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Loss-of-function mutations of microRNA-142-3p promote ASH1L expression to induce immune evasion and hepatocellular carcinoma progression

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World Journal of Gastroenterology 2025年第1期31卷 126-145页

作者： Xing-Hui Yu Yan Xie Jian Yu Kun-Ning Zhang Zhou-Bo Guo Di Wang Zhao-Xian Li Wei-Qi Zhang Yu-Ying Tan Li Zhang Wen-Tao Jiang School of Medicine Nankai UniversityTianjin 300192China Tianjin Key Laboratory of Molecular Diagnosis and Treatment of liver Cancer Tianjin First Center HospitalTianjin 300192China Department of liver Transplantation Tianjin First Center HospitalTianjin 300192China First Central Clinical School Tianjin Medical UniversityTianjin 300192China

BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated *** therapeutic targets are beneficial to treat and predict the ***,the exact molecular mechanisms leading to the progression of HCC are still *** has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor *** this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between *** To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC *** In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC ***,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,*** statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank *** In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival ***1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated ***,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via *** the exploration mechanism,we found ASH1L may promote an immunosuppressive mi

关键词： Hepatocellular carcinoma MicroRNA-142-3p ASH1L Immune evasion Tumor immune microenvironment Apoptosis

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Importance of fatigue and its measurement in chronic liver disease

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World Journal of Gastroenterology 2019年第28期25卷 3669-3683页

作者： Lynn H Gerber Ali A Weinstein Rohini Mehta Zobair M Younossi Department of Medicine Beatty Center for Liver and Obesity Research Inova Health System Falls Church VA 22042 United States center for the Study of Chronic Illness and Disability George Mason University Fairfax VA 22030 United States beatty center for liver and obesity research Inova Health System Falls Church VA 22042 United States

The mechanisms of fatigue in the group of people with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are protean. The liver is central in the pathogenesis of fatigue because it uniquely regulates much of the storage, release and production of substrate for energy generation. It is exquisitely sensitive to the feedback controlling the uptake and release of these energy generation substrates. Metabolic contributors to fatigue, beginning with the uptake of substrate from the gut, the passage through the portal system to hepatic storage and release of energy to target organs (muscle and brain) are central to understanding fatigue in patients with chronic liver disease. Inflammation either causing or resulting from chronic liver disease contributes to fatigue, although inflammation has not been demonstrated to be causal. It is this unique combination of factors, the nexus of metabolic abnormality and the inflammatory burden of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis that creates pathways to different types of fatigue. Many use the terms central and peripheral fatigue. Central fatigue is characterized by a lack of self-motivation and can manifest both in physical and mental activities. Peripheral fatigue is classically manifested by neuromuscular dysfunction and muscle weakness. Therefore, the distinction is often seen as a difference between intention (central fatigue) versus ability (peripheral fatigue). New approaches to measuring fatigue include the use of objective measures as well as patient reported outcomes. These measures have improved the precision with which we are able to describe fatigue. The measures of fatigue severity and its impact on usual daily routines in this population have also been improved, and they are more generally accepted as reliable and sensitive. Several approaches to evaluating fatigue and developing endpoints for treatment have relied of biosignatures associated with fatigue. These have bee

关键词： Fatigue Chronic liver disease Non-alcoholic fatty liver diseases Nonalcoholic steatohepatitis Measurement Patient-reported outcomes

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Current status of drug therapy for chronic hepatitis B

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World Journal of Gastroenterology 2025年第2期31卷 1-12页

作者： Chuang Jiang Zhi-Hong Zhang Jia-Xin Li Division of liver Surgery Department of General Surgery and Laboratory of Liver Surgeryand State Key Laboratory of Biotherapy and Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of General Surgery Dafang County People's HospitalBijie 551600Guizhou ProvinceChina

In this editorial,we comment on the article by Meng et *** hepatitis B(CHB)is a significant global health problem,particularly in developing *** B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular *** and treatment of HBV are key measures to reduce *** present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a ***-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’*** will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.

