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Hepatocellular SETDB1 Regulates Hepatic Ischemia-Reperfusion Injury through Targeting Lysine Methylation of ASK1 Signal

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Research 2024年第3期6卷 305-317页

作者： Kang Xia Tianyu Wang Zhongbao Chen Jiayu Guo Bo Yu Qi Chen Tao Qiu Jiangqiao Zhou Shusen Zheng Department of organ transplantation Renmin Hospital of Wuhan UniversityWuhanChina Department of Urology Renmin Hospital of Wuhan UniversityWuhanChina. Department of general surgery Renmin Hospital of Wuhan UniversityWuhanChina Division of hepatobiliary and pancreatic surgery Department of SurgeryFirst Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina key laboratory of Combined Multi-organ transplantation Ministry of Public HealthHangzhouChina key laboratory of organ transplantation HangzhouZhejiang ProvinceChina key laboratory of the Diagnosis and Treatment of organ transplantation CAMSHangzhouChina.

Background: Hepatic ischemia-reperfusion injury (HIRI) stands as an unavoidable complication arising from liver surgery, profoundly intertwined with its prognosis. The role of lysine methyltransferase SET domain bifurcated 1 (SETDB1) in HIRI remains elusive, despite its confirmation as a potential therapeutic target for diverse diseases. Here, we investigated the mechanism by which SETDB1 regulated HIRI. Methods: RNA sequencing data were used to identify the expression and potential targets of SETDB1 through bioinformatics analysis. To elucidate the impact of SETDB1 on HIRI, both an in vivo model of HIRI in mice and an in vitro model of hepatocyte hypoxia/reoxygenation were established. Biochemical and histological analyses were used to investigate the influence of SETDB1 on liver damage mediated by HIRI. Chromatin immunoprecipitation and coimmunoprecipitation were implemented to explore the in-depth mechanism of SETDB1 regulating HIRI. Results: We confirmed that hepatocellular SETDB1 was up-regulated during HIRI and had a close correlation with HIRI-related inflammation and apoptosis. Moreover, inhibition of SETDB1 could mitigate HIRI-induced liver damage, inflammation, and apoptosis. Through our comprehensive mechanistic investigation, we revealed that SETDB1 interacts with apoptosis-signal-regulating kinase 1 (ASK1) and facilitates the methylation of its lysine residues. Inhibition of SETDB1 resulted in reduced phosphorylation of ASK1, leading to a marked suppression of downstream c-Jun N-terminal kinase (JNK)/p38 signaling pathway activation. The therapeutic effect on inflammation and apoptosis achieved through SETDB1 inhibition was nullified by the restoration of JNK/p38 signaling activation through ASK1 overexpression. Conclusions: The findings from our study indicate that SETDB1 mediates lysine methylation of ASK1 and modulates the activation of the ASK1–JNK/p38 pathway, thus involved in HIRI-induced inflammation and apoptosis. These results suggest that SETD

关键词： SETDB1 inflammation ASK1

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Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

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Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng Zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng Zhang Xiaodan Zhang Shuijun Zhang Wenzhi Guo Department of hepatobiliary and pancreatic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China henan Diagnosis&Treatment League for Hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China henan Innovative Research Group for hepatobiliary&pancreatic surgery and digestive organ transplantation Zhengzhou 450052China henan organ transplantation Quality Control Centre Zhengzhou 450052China henan Engineering Technology Research Center for organ transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General surgery Huashan HospitalFudan University Shanghai 200040China Cancer Metastasis Institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

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Deep learning-based radiomics allows for a more accurate assessment of sarcopenia as a prognostic factor in hepatocellular carcinoma

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 83-90页

作者： Zhikun LIU Yichao WU Abid Ali KHAN Lun LU Jianguo WANG Jun CHEN Ningyang JIA Shusen ZHENG Xiao XU key laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou310006China Zhejiang University School of Medicine Hangzhou310058China Department of Radiology Easter Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai200438China Department of hepatobiliary and pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou310003China NHC key laboratory of Combined Multi-organ transplantation Hangzhou310003China Department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou310022China

Hepatocellular carcinoma(HCC)is one of the most common malignancies and is a major cause of cancer-related mortalities worldwide(Forner et al.,2018;He et al.,2023).Sarcopenia is a syndrome characterized by an accelerated loss of skeletal muscle(SM)mass that may be age-related or the result of malnutrition in cancer patients(Cruz-Jentoft and Sayer,2019).Preoperative sarcopenia in HCC patients treated with hepatectomy or liver transplantation is an independent risk factor for poor survival(Voron et al.,2015;van Vugt et al.,2016).

