Allogeneic skin transplantation is an important clinical treatment for many diseases. Although Galectin-9 demonstrates multifaceted roles in modulating immune cell homeostasis and inflammation, its precise impact on balancing effector T cells and Tregs during allogeneic skin transplantation remains uncertain. This work was performed to evaluate the modulation of the survival time of allogeneic skin grafts by Gal-9 and to explore the critical mechanism involved in this process. Skin graft transplantation was conducted using C57BL/6 and BALB/c mice. Additionally, the levels of IL-2, IFN-γ, IL-4, and IL-17A were measured. Hematoxylin and eosin staining assay was performed to analyze the pathological conditions of skin grafts of experiment mice. The results revealed that Gal-9 noticeably prolonged the survival of the allogeneic skin graft and ameliorated the damage caused by acute immune rejection. Furthermore, Gal-9 resulted in selective reduction of effectors T cells such as Th1, and Th17. Simultaneously, Gal-9 didn't attenuate the protective function for allograft, which alleviated the immune rejection caused by abnormal immune imbalance. Gal-9 exhibited a therapeutic effect on the allogeneic skin graft by selectively reducing CD4+TIM-3+ T effector cells and inducing a shift from a Th1 to an anti-inflammatory Th2 response. Furthermore, Gal-9 did not attenuate the protective function. Our present study may represent a novel therapeutic candidate for modulating effector T cells and Tregs imbalance-based therapy of allograft transplantation.

Sensitized recipients have an increased risk of kidney transplantation due to the immune memory of human leucocyte antigen. They lag on the waiting list and have poorer outcomes of transplantation. The society should give every patient an equal opportunity for treatment. Facing this worldwide problem, Chinese transplant community has some practical difficulties under current status of transplantation development in our country. It requires the cooperation of transplant laboratories, organ procurement organizations, clinicians, and the national organ allocation system to explore a path of solution.

Background . Th17 cell differentiation is involved in the development and progression of many diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Present study mainly focused on the role of LINC-XIST in Th17 cell differentiation. Methods . The naïve CD4+ T cells were isolated from human whole blood. Cells were cultured under Th17 cell-polarizing condition for 6 days. The expression of LINC-XIST and miR-153-3p was measured by qPCR. The relationship between LINC-XIST, miR-153-3p, and ETS1 was predicted by TargetScan website and authenticated by luciferase reporter assay. ELISA assays were conducted to evaluate the IL-17 concentration. Western blot was utilized to measure the protein expression of ETS1. Th17 cell frequency was examined by flow cytometry. Results . The expression of XIST markedly decreased and miR-153-3p expression markedly increased with Th17 cell differentiation. The mRNA expression of IL-17, IL-17 concentration, and Th17 cell frequency were observably decreased in overexpressed LINC-XIST group. Luciferase reporter assay authenticated that miR-153-5p was directly regulated by LINC-XIST. miR-153-3p inhibitor observably decreased IL-17 concentration, mRNA expression of IL-17, and Th17 cell frequency while si-XIST reversed this impact. ETS1 was confirmed to be regulated by miR-153-5p via luciferase reporter assay. In addition, ETS1 markedly decreased IL-17 mRNA expression, IL-17 concentration, and Th17 cell frequency while miR-153-5p mimic reversed this impact. Conclusion . LNCRNA XIST inhibited miR-377-3p to hinder Th17 cell differentiation through upregulating ETS1.

Background Kidneys obtained from deceased donors increase the incidence of delayed graft function (DGF) after renal transplantation. Here we investigated the influence of the risk factors of donors with DGF, and developed a donor risk scoring system for DGF prediction. Methods This retrospective study was conducted in 1807 deceased kidney donors and 3599 recipients who received donor kidneys via transplants in 29 centers in China. We quantified DGF associations with donor clinical characteristics. A donor risk scoring system was developed and validated using an independent sample set. Results The incidence of DGF from donors was 19.0%. Six of the donor characteristics analyzed, i.e., age, cause of death, history of hypertension, terminal serum creatinine, persistence of hypotension, and cardiopulmonary resuscitation (CPR) time were risk factors for DGF. A 49-point scoring system of donor risk was established for DGF prediction and exhibited a superior degree of discrimination. External validation of DGF prediction revealed area under the receiver-operating characteristic (AUC) curves of 0.7552. Conclusions Our study determined the deceased donor risk factors related to DGF after renal transplantation pertinent to the Chinese cohort. The scoring system developed here had superior diagnostic significance and consistency and can be used by clinicians to make evidence-based decisions on the quality of kidneys from deceased donors and guide renal transplantation therapy.

