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High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species

Science China(Life Sciences) 2024年第5期67卷 879-891页

作者： Nianyi Zeng Fan Wu Junqi Lu Xiang Li Shaomei Lin Lang Zhou Zhongwei Wang Guangyan Wu Qingfa Huang Daowen Zheng Jie Gao Shan Wu Xiaojiao Chen Muxuan Chen Fanguo Meng Haitao Shang Yan He Peng Chen Hong Wei Zhuang Li Hongwei Zhou Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510282China department of Environmental Health Guangdong Provincial Key Laboratory of Tropical Disease ResearchSchool of Public Health and Tropical MedicineSouthern Medical UniversityGuangzhou 510515China Redox medical Center for Public Health Soochow UniversitySuzhou 215301China Precision Medicine Institute The First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China department of Pathophysiology Guangdong Provincial Key Laboratory of ProteomicsSchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet(HFD)-associated metabolic ***,the underlying mechanism remains *** the present study,by comparing HFD-and normal diet(ND)-treated mice,we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut *** sequencing revealed that the HFD upregulates gut microbial functions related to redox reactions,as confirmed by the increased reactive oxygen species(ROS)levels in fecal microbiota incubation in vitro and in the lumen,which were detected using in vivo fluorescence *** microbial ROS-producing capability induced by HFD can be transferred through fecal microbiota transplantation(FMT)into germ-free(GF)mice,downregulating the gut barrier tight ***,mono-colonizing GF mice with an Enterococcus strain excelled in ROS production,damaged the gut barrier,induced mitochondrial malfunction and apoptosis of the intestinal epithelial cells,and exacerbated fatty liver,compared with other low-ROS-producing Enterococcus *** administration of recombinant high-stability-superoxide dismutase(SOD)significantly reduced intestinal ROS,protected the gut barrier,and improved fatty liver against the *** conclusion,our study suggests that extracellular ROS derived from gut microbiota play a pivotal role in HFD-induced gut barrier disruption and is a potential therapeutic target for HFD-associated metabolic diseases.

关键词： fatty liver disease gut microbiota gut barrier high-fat diet oxidative stress reactive oxygen species

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Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

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Chinese medical Journal 2024年第6期137卷 657-668页

作者： Shuguang Zhu Xiaowen Wang Haoqi Chen Wenfeng Zhu Xuejiao Li Ruiwen Cui Xiaomeng Yi Xiaolong Chen Hua Li Genshu Wang department of Hepatic Surgery Liver TransplantationThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Hepatology lab The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of General Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Organ Transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Renal Transplantation Guangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China department of Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Hepatic Surgery Liver TransplantationGuangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China

Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in *** a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological ***,it remains elusive whether and how YAP may control autophagy activation during ***:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy *** an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of ***:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of ***-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with *** addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of *** Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

关键词： YAP-signaling proteins Autophagy c-Jun N-terminal kinase Ischemia-reperfusion injury liver transplantation

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Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe^(-/-)mice

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Life Metabolism 2024年第3期3卷 46-59页

作者： Yajuan Deng Xiaoyu Yang Xueru Ye Youwen Yuan Yanan Zhang Fei Teng Danming You Xuan Zhou Wenhui Liu Kangli Li Shenjian Luo Zhi Yang Ruxin Chen Guojun Shi Jin Li Huijie Zhang department of Endocrinology and Metabolism Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China guangdong provincial key laboratory of Shock and Microcirculation Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China State key laboratory of Organ Failure Research National Clinical Research Center for Kidney DiseaseNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China department of Endocrinology The Second Hospital of Shanxi Medical UniversityShanxi Medical UniversityTaiyuanShanxi 030001China department of Endocrinology and Metabolism Guangdong Provincial Key Laboratory of DiabetologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China

Atherosclerosis is the major contributor to cardiovascular mortality *** day fasting(ADF)has gained growing attention due to its metabolic ***,the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal *** present study was designed to investigate the effects of ADF on atherosclerosis in apolipoprotein E-deficient(Apoe^(-/-))***-week-old male Apoe^(-/-)mice fed with Western diet(WD)were randomly grouped into ad libitum(AL)group and ADF group,and ADF aggravated both the early and advanced atherosclerotic lesion formation,which might be due to the disturbed cholesterol profiles caused by ADF *** significantly altered cholesterol metabolism pathways and down-regulated integrated stress response(ISR)in the *** hepatic expression of activating transcription factor 3(ATF3)was suppressed in mice treated with ADF and hepatocyte-specific overexpression of Aft3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe^(-/-)***,the expression of ATF3 could be regulated by Krüppel-like factor 6(KLF6)and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR *** conclusion,ADF aggravates atherosclerosis progression in Apoe^(-/-)mice fed on *** inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6,subsequently inhibiting ATF3 *** suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe^(-/-)*** findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.

