左旋氨氯地平联合一线降压药治疗高血压疗效的系统评价

目的：系统评价左旋氨氯地平联合一线降压药治疗高血压的疗效,为临床提供循证依据。方法：计算机检索Ovid Medline、EMBase、Cochrane Library、CNKI、CBM、VIP和WanFang Data,检索时限均从建库至2017年12月,对每项纳入研究进行偏倚风险评价,并采用Rev Man 5.3软件进行Meta分析。结果：共纳入147个RCTs,Meta分析结果显示：（1）左旋氨氯地平联合ACEI在SBP降低值[SMD=0.92,95% CI（0.79,1.04）,P < 0.000 01],DBP降低值[SMD=0.87,95% CI（0.72,1.03）,P < 0.000 01]和总有效率[RR=1.23,95% CI（1.20,1.26）,P < 0.000 01]方面均优于对照组,差异具有统计学意义;（2）左旋氨氯地平联合ARB在SBP降低值[SMD=1.29,95% CI（1.10,1.48）,P < 0.000 01],DBP降低值[SMD=0.94,95% CI（0.79,1.09）,P < 0.000 01]和总有效率[RR=1.22,95% CI（1.20,1.25）,P < 0.000 01]方面均优于对照组,差异具有统计学意义;（3）左旋氨氯地平联合β受体拮抗剂在SBP降低值[SMD=0.88,95% CI（0.39,1.36）,P=0.000 5],DBP降低值[SMD=0.80,95% CI（0.35,1.25）,P=0.000 5]和总有效率[RR=1.18,95% CI（1.12,1.23）,P < 0.000 01]方面优于对照组,差异具有统计学意义;（4）左旋氨氯地平联合利尿剂在SBP降低值[SMD=1.34,95% CI（0.78,1.90）,P < 0.000 01],DBP降低值[SMD=0.72,95% CI（0.20,1.24）,P=0.007]方面优于对照组,差异具有统计学意义。结论：基于现有临床证据,左旋氨氯地平联合一线降压药降压效果优于单一用药方案。     

Phloroglucinol averts isoprenaline hydrochloride induced myocardial infarction in rats

Myocardial infarction (MI) is indicated by the symptoms like sharp chest pain, sweating, palpitations, and nervousness finally leading to heart attack. MI occurs mainly due to the risk factors like smoking, elevated blood pressure, diabetes, hypercholesterolemia, obesity, decreased HDL level, elevated LDL level, hyperlipoproteinemia and aging consequently leads to demandable coronary blood supply, oxidative stress, and acute necrosis of the myocardium. Cardioprotective potential of the phloroglucinol (PG) was assessed by treating isoprenaline hydrochloride (ISO; 85 mg/kg b.w., s.c.) induced MI model in rats. Pretreatment with PG in a dose of 30 mg/kg was done for 28 days and followed by ISO (for MI induction) on 29th and 30th days, exhibited decline in the abnormalities in the ECG patterns, cardiac marker enzymes, enzymic and nonenzymic antioxidants, lipid peroxidation, lipid profiles, and histopathological investigations compared to isoprenaline alone treated group. On the whole, the present investigations elucidate the significance of PG in alleviating the pathological process and appreciably prevent the induction of MI in experimental rats.     

Structure-based cleavage mechanism of Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage

We report on crystal structures of ternary Thermus thermophilus Argonaute (TtAgo) complexes with 5′-phosphorylated guide DNA and a series of DNA targets. These ternary complex structures of cleavage-incompatible, cleavage-compatible, and postcleavage states solved at improved resolution up to 2.2 Å have provided molecular insights into the orchestrated positioning of catalytic residues, a pair of Mg²⁺ cations, and the putative water nucleophile positioned for in-line attack on the cleavable phosphate for TtAgo-mediated target cleavage by a RNase H-type mechanism. In addition, these ternary complex structures have provided insights into protein and DNA conformational changes that facilitate transition between cleavage-incompatible and cleavage-compatible states, including the role of a Glu finger in generating a cleavage-competent catalytic Asp-Glu-Asp-Asp tetrad. Following cleavage, the seed segment forms a stable duplex with the complementary segment of the target strand.Argonaute (Ago) proteins, critical components of the RNA-induced silencing complex, play a key role in guide strand-mediated target RNA recognition, cleavage, and product release (reviewed in refs. 1–3). Ago proteins adopt a bilobal scaffold composed of an amino terminal PAZ-containing lobe (N and PAZ domains), a carboxyl-terminal PIWI-containing lobe (Mid and PIWI domains), and connecting linkers L1 and L2. Ago proteins bind guide strands whose 5′-phosphorylated and 3′-hydroxyl ends are anchored within Mid and PAZ pockets, respectively (4–7), with the anchored guide strand then serving as a template for pairing with the target strand (8, 9). The cleavage activity of Ago resides in the RNase H fold adopted by the PIWI domain (10, 11), whereby the enzyme’s Asp-Asp-Asp/His catalytic triad (12–15) initially processes loaded double-stranded siRNAs by cleaving the passenger strand and subsequently processes guide-target RNA duplexes by cleaving the target strand (reviewed in refs. 16–18). Such Mg²⁺ cation-mediated endonucleolytic cleavage of the target RNA strand (19, 20) resulting in 3′-OH and 5′-phosphate ends (21) requires Watson–Crick pairing of the guide and target strands spanning the seed segment (positions 2–2′ to 8–8′) and the cleavage site (10′–11′ step on the target strand) (9). Insights into target RNA recognition and cleavage have emerged from structural (9), chemical (22), and biophysical (23) experiments.Notably, bacterial and archaeal Ago proteins have recently been shown to preferentially bind 5′-phosphoryated guide DNA (14, 15) and use an activated water molecule as the nucleophile (reviewed in ref. 24) to cleave both RNA and DNA target strands (9). Structural studies have been undertaken on bacterial and archaeal Ago proteins in the free state (10, 15) and bound to a 5′-phosphorylated guide DNA strand (4) and added target RNA strand (8, 9). The structural studies of Thermus thermophilus Ago (TtAgo) ternary complexes have provided insights into the nucleation, propagation, and cleavage steps of target RNA silencing in a bacterial system (9). These studies have highlighted the conformational transitions on proceeding from Ago in the free state to the binary complex (4) to the ternary complexes (8, 9) and have emphasized the requirement for a precisely aligned Asp-Asp-Asp triad and a pair of Mg²⁺ cations for cleavage chemistry (9), typical of RNase H fold-mediated enzymes (24, 25). Structural studies have also been extended to binary complexes of both human (5, 6) and yeast (7) Agos bound to 5′-phosphorylated guide RNA strands.Despite these singular advances in the structural biology of RNA silencing, further progress was hampered by the modest resolution (2.8- to 3.0-Å resolution) of TtAgo ternary complexes with guide DNA (4) and added target RNAs (8, 9). This precluded identification of water molecules coordinated with the pair of Mg²⁺ cations, including the key water that acts as a nucleophile and targets the cleavable phosphate between positions 10′-11′ on the target strand. We have now extended our research to TtAgo ternary complexes with guide DNA and target DNA strands, which has permitted us to grow crystals of ternary complexes that diffract to higher (2.2–2.3 Å) resolution in the cleavage-incompatible, cleavage-compatible, and postcleavage steps. These high-resolution structures of TtAgo ternary complexes provide snapshots of distinct key steps in the catalytic cleavage pathway, opening opportunities for experimental probing into DNA target cleavage as a defense mechanism against plasmids and possibly other mobile elements (26, 27).     

药品检测机构生物安全柜全生命周期管理探讨

建立药品检测机构生物安全柜管理方法。从生物安全柜的选择、检测、使用年限、注意事项、维修维护和档案6个方面介绍生物安全柜的管理要点,并从检测数据分析建议使用年限7年。生物安全柜的规范管理,是实验室人员安全数据准确的前提和保障。     

