapy based on the use of proton pump inhibitors and based on the use of potassium-competing acid blockers(P-CAB) was absolutely correct and timely. A large number of comparative studies are available in scientific medical databases. Confirmation of the high level of effectiveness of potassium-competing acid blockers has practical significance for use in various eradication treatment regimens."
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Ozercan M, Tawheed A, Ismail A, Amer MS, El-Kassas M. Vonoprazan and proton pump inhibitors: Which is superior for Helicobacter pylori eradication? World J Gastroenterol 2025; 31(17): 103156 [DOI: 10.3748/wjg.v31.i17.103156]
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"Title: Cardiac Metastatic Tumors: Revisiting Mechanisms and Future Perspectives
To the Editor
We read with great interest the article by Luo et al.[1] titled "Comprehensive understanding of a rare disease: Cardiac metastatic tumor, a double-center 10-year case review," recently published in World Journal of Cardiology. We congratulate the authors for providing valuable clinical insights into the rare and underrecognized entity of cardiac metastatic tumors (CMTs).
The study's finding that intracardiac metastases are associated with a poorer prognosis compared to pericardial involvement aligns with prior autopsy-based observations[2,3], emphasizing the prognostic importance of metastatic localization within the cardiac structure. The authors' inclusion of cardiac biomarkers, such as BNP and troponin, as predictors of adverse outcomes is particularly commendable and may represent a step toward more precise risk stratification.
Building upon these important findings, we wish to highlight several emerging directions that could deepen our understanding of CMTs:
First, organotropism and pre-metastatic niche formation are increasingly recognized as critical determinants of metastatic dissemination[4,5]. Experimental studies have demonstrated that cardiac tissue exhibits a unique extracellular matrix composition and a dynamic immunological environment, which may preferentially attract circulating tumor cells[6]. Investigating the role of cardiac-specific chemokine axes, such as CXCL12-CXCR4 signaling, may provide new insights into the molecular determinants of cardiac colonization.
Second, advanced imaging modalities warrant greater emphasis in the diagnostic pathway. While echocardiography remains the first-line modality, cardiac magnetic resonance (CMR) imaging and ^18F-FDG PET-CT possess superior tissue characterization capabilities, enabling differentiation between malignant and benign cardiac masses with higher sensitivity and specificity[7,8]. Early integration of these modalities could significantly alter the therapeutic trajectory for patients with occult cardiac involvement.
Third, therapeutic approaches for CMTs remain largely individualized and empirical. Although palliative strategies predominate, isolated reports suggest that surgical resection or stereotactic radiotherapy may improve quality of life and survival in carefully selected patients[9]. Prospective studies incorporating molecular tumor profiling—such as HER2, EGFR, or ALK status—may refine patient selection and therapeutic planning[10].
Moreover, given the rising incidence of CMTs in the era of improved oncological survival, it is imperative to establish multicenter registries and collaborative research networks focusing specifically on cardiac oncology. Standardizing diagnostic criteria, staging systems, and treatment algorithms would provide an urgently needed framework for evidence-based clinical decision-making.
In conclusion, Luo et al. have made a valuable contribution by elucidating the clinical and prognostic characteristics of CMTs. Future investigations integrating molecular oncology, advanced imaging, and standardized therapeutic strategies will be pivotal to improving the outcomes of patients with this rare but increasingly encountered condition.
References
1.Luo LY, Yang TS, He Z, Lin L, Luo XL. Comprehensive understanding of a rare disease: Cardiac metastatic tumor, a double-center 10-year case review. World J Cardiol. 2025;17(2):101851. doi:10.4330/wjc.v17.i2.101851
2.Bussani R, De-Giorgio F, Abbate A, Silvestri F. Cardiac metastases. J Clin Pathol. 2007;60(1):27-34. doi:10.1136/jcp.2005.035105
3.Lam KY, Dickens P, Chan AC. Tumors of the heart: a 20-year experience with a review of 12,485 consecutive autopsies. Arch Pathol Lab Med. 1993;117(10):1027-1031.
4.Peinado H, Zhang H, Matei IR, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer. 2017;17(5):302-317. doi:10.1038/nrc.2017.6
5.Labelle M, Hynes RO. The initial hours of metastasis: the importance of cooperative host-tumor cell interactions during hematogenous dissemination. Cancer Discov. 2012;2(12):1091-1099. doi:10.1158/2159-8290.CD-12-0329
6.Shinde AV, Frangogiannis NG. Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol. 2014;70:74-82. doi:10.1016/j.yjmcc.2013.12.011
7.Bogaert J, Francone M. Cardiac tumors and masses: the role of cardiovascular magnetic resonance imaging. Eur Radiol. 2009;19(1):14-27. doi:10.1007/s00330-008-1161-0
8.Rahbar K, Seifarth H, Schäfers M, et al. Differentiation of malignant and benign cardiac tumors using 18F-FDG PET/CT. J Nucl Med. 2012;53(6):856-863. doi:10.2967/jnumed.111.099028
9.Yusuf SW, Bathina JD, Qureshi S, et al. Cardiac tumors in cancer patients: diagnosis, management, and prognosis. Oncologist. 2007;12(4):443-450. doi:10.1634/theoncologist.12-4-443
10.Nguyen DX, Bos PD, Massagué J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274-284. doi:10.1038/nrc2622"
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Luo LY, Yang TS, He Z, Lin L, Luo XL. Comprehensive understanding of a rare disease: Cardiac metastatic tumor, a double-center 10-year case review. World J Cardiol 2025; 17(2): 101851 [PMID: 40061273 DOI: 10.4330/wjc.v17.i2.101851]
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"The low-cost and easy-to-obtain characteristics of the TyG index introduced in this article make it feasible for clinical translation, especially in resource-limited settings. However, the universality of the TyG index threshold is questionable, and the influence of metabolic characteristics (e.g., diet and genetics) in different populations needs to be considered. In addition, the role of TyG index in early gastric cancer and its relationship with the dynamic changes of tumor microenvironment have not been elucidated. It is worth noting that high TyG index may reflect enhanced metabolic reserve in advanced patients, while may promote malignant transformation in precancerous lesions, and this "double-edged sword" effect needs to be further explored."
