Measurement of donor‐specific HLA antibodies following plasma exchange therapy predicts clinical outcome in pediatric heart and lung transplant recipients with antibody‐mediated rejection

Therapeutic plasma exchange (TPE) is an increasingly utilized immunosuppressive adjunct for treatment of antibody‐mediated rejection (AMR) following organ transplantation. TPE works through removal of donor‐specific HLA antibodies (DSAs) in the recipient's plasma. However, there is no clear laboratory measure evaluating efficacy of removal of DSAs or predicting clinical outcome. We hypothesized that semi‐quantitative DSA measurement by multiplex HLA antibody immunoassay may provide qualitative and quantitative data for DSA clearance and predict treatment efficacy. To evaluate this, we retrospectively investigated DSA concentrations and clinical outcome for 21 pediatric patients who received 31 cycles of TPE peri‐operatively as an adjunct treatment for transplantation in the setting of a positive cytotoxic crossmatch (CXM) and in recipients with AMR following heart or lung transplantation. Immunoassay measurement of DSAs during 15/20 cycles correlated significantly with clinical outcome in the AMR treatment group (P = 0.02), demonstrating the utility of DSA measurement in predicting clinical outcome. In contrast, immunoassay correlated with clinical outcome in only 7/11 patients treated peri‐operatively with TPE for CXM‐positive transplantations (P = 0.58). Changes in mean fluorescence intensity (MFI) for the DSAs correlated better with clinical response than surrogate CXM titers in a subset of patients. We conclude that semi‐quantitative measurement of DSAs by immunoassay can predict clinical response to TPE for treatment of AMR is more reliable than surrogate CXM titer, and should be used to guide TPE treatment of AMR. J. Clin. Apheresis 28:301–308, 2013. © 2013 Wiley Periodicals, Inc.     

香青兰总黄酮对血管紧张素Ⅱ诱导血管平滑肌细胞黏附分子及基质金属蛋白酶表达的影响

目的：研究香青兰总黄酮对血管紧张素Ⅱ（AngⅡ）诱导的大鼠主动脉血管平滑肌细胞（VSMC）黏附分子及基质金属蛋白酶（MMPs）表达的影响。方法：采用贴壁法培养大鼠胸主动脉平滑肌细胞,以AngⅡ为诱导剂,建立VSMC细胞增殖的模型,分别应用10^-7 mol·L^-1AngⅡ以及AngⅡ+不同浓度香青兰总黄酮组（25,50,100 μg·mL^-1）作用24 h,并设空白对照组进行比较。采用免疫组化法检测细胞中细胞间黏附分子（ICAM-1）、血管间黏附分子（VCAM-1）的表达水平。RT-PCR方法检测细胞MMP-2、MMP-9的mRNA表达水平。结果：与对照组比较,AngⅡ组能显著刺激大鼠VSMC细胞内ICAM-1、VCAM-1、MMP-2、MMP-9的表达,香青兰总黄酮不同剂量组联合AngⅡ可在一定程度上抑制AngⅡ诱导的VSMC细胞内ICAM-1、VCAM-1、MMP-2、MMP-9的表达,且呈现一定的剂量依赖关系趋势。结论：香青兰总黄酮具有抑制AngⅡ诱导VSMC黏附分子及基质金属蛋白酶表达的作用。     

