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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1148-1154页

作者： Yi-Long Wu Wei-Jie Ou Ming Zhong Su Lin yue-yong zhu Endoscopy Center the First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina Department of Hepatol-ogy Hepatology Research Institutethe First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina Endocri-nology Department Metabolic Diseases Research Institutethe First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina Fujian Diabetes Research Institute the First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina Clinical Research Center for Liver and Intestinal Diseases of Fujian Province FuzhouFujianChina

Background and Aims:Acute liver failure(ALF)is as-sociated with high *** D(GSDMD)is the executioner of pyroptosis and is involved in the patho-physiology of immune dysregulation This study investi-gated the role of the GSDMD inhibitor necrosulfonamide(NSA)in ***:An ALF model was established by lipopolysaccharide/D-galactosamine challenge in C57BL/6J *** were divided into four groups:normal controls(control group),ALF group(ALF group),dimethyl sulfoxide group(DMSO group),and NSA intervention group(NSA group).Survival was monitored,liver damage was de-termined by hematoxylin and eosin staining,and serum alanine aminotransferase(ALT).Underlying mechanisms were explored by quantitative real-time PCR,western blot-ting,and enzyme-linked immunosorbent ***:Pyroptosis was activated in ALF model *** treat-ed with GSDMD inhibitor NSA developed less severe liver *** reduced the expression of GSDMD,NLRP3,cleaved caspase-1,cleaved caspase-11,and secretion of interleukin-1 beta in ALF mice ***:Py-roptosis was activated in *** alleviated ALF via the pyroptosis pathway.

关键词： Liver failure Acute Pyroptosis GSDMD GSDMD-NT Necrosul-fonamide

Noninvasive models for assessment of liver fibrosis in patients with chronic hepatitis B virus infection

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World Journal of Gastroenterology 2016年第29期22卷 6663-6672页

作者： Da-Wu Zeng Jing Dong Yu-Rui Liu Jia-Ji Jiang yue-yong zhu Liver Center The First Affiliated Hospital Fujian Medical University

There are approximately 240 million patients with chronic hepatitis B virus(HBV) infection worldwide. Up to 40% of HBV-infected patients can progress to liver cirrhosis, hepatocellular carcinoma or chronic end-stage liver disease during their lifetime. This, in turn, is responsible for around 650000 deaths annually worldwide. Repeated hepatitis flares may increase the progression of liver fibrosis, making the accurate diagnosis of the stage of liver fibrosis critical in order to make antiviral therapeutic decisions for HBV-infected patients. Liver biopsy remains the "gold standard" for diagnosing liver fibrosis. However, this technique has recently been challenged by the development of several novel noninvasive tests to evaluate liver fibrosis, including serum markers, combined models and imaging techniques. In addition, the cost and accessibility of imaging techniques have been suggested as additional limitations for invasive assessment of liver fibrosis in developing countries. Therefore, a noninvasive assessment model has been suggested to evaluate liver fibrosis, specifically in HBVinfected patients, owing to its high applicability, interlaboratory reproducibility, wide availability for repeated assays and reasonable cost. The current review aims to present the status of knowledge in this new and exciting field, and to highlight the key points in HBVinfected patients for clinicians.

关键词： Liver biopsy Hepatitis B noninvasive serum biomarkers Fibrosis

Modified model for end-stage liver disease improves shortterm prognosis of hepatitis B virus-related acute-on-chronic liver failure

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World Journal of Gastroenterology 2017年第40期23卷 7303-7309页

作者： wei chen jia you jing chen qi zheng jia-ji jiang yue-yong zhu Center for Liver Diseases the First Affiliated HospitalFujian Medicine University

AIM To investigate whether the short-term prognosis of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF) could be improved by using a modified model for end-stage liver disease(MELD) including serum *** This clinical study was conducted at the First Affiliated Hospital, Fujian Medicine University, China. From 2009 to 2015, 236 patients diagnosed with HBV-related ACLF at our center were recruited for this 3-month followup study. Demographic data and serum lactate levels were collected from the patients. The MELD scores with or without serum lactate levels from survival and nonsurvival groups were recorded and *** Two hundred and thirty-six patients with HBV-ACLF were divided into two groups: survival group(S) andnon-survival group(NS). Compared with the NS group, the patients in survival the S group had a significantly lower level of serum lactate(3.11 ± 1.98 vs 4.67 ± 2.43, t = 5.43, P < 0.001) and MELD score(23.33 ± 5.42 vs 30.37 ± 6.58, t = 9.01, P = 0.023). Furthermore, serum lactate level was positively correlated with MELD score(r = 0.315, P < 0.001). Therefore, a modified MELD including serum lactate was developed by logistic regression analysis(0.314 × lactate + 0.172 × MELD-5.923). In predicting 3-month mortality using the MELD-LAC model, the patients from the S group had significantly lower baseline scores(-0.930 ± 1.34) when compared with those from the NS group(0.771 ± 1.32, t = 9.735, P < 0.001). The area under the receiver operating characteristic curve(AUROC) was 0.859 calculated by using the MELD-LAC model, which was significantly higher than that calculated by using the lactate level(0.790) or MELD alone(0.818). When the cutoff value was set at-0.4741, the sensitivity, specificity, positive predictive value and negative predictive value for predicting short-term mortality were 91.5%, 80.10%, 94.34% and 74.62%, respectively. When the MELD-LAC scores at baseline level were set at-0.5561 and 0.6879, the corresp

