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c-Myc-driven glycolysis polarizes functional regulatory B cells that trigger pathogenic inflammatory responses

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1735-1745页

作者： Xu-Yan wang Yuan Wei Bo Hu Yuan Liao Xiaodong wang Wen-Hua Wan Chun-Xiang Huang Mahepali Mahabati Zheng-Yu Liu Jing-Rui Qu Xiao-Dan Chen Dong-Ping Chen Dong-Ming Kuang xue-hao wang Yun Chen MOE Key Laboratory of Gene Function and Regulation Guangdong Province Key Laboratory of Pharmaceutical Functional GenesSchool of Life SciencesSun Yat-sen UniversityGuangzhouChina Department of Laboratory Medicine the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouChina School of Pharmaceutical Sciences Shenzhen University Health Science CenterShenzhenChina Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Living Donor Liver Transplantation(Nanjing Medical University)NanjingChina Department of Immunology Key Laboratory of Human Functional Genomics of Jiangsu ProvinceNanjing Medical UniversityNanjingChina Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina

B cells secreting IL-10 functionally are recognized as functional regulatory B(B_(reg))cells;however,direct evidence concerning the phenotype,regulation,and functional and clinical relevance of IL-10-secreting B_(reg)cells in humans is still lacking.Here,we demonstrate that,although IL-10 itself is anti-inflammatory,IL-10+functional B_(reg)cells in patients with systemic lupus erythematosus(SLE)display aggressive inflammatory features;these features shift their functions away from inducing CD8^(+)T cell tolerance and cause them to induce a pathogenic CD4^(+)T cell response.

关键词： inflammatory clinical functional

Ankaflavin ameliorates steatotic liver ischemiareperfusion injury in mice

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 619-625页

作者： hao-Jun Yang Li-Ming Tang Xian-Ju Zhou Jun Qian Jie Zhu Ling Lu xue-hao wang Liver Transplantation Center First Affiliated Hospital of Nanjing Medical University Department of General Surgery Changzhou No. 2 People's HospitalAffiliated Hospital of Nanjing Medical University Department of Neurology Laboratory of Neurological DiseasesChangzhou No. 2 People's HospitalAffiliated Hospital of Nanjing Medical University

BACKGROUND： It is well-known that steatotic liver is more susceptible to ischemia-reperfusion （I/R） injury during liver transplantation, liver resection and other liver surgeries. The increasing incidence of non-alcoholic fatty liver disease （NAFLD） decreases the availability of liver donors. Although steatotic liver is now accepted as a source of liver for trans- plantation, NAFLD exacerbates the liver injury after liver surgery. The present study was to investigate the protective role of ankaflavin in steatotic liver I/R injury.

关键词： ankaflavin ischemia-reperfusion Kupffer cells steatotic liver

Oleanolic acid attenuates liver ischemia reper-fusion injury by HO-1/Sesn2 signaling pathway

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Hepatobiliary & Pancreatic Diseases International 2016年第5期15卷 519-524页

作者： Bao-Bin hao Xiong-Xiong Pan Ye Fan Ling Lu Xiao-Feng Qian xue-hao wang Feng Zhang Jian-Hua Rao Department of Liver Surgery First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Living Donor Liver Transplantation of Ministry of Public HealthNanjing 210029China

BACKGROUND: Ischemia reperfusion injury (IRI) is unavoid-able in liver transplantation and hepatectomy. The present study aimed to explore the possible mechanism and the effect of oleanolic acid (OA) in hepatic IRI. METHODS: Mice were randomly divided into 6 groups based on different treatment. IRI model: The hepatic artery, portal vein, and bile duct to the left and median liver lobes (70% of the liver) were occluded with an atraumatic bulldog clamp for 90 minutes and then the clamp was removed for reperfusion. The mice were sacriifced 6 hours after reperfusion, and blood and liver tissues were collected. Liver injury was evaluated by biochemical and histopathologic examinations. The expressions of Sesn2, PI3K, Akt and heme oxygenase-1 (HO-1) were mea-sured with quantitative real-time RT-PCR and Western blotting. RESULTS: The serum aminotransferases level and scores of he-patic histology were increased after reperfusion. The increase was attenuated by pretreatment with OA (P CONCLUSIONS: Our results demonstrate that OA can attenu-ate hepatic IRI. The protective mechanism may be related to the OA-induced HO-1/Sesn2 signaling pathway.