关键词： alternate day fasting atherosclerosis cholesterol integrated stress response activating transcription factor 3

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A novel mouse model of PEDF-associated serious liver inflammation,hepatic tumorigenesis and cardiovascular injury mimics human nonalcoholic steatohepatitis

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Genes & diseases 2024年第1期11卷 11-14页

作者： Xinghui Li Haiping Wang Yandi Wu Li Zou Shijie Dengg Xintu Fu Tongsheng Huang Conghui Shen Teng Wu Weibin Cai guangdong Engineering&Technology Research Center for disease-Model Animals Laboratory Animal CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China department of Biochemistry Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouGuangdong 510080China School of Pharmacy Guangdong Pharmaceutical UniversityGuangzhouGuangdong 510006China guangdong provincial key laboratory of Digestive Cancer Research The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhenGuangdong 518107China

There are no approvedtherapeuticdrugs for nonalcoholic steatohepatitis(NASH)due to the many bottlenecks,including the lack of preclinical animal models that can perfectly mimic human NASH features,such as systemic metabolic disorders,hepatic steatosis,intense liver inflammation and fibrosis,liver tumorigenesis,and cardiovascularcomplications.i,2"Pigment"epitheliumderived factor(PEDF)is a lipid metabolism regulator with high expression in the liver,and its reduced expression in the liver is closely related to the development of nonalcoholic fatty liver disease(NAFLD).

关键词： inflammation PEDF hepatic

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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei Sun Arabella H.Wan Shijia Yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu Ke department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China department of medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA department of Hepatic Surgery and liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China guangdong provincial key laboratory of liver disease Research Guangzhou 510630China department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model Romidepsin EGFR liver cancer

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Plasma microRNA-15a/16-1-based machine learning for early detection of hepatitis B virus-related hepatocellular carcinoma

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liver Research 2024年第2期8卷 105-117页

作者： Huan Wei Songhao Luo Yanhua Bi Chunhong Liao Yifan Lian Jiajun Zhang Yuehua Huang guangdong provincial key laboratory of liver disease Research The Third Affiliated Hospital of Sun Yat-sen University Guangzhou China School of Mathematics Sun Yat-sen University Guangzhou China School of Public Health Sun Yat-sen University Guangzhou China guangdong Province key laboratory of Computational Science Sun Yat-sen University Guangzhou China department of Infectious diseases The Third Affiliated Hospital of Sun Yat-sen University Guangzhou China

Background and aims Hepatocellular carcinoma (HCC), which is prevalent worldwide and has a high mortality rate, needs to be effectively diagnosed. We aimed to evaluate the significance of plasma microRNA-15a/16-1 (miR-15a/16) as a biomarker of hepatitis B virus-related HCC (HBV-HCC) using the machine learning model. This study was the first large-scale investigation of these two miRNAs in HCC plasma samples. Methods Using quantitative polymerase chain reaction, we measured the plasma miR-15a/16 levels in a total of 766 participants, including 74 healthy controls, 335 with chronic hepatitis B (CHB), 47 with compensated liver cirrhosis, and 310 with HBV-HCC. The diagnostic performance of miR-15a/16 was examined using a machine learning model and compared with that of alpha-fetoprotein (AFP). Lastly, to validate the diagnostic efficiency of miR-15a/16, we performed pseudotemporal sorting of the samples to simulate progression from CHB to HCC. Results Plasma miR-15a/16 was significantly decreased in HCC than in all control groups ( P < 0.05 for all). In the training cohort, the area under the receiver operating characteristic curve (AUC), sensitivity, and average precision (AP) for the detection of HCC were higher for miR-15a (AUC = 0.80, 67.3%, AP = 0.80) and miR-16 (AUC = 0.83, 79.0%, AP = 0.83) than for AFP (AUC = 0.74, 61.7%, AP = 0.72). Combining miR-15a/16 with AFP increased the AUC to 0.86 (sensitivity 85.9%) and the AP to 0.85 and was significantly superior to the other markers in this study ( P < 0.05 for all), as further demonstrated by the detection error tradeoff curves. Moreover, miR-15a/16 impressively showed potent diagnostic power in early-stage, small-tumor, and AFP-negative HCC. A validation cohort confirmed these results. Lastly, the simulated follow-up of patients further validated the diagnostic efficiency of miR-15a/16. Conclusions We developed and validated a plasma miR-15a/16-based machine learning model, which exhibited better diagnostic perfo

关键词： Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) microRNA-15a microRNA-16-1 Biomarker Machine learning Pseudotemporal ordering

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Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

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Bone Research 2024年第2期12卷 421-437页

作者： Hongzhen Chen Xuekun Fu Xiaohao Wu Junyi Zhao Fang Qiu Zhenghong Wang Zhuqian Wang Xinxin Chen Duoli Xie Jie Huang Junyu Fan Xu Yang Yi Song Jie Li Dongyi He Guozhi Xiao Aiping Lu Chao Liang department of Systems Biology School of Life SciencesSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Institute of Integrated Bioinfomedicine and Translational Science(IBTS) School of Chinese MedicineHong Kong Baptist UniversityHong Kong SAR 999077China department of Biochemistry School of MedicineSouthern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China Division of Immunology and Rheumatology Stanford UniversityStanfordCA 94305USA VA Palo Alto Health Care System Palo AltoCA 94304USA Institute of Plant and Food Science Department of BiologySouthern University of Science and TechnologyShenzhen 518055China department of Rheumatology Guanghua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai University of Traditional Chinese MedicineShanghaiChina department of Computational Biology St.Jude Children’s Research HospitalMemphisTNUSA department of laboratory Medicine Peking University Shenzhen HospitalShenzhenChina guangdong-Hong Kong-Macao Joint lab on Chinese Medicine and Immune disease Research Guangzhou 510006China Shanghai University of Traditional Chinese Medicine Shanghai 200032China State key laboratory of Proteomics National Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics100850 BeijingChina