关键词： Hepatitis B virus Liver failure Model for end-stage liver disease score Prognosis Serum lactate level

Ceruloplasmin, a reliable marker of fibrosis in chronic hepatitis B virus patients with normal or minimally raised alanine aminotransferase

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World Journal of Gastroenterology 2016年第43期22卷 9586-9594页

作者： Da-Wu Zeng Jing Dong Jia-Ji Jiang yue-yong zhu Yu-Rui Liu Liver Center The First Affiliated Hospital Fujian Medical University

AIM To develop a non-invasive model to evaluate significant fibrosis and cirrhosis by investigating the association between serum ceruloplasmin(CP) levels and liver fibrosis in chronic hepatitis B(CHB) patients with normal or minimally raised alanine aminotransferase(ALT).METHODS Serum samples and liver biopsy were obtained from 193 CHB patients with minimally raised or normal ALT who were randomly divided into a training group(n = 97) and a validation group(n = 96). Liver histology was evaluated by the METAVIR scoring system. Receiver operator characteristic curves were applied to the diagnostic value of CP for measuring liver fibrosis in CHB patients. Spearman rank correlation analyzed the relationship between CP and liver fibrosis. A noninvasive model was set up through multivariate logistic regression *** Serum CP levels individualized various fibrosis stages via area under the curve(AUC) values. Multivariate analysis revealed that CP levels were significantlyrelated to liver cirrhosis. Combining CP with serum GGT levels, a CG model was set up to predict significant fibrosis and liver cirrhosis in CHB patients with normal or minimally raised ALT. The AUC, sensitivity, specificity, positive predictive value, and negative predictive value were 0.84, 83.1%, 78.6%, 39.6%, and 96.5% to predict liver cirrhosis, and 0.789, 80.26%, 68.38%, 62.25%, and 84.21% to predict significant fibrosis. This model expressed a higher AUC than FIB-4(age, ALT, aspartate aminotransferase, platelets) and GP(globulin, platelets) models to predict significant fibrosis(P = 0.019 and 0.022 respectively) and revealed a dramatically greater AUC than FIB-4(P = 0.033) to predict liver *** The present study showed that CP was independently and negatively associated with liver fibrosis. Furthermore, we developed a novel promising model(CG), based on routine serum markers, for predicting liver fibrosis in CHB patients with normal or minimally raised ALT.

关键词： Chronic hepatitis B Liver biopsy Fibrosis Cirrhosis Ceruloplasmin

Clinic-pathological features of metabolic associated fatty liver disease with hepatitis B virus infection

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World Journal of Gastroenterology 2021年第4期27卷 336-344页

作者： Ming-Fang Wang Bo Wan Yin-Lian Wu Jiao-Feng Huang yue-yong zhu You-Bing Li Department of Liver Research Center The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005Fujian ProvinceChina Institute of Neurology University College LondonLondon WC1N 3BGUnited Kingdom

BACKGROUND Metabolic associated fatty liver disease(MAFLD)is a novel concept proposed in *** To compare the characteristics of MAFLD and MAFLD with hepatitis B virus(HBV)*** Patients with histopathologically proven MAFLD from a single medical center were *** were divided into MAFLD group(without HBV infection)and HBV-MAFLD group(with HBV infection).Propensity score matching was utilized to balance the baseline characteristics between two *** A total of 417 cases with MAFLD were included,359(86.1%)of whom were infected with *** were significantly more males in the HBV-MAFLD group than in the MAFLD group(P0.05).The rank sum test results showed that the degree of liver steatosis in the MAFLD group was more severe than that in the HBV-MAFLD group,while the degree of inflammation and fibrosis in the liver was less severe(P<0.05).In multivariate analysis,HBV infection was associated with significantly lower grade of hepatic steatosis[odds ratio(OR)=0.088,95%confidence interval(CI):0.027-0.291]but higher inflammation level(OR=4.059,95%CI:1.403-11.742)and fibrosis level(OR=3.016,95%CI:1.087-8.370)after adjusting for age,gender,and other metabolic *** HBV infection is associated with similar metabolic risks,lower steatosis grade,higher inflammation,and fibrosis grade in MAFLD patients.

