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Premorbid Steatohepatitis Increases the Seriousness of Dextran Sulfate Sodium-induced Ulcerative Colitis in Mice

Journal of Clinical and Translational Hepatology 2022年第5期10卷 847-859页

作者： Meng-Yu Wang Zi-Xuan Wang Lei-Jie Huang Rui-Xu Yang Zi-Yuan Zou Wen-Song Ge Tian-Yi Ren Jian-Gao Fan Department of gastroenterology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina shanghai key lab of pediatric gastroenterology and nutrition ShanghaiChina

Background and Aims:The concurrence of nonalcoholic steatohepatitis(NASH)and ulcerative colitis(UC)is increasingly seen in clinical practice,but the underlying mechanisms remain *** study aimed to develop a mouse model of the phenomenon by combining high-fat high-cholesterol diet(HFHCD)-induced NASH and dextran sulfate sodium(DSS)-induced UC,that would support mechanistic ***:Male C57BL/6 mice were randomly assigned to two groups receiving either a chow diet or HFHCD for 12 weeks of NASH *** mice were divided into four subgroups for UC modeling:(1)A control group given a chow diet with normal drinking water;(2)A colitis group given chow diet with 2%DSS in drinking water;(3)A steatohepatitis group given HFHCD with normal drinking water;and(4)A steatohepatitis+colitis group given HFHCD with 2%DSS in drinking ***:NASH plus UC had high mortality(58.3%).Neither NASH nor UC alone were *** DSS-induced colitis did not exacerbate histological liver injury in HFHCD-fed mice,premorbid NASH significantly increased UC-related gut injury compared with UC *** was characterized by a significantly shorter colon,more colonic congestion,and a higher histopathological score(p<0.05).Inflammatory(tumor necrosis factor-alpha,interleukin 1 beta,C-C motif chemokine ligand 2,and nuclear factor kappa B)and apoptotic(Bcl2,Bad,Bim,and Bax)signaling pathways were significantly altered in distal colon tissues collected from mice with steatohepatitis+colitis compared with the other experimental ***:Premorbid steatohepatitis significantly aggravated DSS-induced colitis and brought about a lethal *** links between NASH and UC pathogeneses can be investigated using this model.

关键词： Inflammatory bowel disease Ulcerative colitis Nonalcoholic fatty liver disease Mouse model Mortality

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Association of maternal obesity and gestational diabetes mellitus with overweight/obesity and fatty liver risk in offspring

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World Journal of gastroenterology 2022年第16期28卷 1681-1691页

作者： Jing Zeng Feng Shen Zi-Yuan Zou Rui-Xu Yang Qian Jin Jing Yang Guang-Yu Chen Jian-Gao Fan Department of gastroenterology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China shanghai key lab of pediatric gastroenterology and nutrition Shanghai 200092China

BACKGROUND Childhood obesity and fatty liver are associated with adverse outcomes such as diabetes,metabolic syndrome,and cardiovascular diseases in *** is very important to identify relevant risk factors and intervene as early as *** present,the relationship between maternal and offspring metabolic factors is *** To estimate the association of maternal obesity and gestational diabetes mellitus(GDM)with overweight/obesity and fatty liver risk in offspring at 8 years of *** The prospective study included mothers who all had a 75-g oral glucose tolerance test at 24-28 wk of gestation and whose offspring completed follow-up at 8 years of *** birth weight,sex,height,weight,and body mass index(BMI)were measured and ***-502 examination with an M probe(Echosens,Paris,France)was prospectively conducted in offspring aged 8 years from the shanghai Prenatal Cohort *** A total of 430 mother-child pairs were included in the analysis.A total of 62(14.2%)mothers were classified as obese,and 48(11.1%)were classified as having *** mean age of the offspring at follow-up was 8 years ***-seven(8.6%)offspring were overweight,14(3.3%)had obesity,and 60(14.0%)had fatty *** prevalence of overweight,obesity and fatty liver in offspring increased significantly across maternal BMI quartiles(all P<0.05).Among offspring of mothers with GDM,12(25.0%)were overweight,4(8.3%)were obese,and 12(25.0%)had fatty liver vs.25(6.5%),10(2.6%)and 48(12.6%),respectively,for offspring of mothers without GDM(all P<0.05).In multiple logistic regression,after adjustment for variables,the OR for fatty liver in offspring was 8.26(95%CI:2.38-28.75)for maternal obesity and *** This study showed that maternal obesity can increase the odds of overweight/obesity and fatty liver in offspring,and GDM status also increases the odds of overweight/obesity in *** management and glycemic control before and during