关键词： cancer patients

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SERPINE2 promotes liver cancer metastasis by inhibiting c-Cbl-mediated EGFR ubiquitination and degradation

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Cancer Communications 2024年第3期44卷 384-407页

作者： Shiyu Zhang Xing Jia Haojiang Dai Xingxin Zhu Wenfeng Song Suchen Bian Hao Wu Shinuo Chen Yangbo Tang Junran Chen Cheng Jin Mengqiao Zhou Haiyang Xie Shusen Zheng Penghong Song Division of hepatobiliary and pancreatic surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China National Health Commission key laboratory of Combined Multi-organ transplantation HangzhouZhejiangP.R.China key laboratory of the Diagnosis and Treatment of organ transplantation Research Unit of Collaborative Diagnosis and Treatment for Hepatobiliary and Pancreatic CancerChinese Academy of Medical SciencesHangzhouZhejiangP.R.China key laboratory of organ transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiangP.R.China State key laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangP.R.China

Background:Liver cancer is a malignancy with high morbidity and mortality *** family E member 2(SERPINE2)has been reported to play a key role in the metastasis of many *** this study,we aimed to investigate the potential mechanism of SERPINE2 in liver cancer ***:The Cancer Genome Atlas database(TCGA),including DNA methy-lation and transcriptome sequencing data,was utilized to identify the crucial oncogene associated with DNA methylation and cancer progression in liver *** from the TCGA and RNA sequencing for 94 pairs of liver cancer tissues were used to explore the correlation between SERPINE2 expression and clin-ical parameters of *** methylation sequencing was used to detect the DNA methylation levels in liver cancer tissues and *** sequencing,cytokine assays,immunoprecipitation(IP)and mass spectrometry(MS)assays,protein stability assays,and ubiquitination assays were performed to explore the regulatory mechanism of SERPINE2 in liver cancer ***-derived xenografts and tumor organoid models were established to determine the role of SERPINE2 in the treatment of liver cancer using ***:Based on the public database screening,SERPINE2 was identified as a tumor promoter regulated by DNA ***2 expression was significantly higher in liver cancer tissues and was associated with the dismal prognosis in patients with liver ***2 promoted liver cancer metas-tasis by enhancing cell pseudopodia formation,cell adhesion,cancer-associated fibroblast activation,extracellular matrix remodeling,and ***/MS assays confirmed that SERPINE2 activated epidermal growth factor receptor(EGFR)and its downstream signaling pathways by interacting with ***,SERPINE2 inhibited EGFR ubiquitination and maintained its protein stability by competing with the E3 ubiquitin ligase,***,EGFR was activated in liver cancer cells after sorafenib treatment,and SER

关键词： liver cancer metastasis DNA methylation SERPINE2 EGFR c-Cbl ubiquitination

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Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

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Cancer Biology & Medicine 2024年第4期21卷 347-362页

作者： Jian Chen Zhe Yang Fengqiang Gao Zhisheng Zhou Junli Chen Di Lu Kai Wang Meihua Sui Zhengxin Wang Wenzhi Guo Guoyue Lyu Haizhi Qi Jinzhen Cai Jiayin Yang Shusen Zheng Xiao Xu Zhejiang University School of Medicine Hangzhou 310030China Institute of organ transplantation Zhejiang UniversityHangzhou 310030China Department of hepatobiliary and pancreatic surgery Shulan Hospital of HangzhouHangzhou 310006China National Center for Healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of General surgery Huashan HospitalFudan UniversityShanghai 200040China Department of hepatobiliary and pancreatic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of hepatobiliary and pancreatic surgery The First Hospital of Jilin UniversityChangchun 130021China Department of Liver transplantation Second Xiangya HospitalCentral South UniversityChangsha 410008China Department of organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266003China Department of Liver surgery and Liver transplantation Center West China HospitalSichuan UniversityChengdu 610044China NHC key laboratory of Combined Multi-organ transplantation Hangzhou 310003China Department of hepatobiliary and pancreatic surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be *** study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with ***:Data for recipients with HCC registered in the China Liver Transplant Registry between January 2015 and December 2020 were *** associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further ***:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male *** analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(Porgan allocation.

