检索结果-南通市图书馆

Metronomic capecitabine inhibits liver transplant rejection in rats by triggering recipients’T cell ferroptosis

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2023年第20期29卷 3084-3102页

作者： Hao Wang Zheng-Lu Wang Sai Zhang De-Jun Kong Rui-Ning yang Lei Cao Jian-Xi Wang Sei Yoshida Zhuo-Lun Song Tao Liu Shun-Li Fan Jia-Shu Ren Jiang-Hong Li zhong-yang shen Hong Zheng The First Central Clinical School Tianjin Medical UniversityTianjin 300190China Department of Organ Transplant Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300190China Key Laboratory of Transplant Medicine Chinese Academy of Medical SciencesTianjin 300190China School of Medicine Nankai UniversityTianjin 300190China Research Institute of Transplant Medicine Nankai UniversityTianjin 300071China Tianjin Key Laboratory for Organ Transplantation Tianjin First Central HospitalSchool of MedicineNankai UniversityTianjin 300071China National Health Commission’s Key Laboratory for Critical Care Medicine Tianjin First Central HospitalTianjin 300071China

BACKGROUND Capecitabine(CAP)is a classic antimetabolic drug and has shown potential antirejection effects after liver transplantation(LT)in clinical studies.Our previous study showed that metronomic CAP can cause the programmed death of T cells by inducing oxidative stress in healthy mice.Ferroptosis,a newly defined non-apoptotic cell death that occurs in response to iron overload and lethal levels of lipid peroxidation,is an important mechanism by which CAP induces cell death.Therefore,ferroptosis may also play an important role in CAP-induced T cell death and play an immunosuppressive role in acute rejection after transplantation.AIM To investigate the functions and underlying mechanisms of antirejection effects of metronomic CAP.METHODS A rat LT model of acute rejection was established,and the effect of metronomic CAP on splenic hematopoietic function and acute graft rejection was evaluated 7 d after LT.In vitro,primary CD3+T cells were sorted from rat spleens and human peripheral blood,and co-cultured with or without 5-fluorouracil(5-FU)(active agent of CAP).The levels of ferroptosis-related proteins,ferrous ion concentration,and oxidative stress-related indicators were observed.The changes in mitochondrial structure were observed using electron microscopy.RESULTS With no significant myelotoxicity,metronomic CAP alleviated graft injury(Banff score 9 vs 7.333,P<0.001),prolonged the survival time of the recipient rats(11.5 d vs 16 d,P<0.01),and reduced the infiltration rate of CD3+T cells in peripheral blood(6.859 vs 3.735,P<0.001),liver graft(7.459 vs 3.432,P<0.001),and spleen(26.92 vs 12.9,P<0.001),thereby inhibiting acute rejection after LT.In vitro,5-FU,an end product of CAP metabolism,induced the degradation of the ferritin heavy chain by upregulating nuclear receptor coactivator 4,which caused the accumulation of ferrous ions.It also inhibited nuclear erythroid 2 p45-related factor 2,heme oxygenase-1,and glutathione peroxidase 4,eventually leading to oxidative damage and ferroptosis of T cells.CONCLUSION

关键词： Capecitabine Ferroptosis T Lymphocytes Immunosuppressive agents Graft rejection Liver transplantation

Liver expression of Nrf2-related genes in different liver diseases

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Hepatobiliary & Pancreatic Diseases International 2015年第5期14卷 485-491页

作者： Ming-Liang Cheng Yuan-Fu Lu Hong Chen zhong-yang shen Jie Liu The Affiliated Hospital of Guizhou Medical University Key Lab for Basic Pharmacology of Ministry of Education Zunyi Medical College The Institute of Organ Transplantation The General Hospital of Chinese People's Armed Police Forces

