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Role of cerebrospinal fluid chimerism in predicating central nervous relapse surveillance for patients of acute leukemia after allogeneic hematopoietic stem cell transplantation 脑脊液嵌合在预测异基因造血干细胞移植后急性白血病患者中枢神经复发监测中的作用
Pub Date : 2019-03-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.03.004
Jun-ying Li, Z. Zhong, Y. You, Liang Tang, Xuan Lu, Han Yan, Huafang Wang, L. Xia, Yu Hu
Objective To explore the role of cerebrospinal fluid chimerism in central nervous relapse surveillance for patients of acute leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods The follow-up data were retrospectively collected and analyzed in 104 patients with acute leukemia after allo-HSCT. Comparisons were made between patients with complete chimerism and mixed chimerism in cerebrospinal fluid. The role of recipient DNA percentage and its changing trend in predicting central nervous relapse were also explored. Analysis was conducted for determining the risk factors of central nervous relapse. And the effectiveness of prophylaxis with intrathecal injection was also examined. Results The incidence of relapse was higher in patients with mixed chimerism (P<0.001), high percentage of recipient DNA (P<0.05) and higher mixed chimerism (P<0.001). Hyperleukocytosis at an initial diagnosis was a risk factor of central nervous relapse. Whether or not intrathecal injection prophylaxis was applied showed no significant difference in relapsing rate. Conclusions Monitoring cerebrospinal fluid chimerism can effectively help predict central nervous relapse among patients of acute leukemia after allo-HSCT. Yet intrathecal injection prophylaxis failed to benefit recipients. Key words: Allogeneic hematopoietic stem cell transplantation; Cerebrospinal fluid; Central nervous relapse
目的探讨脑脊液嵌合在急性白血病同种异体造血干细胞移植(alloo - hsct)术后中枢神经复发监测中的作用。方法回顾性分析104例急性白血病同种异体造血干细胞移植后的随访资料。对脑脊液完全嵌合和混合嵌合患者进行了比较。探讨受体DNA百分比及其变化趋势在预测中枢神经系统复发中的作用。分析中枢神经复发的危险因素。并对鞘内注射预防的有效性进行了探讨。结果混合嵌合患者复发率高(P<0.001),受体DNA比例高(P<0.05),混合嵌合患者复发率高(P<0.001)。初始诊断时白细胞增多是中枢神经系统复发的危险因素。有无鞘内注射预防,复发率无显著性差异。结论监测脑脊液嵌合可有效预测急性白血病患者同种异体造血干细胞移植后中枢神经系统的复发。然而,鞘内注射预防未能使接受者受益。关键词:异基因造血干细胞移植;脑脊液;中枢神经复发
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引用次数: 0
Efficacy of haploidentical allogeneic hematopoietic stem cell transplantation for severe aplastic anemia: a report of 40 cases 单倍体同种异体造血干细胞移植治疗严重再生障碍性贫血40例疗效分析
Pub Date : 2019-03-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.03.007
Hongfei Wu, Xinsheng Xie, D. Wan, R. Guo, Chong Wang, Ling Sun, Hui Sun, Zhongxing Jiang
Objective To explore the efficacy and prognosis of haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA). Methods The clinical data were retrospectively analyzed for 40 SAA cases undergoing haplo-HSCT from September 2013 to February 2018. The conditioning regimen contained cyclophosphamide, fludarabine and antithymocyte globulin with or without busulfan or low-dose total body irradiation. Cyclosporin A, short-term methotrexate and mycophenolate mofetil were dosed for preventing graft versus host disease (GVHD). The median counts of mononuclear cell and CD34+ stem cell were 5.3(2.0~13.5)×108/kg and 5.6(1.6~15.9)×106/kg respectively. Results Among them, hematopoietic reconstitution was achieved (n=36, 90.0 %). The median times for myeloid engraftment and platelet engraftment were 15(10-25) and 17(10~58) days respectively. The incidence of acute graft-versus-host disease(aGVHD)was (35.0±6.8) %. The incidence of chronic GVHD (cGVHD) was (23.0±7.4) %. And 28 SAA cases (70.0 %) survived during a median follow-up period of 353(30~1226) days, The cumulative overall survival (OS) was (67.8±7.8) %, the average survival time (883±82)days and transplantation-related death (TRM) within 100 days (10.0±3.1) %. Conclusions Haplo-HSCT is an effective treatment for SAA patients. And a larger number of cases are required for enhancing OS. Key words: Allogeneic hematopoietic stem cell transplantation; Aplastic anemia; Human leukocyte antigen
目的探讨单倍体同种异体造血干细胞移植(haploo - hsct)治疗重度再生障碍性贫血(SAA)的疗效和预后。方法回顾性分析2013年9月至2018年2月行单倍hsct的40例SAA患者的临床资料。调理方案包括环磷酰胺、氟达拉滨和抗胸腺细胞球蛋白,加或不加布磺胺或低剂量全身照射。环孢素A、短期甲氨蝶呤和霉酚酸酯用于预防移植物抗宿主病(GVHD)。单个核细胞和CD34+干细胞的中位数分别为5.3(2.0~13.5)×108/kg和5.6(1.6~15.9)×106/kg。结果其中造血功能重建36例,占90%。骨髓移植和血小板移植的中位时间分别为15(10 ~ 25)天和17(10~58)天。急性移植物抗宿主病(aGVHD)发生率为(35.0±6.8)%。慢性GVHD (cGVHD)的发生率为(23.0±7.4)%。28例(70.0%)SAA患者中位随访353(30~1226)d,累计总生存率(OS)为(67.8±7.8)%,平均生存时间(883±82)d, 100 d内移植相关死亡(TRM)为(10.0±3.1)%。结论单倍移植是治疗SAA的有效方法。并且需要更多的案例来增强操作系统。关键词:异基因造血干细胞移植;再生障碍性贫血;人白细胞抗原