关键词： Sex liver transplantation hepatocellular carcinoma outcome recipient donor

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Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2024年

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu Department of hepatobiliary and pancreatic surgery People's Hospital of Lishui Affiliated Lishui Hospital of Wenzhou Medical University The First Affiliated Hospital of Lishui University NHFPC key laboratory of Combined Multi-organ transplantation key laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang province Department of Hepatobiliary and Pancreatic Surgery Hangzhou First People's Hospital Department of hepatobiliary and pancreatic surgery The First Affiliated Hospital Zhejiang University School of Medicine Department of Urology The Second Affiliated Hospital Zhejiang University School of Medicine Department of hepatobiliary and pancreatic surgery Department of Liver Transplantation Shulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor,Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).With the prolongation of the recipient's survival time, the incidence of PTHT is increasing, becoming an important factor that affects the recipient's quality of life and survival time. Recipients with various metabolic complications, including PTHT,have a 1.78 times higher risk of atherosclerotic cardiovascular disease(ASCVD)development and death than recipients without these complications(JiménezPérez et al., 2016).

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Dynamic immune recovery process after liver transplantation revealed by single-cell multi-omics analysis

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The Innovation 2024年第3期5卷 55-68页

作者： Rui Wang Xiao Peng Yixin Yuan Baojie Shi Yuan Liu Hengxiao Ni Wenzhi Guo Qiwei Yang Pingguo Liu Jie Wang Zhaojie Su Shengnan Yu Dehua Liu Jinyan Zhang Junjie Xia Xueni Liu Hao Li Zhengfeng Yang Zhihai Peng organ transplantation Clinical Medical Center of Xiamen University Department of General SurgeryXiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China organ transplantation Institute of Xiamen University Xiamen Human Organ Transplantation Quality Control CenterXiamen Key Laboratory of Regeneration MedicineFujian Provincial Key Laboratory of Organ and Tissue RegenerationSchool of MedicineXiamen UniversityXiamen 361102China Department of General surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China State key laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Department of hepatobiliary and pancreatic surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of hepatobiliary&pancreatic surgery The National Key Clinical SpecialtyZhongshan Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China Precision Research Center for Refractory Diseases Institute for Clinical ResearchShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 201620China

Elucidating the temporal process of immune remodeling under immunosuppressive treatment after liver transplantation(LT)is critical for precise clinical management ***,we performed a single-cell multi-omics analysis of peripheral blood mononuclear cells(PBMCs)collected from LT patients(with and without acute cellular rejection[ACR])at 13 time *** was performed in two independent cohorts with additional LT patients and healthy *** study revealed a four-phase recovery process after LT and delineated changes in immune cell composition,expression programs,and interactions along this *** intensity of the immune response differs between the ACR and non-ACR ***,the newly identified inflamed NK cells,CD14+RNASE2+monocytes,and FOS-expressing monocytes emerged as predictive indicators of *** study illuminates the longitudinal evolution of the immune cell landscape under tacrolimus-based immunosuppressive treatment during LT recovery,providing a four-phase framework that aids the clinical management of LT patients.

关键词： process analysis precise

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HepG2.2.15-derived exosomes facilitate the activation and fibrosis of hepatic stellate cells

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World Journal of Gastroenterology 2024年第19期30卷 2553-2563页

作者： Yang Gao Li Li Sheng-Ning Zhang Yuan-Yi Mang Xi-Bing Zhang Shi-Ming Feng Department of hepatobiliary pancreatic and Vascular surgery The Affiliated Calmette Hospital of Kunming Medical University and The First Hospital of KunmingKunming 650011Yunnan ProvinceChina