关键词： Fatty liver disease Metabolic associated fatty liver disease Hepatitis B virus Biopsy Clinic-pathological features

Efficacy and safety of autologous stem cell transplantation for decompensated liver cirrhosis:A retrospective cohort study

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World Journal of Stem Cells 2018年第10期10卷 138-145页

作者： Ming-Fang Wang You-Bing Li Xiao-Juan Gao Hao-Yang Zhang Su Lin yue-yong zhu Liver Center the First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Fujian Provincial Governmental Hospital Fuzhou 350001Fujian ProvinceChina School of Biological Sciences the University of Hong KongHong KongChina

AIM To evaluate the long-term efficacy and safety of autologous stem cell transplantation(SCT) for decompensated liver *** Consecutive patients with decompensated liver cirrhosis were included and assigned into the SCT group and non-transplantation(non-SCT) group according to whether they received SCT treatment. Patients werefollowed up for ten years. The long-term survival rate and incidence of hepatocellular carcinoma(HCC) were compared between groups.

关键词： Decompensated liver cirrhosis Stem cell transplantation Hepatocellular carcinoma Propensity score matching

Development of a novel score for the diagnosis of bacterial infection in patients with acute-on-chronic liver failure

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World Journal of Gastroenterology 2020年第32期26卷 4857-4865页

作者： Su Lin Yan-Yan Yan Yin-Lian Wu Ming-Fang Wang yue-yong zhu Xiao-Zhong Wang Department of Gastroenterology Union Hospital of Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina Liver Research Center The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina Clinical Liver Center The 180th Hospital of People’s Liberation ArmyQuanzhou Fujian Province362100China

BACKGROUND The diagnosis of bacterial infection is difficult in patients with acute-on-chronic liver failure(ACLF).AIM To evaluate the diagnostic accuracy of widely used parameters for bacterial infection in ACLF and to develop a simple scoring system to improve diagnostic *** This was a retrospective ***(PCT),white blood cells(WBC),proportion of neutrophils(N%),and C-reactive protein(CRP)were *** regression was used to select variables for the scoring models and receiver operating characteristic curve(ROC)analysis was used to evaluate the diagnostic value of different *** This study included 386 patients with ACLF,169(43.78%)of whom had bacterial infection on *** area under the ROC(AUROC)of PCT,CRP,WBC and N%for the diagnosis of bacterial infection ranged from 0.637 to 0.692,with no significant difference between *** regression showed that only N%,PCT,and CRP could independently predict infection.A novel scoring system(infection score)comprised of N%,PCT and CRP was *** AUROC of the infection score was 0.740,which was significantly higher than that for the other four indices(infection score vs N%,PCT,CRP,and WBC,P=0.0056,0.0001,0.0483 and 0.0008,respectively).The best cutoff point for the infection score was 4 points,with a sensitivity of 78.05%,a specificity of 55.29%,a positive predictive value of 57.91%and a negative predictive value of 76.16%.CONCLUSION The infection score is a simple and useful tool for discriminating bacterial infection in ACLF.

关键词： Acute on chronic liver failure Bacterial infection Score

Validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

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World Journal of Gastroenterology 2021年第34期27卷 5753-5763页

作者： Yin-Lian Wu Rahul Kumar Ming-Fang Wang Medha Singh Jiao-Feng Huang yue-yong zhu Su Lin Department of Hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350005Fujian ProvinceChina Department of Gastroenterology and Hepatology Duke-NUS academic Medical CentreChangi General HospitalSingapore 529889Singapore Department of General Medicine Tan Tock Seng HospitalSingapore 308433Singapore