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引用次数: 1
Analysis of influencing factors of blood concentration of tacrolimus in Chinese pediatric living donor liver transplant patients 中国儿童活体肝移植患者他克莫司血药浓度的影响因素分析
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.009
Yi Qin, Xiaoshuo Wang, Meiling Yan, Wei Gao, Fan Chen, Yi Zhang
Objective To explore the influencing factors of blood concentration of tacrolimus in pediatric living donor liver transplant recipients and provide rationales for individualized administration of tacrolimus. Methods Trough concentrations (C0), doses of tacrolimus, recipient age, gender, body weight, donor and recipient CYP3A5 genotypes, hematocrit (HCT) and liver/kidney function related indicators at 3, 5, 7, 14 days, 1 month, 2 months and 3 months post living donor liver transplantation were collected from a total of 100 pediatric recipients. Taking ratio of concentration to dose (C0/D) as a dependent variable, the influencing factors of blood concentration of tacrolimus were analyzed by multivariate stepwise regression. Results The influencing factors of blood tacrolimus concentration at 3d post-transplantation were recipient CYP3A5 genotyp, donor CYP3A5 genotype and weight of recipients. The major influencing factors at 5d post-transplantation were recipient & donor CYP3A5 genotypes, recipient weight and HCT. The major relevant factors at 7d post-transplantation were CYP3A5 of recipients, age and HCT. The influencing factors at 14 days were the same as those at 2 months, i. e. CYP3A5 genotype and weight of recipients. At 1 month the major influencing factors were weight of recipients, CYP3A5 of recipients and alkaline phosphatase (ALP); CYP3A5 genotype and weight of recipients at 3 months. Further study on CYP3A5 genotype of donors and recipients, the C0/D ratio of CYP3A5 genotype non-expression group was significantly higher than that of expression group in recipients and C0/D ratio of donor CYP3A5 genotype non-expression group was significantly higher than that of expression group. Conclusions The influencing factors of concentration of tacrolimusvary at different timepoints after liver transplantation. Paying close attention to the changes of CYP3A5 genotype, weight of recipients and related biochemical indexes and considering various influencing factors facilitate individualized dosing for improving the prognosis of pediatric recipients. Key words: Pediatric; Liver transplantation; Living donor; Tacrolimus; Blood concentration
目的探讨儿童活体肝移植受者他克莫司血药浓度的影响因素,为他克莫司个体化用药提供依据。方法收集100例儿童活体肝移植术后3、5、7、14天、1个月、2个月、3个月时他克莫司谷浓度(C0)、剂量、受体年龄、性别、体重、供、受体CYP3A5基因型、血细胞比容(HCT)和肝肾功能相关指标。以浓度剂量比(C0/D)为因变量,采用多因素逐步回归分析他克莫司血药浓度的影响因素。结果影响移植后3d血药浓度的因素有受体CYP3A5基因型、供体CYP3A5基因型和受体体重。移植后5d的主要影响因素是受体和供体CYP3A5基因型、受体体重和HCT。移植后7d的主要相关因素是受体的CYP3A5、年龄和HCT。第14天的影响因素与第2个月相同,即CYP3A5基因型和受体体重。1个月时主要影响因素为体重、受体CYP3A5和碱性磷酸酶(ALP);3个月时受体CYP3A5基因型和体重。进一步研究供体和受体CYP3A5基因型,CYP3A5基因型不表达组的C0/D比值显著高于受体CYP3A5基因型不表达组,供体CYP3A5基因型不表达组的C0/D比值显著高于表达组。结论肝移植术后不同时间点他克莫司浓度的影响因素不同。密切关注CYP3A5基因型、受者体重及相关生化指标的变化,综合考虑各种影响因素,有利于个体化给药,改善儿科受者预后。关键词:儿科;肝移植;活体供;他克莫司;血药浓度
{"title":"Analysis of influencing factors of blood concentration of tacrolimus in Chinese pediatric living donor liver transplant patients","authors":"Yi Qin, Xiaoshuo Wang, Meiling Yan, Wei Gao, Fan Chen, Yi Zhang","doi":"10.3760/CMA.J.ISSN.0254-1785.2019.02.009","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.0254-1785.2019.02.009","url":null,"abstract":"Objective \u0000To explore the influencing factors of blood concentration of tacrolimus in pediatric living donor liver transplant recipients and provide rationales for individualized administration of tacrolimus. \u0000 \u0000 \u0000Methods \u0000Trough concentrations (C0), doses of tacrolimus, recipient age, gender, body weight, donor and recipient CYP3A5 genotypes, hematocrit (HCT) and liver/kidney function related indicators at 3, 5, 7, 14 days, 1 month, 2 months and 3 months post living donor liver transplantation were collected from a total of 100 pediatric recipients. Taking ratio of