肾移植是治疗终末期肾病的唯一有效手段.自2015年1月1日起,公民逝世后捐献器官(DCD)已成为我国器官移植唯一合法来源.供体短缺使供肾的应用标准逐渐扩大,供肾质量的差异显著影响肾移植预后.在此,我们通过归纳综合国内外临床经验及相关操作指南,对供肾质量评估和维护,以及肾功能预测指标进行总结,制定了供肾质量控制标准,对临床肾移植提供一定的理论指导.

如何改善移植肾的长期预后和解决供肾短缺仍是困扰临床医师的两大难题,其中缺血-再灌注损伤(IRI)、排斥反应、感染、免疫抑制治疗是肾移植研究领域的重要问题.因此,加强肾移植领域文献学习,了解移植肾相关疾病的本质及国际前沿研究热点,有助于临床进一步改善移植肾功能和延长移植肾的存活时间.本文就2020年第3季度肾移植领域的研究热点、最新进展并结合第12期岭南读书会的会议纪要作一文献解读,并从IRI、排斥反应和感染3个方面进行综述.

器官移植受者的生存质量与免疫状态密切相关.与其他实体器官移植相比,肺移植受者的长期预后较差,其涉及的免疫学机制更为复杂,既有共性又有特性.因此,深入了解同种异体肺移植免疫应答过程中的免疫学机制对于改善肺移植受者的长期生存尤为重要.本文从肺脏免疫细胞组成的独特性、肺移植术后排斥反应特点、肺移植病原体感染的早期预警和鉴别诊断以及肺移植相关并发症等方面进行探讨,总结同种异体肺移植涉及免疫学相关的临床诊断和基础研究进展,旨在阐述肺移植的免疫学特点,为临床提高肺移植受者的长期生存率以及移植物失功的防治水平等提供理论依据.

目的:对比脂多糖(lipopolysaccharide,LPS)腹腔注射及盲肠结扎穿刺(cecum ligation and puncture,CLP)诱导脓毒血症肾损伤建模方法的肾脏损伤情况及炎症过程特点.方法:将48只8～10周龄C57BL/6雄性小鼠分为LPS组(n = 16),磷酸盐缓冲溶液(phosphate buffer saline,PBS)组(n=8),CLP组(n= 16)和假手术组(sham组,n=8).LPS组根据小鼠体质量注射LPS溶液20 mg/kg(浓度1 mg/ml),PBS组注射等量PBS,CLP组在距结肠末端1 cm行结扎术,并用21号针对穿两孔后关闭腹腔,sham组仅开腹暴露盲肠闭合腹腔.分别在建模后0 h、6 h、12 h、24 h、48 h处死小鼠,比较观察期内各组小鼠肾功能指标、病理损伤及炎症指标变化.用免疫荧光染色观察肾小管上皮细胞的凋亡.结果:PBS组及sham组小鼠建模前后血清肌酐、尿素氮水平比较,差异无统计学意义(P＞0.05);而LPS组和CLP组小鼠肌酐、尿素氮迅速升高,均在24 h达峰值,分别与建模前比较,差异有统计学意义(均P＜0.05),且48 h后均逐渐恢复.肾脏病理检查提示,LPS组及CLP组均显示肾小管上皮细胞空泡形成明显增多,小管坏死及凋亡不明显,但炎症反应过程有显著差别,其中LPS组白介素6、肿瘤坏死因子等炎症因子水平较CLP组迅速升高,6 h达到峰值后逐渐降低,且CLP组下降较LPS组缓慢.细胞凋亡染色显示LPS组和CLP组均存在局部凋亡,而PBS组和sham组均未见明显凋亡.结论:LPS腹腔注射及CLP均能成功建立脓毒血症肾损伤模型,其中LPS模型的全身性炎症反应剧烈,重复性好,而CLP模型更贴近临床败血症的炎症特点,在科研实践中可根据需要选择合适的模型.