关键词： oleanolic acid liver injury ischemia reperfusion HO-1 Sesn2

Effects of multimodal fast-track surgery on liver transplantation outcomes

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Hepatobiliary & Pancreatic Diseases International 2017年第4期16卷 364-369页

作者： Jian-Hua Rao Feng Zhang hao Lu Xin-Zheng Dai Chuan-Yong Zhang Xiao-Feng Qian xue-hao wang Ling Lu Liver Transplantation Center First Affiliated Hospital of Nanjing Medical University Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health Nanjing 210029China

BACKGROUND: Fast-track surgery and enhanced recovery after surgery have been applied to many surgical procedures; however, data on fast-track surgery and enhanced recovery after surgery following liver transplantation is limited. This study aimed to conduct a prospective study to determine the effects of fast-track surgery on prognosis after liver transplantation. METHODS: This was a prospective, single-blinded, randomized study. One hundred twenty-eight patients undergoing liver transplantation were selected for the fast-track (FT group, n=54) or conventional process (NFT group, n=74). The primary endpoints were intensive care unit (ICU) stay and hospital stay. The secondary endpoints were as follows: operative time, anhepatic phase time, intraoperative blood loss, intraoperative blood transfusion volume, postoperative complications, readmission rate, and postoperative mortality. RESULTS: There was no significant difference in preoperative demographics between the two groups. The median ICU stay was 2 days (range 1-7 days) in the FT group and 5 days (range 3-12 days) in the NFT group (P<0.01). Furthermore, the hospital stay was also significantly reduced in the FT group (P<0.01). The operative time, anhepatic phase time, intraoperative blood loss, and intraoperative blood transfusion volume were decreased in the FT group compared with the NFT group (P<0.05). Based on Spearman correlation analysis, the ICU stay and hospital stay may be positively correlated with operative time, anhepatic phase time and intraoperative blood loss. There were no differences in the incidence of postoperative complications, readmissions, and postoperative mortality between the two groups. CONCLUSION: Fast-track procedures effectively reduce the ICU stay and hospital stay without adversely affecting prognosis. This study demonstrated that fast-track protocols are safe and feasible in liver transplantation.

关键词： fast-track surgery liver transplantation surgical drainage ICU days hospital stay

Drainage by urostomy bag after blockage of abdominal drain in patients with cirrhosis undergoing hepatectomy

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Hepatobiliary & Pancreatic Diseases International 2013年第1期12卷 99-102页

作者： Guo-Qiang Li Feng Zhang hao Lu Ling Lu Xiang-Cheng Li xue-hao wang Bei-Cheng Sun Liver Transplantation Center First Affiliated HospitalNanjing Medical University Key Laboratory of Living Donor Liver Transplantation of Ministry of Public Health

Abdominal drainage was previously recommended as a post-hepatectomy procedure for patients with cirrhosis.This report introduces a simple technique that prevents leakage of ascitic fluid after cirrhotic hepatectomy complicated by blockage of the abdominal drain.In 59 patients who had had cirrhotic hepatectomy complicated by leakage of ascites in the drain site after drainage removal between January 2001 and April 2011,31 underwent suture ligation(sutured group) and 28 were given urostomy bag at the abdominal drainage site(drainage group).The mean length of postoperative hospital stay in the drainage group was shorter than in the sutured group(16.11±2.61 vs 34.23±4.86 days,P=0.000).Meanwhile,the drainage group showed decreased postoperative complications,including leakage of ascites,wound infection,and collection of ascites.Drainage by urostomy bag can prevent prolonged leakage of ascitic fluid after the blockage of abdominal drains in patients undergoing cirrhotic hepatectomy.