HLA-G5在健康人和肝肾移植受者体内的表达分析

目的了解国内健康人和器官移植受者体内人类白细胞抗原-G5(HLA-G5)的表达情况,并探索其表达的时间规律。方法分别采集30例健康人(健康查体正常)、50例肝移植受者(肝移植术后3个月且肝功能稳定)、50例肾移植受者(肾移植术后3个月且肾功能稳定)的外周血各3ml,并采集33例肝肾移植受者术前及术后1周、4周、12周、1年的外周血各3ml。提取血清,采用酶联免疫法(ELISA)检测HLA-G5水平。结果30例健康人中,28例HLA-G5的A值低于0.5,根据标准曲线含量为0.0ng/ml,2例分别为8、9ng/ml。50例肝移植受者HLA-G5表达阳性者16例,阳性率为32%,其中4例含量高于30ng/ml。50例肾移植受者HLA-G5表达阳性者10例,阳性率为20%,有1例含量为25ng/ml。健康人、肝移植、肾移植3组血清中HLA-G5平均含量分别为0.56±0.20、8.34±1.50和3.26±0.25ng/ml。对33例肝肾移植受者进行动态检测显示,有1例患者术前和术后1周HLA-G5呈阳性,4例术后4周阳性,12例术后12周阳性,追踪至术后1年有11例阳性。结论HLA-G5在健康人体内低表达,与器官移植免疫耐受有一定相关性。在移植后移植物接受良好的情况下,HLA-G5有不同水平的表达,肝移植受者的HLA-G5表达量高于肾移植受者。33例肝肾移植受者的动态结果证实了HLA-G5的表达从mRNA转录到蛋白表达的时间为15~60d的观点,HLA-G5的表达在第60天到达高峰,并具有稳定性。     

早期乳酸清除率及APACHEⅡ评分对老年重症肺炎患者预后判断的研究

目的:探讨早期乳酸清除率和急性生理学和慢性健康状况Ⅱ(APACHEⅡ)评分对老年重症肺炎患者预后的临床意义。方法:对重症医学科收治的47例老年重症肺炎患者,平均年龄(83.1±8.4)岁,分别于入院时和明确诊断后6 h测定动脉血乳酸,计算乳酸清除率。在患者入院第1个24 h内进行APACHEⅡ评分。以患者入院后28 d预后为研究终点,将患者分为存活组和死亡组,比较两组患者早期乳酸清除率及APACHEⅡ评分。根据明确诊断后6 h乳酸清除率将患者分为高乳酸清除率组(乳酸清除率≥10%)和低乳酸清除率组(乳酸清除率<10%),比较两组患者APACHEⅡ评分、机械通气率、病死率。采用受试者工作特征(ROC)曲线分析乳酸清除率预测老年重症肺炎患者预后的价值。结果:存活组和死亡组的乳酸清除率分别为(19.7±6.4)%和(7.7±10.1)%,差异有统计学意义(P<0.01);高乳酸清除率组和低乳酸清除率组28 d病死率分别为26.7%(8/30)和58.8%(10/17),高乳酸清除率组低于低乳酸清除率组(P<0.05);乳酸清除率预测老年重症肺炎患者28 d病死率最佳临界点为20%,敏感性68.9%,特异性67.9%。结论:早期乳酸清除率与APACHEⅡ评分正相关,两者可作为判断老年重症肺炎患者预后的指标。     

血管紧张素Ⅱ对心脏成纤维细胞TRPM7通道功能的影响

目的:研究心脏成纤维细胞(CFs)膜上的TRPM7通道的电生理特性。方法:将分离培养出来的乳鼠CFs用6种不同浓度的血管紧张素Ⅱ(AngⅡ)干预至12h,分别测量各组胶原蛋白的表达水平,从而挑选出最佳诱导纤维化的AngⅡ浓度,最佳浓度的AngⅡ分别将CFs干预至5个不同的时间,记录相应的CFs膜上的TRPM7电流及各组的胶原蛋白水平。结果:诱导心脏纤维化最大的AngⅡ浓度是1nmol/L,最佳诱导纤维化浓度干预0,6,12,24,48h后CFs的TRPM7与胶原蛋白Ⅲ的表达水平最初升高,于12h达到最高水平,之后呈现递减水平,且在CFs膜上记录到的TRPM7内外向电流也呈现相应的先增加后降低趋势,与两种蛋白的表达水平正相关。结论:CFs膜上的TRPM7电流在AngⅡ的作用下,呈现先增加后减少的趋势,是AngⅡ介导CFs增殖与凋亡从而导致心脏纤维化的重要途径之一。     