concentration to dose (C0/D) as a dependent variable, the influencing factors of blood concentration of tacrolimus were analyzed by multivariate stepwise regression. \u0000 \u0000 \u0000Results \u0000The influencing factors of blood tacrolimus concentration at 3d post-transplantation were recipient CYP3A5 genotyp, donor CYP3A5 genotype and weight of recipients. The major influencing factors at 5d post-transplantation were recipient & donor CYP3A5 genotypes, recipient weight and HCT. The major relevant factors at 7d post-transplantation were CYP3A5 of recipients, age and HCT. The influencing factors at 14 days were the same as those at 2 months, i. e. CYP3A5 genotype and weight of recipients. At 1 month the major influencing factors were weight of recipients, CYP3A5 of recipients and alkaline phosphatase (ALP); CYP3A5 genotype and weight of recipients at 3 months. Further study on CYP3A5 genotype of donors and recipients, the C0/D ratio of CYP3A5 genotype non-expression group was significantly higher than that of expression group in recipients and C0/D ratio of donor CYP3A5 genotype non-expression group was significantly higher than that of expression group. \u0000 \u0000 \u0000Conclusions \u0000The influencing factors of concentration of tacrolimusvary at different timepoints after liver transplantation. Paying close attention to the changes of CYP3A5 genotype, weight of recipients and related biochemical indexes and considering various influencing factors facilitate individualized dosing for improving the prognosis of pediatric recipients. \u0000 \u0000 \u0000Key words: \u0000Pediatric; Liver transplantation; Living donor; Tacrolimus; Blood concentration","PeriodicalId":9885,"journal":{"name":"Chineae Journal of Organ Transplantation","volume":"1 1","pages":"102-106"},"PeriodicalIF":0.0,"publicationDate":"2019-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78188411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effect of ETaR siRNA on renal ischemia-reperfusion injury in rats by changing the immuno-microenvironment of kidney ETaR siRNA通过改变肾脏免疫微环境对大鼠肾缺血再灌注损伤的保护作用
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.002
Yichen Jia, Long Zheng, Long Li, Jiawei Li, Ming Xu, T. Zhu
Objective To explore the protective effect of ETaR siRNA on renal ischemia reperfusion injury (IRI) by changing the immuno-microenvironment in rats. Methods A total of 40 male Sprague-Dawley (SD) rats were randomized into four groups of sham, IR, negative siRNA and ETaR siRNA. A renal IRI model was generated by clamping left renal artery. ETaR siRNA was delivered into kidney through renal vein by a retrograde 'hydrodynamic’ injection. Blood samples were collected for detecting renal function and kidney tissue harvested for Hematoxylin & Eosin (HE) staining, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, polymerase chain reaction (PCR) and Western blot at 48 h post-reperfusion. Results Serum creatinine, blood urea nitrogen and renal apoptotic cells increased and renal tissue was injured after IR. The changes were inhibited by ETaR siRNA. PCR showed that ETaR siRNA treatment significantly down-regulated the expressions of inflammatory factors TNF-α, IFN-γ and IL-6 and transcription factor NF-κB induced by IR. Conclusions ETaR siRNA can effectively improve the immuno-microenvironment and thereby alleviate renal ischemia reperfusion injury. Key words: Rats; Kidney; Endothelin receptor; Small interfering RNA; Immuno-microenvironment; Reperfusion injury
目的探讨ETaR siRNA通过改变免疫微环境对大鼠肾缺血再灌注损伤(IRI)的保护作用。方法选取雄性SD大鼠40只,随机分为sham组、IR组、阴性siRNA组和ETaR siRNA组。通过夹持左肾动脉建立肾IRI模型。ETaR siRNA通过肾静脉逆行“流体动力学”注射进入肾脏。再灌注后48 h,采集血样检测肾功能,采集肾组织进行苏木精&伊红(HE)染色、tdt介导的dUTP镍端标记(TUNEL)染色、聚合酶链反应(PCR)和Western blot。结果IR后大鼠血清肌酐、血尿素氮及肾细胞凋亡增加,肾组织损伤。这些变化被ETaR siRNA抑制。PCR结果显示,ETaR siRNA处理显著下调IR诱导的炎症因子TNF-α、IFN-γ、IL-6及转录因子NF-κB的表达。结论ETaR siRNA可有效改善免疫微环境,从而减轻肾缺血再灌注损伤。关键词:大鼠;肾脏;内皮素受体;小干扰RNA;Immuno-microenvironment;再灌注损伤
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引用次数: 0
Inhibition of islet allograft rejection by Qa-1/PD-L1 artificial liposome
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.003
M. Guo, Zhao Yuanyu, Hao Yin, Jia-Yong Dong, Ji Junsong, Lu‐Yue Qi, Hang Yuan, F. Teng, Wen-Yuan Guo
