Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models

Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE₂) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE₂ receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE₂/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.     

激光联合复方血栓通胶囊治疗糖尿病视网膜病变合并黄斑水肿的疗效观察

目的:分析糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效。方法:选取我院2017年1月—2019年1月收治的200例糖尿病视网膜病变合并黄斑水肿患者为研究对象,随机分为两组。对照组单独行激光治疗,观察组于对照组基础上联合复方血栓通胶囊治疗,对比两组临床疗效、治疗前后IL-6(白介素-6)、VEGF(血管内皮生长因子)、NOS(血清一氧化氮合成酶)水平变化情况。结果:对照组总有效率(68.00%,68/100)较观察组总有效率(98.00%,98/100)更高(P<0.05);与对照组对比,观察组治疗后NOS水平更高,IL-6、VEGF水平更低(P<0.05)。结论:糖尿病视网膜病变合并黄斑水肿联合采用激光与复方血栓通胶囊治疗的临床疗效显著,值得推广。     

沙利度胺联合TACE治疗原发性肝癌疗效与安全性的系统评价

目的:系统评价沙利度胺(thalidomide,TLD)联合肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)治疗原发性肝癌(primary hepatic carcinomas,PHC)的疗效和安全性.方法:计算机检索Cochrane Library(2014年第3期)、Web of Science(1986/2014-03)、Pub Med(1966/2014-03)、CNKI(1917/2014-03)、维普(1989/2014-03)、万方数据库(1998/2014-03),收集所有TLD联合TACE治疗PHC的随机对照试验.由两名评价员严格按照纳入标准选择文献,提取资料,并参照Cochrane系统评价的要求,对选择纳入的随机对照试验进行方法学质量评估后,采用Cochrane协作网提供的Rev Man 5.2软件对总有效率、疾病控制率、生活质量KPS评分、不同年限生存率、甲胎蛋白的变化、血管内皮生长因子(vascular endothelial growth factor,VEGF)的变化及不良反应发生率进行Meta分析.结果:最终纳入22项随机对照试验,包括1590例PHC患者,Meta分析结果显示,TLD联合TA C E组治疗P H C的总有效率(R R合并=1.29,95%C I:1.15-1.44)、疾病控制率(R R合并=1.27,95%CI:1.16-1.39)、生活质量KPS评分(MD合并=9.23,95%CI:6.90-11.55)、半年生存率(RR合并=1.10,95%C I:1.01-1.20)、1年生存率(RR合并=1.25,95%C I:1.13-1.39)、2年生存率(RR合并=1.45,95%CI:1.18-1.78)、3年生存率(R R合并=1.7 0,9 5%C I:1.1 6-2.5 0)、V E G F水平的变化(M D合并=-123.64,95%C I:-143.72--103.55)优于单纯TACE组,差异有统计学意义(均P0.05);不良反应发生率:在药物性皮疹发生率方面,TLD联合TACE组明显高于单纯TACE组,差异有统计学意义(RR=4.50,95%CI:2.34-8.64,P0.00001);在减少消化系应发生率(RR=1.08,95%CI:0.93-1.25)、降低骨髓抑制发生率(RR=1.12,95%CI:0.82-1.52)、降低肝功能异常发生率方面(R R=1.00,95%C I:0.72-1.39),T L D联合TA C E组与单纯TA C E组相近似,差异无统计学意义(均P0.05).结论:目前研究显示,与单纯TACE疗法相比,TLD联合TACE治疗PHC在总有效率、疾病控制率、生活质量KPS评分、半年生存率、1、2、3年生存率、降低V E G F方面具有明显的优势,但在安全性方面,TLD联合TACE组在药物性皮疹发生率方面明显高于单纯TACE组,而在消化系反应、骨髓抑制率、肝功能异常方面与单纯TACE组相似.     

