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Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & Diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li department of Infectious Diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key Laboratory for diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the *** tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP *** of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver *** DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B *** herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver *** review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases Liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

Development of a prognostic scoring system for hepatic vena cava Budd-Chiari syndrome with hepatocellular carcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 370-375页

作者： Sheng-Yan Liu Lu-Hao Li Zhao-Chen Liu Su-Xin Li Xiao-Wei Dang department of Hepatopancreatobiliary Surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Budd-Chiari Syndrome diagnosis and Treatment Center of Henan Province Zhengzhou 450052China

Background:Hepatocellular carcinoma(HCC)is a serious complication of hepatic vena cava Budd-Chiari syndrome(HVC-BCS)that significantly reduces the survival time of *** study aimed to analyze the prognostic factors influencing the survival of HVC-BCS patients with HCC and to develop a prognostic scoring ***:The clinical and follow-up data of 64 HVC-BCS patients with HCC who received invasive treatment at the First Affiliated Hospital of Zhengzhou University between January 2015 and December 2019 were retrospectively ***-Meier curves and log-rank tests were used to analyze the survival curve of patients and the difference in prognoses between the *** and multivariate Cox regression analyses were performed to analyze the influence of biochemical,tumor,and etiological characteristics on the total survival time of patients,and a new prognostic scoring system was developed according to the regression coefficients of the independent predictors in the statistical *** prediction efficiency was evaluated using the time-dependent receiver operating characteristics curve and concordance ***:Multivariate analysis showed that serum albumin level7 cm(HR=8.623,95%CI:3.771-19.715,P<0.001),and inferior vena cava stenosis(HR=3.612,95%CI:1.646-7.928,P=0.001)were independent predictors of survival.A prognostic scoring system was developed according to the above-mentioned independent predictors,and patients were classified into grades A,B,C and *** differences in survival were found among the four ***:This study successfully developed a prognostic scoring system for HVC-BCS patients with HCC,which is helpful for clinical evaluation of patient prognosis.

关键词： Budd-Chiari syndrome Hepatocellular carcinoma Prognostic factors Inferior vena cava stenosis Prognostic scoring system

Advances in the Treatment of Autoimmune Hepatitis

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 878-885页

作者： Zelu Meng Yida Yang State Key Laboratory for diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesDepartment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

Autoimmune hepatitis(AIH)is a chronic,progressive inflammatory liver disease caused by autoimmune reactions,with an unknown *** left untreated,it can progress to cirrhosis,liver failure,or even *** most patients respond well to first-line treatments,a significant number experience poor responses or intolerance,requiring the use of second-or third-line *** research into the pathogenesis of AIH is leading to the development of novel therapeutic *** review summarized recent advancements in the treatment of AIH both domestically and internationally.

关键词： Hepatitis,Autoimmune Immunosuppression Treatment Management Update Remission Induction Long-term Prognosis

pH-controlled reversible sol-gel inversion by cerous phosphate nanofibers for hemostasis

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Rare Metals 2024年第10期43卷 5141-5151页

作者： Tuo Su Jun-Chen Xu Wei Yu Dan Su Di-Er Shi Yi-Chao Pang Yao Ying Wang-Chang Li Juan Li Jing-Wu Zheng Liang Qiao Sheng-Lei Che Jing Yu Research Center of Magnetic and Electronic Materials College of Materials Science and EngineeringZhejiang University of Technology State Key Laboratory for diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang University Key Laboratory of Drug Safety Evaluation and Research of Zhejiang Province Department of Clinical MedicineHangzhou Medical College department of Chemistry Zhejiang University Clinical Medical College Yangzhou University

Developing biomimetic soft materials that display stimuli responsiveness using solely inorganic materials has been regarded as a challenge owing to that such materials?properties typically vary from those of living ***,biomimetic soft materials have been developed using organic materials or inorganic materials modified with organic small *** this study,we prepared cerium phosphate nanofibers （CePO4NFs） by using inorganic agents only without further *** CePO4NFs demonstrate sol-ge switching properties in response to pH value,allowing them to form a gel under high hydroxide ion （OH-） concentrations and turn back into sol under low *** formation of gel could be ascribed to the physical cross-linking of the nanofibers induced by the attractive electrostatic force of OH-and surface Ce3+.As a result,CePO4NFs are able to form a gel when in contac with blood of high pH value for *** specific clotting mechanism makes them better candidates for hemostasis of heavy bleeding.