Objective To explore the effects of Qa-1 and PD-L1 loaded artificial liposomal treatment in allograft rejection and its outcomes. Methods The extracellular domains of Qa-1 and PD-L1 were loaded on liposome surface by streptavidin-biotin system. Mixed lymphocyte reaction (MLR) was performed for measuring Qa-1/PD-L1 liposome biological function. Then liposome was co-transplanted with allo-islets via portal vein. The levels of blood glucose and C-peptide were detected daily after transplantation. Also hepatic lymphocytes after transplantation were isolated for determining the proportion of activated cells and signaling pathway changes. Results Artificial liposome could be easily loaded with biotinylated peptide and its diameter was between 50 to 500 nm. Qa-1/PD-L1 liposome could significantly suppress lymphocyte proliferation, activation and secretion of IFN-γ in MLR by an activation of SHP1/2 and an inhibition of Syk pathway. Qa-1/PD-L1 liposomes could suppress the activation of hepatic lymphocytes in vivo by activating SHP1/2, protecting islet allografts and maintaining a normal level of blood glucose in recipients. Conclusions Qa-1/PD-L1 loaded liposome can effectively suppress allograft rejection and improve the outcomes of islet transplantation. Key words: Mouse; Islet transplantation; Qa-1; PD-L1; Graft rejection; SHP1/2
目的探讨Qa-1和PD-L1负载人工脂质体治疗同种异体移植排斥反应的效果及预后。方法利用链霉亲和素-生物素系统在脂质体表面负载Qa-1和PD-L1的胞外结构域。采用混合淋巴细胞反应(MLR)检测Qa-1/PD-L1脂质体生物学功能。脂质体经门静脉与异体胰岛共移植。移植后每日检测血糖、c肽水平。同时分离移植后的肝淋巴细胞,测定活化细胞的比例和信号通路的变化。结果制备的人工脂质体直径在50 ~ 500 nm之间,易于装载生物素化肽。Qa-1/PD-L1脂质体可通过激活SHP1/2和抑制Syk通路,显著抑制MLR淋巴细胞增殖、IFN-γ的激活和分泌。在体内,Qa-1/PD-L1脂质体可通过激活SHP1/2来抑制肝淋巴细胞的激活,保护异体胰岛移植物,维持受体正常血糖水平。结论Qa-1/PD-L1脂质体可有效抑制异体移植排斥反应,改善胰岛移植预后。关键词:鼠标;胰岛移植;Qa-1;PD-L1;移植排斥;SHP1/2
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引用次数: 0
A comparative study of unrelatedversus matched-sibling donor allogeneic hematopoietic stem cell transplantation for leukemic children 非亲缘与配对兄弟姐妹供体异基因造血干细胞移植治疗白血病儿童的比较研究
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.012
Binglei Zhang, Jian Zhou, Yanli Zhang, R. Gui, Yuewen Fu, Y. Zu, F. Yu, Hui-fang Zhao, Zhen Li, B. Fang, Xudong Wei
Objective To evaluate the efficacy of unrelated donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) for leukemic children. Methods Clinical data of 54 leukemic children undergoing allo-HSCT were retrospectively analyzed from May 2006 to March 2018. According to the source of donor, they were divided into matched sibling donor allo-HSCT group (MSD, n=27) and unrelated donor group (URD, n=27). The clinical outcomes of leukemic children receiving URD allo-HSCT were assessed and those in MSD allo-HSCT group were enrolled as control. Results One patient with refractory AML was not implanted in URD group and the remaining 53 cases were successful in hematopoietic reconstitution. The time of neutrophil and platelet, the incidence of acute graft-versus-host disease (aGVHD), chronic GVHD (cGVHD), generalized cGVHD and their transplant-related complications including pulmonary complications, hemorrhagic cystitis between two groups were not statistically different (P>0.05). The incidence of serious aGVHD, cytomegalovirus (CMV) and EB virus (EBV) infection was significantly higher in URD group than that in MSD group (P 0.05). Conclusions In leukemic children, although the incidence of complications post URD allo-HSCT is significantly increased, the prognosis is comparable to MSD allo-HSCT. It is a good choice when there is no suitable sibling donor. Key words: Allogeneic hematopoietic stem cell transplantation; Children; Leukemia; Unrelated donor; Matched sibling donor
目的探讨非亲属供体异体造血干细胞移植治疗儿童白血病的疗效。方法回顾性分析2006年5月至2018年3月54例接受同种异体造血干细胞移植的白血病患儿的临床资料。根据供体来源将其分为匹配的兄弟姐妹供体同种异体造血干细胞组(MSD, n=27)和无血缘关系供体组(URD, n=27)。评估接受URD同种异体造血干细胞移植的白血病儿童的临床结果,并将MSD同种异体造血干细胞移植组的儿童作为对照。结果1例难治性急性髓系白血病患者未植入URD,其余53例患者造血重建成功。两组患者的中性粒细胞和血小板时间、急性移植物抗宿主病(aGVHD)、慢性移植物抗宿主病(cGVHD)、全身性移植物抗宿主病(cGVHD)发生率及肺并发症、出血性膀胱炎等移植物相关并发症发生率比较,差异均无统计学意义(P < 0.05)。URD组严重aGVHD、巨细胞病毒(CMV)、EB病毒(EBV)感染发生率显著高于MSD组(P < 0.05)。结论在白血病儿童中,虽然URD异体造血干细胞移植后并发症的发生率明显增加,但预后与MSD异体造血干细胞移植相当。当没有合适的兄弟姐妹供体时,这是一个很好的选择。关键词:异基因造血干细胞移植;孩子;白血病;无关的捐赠;匹配的兄弟姐妹供体
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引用次数: 0
Berberine prevents steatotic liver ischemia reperfusion injury by inhibiting endoplasmic reticulum stress and autophagy 小檗碱通过抑制内质网应激和自噬来预防脂肪变性肝缺血再灌注损伤