关键词： abdominal drain ascitic fluid leak hepatectomy urostomy bag

Successful disintegration,dissolution and drainage of intracholedochal hematoma by percutaneous transhepatic intervention

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World Journal of Gastroenterology 2012年第47期18卷 7122-7126页

作者： Jian-Jie Qin Yong-Xiang Xia Ling Lv Zhao-Jing wang Feng Zhang xue-hao wang Bei-Cheng Sun Liver Transplantation Center the First Affiliated Hospital of Nanjing Medical University Key Laboratory of Living Donor Liver Transplantation Ministry of Public Health

Hemobilia is a rare biliary complication of liver transplantation.The predominant cause of hemobilia is iatrogenic,and it is often associated with traumatic operations,such as percutaneous liver intervention,endoscopic retrograde cholangiopancreatography,cholecystectomy,biliary tract surgery,and liver transplantation.Percutaneous transhepatic cholangiography and liver biopsy are two major causes of hemobilia in liver transplant recipients.Hemobilia may also be caused by coagulation defects.It can form intracholedochal hematomas,causing obstructive jaundice.Herein we describe a patient with an intracholedochal hematoma resulting in significant obstructive jaundice after liver transplantation for fulminant hepatic failure.Previous studies have shown that percutaneous transhepatic manipulation is a major cause of hemobilia after liver transplantation,but in our case,percutaneous transhepatic intervention was used to relieve the biliary obstruction and dissolve the biliary clot,with a good outcome.

关键词：肝移植血肿崩解度引流溶出肝功能衰竭功能障碍胆道

Liver transplantation for polycystic liver with massive hepatomegaly: A case report

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World Journal of Gastroenterology 2009年第40期15卷 5112-5113页

作者： Wei-Wei Jiang Feng Zhang Li-Yong Pu xue-hao wang Lian-Bao Kong Department of Neonatal Surgery Nanjing Children's Hospital Affiliated to Nanjing Medical University 72 Guangzhou Road Nanjing 210008 Jiangsu Province China Department of Liver Transplantation Center The First Affiliated Hospital of Nanjing Medical University The National Institute of Living Donor Liver Transplantation 300 Guangzhou Road Nanjing 210029 Jiangsu Province China

A previous study has shown that liver or combined liver-kidney transplantation can be a valuable surgical technique for the treatment of polycystic liver disease. Herein, we present the case of a 35-year-old woman with polycystic liver disease, who underwent orthotopic liver transplantation (OLT) on November 11, 2008. The whole-size graft was taken from a deceased donor (a 51-year-old man who died of a heart attack). Resection in a patient with massive hepatomegaly is very difficult. Thus, after intercepting the portal hepatic vein, left hepatectomy was performed, then the vena cava was intercepted, the second and third porta hepatic isolated, and fi nally, right hepatectomy was performed. OLT was performed successfully. The recipient did well after transplantation. This case suggested that OLT is an effective therapeutic option for polycystic liver disease and left hepatectomy can be performed fi rst during OLT if the liver is over enlarged.

关键词：肝移植手术治疗肝门静脉肝切除肝脏肾移植肝疾病 OLT

Role of transforming growth factor-betal-smad signal transduction pathway in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第4期12卷 644-648页

作者： Guo-Zhong Ji xue-hao wang Lin Miao Zheng Liu Ping Zhang Fa-Ming Zhang Jian-Bing Yang Department of Gastroenterology Second Affiliated Hospital of Nanjing Medical University Nanjing 210011 Jiangsu Province China Department of Hepatic Surgery First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China Qidong Liver Cancer Institute Qidong 226200 Jiangsu Province China

