Neonatal mouse testis-derived multipotent germline stem cells improve the cardiac function of acute ischemic heart mouse model

Multipotent germline stem (mGS) cells have been established from neonatal mouse testes. We previously reported that undifferentiated mGS cells are phenotypically similar to embryonic stem cells and that fetal liver kinase 1 (Flk1)⁺ mGS cells have a similar potential to differentiate into cardiomyocytes and endothelial cells compared with Flk1⁺ embryonic stem cells. Here, we transplanted these Flk1⁺ mGS cells into an ischemic heart failure mouse model to evaluate the improvement in cardiac function. Significant increase in left ventricular wall thickness of the infarct area, left ventricular ejection fraction and left ventricular maximum systolic velocity was observed 4 weeks after when sorted Flk1⁺ mGS cells were transplanted directly into the hearts of the acute ischemic model mice. Although the number of cardiomyocytes derived from Flk1⁺ mGS cells were too small to account for the improvement in cardiac function but angiogenesis around ischemic area was enhanced in the Flk1⁺ mGS cells transplanted group than the control group and senescence was also remarkably diminished in the early phase of ischemia according to β-galactosidase staining assay. In conclusion, Flk1⁺ mGS cell transplantation can improve the cardiac function of ischemic hearts by promoting angiogenesis and by delaying host cell death via senescence.     

急性心梗患者PCI术中并发心室纤颤的影响因素及Gensini评分、血钾对其预测价值

摘要 目的：探讨分析AMI患者PCI术中并发VF的影响因素以及冠脉Gensini评分、血钾对其预测价值。方法：从2016年6月至2019年6月于我院就诊的AMI患者中筛选出356例,对其临床资料进行回顾性分析。以AMI患者PCI术中是否并发VF为依据进行组别划分,分为VF组（49组）、NVF组（未并发VF,307例）。整理比较两组一般资料、临床资料,并对两组患者冠脉造影特征、冠脉Gensini评分作对比分析,对AMI患者PCI术中并发VF的可疑性影响因素行多因素Logistic回顾分析,以确定其危险因素,并对危险因素行ROC曲线分析以确定其预测价值。结果：VF组和NVF组在性别、年龄、吸烟史、饮酒史、高血压史、糖尿病史、既往应用β受体阻滞剂及阿司匹林,入院时收缩压和心率方面,均无统计学差别（P>0.05）,临床血指标检测上,VF组血钾水平明显低于NVF组,差异具有统计学意义（P<0.05）,冠脉造影检查显示VF组TIMI血流0级、Gensini积分高及血栓负荷重例数高于NVF组,差异具有统计学意义（P<0.05）。多因素Logistic回归分析显示TIMI血流分级0级、血钾、Gensini评分为AMI患者PCI术中并发VF的独立危险因素（P<0.05）。ROC曲线分析结果显示,TIMI血流分级0级、血钾、Gensini评分均对AMI患者PCI术中并发VF具有一定的预测价值,其ROC曲线下面积分别为0.619、0.816、0.842（P值均＜0.05）,提示血钾、Gensini评分具有中等预测价值,TIMI血流分级0级预测价值较低。当血钾、Gensini评分分别处4.05、89.95最佳截断值时,其敏感度分别为100%、63.3%,特异度分别为为41.8%、94.1%。结论：TIMI血流分级0级、血钾、Gensini评分为AMI患者PCI术中并发VF的独立危险因素。TIMI血流分级0级、血钾、Gensini评分均对AMI患者PCI术中并发VF具有一定的预测价值。血钾、Gensini评分具中等预测价值,TIMI血流分级0级预测价值较低。     

