基质金属蛋白酶及其抑制剂在心血管疾病中的研究进展

基质金属蛋白酶（MMPs）及其抑制剂（TIMPs）在心肌细胞的损伤、心肌重构中有着重要的影响,因其发生发展过程复杂,主要机理目前还不完全明确,但众多研究表明,MMPs和TIMPs的动态平衡在心肌损伤中起着至关重要的作用,甚至可以为心肌梗死的早期检测和及早治疗而开发出一种新型的检测试剂,可以有效提高心血管疾病的早期诊断,对后续的治疗起到准确、科学的指导作用。下面就基质金属蛋白酶及其抑制剂在心血管疾病方面近几年的研究结果进行综述。     

中医药治疗系统性红斑狼疮证型及用药规律演变研究

目的:基于文献整理探讨中医药治疗系统性红斑狼疮(Systemic lupus erythematosus,SLE)的证候分类及用药规律演变。方法:检索中国知网(CNKI)、维普中文科技期刊数据库、中国学术期刊数据库中中医药治疗SLE的相关文献,时间限定为从数据库建立至2018年7月。对证型及药物进行分类并统计分析。结果:纳入文献725篇,总结归纳高频证型11个,出现频次最高的五个证型分别为热毒炽盛证、脾肾两(阳)虚证、阴虚内热(火旺)证、肝肾两(阴)虚证、气阴两虚证,累计频率62.11%。1965-2018年间,阴虚内热(火旺)证呈明显增长趋势;热毒炽盛证、脾肾两(阳)虚证及气阴两虚证在1965-2010年间呈增长趋势,在2011-2018年间呈下降趋势;肝郁气滞(脾虚)证在1965-2018年间呈下降趋势;其余证型均呈动态波动。涉及组方1522个,药物309味,使用15910次,总使用频率最高的5味药分别为生地黄、牡丹皮、茯苓、黄芪、甘草,总累计频率16.42%。使用频率最高药类为清热药和补虚药;生地黄、牡丹皮等清热药的使用频率趋势与热毒炽盛证保持一致,不同年份高频用药大致相似,用药频率存在较小差异。结论:SLE在内以阴阳亏虚为主,在外与热毒侵袭相关,属于本虚标实,其发展与生态环境、社会环境、药物使用等紧密相关,治当以清热凉血、活血祛瘀、益气养阴,并结合个人体质及环境变化辨证治疗。     

正柴胡饮冲剂治疗感冒208例疗效分析

用正柴胡饮冲剂临床观察208例风寒感冒病人,随机分为常规剂量组和大剂量组,结果显示：两组治愈率无显著性差异,均能有效地改善临床症状、较快地降低体温、改善血白细胞计数及分类异常情况,说明本药为临床治疗风寒束表型感冒的有效药物。     

高压性小脑出血的外科治疗

目的探讨外科手术治疗高压性小脑出血的疗效。方法分别采取单纯后颅凹减压术和后颅凹减压加侧脑室外引流治疗高压性小脑出血。结果28例行单纯后颅凹减压术,9例行后颅凹减压加侧脑室外引流术,血肿清除90%以上30例,70%以上7例,无再出血病例。治愈22例,好转10例,死亡5例。结论小脑出血病情凶险,积极手术可取得良好的治疗效果。     

Three new shRNA expression vectors targeting the CYP3A4 coding sequence to inhibit its expression

RNA interference (RNAi) is useful for selective gene silencing. Cytochrome P450 3A4 (CYP3A4), which metabolizes approximately 50% of drugs in clinical use, plays an important role in drug metabolism. In this study, we aimed to develop a short hairpin RNA (shRNA) to modulate CYP3A4 expression. Three new shRNAs (S1, S2 and S3) were designed to target the coding sequence (CDS) of CYP3A4, cloned into a shRNA expression vector, and tested in different cells. The mixture of three shRNAs produced optimal reduction (55%) in CYP3A4 CDS-luciferase activity in both CHL and HEK293 cells. Endogenous CYP3A4 expression in HepG2 cells was decreased about 50% at both mRNA and protein level after transfection of the mixture of three shRNAs. In contrast, CYP3A5 gene expression was not altered by the shRNAs, supporting the selectivity of CYP3A4 shRNAs. In addition, HepG2 cells transfected with CYP3A4 shRNAs were less sensitive to Ginkgolic acids, whose toxic metabolites are produced by CYP3A4. These results demonstrate that vector-based shRNAs could modulate CYP3A4 expression in cells through their actions on CYP3A4 CDS, and CYP3A4 shRNAs may be utilized to define the role of CYP3A4 in drug metabolism and toxicity.KEY WORDS: RNAi, Cytochrome P450, CYP3A4, shRNA, Chemosensitivity     