AIM:To explore the role of transforming growth factor-beta1(TGF-β1)-smad signal transduction pathway inpatients with hepatocellular carcinoma.METHODS:Thirty-six hepatocellular carcinoma speci-mens were obtained from Qidong Liver Cancer Instituteand Department of Pathology of the Second AffiliatedHospital of Nanjing Medical University.All primary anti-bodies(polyclonal antibodies)to TGF-β1,type Ⅱ Trans-forming growth factor-beta receptor(TβR-Ⅱ),nuclear fac-tor-kappaB(NF-KB),CD34,smad4 and smad7,secondaryantibodies and immunohistochemical kit were purchasedfrom Zhongshan Biotechnology Limited Company(Bei-jing,China).The expressions of TGF-β1,TβR-Ⅱ,NF-kB,smad4 and smad7 proteins in 36 specimens ofhepatocellular carcinoma(HCC)and its adjacent tissuewere separately detected by immunohistochemistry toobserve the relationship between TGF-β1 and TβR-Ⅱ,between NF-kB and TGF-β1,between smad4 and smad7and between TGF-β1 or TβR-Ⅱ and microvessel density(MVD).MVD was determined by labelling the vesselendothelial cells with CD34.RESULTS:The expression of TGF-β1,smad7 and MVDwas higher in HCC tissue than in adjacent HCC tissue(P<0.01,P<0.05,P<0.01 respectively).The expressionof TβR-Ⅱ and smad4 was lower in HCC tissue than in its adjacent tissue(P<0.01,P<0.05 respectively).Theexpression of TGF-β1 protein and NF-kB protein wasconsistent in HCC tissue.The expression of TGF-β1 andMVD was also consistent in HCC tissue.The expressionof TβR-Ⅱ was negatively correlated with that of MVD inHCC tissue.CONCLUSION:The expressions of TGF-β1,TβR-Ⅱ,NF-kB,smad4 and smad7 in HCC tissue,which are ma-jor up and down stream factors of TGF-β1-smad signaltransduction pathway,are abnormal.These factors areclosely related with MVD and may play an important rolein HCC angiogenesis.The inhibitory action of TGF-β1 isweakened in hepatic carcinoma cells because of abnor-mality of TGF-β1 receptors(such as TβR-Ⅱ)and postre-ceptors(such as smad4 and smad7).NF-kB may causeactivation and production of TGF-β1.

关键词：转化生长因子信号转导肝细胞癌病理机制

Requirements for transfusion and postoperative outcomes in orthotopic liver transplantation:A meta-analysis on aprotinin

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World Journal of Gastroenterology 2008年第9期14卷 1425-1429页

作者： Cun-Ming Liu Jing Chen xue-hao wang Department of Anesthesiology First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China Department of Hepatobiliary Surgery First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China

AIM:To study the effect of aprotinin used in orthotopic liver transplantation (OLT) on the intraoperative requirement for blood products and on the incidence of laparotomy for bleeding, thrombotic events and mortality. METHODS: A systematic review of the literature in the electronic database Medline and the Clinic Trials Registry Database was performed. Literature that did not fit our study were excluded. Patients in the reviewed studies were divided into two groups; one group used aprotinin (aprotinin group) while the other did not (control group). The data in the literature that fit our requirements were recorded. Weighted mean differences (WMD) in the requirements for blood products between the aprotinin group and the control group were tested using a fixed effect model. A Z test was performed to examine their reliability; the Fleiss method of fixed effect model was used to analyze data on postoperative events, and odds ratios (ORs) were tested and merged. RESULTS: Seven citations were examined in our study. Among them, a requirement for blood products was reported in 4 studies including 321 patients, while postoperative events were reported in 5 studies including 477 patients. The requirement for red blood cells and fresh frozen plasma in the aprotinin group was statistically lower than that in the control group (WMD=-1.80 units, 95% CI,-3.38 to-0.22; WMD=-3.99 units, 95% CI,-6.47 to-1.50, respectively). However, no significant difference was indicated in the incidence of laparotomy for bleeding, thrombotic events and mortality between the two groups. Analysis on blood loss, anaphylactic reactions and renal function was not performed in this study due to a lack of sufficient information.CONCLUSION: Aprotinin can reduce the intraoperative requirement for blood products in OLT, and has no significant effect on the incidence of laparotomy for bleeding, thrombotic events and mortality.

关键词：肝移植输血元分析同位移植