关键词： Chronic hepatitis B Hepatitis B virus Anti virus Drug treatment Therapy

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Summary of the current guidelines for managing iatrogenic colorectal perforations and the evolving role of endoluminal vacuum therapy

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World Journal of Clinical Cases 2025年第6期13卷 1-8页

作者： Ahmed Tawheed Ibrahim Halil Bahcecioglu Mehmet Yalniz Mubin Ozercan Ali Cagri Oral Mohamed El-Kassas Department of Endemic Medicine Faculty of MedicineHelwan UniversityCairo 11795Egypt Department of Gastroenterology Firat UniversityElazig 23119Türkiye liver Disease research center College of MedicineKing Saud UniversityRiyadh 7805Saudi Arabia

Colonoscopy represents a safe procedure that is widely used in medical practice either to diagnose or treat various gastrointestinal *** the last few years,the incidence rate of perforations in colonoscopic procedures has increased,especially in therapeutic *** recent advancements in endoscopic techniques and gastrointestinal tumoral resection procedures such as endoscopic mucosal resection,endoscopic full-thickness resection,and endoscopic submucosal dissection(ESD)could be a risk factor for this increased *** incidence rate of mortality of serious colonoscopic perforations is 7.1%.The management plan for these perforations starts with conservative treatment in mild cases,endoscopic closure,and surgical management in severe ***,endoluminal vacuum therapy was found to be effective in the management of colorectal perforations and this has been reported in multiple case *** editorial provides an overview of the current guidelines for the management of iatrogenic colorectal *** insights are from the perspectives of endoscopists and *** also present a management algorithm based on the guidelines of the European Society of Gastrointestinal Endoscopy,the American Gastroenterological Association,and the World Society of Emergency *** also discussed in brief the use of endoluminal vacuum therapy in colorectal perforations.

关键词： Colon Rectum Iatrogenic colonic perforation Colonoscopy Guidelines Endovacuum Endolumical vacuum therapy Endoscopic management

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Effectiveness of exercise in hepatic fat mobilization in nonalcoholic fatty liver disease: Systematic review

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World Journal of Gastroenterology 2016年第27期22卷 6318-6327页

作者： Pegah Golabi Cameron T Locklear Patrick Austin Sophie Afdhal Melinda Byrns Lynn Gerber Zobair M Younossi Betty and Guy beatty center for Integrated research Inova Health System Department of Medicine Center for Liver Disease Inova Fairfax Hospital Health Sciences Library Inova Fairfax Hospital

AIM: To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease(NAFLD) ***: Ovid-Medline, Pub Med, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "nonalcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy(H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. RESULTS: Eight studies met selection criteria(6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared thetwo interventions. The beneficial effects of exercise on intrahepatic triglyceride(IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid ***: Prescribed exercise in subjects with NAFLD red

关键词： Non-alcoholic fatty liver disease Exercise Diet Fat mobilization Lifestyle modification

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Prognostic model for esophagogastric variceal rebleeding after endoscopic treatment in liver cirrhosis: A Chinese multicenter study

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World Journal of Gastroenterology 2025年第2期31卷 85-101页

作者： Jun-Yi Zhan Jie Chen Jin-Zhong Yu Fei-Peng Xu Fei-Fei Xing De-Xin Wang Ming-Yan Yang Feng Xing Jian Wang Yong-Ping Mu Cell Biology Laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of liver Diseases Shanghai Academy of Chinese MedicineShanghai 201203China Clinical Key Laboratory of Traditional Chinese Medicine of Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Key Laboratory of liver and Kidney Disease of the Ministry of Education Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Gastroenterology and Hepatology Zhongshan Hospital Affiliated to Fudan UniversityShanghai 200032China Shanghai Institute of liver Disease Fudan UniversityShanghai 200032China Evidence-Based Medicine center Fudan UniversityShanghai 200032China Department of Gastrointestinal Endoscopy Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Hepatology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 201203China