大鼠视前内侧区的传出性神经纤维联系—WGA—HRP法研究

应用WGA-HRP顺行轴突运输研究大鼠视前内侧区传出性神经纤维投射。结果表明:视前内侧区的上行投射向嘴侧经斜角带进入外侧隔核;经髓纹进入缰核;经无名质进入杏仁前区及经终纹进入杏仁内侧核,另有标记纤维经内侧前脑束向外下行,经视束上方进入杏仁内侧核。下行投射经内侧前脑束进入下丘脑室旁核、外侧区、内侧核、后核、弓状核、乳头体前腹核和乳头体上核。继续向尾侧,标记纤维进入中脑腹侧背盖区,并投射到中缝正中核及中缝背核。     

MORPHOLOGICAL DIFFERENCES IN HEARTS OF RATS WELL ADAPTED AND POORLY ADAPTED TO CHRONIC HYPOXIA

We carried out an experiment to analyze morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia. Male and female Wistar rats, 1 week, 4 weeks and 9 weeks old, were employed on the assumption that adaptive ability was dependent on age and sex. These rats were raised at an altitude of 2,400 m and were kept for 7 to 9 weeks. Control groups were maintained at an altitude of 600 m during the same period of time. Each group consisted of 4 to 6 rats. At the end of the experiment, body weight, heart weight, ratio of heart weight to body weight and hematocrit were measured, and ventricular wall thickness, myocardial fiber diameter, capillary supply and mitochondria were morphometrically studied. Of the 6 experimental groups, the 4-week-old male rats (M2) had the highest body weight, as compared with the other experimental groups. In addition, relative to these other experimental groups, the following features were found for M2. Heart weight was intermediate, heart weight/body weight ratio was low and hematocrit was also low. Ventricular wall thickness was intermediate in the right ventricle (RV) and interventricular septum (IVS) but was thin in the left ventricle (LV). Myocardial fiber diameter was intermediate in the RV, large in the IVS and small in the LV. Capillary supply was intermediate in the RV and dense in the IVS and LV. Mitochondria were small but cristal density and percentage area, estimated from electron micrographs, were found to be high. These data showed that in well developed rats under chronic hypoxia, there is good development of capillary supply with corresponding restriction of cardiac hypertrophy, while hematocrit count and mitochondria are also affected.     

Expression of the GLUT1 glucose transporter and p53 in carcinomas of the pancreatobiliary tract

Only few studies have evaluated the usefulness of the GLUT1 and p53 status of pancreatobiliary tract carcinomas in revealing tumorigenesis. We studied GLUT1 and p53 immunoexpression in a total of 355 cases of the pancreatobiliary carcinoma to determine the biological significance of GLUT1 and p53 expression. Positive expression of GLUT1 was identified in 38 out of 67 (57.7%) ampulla of Vater (AV) carcinomas, in 27 out of 52 (51.8%) pancreatic (PA) carcinomas, in 38 out of 121 (31.4%) extrahepatic bile duct (EBD) carcinomas, and in 53 out of 115 (46.5%) gallbladder (GB) carcinomas. GLUT1 expression in pancreatobiliary carcinomas showed some positive correlation with histological grade, T stage, N stage, TNM stage, and lymphatic invasion. However, p53 expression showed no correlation with any prognostic factors. In the Kaplan–Meier test, positive GLUT1 expression was a poor prognostic factor in the pancreatobiliary tract cancers; however, only GB cancers were statistically significant (P=0.002). Our results suggest that GLUT1 expression in the AV, EBD, and GB carcinomas is associated with some prognostic factors, and GLUT1 expression is associated with a worse prognosis in the patients with GB carcinomas.