World Journal of Gastroenterology最新文献

{"title":"Role of preoperative circulating tumor DNA in predicting occult metastases in resectable and borderline resectable pancreatic ductal adenocarcinoma.","authors":"Takeshi Murakami, Masafumi Imamura, Yasutoshi Kimura, Kazunori Watanabe, Yoshihito Shinohara, Toru Nakamura, Siew-Kee Low, Masayo Motoya, Yujiro Kawakami, Yoshiharu Masaki, Tomohiro Kubo, Makoto Yoshida, Eiji Yoshida, Toru Kato, Kazuharu Kukita, Daisuke Kyuno, Ichiro Takemasa","doi":"10.3748/wjg.v31.i32.109383","DOIUrl":"10.3748/wjg.v31.i32.109383","url":null,"abstract":"<p><strong>Background: </strong>Some patients with resectable or borderline resectable pancreatic ductal adenocarcinoma (PDAC) may have distant metastases, undetected on preoperative imaging or early recurrence, within 6 months after surgery. Occult metastases (OMs) must be accurately predicted to optimize multidisciplinary treatment.</p><p><strong>Aim: </strong>To investigate the efficacy of circulating tumor DNA (ctDNA) in predicting OM.</p><p><strong>Methods: </strong>Two Japanese institutions prospectively collected preoperative plasma samples from PDAC patients between July 2019 and September 2021 and evaluated ctDNA using a targeted next-generation sequencing panel covering 52 cancer-related genes.</p><p><strong>Results: </strong>Among 135 PDAC patients, 38 had OM and 35 were positive for ctDNA. The ctDNA positivity rate was significantly higher in patients with OM than in patients without OM. ctDNA-positive patients had significantly shorter median recurrence-free survival than ctDNA-negative patients. Logistic multivariate regression revealed ctDNA positivity as an independent predictor of OM.</p><p><strong>Conclusion: </strong>Preoperative ctDNA in resectable PDAC is an independent predictor of OM and indicates poor prognosis following pancreatectomy and may be a useful biomarker in determining multidisciplinary patient care.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 32","pages":"109383"},"PeriodicalIF":5.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-effectiveness of transient elastography for liver fibrosis screening in Thai patients with diabetes mellitus.","authors":"Chayanis Kositamongkol, Pichaya Tantiyavarong, Alissa Ratanatawan, Pimsiri Sripongpun, Prawej Mahawithitwong, Prawat Kositamongkol, Surasak Saokaew, Pochamana Phisalprapa","doi":"10.3748/wjg.v31.i32.110333","DOIUrl":"10.3748/wjg.v31.i32.110333","url":null,"abstract":"<p><strong>Background: </strong>The association between diabetes mellitus (DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) is well documented, with DM increasing the risk of developing MASLD and liver fibrosis.</p><p><strong>Aim: </strong>To evaluate the cost-effectiveness and budget impact of transient elastography (TE) for detecting significant fibrosis in Thai patients with DM.</p><p><strong>Methods: </strong>We conducted a lifetime cost-utility analysis from a societal perspective, combining a decision tree with a Markov model. Four alternatives were compared: Fibrosis-4 (FIB-4) index triage followed by TE, steatosis-associated fibrosis estimator (SAFE) score triage followed by TE, standalone TE, and no screening. Clinical probabilities, utilities, and costs came from previous studies and Siriraj Hospital data. Costs and quality-adjusted life-years (QALYs) were discounted 3% annually, and incremental cost-effectiveness ratios (ICERs) were judged against the 160000-Thai baht (THB; 4619 United States dollars [USD])/QALY threshold. A 5-year budget impact was evaluated from the payer perspective.</p><p><strong>Results: </strong>Among the screening methods evaluated, TE alone yielded the highest total lifetime costs of 200403 THB (5785 USD) and the highest QALYs of 12.81. Compared to no screening, all strategies demonstrated cost-effectiveness with ICERs of 75961, 80385, and 98965 THB (2193, 2321, and 2857 USD)/QALY gained for FIB-4 + TE, SAFE + TE, and TE alone, respectively. Extended dominance favored SAFE + TE, yet probabilistic analysis showed FIB-4 + TE had the highest cost-effectiveness probability and the smallest budget impact. Estimated annual budget impacts amounted to 470.7-755.8 million THB (13.6-21.8 million USD).</p><p><strong>Conclusion: </strong>Implementing screening for significant fibrosis in patients with DM is cost-effective. In resource-limited settings, prioritizing the FIB-4 index as a triage tool before TE is recommended.