BACKGROUND Rebleeding after recovery from esophagogastric variceal bleeding(EGVB)is a severe complication that is associated with high rates of both incidence and *** its clinical importance,recognized prognostic models that can effectively predict esophagogastric variceal rebleeding in patients with liver cirrhosis are *** To construct and externally validate a reliable prognostic model for predicting the occurrence of esophagogastric variceal *** This study included 477 EGVB patients across 2 cohorts:The derivation cohort(n=322)and the validation cohort(n=155).The primary outcome was rebleeding events within 1 *** least absolute shrinkage and selection operator was applied for predictor selection,and multivariate Cox regression analysis was used to construct the prognostic *** validation was performed with bootstrap *** assessed the discrimination,calibration and accuracy of the model,and performed patient risk *** Six predictors,including albumin and aspartate aminotransferase concentrations,white blood cell count,and the presence of ascites,portal vein thrombosis,and bleeding signs,were selected for the rebleeding event prediction following endoscopic treatment(REPET)*** predicting rebleeding within 1 year,the REPET model ex-hibited a concordance index of 0.775 and a Brier score of 0.143 in the derivation cohort,alongside 0.862 and 0.127 in the validation ***,the REPET model revealed a significant difference in rebleeding rates(P<0.01)between low-risk patients and intermediate-to high-risk patients in both *** We constructed and validated a new prognostic model for variceal rebleeding with excellent predictive per-formance,which will improve the clinical management of rebleeding in EGVB patients.

关键词： Esophagogastric variceal bleeding Variceal rebleeding liver cirrhosis Prognostic model Risk stratification Secondary prophylaxis

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Red cell distribution width/platelet ratio predicts decompensation of metabolic dysfunction-associated steatotic liver disease-related compensated advanced chronic liver disease

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World Journal of Gastroenterology 2025年第3期31卷 1-10页

作者： Ming-Hua Zheng Amedeo Lonardo Department of Hepatology MAFLD Research CenterThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina Department of Internal Medicine Azienda Ospedaliero-Universitaria of Modena(2023)Modena 41126Italy

Prognostication of compensated advanced chronic liver disease(cACLD)is of paramount importance for the physician-and-patient communication and for rational clinical *** paper published by Dallio et al reports on red cell distribution width(RDW)/platelet ratio(RPR)as a non-invasive biomarker in predicting decompensation of metabolic dysfunction-associated steatotic liver disease(MASLD)-related *** from other biomarkers and algorithms,RPR is inexpensive and widely available,based on parameters which are included in a complete blood *** is computed on the grounds of two different items,one of which,RDW,mirrors the host’s response to a variety of disease stimuli and is *** second parameter involved in RPR,platelet count,is more specific and has been used in the hepatological clinic to discriminate cirrhotic from non-cirrhotic chronic liver disease for *** disease is the primary cause of mortality among MASLD subjects,followed by extra-hepatic cancers and liver-related ***,MASLD biomarkers should be validated not only in terms of liver-related events but also in the prediction of major adverse cardiovascular events and cardiovascular mortality and extra-hepatic *** sized multi-ethnic confirmatory investigation is required to define the role and significance of RPR in the stratification of MASLD-cACLD.

关键词： Cirrhosis liver fibrosis Natural course Prognostication Stratification

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Cystatin C is a biomarker for predicting acute kidney injury in patients with acute-on-chronic liver failure

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World Journal of Gastroenterology 2013年第48期19卷 9432-9438页

作者： Zhi-Hong Wan Jian-Jun Wang Shao-Li You Hong-Ling Liu Bing Zhu Hong Zang Chen Li Jing Chen Shao-Jie Xin liver Failure Treatment and research center Beijing 302 Hospital

AIM:To investigate serum cystatin C level as an early biomarker for predicting acute kidney injury(AKI)in patients with acute-on-chronic liver failure(ACLF).METHODS:Fifty-six consecutive patients with hepatitis B virus-related ACLF who had normal serum creatinine(Cr)level(liver Failure Treatment and research center of Beijing 302 Hospital between August 2011 and October *** patients with chronic hepatitis B(CHB)and 30 healthy controls in the same study period were also *** of serum cystatin C(CysC)was performed by a particle-enhanced immunonephelometry assay using the BN Prospec nephelometer *** ACLF patients were followed during their hospitalization ***:In the ACLF group,serum level of CysC was 1.1±0.4 mg/L,which was significantly higher(P<0.01)than those in the healthy controls(0.6±0.3mg/L)and CHB patients(0.7±0.2 mg/L).During the hospitalization period,eight ACLF patients developed *** regression analysis indicated that CysC level was an independent risk factor for AKI development(odds ratio=1.8;95%CI:1.4-2.3,P=0.021).The cutoff value of serum CysC for prediction of AKI in ACLF patients was 1.21 mg/*** baseline CysC-based estimated glomerular filtration rate(eGFR CysC)was significantly lower than the creatinine-based eGFR(eGFR CG and eGFR MDRD)in ACLF patients with AKI,suggesting that baseline eGFR CysC represented early renal function in ACLF patients while the Cr levels were still within the normal ***:Serum CysC provides early prediction of renal dysfunction in ACLF patients with a normal serum Cr level.