不同规格怀牛膝不同极性部位HPLC指纹图谱

目的研究并比较不同规格怀牛膝不同极性部位的HPLC指纹图谱,探索其内部质量差异,为该药材的规格标准完善及临床用药提供参考。方法将怀牛膝用体积分数75%乙醇水浴回流提取,得体积分数75%乙醇回流提取物,用40 mL水溶解后,依次用石油醚、三氯甲烷、乙酸乙酯、正丁醇进行萃取,得到各萃取相及萃取后的水相,浓缩至浸膏,采集各部位HPLC指纹图谱;运用相似度、综合聚类法进行数据分析,同时对其不同部位的指纹图谱进行比对分析。结果石油醚、氯仿部位均标定了11个共有峰,乙酸乙酯部位标定了10个共有峰,正丁醇部位标定了19个共有峰,水部位标定8个共有峰;氯仿部位指纹图谱相似度差异较大,其他部位指纹图谱相似度差异较小,均在0.9以上;石油醚部位指纹图谱差异主要体现在峰高,乙酸乙酯部位、氯仿部位、水部位的化学成分种类及峰高均存在差异;综合聚类分析能将不同规格怀牛膝区分开。结论不同规格怀牛膝内部质量存在差异;实验中所建立的HPLC指纹图谱可以全面反映不同规格怀牛膝的化学成分分布,为不同规格怀牛膝的整体质量评价提供参考。     

培养护生养成阅读药物说明书的习惯

同类药物因原料来源、附加成分和生产厂家不同而商品名称各异，有些名称相似的药物其性能却完全不同。临床实习护生常反映课本讲授的药物知识与临床用药相差甚远，不知如何记住所有的药物。为此，作者在临床教学中培养学生养成阅读药物说明书的习惯，收到良好效果。     

亚甲蓝甘油合剂封闭治疗三叉神经痛108例

目的观察亚甲蓝甘油合剂封闭治疗三叉神经痛的临床疗效并探讨其治疗机制。方法按国际头面痛学会分类委员会确定的诊断标准,108例原发性三叉神经患者随机分为两组:A组为亚甲蓝甘油合剂组(n=54),B组为单纯甘油合剂组(n=54);采用徐贵印推荐的三维测角穿刺半月神经节进行封闭治疗,对治疗后1周、3个月和2年分别进行疗效评判和随访观察。结果两组治疗后1周、3个月优良率比较差异无统计学意义(P>0.05),两年后优良率比较差异有统计学意义(P<0.05);两组并发症没有明显差异,2例出现视力下降,3例因解剖变异未能穿刺成功,仅在卵圆孔周围进行了注射,外加眶下孔以及骸孔封闭。结论亚甲蓝甘油合剂用于治疗三叉神经痛远期疗效优于单纯甘油合剂,且亚甲蓝对神经未见明显损害(经2年随访)。     

Efficacy and safety of herbal medicines for idiopathic Parkinson's disease: a systematic review.

The objective of this study is to assess the efficacy and safety of herbal medicines (HMs), as a monotherapy or adjunct therapy, compared to placebo or conventional approaches in the treatment of idiopathic Parkinson's disease (PD). We conducted a systematic review of randomized controlled trials from both conventional and alternative medicine sources. Outcome measures were overall improvement, quality of life, reduction of levodopa dose, and adverse events. Nine studies were included, each testing a different HM. Six of the trials had limited internal validity due to major flaws in design, including the lack of proper randomization; insufficient blinding; unclear inclusive criteria in terms of diagnostic criteria, baseline staging, and duration of disease; lack of proper sample size calculation; and insufficient data analysis. Imbalances in gender and ethnicity among the patients in the included trials were observed. No major adverse events emerged, and no specific pattern was detected from the trials describing such data. In addition to major methodological defects, heterogeneity in (1) HM tested, (2) control treatment, and (3) outcome measure hindered in-depth data analysis and synthesis. Current evidence is insufficient to evaluate the efficacy and safety of various HMs. Further studies with improved trial design and reporting, with assessment on cost-effectiveness, quality of life, and qualitative data are warranted.