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 32","pages":"110333"},"PeriodicalIF":5.4,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DeepGut: A collaborative multimodal large language model framework for digestive disease assisted diagnosis and treatment.","authors":"Xiao-Han Wan, Mei-Xia Liu, Yan Zhang, Guan-Jun Kou, Lei-Qi Xu, Han Liu, Xiao-Yun Yang, Xiu-Li Zuo, Yan-Qing Li","doi":"10.3748/wjg.v31.i31.109948","DOIUrl":"10.3748/wjg.v31.i31.109948","url":null,"abstract":"<p><strong>Background: </strong>Gastrointestinal diseases have complex etiologies and clinical presentations. An accurate diagnosis requires physicians to integrate diverse information, including medical history, laboratory test results, and imaging findings. Existing artificial intelligence-assisted diagnostic tools are limited to single-modality information, resulting in recommendations that are often incomplete and may be associated with clinical or legal risks.</p><p><strong>Aim: </strong>To develop and evaluate a collaborative multimodal large language model (LLM) framework for clinical decision-making in digestive diseases.</p><p><strong>Methods: </strong>In this observational study, DeepGut, a multimodal LLM collaborative diagnostic framework, was developed to integrate four distinct large models into a four-tiered structure. The framework sequentially accomplishes multimodal information extraction, logical \"chain\" construction, diagnostic and treatment suggestion generation, and risk analysis. The model was evaluated using objective metrics, which assess the reliability and comprehensiveness of model-generated results, and subjective expert opinions, which examine the effectiveness of the framework in assisting physicians.</p><p><strong>Results: </strong>The diagnostic and treatment recommendations generated by the DeepGut framework achieved exceptional performance, with a diagnostic accuracy of 97.8%, diagnostic completeness of 93.9%, treatment plan accuracy of 95.2%, and treatment plan completeness of 98.0%, significantly surpassing the capabilities of single-modal LLM-based diagnostic tools. Experts evaluating the framework commended the completeness, relevance, and logical coherence of its outputs. However, the collaborative multimodal LLM approach resulted in increased input and output token counts, leading to higher computational costs and extended diagnostic times.</p><p><strong>Conclusion: </strong>The framework achieves successful integration of multimodal diagnostic data, demonstrating enhanced performance enabled by multimodal LLM collaboration, which opens new horizons for the clinical application of artificial intelligence-assisted technology.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"109948"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the oncogenic potential of SARS-CoV-2 in the gastrointestinal tract.","authors":"Dimitrina Georgieva Miteva, Milena Gulinac, Milena Peruhova, Tsvetelina Velikova","doi":"10.3748/wjg.v31.i31.105665","DOIUrl":"10.3748/wjg.v31.i31.105665","url":null,"abstract":"<p><p>Recent research has increasingly highlighted the potential oncogenic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within the gastrointestinal tract. Growing evidence suggests that SARS-CoV-2 may contribute to the development of gastrointestinal malignancies through several mechanisms, including sustained chronic inflammation, disruption of normal cellular homeostasis, and potential viral integration into host cells. These pathological processes have the potential to dysregulate critical cellular pathways, thereby promoting cancer development in vulnerable populations. A thorough understanding of how SARS-CoV-2 interacts with the development of gastrointestinal cancer is essential for optimizing patient care and establishing comprehensive, long-term monitoring protocols. This review highlighted the pressing need for ongoing research into the complex relationship between SARS-CoV-2 infection and the risk of gastrointestinal cancer.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"105665"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Important role of tumor deposits and negative lymph nodes in prognosis of N1c colorectal cancer patients.","authors":"Zhi-Gang Sun, Shao-Xuan Chen, Bai-Long Sun, Da-Kui Zhang, Ding-Rong Zhong, Tong-Yin Zhang, Yu-Wan Hu, Zi-Han Han, Wen-Xiao Wu, Zhi-Yong Hou, Li Yao, Ya-Jun Zhang, Hong-Liang Sun, Jian-Zheng Jie","doi":"10.3748/wjg.v31.i31.109857","DOIUrl":"10.3748/wjg.v31.i31.109857","url":null,"abstract":"<p><strong>Background: </strong>The number of tumor deposits (TDs) does not play a part in the current tumor node metastasis staging. Negative lymph node (NLN) status is associated with the prognosis of colorectal cancer (CRC), but its clear role in N1c stage remains to be defined.