目的 探讨骨髓间充质干细胞(BMSC)对小鼠缺血-再灌注急性肾损伤(IR-AKI)过程中白细胞介素(IL)-10和肿瘤坏死因子(TNF)-α表达的影响.方法 将小鼠随机分为假手术组(对照组)、缺血-再灌注损伤组(IRI组)和BMSC治疗组(BMSC组),每组6只.检测各组小鼠肾功能及病理学改变;检测各组小鼠肾组织细胞凋亡情况;检测各组小鼠血清IL-10和TNF-α的表达水平.将小鼠BMSC随机分为对照组和缺氧复氧组(IRI组),检测各组细胞上清IL-10和TNF-α的表达水平.结果 对照组小鼠肾组织结构正常,IRI组肾组织结构损伤严重,BMSC组损伤较轻.与对照组比较,IRI组和BMSC组肾组织损伤评分较高;与IRI组比较,BMSC组小鼠肾组织损伤学评分较低(均为P<0.05).与对照组比较,IRI组小鼠血清肌酐(Scr)和血尿素氮(BUN)水平升高,BMSC组BUN水平升高;与IRI组比较,BMSC组小鼠Scr和BUN水平下降(均为P<0.05).IRI组肾组织凋亡细胞数量多于BMSC组和对照组,BMSC组凋亡细胞数量多于对照组(均为P<0.05).与对照组比较,IRI组小鼠血清IL-10和TNF-α水平均升高,BMSC组小鼠血清TNF-α水平下降,IL-10水平升高;与IRI组比较,BMSC组小鼠血清IL-10和TNF-α水平均下降(均为P<0.05).IRI组细胞上清IL-10、TNF-α水平与对照组比较,差异均无统计学意义(P=0.080、0.627).结论 BMSC输注可降低肾IRI及炎症反应,其机制可能是通过抑制TNF-α表达,而非促进IL-10的表达.

We sincerely appreciate your professional comments and we are not surprised that you have concerns about the organ resources. That is because using organs procured from executed prisoners is considered unethical and the articles suspected involving relevant data are often rejected by many academic journals. But I want to say that from Jan 1, 2015, no organ from executed prisoners is used any more in China.

目的 探讨再次肾移植病人临床管理策略及其临床疗效.方法 依据解放军总医院第八医学中心和北大国际医院制订的再次肾移植临床管理策略对2017年6月～2019年6月共17例再次肾移植病人规范性管理,均选择公民逝世后器官捐献(DCD)供肾移植,观察术后急性排斥反应(AR)、移植肾功能延迟恢复(DGF)、肺部感染等临床指标.结果 二次移植14例(82.4％),三次移植3例(17.6％);移植肾切除5例(29.4％),移植肾保留12例(70.6％);预存抗体阳性脱敏5例(29.4％),抗体阴性非脱敏12例(70.6％).AR共4例(23.5％),肺部感染共6例(35.3％),DGF共1例(5.9％).移植肾切除组AR 1例(20％)肺部感染1例(20％);移植肾保留组AR 3例(25％),肺部感染5例(41.7％).脱敏组AR 1例(20％),肺部2例(40％);非脱敏组AR 3例(25％)肺部感染4例(33.3％).中位随访时间14.5个月(6～36个月),1年人肾存活率94.1％,1例(5.9％)死亡.结论 合理规范的临床管理策略可使再次肾脏移植获得较好的临床效果.不切除失功的移植肾病人肺部感染机率明显高于移植肾切除病人.脱敏治疗可以明显降低再次肾脏移植的排斥风险,且不会明显增加感染机会.

中华医学会2019年器官移植学年会于2019年10月25日至27日在长沙举行,本次大会以“传承、创新、规范、提升”为主题.共有1 600余位国内外器官移植及相关学科的老中青专家学者参加,聚焦学术热点,分享交流经验,推动器官移植发展由“数量规模型”向“质量提升型”转变,促进器官移植科学、平衡、规范和高质量发展的经验和做法.大会共收到稿件1 117篇,大会发言279人次,在14个分会场进行了多种形式的学术交流.同时,为配合器官移植规范化诊疗体系的构建,推进器官移植规范化发展,对新修订的《中国器官移植诊疗技术操作规范》中24个章节进行解读.

