Smad2 increases the apoptosis of activated human hepatic stellate cells induced by TRAIL

The activation of hepatic stellate cells (HSCs) plays a critical role in the development of liver fibrosis. The induction of apoptosis in activated HSCs during the recovery phase of hepatic fibrosis represents a potential anti-fibrotic therapy. We have previously shown that Smad2 protects against hepatic fibrogenesis; however, the role of Smad2 in the regulation of activated HSC apoptosis remains unknown. We hypothesized that Smad2 regulates the apoptosis of activated HSCs, leading to the resolution of liver fibrosis. To test this hypothesis, the livers of rats were harvested at 0 and 4 weeks after hepatic fibrosis was established by CCl₄ injection. Furthermore, TGF-β1-activated HSCs were treated with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) following the silencing or overexpression of Smad2. Both the phosphorylation of Smad2 and TRAIL were detected in fibrotic liver tissues. The results of TUNEL and α-SMA double-staining showed an increase in the apoptosis of activated HSCs during the spontaneous recovery phase. The knockdown of Smad2 reduced TRAIL-induced apoptosis in TGF-β1-activated human LX-2 cells and resulted in an increased expression of α-SMA and collagen I (Col. I). In contrast, the overexpression of Smad2 increased TRAIL-induced HSC apoptosis and reduced the expression of α-SMA and Col. I. The mechanisms underlying these findings were associated with the Smad2-mediated down-regulation of X-linked inhibitor of apoptosis protein (XIAP), resulting in enhanced caspase-3 activity and apoptosis. In conclusion, Smad2 enhances TRAIL-induced apoptosis in activated HSCs, which facilitates the resolution of hepatic fibrosis.     

贝那普利降压疗效与校正QT间期的关系

目的探讨原发性高血压患者心电图心率校正QT间期(QTc)和贝那普利降压疗效之间的关系.方法采用前瞻性队列研究方法调查安徽A县899名高血压病患者的基线心电图、治疗15 d前后的血压变化及相关临床和流行病学特点等情况.结果 QTc和血压下降呈负相关.QTc每增加0.1秒1/2,收缩压和舒张压的下降值分别减少3.6 mmHg和3.3 mmHg,且差异均有显著性(P＜0.05).将QTc三等分后,随着QTc等分的增加,收缩压和舒张压的下降值均逐渐减少,且差异具有显著性(P＜0.05);将QTc等分后的变量放入方程中进行趋势性分析,发现在收缩压和舒张压组中的负相关关系具有显著性(P＜0.05).随着QTc等级的增加,舒张压有效率逐渐降低,且有显著性差异(P＜0.05),收缩压的效应关系不如舒张压明显.结论 QTc和贝那普利降压疗效呈负相关,对贝那普利短期降压疗效具有重要的预测价值.     

项目记忆和源记忆的功能磁共振成像研究

目的探讨项目记忆和源记忆的神经基础及其是否存在性别差异。方法健康男女各8名，实验材料为504个高频双汉字词，项目记忆和源记忆实验任务，Block设计，GE1．5T采集功能磁共振成像（mRI）数据，用SPM99分析，得到男女脑功能激活图（P〈0．002，体素块〉20）。结果在P〈0．002，体素块〉20时，女性项目记忆激活双前额叶背外侧BA6（激活数目左右侧分别为62和11个），源记忆较多激活左前额叶背外侧BA6／46（激活数目为59个）；男性项目记忆激活右前额叶背外侧BA6／46（激活数目为64个），源记忆激活双前额叶背外侧BA6（左右侧分别为9和40个）。结论项目记忆更多激活右侧前额叶背外侧，而源记忆更多激活左侧前额叶背外侧。女性较多地引起左前额叶背外侧激活；而男性较多地引起右前额叶背外侧激活。     

肌蒂移植术治疗陈旧性脊髓损伤(附56例报告)

作者采用肌蒂移植术治疗胸腰段陈旧性脊髓损伤56例.脊髓功能恢复率提高至Franke 1个等级以上者占76.8%(43/56).本文讨论了肌蒂移植术对陈旧性脊髓损伤的适应证.安徽省宿州市骨伤科医院淮北煤矿基建局医院     

早期新生儿死亡病因学研究进展

早期新生儿死亡属于围产儿死亡的一部分,其定义为新生儿出生后0~6天死亡。通常认为男性新生儿、先天异常、早产、低出生体重和5分钟Apgar评分低于7分等是早期新生儿死亡最常见的相关因素。但是仍有相当多的早期新生儿死亡病因不明,其为产科及儿科医务人员比较棘手的问题,也容易引发医患矛盾。近年来发现,除上述常见的病因外,基因缺陷和代谢性疾病在早期新生儿死亡中亦占有相当的比例,而通过全基因测序和串联质谱检测技术,可能对寻找部分既往被归于不明原因早期新生儿死亡病例的病因有一定的帮助。该文就早期新生儿死亡病因及可能机制、病因评估方法等进行综述。     

