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Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

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World Journal of gastroenterology 2024年第28期30卷 3428-3446页

作者： Aritoshi Koizumi Kosuke Kaji Norihisa Nishimura Shohei Asada Takuya Matsuda Misako Tanaka Nobuyuki Yorioka Yuki Tsuji Koh Kitagawa Shinya Sato Tadashi Namisaki Takemi Akahane Hitoshi Yoshiji department of gastroenterology Nara Medical UniversityKashihara 634-8521Japan

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver *** proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ***,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary ***,the benefits of EFN for ALD treatment is *** To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse *** ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 ***(3 and 10 mg/kg/day)was orally administered during the experimental *** and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier *** EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based *** The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN *** promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARα***,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)*** improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory *** protective effect on intestinal bar

关键词： Liver fibrosis Ethanol Gut barrier function Apoptosis Autophagy Peroxisome proliferator activated receptor

Intestinal microecological transplantation for a patient with chronic radiation enteritis:A case report

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World Journal of gastroenterology 2024年第19期30卷 2603-2611页

作者： Lin Wang Yan Li Yu-Jing Zhang Li-Hua Peng department of gastroenterology and Hepatology The First Medical CenterChinese PLA General HospitalBeijing 100853China department of gastroenterology and Hepatology Chinese PLA Medical SchoolBeijing 100853China

BACKGROUND The gut microbiota is strongly associated with radiation-induced gut *** study aimed to assess the effectiveness and safety of intestinal microecological transplantation for treating patients with chronic radiation *** SUMMARY A 64-year-old female with cervical cancer developed abdominal pain,diarrhea,and blood in the stool 1 year after *** electronic colonoscopy was performed to diagnose chronic radiation *** courses of intestinal microecological transplantation and full-length 16S rRNA microbiological analysis were *** patient experienced short-and long-term relief from symptoms without adverse *** 16S rRNA sequencing revealed significant differences in the intestinal flora’s composition between patient and healthy *** bacteria,such as Escherichia fergusonii and Romboutsia timonensis,were more in the *** bacteria such as Faecalibacterium prausnitzii,Fusicatenibacter saccharivorans,Ruminococcus bromii,and Bifidobacterium longum were more in the healthy *** microbiota transplantation resulted in a significant change in the patient's intestinal flora *** composition converged with the donor's flora,with an increase in core beneficial intestinal bacteria,such as Eubacterium rectale,and a decrease in pathogenic *** in the intestinal flora corresponded with the patients'alleviating clinical *** Intestinal microecological transplantation is an effective treatment for relieving the clinical symptoms of chronic radiation enteritis by altering the composition of the intestinal *** study provides a new approach for treating patients with chronic radiation enteritis.

关键词： Chronic radiation enteritis Gut microbial transplantation Intestinal microecology Cancer Quality of life Case report

Development and validation of a new prognostic model for patients with acute-on-chronic liver failure in intensive care unit

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World Journal of gastroenterology 2024年第20期30卷 2657-2676页

作者： Zong-Yi Zhu Xiu-Hong Huang Hui-Qing Jiang Li Liu department of gastroenterology The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina department of gastroenterology Weixian People's HospitalXingtai 054700Hebei ProvinceChina