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Zhao CF, Liu XL, Wu NB, Xu ZF. Triglyceride-glucose index as a prognostic indicator in advanced gastric cancer: Insights and future research. World J Gastroenterol 2025; 31(17): 104794 [DOI: 10.3748/wjg.v31.i17.104794]
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"1、The study would be further strengthened if the authors could elaborate in greater detail on how STAT3 was identified and the specific mechanisms by which miR-137-3p regulates STAT3.
2、Frankly, the impact of miR-137-3p on p-STAT3 appears minimal, as shown in Figure 3B.
3、A more in-depth exploration of UBE3C’s role in modulating the STAT3 signaling pathway and its mechanistic underpinnings would enhance the study. For instance, investigating whether miR-137-3p influences STAT3 signaling following UBE3C knockdown could yield valuable insights."
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Zhang WY, Liu SM, Wang HB, Deng CY. Exosomal miR-137-3p targets UBE3C to activate STAT3, promoting migration and differentiation into endometrial epithelial cell of human umbilical cord mesenchymal stem cells under hypoxia. World J Stem Cells 2025; 17(4): 100359 [PMID: 40308888 DOI: 10.4252/wjsc.v17.i4.100359]
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"comment to Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced gastrointestinal dysfunction in Parkinson's disease mice
We are delighted to have read the article titled "Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydr- opyridine-induced gastrointestinal dysfunction in Parkinson's disease mice" authored by Xin-Yu Wang’s team in the World Journal of Gastroenterology.
Parkinson’s disease (PD) is a multicentric neurodegenerative disorder characterized by the accumulation and aggregation of alfa-synuclein (α-syn) in the substantia nigra in the central nervous system (CNS) and in other neural structures(1). It is the second most common and the most rapidly rising neurodegenerative disease in the world(2). While the exact causes behind the increasing incidence and prevalence of PD remain unclear, contributing factors may include longer life expectancy, declining smoking rates, and exposure to environmental pollutants and toxins(3). Among the earliest manifestations of PD are gastrointestinal (GI) symptoms, which often precede the onset of motor impairments. GI dysfunction in PD is closely linked to the gut-brain axis, reflecting the bidirectional communication between the CNS and the GI tract in both health and disease (4). However, there are still limitations in the research on the relationship between PD and GI dysfunction, and the specific molecular mechanism has not been fully elucidated.
In this study, the findings of Xin-Yu Wang’s team provide valuable insights and innovative approaches for PD treatment. This paper represents the first systematic demonstration that rhapontin alleviates gut-brain axis dysfunction in PD by activating colonic NRF2, thereby offering a novel therapeutic target for the disease. By integrating network pharmacology predictions with experimental validation, this study enhances its scientific robustness and credibility. Furthermore, a key discovery of this study is that the anti-inflammatory effects of rhapontin are predominantly localized to the intestinal tract rather than being mediated through the brain-derived NRF2 pathway. This provides experimental evidence supporting the "enteric pathology hypothesis" of PD (5). Overall, these findings present critical theoretical support for rhapontin as a promising therapeutic agent for GI dysfunction in PD.
However, we have several exploratory comments regarding certain aspects of the study.
First, extensive research has established the critical role of the gut-brain axis in mediating GI dysfunction associated with PD through interconnected pathophysiological mechanisms. For example, gut microbiota dysbiosis can compromise intestinal barrier integrity, leading to a "leaky gut" phenomenon. This allows lipopolysaccharides (LPS) to trigger immune cell activation and the release of pro-inflammatory cytokines, which contribute to systemic inflammation and increased blood-brain barrier (BBB) permeability. Consequently, peripheral inflammatory signals can spread to the CNS, and after that, pathological α-syn will aggregate in the dorsal motor nucleus of the vagus nerve (DMV) and the substantia nigra. The levels of pathological α-syn also increase mitochondrial fragmentation in the DMV, ultimately leading to PD pathophysiology (6). Pathogenic α-syn may spread from the gut to the brain, leading to the degeneration of the nigrostriatal dopaminergic system, thus increasing the risk of developing PD (7, 8). Supporting this, animal studies have shown that fecal microbiota transplantation from PD patients induces α-syn aggregation and dopaminergic neuron loss (9). Additionally, gut microbiota also can regulate neurotransmitter homeostasis by modulating dopamine (DA) and serotonin production, while short-chain fatty acids (SCFAs) help mitigate intestinal inflammation, reduce oxidative stress, and enhance BBB integrity to protect DA neurons(6, 10-12). One of the characteristics of PD is the progressive loss of DA neurons in the substantia nigra pars compacta (13). Lastly, dysbiotic gut microbiome (dysbiome) can impair mitochondrial energy metabolism, trigger the TLR4/NF-κB pathway, and exacerbate oxidative stress, ultimately leading to the degeneration of nigral dopaminergic neurons (6). Collectively, these mechanisms form a core network through which the gut-brain axis contributes to PD pathogenesis. In this study, only studied the effect between rhapontin and the gastrointestinal dysfunction caused by PD, without systematically combining the gut-brain axis with PD for research. Additionally, although gut microbiota play a pivotal role in the gut-brain axis of PD, the study does not evaluate the influence of rhapontin on microbiota composition or function (14-16). It remains unclear whether rhapontin indirectly activates NRF2 or reduces inflammation by modulating specific microbial populations. Future studies could explore this by employing approaches such as 16S rRNA sequencing or metagenomics to assess changes in fecal microbiota composition, alongside quantifying microbiota-derived metabolites. Such investigations would provide deeper insights into the gut-brain axis dynamics and further elucidate rhapontin’s mechanisms of action.