巢式PCR-RFLP检测直肠癌K-ras癌基因第12位密码子点突变及意义

采用巢式ＰＣＲ－ＲＦＬＰ技术,对２６例直肠癌患者标本进行Ｋ－ｒａｓ第１２位密码子点突变进行检测,结果显示：２６例直肠癌患者中有１３例有Ｋ－ｒａｓ点突变,阳性率达５０％。突变发生与年龄相关,与性别、Ｄｕｋｅｓ分期及有无转移无关。肿瘤分化程度越差突变率越高。发生Ｋ－ｒａｓ点突变者预后较差     

心肌肌钙蛋白Ⅰ在急性心肌梗死和不稳定心绞痛中的应用价值

目的　探讨心肌肌钙蛋白 (CTnⅠ )在诊断急性心肌梗死 (AMI)和不稳定心绞痛 (UAP)的应用价值。方法　对 31例AMI和 4 0例不稳定心绞痛 (UAP)病人进行血清CTnⅠ、肌酸激酶 (CK)和肌酸激酶同功酶 (CK MB)检测 ,并进行两组间比较分析。结果　 31例AMI病人中 2 9例病人血清CTnⅠ明显升高 ,4 0例UAP病人中仅 2例血清CTnⅠ轻度升高。血清CTnⅠ诊断AMI的敏感性为 96 7% ,而CK和CK MB的敏感性分别为 80 %、80 %。血清CTnⅠ诊断AMI的特异性为 94 4 % ,而CK MB的特异性为 77 7%、77 7%。CTnⅠ的敏感性和特异性显著高于CK和CK MB(P <0 0 1)。结论　心肌肌钙蛋白Ⅰ对于AMI的诊断具有很高的敏感性和特异性 ,能早期诊断AMI。此外 ,CTnⅠ在鉴别急性心肌梗死和不稳定心绞痛也具有重要的临床价值 ,心肌肌钙蛋白Ⅰ是一种心肌损伤的特异性标志物。     

瘢痕疙瘩的形成与Langerhans细胞的相关性研究

目的 探讨Langerhans细胞与瘢痕疙瘩形成的相关性。方法 应用免疫组织化学（ABC）法观察S-100蛋白在瘢痕疙瘩的浸润部、增生部、老化部与正常皮肤组织中表达。结果瘢痕疙瘩组织浸润部、增生部中S-100蛋白免疫反应阳性的Langerhans细胞明显增多。统计学处理：瘢痕疙瘩的增生部、浸润部与正常皮肤之间差异有显著性（P〈0．01），瘢痕疙瘩的浸润部、增生部、老化部差异有显著性（浸润部〉增生部〉老化部或正常皮肤（P〈0．01），而正常皮肤与瘢痕疙瘩老化部之间差异无显著性（P〉0．05）。结论 Langer—hans细胞在瘢痕疙瘩的形成过程中可能起到很重要的作用。     

经胸超声测定冠状窦血流评价经PCI术后血流变化

目的应用经胸超声测定冠状静脉窦血流储备评价经皮冠状动脉血运重建术（PCI）后冠脉血流情况。方法选择62例临床诊断为急性心肌梗死的患者，经冠脉造影证实为左冠脉系统狭窄，均接受PTCA和支架置入，经胸超声等长握力试验测定手术前后冠状窦血流储备。结果术后冠状窦收缩期和舒张期峰值血流及积分均较术前增大，血流及积分储备较术前明显增加，差异具有显著性（P〈0．05）。结论经胸超声测定冠状窦血流可用于初步评价冠脉术后的血流灌注。     

Functional interplay between the ATP binding cassette Msr(D) protein and the membrane facilitator superfamily Mef(E) transporter for macrolide resistance in Escherichia coli

Macrolides have wide clinical applications in the treatment of community-acquired respiratory tract infections, among which streptococci are the most frequent causative agents. An active efflux-based mechanism of macrolide resistance, referred to as the M phenotype in streptococcal isolates, has been associated with the presence of mef genes that encode a subset of major facilitator superfamily (MFS) transporters like Mef(E). An msr(D) gene, adjacent to and co-transcribed with mef in the presence of erythromycin, has also been implicated in drug efflux, but its role remains elusive. Msr(D) belongs to the ATP binding cassette (ABC) proteins and harbors two fused nucleotide-binding domains with no membrane-spanning domains. The present work indicates that the major resistance traits of the M phenotype in Escherichia coli may be due to Msr(D) and not to Mef(E). Fluorescence microscopy using Mef(E) tagged with GFP linked low efficacy of the chimera in conferring macrolide resistance with improper subcellular localization. The active role of Msr(D) in directing Mef(E)-GFP to the cell poles was demonstrated, as was synergistic effect in terms of levels of resistance when both proteins were expressed. A trans-dominant negative mutation within ABC Msr(D) affecting MFS Mef(E) strongly suggests that both proteins can interact in vivo, and such a physical interaction was supported in vitro. This is the first reported example of a functional interplay between an ABC component and an MFS transporter. The direct involvement of Msr(D) in the efflux of macrolides remains to be demonstrated.