BACKGROUND Cirrhotic patients with acute-on-chronic liver failure(ACLF)in the intensive care unit(ICU)have a poor but variable *** prognosis evaluation can guide the rational management of patients with ***,existing prognostic scores for ACLF in the ICU environment lack sufficient *** To develop a new prognostic model for patients with ACLF in *** Data from 938 ACLF patients in the Medical Information Mart for Intensive Care(MIMIC)database were used to develop a new prognostic model(MIMIC ACLF)for ***,calibration and clinical utility of MIMIC ACLF were assessed by area under receiver operating characteristic curve(AUROC),calibration curve and decision curve analysis(DCA),*** ACLF was then externally validated in a multiple-center cohort,the Electronic Intensive Care Collaborative Research Database and a single-center cohort from the Second Hospital of Hebei Medical University in *** The MIMIC ACLF score was determined using nine variables:ln(age)×2.2+ln(white blood cell count)×0.22-ln(mean arterial pressure)×2.7+respiratory failure×0.6+renal failure×0.51+cerebral failure×0.31+ln(total bilirubin)×0.44+ln(internationalized normal ratio)×0.59+ln(serum potassium)×*** MIMIC cohort,the AUROC(0.81/0.79)for MIMIC ACLF for 28/90-day ACLF mortality were significantly greater than those of Chronic Liver Failure Consortium ACLF(0.76/0.74),Model for End-stage Liver Disease(MELD;0.73/0.71)and MELD-Na(0.72/0.70)(all P<0.001).The consistency between actual and predicted 28/90-day survival rates of patients according to MIMIC ACLF score was excellent and superior to that of existing *** net benefit of MIMIC ACLF was greater than that achieved using existing scores within the 50%threshold *** superior predictive accuracy and clinical utility of MIMIC ACLF were validated in the external *** We developed and validated a new prognostic model with satisfactory accuracy

关键词： Acute-on-chronic liver failure Cirrhosis Risk stratification Prognosis Model Scores

Minocycline in the eradication of Helicobacter pylori infection: A systematic review and meta-analysis

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World Journal of gastroenterology 2024年第17期30卷 2354-2368页

作者： Kai Zhou Cai-Ling Li Hua Zhang Bao-Jun Suo Yu-Xin Zhang Xin-Lu Ren Yu-Xin Wang Chang-Min Mi Ling-Ling Ma Li-Ya Zhou Xue-Li Tian Zhi-Qiang Song department of gastroenterology Peking University Third HospitalBeijing 100191China

BACKGROUND Difficulty in obtaining tetracycline,increased adverse reactions,and relatively complicated medication methods have limited the clinical application of the classic bismuth quadruple ***,the search for new alternative drugs has become one of the research *** recent years,minocycline,as a semisynthetic tetracycline,has demonstrated good potential for eradicating Helicobacter pylori(***)infection,but the systematic evaluation of its role remains *** To explore the efficacy,safety,and compliance of minocycline in eradicating *** *** We comprehensively retrieved the electronic databases of PubMed,Embase,Web of Science,China National Knowledge Infrastructure,SinoMed,and Wanfang database as of October 30,2023,and finally included 22 research reports on *** eradication with minocycline-containing regimens as per the inclusion and exclusion *** eradication rates of *** were calculated using a fixed or a random effect model,and the heterogeneity and publication bias of the studies were *** The single-arm meta-analysis revealed that the minocycline-containing regimens achieved good overall *** eradication rates,reaching 82.3%[95%confidence interval(CI):79.7%-85.1%]in the intention-to-treat analysis and 90.0%(95%CI:87.7%-92.4%)in the per-protocol *** overall safety and compliance of the minocycline-containing regimens were good,demonstrating an overall incidence of adverse reactions of 36.5%(95%CI:31.5%-42.2%).Further by traditional meta-analysis,the results showed that the minocycline-containing regimens were not statistically different from other commonly used eradication regimens in eradication rate and incidence of adverse *** of the adverse reactions were mild to moderate and well-tolerated,and dizziness was relatively prominent in the minocycline-containing regimens(16%).CONCLUSION The minocycline-containing regimens demonstrated good efficacy,safety,and

关键词： Helicobacter pylori Minocycline Eradication Safety Resistance

Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of gastroenterology 2024年第8期30卷 901-918页

作者： Yi-Ying Wang Mei-Mei Shen Jian Gao department of gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of *** To explore the role of MTDH on stemness and immune infiltration in *** MTDH expression in HCC tissues was detected using TCGA and GEO *** was used to analyze the tissue *** was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell *** invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing ***,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free *** expression was determined by western blotting and quantitative reverse transcri-ption *** cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like *** effects of MTDH inhibition on tumor growth were evaluated in *** correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB *** HCC tissues expressed higher levels of MTDH than normal liver *** MTDH expression was associated with a poor *** cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these *** inhibition suppressed HCC progression and CD133 expression in *** was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T *** was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 a