关键词： Maternal obesity Gestational diabetes mellitus Offspring overweight/obesity Offspring fatty liver FibroScan

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Emerging role of regulated cell death in intestinal failure-associated liver disease

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 228-233页

作者： Si-Yang Cheng Lu Jiang Ying Wang Wei Cai Department of pediatric Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China shanghai key laboratory of pediatric gastroenterology and nutrition Shanghai 200092China shanghai Institute for pediatric Research Shanghai 200092China Division of pediatric gastroenterology and nutrition Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China

Intestinal failure-associated liver disease(IFALD)is a common complication of long-term parenteral nutrition that is associated with significant morbidity and *** is mainly characterized by cholestasis in children and steatohepatitis in ***,there is no effective approach to prevent or reverse the *** cell death(RCD)represents a fundamental biological paradigm that determines the outcome of a variety of liver *** cell death is reclassified into several types,based on the mechanisms and morphological *** evidence has linked different modes of RCD,such as apoptosis,necroptosis,ferroptosis,and pyroptosis to the pathogenesis of liver *** studies have shown that different modes of RCD are present in animal models and patients with *** the pathogenic roles of cell death may help uncover the underlying mechanisms and develop novel therapeutic strategies in *** this review,we discuss the current knowledge on how RCD may link to the pathogenesis of *** highlight examples of cell death-targeted interventions aiming to attenuate the disease,and provide perspectives for future basic and translational research in the field.

关键词： Parenteral nutrition Apoptosis Necroptosis Cholestasis Steatosis

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World Journal of pediatrics 2022年第4期18卷 271-277页

作者： Yi Cao Wei-Hui Yan Li-Na Lu Yi-Jing Tao Hai-Xia Feng Qing-Qing Wu Yi-Jing Chu Wei Cai Ying Wang Division of pediatric gastroenterology and nutrition Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of MedicineNo.1665Kongjiang Rd.ShanghaiChina shanghai Institute for pediatric Research ShanghaiChina shanghai key laboratory of pediatric gastroenterology and nutrition No.1665Kongjiang Rd.ShanghaiChina

Background Children with intestinal failure(IF)have frequent catheter-related bloodstream infections(CRBSIs).This study aimed to analyze the clinical presentation and laboratory parameters of CRBSIs in children with *** This 6-year retrospective study was conducted among IF children with CRBSIs at an intestinal rehabilitation center in *** data were collected,including data of temperature and gastrointestinal ***/catheter culture,fecal tests,and calculation of inflammatory index were performed,which were obtained within 1 week since CRBSI *** Fifty children with 87 CRBSIs were identified,of which there were 17 suspected and 70 confirmed ***-two pathogens were cultured from 70 positive blood cultures:63%were Gram-positive organisms,23%were Gram-negative organisms,and 11%were fungal ***,48.6%were enteric organisms;47.2%of bacterial pathogens were consistent between fecal and blood ***,46.3%fecal routines showed abnormalities including increased white blood cells,occult blood positive and the presence of fat *** consistent symptom at onset of CRBSIs was fever and gastrointestinal symptoms including increased stool output,abdominal distension,or both.C-reactive protein(CRP)and procalcitonin(PCT)were elevated,i.e.,16.5 mg/L[interquartile range(IQR)8.7-44.7]and 0.48 ng/mL(IQR 0.2-1.76),*** IF children had a high rate of CRBSIs,of which larger proportions were due to Gram-positive and enteric *** and/or gastrointestinal symptoms,combined with elevated CRP and PCT,is conducive to the early diagnosis of CRBSIs in IF patients.