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.013
Nan Zhang, M. Sheng, Man Wu, Xinyue Zhang, Yijie Ding, Wenli Yu, H. Du
Objective To explore the effect of berberine (BBR) on steatotic liver ischemia reperfusion injury and analyze the role of endoplasmic reticulum stress and autophagy. Methods Thirty-four Wistar rats were fed with a high-fat diet for 12 weeks and 2 rats were randomly selected after 8 weeks to observe pathological changes and confirm the model of steatotic liver successfully. Then before opening and closing abdominal cavity, 32 rats were divided into I/R group (normal saline was intragastrically 4 weeks before performing cold I/R treatment), BBR group (normal saline was replaced by BBR, BBR was intragastrically at a dose of 300 mg·kg-1·d-1 weeks and others were the same as I/R group) and TG group (TG was intraperitoneally at a dose of 0.2 mg·kg-1 24h pre-operation and others were the same as BBR group ). Then the rats were sacrificed at 6h post-reperfusion. Blood samples were collected from inferior vena cava and hepatic tissues harvested. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected, histopathologic changes observed by Hematoxylin & Eosin (HE) staining, oxidative stress and inflammation determined by ELISA kit and the expressions of p-PERK, CHOP, Bip, LC3, Beclin-1 and p62 detected by Western blot. Results As compared with Sham group, the serum levels of ALT and AST were significantly higher in I/R, BBR and TG groups (P<0.05). And hepatic histological changes were severe and oxidative stress increased in parallel with the enhancement of pro-inflammation (P<0.05). In BBR group, the level of hepatic enzymes declined, liver injury was milder, oxidative stress decreased and pro-inflammation was lesser compared with I/R and TG groups (P<0.05). Additionally, as compared with sham group, the expressions of p-PERK, CHOP, Bip, LC3, Beclin-1 and p62 were up-regulated in I/R and BBR groups (P<0.05). TG group increased the levels of LC3, Beclin-1 and p62 (P<0.05). Interestingly, compared with I/R group, BBR pretreatment down-regulated the expressions of p-PERK, CHOP, Bip, LC3, Beclin-1 and p62 (P<0.05). TG group had the higher expressions of LC3, Beclin-1 and p62 than those of BBR group (P<0.05). Conclusions BBR pretreatment can protect steatotic liver ischemia reperfusion injury. And the mechanisms may be attributed to the inhibitions of endoplasmic reticulum stress and autophagy. Key words: Rat; Steatotic liver; Berberine; Ischemia reperfusion injury; Endoplasmic reticulum stress; Autophagy
目的探讨小檗碱(BBR)对脂肪变性肝缺血再灌注损伤的影响,并分析其内质网应激和自噬的作用。方法采用高脂饲料喂养12周的Wistar大鼠34只,8周后随机取2只,观察病理变化,成功确认脂肪变性肝模型。在开闭腹腔前,将32只大鼠分为I/R组(在进行冷I/R治疗前4周灌胃生理盐水)、BBR组(以BBR代替生理盐水,BBR灌胃剂量为300 mg·kg-1·d-1周,其余与I/R组相同)和TG组(TG术前24h腹腔灌胃剂量为0.2 mg·kg-1,其余与BBR组相同)。再灌注后6h处死大鼠。采集下腔静脉和肝组织的血液样本。检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,苏木精伊红(HE)染色观察组织病理变化,ELISA试剂盒检测氧化应激和炎症反应,Western blot检测p-PERK、CHOP、Bip、LC3、Beclin-1、p62表达。结果与Sham组比较,I/R、BBR、TG组大鼠血清ALT、AST水平均显著升高(P<0.05)。肝组织改变严重,氧化应激水平随促炎症水平升高而升高(P<0.05)。与I/R和TG组相比,BBR组肝酶水平下降,肝损伤较轻,氧化应激降低,促炎症反应减轻(P<0.05)。I/R和BBR组P - perk、CHOP、Bip、LC3、Beclin-1、p62表达上调(P<0.05)。TG组LC3、Beclin-1、p62水平升高(P<0.05)。有趣的是,与I/R组相比,BBR预处理可下调P - perk、CHOP、Bip、LC3、Beclin-1和p62的表达(P<0.05)。TG组LC3、Beclin-1、p62的表达高于BBR组(P<0.05)。结论BBR预处理对脂肪变性肝缺血再灌注损伤具有保护作用。其机制可能与抑制内质网应激和自噬有关。关键词:大鼠;肝脏脂肪变性;小檗碱;缺血再灌注损伤;内质网应力;自噬
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引用次数: 0
Application of image post-processing technique to measure spleen volume and evaluate the effect of orthotopic liver transplantation on relieving hypersplenism 应用图像后处理技术测量脾脏体积,评价原位肝移植缓解脾功能亢进的效果
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.010
Jian He, Qingjun Guo, Yan Xie, Li Zhang, D. Tian, Hong-hai Wang, Chiyi Chen, Wentao Jiang
