Targeted delivery of hyaluronic acid-coated solid lipid nanoparticles for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease. Long-term, high-dose glucocorticoid therapy can be used to treat the disease, but the fact that the drug distributes systemically can give rise to severe adverse effects. Here we develop a targeted system for treating RA in which the glucocorticoid prednisolone (PD) is encapsulated within solid lipid nanoparticles (SLNs) coated with hyaluronic acid (HA), giving rise to HA-SLNs/PD. HA binds to hyaluronic receptor CD44, which is over-expressed on the surface of synovial lymphocytes, macrophages and fibroblasts in inflamed joints in RA. As predicted, HA-SLNs/PD particles accumulated in affected joint tissue after intravenous injection into mice with collagen-induced arthritis (CIA), and HA-SLNs/PD persisted longer in circulation and preserved bone and cartilage better than free drug or drug encapsulated in SLNs without HA. HA-SLNs/PD reduced joint swelling, bone erosion and levels of inflammatory cytokines in serum. These results suggest that encapsulating glucocorticoids such as PD in HA-coated SLNs may render them safe and effective for treating inflammatory disorders.     

医教协同加强培养医学生人文素质教育的实践研究△

目的：通过医教协同、院校合作培养,提升医学生人文素质。方法：在调查研究的基础上,院校双方达成共识,制订具体的培养方案,在实施过程中总结完善。结果：医学生的人文素质得到提升。结论：医教协同、院校深入合作加强医学人文素质教育能够有效提升医学生的整体素质。     

参一胶囊联合洛铂和吉西他滨治疗复发性卵巢癌的临床研究

目的探讨采用参一胶囊联合洛铂和吉西他滨治疗复发性卵巢癌患者的有效性和安全性。方法选取安徽医科大学附属巢湖医院2013年1月—2014年1月收治的复发性卵巢癌患者150例,随机分成对照组和治疗组,每组各75例。对照组患者在第1、8天分别静脉滴注注射用盐酸吉西他滨,1 g/m~2加入生理盐水500 m L,第2天静脉滴注注射用洛铂,50 mg/m~2加入生理盐水250 m L。治疗组患者在对照组基础上饭前口服参一胶囊,2粒/次,2次/d。21 d为1个疗程,两组患者连续治疗2个疗程。评价两组患者近期和远期疗效,同时比较治疗前后两组患者生活质量(QOL)评分、CA125血清水平和不良反应情况。结果治疗后,对照组客观缓解率和疾病控制率分别为44.00%和69.33%,均分别显著低于治疗组的68.00%和89.33%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者QOL评分显著升高(P0.05),CA125血清水平显著降低(P0.05);且治疗组患者的QOL评分和CA125血清水平改善更明显(P0.05)。治疗后2个月随访结果表明,治疗组患者疾病进展时间、总生存期和1年生存率均显著优于对照组患者(P0.05)。治疗期间,治疗组患者在白细胞下降,血小板下降及肝肾功能损伤等不良反应方面要显著低于对照组患者,两组比较差异具有统计学意义(P0.05)。结论参一胶囊联合洛铂和吉西他滨治疗复发性卵巢癌效果明显,安全性高,具有一定的临床推广应用价值。     

Pharmacoperone drugs: targeting misfolded proteins causing lysosomal storage-, ion channels-, and G protein-coupled receptors-associated conformational disorders

Introduction: Conformational diseases are caused by structurally abnormal proteins that cannot fold properly and achieve their native conformation. Misfolded proteins frequently originate from genetic mutations that may lead to loss-of-function diseases involving a variety of structurally diverse proteins including enzymes, ion channels, and membrane receptors. Pharmacoperones are small molecules that cross the cell surface plasma membrane and reach their target proteins within the cell, serving as molecular scaffolds to stabilize the native conformation of misfolded or well-folded but destabilized proteins, to prevent their degradation and promote correct trafficking to their functional site of action. Because of their high specificity toward the target protein, pharmacoperones are currently the focus of intense investigation as therapy for several conformational diseases.

Areas covered: This review summarizes data on the mechanisms leading to protein misfolding and the use of pharmacoperone drugs as an experimental approach to rescue function of distinct misfolded/misrouted proteins associated with a variety of diseases, such as lysosomal storage diseases, channelopathies, and G protein-coupled receptor misfolding diseases.