目的:探讨程序优化下后腹腔镜下左侧活体供肾切取术(LLDN)238例的临床经验及安全性.方法:选择2011年11月－2019年3月在中国人民解放军总医院第八医学中心移植外科由单一术者行后腹腔镜下左侧亲属供肾切取术的238例供者资料.手术常规取腰部3个穿刺点,采用程序化供肾切取的游离顺序:①充分利用肾周无血管解剖层面,首先游离肾脏腹侧面,快速显露肾静脉腹侧,然后从逆时针方向游离肾下极、输尿管、肾动脉和肾静脉背侧、肾上极,最后与肾静脉腹侧面汇合.在肾脏游离过程中完成血管属支的处理和输尿管的显露;②保留输尿管周围脂肪,尽可能保护输尿管的血供,游离输尿管至跨髂血管处剪断;③充分游离供肾及动静脉后,将腹侧Trocar切口延长5 cm,术者左手握住肾脏,牵引供肾血管,用Hem-o-lok分别夹闭肾动脉和肾静脉后剪断,迅速取出供肾交台下灌注及修整.结果:238例供肾切取手术均成功,无中转开腹及供肾废弃,供者100％安全.左肾动脉多支30例,其中2支25例,3支5例(3例全部术中吻合,2例第3支细小分支CTA未显影,术中偶然发现结扎废弃).腔镜操作手术时间37～186 min,平均(73±22)min.热缺血时间1.1～4.5 min,平均(2.3± 0.8)min.出血10～350 mL,平均(45±20)mL,均未输血.发生手术并发症6例,淋巴瘘1例,短期自愈,腰静脉损伤出血2例,被膜下血肿3例,均无严重并发症.术后住院时间5～10 d,平均(6.3土1.2)d.238例供者随访1～15个月,平均7个月,均健康.结论:程序优化下后腹腔镜下亲属供肾切取术安全可靠,可以降低学习曲线,提高供肾质量.

肾移植是治疗终末期肾病最有效的方法，但依然面临着许多难以解决的问题，其中移植排斥反应和移植术后感染依然是影响肾移植受者生存最主要的因素。免疫系统在移植排斥和移植感染中均发挥着至关重要的作用，但是其相关机制尚未完全阐明。单细胞测序技术的发展为解析移植排斥及感染过程中复杂的免疫调控网络提供了有效的技术方法，并将推动对移植免疫应答机制以及移植感染机制更为全面而深刻的理解。.

Objective:To explore the efficacy and safety of simultaneous pancreas and kidney transplantation(SPK)from donors of different ages.Methods:A total of 146 SPK operations were completed at Second Affiliated Hospital of Guangzhou Medical University from September 2016 to June 2020. The donors were divided into three groups: < 18 yrs group(18 cases), 18 to 39 yrs group(85 cases)and 40 yrs and up group(43 cases). The similarities and differences of SPK efficacy were analyzed for different ages.Results:During a follow-up period of (1~45) months, no statistically significant differences existed in postoperative recovery time, transplanted renal function or transplanted pancreatic function. Graft function at 10 days post-operation normalized and no statistical difference existed among three groups. Glycosylated hemoglobin of three groups at 6 month showed no statistical difference among three groups. Medical complication was perioperative infection. And acute rejection was manifested as pancreas duodenum rejection. The incidence of three groups were 0.06, 0.22 and 0.16; the incidence of kidney acute rejection 0.11, 0.05 and 0.09; the incidence of combined acute pancreas and kidney rejection 0.11, 0.05 and 0.09 and three groups showed no statistical difference. Severe surgical complication was poor healing of incision. The incidence of three groups were 0.11, 0.13 and 0.14 and the major serious complications included intestinal leakage, arterial thrombosis and venous thrombosis. The incidence of intestinal leakage in three groups were 0, 0.01 and 0.05, arterial thrombosis 0, 0.01 and 0.05 and venous thrombosis 0, 0 and 0.05 respectively. Thus no statistical difference existed in the incidence of surgical complications. Patient survival rates in 1-year and 3-year post-transplantation in three groups were 85.0%, 95.0% and 90.4%; pancreatic graft survival rates 85%, 91% and 85.8%; despite death, the pancreatic graft survival rates were 100%, 95.8% and 90.6%; kidney graft survival rate 85.0%, 95.0% and 90.4%.Conclusions:After thorough evaluations, detailed surgical procedures and refined surgical skills, SPK from pediatric and elderly donors with certain age limits has similar clinical outcomes to that from adult donors. Besides, elderly donors still need to be carefully evaluated and long-term follow-ups should be further observed.