基于分子网络研究四逆散抗抑郁症作用的潜在生物学机制

目的 基于分子网络研究四逆散治疗抑郁症的潜在生物学机制。方法 借助于中药系统药理学数据库和分析平台（TCMSP）数据库筛选四逆散的活性成分,筛选条件为口服利用率、药物相似性和血脑屏障透过率,并挖掘四逆散活性成分靶点和抑郁症的治疗靶点。利用韦恩图找到活性成分靶点和疾病靶点的交集靶点,对应相应成分定义为四逆散抗抑郁的有效成分。利用String在线数据库进行交集靶点蛋白质-蛋白质相互作用网络的预测,并利用DAVID数据库进行交集靶点KEGG信号通路的富集分析。最后使用Cytoscape 3.6软件进行活性成分-靶点网络及有效成分-靶点-信号通路的构建和拓扑分析。结果 筛选出了四逆散107个有效成分和28个重要的抗抑郁症靶点。四逆散抗抑郁症的重要靶点显著富集于神经活性配体-受体相互作用、5-羟色胺能突触、多巴胺能突触、逆行内源性大麻素信号传导、钙信号通路等10个信号通路中。结论 本研究从分子网络的角度初步揭示了四逆散治疗抑郁症的潜在作用机制,其主要的生物学机制可能与以神经活性配体-受体相互作用为中心的信号通路有关。     

疏风解毒胶囊治疗肺炎配伍合理性及其机制研究

目的 对疏风解毒胶囊进行拆方研究,研究清热解毒组分、解表组分及其配伍组合分别对急性肺炎模型大鼠血清细胞因子水平的影响,从而分析疏风解毒胶囊配伍合理性。方法 制备肺炎链球菌致肺炎大鼠模型,分为对照组、模型组、头孢氨苄组、疏风解毒胶囊全方组（全方组）、疏风解毒胶囊解表组（解表组）、疏风解毒胶囊清热解毒组（清热解毒组）,连续给药6 d,检测各组大鼠血清中白细胞介素-1α（IL-1α）、IL-1β、IL-2、IL-4、IL-6、IL-10、肿瘤坏死因子-α（TNF-α）、α干扰素（IFN-α）、IFN-γ水平,评价组方配伍的合理性。结果 疏风解毒胶囊全方、解表组分、清热解毒组分均能显著降低IL-1α、IL-1β、IL-2、IL-4、IL-10水平,全方组大鼠在IL-1β水平上Q值>1;疏风解毒胶囊全方、解表组分、清热解毒组分均能显著降低TNF-α、IFN-γ水平,疏风解毒胶囊全方、解表组分能显著降低IFN-α水平;全方组大鼠在TNF-α、IFN-α水平这2个指标上Q值>1。结论 疏风解毒胶囊有显著的调节免疫功能的作用,解表组分和清热解毒组分有显著的协同作用。     

注射用丹参多酚酸治疗急性脑梗死的疗效及对认知功能、Hcy、NSE、S-100β、GFAP的影响

目的 探讨注射用丹参多酚酸治疗急性脑梗塞的效果及对认知功能、同型半胱氨酸（Hcy）、神经元特异性烯醇化酶（NSE）、S-100β、胶质纤维酸性蛋白（GFAP）的影响。方法 选取唐山市人民医院2017年10月-2018年10月收治的急性脑梗塞患者162例,采用随机数字表法分为两组（各81例）,对照组实施常规治疗,观察者在常规治疗基础上联用注射用丹参多酚酸100 mg/次,静脉滴注,1次/d,连续治疗14 d,于治疗前后检测Hcy、NSE、S-100β和GFAP,并评定患者认知功能、神经功能,比较两组临床疗效及不良反应。结果 两组患者治疗后Hcy、NSE、S-100β、GFAP、美国国立卫生研究院卒中量表（NHISS）评分均较治疗前降低（P<0.05）,简易精神状态评价量表（MMSE）评分、蒙特利尔认知评估量表（MOCA）评分较治疗前增加（P<0.05）;且观察组患者治疗后Hcy、NSE、S-100β、GFAP、NHISS评分低于对照组（P<0.05）,治疗后MMSE评分、MOCA评分高于对照组（P<0.05）。观察组患者总有效率高于对照组（P<0.05）;两组不良反应比较,差异无统计学意义（P>0.05）。结论 注射用丹参多酚酸治疗急性脑梗塞的效果显著,可改善认知功能和神经功能状况,并改善Hcy、NSE、S-100β、GFAP等指征。