AMI患者血浆NT—proBNP水平与心肌缺血及预后关系的研究

目的：探讨急性心肌梗死（AMI）患者血浆N末端B型尿钠肽前体（NT-proBNP）的水平与心肌缺血及预后的关系。方法：98例急性心肌梗死患者根据患者是否行直接PCI手术治疗,分为PCI手术治疗组和非PCI治疗组,观察缺血改善情况与NT-proBNP水平的关系,同时根据治疗后NT-proBNP的水平分为三组,A组NT-proBNP〈125pg／ml、B组125pg／ml≤NT-proBNP〈450pg／ml、C组NT-proBNP≥450pg／ml,观察NT—proBNP的水平与预后的关系。结果：行PCI组NT—proBNP的水平下降程度（438．3±134．5）明显高于未行PCI组者（158．6±146．1,P〈0．05）,MACE的发生情况C组明显高于A组（P=0．006〈0．01）,也高于B组（P=0．028〈0．05）,A组与B组相比,B组的MACE发生率有上升的趋势,但是无统计学意义（P=0．432〉0．05）.结论：急性心肌梗死患者早期血浆NT-proBNP的水平在一定程度上可以反应心肌的缺血程度,且与患者的预后成明显的负相关。     

心肌型脂肪酸结合蛋白胶体金检测试纸条的制备和初步应用

目的应用胶体金免疫层析法制备检测全血或血清样本中心肌型脂肪酸结合蛋白（H-FABP）的检测试纸条,用于急性心肌梗塞（AMI）的早期辅助诊断。方法采用柠檬酸三钠还原法制备胶体金,标记鼠抗心肌型脂肪酸结合蛋白单克隆抗体,喷于玻璃纤维膜上制成胶体金结合物垫,将另一株鼠抗心肌型脂肪酸结合蛋白单克隆抗体和抗鼠二抗分别包被检测线和质控线,组装成试纸条进行灵敏性、特异性、精密性、稳定性及临床样品检测。结果该试纸条的检测灵敏度为10ng／mL,15min内可判定结果;与肌钙蛋白I、C反应蛋白、肌酸激酶、人心肌肌红蛋白无交叉反应。检测240份临床标本,与临床诊断结果进行配对分析,阳性符合率95．83％、阴性符合率100％、总符合率97．92％。结论制备的H-FABP检测试纸条有良好的灵敏性、特异性,可用于早期AMI的辅助诊断。     

The HMGB1–TLR4 axis contributes to myocardial ischemia/reperfusion injury via regulation of cardiomyocyte apoptosis

Toll-like receptor 4 (TLR4) and its ligand high mobility group box 1 (HMGB1), are known for playing central roles in ischemia–reperfusion injury in myocardium. However, the detailed mechanisms of TLR4 and HMGB1 are not fully understood. The aim of this study was to investigate the effects and possible mechanisms of the HMGB1–TLR4 axis and cardiomyocyte apoptosis on myocardial ischemic damage. Artificial oxygen ventilated anesthetized C3H/HeN mice and C3H/HeJ mice were subjected to 30 min of left anterior descending coronary artery occlusion followed by 6 h of reperfusion. The myocardial infarct size, HMGB1 levels, apoptosis index, Bax, Bcl-2 and TNF-α mRNA levels were assessed. The results showed that a lowered amount of cardiomyocyte apoptosis and infarct size in the myocardium of TLR4-mutant mice after myocardial I/R and that TLR4 deficiency notably inhibited the expression of HMGB1 and TNF-a, both of which were up-regulated by ischemia/reperfusion. These findings suggest that the HMGB1–TLR4 axis plays a pathogenic role in triggering cardiomyocyte apoptosis during myocardial I/R injury and that the possible mechanism for this process is the result of released cytokines and inflammatory response involved in the HMGB1/TLR4-related pathway.     