Secondly, rhapontin is a stilbenoid glucoside compound, found in medicinal plant of rhubarb rhizomes. Research into the anti-inflammatory mechanisms of rhapontin has revealed its multi-pathway synergistic effects. For example, in LPS-induced endothelial cell inflammation models, rhapontin effectively suppresses nitric oxide (NO) and TNF-α production while downregulating the expression of Inducible Nitric Oxide Synthase (iNOS), Cyclooxygenase-2 (COX-2), and NADPH Oxidase - related genes (NOX-related genes). These effects are primarily achieved by inhibiting the activation of key proteins in the Nuclear Factor-kappa B (NF-κB) and Mitogen - Activated Protein Kinase (MAPK) signaling pathways(17). In terms of antioxidant regulation, rhapontin activates the NRF2 signaling pathway, which reduces Tumor Necrosis Factor-alpha (TNF-α) and Matrix Metalloproteinase-2 (MMP-2) levels in diabetic retinopathy models, while enhancing the expression of Interleukin – 10 (IL-10) and Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) and inhibiting NF-κB nuclear translocation(18). Its anti-fibrotic properties are mediated through dual mechanisms: activating Adenosine Monophosphate - Activated Protein Kinase (AMPK) and inhibiting the Transforming Growth Factor – beta (TGF-β)/Smad pathway, which helps reverse abnormal extracellular matrix deposition and prevents the progression of pulmonary fibrosis(19). Additionally, rhapontin has been shown to improve colonic epithelial barrier function via Sirtuin 1 (SIRT1) signaling activation(20). Together, these findings systematically highlight rhapontin's integrative therapeutic effects through coordinated modulation of NF-κB/MAPK, AMPK/TGF-β/Smad, and SIRT1 signaling networks, addressing inflammation, oxidative stress, and fibrosis.
The current study demonstrated that rhapontin effectively reduces inflammation by decreasing the levels of pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, while also activating the NRF2 signaling pathway to improve gastrointestinal function. However, the study did not explore rhapontin's potential role in preventing the progression of pulmonary fibrosis through AMPK activation and inhibition of the TGF-β/Smad pathway, nor did it investigate its effects on improving colonic epithelial barrier function via activation of the SIRT1 signaling pathway. Additionally, while network pharmacology was used to predict shared targets between PD and rhapontin, and the top 10 key targets were identified using a protein-protein interaction (PPI) network, the relationship between these targets and NRF2 remains poorly defined. Moreover, the study lacks detailed mechanistic insights into the specific signaling pathways associated with NRF2, including its upstream and downstream regulatory mechanisms—an area that requires further investigation. The article also does not clearly explain how NRF2 was identified as a key target. o address these research gaps, future studies could employ techniques such as Western blotting (WB) and co-immunoprecipitation (Co-IP) to validate the protein-protein interactions between rhapontin's potential targets and NRF2. Additionally, methods such as quantitative real-time polymerase chain reaction (qPCR) or RNA sequencing could be used to analyze downstream gene expression regulated by NRF2. These approaches would provide a more comprehensive understanding of the molecular mechanisms underlying rhapontin's anti-inflammatory effects, offering deeper insights into its therapeutic potential for PD.
In evaluating the experimental section of this study, some points warrant further discussion. First, regarding the presentation of the results: Figure 2A does not clearly label which specific experimental group each result corresponds to, making interpretation challenging. Additionally, the WB image in Figure 5A lacks clarity and does not exhibit an obvious trend in the results, which may hinder the ability to draw definitive conclusions. Second, concerning the experimental methods: the study utilized only two approaches—the open field test and the pole-climbing test—to assess the motor abilities of mice. While these methods provide useful insight, they may be insufficient for a comprehensive evaluation of motor behavior in PD. Incorporating additional behavioral experiments, such as the Morris water maze, eight-arm radial maze, and elevated plus maze, could allow for a more thorough assessment of motor and cognitive functions in the mouse model (21).
In summary, Wang XY’s team has conducted pioneering research, offering significant insights into the therapeutic potential of rhapontin for GI dysfunction in PD. This work is highly commendable, and we look forward to the authors addressing the aforementioned concerns in future studies through more detailed experimental design and exploration. Such efforts would further enhance the robustness and comprehensiveness of their findings.
1. Koga S, Sekiya H, Kondru N, Ross OA, Dickson DW Neuropathology and molecular diagnosis of Synucleinopathies. Mol Neurodegener. 2021;16(1):83.
2. delete Global, regional, and national burden of Parkinson's disease, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018;17(11):939-53.
3. Bloem BR, Okun MS, Klein C Parkinson's disease. Lancet. 2021;397(10291):2284-303.
4. Gao V, Crawford CV, Burré J The Gut-Brain Axis in Parkinson's Disease. Cold Spring Harb Perspect Med. 2025;15(1).
5. Safarpour D, Sharzehi K, Pfeiffer RF Gastrointestinal Dysfunction in Parkinson's Disease. Drugs. 2022;82(2):169-97.
6. Munoz-Pinto MF, Candeias E, Melo-Marques I, Esteves AR, Maranha A, Magalhães JD, Carneiro DR, Sant'Anna M, Pereira-Santos AR, Abreu AE, Nunes-Costa D, Alarico S, Tiago I, Morgadinho A, Lemos J, Figueiredo PN, Januário C, Empadinhas N, Cardoso SM Gut-first Parkinson's disease is encoded by gut dysbiome. Mol Neurodegener. 2024;19(1):78.
7. Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA, Shen C, Lee H, Kulkarni S, Pasricha PJ, Lee G, Pomper MG, Dawson VL, Dawson TM, Ko HS Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. Neuron. 2019;103(4):627-41.e7.
8. Van Den Berge N, Ferreira N, Gram H, Mikkelsen TW, Alstrup AKO, Casadei N, Tsung-Pin P, Riess O, Nyengaard JR, Tamgüney G, Jensen PH, Borghammer P Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats. Acta Neuropathol. 2019;138(4):535-50.
9. Tan AH, Lim SY, Lang AE The microbiome-gut-brain axis in Parkinson disease - from basic research to the clinic. Nat Rev Neurol. 2022;18(8):476-95.