Objective To employ image post-processing technique measuring splenic volume for evaluating the mitigation effect of end-stage liver disease patients complicated with different degrees of hypersplenism undergoing orthotopic liver transplantation. Methods For 55 end-stage liver disease patients with hypersplenism undergoing orthotopic liver transplantation, the changes in splenic volume were measured before and after transplantation by image post-processing system Advantage Workstation 46 (AW46) and the changes of splenic thickness, portal flow velocity and platelet counts observed during perioperative period. Results Postoperative splenic volumes of 55 recipients were (562.90±49.16) cm3, significantly decreased than preoperative (850.50±77.99) cm3 (P<0.05) and reduction ratio was (31.70±2.76)%. Splenic thickness at different postoperative timepoints was significantly lower than that pre-operation (P<0.05) and stabilized at 1 month post-transplantation; Splenic volume was positively correlated with splenic thickness (r=0.78, P<0.05). Portal flow velocity at different postoperative timepoints increased significantly as compared with preoperative (P<0.05), peaked at (380.70±21.80) mm/s at 1 month post-transplantation, declined and stabilized at 3 months post-transplantation. Platelet counts (PLT) at different postoperative timepoints were significantly higher than those at pre-operation (P<0.05), peaked (193.40±10.36)×109/L at 2 weeks post-transplantation, dropped and remained at 2 months post-transplantation; Splenic volume was negatively correlated with PLT (r=-0.44, P<0.05). And hypersplenism recovery rate and recurrence rate within 10 months post-transplantation was (78.79±2.29)% and (17.75±2.31)% respectively. Conclusions Orthotopic liver transplantation can effectively alleviate hypersplenism for most end-stage liver diseases. Using image post-processing system, splenic volume may be calculated and blood routine and ultrasound are simultaneously used for assessing the outcomes of liver transplantation on hypersplenism. Key words: Hypersplenism; Liver transplantation; Spleen volume; Platelet
目的应用图像后处理技术测量脾脏体积,评价终末期肝病合并不同程度脾功能亢进患者行原位肝移植的缓解效果。方法采用图像后处理系统Advantage Workstation 46 (AW46)对55例终末期肝病脾功能亢患者行原位肝移植,观察移植前后脾体积变化,围手术期脾厚度、门静脉血流速度及血小板计数的变化。结果55例受术者术后脾体积为(562.90±49.16)cm3,明显低于术前(850.50±77.99)cm3 (P<0.05),缩小率为(31.70±2.76)%。术后各时间点脾厚度均显著低于术前(P<0.05),并在移植后1个月趋于稳定;脾体积与脾厚度呈正相关(r=0.78, P<0.05)。术后不同时间点门静脉流速与术前比较均显著升高(P<0.05),移植后1个月门静脉流速达到峰值(380.70±21.80)mm/s,移植后3个月门静脉流速下降并趋于稳定。术后各时间点血小板计数(PLT)均显著高于术前(P<0.05),在移植后2周达到峰值(193.40±10.36)×109/L,在移植后2个月下降并保持不变;脾体积与PLT呈负相关(r=-0.44, P<0.05)。移植后10个月内脾功能亢进的恢复率为(78.79±2.29)%,复发率为(17.75±2.31)%。结论原位肝移植可有效缓解多数终末期肝病的脾功能亢进。利用图像后处理系统,计算脾脏体积,同时利用血常规和超声来评估脾功能亢进肝移植的预后。关键词:脾功能亢进;肝移植;脾脏体积;血小板
{"title":"Application of image post-processing technique to measure spleen volume and evaluate the effect of orthotopic liver transplantation on relieving hypersplenism","authors":"Jian He, Qingjun Guo, Yan Xie, Li Zhang, D. Tian, Hong-hai Wang, Chiyi Chen, Wentao Jiang","doi":"10.3760/CMA.J.ISSN.0254-1785.2019.02.010","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.0254-1785.2019.02.010","url":null,"abstract":"Objective \u0000To employ image post-processing technique measuring splenic volume for evaluating the mitigation effect of end-stage liver disease patients complicated with different degrees of hypersplenism undergoing orthotopic liver transplantation. \u0000 \u0000 \u0000Methods \u0000For 55 end-stage liver disease patients with hypersplenism undergoing orthotopic liver transplantation, the changes in splenic volume were measured before and after transplantation by image post-processing system Advantage Workstation 46 (AW46) and the changes of splenic thickness, portal flow velocity and platelet counts observed during perioperative period. \u0000 \u0000 \u0000Results \u0000Postoperative splenic volumes of 55 recipients were (562.90±49.16) cm3, significantly decreased than preoperative (850.50±77.99) cm3 (P<0.05) and reduction ratio was (31.70±2.76)%. Splenic thickness at different postoperative timepoints was significantly lower than that pre-operation (P<0.05) and stabilized at 1 month post-transplantation; Splenic volume was positively correlated with splenic thickness (r=0.78, P<0.05). Portal flow velocity at different postoperative timepoints increased significantly as compared with preoperative (P<0.05), peaked at (380.70±21.80) mm/s at 1 month post-transplantation, declined and stabilized at 3 months post-transplantation. Platelet counts (PLT) at different postoperative timepoints were significantly higher than those at pre-operation (P<0.05), peaked (193.40±10.36)×109/L at 2 weeks post-transplantation, dropped and remained at 2 months post-transplantation; Splenic volume was negatively correlated with PLT (r=-0.44, P<0.05). And hypersplenism recovery