BACKGROUND： The KEAP1-Nrf2 antioxidant signaling pathway is important in protecting liver from various insults. However,little is known about the expression of Nrf2-related genes in human liver in different diseases.METHODS： This study utilized normal donor liver tissues（n=35）, samples from patients with hepatocellular carcinoma（HCC, n=24）, HBV-related cirrhosis（n=27）, alcoholic cirrhosis（n=5） and end-stage liver disease（n=13）. All of the liver tissues were from the Oriental Liver Transplant Center, Beijing,China. The expressions of Nrf2 and Nrf2-related genes, including its negative regulator Kelch-like ECH-associated protein 1（KEAP1）, its targeted gene NAD（P）H-quinone oxidoreductase 1（NQO1）, glutamate-cysteine ligase catalytic subunit（GCLC） and modified subunit（GCLM）, heme oxygenase 1（HO-1） and peroxiredoxin-1（PRDX1） were evaluated. RESULTS： The expression of Nrf2 was decreased in HCC, increased in alcoholic cirrhosis and end-stage liver disease. The expression of KEAP1 was increased in all of the liver samples.The most notable finding was the increased expression of NQO1 in HCC（18-fold）, alcoholic cirrhosis（6-fold）, endstage liver disease（5-fold） and HBV-related cirrhosis（3-fold）.Peri-HCC also had 4-fold higher NQO1 m RNA as compared to the normal livers. GCLC m RNA levels were lower only in HCC, as compared to the normal livers and peri-HCC tissues.GCLM m RNA levels were higher in HBV-related cirrhosis and end-stage liver disease. HO-1 m RNA levels were increased in all liver tissues except for HCC. Peri-HCC had higher PRDX1 m RNA levels compared with HCC and normal livers.CONCLUSION： Nrf2 and Nrf2-related genes are aberrantly expressed in the liver in different diseases and the increase of NQO1 was the most notable finding, especially in HCC.

关键词： Nrf2-related gene expression cirrhosis hepatocellular carcinoma end-stage liver disease

Effect of donor age on graft function and longterm survival of recipients undergoing living donor liver transplantation

在线全文

学校读者我要写书评

暂无评论

Hepatobiliary & Pancreatic Diseases International 2015年第1期14卷 50-55页

作者： Kai Wang Wen-Tao Jiang Yong-Lin Deng Cheng Pan zhong-yang shen Department of Transplant Surgery Tianjin First Center Hospital Key Laboratory of Organ Transplantation of Tianjin

BACKGROUND： Donor shortage is the biggest obstacle in organ transplantation. Living donor liver transplantation（LDLT） has been considered as a valuable approach to shortening waiting time. The objectives of this study were to investigate the feasibility of utilizing donors older than 50 years in LDLT and to evaluate the graft function and recipient survival.METHODS： All LDLT cases（n=159） were divided into the older（donor age ≥50 years, n=10） and younger（donor age 〈50 years,n=149） donor groups. Donor graft and recipient condition pre-,intra- and post-operation were compared between the two groups.In particular, graft functions and recipient survivals were analyzed.RESULTS： The median donor age was 58.5（52.5-60.0） years in the older donor group and 25.0（23.0-32.0） in the younger donor group. There was no significant difference in cold ischemic time, anhepatic phase and operation time between the older and younger donor groups（P〉0.05）. However, the volume of red blood cell transfused in operation was greater in the older donor group than in the younger donor group（1900 vs 1200 m L, P=0.023）. The 1-, 3- and 5-year graft survival rates were 90%, 80% and 80% for the older donor group, and 92%, 87% and 87% for the younger donor group, respectively（P=0.459）.The 1-, 3- and 5-year survival rates were 100%, 90% and 90% for recipients with older grafts, and 93%, 87% and 87% for those with younger grafts, respectively（P=0.811）.CONCLUSION： It is safe for a LDLT recipient to receive liver from donors older than 50 years, and there is no significant adverse effect on graft function and long-term patients’ survival.

关键词： living donor liver transplantation donor age graft liver function long-term survival

Effect of CXCR3/HO-1 genes modified bone marrow mesenchymal stem cells on small bowel transplant rejection

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2017年第22期23卷 4016-4038页

作者： Ming-Li Yin Hong-Li Song yang yang Wei-Ping Zheng Tao Liu zhong-yang shen Tianjin First Central Hospital Clinic Institute Tianjin Medical University Department of Organ Transplantation Tianjin First Central HospitalTianjin Clinical Research Center for Organ Transplantation and Tianjin Key Laboratory of Organ Transplantation Department of Organ Transplantation Tianjin First Central Hospital Tianjin First Central Hospital and Key Laboratory of Emergency and Care Medicine of Ministry of Health