10. Du J, Zhang P, Tan Y, Gao C, Liu J, Huang M, Li H, Shen X, Huang P, Chen S Idiopathic Rapid Eye Movement Sleep Behavior Disorder (iRBD) Shares Similar Fecal Short-Chain Fatty Acid Alterations with Multiple System Atrophy (MSA) and Parkinson's Disease (PD). Mov Disord. 2024;39(8):1397-402.
11. Nishiwaki H, Hamaguchi T, Ito M, Ishida T, Maeda T, Kashihara K, Tsuboi Y, Ueyama J, Shimamura T, Mori H, Kurokawa K, Katsuno M, Hirayama M, Ohno K Short-Chain Fatty Acid-Producing Gut Microbiota Is Decreased in Parkinson's Disease but Not in Rapid-Eye-Movement Sleep Behavior Disorder. mSystems. 2020;5(6).
12. Wang Q, Luo Y, Ray Chaudhuri K, Reynolds R, Tan EK, Pettersson S The role of gut dysbiosis in Parkinson's disease: mechanistic insights and therapeutic options. Brain. 2021;144(9):2571-93.
13. Tolosa E, Garrido A, Scholz SW, Poewe W Challenges in the diagnosis of Parkinson's disease. Lancet Neurol. 2021;20(5):385-97.
14. Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell. 2016;167(6):1469-80.e12.
15. Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G, Zhang D Fecal microbiota transplantation protects rotenone-induced Parkinson's disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome. 2021;9(1):226.
16. Metta V, Leta V, Mrudula KR, Prashanth LK, Goyal V, Borgohain R, Chung-Faye G, Chaudhuri KR Gastrointestinal dysfunction in Parkinson's disease: molecular pathology and implications of gut microbiome, probiotics, and fecal microbiota transplantation. J Neurol. 2022;269(3):1154-63.
17. Li R, Chinnathambi A, Alharbi SA, Shair OHM, Veeraraghavan VP, Surapaneni KM, Rengarajan T Anti-inflammatory effects of rhaponticin on LPS-induced human endothelial cells through inhibition of MAPK/NF-κβ signaling pathways. J Biochem Mol Toxicol. 2021;35(5):e22733.
18. Shi Q, Cheng Y, Dong X, Zhang M, Pei C, Zhang M Effects of rhaponticin on retinal oxidative stress and inflammation in diabetes through NRF2/HO-1/NF-κB signalling. J Biochem Mol Toxicol. 2020;34(11):e22568.
19. Tao L, Cao J, Wei W, Xie H, Zhang M, Zhang C Protective role of rhapontin in experimental pulmonary fibrosis in vitro and in vivo. Int Immunopharmacol. 2017;47:38-46.
20. Wei W, Wang L, Zhou K, Xie H, Zhang M, Zhang C Rhapontin ameliorates colonic epithelial dysfunction in experimental colitis through SIRT1 signaling. Int Immunopharmacol. 2017;42:185-94.
21. Tuersong T, Wu QF, Chen Y, Shan Li P, Yong YX, Shataer M, Shataer S, Ma LY, Yang XL Integrated network pharmacology, metabolomics, and microbiome studies to reveal the therapeutic effects of Anacyclus pyrethrum in PD-MCI mice. Phytomedicine. 2025;142:156729."
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Wang XY, Liu F, Wang QT, Li SZ, Ye YZ, Chen T, Cai BC. Rhapontin activates nuclear factor erythroid 2-related factor 2 to ameliorate 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced gastrointestinal dysfunction in Parkinson's disease mice. World J Gastroenterol 2025; 31(15): 104875 [PMID: 40309229 DOI: 10.3748/wjg.v31.i15.104875]
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"Name of Journal:World Journal of Hepatology
Manuscript NO:
Manuscript Type: LETTER TO THE EDITOR
Commentary: Multi-omics reveals the associations among the fecal metabolome,intestinal bacteria, and serum indicators in patients with
hepatocellular carcinoma
Biao Wen,Yin-Ping Wang
Biao Wen,Yin-Ping Wang,Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610000, Sichuan Province, China
Author contributions:Yin-Ping Wang wrote the original draft; Biao Wen contributed to conceptualization, writing, reviewing and editing; Yin-Ping Wang and Biao Wen participated in drafting the manuscript; and all authors have read and approved the final version of the manuscript.
Supported by
ORCID number：0000-0001-5226-5981
Corresponding author:Biao Wen,MD, PhD,Assistant Professor,Department of Gastroenterology, The First Affiliated Hospital of Chengdu Medical College,No. 312, Middle Section of Baoguang Avenue, Xindu District, Chengdu 610000, Sichuan Province, China. 820695761@qq.com
Received:
Revised:
Accepted:
Published online:
Abstract:
Recently, Feng J et al. published an important study. The research team revealed the associations of fecal metabolomics, intestinal bacteria and serum indicators in patients with hepatocellular carcinoma (HCC) through multi-omics analysis. The research results indicate that the composition of the metabolome and intestinal bacteria in fecal samples is expected to become a potential biomarker for the diagnosis of HCC. After a thorough review of their work, we put forward two insights regarding the impact of hepatitis B virus and antiviral drugs on the intestinal flora of HCC, the changes in intestinal microbiota in HCC and healthy control groups.
Key Words: Liver neoplasms; Gastrointestinal microbiome; Antiviral drug; Comment;
Core Tip: We conducted a rigorous assessment of the research by Feng et al., and put forward expert suggestions regarding the changes of HCC in the gut microbiota and the impact of hepatitis B virus and related antiviral drugs on the microbiota, in order to advance this scientific field.
TO THE EDITOR
After reading the study titled "Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma" by Feng et al. published in the World Journal of Gastroenterology, we found it highly insightful. The authors employed integrated metabolomic and microbiomic approaches to elucidate the linkages between fecal metabolites, gut microbiota, and serum biomarkers in hepatocellular carcinoma (HCC) patients, providing new perspectives for the early diagnosis of HCC. Here, we would like to share our perspectives on the following aspects: The impact of hepatitis B virus (HBV) and antiviral therapies on gut microbiota alterations in HCC; Gut microbial differences between HCC patients and healthy controls.
