Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊的临床疗效研究

目的:探究桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊的临床疗效。方法:收集2016年12月-2018年12月我院收治的老年出血性玻璃体混浊患者67例,共67眼,根据随机对照表分为对照组和试验组,其中试验组34例,对照组33例,对照组予以银杏酮酯滴丸;试验组在对照组的基础上联用桃红四物汤。两组均服用30 d。治疗结束后对比分析两组患者临床疗效、出血吸收时间、血液流变学及视网膜中央动脉血流动力学。结果:治疗后两组患者高切全血粘度、低切全血粘度、纤维蛋白原、阻力指数(Resistance Index,RI)低于治疗前,收缩期峰值速度(Peak Systolic Velocity,PSV)、舒张末期血流速度(End Diastolic Velocity,EDV)高于治疗前,差异具有统计学意义(P<0.05);治疗后试验组临床总有效率、PSV、EDV高于对照组,出血吸收时间、高切全血粘度、低切全血粘度、纤维蛋白原、RI低于对照组,差异具有统计学意义(P<0.05)。结论:桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊临床疗效显著,适宜临床应用推广。     

基于“证治代谢组学”假说探讨中药（单体/复方）药效物质基础的研究思路与实践＊

中药(单体/复方)药效物质基础研究是中医药现代研究的关键问题之一。然而,目前运用的生化和分子生物学方法很难诠释其多靶点、整体性和动态性的整合调节作用。课题组提出的"证治代谢组学"假说理论指出,不同的证候存在"证相关代谢谱群"和"证相关生物标志物",这可能是中药药效物质基础所在,辨证论治后偏离的代谢网络功能呈现回归趋势。基于"证治代谢组学"假说开展中药(单体/复方)药效物质基础研究,这将为阐释中药(单体/复方)防病治病和养生保健的科学内涵及其对疾病个体的整合调节作用提供新的思路。本文以冠心病为研究载体、气阴虚血瘀证为切入点、活血保心丸为干预措施,就该研究思路的内涵与总体模式、提出的背景与依据、实践的方式与可行性、创新与特色及其研究意义等进行了简要介绍。     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

复方华蟾胶囊抗小鼠肿中瘤作用的实验研究

目的了解复方华蟾胶囊抗小鼠移植性肿瘤的作用.方法以小鼠肝癌22(H22)、小鼠肉瘤180(S180)为瘤株,应用动物移植性肿瘤的体内试验法对药物进行抗癌药效学试验.结果复方华蟾胶囊灌胃4,2 g/kg@d,连续14 d,对小鼠移植性肝癌实体型生长有明显的抑制作用,抑瘤率分别为38.09%,30.95%.对小鼠移植性S180实体型生长有明显的抑制作用,抑瘤率分别为34.7%,30.08%.复方华蟾胶囊对荷瘤小鼠的胸腺和脾脏重量无影响.结论复方华蟾胶囊在试验条件下有一定抗肿瘤作用.     

老年护理院医院感染病原菌及其耐药特征分析

目的探讨目前老年护理医院院内感染病原菌及其耐药特征。方法对2000年4月-2004年3月徐汇区两家老年护理院出院病人的病史进行统计分析。结果两家老年护理院共计发生医院感染939例次，医院感染率12．86％，检出病原菌284株，阳性率30．28％；病原菌以革兰阴性菌为主，占44．65％，其次为真菌、革兰阳性菌，分别为29．12％、25．92％，位于前3位的病原菌分别为其他真菌（14．36％）、白色念珠菌（12．23％）、铜绿假单胞菌（8．69％）；除嗜麦芽寡养单胞菌外，革兰阴性菌以亚胺培南最敏感，敏感率87％，对氨苄西林、阿莫西林的耐药率〉51％，对头孢哌酮、哌拉西林的耐药率〉33％；MRSA和MRSE的检出率高达86．76％和76．32％；混合感染率34．51％。结论老年护理院医院感染率高．真菌所占的比例高；细菌对抗菌药物的耐药性相当严重。     

中药内外并用抗尖锐湿疣复发的临床研究

目的：观察中药消疣丸/消疣擦剂内服外用防止尖锐湿疣复发的作用.方法：应用免疫学方法，检测患者治疗前后外周血T淋巴细胞亚群CD3、CD4、CD8的百分率和CD4/CD8的比值.结果：局部消除疣体后中药消疣丸/消疣擦剂内服外用对防止尖锐湿疣复发有显著疗效，痊愈率为99.66%，复发率为3.33%，与对照组相比有显著差异（P〈0.05）.结论：中药内服外用抗尖锐湿疣复发效果好。     

大型尿基复合肥养分偏差的原因分析及措施

介绍大型尿基复合肥装置在生产中引起产品养分偏差的原因及采取的操作措施。     

兔内听动脉阻断与听觉改变的关系

目的 探讨实验性内听动脉阻断与术后听力改变的关系及术中听觉监控的方法。方法 实验兔乙状窦后进路暴露小脑桥脑角，下压小脑暴露内听道及第Ⅷ神经复合体，分辨出内听动脉，予阻断不同时间，分别行蜗神经直接复合动作电位(DCAP)和畸变产物耳声发射记录(DPOAE)。结果对照组DCAPN1波潜伏期值无明显改变。内耳血供阻断10s和30s组在压迫开始后3min，DCAPN1波潜伏期值均恢复为初始值。内耳血供阻断1min组在压迫开始后3h，DCAPN1波潜伏期值未恢复为初始值假手术组DPOAE幅值无明显改变，内耳血供阻断10s、30s对DPOAE幅值无影响，内耳血供阻断1min使得DPOAE幅值下降结论兔内耳血供阻断1min可能造成兔听觉不可逆损伤。DCAP、DPOAE能有效、持续地监控内耳血供阻断，是耳神经外科手术中实用的听觉监测手段。     

市售三厂家18种复方氨基酸注射液的质量评价

目的对市售3厂家(A、B和E)共9批18种复方氨基酸注射液进行质量比较。方法参考国内外同类产品质量标准,从澄明度、透光率、性状、pH值、不溶性微粒、抗氧剂量、细菌内毒素和含量等方面进行比较。结果外观均为无色澄明液体,430nm波长处透光率均大于99%,pH在5.42～6.61间;A、B、E3厂不溶性微粒≥10、≥25μm的粒子数分别为1.41、0.32,0.83、0.21和1.55、0.56个/ml;抗氧剂的量分别为<33、近330和>500mg/L;细菌内毒素检查与含量测定符合中国药典及国家标准要求。结论不同厂家的产品质量确实存在一定的差异。