红细胞负载丹参酮ⅡA磺酸钠给药系统的大鼠体内药动学研究

目的 建立大鼠血浆中丹参酮ⅡA磺酸钠(STS)检测的高效液相色谱法,并对红细胞负载STS给药系统静脉注射后大鼠体内药动学进行研究.方法 SD大鼠尾静脉注射载药红细胞液,给药剂量5.0 mg/kg,采用高效液相色谱法测定药物的质量浓度,以软件DAS 2.0拟合药动学参数.结果 丹参酮ⅡA磺酸钠在0.25~25.00 μg/mL范围内呈良好线性关系,回收率、精密度和稳定性均符合检测要求.大鼠尾静脉注射载药红细胞后,STS的t1/2α为(0.139±0.54)h,t1/2β为(3.268±1.10)h,Cmax为(6.88±2.07)mg/L,AUC0-∞为(10.19 ±0.72)(mg·h)/L.结论 该方法简便准确,可用于STS血浆样品的含量测定和药动学研究.     

马岛战争和二战中海战伤发生特点及其对我军海战伤救治的启示

Casualties in naval battles,such as Malvinas War and World War Ⅱ,demonstrate different characteristics from those that occur in land battles,and are characterized by higher rate of mass casualties,higher incidences of burns and inhalation injuries,and higher prevalence rates of frozen injuries,drowning,seawater immersion injuries and combat stress reaction.Enlightenments of these features for our naval combat casualties care include:①Simple and fixed procedures should be established for mass casualties.②For burns and inhalation injuries,treatment measures should be set up,and related facilities should be equipped in warships and hospital ships.③Targeted strategies should be developed for frozen injuries,drowning,seawater immersion injuries and combat stress reaction.However,because of the improved killing effect of modern weapons and the changes of our national security strategy,the characteristics of casualties in our possible naval combats in the future differ from the above-mentioned features.So,in consideration of our national security strategy,features of various ships in modern naval combat,killing characteristics of different weapons and possible combat areas,we need to establish a reliable prediction model for casualties in modern offshore and far-offshore naval battles,and develop navel combat care skills and medical support strategies.     

IgA肾病血瘀证及丹参治疗机制研究进展

通过对IgA肾病中西医治疗及丹参现代药理研究的相关文献进行收集、归纳、总结,分析丹参对IgA肾病的治疗机制,了解丹参在IgA肾病领域的应用价值。中医学认为血瘀在IgA肾病中占有举足轻重的地位,是重要的邪实之一,近于贯穿本病的始末,是影响本病发展转归的重要因素。西医认为IgA肾病多存在肾内小动脉病变。丹参对肾内小动脉有调节作用,主要体现在其有抗凝血、抑制血小板聚集、抗血栓形成的作用;同时现代药理研究表明丹参有抗肾小球硬化、改善肾脏微循环、延缓肾脏纤维化等功能,进而对肾脏有保护作用。参考文献40篇。     

Impact of HLA-compatibilities in patients undergoing liver transplantation for HBV-cirrhosis

Liver transplantation (OLT) for end-stage chronic hepatitis-B-virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)-matching influences the outcome after OLT. In a retrospective analysis we reviewed 84 recipients of liver transplants for end-stage HBV-cirrhosis and complete HLA-typing for outcome after OLT. Follow-up ranges from 1 to 110 months (median = 55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)-based quadruple induction therapy or Tacrolimus-based induction protocols. Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long-term. Actuarial 1- and 5-yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis-B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA-A, -B compatibilities (p = 0.02), whereas the degree of HLA-DR compatibilities did not influence the outcome. The occurrence of HBV-reinfection was significantly lower in HLA-A, -B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV-reinfection and 1 or 2 HLA-B compatibilities when compared with patients with HBV-reinfection and a complete HLA-B mismatch (p = 0.02). In conclusion, this retrospective analysis shows that more HLA-A, -B compatibilities seems to be associated with an improved graft survival in patients after OLT for end-stage HBV infection.