The first point: The changes in the gut microbiota of HCC and healthy control groups vary in different studies and may be influenced by multiple factors
More and more studies have shown that the intestinal microbiota is related to the occurrence of HCC and is expected to become a biomarker for the diagnosis of HCC. In the study by Feng et al., it was concluded that Lachnospira, Streptococcus and Veillonella are representative differential bacterial genera in the feces of HCC patients. These three bacterial genera and their related metabolites may serve as unique biomarkers [1]. Most studies have shown that there are differences in theα-diversity orβ-diversity of the intestinal microbiota between HCC patients and healthy control groups. However, these differences may vary when further studying the intestinal microbiota of HCC patients, such as at the genus level or species level.
Zhang et al. found that Enterococcaceae, Lactobacillus, Bacillus and Gammaproteobacteria can be used as diagnostic markers for primary liver cancer (PLC). In addition, a correlation analysis was conducted, and the results showed that Veillonella was significantly positively correlated with alpha-fetoprotein (AFP) in PLC patients[2]. In 2023, Zhang et al. demonstrated that at the family level, the abundance of Lachnospiraceae, Coriobacteriaceae, Eggerthellaceae and Synergistaceae in the liver cancer group was significantly reduced compared with the normal group. The abundances of Enterobacteriaceae, Fusobacteriaceae, Lactobacillus and Erysierysiaceae increased significantly. At the horizontal level, compared with the normal group, The liver cancer groups included Blautia, Fusicatenibacter, Anaerostipes, Lachnospiraceae_ND3007_group, GG-56, Eggerthella, Lachnospiraceae_FCS020_group and The abundance of Olsenella was significantly reduced. The abundance of Escherichia coli - Shigella, Prevotella_2 Tyzzerella_4, Clostridium erysipelum and Prevotella_2 Tyzzerella ₄ increased significantly. Meanwhile, alpha-fetoprotein (AFP) is positively correlated with the abundance of Streptococcus[3];Yang et al. confirmed through a prospective study that in terms of intestinal samples, the average relative abundance of Proteobacteria in the HCC group was significantly higher than that in the control group. The abundance of Streptococcus in oral and fecal samples of HCC patients was higher than that in the control group. Meanwhile, during the transition from a healthy state to liver cirrhosis and HCC, the content of streptococcus in the hepatocellular carcinoma and liver cirrhosis groups was much higher than that in the control group, and showed an upward trend during the disease progression. From the analysis of microbial correlations and clinical characteristics and functions among each group, both Streptococcus and Virongella were identified in the microbial communities of oral and intestinal samples, and both were in key positions in the microbial correlation network of fecal samples. Streptococcus and Virongella showed a consistent trend. Among them, the microbiome distribution was positively correlated with MELD, Child-Pugh, age, CCI, AFP, AST, ALT, GGT, Cre, LDL, Tchol, PT and INR, and negatively correlated with ALB, BMI, HDL, TG and PLT in HCC patients. This study has similarities with that of Feng J et al[4];In 2024, the research results of Jinato et al. indicated that HCC was enriched with five genera, including Bacteroides, Streptococcus, Ruminococcus, Veronistella and Clostridium erysibiricum. And Romboutsia, UCG-002, Lachnospiraceae NK4A-136, Eubacterium hallii group, Lachnospiraceae ND-3007 group, Erysipelotrichaceae Seven genera such as UCG-003 and Bilophila have low abundance in HCC patients[5].
From the above, it can be known that some studies have mentioned the three bacterial genera, Streptococcus, Veronella, and Lachnospira, in the HCC and healthy groups, showing an increase in the abundance of Streptococcus and Veronella, while the relative abundance of Lachnospira has decreased. However, in different studies, The reasons for the incomplete similarity in the abundance and structure of the intestinal microbiota between HCC and the healthy control group may be related to the drug use, alcohol consumption, diet, racial and regional differences of HCC patients[6];A Western diet high in fat, cholesterol or sugar can induce dysbiosis of the gut microbiome, a reduction in symbiotic probiotics and an increase in opportunistic pathogens[7];For example, the formation of NAFLD-HCC induced by dietary cholesterol is related to intestinal flora imbalance, and the composition of the microbiota changes with the formation stage of NAFLD-HCC: Mucispirillum, Desulfovibrio, Anaerotruncus and Desulfovibrionaceae increased successively; Bifidobacterium and Bacteroides were depleted in mice fed with HFHC, which was also confirmed in patients with human hypercholesterolemia[8].Therefore, it is still necessary to further verify the unique biomarkers of HCC.
The second point: Distinguish the independent effects of HBV infection and HCC and include data on the use of antiviral drugs
Hepatitis B virus infection can directly disrupt the intestinal flora balance through systemic inflammatory responses and disorders of the hepatoenteric axis. The study by Shen et al. indicated that the flora composition of patients with HBV-CLD (such as enrichment of Streptococcus and reduction of Bifidobacterium) was significantly different from that of the healthy control group. It is suggested that HBV infection itself has unique microbiota characteristics; Meanwhile, antiviral drug treatment can partially reverse the dysbiosis caused by HBV[9-10]; Jinato et al. studied the changes in the gut microbiota between Viral (virus-HCC) and non-viral (NNC-HCC) -related hepatocellular carcinomas and found that compared with virus-HCC, the NNC-HCC subgroup significantly reduced various bacteria that produce short-chain fatty acids and the reduction of fecal butyrate[5];Liu et al. also analyzed the intestinal microbiota changes in hepatitis B virus-associated hepatocellular carcinoma. The research results showed that there were differences in the abundance of bacteria in the intestines of patients with B-HCC and NNBNC-HCC, and these bacteria were respectively involved in different functions or biological pathways[11].
Therefore, whether there is HBV infection and whether antiviral treatment is used may have an impact on the changes in the intestinal flora. In the study by Feng J et al., we found that HBV accounted for a high proportion (78.95%) in the HCC population. Based on previous studies, stratified comparison of HCC patients with HBV(+) and HBV(-), as well as recording the use of antiviral drugs and analyzing their effects, can more accurately clarify the microbiota characteristics of HCC itself.