关键词： Cerium phosphate nanofibers Hemostasis pH-responsive Reversible Sol-gel switching

Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer

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World Journal of Clinical Cases 2024年第4期12卷 700-720页

作者： Zi-Zheng Wu Yuan-Jun Wei Tong Li Jie Zheng Yin-Feng Liu Meng Han diagnosis and Treatment Center The First Hospital of QinhuangdaoQinhuangdao 066000Hebei ProvinceChina department of General Surgery Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina Breast Disease diagnosis and Treatment Center The First Hospital of QinhuangdaoHebei Medical UniversityQinhuangdao 066000Hebei ProvinceChina Breast Disease diagnosis and Treatment Center Chengde Medical CollegeChengde 067000Hebei ProvinceChina

BACKGROUND Breast cancer(BC),a leading malignant disease,affects women all over the *** associated fibroblasts(CAFs)stimulate epithelial-mesenchymal transition,and induce chemoresistance and *** To establish a CAFs-associated prognostic signature to improve BC patient out-come *** We retrieved the transcript profile and clinical data of 1072 BC samples from The Cancer Genome Atlas(TCGA)databases,and 3661 BC samples from the The Gene Expression *** and immune cell infiltrations were quantified using CIBERSORT ***-associated gene identification was done by weighted gene co-expression network analysis.A CAF risk signature was established via univariate,least absolute shrinkage and selection operator regression,and mul-tivariate Cox regression *** receiver operating characteristic(ROC)and Kaplan-Meier curves were employed to evaluate the predictability of the ***,a nomogram was developed with the risk score and patient clinical *** Spearman's correlations analysis,the relationship between CAF risk score and gene set enrichment scores were *** samples were collected to validate gene expression by quantitative real-time polymerase chain reaction(qRT-PCR).RESULTS Employing an 8-gene(IL18,MYD88,GLIPR1,TNN,BHLHE41,DNAJB5,FKBP14,and XG)signature,we attemp-ted to estimate BC patient *** on our analysis,high-risk patients exhibited worse outcomes than low-risk *** analysis revealed the risk score as an independent indicator of BC patient *** analysis exhibited satisfactory nomogram *** area under the curve showed 0.805 at 3 years,and 0.801 at 5 years in the TCGA *** also demonstrated that a reduced CAF risk score was strongly associated with enhanced chemotherapeutic *** risk score was significantly correlated with most hallmark gene ***,the prognostic signature were further validated by qRT-

关键词： Breast cancer Prognosis Gene signature The Cancer Genome Atlas The Gene Expression Omnibus

Polylactic acid micro/nanoplastic-induced hepatotoxicity: Investigating food and air sources via multi-omics

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Environmental Science and Ecotechnology 2024年第5期21卷 294-308页

作者： Hua Zha Shengyi Han Ruiqi Tang Dan Cao Kevin Chang Lanjuan Li State Key Laboratory for diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouChina department of Statistics The University of AucklandAucklandNew Zealand

Micro/nanoplastics(MNPs)are detected in human liver,and pose significant risks to human *** exposure to MNPs derived from non-biodegradable plastics can induce toxicity in mouse ***,nasal exposure to non-biodegradable plastics can cause airway dysbiosis in ***,the hepatotoxicity induced by foodborne and airborne biodegradable MNPs remains poorly *** we show the hepatotoxic effects of biodegradable polylactic acid(PLA)MNPs through multi-omics analysis of various biological samples from mice,including gut,fecal,nasal,lung,liver,and blood *** results show that both foodborne and airborne PLA MNPs compromise liver function,disrupt serum antioxidant activity,and cause liver ***,foodborne MNPs lead to gut microbial dysbiosis,metabolic alterations in the gut and serum,and liver transcriptomic *** MNPs affect nasal and lung microbiota,alter lung and serum metabolites,and disrupt liver *** gut Lachnospiraceae_NK4A136_group is a potential biomarker for foodborne PLA MNP exposure,while nasal unclassified_Muribaculaceae and lung Klebsiella are potential biomarkers for airborne PLA MNP *** relevant results suggest that foodborne PLA MNPs could affect the“gut microbiota-gutliver”axis and induce hepatoxicity,while airborne PLA MNPs could disrupt the“airway microbiota-lungliver”axis and cause *** findings have implications for diagnosing PLA MNPs-induced hepatotoxicity and managing biodegradable materials in the *** current study could be a starting point for biodegradable MNPs-induced *** research is needed to verify and inhibit the pathways that are crucial to MNPs-induced hepatotoxicity.