rate and recurrence rate within 10 months post-transplantation was (78.79±2.29)% and (17.75±2.31)% respectively. \u0000 \u0000 \u0000Conclusions \u0000Orthotopic liver transplantation can effectively alleviate hypersplenism for most end-stage liver diseases. Using image post-processing system, splenic volume may be calculated and blood routine and ultrasound are simultaneously used for assessing the outcomes of liver transplantation on hypersplenism. \u0000 \u0000 \u0000Key words: \u0000Hypersplenism; Liver transplantation; Spleen volume; Platelet","PeriodicalId":9885,"journal":{"name":"Chineae Journal of Organ Transplantation","volume":"7 1","pages":"107-110"},"PeriodicalIF":0.0,"publicationDate":"2019-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91328210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
ABO-incompatible kidney transplantation in highly presensitized recipients using deceased donors: a case report and literature review abo血型不相容肾移植在高度敏感的受者使用死者供者:一个病例报告和文献综述
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.005
Lan Zhu, H. Feng, Lu Wang, Zhiliang Guo, Juan Wang, Liang Huang, Hui Guo, Gang Chen
Objective To explore the feasibility and safety of kidney transplantation in highly sensitized recipients by using ABO incompatible (ABOi) and yet human leucocyte antigen (HLA) supremely matched deceased donor kidneys and summarize the literatures as well. Methods A kidney graft from a deceased donor of blood type B was transplanted to a highly presensitized recipient of blood type O to achieve a HLA matching number of 7/8 in May 2018. Donor specific antibody (DSA) against HLA was negative and baseline anti-B IgM 1∶16. Plasmapheresis (PP) plus intravenous immunoglobulin (IVIG) plus anti-CD20 antibodies were offered on operation day. Clinical data was retrospectively analyzed. Results Renal graft functioned immediately and achieved a normal level of serum creatinine (SCr) at d2 after transplantation. However, the value of SCr increased to 131 μmol/l at d9 with a simultaneously elevated level of anti-B IgM from 1∶2 at d7 to 1∶16. A renal graft biopsy at d11 showed mild inflammation in peritubular capillaries and focal tubulitis with minimal interstitial infiltration. No de novo DSA was detected. Then PP plus IVIG were then given twice, followed by an administration of IVIG alone for another 2 days (20 g/d). After treatments, SCr had a range of 120-140 μmol/l and anti-B IgM level decreased to 1∶4 at d21 post-transplantation. During a follow-up of 6 months, there was no onset of proteinuria or infection and the last value of SCr was 114 μmol/L. Conclusions In HLA highly sensitized recipients awaiting for transplant opportunities, successful prevention of HLA antibodies-mediated rejection may be achieved by using ABO incompatible and yet HLA compatible deceased donors. Key words: Kidney transplantation; Sensitization; ABO incompatible; HLA; Donor specific antibodies
目的探讨ABO不相容(ABOi)和人类白细胞抗原(HLA)高度匹配的已故供体肾脏在高度敏感受者肾移植中的可行性和安全性,并对相关文献进行总结。方法2018年5月,将一名已故B型血供者的肾移植给一名高度现敏的O型血供者,达到7/8的HLA匹配数。供体HLA特异性抗体(DSA)阴性,基线抗- b IgM 1∶16。在手术当天给予血浆置换(PP)联合静脉注射免疫球蛋白(IVIG)加抗cd20抗体。回顾性分析临床资料。结果移植肾术后即刻恢复功能,血清肌酐(SCr)达到正常水平。而SCr在d9时升高至131 μmol/l,同时抗- b - IgM水平由d7时的1∶2升高至1∶16。11岁肾移植活检显示小管周围毛细血管轻度炎症,局灶性小管炎伴少量间质浸润。未发现新生DSA。然后给予PP加IVIG 2次,随后单独给予IVIG 2天(20 g/d)。处理后SCr为120 ~ 140 μmol/l,抗b IgM水平在移植后21 d降至1∶4。随访6个月,无蛋白尿和感染发生,SCr末值为114 μmol/L。结论:在等待移植机会的HLA高度敏感受者中,可以通过使用ABO不相容和HLA兼容的已故供者来成功预防HLA抗体介导的排斥反应。关键词:肾移植;敏化;ABO血型不相容;HLA;供体特异性抗体
{"title":"ABO-incompatible kidney transplantation in highly presensitized recipients using deceased donors: a case report and literature review","authors":"Lan Zhu, H. Feng, Lu Wang, Zhiliang Guo, Juan Wang, Liang Huang, Hui Guo, Gang Chen","doi":"10.3760/CMA.J.ISSN.0254-1785.2019.02.005","DOIUrl":"https://doi.org/10.3760/CMA.J.ISSN.0254-1785.2019.02.005","url":null,"abstract":"Objective \u0000To explore the feasibility and safety of kidney transplantation in highly sensitized recipients by using ABO incompatible (ABOi) and yet human leucocyte antigen (HLA) supremely matched deceased donor kidneys and summarize the literatures as well. \u0000 \u0000 \u0000Methods \u0000A kidney graft from a deceased donor of blood type B was transplanted to a highly presensitized recipient of blood type O to achieve a HLA matching number