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Overexpression of chaperonin containing TCP1, subunit 3 predicts poor prognosis in hepatocellular carcinoma

World Journal of Gastroenterology 2015年第28期21卷 8588-8604页

作者： Xiao Cui Zhi-Ping Hu Zhao Li Peng-Ji Gao Ji-Ye Zhu Department of Hepatobiliary Surgery Peking University People’s Hospital beijing key Surgical Basic Research laboratory of liver cirrhosis and liver cancer Peking University People’s Hospital

AIM:To investigate the value of chaperonin containing TCP1,subunit 3(CCT3) to predict the prognosis of patients with hepatocellular carcinoma(HCC) and determine its function in HCC ***:CCT3 expression levels were examined in human non-cancerous liver tissues and a variety of HCC cell lines by quantitative real-time PCR and ***3 expression was suppressed by small interfering *** effects of reducing CCT3 expression in HCC cells were ***3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide(MTT) assay,cell counting experiment,cell cycle assay,apoptosis assay and invasion assay were employed to evaluate cell functions in *** was performed on HCC *** addition,CCT3 expression in HCC specimens was also assessed at the protein and mRNA *** between clinicopathological characteristics and prognosis were analyzed,along with the possible mechanisms involved in CCT3's function in HCC ***:The expression levels of CCT3 mRNA and protein were upregulated in HCC cell lines in contrast to adjacent non-cancerous *** CCT3 expression not only suppressed cell proliferation in cell counts,MTT assay,cell cycle assay and induced cell apoptosis(P cancer cells in HCC specimens(58of 104 patients,55.8%) was associated with poor prognosis in HCC patients(3-year survival rate,55.5%vs 84.2%,P = 0.020) after *** analyses showed that signal transducer and activator of transcription 3(STAT3) activation was decreased even when stimulated by interleukin-6 after knocking down CCT3 in the HepG2 cell ***:Overexpression of CCT3 in the nuclei of cancerous cells is associated with HCC ***3 may be a target that affects the activation of STAT3 in HCC.

关键词： Hepatocellular carcinoma Chaperonin ContainingTCP1, Subunit 3 Cell growth Invasion Prognosis

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Pathogenesis of liver cirrhosis

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World Journal of Gastroenterology 2014年第23期20卷 7312-7324页

作者： Wen-Ce Zhou Quan-Bao Zhang Liang Qiao Department of General Surgery Ⅱ the First Hospital of Lanzhou University liver cancer Institute Zhongshan HospitalFudan University and Key Laboratory of Carcinogenesis and Cancer InvasionMinistry of Education Storr liver Unit Westmead Millennium InstituteDepartment of Medicine and Western Clinical Schoolthe University of SydneyWestmeadNSW 2145Australia

liver cirrhosis is the final pathological result of various chronic liver diseases,and fibrosis is the precursor of *** types of cells,cytokines and miRNAs are involved in the initiation and progression of liver fibrosis and *** of hepatic stellate cells(HSCs)is a pivotal event in *** and capillarization of liver sinusoidal endothelial cells are major contributing factors to hepatic dysfunction in liver *** Kupffer cells destroy hepatocytes and stimulate the activation of *** cycles of apoptosis and regeneration of hepatocytes contribute to pathogenesis of *** the molecular level,many cytokines are involved in mediation of signaling pathways that regulate activation of HSCs and ***,miRNAs as a post-transcriptional regulator have been found to play a key role in fibrosis and *** animal models of liver fibrosis and cirrhosis,as well as the recently identified critical cellular and molecular factors involved in the development of liver fibrosis and cirrhosis will facilitate the development of more effective therapeutic approaches for these conditions.

关键词： cirrhosis Pathogenesis Hepatic stellate cells Cytokine miRNA Animal model Therapy

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Differences of core genes in liver fibrosis and hepatocellular carcinoma:Evidence from integrated bioinformatics and immunohistochemical analysis

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World Journal of Gastrointestinal Oncology 2022年第7期14卷 1265-1280页

作者： Yue Li Shou-Li Yuan Jing-Ya Yin Kun Yang Xin-Gang Zhou Wen Xie Qi Wang Department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China beijing key laboratory of Emerging Infectious Diseases Beijing 100015China key laboratory of Animal Ecology and Conservation Biology Institute of ZoologyBeijing 100101China Center of liver Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

BACKGROUND liver fibrosis and hepatocellular carcinoma(HCC)are common adverse consequences of chronic liver *** interaction of various risk factors may cause them to *** of specific biomarkers is of great significance for understanding the occurrence,development mechanisms,and determining the novel tools for diagnosis and treatment of both liver fibrosis and *** To identify liver fibrosis-related core genes,we analyzed the differential expression pattern of core genes in liver fibrosis and *** Gene expression profiles of three datasets,GSE14323,GSE36411,and GSE89377,obtained from the Gene Expression Omnibus(GEO)database,were analyzed,and differentially expressed genes(DEGs)between patients with liver cirrhosis and healthy controls were identified by screening via R software packages and online tool for Venn *** WebGestalt online tool was used to identify DEGs enriched in biological processes,molecular functions,cellular components,and Kyoto Encyclopedia of Genes and Genomes *** protein–protein interactions of DEGs were visualized using Cytoscape with ***,the expression pattern of core genes was analyzed using Western blot and immunohistochemistry in a carbon tetrachloride(CCl_(4))-induced liver cirrhosis mouse model and in patient liver ***,Kaplan-Meier curves were constructed using the Kaplan-Meier plotter online *** Forty-five DEGs(43 upregulated and 2 downregulated genes)associated with liver cirrhosis were identified from three GEO *** hub genes were identified,which were upregulated in liver *** blot and immunohistochemical analyses of the three core genes,decorin(DCN),dermatopontin(DPT),and SRY-box transcription factor 9(SOX9),revealed that they were highly expressed in the CCl4-induced liver cirrhosis mouse *** expression levels of DCN and SOX 9 were positively correlated with the degree of fibrosis,and SOX 9 level in HCC patients was significant

关键词： liver cirrhosis Hepatocellular carcinoma Bioinformatical analysis Decorin Dermatopontin SRY-box transcription factor 9

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Serum vascular endothelial growth factor is a potential biomarker of metastatic recurrence after curative resection of hepatocellular carcinoma

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World Journal of Gastroenterology 2000年第4期6卷 565-568页

作者： Qi Niu Zhao You Tang Zeng Chen Ma Lun Xiu Qin Lian Hai Zhang liver cancer Institute&Zhongshan Hospital Shanghai Medical UniversityShanghai 200032China

Hepatocellular carcinoma (HCC) is one of the most common malignancies in China. To date, surgery is still the best solution to it. However, metastatic recurrences after curative hepatic resections are very common. Tang et al have reported that recurrence rate within 5 years of curative hepatic resection is 61.5% [1]. As curative hepatic resection has a high tendency for metastatic recurrence, therapeutic interventions such as transarterial embolization and antiangiogenesis have been tried to further improve prognosis of HCC patients. Therefore, establishing a dependable, sensitive, easy, and economical method to predict metastatic recurrence following curative hepatic resection is of clinical urgency.

关键词： endothelium vascular endothelial growth factor carcinoma hepatocellular enzyme-linked immunosorbent assay liver neoplasms liver cirrhosis immunohistochemistry

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Circulating cell-free DNA for cancer early detection

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The Innovation 2022年第4期3卷 44-60页

作者： Qiang Gao Qiang Zeng Zhijie Wang Chengcheng Li Yu Xu Peng Cui Xin Zhu Huafei Lu Guoqiang Wang Shangli Cai Jie Wang Jia Fan Department of liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationFudan UniversityShanghai 200032China key laboratory of Medical Epigenetics and Metabolism Institutes of Biomedical SciencesFudan UniversityShanghai 200032China Health Management Institute The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China State key laboratory of Molecular Oncology Department of Medical OncologyNational Cancer Center/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100006China Burning Rock Biotech Guangzhou 510320China

Effective screening modalities are currently available for only a small subset of cancers,and they generally have suboptimal performance with complicated ***,there is an urgent need to develop simple,accurate,and non-invasive methods for early detection of *** and epigenetic alterations in plasma circulating cell-free DNA(cfDNA)have shown the potential to revolutionize methods of early detection of cancers and facilitate subsequent diagnosis to improve survival of *** medical interest in cfDNA assays has been inspired by emerging single-and multi-early detection of cancers *** review summarizes current technological and clinical advances,in the hopes of providing insights into the development and applications of cfDNA assays in various cancers and clinical *** key phases of clinical development of biomarkers are highlighted,and the future developments of cfDNA-based liquid biopsies in early detection of cancers are *** is hoped that this study can boost the potential integration of cfDNA-based early detection of cancers into the current clinical workflow.

关键词： alterations diagnosis subsequent

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Hepatocellular Carcinoma Risk Scores from Modeling to Real Clinical Practice in Areas Highly Endemic for Hepatitis B Infection

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Journal of Clinical and Translational Hepatology 2023年第7期11卷 1508-1519页

作者： Xin Hao Rong Fan Hong-Mei Zeng Jin-Lin Hou Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityState Key Laboratory of Organ Failure ResearchGuangdong Provincial Key Laboratory of Viral Hepatitis ResearchGuangdong Provincial Institute of Liver DiseasesGuangzhouGuangdongChina National cancer Center/National Clinical Research Center for cancer/cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Hepatocellular carcinoma(HCC)accounts for the majority of primary liver cancers and represents a global health *** cancer ranks third in cancer-related mortality with 830,000 deaths and sixth in incidence with 906,000 new cases annually *** most commonly occurs in patients with underlying liver disease,especially chronic hepatitis B virus(HBV)infection in highly endemic *** HCC risk based on scoring models for patients with chronic liver disease is a simple,effective strategy for identifying and stratifying patients to improve the early diagnosis rate and prognosis of *** examined 23 HCC risk scores published worldwide in CHB patients with(n=10)or without(n=13)antiviral *** also described the characteristics of the risk score’s predictive performance and application *** the future,higher predictive accuracy could be achieved by combining novel technologies and machine learning algorithms to develop and update HCC risk score models and integrated early warning and diagnosis systems for HCC in hospitals and communities.

关键词： Hepatocellular carcinoma Chronic hepatitis B HCC risk score HCC screening

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Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients

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World Journal of Hepatology 2024年第10期16卷 1158-1168页

作者： Wei-Hua Cao Ya-Qin Zhang Xin-Xin Li Zi-Yu Zhang Ming-Hui Li Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityPeking University Ditan Teaching HospitalBeijing 100015China

Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and ***,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in *** to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various *** recent years,the systematic treatment of HCC has gradually come out of the *** addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of *** present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese ***,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide *** review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy str

关键词： Hepatitis B virus Hepatocellular carcinoma Immune checkpoint inhibitors Peginterferon alpha Systematic treatment

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Baseline Hepatitis B Virus DNA Level is a Promising Factor for Predicting the 3^rd Month Virological Response to Entecavir Therapy： A Study of Strict Defined Hepatitis B virus Induced cirrhosis

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Chinese Medical Journal 2015年第14期128卷 1867-1872页

作者： Yang Xu Xiao-Ning Wu Yi-Wen Shi Wei Wei Ai-Ting Yang Ya-Meng Sun Wen-Shan Zhao Hong You Department of liver Research Center Beijing Friendship Hospital Capital Medical University Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis and National Clinical Research Center of Digestive Diseases Beijing 100050 China Clinical Epidemiology and Evidence-based Medicine Center Beijing Friendship Hospital Capital Medical University Beijing 100050 China

Background： cirrhosis is a common complication of chronic hepatitis B. It remains unclear if viral and biochemical parameters at baseline affect virological response to entecavir and therefore warrant investigation. In the present study, we aimed to eval uate the efficacy of entecavir therapy by monitoring virological response at the end of the 3^rd month of treatment and try to figure out whether baseline factors could help predict it in a cohort of hepatitis B virus （HBV） compensated cirrhosis patients and to determine the cut-off value of a predicting parameter.Methods： A total of 91 nucleos（t）ide-naive patients with HBV induced cirrhosis （compensatory stage） were enrolled in a prospective cohort. HBV DNA and alanine aminotransferase （ALT） were tested at baseline and monitored every 3-6 months after starting therapy. Results： Of all 91 patients, the median follow-up time was 12 （9-24） months. Overall, 64 patients （70.3%） achieved virological response in the 3^rd month. Univariate analysis showed that the 3^rd month virological response can be predicted by baseline HBV DNA levels （P 〈 0.001, odds ratio [OR]： 2.13, 95% confidence interval [CI]： 1.44-3.15）, ALT value （P = 0.023, OR： 1.01, 95% CI： 1.00 1.01 ） and hepatitis B e antigen （HBeAg） negativity （P = 0.016, OR： 0.30, 95% CI： 0.11-0.80）. Multiple regression analysis showed baseline H BV DNA level was the only parameter related to full virological response. Higher baseline HBV DNA strata indicated a higher probability that HBV DNA remains detectable at the 3^rd month （P = 0.001）. Area under receiver operating characteristic curve for determining the 3^rd month virological response by baseline HBV DNA was 77.6% （95% CI： 66.7-85.2%）, with a best cut-offvalue of 5.8 log10. Conclusions： Baseline HBV DNA, HBeAg negativity, and ALT were independent factors contributing to virological response at the 3^rt month. Further, multiple regression showed that HBV DNA level was the only parameter predicting full virolog

关键词： Area Under Receiver Operating Characteristic Curve Baseline Parameters cirrhosis Entecavir Hepatitis B viral

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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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The role of roof plate-specific spondins in liver homeostasis and disease

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liver Research 2022年第3期6卷 139-145页

作者： Le Yang Wenhui Yue Hang Zhang Yue Gao Lin Yang Liying Li Department of Cell Biology Municipal Laboratory for Liver Protection and Regulation of RegenerationCapital Medical UniversityBeijingChina

As evolutionarily conserved signals,roof plate-specific spondins(R-spondins;RSPOs)are a family with four members(RSPO1e4)exerting distinctly different *** have five receptors and correlate with different signaling pathways through these receptors and then perform various ***,their best-known molecular function is the capacity to enhance WNT signaling pathways,which play critical roles in several processes.A recent study shows that RSPOs not only potentiate the WNT/beta(b)-catenin signaling pathway but are also involved in the WNT/planar cell polarity signaling *** influence liver homeostasis and the development of multiple liver ***1 increases cell proliferation,protects hepatocytes from injury,improves liver regenerative potential,and affects liver metabolic ***2 not only regulates proliferation-associated genes and promotes differentiation in the liver but also participates in liver fibrosis through the WNT/b-catenin signaling ***3 is a key determinant of proper liver function,such as promoting hepatocyte regeneration and maintaining liver ***3 is upregulated in liver fibrosis and livers of patients with nonalcoholic ***,RSPO2 and RSPO3 are confirmed as oncogenes and involved in the occurrence of liver *** role of RSPO4 in the liver remains *** this review,the structural and biochemical properties of RSPOs and their receptors and their roles in liver homeostasis and disease are summarized.

关键词： Roof plate-specific spondin(RSPO) Leucine-rich repeat-containing G-proteincoupled receptor(LGR) Zinc and ring finger 3(ZNRF3) Ring finger protein 43(RNF43) WNT signaling pathway liver homeostasis liver fibrosis liver cancer

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