AIM To investigate whether bone marrow mesenchymal stem cells(BMMSCs) modified with the HO-1 and CXCR3 genes can augment the inhibitory effect of BMMSCs on small bowel transplant rejection.METHODS Lewis rat BMMSCs were cultured in vitro. Thirdpassage BMMSCs were transduced with the CXCR3/HO-1 genes or the HO-1 gene alone. The rats were divided into six groups and rats in the experimental group were pretreated with BMMSCs 7 d prior to smallbowel transplant. Six time points(instant, 1 d, 3 d, 7 d, 10 d, and 14 d)(n = 6) were chosen for each group. Hematoxylin-eosin staining was used to observe pathologic rejection, while immunohistochemistry and Western blot were used to detect protein expression. Flow cytometry was used to detect T lymphocytes and enzyme linked immunosorbent assay was used to detect cytokines.RESULTS The median survival time of BMMSCs from the CXCR3/HO-1 modified group(53 d) was significantly longer than that of the HO-1 modified BMMSCs group(39 d), the BMMSCs group(26 d), and the NS group(control group)(16 d)(P < 0.05). Compared with BMMSCs from the HO-1 modified BMMSCs, BMMSCs, and NS groups, rejection of the small bowel in the CXCR3/HO-1 modified group was significantly reduced, while the weight of transplant recipients was also significantly decreased(P < 0.05). Furthermore, IL-2, IL-6, IL-17, IFN-γ, and TNF-α levels were significantly decreased and the levels of IL-10 and TGF-β were significantly increased(P < 0.05). CONCLUSION BMMSCs modified with the CXCR3 and HO-1 genes can abrogate the rejection of transplanted small bowel more effectively and significantly increase the survival time of rats that receive a small bowel transplant.

关键词：骨头髓间充质的干细胞 CXCR3 HO-1 小肠移植拒绝

Complex liver retransplantation to treat graft loss due to long-term biliary tract complication after liver transplantation: A case report

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Clinical Cases 2020年第3期8卷 568-576页

作者： Jiang Li Qing-Jun Guo Wen-Tao Jiang Hong Zheng zhong-yang shen Department of Liver Transplant Tianjin First Central Hospital

BACKGROUND Loss of graft function after liver transplantation(LT) inevitably requires liver retransplant. Retransplantation of the liver(Re LT) remains controversial because of inferior outcomes compared with the primary orthotopic LT(OLT).Meanwhile, if accompanied by vascular complications such as arterial and portal vein(PV) stenosis or thrombosis, it will increase difficulties of surgery. We hereby introduce our center’s experience in Re LT through a complicated case of ReLT.CASE SUMMARY We report a patient who suffered from hepatitis B-associated cirrhosis and underwent LT in December 2012. Early postoperative recovery was uneventful.Four months after LT, the patient’s bilirubin increased significantly and he was diagnosed with an ischemic-type biliary lesion caused by hepatic artery occlusion. The patient underwent percutaneous transhepatic cholangial drainage and repeatedly replaced intrahepatic biliary drainage tube regularly for 5 years.The patient developed progressive deterioration of liver function and underwent liver re-transplant in January 2019. The operation was performed in a classic OLT manner without venous bypass. Both the hepatic artery and PV were occluded and could not be used for anastomosis. The donor PV was anastomosed with the recipient’s left renal vein. The donor hepatic artery was connected to the recipient’s abdominal aorta. The bile duct reconstruction was performed in an end-to-end manner. The postoperative process was very uneventful and the patient was discharged 1 mo after retransplantation.CONCLUSION With the development of surgical techniques, portal thrombosis and arterial occlusion are no longer contraindications for ReLT.

关键词： Liver retransplantation Biliary tract complication Ischemic type biliary lesion Portal vein thrombosis Arterial occlusion Graft liver failure Case report

Glypican-3 expression and its relationship with recurrence of HCC after liver transplantation

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2012年第19期18卷 2408-2414页

作者： Yu-Liang Wang Zhi-Jun zhu Da-Hong Teng Zhi Yao Wei Gao zhong-yang shen Department of Transplantation Surgery Tianjin First Central Hospital Key Laboratory for Critical CareMedicine of the Ministry of Health Tianjin 300192 China Department of Immunology TianjinMedical University Tianiin 300070 China

AIM:To investigate the diagnostic value of glypican-3(GPC3) and its relationship with hepatocellular carcinoma(HCC) recurrence after liver transplantation.METHODS:HCC tissue samples(n = 31) obtained from patients who had undergone liver transplantation were analyzed.GPC3 mRNA and protein expression were analyzed by TaqMan real-time reverse transcription-polymerase chain reaction and immunohistochemistry.Correlation between the GPC3 expression and clinicopathological features was analyzed.The potential prognostic value of GPC3 was investigated by comparing recurrence-free survival between HCC patients with and without GPC3 expression.RESULTS:Using a cutoff value of 3.5 × 10-2,20 of 31 cancerous tissues had expression values of > 3.5 × 10-2,whereas 3 of 31 adjacent non-neoplastic parenchyma and 0 of 20 control liver tissues had expression values of > 3.5 × 10-2(P 3.5 × 10-2) and those without vascular invasion(P < 0.05 for both).CONCLUSION:GPC3 expression may serve as a valuable diagnostic marker for HCC.GPC3 mRNA overexpression may be an adverse indicator for HCC patients after liver transplantation.