</p><p><strong>Aim: </strong>To evaluate the combination of TDs and NLNs as potential prognostic indicators in N1c CRC.</p><p><strong>Methods: </strong>We retrospectively identified 107 consecutive patients who had N1c CRC radically resected at China-Japan Friendship Hospital. The combination of TDs and NLNs was calculated by the formula NLNTD = NLN/(TD + 1). Cutoff values of NLNs and NLNTD were determined using the R package \"survminer\". Disease-free survival (DFS), overall survival (OS) and cancer-specific survival (CSS) were determined using the Kaplan-Meier method to assess the impact of NLNTD on prognosis. Results were compared using the log-rank test.</p><p><strong>Results: </strong>The median follow-up time was 63.17 (45.33-81.37) months for DFS, with 33.64% (36/107) of patients experiencing recurrence during follow-up. Five-year DFS was 66.0% (57.3%-76.0%). There was no significant difference in prognosis between patients with > 12 and ≤ 12 NLNs (<i>P</i> = 0.058) for DFS. Similar results were seen according to the number of TDs. The definition of NLNTD = NLN/(TD + 1) with a cutoff value of 6 divided patients into two groups with different DFS (<i>P</i> = 0.005). Five-year DFS for patients with NLNTD > 6 was 73.5% (63.6%-85.0%), compared with 50.0% (35.7%-70.0%) for those with NLNTD ≤ 6. These two groups had different prognosis without perineural invasion (<i>P</i> = 0.012) or lymphovascular invasion (<i>P</i> = 0.002) even neither (<i>P</i> = 0.053). Similar results were seen for OS and CSS.</p><p><strong>Conclusion: </strong>NLNTD could serve as important prognostic factor for outcomes in N1c CRC patients. These patients could be stratified for prognosis through NLNTD and the high-risk should be given more attention during treatment.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"109857"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal muscle alterations in metabolic dysfunction-associated steatotic liver disease: A critical review of diagnostic, mechanistic, and therapeutic intersections.","authors":"Vaynika Gupta, Ashwin Krishnamoorthy","doi":"10.3748/wjg.v31.i31.110481","DOIUrl":"10.3748/wjg.v31.i31.110481","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations, such as sarcopenia, myosteatosis, and metabolic dysregulation, which play a key role in its pathogenesis and progression. Recent literature, including an article by Isakov, highlights the bidirectional interactions between muscle and liver, underscoring shared mechanisms such as insulin resistance, inflammation, and myokine imbalance. This letter reflects on key findings from the review, noting strengths such as its integration of mechanistic insights, discussion of emerging biomarkers, and emphasis on lifestyle and pharmacological interventions. It also identifies areas for further development, including standardization of diagnostic criteria and more rigorous evaluation of translational data. As muscle health gains prominence in metabolic dysfunction-associated steatotic liver disease research, multidisciplinary strategies that target both hepatic and muscular systems may offer more effective avenues for prevention and treatment.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"110481"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into a machine learning-based prediction model for colorectal polyp recurrence after endoscopic mucosal resection.","authors":"Guang-Yao Li, Lu-Lu Zhai","doi":"10.3748/wjg.v31.i31.109389","DOIUrl":"10.3748/wjg.v31.i31.109389","url":null,"abstract":"<p><p>In 2025, Shi <i>et al</i> constructed a model utilizing machine learning techniques to predict the one-year recurrence of colorectal polyps following endoscopic mucosal resection, showing excellent discriminatory performance with an area under the curve exceeding 0.90. However, limitations exist regarding its narrow temporal scope, potential overestimation due to feature collinearity and imputation opacity, and limited generalizability due to single-center derivation and validation. Moreover, no clear clinical implementation strategy was outlined. Prospective multicenter validation and integration of endoscopist variability, longitudinal outcome data, and deployment mechanisms are warranted to ensure broader applicability and clinical utility.