Expert commentary: The fact that many misfolded proteins may retain function, offers a unique therapeutic opportunity to cure disease by directly correcting misrouting through administering pharmacoperone drugs thereby rescuing function of disease-causing, conformationally abnormal proteins.     

正交实验法优化中药香囊质量标准的研究

目的:优化中药香囊的质量标准.方法:通过单因素法及正交实验法对药粉细度、载药量、棉花用量进行优化,确定中药香囊的质量标准.结果:中药香囊优化的质量标准为:药粉细度40目;载药量30g;棉花用量40g.结论:中药香囊通过优化质量标准,具有较好的灭菌作用.     

体外红细胞计数法测定养血注射液溶血性的试验

目的:观察养血注射液溶血性.方法:采用体外红细胞计数法测定养血注射液的溶血性.结果:养血注射液溶血率低于5％.结论:养血注射液溶血率低,安全性较好.     

2型糖尿病和抑郁症共同发病机理的研究进展

越来越多的证据表明,抑郁症和2型糖尿病（T2DM）有着共同的发病机理,尤其表现在固有免疫的过度激活所导致的细胞因子介导的炎症反应上,并可能与下丘脑-垂体-肾上腺（HPA）轴功能失调有关。加深对T2DM和抑郁症共同发病机理的认识,将为研制同时治疗这两种疾病的新型药物提供崭新的思路,同时也将极大地促进糖尿病患者的一级预防。2型糖尿病;抑郁症;发病机理     

基于网络药理学的注射用益气复脉(冻干)作用机制研究

目的 基于网络药理学平台研究注射用益气复脉（冻干,YQFM）治疗心血管疾病的作用机制。方法 在前期研究基础上结合文献选出YQFM主要化合物结构母核,通过DRAR-CPI服务器对结构母核进行模拟分子-靶蛋白对接,筛选靶点;对获取的靶点信息通过KEGG数据库进行注释,结合文献对所得通路进行分析;利用Cytoscape 3.6.0软件,构建上述靶点的“化合物-靶点-通路-网络”整合模型;阐述YQFM治疗心血管疾病的作用机制。结果 本研究共筛选了7个化合物母核：20（S）-原人参三醇、齐墩果酸、2''-羟基异麦冬黄酮A、麦冬黄酮B、麦冬皂苷元、五味子甲素、五味子乙素;主要对应GASP、AKT、INS、AKT、GSK3β、JNK、GSK3β、ERK1、ERK2等127个作用靶点,以及丝裂原活化蛋白激酶（MAPK）、腺苷酸活化蛋白激酶（AMPK）心血管功能及糖脂代谢相关、肿瘤坏死因子（TNF）、雷帕霉素靶蛋白（mTOR）炎症相关等信号通路。结论 YQFM主要通过心血管保护、炎症与免疫调节、以及糖脂代谢干预等多条途径实现气阴两虚证的心血管疾病治疗作用。网络药理学方法可以简便、系统地预测YQFM的主要药效成分的网络机制,为中医药治疗心血管疾病提供研究方向。     

佳木斯市学龄儿童注意缺陷多动障碍流行病学调查研究

目的:了解佳木斯市6～14岁儿童注意缺陷多动障碍的患病情况.方法:采取分阶段整群抽样的方法,选取佳木斯市区10所小学,每个年级随机抽取1个班,一共入组了1832人.结果:总检出患病人数为113人,整体发病率为6.168％.其中男生947人,检出患者76人,发病率为8.0％;女生885人,检出患者37人,发病率为4.1％.男患女患比值为2.05:1.其中6岁儿童患病率为4.7％,男性患病率6.3％,女性患病率为2.9％;7岁儿童患病率为5.6％,男性患病率6.9％,女性患病率为4.2％;8岁儿童患病率为8.5％,男性患病率10.9％,女性患病率为6.2％;9岁儿童患病率为11.6％,男性患病率15.5％,女性患病率为7.1％;10岁儿童患病率为6.7％,男性患病率8.4％,女性患病率为4.8％;11岁儿童患病率为5.9％,男性患病率7.4％,女性患病率为4.2％;12岁儿童患病率为4.7％,男性患病率5.9％,女性患病率为3.5％;13岁儿童患病率为3.8％,男性患病率4.5％,女性患病率为3.9％;14岁儿童患病率为2.6％,男性患病率5.3％,女性患病率为0％.结论:佳木斯地区学龄儿童注意缺陷多动障碍的发病水平与全国水平基本一致,男生发病率明显高于女生,9岁儿童患病率最高.