关键词：肝移植肝癌复发 mRNA表达诊断价值 TaqMan 聚合酶链反应相关性分析

Simultaneous partial splenectomy during liver transplantation for advanced cirrhosis patients combined with severe splenomegaly and hypersplenism

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2021年第7期27卷 654-665页

作者： Wen-Tao Jiang Jian yang Yan Xie Qing-Jun Guo Da-Zhi Tian Jun-Jie Li zhong-yang shen Department of Liver Transplantation Tianjin First Center HospitalFirst Clinical Institute of Tianjin Medical UniversityTianjin 300192China Organ Transplantation Center Tianjin First Center HospitalTianjin 300192China Department of Hepatological Surgery Zibo Central HospitalZibo 255000Shandong ProvinceChina

BACKGROUND The most effective treatment for advanced cirrhosis and portal hypertension is liver transplantation(LT).However,splenomegaly and hypersplenism can persist even after LT in patients with massive splenomegaly.AIM To examine the feasibility of performing partial splenectomy during LT in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism.METHODS Between October 2015 and February 2019,762 orthotopic LTs were performed for patients with end-stage liver diseases in Tianjin First Center Hospital.Eighty-four cases had advanced cirrhosis combined with severe splenomegaly and hypersplenism.Among these patients,41 received partial splenectomy during LT(PSLT group),and 43 received only LT(LT group).Patient characteristics,intraoperative parameters,and postoperative outcomes were retrospectively analyzed and compared between the two groups.RESULTS The incidence of postoperative hypersplenism(2/41,4.8%)and recurrent ascites(1/41,2.4%)in the PSLT group was significantly lower than that in the LT group(22/43,51.2%;8/43,18.6%,respectively).Seventeen patients(17/43,39.5%)in the LT group required two-stage splenic embolization,and further splenectomy was required in 6 of them.The operation time and intraoperative blood loss in the PSLT group(8.6±1.3 h;640.8±347.3 mL)were relatively increased compared with the LT group(6.8±0.9 h;349.4±116.1 mL).The incidence of postoperative bleeding,pulmonary infection,thrombosis and splenic arterial steal syndrome in the PSLT group was not different to that in the LT group,respectively.CONCLUSION Simultaneous PSLT is an effective treatment and should be performed in patients with advanced cirrhosis combined with severe splenomegaly and hypersplenism to prevent postoperative persistent hypersplenism.

关键词： Liver transplantation Partial splenectomy Hypersplenism Splenomegaly Liver cirrhotic Megalosplenia

A retrospective study of the occurrence of ischemic-type biliary lesions post liver transplantation

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Science China(Life Sciences) 2016年第5期59卷 529-531页

作者： Rui Shi Ya-Min Zhang Yong-Lin Deng Hong Zheng Cheng Pan zhong-yang shen Tianjin Key Laboratory of Organ Transplantation Department of Hepatobiliary Surgery First Center Hospital Clinic Institute Tianjin Medical University

Dear Editors,Ischemic-type biliary lesions(ITBLs)significantly reduce patient and graft survival rates.Research data regarding the causes of ITBL are rare.ITBLs is an important cause of post liver transplantation graft loss and patient death.The exact cause of this type of biliary complication remains unclear.To establish strategies for ITBL treatment or prevention,the risk factors of ITBL must be elucidated.The objective of this single-center retrospective study was to investigate the risk factors of ITBL in orthotopic liver transplantation(OLT)patients.

关键词：肝移植胆道病变血型预防方法风险因素危险因素存活率

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

在线全文

学校读者我要写书评

暂无评论

World Journal of Gastroenterology 2017年第19期23卷 3449-3467页

作者： Liu yang zhong-yang shen Rao-Rao Wang Ming-Li Yin Wei-Ping Zheng Bin Wu Tao Liu Hong-Li Song the First Central Clinical College Tianjin Medical University Department of Organ Transplantation Tianjin First Central Hospital Tianjin First Central Hospital and Key Laboratory of Emergency and Care Medicine of Ministry of Health Department of Organ Transplantation Tianjin First Central Hospital and Tianjin Key Laboratory of Organ Transplantation

AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat model.METHODS BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff technique.Recipients were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/BMMSCs.Liver function was examined at six time points.The levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent assay.The portal vein pressure(PVP)was detected by Power Lab ML880.The expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western blotting.ATPase in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron microscope.RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,compared with those of the NS group and BMMSCs g

关键词： Reduced-size liver transplantation Bone marrow mesenchymal stem cells Microcirculation Heme oxygenase-1 Energy metabolism