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"109389"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of N-acetylcysteine <i>vs</i> dexamethasone in preventing postembolization syndrome post-transarterial chemoembolization in hepatocellular carcinoma: A randomized controlled trial.","authors":"Preeyamas Koonsiripaiboon, Witchakorn Ruamtawee, Nitipon Simasingha, Wasu Tanasoontrarat, Torpong Claimon, Supatsri Sethasine","doi":"10.3748/wjg.v31.i31.109630","DOIUrl":"10.3748/wjg.v31.i31.109630","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) is a major health concern in Thailand, with most patients diagnosed at the intermediate stage. Transarterial chemoembolization (TACE) is the standard treatment; however, postembolization syndrome (PES) remains a common complication. Although both dexamethasone (DEXA) and N-acetylcysteine (NAC) have shown efficacy in reducing PES, no study has directly compared their effects.</p><p><strong>Aim: </strong>To compare the incidence of PES between DEXA and NAC in intermediate-stage HCC patients undergoing conventional TACE (cTACE).</p><p><strong>Methods: </strong>A randomized, double-blind, controlled trial was conducted at two tertiary hospitals in Thailand from November 2024 to April 2025. Eligible HCC patients (aged 18-70 years) were randomized (1:1) to receive either NAC (150 mg/kg/hour loading dose, followed by 50 mg/kg over 4 hours, then 6.25 mg/kg/ hour for 48 hours post-cTACE) or DEXA (8 mg IV 1 hour before cTACE). cTACE was performed by blinded interventional radiologists. The primary outcome was PES occurrence within 48 hours, assessed using South West Oncology Group toxicity coding and the Common Terminology Criteria for Adverse Events. The secondary outcomes were post-cTACE liver decompensation and the dynamic changes in the albumin-bilirubin (ALBI) score.</p><p><strong>Results: </strong>A total of 56 intermediate-stage HCC patients were included (DEXA, <i>n</i> = 28; NAC, <i>n</i> = 28). Most had preserved liver function, with 92.9% classified as Child-Pugh A. The maximum tumor size was 6.2 cm, and 85.7% had multiple lesions. Additionally, 39 patients (69.6%) met the beyond up-to-7 criteria. Overall, 27 patients (48.2%) developed PES. After adjusting for confounding factors, the NAC group had a significantly lower incidence of PES than the DEXA group (32.1% <i>vs</i> 64.3%; adjusted odds ratio = 0.17, 95% confidence interval: 0.03-0.87, <i>P</i> = 0.033). Only two patients (3.6%) developed post-cTACE liver decompensation. Furthermore, 51.8% patients experienced worsening ALBI scores within 48 hours post-procedure; however, the rate of ALBI score worsening did not significantly differ between the groups.</p><p><strong>Conclusion: </strong>Compared with DEXA, NAC significantly reduces the incidence of PES, regardless of its impact on liver function recovery. Therefore, NAC is a preferable option for reducing PES in Barcelona Clinic Liver Cancer-B stage HCC patients with preserved liver function.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"109630"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-126-3p as a predictive biomarker for patients with primary biliary cholangitis refractory to ursodeoxycholic acid.","authors":"Shi-Da Pan, Chu-Yue Xiong, Ying-Juan Shen, Jia-He Tian, Yi-Lin Wang, Jia-Ning Wang, Si-Yu Wang, Feng-Yi Li, Li-Feng Wang, Qin Qiu, Luo Yang, Xiao-Meng Liu, Jun-Qing Luan, Zheng-Sheng Zou, Fu-Sheng Wang, Fan-Ping Meng","doi":"10.3748/wjg.v31.i31.109828","DOIUrl":"10.3748/wjg.v31.i31.109828","url":null,"abstract":"<p><strong>Background: </strong>Ursodeoxycholic acid (UDCA) is the first-line therapeutic agent for primary biliary cholangitis (PBC). However, a subset of patients exhibit a suboptimal response to UDCA, and reliable predictive biomarkers remain elusive. Studies have implicated plasma microRNAs (miRNAs) in the pathophysiological progression of PBC, with certain miRNAs demonstrating potential as diagnostic and disease progression biomarkers. However, biomarkers capable of predicting the therapeutic efficacy of UDCA have not yet been identified.</p><p><strong>Aim: </strong>To investigate differentially expressed miRNAs in PBC patients with divergent UDCA treatment responses and to explore potential biomarkers that predict treatment response in PBC.</p><p><strong>Methods: </strong>Plasma samples from treatment-naive PBC patients receiving ≥ 1 year of standard UDCA treatment were collected. Efficacy was evaluated using the Paris I criteria. Patient samples were divided into discovery group (<i>n</i> = 10) and validation group (<i>n</i> = 30), with further stratification of patients into drug-resistant and drug-sensitive (DS) cohorts. Next-generation sequencing and quantitative real-time polymerase chain reaction were used to screen, functionally analyze, and validate the pre-treatment miRNA profiles of the treatment groups.