BACKGROUND Non-invasive fibrosis scores are not yet validated in the newly defined metabolic associated fatty liver disease(MAFLD).AIM To evaluate the diagnostic performance of four non-invasive scores including aspartate aminotransferase to platelet ratio index(APRI),fibrosis-4 index(FIB-4),body mass index,aspartate aminotransferase/alanine aminotransferase ratio,diabetes score(BARD),and nonalcoholic fatty liver disease fibrosis score(NFS)in patients with *** Consecutive patients with histologically confirmed MAFLD were *** discrimination ability of different non-invasive scores was *** A total of 417 patients were included;156(37.4%)of them had advanced fibrosis(Metavir≥F3).The area under receiver operating characteristic curve of FIB-4,NFS,APRI,and BARD for predicting advanced fibrosis was 0.736,0.724,0.671,and 0.609,*** area under receiver operating characteristic curve of FIB-4 and NFS was similar(P=0.523),while the difference between FIB-4 and APRI(P=0.001)and FIB-4 and BARD(P<0.001)was statistically *** best thresholds of FIB-4,NFS,APRI,and BARD for diagnosis of advanced fibrosis in MAFLD were 1.05,-2.1,0.42,and 2.A subgroup analysis showed that FIB-4,APRI,and NFS performed worse in the pure MAFLD group than in the hepatitis B virus-MAFLD *** APRI and BARD scores do not perform well in *** FIB-4 and NFS could be more useful,but a new threshold is *** non-invasive scoring systems for fibrosis are required for MAFLD.

关键词： Metabolic associated fatty liver disease Non-invasive fibrosis scores Fibrosis-4 index Non-alcoholic fatty liver disease fibrosis score Aspartate aminotransferase to platelet ratio index BARD

Gut microbiota of hepatitis B virus-infected patients in the immunetolerant and immune-active phases and their implications in metabolite changes

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World Journal of Gastroenterology 2022年第35期28卷 5188-5202页

作者： Ya-Nan Li Na-Ling Kang Jia-Ji Jiang yue-yong zhu Yu-Rui Liu Da-Wu Zeng Fei Wang Department of Hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Pharmacy Fujian Geriatric HospitalFuzhou 350001Fujian ProvinceChina

BACKGROUND The microbes and metabolomics of microbiota dysbiosis in the gut in the different phases of hepatitis B virus(HBV) infection are not fully *** To investigate the specific gut microbiota and metabolites of the immune-tolerant(IT) and immune-active(IA) phases of chronic hepatitis B(CHB).METHODS Clinical fecal samples from healthy individuals and patients in the IT and IA phases of HBV infection were collected. Next, non-target metabolomics, bioinformatics, and 16S rDNA sequencing analyses were *** A total of 293 different metabolites in 14 phyla, 22 classes, 29 orders, 51 families, and 190 genera were identified. The four phyla of Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the most abundant, accounting for 99.72%, 99.79%, and 99.55% in the healthy controls, IT-phase patients, and IA-phase patients, respectively. We further identified 16 genera with different richness in the IT phase and IA phase of HBV infection. Of the 134 named metabolites, 57 were upregulated and 77 were downregulated. A total of 101 different metabolic functions were predicted in this study, with 6 metabolic pathways having the highest enrichments, namely carbohydrate metabolism(14.85%), amino acid metabolism(12.87%), lipid metabolism(11.88%), metabolism of cofactors and vitamins(11.88%), xenobiotic biodegradation(9.9%), and metabolism of terpenoids and polyketides(7.92%).CONCLUSION These findings provide observational evidence of compositional alterations of the gut microbiome and some related metabolites in patients with IT-phase or IA-phase HBV infection. Further studies should investigate whether microbiota modulation can facilitate the progression of CHB and the cause-effect relationship between the gut microbiota and CHB.

关键词： Microbes Metabolomics Gut microbiota Immune-tolerant phase Hepatitis B virus

A novel small-animal locomotor activity recording device for biological clock research

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Animal Models and Experimental Medicine 2024年第1期7卷 71-76页

作者： Yi-Long Wu Ming Zhong Jun Yin Wei-Jie Ou Yu-Bin zhuang Nan-Wen Zhang Su Lin yue-yong zhu Endoscopy Center The First Affiliated HospitalFujian Medical UniversityFuzhouChina Department of Endocrinology The First Affiliated HospitalFujian Medical UniversityFuzhouChina Chuangke Workshop Technology Co. LtdShenzhenChina Department of Digestive Nutrition Fujian Children's HospitalFuzhouChina Experimental Animal Center Fujian Medical UniversityFuzhouChina Department of Pharmacology Fujian Medical UniversityFuzhouChina Department of Hepatology Hepatology Research InstituteClinical Research Center for Liver and Intestinal Diseases of Fujian ProvinceThe First Affiliated HospitalFujian Medical UniversityFuzhouChina

The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian *** study demonstrated how to construct a simple and intelligent running-wheel recording *** running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's ***,the RJ25 adaptor relayed the running signal to the main control ***,the main control board was connected to the USB port of the computer with the USB *** were collected using the online-accessible,self-created software *** Magturning,generated data were saved and exported in real ***,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light *** conclusion,this new device can record circadian activity of *** device is appropriate for interdisciplinary investigations related to biological clock research.

关键词： biological clock circadian rhythm intelligent equipment locomotor activity running wheel