关键词： Acute-on-chronic liver failure Cystatin C Creatinine Acute kidney injury Prediction

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Mitochondrial DNA from hepatocytes as a ligand for TLR9: Drivers of nonalcoholic steatohepatitis?

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World Journal of Gastroenterology 2016年第31期22卷 6965-6971页

作者： Priya Handa Akhila Vemulakonda Kris V Kowdley Misael Uribe Nahum Méndez-Sánchez Senior research Scientist Organ Care Research and Liver Care Network Swedish Medical Center liver research Unit Medica Sur Clinic and Foundation

Nonalcoholic fatty liver disease(NAFLD) is the most common liver disease worldwide, affecting approximately one third of the Western world. It consists of a wide spectrum of liver disorders, ranging from fatty liver to nonalcoholic steatohepatitis(NASH), which consists of steatosis, ballooning injury and inflammation. Despite an alarming growth in the statistics surrounding NAFLD, there are as yet no effective therapies for its treatment. Innate immune signaling has been thought to play a significant role in initiating and augmenting hepatic inflammation, contributing to the transition from nonalcoholic fatty liver to NASH. An immune response is triggered by countless signals called damage-associated molecular patterns(DAMPs) elicited by lipid-laden and damaged hepatocytes, which are recognized by pattern recognition receptors(PRRs) on hepatic immune cells to initiate inflammatory signaling. In this editorial, in addition to summarizing innate immune signaling in NAFLD and discussing potential therapies that target innate immune pathways, we have described a recent study that demonstrated that mitochondrial DNA serves as a DAMP activating a hepatic PRR, TLR9, in mice and in the plasma of NASH patients. In addition to identifying a new ligand for TLR9 during NASH progression, the study shows that blocking TLR9 reverses NASH, paving the way for the development of future NASH therapy.

关键词： TLR9 Damage-associated molecular patterns Products of microbial metabolism produced by pathogens Mitochondrial DNA Hepatocytes Nonalcoholic steatohepatitis Nonalcoholic fatty liver disease Inflammation Innate immune signaling Kupffer cells Therapy

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Non-coding RNAs in hepatitis C-induced hepatocellular carcinoma:Dysregulation and implications for early detection,diagnosis and therapy

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World Journal of Gastroenterology 2013年第44期19卷 7836-7845页

作者： Weihong Hou Herbert L Bonkovsky the liver Digestive and Metabolic Disorders Laboratory and the Liver-Biliary-Pancreatic Center Cannon Research Center Carolinas Medical CenterCharlotte NC 28203 United States

Hepatitis C virus(HCV)infection is one of main causes of hepatocellular carcinoma(HCC)and the prevalence of HCV-associated HCC is on the rise *** is particularly important and helpful to identify potential markers for screening and early diagnosis of HCC among high-risk individuals with chronic hepatitis C,and to identify target molecules for the prevention and treatment of *** noncoding RNAs,mainly microRNAs(miRNAs),and long non-coding RNAs(lncRNAs)with size greater than 200nucleotides,are likely to play important roles in a variety of biological processes,including development and progression of *** the most part their underlying mechanisms of action remain largely *** recent years,with the advance of high-resolution of microarray and application of next generation sequencing techniques,a significant number of non-coding RNAs(ncRNAs)associated with HCC,particularly caused by HCV infection,have been found to be differentially expressed and to be involved in pathogenesis of HCVassociated *** this review,we focus on recent studies of ncRNAs,especially miRNAs and lncRNAs related to HCV-induced *** summarize those ncRNAs aberrantly expressed in HCV-associated HCC and highlight the potential uses of ncRNAs in early detection,diagnosis and therapy of HCV-associated *** also discuss the limitations of recent studies,and suggest future directions for research in the ***,lncRNAs and their target genes may represent new candidate molecules for the prevention,diagnosis and treatment of HCC in patients with HCV *** of the potential uses of miRNAs and lncRNAs as diagnostic tools or therapies are still in their infancy.

关键词： MicroRNA Long non-coding RNAs Non-coding RNAs Hepatitis C virus Hepatocellular carcinoma

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