of 7/8 in May 2018. Donor specific antibody (DSA) against HLA was negative and baseline anti-B IgM 1∶16. Plasmapheresis (PP) plus intravenous immunoglobulin (IVIG) plus anti-CD20 antibodies were offered on operation day. Clinical data was retrospectively analyzed. \u0000 \u0000 \u0000Results \u0000Renal graft functioned immediately and achieved a normal level of serum creatinine (SCr) at d2 after transplantation. However, the value of SCr increased to 131 μmol/l at d9 with a simultaneously elevated level of anti-B IgM from 1∶2 at d7 to 1∶16. A renal graft biopsy at d11 showed mild inflammation in peritubular capillaries and focal tubulitis with minimal interstitial infiltration. No de novo DSA was detected. Then PP plus IVIG were then given twice, followed by an administration of IVIG alone for another 2 days (20 g/d). After treatments, SCr had a range of 120-140 μmol/l and anti-B IgM level decreased to 1∶4 at d21 post-transplantation. During a follow-up of 6 months, there was no onset of proteinuria or infection and the last value of SCr was 114 μmol/L. \u0000 \u0000 \u0000Conclusions \u0000In HLA highly sensitized recipients awaiting for transplant opportunities, successful prevention of HLA antibodies-mediated rejection may be achieved by using ABO incompatible and yet HLA compatible deceased donors. \u0000 \u0000 \u0000Key words: \u0000Kidney transplantation; Sensitization; ABO incompatible; HLA; Donor specific antibodies","PeriodicalId":9885,"journal":{"name":"Chineae Journal of Organ Transplantation","volume":"36 1","pages":"83-87"},"PeriodicalIF":0.0,"publicationDate":"2019-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77990119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Three cases of orthotopic cardiac transplantation for congenital dextrocardia 原位心脏移植治疗先天性右心3例
Pub Date : 2019-02-20 DOI: 10.3760/CMA.J.ISSN.0254-1785.2019.02.011
N. Dong, Jin-ping Liu, Guo-hua Wang, Yixuan Wang, Jie Cai, Jing Zhang
Objective To summarize the surgical strategies of orthotopic cardiac transplantation for congenital dextrocardia. Methods Three patients with congenital dextrocardia suffered from end-stage heart failure and underwent orthotopic cardiac transplantation from March 2014 to September 2017. They were aged 10, 29, 13 years respectively. Donor hearts were from brain death donors and procured with extra length on inferior vena cava, aorta and pulmonary artery tissues. After cardiectomy, left atrial-atrial anastomosis was performed initially between donor’s left-upper pulmonary vein orifices and recipient’s left-lower pulmonary vein orifices. Apex was orientated at a 90 degrees’ clockwise to right. Then aorta, inferior and superior vena cava and last pulmonary artery were anastomosed continuously. The prosthetic conduits were also used owing to a lack of tissue. Results All operations were successful. The cold ischemic time was (130-375)(251.00±122.53) min, cardiopulmonary bypass time (127-212)(179.67±55.72) min and aortic clamp time (38-105)(65.33±35.166) min. Two patients had stable hemodynamics and recovered well after HTx. During a follow-up period of 1.5-3.5 years, echocardiography showed excellent cardiac functions without blood flow obstruction. Chest radiology showed well-placed donor heart in right mediastinum. One left-sided patient with total cavopulmonary connection before HTx died at 59 days after HTx because of pneumonia and multiple organ failure. Conclusions Heart transplantation is curative for patients with congenital dextrocardia and surgical strategies are the key factor of successful treatment. Key words: Congenital heart disease; Dextrocardia; Heart transplantation
目的总结原位心脏移植治疗先天性右心的手术策略。方法2014年3月至2017年9月,3例终末期心力衰竭的先天性右心患者行原位心脏移植手术。年龄分别为10岁、29岁和13岁。供体心脏来自脑死亡供体,并在下腔静脉、主动脉和肺动脉组织上获得额外的长度。心脏切除术后,首次在供体左上肺静脉口与受体左下肺静脉口之间进行左房房吻合。顶点方向为顺时针向右90度。然后连续吻合主动脉、下腔静脉、上腔静脉和末段肺动脉。由于缺乏组织,也使用了假体导管。结果所有手术均成功。冷缺血时间为(130 ~ 375)(251.00±122.53)min,体外循环时间为(127 ~ 212)(179.67±55.72)min,主动脉夹持时间为(38 ~ 105)(65.33±35.166)min。两例患者血流动力学稳定,HTx术后恢复良好。随访1.5 ~ 3.5年,超声心动图显示心功能良好,无血流阻塞。胸部x线显示供体心脏位于右侧纵膈。1例左侧全腔隙肺连接患者在HTx术后59天因肺炎和多器官衰竭死亡。结论心脏移植治疗先天性右心是有效的,手术策略是治疗成功的关键因素。关键词:先天性心脏病;右位心;心脏移植
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引用次数: 1
期刊
Chineae Journal of Organ Transplantation
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