All in all, the changes in the gut microbiota are related to the occurrence and development of HCC. The inconsistency in the research on the gut microbiota related to HCC reflects the complexity of the disease and the dynamics of host-microbiota interactions. Future studies need to directly compare the microbiota, metabolome and immune characteristics of patients with HBV(+)HCC and HBV(-)HCC through larger sample cohorts of HCC, and combine animal models to verify the causal mechanism in order to reveal more robust microbiota characteristics and their mechanism of action in the occurrence and development of HCC. We look forward to the author team conducting follow-up research in this direction and promoting the innovation of early diagnosis techniques for HCC. Once again, we thank the authors for their outstanding work, which has opened up new ideas for HCC research.
Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.
1.Feng J, Wang J P, Hu J R, et al. Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma[J]. World Journal of Gastroenterology, 2025, 31(15).
2.Zhang L, Wu YN, Chen T, Ren CH, Li X, Liu GX. Relationship between intestinal microbial dysbiosis and primary liver cancer. Hepatobiliary Pancreat Dis Int. 2019 Apr;18(2):149-157. doi: 10.1016/j.hbpd.2019.01.002. Epub 2019 Jan 4. PMID: 30661942.
3.Zhang W, Xu X, Cai L, Cai X. Dysbiosis of the gut microbiome in elderly patients with hepatocellular carcinoma. Sci Rep. 2023 May 13;13(1):7797. doi: 10.1038/s41598-023-34765-w. PMID: 37179446; PMCID: PMC10182990.
4.Yang J, He Q, Lu F, Chen K, Ni Z, Wang H, Zhou C, Zhang Y, Chen B, Bo Z, Li J, Yu H, Wang Y, Chen G. A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma. Gut Microbes. 2023 Jan-Dec;15(1):2201159. doi: 10.1080/19490976.2023.2201159. PMID: 37089022; PMCID: PMC10128432.
5.Jinato T, Anuntakarun S, Satthawiwat N, Chuaypen N, Tangkijvanich P. Distinct alterations of gut microbiota between viral- and non-viral-related hepatocellular carcinoma. Appl Microbiol Biotechnol. 2024 Dec;108(1):34. doi: 10.1007/s00253-023-12845-1. Epub 2024 Jan 6. PMID: 38183473; PMCID: PMC10771587.
6.Arnold M, Abnet CC, Neale RE, Vignat J, Giovannucci EL, McGlynn KA, Bray F. Global Burden of 5 Major Types of Gastrointestinal Cancer. Gastroenterology. 2020 Jul;159(1):335-349.e15. doi: 10.1053/j.gastro.2020.02.068. Epub 2020 Apr 2. PMID: 32247694; PMCID: PMC8630546.
7.Pan Y, Zhang X. Diet and gut microbiome in fatty liver and its associated liver cancer. J Gastroenterol Hepatol. 2022 Jan;37(1):7-14. doi: 10.1111/jgh.15713. Epub 2021 Nov 3. PMID: 34664301.
8.Zhang X, Coker OO, Chu ES, Fu K, Lau HCH, Wang YX, Chan AWH, Wei H, Yang X, Sung JJY, Yu J. Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites. Gut. 2021 Apr;70(4):761-774. doi: 10.1136/gutjnl-2019-319664. Epub 2020 Jul 21. PMID: 32694178; PMCID: PMC7948195.
9.Shen Y, Wu SD, Chen Y, Li XY, Zhu Q, Nakayama K, Zhang WQ, Weng CZ, Zhang J, Wang HK, Wu J, Jiang W. Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response. Gut Microbes. 2023 Jan-Dec;15(1):2155018. doi: 10.1080/19490976.2022.2155018. PMID: 36519342; PMCID: PMC9757487.
10.Li YG, Yu ZJ, Li A, Ren ZG. Gut microbiota alteration and modulation in hepatitis B virus-related fibrosis and complications: Molecular mechanisms and therapeutic inventions. World J Gastroenterol. 2022 Jul 28;28(28):3555-3572. doi: 10.3748/wjg.v28.i28.3555. PMID: 36161048; PMCID: PMC9372803.
11.Liu Q, Li F, Zhuang Y, Xu J, Wang J, Mao X, Zhang Y, Liu X. Alteration in gut microbiota associated with hepatitis B and non-hepatitis virus related hepatocellular carcinoma. Gut Pathog. 2019 Jan 18;11:1. doi: 10.1186/s13099-018-0281-6. PMID: 30675188; PMCID: PMC6337822.
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Feng J, Wang JP, Hu JR, Li P, Lv P, He HC, Cheng XW, Cao Z, Han JJ, Wang Q, Su Q, Liu LX. Multi-omics reveals the associations among the fecal metabolome, intestinal bacteria, and serum indicators in patients with hepatocellular carcinoma. World J Gastroenterol 2025; 31(15): 104996 [PMID: 40309232 DOI: 10.3748/wjg.v31.i15.104996]
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"The author has provided an interesting study to associate between Epstein-Barr virus and ulcerative colitis with surgery or not. Meanwhile, the similar virus of Cytomegalovirus also presented a high level in this investigation as data indicated in this study. Maybe author can perform a demonstration to clarify the more connection between the two distinct groups of herpes simplex virus in the development of ulcerative colitis."