关键词： Enteric pathogens Fecal examination Gastrointestinal symptoms

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The gut microbiome and intestinal failure-associated liver disease

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Hepatobiliary & Pancreatic Diseases International 2023年第5期22卷 452-457页

作者： Lu Jiang Juan Xu Si-Yang Cheng Ying Wang Wei Cai Division of pediatric gastroenterology and nutrition Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China shanghai Institute for pediatric Research Shanghai 200092China shanghai key laboratory of pediatric gastroenterology and nutrition Shanghai 200092China Department of pediatric Surgery Xinhua HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200092China

Intestinal failure-associated liver disease(IFALD)is a common hepatobiliary complication resulting from long-term parenteral nutrition(PN)in patients with intestinal *** spectrum of IFALD ranges from cholestasis,steatosis,portal fibrosis,to *** of IFALD is a multifactorial process,in which gut dysbiosis plays a critical role in its initiation and progression in conjunction with increased intestinal permeability,activation of hepatic immune responses,and administration of lipid *** microbiota manipulation including pre/probiotics,fecal microbiota transplantation,and antibiotics has been studied in IFALD with varying *** this review,we summarize current knowledge on the taxonomic and functional changes of gut microbiota in preclinical and clinical studies of *** also review the function of microbial metabolites and associated signalings in the context of *** providing microbiota-targeted interventions aiming to optimize PN-induced liver injury,our review provides perspectives for future basic and translational investigations in the field.

关键词： Parenteral nutrition Microbiota Bile acid Short-chain fatty acid Prebiotics Probiotics

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Efficacy of Intragastric Balloons in the Markers of Metabolic Dysfunction-associated Fatty Liver Disease:Results from Meta-analyses

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Journal of Clinical and Translational Hepatology 2021年第3期9卷 353-363页

作者： Zi-Yuan Zou Jing Zeng Tian-Yi Ren Yi-Wen Shi Rui-Xu Yang Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghaiChina

Background and Aims:Nonalcoholic fatty liver disease,now renamed metabolic dysfunction-associated fatty liver disease(MAFLD),is common in obese *** balloon(IGB),an obesity management tool with low complication risk,might be used in MAFLD treatment but there is still unexplained heterogeneity in results across ***:We conducted a systematic search of 152 citations published up to September ***-analyses,stratified analyses,and meta-regression were performed to evaluate the efficacy of IGB on homeostasis model assessment of insulin resistance(HOMA-IR),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transpeptidase(GGT),and to identify patients most appropriate for IGB ***:Thirteen observational studies and one randomized controlled trial met the inclusion criteria(624 participants in total).In the overall estimate,IGB therapy significantly improved the serum markers change from baseline to follow-up[HOMA-IR:1.56,95%confidence interval(CI)=1.16–1.95;ALT:11.53 U/L,95%CI=7.10–15.96;AST:6.79 U/L,95%CI=1.69–11.90;GGT:10.54 U/L,95%CI=6.32–14.75].In the stratified analysis,there were trends among participants with advanced age having less change in HOMA-IR(1.07 vs.1.82).The improvement of insulin resistance and liver biochemistries with swallowable IGB therapy was no worse than that with endoscopic *** meta-regression analyses showed that greater HOMA-IR loss was predicted by younger age(p=0.0107).Furthermore,effectiveness on ALT and GGT was predicted by basal ALT(p=0.0004)and GGT(p=0.0026),***:IGB is effective among the serum markers of *** patients had a greater decrease of HOMA-IR after IGB therapy.

关键词： Intragastric balloon Nonalcoholic fatty liver disease Insulin resistance Age groups Treatment outcome

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From NAFLD to MAFLD: Not just a change in the name

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Hepatobiliary & Pancreatic Diseases International 2022年第6期21卷 511-513页

作者： Jing Zeng Jian-Gao Fan Department of gastroenterology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China shanghai key lab of pediatric gastroenterology and nutrition Shanghai 200092China

The names of many diseases have changed over time,and the criteria of successfully changing the name of a disease should make sense,be easy to say and write,get quick endorsement by professional societies,and keep the same *** general,a change in the name of a disease usually represents an improve-ment in the understanding of the disease,whether on clinical set-tings and natural history or pathophysiological *** suc-cessful renamed liver diseases in history include from non-A non-B hepatitis,non-B non-C hepatitis,primary biliary cirrhosis to hep-atitis C,hepatitis E and primary biliary cholangitis,***,the rename of the disease that is finally used usually clearly indicates its main characteristics.