关键词： Micro/nanoplastics Hepatotoxicity Microbiota dysbiosis Metabolic disruption Transcriptomic dysregulation

Causal Relationship Between Gut Microbiota and Liver Cirrhosis:16S rRNA Sequencing and Mendelian Randomization Analyses

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 123-133页

作者： Mengqin Yuan Xue Hu Lichao Yao Ping Chen Zheng Wang Pingji Liu Zhiyu Xiong Yingan Jiang Lanjuan Li department of Infectious Diseases Renmin Hospital of Wuhan UniversityWuhanHubeiChina State Key Laboratory for diagnosis and Treatment of Infectious Diseases National Clinical Research Centre for Infectious DiseasesCollaborative Innovation Centre for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

Background and Aims:Accumulating evidence highlights the association between the gut microbiota and liver ***,the role of the gut microbiota in liver cirrhosis remains ***:We first assessed the differences in the composition of the bacterial community between CCl4-induced liver cirrhosis and control mice using 16S rRNA *** then performed a two-sample Mendelian randomization(MR)analysis to reveal the underlying causal relationship between the gut microbiota and liver *** relationships were analyzed using primary inverse variance weighting(IVW)and other supplemental MR ***,fecal samples from liver cirrhosis patients and healthy controls were collected to validate the results of the MR ***:Analysis of 16S rRNA sequencing indicated significant differences in gut microbiota composition between the cirrhosis and control *** analyses suggested that Alphaproteobacteria,Bacillales,NB1n,Rhodospirillales,Dorea,Lachnospiraceae,and Rhodospirillaceae were positively correlated with the risk of liver cirrhosis,whereas Butyricicoccus,Hungatella,Marvinbryantia,and Lactobacillaceae displayed the opposite ***,the weighted median and MR-PRESSO estimates further showed that only Butyricicoccus and Marvinbryantia presented stable negative associations with liver *** significant heterogeneity or horizontal pleiotropy was observed in the sensitivity ***,the result of 16S rRNA sequencing also showed that healthy controls had a higher relative abundance of Butyricicoccus and Marvinbryantia than liver cirrhosis ***:Our study provides new causal evidence for the link between gut microbiota and liver cirrhosis,which may contribute to the discovery of novel strategies to prevent liver cirrhosis.

关键词： 16S rRNA gene sequencing Liver cirrhosis Gut microbiota Causality Two-sample Mendelian randomization study

Intracellular RNA Labeling Technologies for the Analysis of RNA Biology

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Chinese Journal of Chemistry 2024年第7期42卷 790-801页

作者： Ruiqi Zhao Xin Fang Xiaocheng Weng department of Clinical Laboratory Center for Gene DiagnosisDepartment of NeurosurgeryZhongnan Hospital of Wuhan UniversityWuhanHubei 430071China College of Chemistryand Molecular Sciences Key Laboratory of Biomedical Polymers-Ministry of EducationWuhan UniversityWuhan Hubei 430072China

As a cornerstone of the central dogma of molecular biology,RNA plays vital roles in living *** the past few decades,many RNA labeling technologies have been developed to elucidate the biological function of *** technologies have signifi-cantly advanced our understanding of RNA secondary structure,localization,and ***,taking advantage of these innovative RNA labeling approaches,plenty of tool kits have been devised for the regulation of RNA-related biological process,such as gene expression and gene *** this review,we primarily focus on an array of intracellular RNA labeling methods,encom-passing chemical probes-based labeling,metabolic labeling,and proximity-dependent *** also provide a brief overview of their applications in the research of RNA ***,the perspectives of RNA labeling are also discussed.

关键词： RNA Chemical probes Metabolic labeling Proximity-dependent labeling RNA structures Gene sequencing RNA recognition

Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive ***,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut *** liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse *** metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC *** abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in *** on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were *** increased abundance of *** and depletion of *** may be hallmarks of the progression of liver cirrhosis to early ***,the administration of *** and *** in the LC-HCC progression could accelerate or retard the progression of ***,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker