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Expression of HLA-G in patients with hepatocellular carcinoma

hepatobiliary & pancreatic Diseases International 2011年第2期10卷 158-163页

作者： Yan Wang,Zhou Ye,Xue-Qin Meng and Shu-Sen ZhengDivision of hepatobiliary and pancreatic surgery key laboratory of Combined Multi-organ transplantation,Ministry of Public Health and key laboratory of organ transplantation Zhejiang province, First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China Division of hepatobiliary and pancreatic surgery key laboratory of Combined Multi-organ transplantation Ministry of Public Health and key laboratory of organ transplantation Zhejiang province First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Human leukocyte antigen G(HLA-G)is a non-classical major histocompatibility complex class I molecule that has multiple immune regulatory functions including the induction of immune *** detection of HLA-G expression might serve as a clinical marker in the prediction of clinical outcomes for certain types of ***, we investigated whether or not HLA-G is also expressed in patients with hepatocellular carcinoma(HCC),and whether the expression has clinical value. METHODS:Serum levels of secreted HLA-G(sHLA-G)were measured by ELISA in 36 patients with HCC,25 patients with liver cirrhosis(LC)and 25 healthy *** expression of HLA-G in liver tissue was further studied using Western blotting in 36 patients with HCC and 25 with *** correlations between HLA-G status and various clinicopathological parameters including survival were analyzed. RESULTS:The ELISA assay showed that the serum levels of sHLA-G in the HCC,LC and healthy groups were 132.6± 31.4,63.5±22.1,and 47.0±15.5 U/ml,*** of variance was used for inter-group comparison and differences were found between the HCC group and the other two groups (both P<0.01),while no difference was found between the LC group and the healthy group(P=0.112).HLA-G protein expression in liver tissue was found in 66.7%(24/36)of the primary sites of HCC,but not in benign lesions(LC). Further,the HLA-G expression in tumors had no significant correlation with the parameters of age,gender,histological grade and alpha-fetoprotein ***,patients with HLA-G-positive tumors had a shorter postoperative survival time than those with HLA-G-negative tumors(P=0.014).Also, univariate analysis showed that HLA-G was an independent prognostic ***:Our results indicated that the expression of HLA-G was a characteristic feature of HCC and patients with positive expression of HLA-G in malignant liver tissue had a poor prognosis.

关键词： human leukocyte antigen G hepatocellular carcinoma prognosis

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Evaluation of hepatitis B viral replication and proteomic analysis of HepG2.2.15 cell line after knockdown of HBx

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hepatobiliary & pancreatic Diseases International 2011年第3期10卷 295-302页

作者： Hai-Yang Xie,Jun Cheng,Chun-Yang Xing,Jin-Jin Wang,Rong Su,Xu-Yong Wei,Lin Zhou and Shu-Sen Zheng Author Affiliations:key laboratory of Combined Multi-organ transplantation,Ministry of Public Health key laboratory of organ transplantation Zhejiang province and Division of hepatobiliary and pancreatic surgery,Department of surgery,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China key laboratory of Combined Multi-organ transplantation Ministry of Public Health key laboratory of organ transplantation Zhejiang province and Division of hepatobiliary and pancreatic surgery Department of Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Hepatitis B virus (HBV) is one of the major pathogens of human liver *** have shown that HBV X protein (HBx) plays an important role in promoting viral gene expression and *** this study we performed a global proteomic profiling to identify the downstream functional proteins of HBx,thereby detecting the mechanisms of action of HBx on virion ***:HBx in the HepG2.2.15 cell line was knocked down by the transfection of small interfering RNA (siRNA).The replication level of HBV was evaluated by microparticle enzyme immunoassay analysis of HBsAg and HBeAg in the culture supernatant,and real-time quantitative PCR analysis of HBV ***-dimensional electrophoresis combined with MALDI-TOF/TOF was performed to analyze the changes in protein expression profile after treatment with HBx ***:Knockdown of HBx disturbed HBV replication in *** target siRNA significantly inhibited the expression of HBsAg,HBeAg and the replication of HBV *** significantly changed proteins (7 upregulated and 5 downregulated) were successfully identified by MALDI-TOF/TOF using proteomics differential expression analysis after the knockdown of *** these identified proteins,HSP70 was validated by Western ***:The results of the study indicated the positive effect of HBx on HBV replication,and a group of downstream target proteins of HBx may be responsible for this effect.

关键词： hepatitis B virus HBx replication proteomics

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C–C motif chemokine ligand 16 inhibits the progression of liver cirrhosis via inactivating hepatic stellate cells

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hepatobiliary & pancreatic Diseases International 2020年第5期19卷 440-448页

作者： Jian-Yong Zhuo Di Lu Zu-Yuan Lin Bei-Ni Cen Xu-Yong Wei Hai-Yang Xie Shu-Sen Zheng Xiao Xu Department of hepatobiliary and pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China NHC key laboratory of Combined Multi-organ transplantation Key Laboratory of the Diagnosis and Treatment of Organ TransplantationCAMSHangzhou 310003China Department of hepatobiliary and pancreatic surgery Shulan(Hangzhou)HospitalHangzhou 310003China

Background:Liver cirrhosis results from many forms of chronic damage,characterized by accumulation of extracellular *** present study aimed to explore a potential non-invasive biomarker and its mechanism in the progression of liver ***:Gene Expression Omnibus(GEO)dataset(GSE15654,n=216)was analyzed to screen genes associated with progression of liver cirrhosis.A total of 181 plasma samples,including healthy control(HC,n=20),chronic hepatitis B(CHB,n=77)and HBV-related liver cirrhosis(LC,n=84),were enrolled for *** vitro and in vivo experiments were employed for the mechanistic ***:GEO dataset analysis showed that relatively low mRNA-expression of C–C motif chemokine ligand 16(CCL16)was associated with elevated Child-Pugh score(P=0.034)and worse prognosis(P=0.025).Plasma CCL16 level decreased in a stepwise pattern,with a median concentration of 10.29,6.57 and 4.47 ng/mL in the HC,CHB and LC groups,respectively(P<0.001).Low plasma CCL16 was significantly related to hepatic dysfunction both in the CHB and LC groups(P<0.05).Combination of CCL16 and ALT showed improved distinguishing capability for LC compared to either *** vitro,CCL16 expression was downregulated by lipopolysaccharide and *** of CCL16 from human normal liver cell line(LO2)reduced the extracellular matrix associated proteins(Col1 and Col4)in human hepatic stellate cell line(LX-2).In vivo,the pathological feature of cirrhosis was alleviated by the hepatocytespecific expression of ***:CCL16 could be a feasible plasma marker to predict the occurrence and progression of liver ***16 might impact liver cirrhosis through inactivating hepatic stellate cells.

关键词： C-C motif chemokine ligand 16 Liver cirrhosis Hepatitis B virus infection

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Romidepsin(FK228) improves the survival of allogeneic skin grafts through downregulating the production of donor-specific antibody via suppressing the IRE1α-XBP1 pathway

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2022年第5期23卷 392-406页

作者： Yuliang GUO Siyu SONG Xiaoxiao DU Li TIAN Man ZHANG Hongmin ZHOU Zhonghua Klaus CHEN Sheng CHANG Institute of organ transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China key laboratory of organ transplantation Ministry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhan 430030China henan key laboratory of digestive organ transplantation Open and Key Laboratory of Hepatobiliary&Pancreatic Surgery and Digestive Organ Transplantation at Henan UniversitiesZhengzhou Key Laboratory of Hepatobiliary&Pancreatic Diseases and Organ TransplantationDepartment of Hepatobiliary and Pancreatic Surgerythe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Cardiothoracic and Vascular surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Antibody-mediated rejection(AMR)is one of the major causes of graft loss after ***,the regulation of B cell differentiation and the prevention of donor-specific antibody(DSA)production have gained increased attention in transplant ***,we established a secondary allogeneic in vivo skin transplant model to study the effects of romidepsin(FK228)on *** survival of grafted skins was monitored *** serum levels of DSA and the number of relevant immunocytes in the recipient spleens were evaluated by flow ***,we isolated and purified B cells from B6mouse spleens in vitro by magnetic bead *** B cells were cultured with interleukin-4(IL-4)and anti-clusters of differentiation 40(CD40)antibody with or without FK228 *** immunoglobulin G1(IgG1)and IgM levels in the supernatant were evaluated by enzyme-linked immunosorbent assay(ELISA).Quantitative reverse transcription-polymerase chain reaction(RT-q PCR)and western blotting were conducted to determine the corresponding levels of messenger RNA(mRNA)and protein expression in cultured cells and the recipient *** results showed that FK228 significantly improved the survival of allogeneic skin ***,FK228 inhibited DSA production in the serum along with the suppression of histone deacetylase 1(HADC1)and HDAC2 and the upregulation of the acetylation of histones H2A and *** also inhibited the differentiation of B cells to plasma cells,decreased the transcription of positive regulatory domain-containing 1(Prdm1)and X-box-binding protein 1(Xbp1),and decreased the expression of phosphorylated inositol-requiring enzyme 1α(p-IRE1α),XBP1,and B lymphocyte-induced maturation protein-1(Blimp-1).In conclusion,FK228 could decrease the production of antibodies by B cells via inhibition of the IRE1α-XBP1 signaling ***,FK228 is considered as a promising therapeutic agent for the clinical treatment of AMR.

关键词： Histone acetylation Romidepsin(FK228) Skin transplantation Donor-specific antibody Unfolded protein response

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Risk factors and incidence of acute pyogenic cholangitis

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hepatobiliary & pancreatic Diseases International 2012年第6期11卷 650-654页

作者： Yun-Sheng Qin, Qi-Yong Li, Fu-Chun Yang , Shu-Sen Zheng Division of hepatobiliary and pancreatic surgery key laboratory of Combined Multi-organ transplantation, Ministry of Public Health key laboratory of organ transplantation Zhejiang province, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China Division of hepatobiliary and pancreatic surgery key laboratory of Combined Multi-organ transplantation Ministry of Public Health and key laboratory of organ transplantation Zhejiang province First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND: Acute cholangitis varies from mild to severe form. Acute suppurative cholangitis (ASC), the severe form of acute cholangitis, is a fatal disease and requires urgent biliary decompression. Which patients are at a high risk of ASC and need emergency drainage is still unclear. The present study aimed to identify the factors for determining early-stage ASC and distinguishing ASC from acute cholangitis. METHODS: We analyzed 359 consecutive patients with acute cholangitis who had been admitted to the First Affiliated Hospital, Zhejiang University School of Medicine from January 2004 to May 2011. Emergency endoscopic retrograde cholangiopancreatography (ERCP) was carried out in all patients to decompress or clear the stones by experienced endoscopists Clinical and therapeutic data were collected, and univariate and multivariate analyses were performed to identify the potential risk factors of ASC. RESULTS: Of the 359 patients, 1 was excluded because of failure of ERCP drainage. Of the remaining 358 patients with an average age of 62.7 years (range 17-90), 162 were diagnosed with ASC, and 196 with non-ASC. ENBD catheters were placed in 343 patients (95.8%), of whom 182 patients had stones removed at the same time, and plastic stent was placed in 25 patients (7.0%) Clinical conditions were improved quickly after emergency biliary drainage in all patients. Complications were identified in 11 patients (3.1%): mild pancreatitis occurred in 8 patients and hemorrhage in 3 patients. There was no mortality. Univariate analysis showed that several variables were associated with ASC: age, fever, decreased urine output, hypotension, tachycardia abnormal white blood cell count (WBC), low platelet, high C reactive protein (CRP), and duration of the disease. Multivariateanalysis revealed that advanced age, hypotension, abnormal WBC, high CRP, and duration of the disease were independent risk factors for ASC. CONCLUSIONS: This study demonstrates that advanced age, hypotension,

关键词： acute cholangitis suppurative endoscopic retrograde cholangiopancreatography

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Liver protection strategies in liver transplantation

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hepatobiliary & pancreatic Diseases International 2015年第1期14卷 34-42页

作者： Jun-Jun Jia Jian-Hui Li Li Jiang Bin-Yi Lin Li Wang Rong Su Lin Zhou Shu-Sen Zheng key laboratory of Combined Multi-organ transplantation Ministry of Health Department of hepatobiliary and pancreatic surgery First Affiliated Hospital Zhejiang University School of Medicine

BACKGROUND： Liver transplantation is the therapy of choice for patients with end-stage liver diseases. However, the gap between the low availability of organs and high demand is continuously increasing. Innovative strategies for organ protection are necessary to expand donor pool and to achieve better outcomes for liver transplantation. The present review analyzed and compared various strategies of liver *** SOURCES： Databases such as PubM ed, Embase and Ovid were searched for the literature related to donor liver protection strategies using following key words：＂ischemia reperfusion injury＂, ＂graft preservation＂, ＂liver transplantation＂, ＂machine perfusion＂ and ＂conditioning＂. Of the 146 studies identified,only those with cutting edge strategies were ***： A variety of therapeutic approaches were proposed to alleviate graft ischemia/reperfusion injury, which included static cold storage, machine perfusion （hypothermic, normothermic and subnormothermic）, manual conditioning （pre,post and remote）, and pharmacological conditioning. Evidences from animal experiments and clinical trials suggested that all these strategies could potentially protect liver graft; however, their clinical applications are limited partially due to their own ***： There are a plenty of methods suggested to decrease the degree of donor liver transplantation-related injury. However, none of these approaches is perfect in clinical practice. More translational researches （molecular and clinical studies） are needed to improve the techniques in liver graft protection.

关键词： ischemia reperfusion injury liver transplantation organ protection conditioning

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Oncogenic role of microRNA-423-5p in hepatocellular carcinoma

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hepatobiliary & pancreatic Diseases International 2015年第6期14卷 613-618页

作者： Li-Ming Wu Jian-Song Ji Zhe Yang Chun-Yang Xing Ting-Ting Pan Hai-Yang Xie Feng Zhang Li Zhuang Lin Zhou Shu-Sen Zheng Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases key laboratory of Combined Multi-organ transplantation Ministry of Public Health key laboratory of organ transplantation of Zhejiang province Division of hepatobiliary and pancreatic surgery First Affiliated HospitalZhejiang University School of Medicine Lishui Hospital of Zhejiang University

BACKGROUND： It has been found that microRNA-423-5p （miR423-Sp） is an oncogenic factor and frequently upregulated in gastric carcinoma. However, the involvement of miR423- 5p in hepatocellular carcinoma （HCC） has been rarely reported. The aim of this study was to assess whether miR423-Sp is aberrantly expressed in HCC tissues, and to characterize its roles in the cancerous biology of HCC.

关键词： hepatocellular carcinoma miR423-5p proliferation invasion oncogene

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Targeting tumor-associated macrophages to synergize tumor immunotherapy

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Signal Transduction and Targeted Therapy 2021年第3期6卷 795-806页

作者： Xiaonan Xiang Jianguo Wang Di Lu Xiao Xu Department of hepatobiliary and pancreatic surgery Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouChina NHC key laboratory of Combined Multi-organ transplantation Key Laboratory of the Diagnosis and Treatment of Organ TransplantationCAMSHangzhouChina Department of hepatobiliary and pancreatic surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhouChina

The current treatment strategies in advanced malignancies remain ***,immunotherapies have raised hope for a successful control of these advanced diseases,but their therapeutic responses are suboptimal and vary considerably among ***-associated macrophages(TAMs)are a major component of the tumor microenvironment(TME)and are often correlated with poor prognosis and therapy resistance,including ***,a deeper understanding of the complex roles of TAMs in immunotherapy regulation could provide new insight into the ***,targeting of TAMs is an emerging field of interest due to the hope that these strategies will synergize with current *** this review,we summarize recent studies investigating the involvement of TAMs in immune checkpoint inhibition,tumor vaccines and adoptive cell transfer therapies,and discuss the therapeutic potential of targeting TAMs as an adjuvant therapy in tumor immunotherapies.

关键词： immunotherapy involvement diseases

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Prognostic factors of recurrent intrahepatic cholangiocarcinoma after hepatectomy:A retrospective study

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World Journal of Gastroenterology 2022年第15期28卷 1574-1587页

作者： Zi-Bo Yuan Hong-Bo Fang Quan-Kai Feng Tao Li Jie Li Department of hepatobiliary and pancreatic surgery the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina henan Research Centre for organ transplantation the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a highly malignant *** is an effective treatment for early ICC,but postoperative recurrence greatly affects patient *** on recurrent ICC after hepatectomy are *** To investigate the clinical characteristics of patients with recurrent ICC after hepatectomy,analyse prognostic factors and explore diagnosis and treatment *** A retrospective analysis was performed on all ICC patients undergoing hepatectomy from January 2013 to August *** with postoperative recurrence were selected according to the inclusion and exclusion *** overall survival was plotted by the Kaplan-Meier method,and differences were assessed by univariate survival analysis using the log-rank *** analysis of cumulative survival was performed using the Cox proportional risk *** During the 8-year study period,103 patients underwent ICC-related hepatectomy,and 54 exhibited postoperative *** median disease-free survival(DFS)was 6 mo,the median overall survival(OS)was 9 mo,and the cumulative OS rates at 1,2 and 3 years after the operation were 40.7%,14.8%and 7.4%,*** median OS after recurrence was 4 mo,and the cumulative OS rates at 1,2 and 3 years after recurrence were 16.1%,6.7%and 3.4%,*** analysis showed that alcohol consumption[hazard ratio(HR)=4.64,95%confidence interval(CI):1.53-14.04,P=0.007]and DFS<6 mo(HR=3.47,95%CI:1.59-7.60,P=0.002)were independent risk factors for the cumulative survival of patients with recurrence,while treatment after recurrence(HR=0.21,95%CI:0.08-0.55,P=0.001)was an independent protective *** median OS time of patients receiving multimodality therapy after recurrence of ICC was 7 mo,which was significantly higher than that of patients receiving only local therapy(3 mo),patients receiving systematic therapy(4 mo)and patients receiving the best supportive therapy(1 mo).Patients

关键词： Intrahepatic cholangiocarcinoma Hepatectomy Recurrence Multimodality therapy Prognosis

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Amino acid metabolism in health and disease

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4597-4628页

作者： Zhe-Nan Ling Yi-Fan Jiang Jun-Nan Ru Jia-Hua Lu Bo Ding Jian Wu Division of hepatobiliary and pancreatic surgery Department of SurgeryThe First Affliated HospitalZhejiang University School of Medicine79 Qingchun RoadHangzhouZhejang Province 310o03P.R.China NHC key laboratory of Combined Multi-organ transplantation HangzhouZhejiang ProvincePR.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 Sciences(2019RU019)HangzhouZhejiang ProvinceP.R.China key laboratory of organ transplantation Research Center for Diagnosis and Treatment of Hepatobiliary DiseasesHangzhouZhejiang ProvinceP.R.China

Amino acids are the building blocks of protein *** are structural elements and energy sources of cells necessary for normal cell growth,differentiation and *** acid metabolism disorders have been linked with a number of pathological conditions,including metabolic diseases,cardiovascular diseases,immune diseases,and *** the case of tumors,alterations in amino acid metabolism can be used not only as clinical indicators of cancer progression but also as therapeutic strategies.

关键词： synthesis. function. metabolism

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