关键词： diseases NAFLD clinical

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Chronic hepatitis B infection with concomitant hepatic steatosis:Current evidence and opinion

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World Journal of gastroenterology 2021年第26期27卷 3971-3983页

作者： Yi-Wen Shi Rui-Xu Yang Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China

With the increasing incidence of obesity and metabolic syndrome worldwide,concomitant nonalcoholic fatty liver disease(NAFLD)in patients with chronic hepatitis B(CHB)has become highly *** risk of dual etiologies,outcome,and mechanism of CHB with concomitant NAFLD have not been fully *** this review,we assessed the overlapping prevalence of metabolic disorders and CHB,assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD,and discussed the remaining clinical issues to be addressed in the outcome of such *** also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological *** CHB patients,it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better *** assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.

关键词： Nonalcoholic fatty liver disease Hepatitis B Metabolic disorders Steatosis Mechanism Disease burden

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Gut microbiome and nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2023年第5期22卷 444-451页

作者： Meng-Yuan Wu Jian-Gao Fan Xiangya School of Medicine Central South UniversityChangsha 410013China Department of gastroenterology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092China shanghai key lab of pediatric gastroenterology and nutrition Shanghai 200092China

Nonalcoholic fatty liver disease(NAFLD)has become the most prevalent chronic liver disease globally and imposed a heavy economic burden on society and *** date,the pathological process of NAFLD is not yet fully *** evidences have demonstrated the pivotal role of gut microbiota in the pathogenesis of NAFLD,and gut dysbiosis has been commonly observed in patients with *** dysbiosis impairs gut permeability,allowing the translocation of bacterial products such as lipopolysaccharides(LPS),short-chain fatty acids(SCFAs),and ethanol to the liver via portal blood *** review aimed to shed light on the underlying mechanisms by which gut microbiota influences the development and progression of *** addition,the potential application of gut microbiome as a non-invasive diagnostic tool and a novel therapeutical target was reviewed.

关键词： Nonalcoholic fatty liver disease Gut microbiome Dysbiosis Intestinal permeability

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Expression of programmed death-1 and its ligands in the liver of biliary atresia

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World Journal of pediatrics 2017年第6期13卷 604-610页

作者： Pan-Liang Wang Jun Wang Ying Zhou Xiao-Song Chen Ke-Jun Zhou Jie Wen Jian-Jun Zhang Wei Cai Department of pediatric Surgery Xinhua HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina Department of Transplantation and Hepatic Surgery Renji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina shanghai key laboratory of pediatric gastroenterology and nutrition ShanghaiChina Department of pediatric Surgery Xinhua HospitalSchool of MedicineShanghai Jiaotong UniversityShanghaiChina shanghai key laboratory of pediatric gastroenterology and nutrition ShanghaiChina shanghai Institute of pediatric Research ShanghaiChina

Background:An aberrant immune response is the predominant pathogenetic factor in biliary atresia (BA).Programmed death-1 (PD-1) and its two ligands,programmed death ligand-1 and programmed death ligand-2 (PD-L1 and PD-L2,respectively) play an important inhibitory role in immune *** aimed to illustrate the expression of these molecules in ***:Liver specimens were obtained from infants with BA during the Kasai procedure (early BA) and fiver transplantation (late BA).Intrahepatic expression of PD-1,PD-L1,and PD-L2 were examined by immunostaining and compared with that in patients with neonatal hepatitis syndrome and normal *** correlation between the expression levels of these molecules in the liver and clinicopathological parameters was analyzed for each ***:Enhanced expression of PD-1 and its ligands occurred in the livers with early *** the BA-affected livers,PD-1 was correlated with the degree of peri-bifiary inflammation,while PD-L2 was linked more directly with portal *** of the three molecules was correlated with the prognosis of the Kasai procedure in patients with early ***:Only PD-1 and PD-L1 are involved in the immune reactions of early *** of the detailed role of PD-L2 in BA requires further research.

关键词： biliary atresia immunostaining liver neonatal hepatitis syndrome programmed death-1

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