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Zhang H, Gu X, He W, Zhao SL, Cao ZJ. Epstein-Barr virus infection is an independent risk factor for surgery in patients with moderate-to-severe ulcerative colitis. World J Gastroenterol 2025; 31(16): 104758 [PMID: 40308799 DOI: 10.3748/wjg.v31.i16.104758]
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"The manuscript 'MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19' by Konstantinos I Papadopoulos, Alexandra Papadopoulou and Tar Choon Aw addresses the problem of personalized therapy of COVID-19. The authors rightly point out that agents that inhibit the activity of the renin-angiotensin system (RAS), such as angiotensin-converting enzyme inhibitors and AT1R antagonists, can have opposite effects from protective to harmful on the course of the disease, and that worsening of symptoms is seen predominantly in the elderly, in patients with type 2 diabetes, cardiovascular and renal disease, and in some other comorbidities. The authors hypothesise that the negative effects of inhibitors of RAS activity are due to their induced dysregulation of erythropoietin secretion and decreased miRNA-155 levels. The paper cites two references to studies that found a decrease in miRNA-155 following exposure to RAS inhibitors. In conclusion, it is suggested that mineralocorticosteroid receptor antagonists and L-type calcium channel blockers may be preferable to RAS inhibitors in elderly patients and in some comorbidities characterised by reduced baseline miRNA-155 levels. However, a number of the points made by the authors need to be thoroughly tested in further studies, as there is evidence of increased miRNA-155 levels in COVID-19 patients (Asadpour-Behzadi et al, 2023, Haroun et al, 2022), reduced severity of cytokine storm in miRNA-155 knockout animals (Soni et al, 2025) and positive correlation of miRNA-155 levels with inflammatory markers in COVID-19 patients (AL-Nuaimi AL-azzawi, 2025). However, these data do not exclude the possibility that optimal elevation of miRNA-155 levels may be protective, as has been shown in patients with coronary artery disease (Zhu et al., 2014, Ban et al., 2023). Given that miRNA-155 regulates the activity of more than 200 genes, such a non-linear dependence of its effects on levels and physiological characteristics of the organism seems legitimate. The article thus raises a pressing issue that will undoubtedly require further research. "
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Papadopoulos KI, Papadopoulou A, Aw TC. MicroRNA-155 modulation by renin-angiotensin system inhibitors may underlie their enigmatic role in COVID-19. World J Exp Med 2025; 15(2): 100748 [DOI: 10.5493/wjem.v15.i2.100748]
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"1. Title
✅ Yes – The title accurately reflects the manuscript’s focus on the discrepancies between diagnostic modalities and histopathologic assessment in Crohn’s disease (CD). It clearly conveys the study’s central theme.
2. Abstract
✅ Yes – The abstract provides a concise yet comprehensive summary of the manuscript’s objectives, key findings, and conclusions. It effectively outlines the challenges in assessing CD and the importance of multimodal evaluation.
3. Key Words
✅ Yes – The selected keywords (Crohn’s disease, transmural inflammation, histopathological scoring system, endoscopy, cross-sectional imaging techniques) are well-chosen and align with the manuscript’s focus.
4. Background
✅ Yes – The introduction thoroughly discusses the current understanding of CD, its transmural nature, and the limitations of existing diagnostic methods. It establishes a strong rationale for the study.
5. Methods
⚠️ No – Since this is a narrative review, the manuscript lacks explicit methodological details (e.g., search strategy, inclusion/exclusion criteria). A more structured approach (e.g., PRISMA guidelines) would strengthen its rigor.
6. Results
✅ Yes – The review successfully synthesizes current evidence on diagnostic discrepancies in CD, highlighting gaps and emerging technologies (e.g., AI, advanced imaging).
✅ Yes – The study contributes meaningfully to the field by emphasizing the need for standardized histologic and imaging assessments in CD management.
7. Discussion
✅ Yes – The discussion logically interprets findings, underscoring the clinical implications of discordant diagnostic modalities. Key points (e.g., transmural healing as a treatment goal) are well-articulated.
✅ Yes – The applicability of findings to clinical practice and research is clearly stated, with actionable insights (e.g., optimizing biopsy protocols).
✅ Yes – The discussion is scientifically sound, balancing technical details (e.g., imaging techniques) with broader relevance to gastroenterology.
8. Illustrations and Tables
❌ No – The manuscript would benefit from visual aids (e.g., tables comparing scoring systems, imaging modalities; diagrams of transmural inflammation).
❌ No – If figures were included, clearer labeling (e.g., arrows for histologic features) would enhance interpretability.
9. Biostatistics
🔘 N/A – Not applicable, as this is a narrative review without original data analysis.
10. Units
✅ Yes – SI units (e.g., mm for wall thickness) are used correctly and consistently.
11. References
✅ Yes – References are up-to-date (including 2024–2025 publications) and authoritative, covering clinical, endoscopic, and histologic aspects of CD.
❌ No – No excessive self-citation or omission of key literature is evident.
12. Quality of Manuscript Organization and Presentation
✅ Yes – The manuscript is well-structured, with a logical flow from background to discussion. Subheadings improve readability.
✅ Yes – Language and grammar are precise, with only minor edits needed (e.g., occasional redundancy in phrasing).
13. Ethics Statements
🔘 N/A – No human/animal studies were conducted; ethics approval is not required.
Overall Evaluation
Scientific Quality: Grade B (Very Good)
Strengths: Comprehensive literature synthesis, clear clinical relevance, and balanced discussion of diagnostic challenges.
Areas for Improvement: Include methodological details for transparency (e.g., how studies were selected). Add tables/figures to summarize complex concepts (e.g., imaging vs. histologic criteria).
Language Quality: Grade A (Excellent)
The writing is polished, with minimal grammatical errors and effective use of technical terminology.
Suggestions for Authors
Enhance Methodology: Briefly describe the review’s approach (e.g., database search terms, timeframe) to bolster reproducibility.
Add Visual Summaries: A table comparing histologic scoring systems or imaging modalities would aid reader comprehension.
Clarify Clinical Takeaways: Consider a bullet-point summary of key recommendations for clinicians (e.g., when to use EUS vs. MRE).
This review provides valuable insights into CD diagnostics and would be further strengthened by these refinements."