BACKGROUND The role of exosomes derived from HepG2.2.15 cells,which express hepatitis B virus(HBV)-related proteins,in triggering the activation of LX2 liver stellate cells and promoting liver fibrosis and cell proliferation remains *** focus was on comprehending the relationship and influence of differentially expressed microRNAs(DE-miRNAs)within these *** To elucidate the effect of exosomes derived from HepG2.2.15 cells on the activation of hepatic stellate cell(HSC)LX2 and the progression of liver *** Exosomes from HepG2.2.15 cells,which express HBV-related proteins,were isolated from parental HepG2 and WRL68 *** blotting was used to confirm the presence of the exosomal marker protein *** activation of HSCs was assessed using oil red staining,whereas DiI staining facilitated the observation of exosomal uptake by LX2 ***,we evaluated LX2 cell proliferation and fibrosis marker expression using 5-ethynyl-2′-deoxyuracil staining and western blotting,***-miRNAs were analyzed using *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were used to annotate the target genes of *** Exosomes from HepG2.2.15 cells were found to induced activation and enhanced proliferation and fibrosis in LX2 cells.A total of 27 miRNAs were differentially expressed in exosomes from HepG2.2.15 *** analysis indicated that these DE-miRNA target genes were associated with cell differentiation,intracellular signal transduction,negative regulation of apoptosis,extracellular exosomes,and RNA *** pathway analysis highlighted ubiquitin-mediated proteolysis,the MAPK signaling pathway,viral carcinogenesis,and the toll-like receptor signaling pathway,among others,as enriched in these *** These findings suggest that exosomes from HepG2.2.15 cells play a substantial role in the activation,proliferation,and fibrosis of LX2 cells and that DE-miRNAs within these exos

关键词： Hepatic stellate cells Liver fibrosis Exosomes Small RNA sequencing HepG2.2.15

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Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2-mediated HMGB2 mRNA translation

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Cancer Communications 2024年第9期44卷 1018-1041页

作者： Hailing Liu Lei Xu Shiwei Yue Hongfei Su Xing Chen Qiumeng Liu Hui Li Huifang Liang Xiaoping Chen Jiefeng He Zeyang Ding Bixiang Zhang Hepatic surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Hubei key laboratory of Hepato‑pancreatic‑Biliary Diseases Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Hepatopancreatobiliary surgery Zhejiang Cancer HospitalHangzhou Institute of Medicine(HIM)Chinese Academy of SciencesHangzhouZhejiangP.R.China Department of hepatobiliary pancreatic Tumor Center Chongqing University Cancer HospitalSchool of MedicineChongqing UniversityChongqingP.R.China key laboratory of organ transplantation Ministry of EducationWuhanHubeiP.R.China Department of hepatobiliary surgery Key Laboratory of Hepatobiliary and Pancreatic Diseases of Shanxi Province(Preparatory)Shanxi Bethune HospitalShanxi Academy of Medical SciencesShanxi Medical UniversityTaiyuanShanxiP.R.China

Background:N4-acetylcytidine(ac4C)represents a novel messenger RNA(mRNA)modification,and its associated acetyltransferaseN-acetyltransferase 10(NAT10)plays a crucial role in the initiation and progression of tumors by regulating mRNA ***,its role in hepatocellular carcinoma(HCC)development and prognosis is largely *** study aimed to elucidate the role of NAT10-mediated ac4C in HCC progression and provide a promising therapeutic ***:The ac4C levels were evaluated by dot blot and ultra-performance liquid chromatography-tandem mass spectrometry with harvested HCC *** expression of NAT10 was investigated using quantitative real-time polymerase chain reaction,western blotting,and immunohistochemical staining across 91 cohorts of HCC *** explore the underlying mechanisms of NAT10-ac4C in HCC,we employed a comprehensive approach integrating acetylated RNA immunoprecipitation and sequencing,RNA sequencing and ribosome profiling analyses,along with RNA immunoprecipitation,RNA pulldown,mass spectrometry,and site-specific mutation *** drug affinity responsive targets stability,cellular thermal shift assay,and surface plasmon resonance assays were performed to assess the specific binding of NAT10 and ***,the efficacy of targeting NAT10-ac4C for HCC treatment was elucidated through in vitro experiments using HCC cells and in vivo HCCmouse ***:Our investigation revealed a significant increase in both the ac4C RNA level and NAT10 expression in ***,elevated NAT10 expression was associated with poor outcomes in HCC ***,silencing NAT10 suppressed HCC proliferation and metastasis in vitro and in ***,NAT10 stimulates the ac4C modification within the coding sequence(CDS)of high mobility group protein B2(HMGB2),which subsequently enhances HMGB2 translation by facilitating eukaryotic elongation factor 2(eEF2)binding to the ac4C sites on HMGB2 mRNA’s C

关键词： N4-acetylcytidine N-acetyltransferase 10 hepatocellular carcinoma mRNA translation targeted therapy

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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China key laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The Institute for organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China Institute of organ transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in Liver Transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 Liver diseases mTOR Stress

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