目的 探讨后腹腔镜下亲属活体右侧供肾切取术的安全性,并总结相关临床经验.方法 回顾性分析2010年2月至2019年6月解放军总医院第八医学中心实施的14例亲属活体右侧供肾切取术临床资料,其中8例为后腹腔镜下供肾切取(腹腔镜组),6例为经腰部开放供肾切取(开放手术组).腹腔镜组供者常规采取左侧卧位,腰部采用三套管法穿刺.采用成组t检验比较两组供者手术时间、腔静脉切口缝合时间、供肾动脉长度、供肾静脉长度、供肾热缺血时间、手术出血量和术后住院时间.P<0.05为差异有统计学意义.结果 14例亲属活体右侧供肾切取术均成功,两组供者术中均未输血,腹腔镜组供肾切取术中均未中转开腹.腹腔镜组与开放手术组供肾静脉长度分别为(2.2±0.4)和(1.2±0.3)cm,术中出血量分别为(45±12)和(80±10)mL,差异均有统计学意义(t=1.042和5.781,P均<0.05).两种术式手术时间、腔静脉切口缝合时间、供肾动脉长度、供肾热缺血时间及术后住院时间差异均无统计学意义(P均>0.05).截至2019年8月,开放手术组和腹腔镜组供者中位随访时间分别为6个月(3～18个月)和8个月(3～24个月),均健康.受者术前及术后应用巴利昔单抗行免疫诱导治疗,术后免疫抑制方案为CNI+抗代谢类药物+糖皮质激素.移植肾功能均于术后2周内恢复,术后均顺利摆脱透析.截至2019年8月,14例受者随访时间3～12个月,期间受者及移植肾功能均正常.结论 亲属活体右侧供肾获取过程中采用腹腔镜联合Satinsky钳技术安全、可行,可较大限度地延长供肾静脉,且术中出血量更少.

目的 探讨心脏死亡器官捐献(donation after cardiac death,DCD)肾移植术后早期(术后1年以内)受者移植肾丢失的原因.方法 回顾性分析50例DCD供肾移植术后早期移植肾丢失受者的临床资料.结果 受者移植肾丢失50例,移植肾丢失的原因包括排斥反应19例(38.0％)、受者带移植肾功能死亡17例(34.0％)、移植肾血管并发症5例(10.0％)、供体来源泛耐药肺炎克雷伯杆菌(carbapenem-resistant Klebsiella pnermoniae,CRKP)感染4例(8.0％)、原发性无功能肾4例(8.0％)、旧肾原发病(膜性肾病)复发1例(2.0％).DCD供肾移植术后1年内受者移植肾丢失的主要原因为排斥反应,次要原因为受者带功能死亡、移植肾血管并发症、原发性无功能肾、耐药菌感染,旧肾原发病复发少见.结论 总结DCD供肾移植术后早期移植物丢失的原因,为器官移植医师提供临床参考,从而有针对性地加强防治,进一步提高DCD供肾移植1年成功率,减少因患者及家属的不满而引起的医疗纠纷.

目的 应用荟萃分析系统评价HCV感染是否为肾移植后糖尿病(PTDM)的相关危险因素.方法 系统检索中国期刊全文数据库、中国生物医学数据库、PubMed数据库、Embase数据库、Google scholar和Web of science database截至2019年12月公开发表的相关文献.应用Stata 15.1统计软件使用随机效应模型进行荟萃分析,计算相对危险度(RR).结果 共纳入22篇文献,包含129981例肾移植受者.荟萃分析结果显示,HCV感染的肾移植受者术后发生PTDM的风险为非HCV感染者的2.5倍(RR=2.50,95％CI:1.95～3.20,P<0.001).在亚洲、高加索和美洲人种中,HCV感染均为肾移植术后PTDM的危险因素.结论 HCV感染是促进肾移植术后发生PTDM的危险因素,感染者需尽早进行清除HCV的相关治疗.

目的 总结肾移植术后患者早期耐碳青霉烯类肺炎克雷伯菌(carbapenem-resistant Klebsiella pneumoniae,CRKP)感染的临床表现、实验室检查、影像和病理检查结果,探讨其临床特征及机制.方法 对2015年1月-2018年12月我中心确诊的12名肾移植术后早期(移植术后3个月内)CRKP感染患者进行回顾性研究.收集患者的症状、体征、实验室检查、化验检查及临床转归等临床特征信息.采用全自动微生物分析鉴定仪进行菌株的鉴定.应用Vitek 2全自动微生物分析鉴定系统联合纸片扩散法进行药物敏感实验.结果 12例患者平均年龄为45.7岁,其中男性8例.11例发生感染相关的系统性炎症反应综合征,5例发生移植肾区出血,5例发现化脓性坏死分泌物;12例患者均伴随感染性指标如血中性粒细胞及降钙素原升高;且随感染时间长短、侵及组织器官不同而具有不容发的临床表现.移植肾病理检查结果显示移植肾内大量出血伴急性炎症细胞浸润,移植肾髓质内见微脓肿形成.药敏试验发现CRKP对替加环素(9例)和复方磺胺甲恶唑(5例)敏感.结论 移植术后早期移植肾CRKP感染的本质是一种出血坏死性炎症,提示筛查供者CRKP、监测受者出血坏死性炎症征象,全程警惕并管控其引发出血风险是提高CRKP感染救治成功率的关键.