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

Scale offers the possibility of identifying adherence to lifestyle interventions in patients with non-alcoholic fatty liver disease

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World Journal of gastroenterology 2024年第25期30卷 3179-3181页

作者： Cen-Qin Liu Bing Hu department of gastroenterology and Hepatology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina department of gastroenterology and Hepatology/Medical Engineering Integration laboratory of Digestive Endoscopy West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disorder,and dietary and lifestyle interventions remain the mainstays of NAFLD *** et al established a prediction system to evaluate adherence to lifestyle interventions in patients with NAFLD and choose optimal ***,we discuss the application scenarios of the scale and the areas warranting further attention,aiming to provide a possible reference for clinical recommend-ations.

关键词： Nonalcoholic fatty liver disease Dietary and lifestyle interventions Scale Adherence Exercise

Efficacy of radiofrequency ablation combined with sorafenib for treating liver cancer complicated with portal hypertension and prognostic factors

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World Journal of gastroenterology 2024年第11期30卷 1533-1544页

作者： Li-Min Yang Hong-Juan Wang Shan-Lin Li Guan-Hua Gan Wen-Wen Deng Yong-Sheng Chang Lian-Feng Zhang department of gastroenterology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina department of gastroenterology Zhoukou Central Hospital of Henan ProvinceZhoukou 466000Henan ProvinceChina department of gastroenterology The First Affiliated Hospital of Xinxiang Medical CollegeXinxiang 453000Henan ProvinceChina

BACKGROUND Patients with liver cancer complicated by portal hypertension present complex challenges in *** To evaluate the efficacy of radiofrequency ablation in combination with sorafenib for improving liver function and its impact on the prognosis of patients with this *** Data from 100 patients with liver cancer complicated with portal hypertension from May 2014 to March 2019 were analyzed and divided into a study group(n=50)and a control group(n=50)according to the treatment *** research group received radiofrequency ablation(RFA)in combination with sorafenib,and the control group only received *** short-term efficacy of both the research and control groups was *** function and portal hypertension were compared before and after ***-fetoprotein(AFP),glypican-3(GPC-3),and AFP-L3 levels were compared between the two groups prior to and after *** occurrence of adverse reactions in both groups was *** 3-year survival rate was compared between the two *** data were compared between the survival and non-surviving *** identify the independent risk factors for poor prognosis in patients with liver cancer complicated by portal hypertension,multivariate logistic regression analysis was *** When comparing the two groups,the research group's total effective rate(82.00%)was significantly greater than that of the control group(56.00%;P<0.05).Following treatment,alanine aminotransferase and aspartate aminotransferase levels increased,and portal vein pressure decreased in both *** degree of improvement for every index was substantially greater in the research group than in the control group(P<0.05).Following treatment,the AFP,GPC-3,and AFP-L3 levels in both groups decreased,with the research group having significantly lower levels than the control group(P<0.05).The incidence of diarrhea,rash,nausea and vomiting,and fatigue in the research group was significantly great

关键词： Radiofrequency ablation Sorafenib Liver cancer Portal hypertension Efficacy Prognosis analysis

An antibiotic-free platform for eliminating persistent Helicobacter pylori infection without disrupting gut microbiota

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3184-3204页

作者： Yongkang Lai Tinglin Zhang Xiaojing Yin Chunping Zhu Yiqi Du Zhaoshen Li Jie Gao department of gastroenterology Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghai 200433China department of gastroenterology Ganzhou People’s Hospital Affiliated to Nanchang UniversityGanzhou 341000China National Key laboratory of Immunity and Inflammation Naval Medical UniversityShanghai 200433China Shanghai Key laboratory of Nautical Medicine and Translation of Drugs and Medical Devices Shanghai 200433China

