扩张型心肌病家系罕见受磷蛋白致病基因突变

目的 对一扩张型心肌病(dilated cardiomyopathy, DCM)家系行候选致病基因全外显子高通量测序,以寻找该家系的致病基因,并分析其基因型和表型的关系。方法 收集在武汉大学人民医院就诊的一位DCM患者及其家系成员的临床资料及血液标本。与先证者及其家属签订知情同意书,绘制家谱图,由我院临床分子诊断中心对先证者进行候选致病基因全外显子高通量测序,获得可疑突变后,用Sanger测序对家系其他成员进行验证,寻找致病基因。结果 家系先证者6号染色体外显子上存在受磷蛋白(phospholamban, PLN)基因的精氨酸缺失突变c.36_38delAAG (p.Arg13del),为该家系的可疑致病基因。先证者目前心脏扩大,心功能显著下降,且超声心动图提示左心室附壁血栓形成,心电图提示肢导低电压以及胸导联R波极度减低。先证者母亲及其大姐因心脏病死亡,二姐目前患有扩张型心肌病,其子女未检测到致病基因。受磷蛋白作为肌质网钙离子循环中的调节蛋白,它的基因表达、分布、功能与心室的收缩功能密切相关。结论 本研究发现DCM家系中存在PLN基因缺失突变：PLN c.36_38delAAG (p.Arg13del),是家族性扩张型心肌病的重要致病基因,此突变在汉族人群中尚属首次报道。     

混合培养对骨髓基质细胞转分化为神经元的影响

目的　研究神经干细胞(NSCs)与骨髓基质细胞(BMSCs)混合培养对骨髓基质细胞转分化为神经元的 影响。　方法　将BMSCs传代培养2d,10μg LbFGF预诱导过夜,DAPI标记后加入到已贴壁分化2d的NSCs中,神 经元培养基混合培养7d后进行神经元特异性烯醇化酶(Nse)染色。对照组于BMSCs传代2d后,一组加bFGF处理 过夜,另一组不加,神经元培养基培养7d后NSE染色。　结果　实验组中部分BMSCs呈NSE染色强阳性,比例为 (13.38±5.79)%,对照组呈NSE阴性　结论　NSCs与BMSCs混合培养可诱导BMSCs转分化为神经元。     

膈神经变异1例

笔者在解剖一具老年女性标本时,发现其左侧膈神经罕见变异,现报道如下: 膈神经在左斜角肌间隙内,在前斜角肌后缘中点靠外0.7 cm处由臂丛上干发出(附图)。稍向外下方与前斜角肌后缘平行行走,经肩胛舌骨肌、锁骨下动静脉表面,于静脉角外侧进入胸腔,伴心包膈动脉走向膈     

Protective effects of trimetazidine on bone marrow mesenchymal stem cells viability in an ex vivo model of hypoxia and in vivo model of locally myocardial ischemia

Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury,but this approach is limited by their poor viability after transplantation.The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia,as well as survival,differentiation,and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI).MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope,and by using flow cytometry following culture in serumfree medium and exposure to hypoxia (5% CO2,95% N2) for 12 h with or without TMZ.Thirty Wistar rats were divided into 3 groups (n=10 each group),including groupⅠ(AMI control),groupⅡ (MSCs transplantation alone),and group Ⅲ (TMZ+MSCs).Rat MSCs (4×107) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation.The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg?kg-1?day-1) from day 3 before AMI to day 28 after AMI.Cardiac structure and function were assessed by echocardiography at 28th day after transplantation.Blood samples were collected before the start of TMZ therapy (baseline),and 24 and 48 h after AMI,and inflammatory cytokines (CRP,TNF-α) were measured.Then the sur-vival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining.The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay.Furthermore,apoptosis-related proteins (Bcl-2,Bax) within the post-infarcted myocardium were detected by using Western blotting.In hypoxic culture,the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serumfree medium and hypoxia environment.In vivo,cardiac infarct size was significantly reduced,and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group.Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis,further increased MSCs viability,further decreased infarct size,and further improved cardiac function as compared with MSCs alone.The baseline levels of inflammatory cyto-kines (CRP,TNF-α) had no significant difference among the groups.In contrast,all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group.Furthermore,Western blotting indicated that the expression of antiapoptotic protein Bcl-2 was upregulated,while the proapoptotic protein Bax was down-regulated in the TMZ+MSCs group,compared with that in the MSCs group.It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.     

腹腔干变异1例

笔者在解剖一具老年女性尸体标本时,发现腹腔干存在罕见变异现象,为积累资料,提供临床参考,现报道如下： 胃脾动脉干外径６．４ｍｍ,在主动脉裂孔稍下方起自腹主动脉前壁,垂直下行 １．３ ｃｍ后分为胃左动脉和脾动脉。胃左动脉外径４．０ ｍｍ,在小网膜内行向左上方,在距起始部位 １．７ ｃｍ和２．９ｃｍ处分别发出胃体支和食管支进入胃体、胃底和食管下段,本干继续上行,向右上方沿肝脏下缘呈弓形走行 １．８ ｃｍ后发出副肝左动脉进入肝左叶,本干则继续走行至门静脉左前方分为２支（图１）。第１支为肝固有动脉,外径３．０ｍ…