不稳定型心绞痛和急性心肌梗死患者血小板指标及超敏C 反应蛋白变化

目的:探讨不稳定型心绞痛(unstable angina pectoris,UAP)、急性心肌梗死(acute myocardial infarction,AMI)患者血小板指标、超敏C反应蛋白(C-reactive protein,hs-CRP)水平变化及意义。方法:选取于我院进行治疗的急性冠脉综合征患者300例中UAP患者121例(UAP组),AMI患者179例(AMI组)。另选100例健康体检者作为对照组。300例急性冠脉综合征患者均口服阿司匹林进行治疗。服用阿司匹林7 d后比较各组血小板指标血小板聚集率、血小板膜糖蛋白CD62p、尿11-脱氢-血栓素B2(11-dehydro-Thromboxane,11-DH-TXB2)及hs-CRP水平变化,同时记录随访1年急性冠脉综合征患者心血管事件发生情况。结果:治疗后UAP组、AMI组二磷酸腺苷(adenosine diphosphate,ADP)及花生四烯酸(arochidonic acid,AA)诱导的血小板聚集率、11-DH-TXB2与对照组差异显著(P0.05),AMI组CD62p、hs-CRP水平均显著高于对照组(P0.05);随访1年,11-DH-TXB2水平≥1500 ng/g者心血管事件发生率为51.02%,11-DH-TXB2水平1500 ng/g者心血管事件发生率为22.28%,二者发生率差异显著(P0.05)。结论:血小板指标、hs-CRP检测对UAP、AMI具有临床意义。     

33株抗心肌肌钙蛋白T (cTnT) 的单克隆抗体制备、鉴定及应用

旨在制备抗心肌肌钙蛋白T(cTnT)的单克隆抗体(m Ab),对单抗进行初步评价鉴定,并建立(cTnT)的化学发光定量检测试剂。首先利用外购的cTnT抗原免疫BALB/c小鼠,利用常规m Ab制备技术和间接ELISA法筛选m Ab,以表达和合成的cTnT片段对筛选到的m Ab进行表位鉴定。使用双抗体夹心ELISA方法筛选检测cTnT抗原的配对m Ab,并建立cTnT全自动化学发光定量检测试剂。使用220例临床标本评价该试剂与罗氏试剂的检测一致性,另外使用238例临床样本和784例体检人群样本评价该试剂的临床应用。我们成功筛选到33株稳定分泌抗cTnT抗体的杂交瘤细胞株,并对单抗的表位进行初步鉴定。我们筛选到能检测10 pg/m L cTnT抗原的配对m Ab E16H8和C8G11,并使用该配对研制出全自动化学发光定量试剂。该试剂与罗氏试剂相关系数r达到0.959 9,检测一致率95%,利用该试剂盒检测临床样本灵敏度为97.5%,特异性为99.15%,99%体检人群的cTnT浓度分布小于0.080 6 ng/m L,符合WHO对急性心肌梗死的定义标准。综上,初步建立了cTnT诊断优势表位单抗,并利用这些优势表位的单抗建立全自动管式化学发光定量检测试剂,与罗氏试剂检测结果符合率高。     

Impact of advanced glycation end products (AGEs) signaling in coronary artery disease

Coronary artery disease remains the leading cause of mortality in adult diabetic population with however, a high predominance also in non-diabetic subjects. In search of common molecular mechanisms and metabolic by-products with potential pathogenic role, increased advanced glycation end products (AGEs) present a critical biomarker for CAD development in both cases. Interaction of AGEs with their transmembrane cell receptor, RAGE in endothelial and smooth muscle cells as well as in platelets, activates intracellular signaling that leads to endothelial injury, modulation of vascular smooth muscle cell function and altered platelet activity. Furthermore, tissue accumulation of AGEs affects current treatment approaches being involved in stent restenosis. The present review provides an update of AGE-induced molecular mechanisms involved in CAD pathophysiology while it discusses emerging therapeutic interventions targeting AGE reduction and AGE-RAGE signaling with beneficial clinical outcome.     

人心脏型脂肪酸结合蛋白快速检测试剂盒的临床验证性研究

目的评价H-FABP快速检测试剂盒对急性心肌梗死(AMI)的早期诊断效果。方法比较H-FABP、CK、CK-MB和cTnT四种心肌标志物在AMI发作后6 h内的敏感性、准确性和时效性;比较H-FABP快速检测试剂盒对AMI患者和非AMI患者诊断的特异性。结果 H-FABP快速检测试剂盒的检测结果与临床诊断结果符合率为100%;在AMI发作后6 h内,H-FABP的敏感性和准确性优于CK、CK-MB,与cTnT相当。8例肾衰竭患者100%显示阳性,心源性疾病中主动脉关闭不全有1例(2.44%),房间隔缺损有2例(4.88%)显示阳性。结论 AMI发作后6 h内,H-FABP快速检测试剂盒对其具有较好的诊断价值。