Helicobacter pylori(***)infection remains the leading cause of gastric adenocarcinoma,and its eradication primarily relies on the prolonged and intensive use of two ***,antibiotic resistance has become a compelling health issue,leading to *** eradication treatment failure ***,the powerlessness of antibiotics against biofilms,as well as intracellular *** and the long-term damage of antibiotics to the intestinal microbiota,have also created an urgent demand for antibiotic-free ***,we describe an antibiotic-free,multifunctional copperorganic framework(HKUST-1)platform encased in a lipid layer comprising phosphatidic acid(PA),rhamnolipid(RHL),and cholesterol(CHOL),enveloped in chitosan(CS),and loaded in an ascorbyl palmitate(AP)hydrogel:AP@CS@Lip@*** platform targets inflammatory sites where *** aggregates through electrostatic ***,hydrolysis by matrix metalloproteinases(MMPs)releases CS-encased nanoparticles,disrupting bacterial urease activity and membrane ***,RHL disperses biofilms,while PA promotes lysosomal acidification and activates host autophagy,enabling clearance of intracellular ***,AP@CS@Lip@HKUST-1 alleviates inflammation and enhances mucosal repair through delayed Cu^(2+) release while preserving the intestinal ***,this platform presents an advanced therapeutic strategy for eradicating persistent *** infection without inducing drug resistance.

关键词： Helicobacter pylori infection Antibiotic-free Biofilms Autophagy Gastric mucosal repair Drug resistance Intestinal microbiota Anti-inflammation

Serotonin receptor 2B induces visceral hyperalgesia in rat model and patients with diarrhea-predominant irritable bowel syndrome

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World Journal of gastroenterology 2024年第10期30卷 1431-1449页

作者： Zheng-Yang Li Yu-Qing Mao Qian Hua Yong-Hong Sun Hai-Yan Wang Xuan-Guang Ye Jing-Xian Hu Ya-Jie Wang Miao Jiang department of gastroenterology Jinshan Hospital of Fudan UniversityShanghai 201508China department of gastroenterology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China department of gastroenterology Dalian Friendship HospitalDalian 116001Liaoning ProvinceChina department of Pathology Jinshan Hospital of Fudan UniversityShanghai 201508China

BACKGROUND Serotonin receptor 2B(5-HT2B receptor)plays a critical role in many chronic pain *** possible involvement of the 5-HT2B receptor in the altered gut sensation of irritable bowel syndrome with diarrhea(IBS-D)was investigated in the present *** To investigate the possible involvement of 5-HT2B receptor in the altered gut sensation in rat model and patients with *** Rectosigmoid biopsies were collected from 18 patients with IBS-D and 10 patients with irritable bowel syndrome with constipation who fulfilled the Rome IV criteria and 15 healthy *** expression level of the 5-HT2B receptor in colon tissue was measured using an enzyme-linked immunosorbent assay and correlated with abdominal pain *** IBS-D rat model was induced by intracolonic instillation of acetic acid and wrap *** in visceral sensitivity and 5-HT2B receptor and transient receptor potential vanilloid type 1(TRPV1)expression were examined following 5-HT2B receptor antagonist *** in visceral sensitivity after administration of the TRPV1 antago-INTRODUCTION Irritable bowel syndrome(IBS)is a chronic functional bowel disorder characterized by recurrent abdominal pain with altered bowel habits that affects approximately 15%of the population worldwide[1].IBS significantly impacts the quality of life of *** the pathogenesis of IBS is not completely understood,the role of abnormal visceral sensitivity in IBS has recently emerged[2,3].5-Hydroxytryptamine(5-HT)is known to play a key role in the physiological states of the gastrointestinal *** 5-HT levels in IBS with diarrhea(IBS-D)patients were greater than those in healthy controls[4],suggesting a possible role of 5-HT in the pathogenesis of *** serotonin receptor 2(5-HT2 receptor)family comprises three subtypes:5-HT2A,5-HT2B,and *** 5-HT2 receptors exhibit 46%-50%overall sequence identity,and all of these receptors preferentially bind to Gq/

关键词： Diarrhea-predominant irritable bowel syndrome Serotonin receptor 2B Transient receptor potential vanilloid type-1 Visceral hypersensitivity Abdominal pain