</p><p><strong>Results: </strong>Forty-nine miRNAs were differentially expressed between the two groups before UDCA treatment (<i>N</i> = 40). MiR-22-5p and miR-126-3p were highly expressed in the DS group before treatment (<i>P</i> < 0.001), whereas miR-7706 exhibited a low expression (<i>P</i> = 0.017). Post-treatment, miR-126-3p maintained low expression in the drug-resistant group (<i>P</i> = 0.003), but showed elevated levels in the DS group (<i>P</i> < 0.001). Logistic regression analysis identified miR-126-3p expression (odds ratio = 34.32, 95% confidence interval: 1.95-605.40, <i>P</i> = 0.016) as a significant factor influencing UDCA treatment response, while miR-22-5p (<i>P</i> = 0.990) and miR-7706 (<i>P</i> = 0.157) showed no significant association. MiR-126-3p levels were negatively correlated with total bilirubin (<i>r</i> = -0.356, <i>P</i> = 0.005) and immunoglobulin G levels (<i>r</i> = -0.311, <i>P</i> = 0.015). The area under the receiver operating characteristic curve was 0.891 (<i>P</i> = 0.0003, 95% confidence interval: 0.772-1.000) with a sensitivity of 82.4% and a specificity of 84.6%.</p><p><strong>Conclusion: </strong>Plasma miRNA expression profiles are heterogenous in patients with PBC with differential responses to UDCA therapy. MiR-126-3p demonstrates predictive potential for a suboptimal response to UDCA in patients with PBC.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"109828"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>TSC22D1</i> promotes liver sinusoidal endothelial cell dysfunction and induces macrophage M1 polarization in non-alcoholic fatty liver disease.","authors":"Wei Ding, Xin-Qi Xu, Ling-Lin Wu, Qun Wang, Yi-Qin Wang, Wei-Wei Chen, Yu-Lin Tan, Yi-Bo Wang, Hua-Ji Jiang, Jun Dong, Yong-Min Yan, Xue-Zhong Xu","doi":"10.3748/wjg.v31.i31.109605","DOIUrl":"10.3748/wjg.v31.i31.109605","url":null,"abstract":"<p><strong>Background: </strong>The progression of non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) and liver fibrosis remains poorly understood, though liver sinusoidal endothelial cells (LSECs) are thought to play a central role in disease pathogenesis.</p><p><strong>Aim: </strong>To investigate the role of <i>TSC22D1</i> in NAFLD fibrosis through its regulation of LSEC dysfunction and macrophage polarization.</p><p><strong>Methods: </strong>We analysed single-cell transcriptomic data (GSE129516) from NASH and normal mouse models and identified <i>TSC22D1</i> as a key regulator in LSECs. <i>In vitro</i> and <i>in vivo</i> experiments were conducted to validate the functional role of <i>TSC22D1</i>. Human LSECs were cultured and transfected to overexpress <i>TSC22D1</i>, and evaluated using flow cytometry, enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction. NAFLD mice were used to assess <i>TSC22D1</i> expression and its effects on LSEC dysfunction, endothelial-mesenchymal transition (EndMT), and microvascularization.</p><p><strong>Results: </strong>Single-cell analysis revealed that <i>TSC22D1</i> mediates intercellular communication between LSECs and macrophages <i>via</i> the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (FN14) signalling pathway, promoting M1 macrophage polarization and exacerbating liver fibrosis. <i>In vitro</i> studies revealed that <i>TSC22D1</i> overexpression in LSECs exacerbated endothelial dysfunction and M1 polarization, whereas TWEAK inhibition attenuated these effects. Mechanistically, <i>TSC22D1</i> drives LSEC microvascularization and EndMT through the TWEAK/FN14 pathway, leading to increased secretion of pro-inflammatory cytokines and M1 macrophage polarization. <i>In vivo</i>, experiments demonstrated that <i>TSC22D1</i> inhibition <i>via</i> adeno-associated virus serotype 8-short hairpin RNA reduced NAFLD progression and liver fibrosis.</p><p><strong>Conclusion: </strong>Our findings indicate a pivotal role of <i>TSC22D1</i> in NAFLD fibrosis, demonstrating its dual function in regulating LSEC dysfunction and inflammatory responses. <i>TSC22D1</i> may be a promising target for the treatment and the prevention and management of NAFLD progression to fibrosis.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":"31 31","pages":"109605"},"PeriodicalIF":5.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400240/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}