Rheumatoid arthritis(RA)is an autoimmune *** studies hold an opinion that gut microbiota is environmentally acquired and associated with RA ***,accumulating evidence demonstrates that genetics also shape the gut *** is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to ***,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched *** than DBA/1J mice and RA *** of *** prevents CIA in DBA/1J *** identify that *** mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of ***-like synoviocytes(FLSs)in RA are activated to undergo tumor-like *** disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of *** treat CIA mice with propionate and show that propionate attenuates ***,a combination of propionate with anti-TNF etanercept synergistically relieves *** results suggest that *** or propionate could be an alternative or complementary approach to the current therapies.

关键词： HDAC3 cytes interferon

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong Gao State key laboratory of Traditional Chinese Medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina key laboratory of Immune Microenvironment and disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu key laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical medical College of Guangzhou University of Chinese Medicine ShenzhenChina Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina department of Biochemistry and Molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina key laboratory of Birth Defects and Related diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin *** the details of the underlying mechanisms are not fully ***,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of *** Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin ***,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic ***,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome *** key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in ***,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

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COVID-19 risk prediction scores for mortality:A validation study from the National Registry of COVID-19 in China

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Chinese medical Journal 2024年第6期137卷 743-745页

作者： Sui Peng Kelvin KF Tsoi Jianfeng Wu Steve HL Yim Haibo Wang Qian Zhou Han Xiao Zongpeng Weng Bin Li Ming Kuang Jianyan Long Joseph JY Sung Haipeng Xiao Clinical Trials Unit The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China Stanley Ho Big Data Decision Analytics Research Centre The Chinese University of Hong KongHong Kong 999077China JC School of Public Health and Primary Care The Chinese University of Hong KongHong Kong 999077China department of Critical Care Medicine The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China department of Geography and Resource Management The Chinese University of Hong KongHong Kong 999077China department of medical ultrasonics Institute of Diagnostic and Interventional UltrasoundThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China department of liver Surgery The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China department of Medicine and Therapeutics The Chinese University of Hong KongHong Kong 999077China department of Endocrinology Precision Medicine InstituteThe First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhouGuangdong 510080China

To the Editor:Coronavirus disease 2019(COVID-19)has evolved into a global pandemic,with over 700 million confirmed cases worldwide and still mounting.^([1])The clinical impact of this pandemic is immense,given the wide spectrum of disease manifestation,ranging from mild respiratory symptoms to severe pulmonary *** high-risk individuals,especially during their initial encounters in clinics and hospital emergency services,is crucial to provide timely effective ***,the timely risk stratification of COVID-19 patients in the emergency room can greatly benefit both infected individuals and healthcare professionals.^([2])This study aims to identify features of serious COVID-19 infection at presentation that may lead to mortality of the patients.

关键词： mortality respiratory prediction

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sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1177-1188页

作者： Song-Man Yu Hai Li Guo-Hong Deng Xian-Bo Wang Xin Zheng Jin-Jun Chen Zhong-Ji Meng Yu-Bao Zheng Yan-Hang Gao Zhi-Ping Qian Feng Liu Xiao-Bo Lu Yu Shi Jia Shang Ruo-Chan Chen Yan Huang department of Infectious diseases Xiangya HospitalCentral South UniversityChangsha 410000Hunan ProvinceChina department of Gastroenterology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China department of Infectious diseases Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100020China department of Infectious diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430020Hubei ProvinceChina department of Infectious diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina department of Infectious disease Taihe HospitalHubei University of MedicineShiyan 442009Hubei ProvinceChina department of Infectious diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina department of Hepatology The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina department of liver Intensive Care Unit Shanghai Public Health Clinical CentreFudan UniversityShanghai 200093China Tianjin Institute of Hepatology Nankai University Second People's HospitalTianjin 300192China Infectious disease Center The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054Xinjiang Uygur Autonomous RegionChina The State key laboratory for Diagnosis and Treatment of Infectious diseases The First Affiliated Hospital of School of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvineChina department of Infectious diseases Henan Provincial People's HospitalZhengzhou 463599Henan ProvineChina department of Infectious diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangsha 110051Hunan ProvineChina

BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and *** triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory *** To explore the prognostic value of sTREM-1 in patients with AD of *** A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at *** enrolled patients were followed-up for at least 1 *** In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD ***,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d *** ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF *** Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

关键词： Soluble triggering receptor expressed on myeloid cell-1 Acute decompensation Cirrhosis Acute-on-chronic liver failure Prognostic biomarker

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