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Fang HM. Intricacy of Crohn’s disease: Incongruity between diagnostic modalities and histopathologic assessment. World J Gastrointest Endosc 2025; 17(4): 103979 [PMID: 40291133 DOI: 10.4253/wjge.v17.i4.103979]
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"Bleeding is a significant complication of acute-on-chronic liver failure (ACLF), with prolonged prothrombin time and thrombocytopenia in these patients elevating the perceived risk of bleeding. We were intrigued by the manuscript by Liu et al. [1], which investigates the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treating thrombocytopenia among ACLF patients. This prospective, open-label study involved 70 ACLF patients with severe thrombocytopenia, who were assigned to either an rhTPO group or a control group. The primary endpoint was the proportion of patients achieving a platelet count greater than 50 × 10^9/L by day 14. The study’s noteworthy findings indicated that rhTPO significantly increased platelet counts in ACLF patients, with a higher proportion reaching the target platelet count in the rhTPO group compared to the control group (60.7% vs. 12.0%). The study concluded that rhTPO effectively elevates platelet counts, improves liver function, and reduces bleeding events in ACLF patients with thrombocytopenia, while maintaining a favorable safety profile. These findings provide promising insights into managing thrombocytopenia in ACLF patients.
While this study holds clinical significance, it also has notable limitations. Liver disease has long been recognized as a condition associated with bleeding disorders, which arise from multiple factors [2,3]. These include thrombocytopenia, low levels of coagulation factors, and decreased fibrinolytic proteins, all contributing to the coagulopathy seen in liver disease [4]. Thrombocytopenia is one of the most common hematological abnormalities and often the first abnormality detected in chronic liver disease patients [5]. While mild to moderate thrombocytopenia rarely has clinical significance due to the low likelihood of spontaneous bleeding, moderate to severe thrombocytopenia can hinder patients from receiving essential interventions, including medications and invasive procedures. Delays in procedures and the need to correct platelet abnormalities can extend hospital stays and increase overall healthcare costs [6,7]. Increasing platelet counts and achieving rebalanced hemostasis appears to be a strategy for controlling the risk of acute bleeding in ACLF patients without raising the risk of thrombosis; however, the impact on disease prognosis requires further investigation [2]. Despite indicating that increasing platelet counts and achieving rebalanced hemostasis may help control the risk of acute bleeding in ACLF patients without increasing the risk of thrombosis, further investigation is necessary to understand the impact on disease prognosis. Additionally, while serum hepatocyte growth factor and thrombopoietin (TPO) levels were measured, key coagulation-related tests were not further explored. Simply correcting thrombocytopenia does not address all facets of coagulation [8]. Furthermore, laboratory tests such as platelet aggregation and thromboelastography were not conducted. These assessments could provide a more comprehensive understanding of the extent to which the coagulopathy in ACLF patients has been addressed, rather than relying solely on platelet counts [9]. Moreover, the study's small sample size limits its statistical power and may introduce confounding factors. The analysis of results was relatively straightforward and did not adequately account for potential confounders. Consequently, the conclusions drawn should be considered preliminary. The exploratory and pilot nature of this study limits its clinical significance. Nonetheless, it remains a valuable contribution to the field, providing direction for future research and establishing a foundational basis for subsequent investigations.
Currently, in addition to rhTPO, there are other treatment options available, such as oral small molecule agonists of TPO receptor like avatrombopag [10]. Further studies comparing these agents are needed to determine the optimal strategies for managing bleeding risk in ACLF patients. Overall, this research offers hope for the management of ACLF patients and points toward future investigation directions.
REFERENCES
1. Liu G, Tang F, Wang T, Yan JQ, Li FH, Ha FS, Zhang X, Jing L, Liang J. Efficacy of recombinant human thrombopoietin in patients with acute-on-chronic liver failure and thrombocytopenia: A prospective, open-label study. World J Gastroenterol. 2025;31 14:105004. doi: 10.3748/wjg.v31.i14.105004.
2. Lisman T, Porte RJ. Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases. Res Pract Thromb Haemost. 2017;1 2:150-161. doi: 10.1002/rth2.12028.
3. Lisman T, Leebeek FW, de Groot PG. Haemostatic abnormalities in patients with liver disease. J Hepatol. 2002;37 2:280-7. doi: 10.1016/s0168-8278(02)00199-x.
4. Stravitz RT, Ellerbe C, Durkalski V, Schilsky M, Fontana RJ, Peterseim C, Lee WM; Acute Liver Failure Study Group. Bleeding complications in acute liver failure. Hepatology. 2018;67 5:1931-1942. doi: 10.1002/hep.29694.
5. Violi F, Basili S, Raparelli V, Chowdary P, Gatt A, Burroughs AK. Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction? J Hepatol. 2011;55 6:1415-27. doi: 10.1016/j.jhep.2011.06.008.
6. Poordad F. Review article: thrombocytopenia in chronic liver disease. Aliment Pharmacol Ther. 2007;26 Suppl 1:5-11. doi: 10.1111/j.1365-2036.2007.03510.x.
7. Moore AH. Thrombocytopenia in Cirrhosis: A Review of Pathophysiology and Management Options. Clin Liver Dis (Hoboken). 2019;14 5:183-186. doi: 10.1002/cld.860.
8. O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA Clinical Practice Update: Coagulation in Cirrhosis. Gastroenterology. 2019;157 1:34-43.e1. doi: 10.1053/j.gastro.2019.03.070.
9. Biswas S, Anand A, Vaishnav M, Mehta S, Swaroop S, Aggarwal A, Arora U, Agarwal A, Elhence A, Mahapatra SJ, Agarwal S, Gunjan D, Sehgal T, Aggarwal M, Dhawan R, Gamanagatti S, Shalimar. Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial. J Vasc Interv Radiol. 2024;35 10:1508-1518.e2. doi: 10.1016/j.jvir.2024.06.014.
10. Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, Allen LF, Hassanein T. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology. 2018;155 3:705-718. doi: 10.1053/j.gastro.2018.05.025.
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Dai ZS, Zhang M, Deng YY, Zhou N, Tian Y. Efficacy of a novel artificial liver versatile plasma purification system in patients with acute-on-chronic liver failure. World J Gastroenterol 2025; 31(14): 103892 [PMID: 40248372 DOI: 10.3748/wjg.v31.i14.103892]
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