Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

医院离退休干部参与社会治理现状

通过文献研究、问卷调查、专家访谈、现地调研等方法,分析医院离退休干部参与社会治理的现状及影响因素,探讨社区对离退休干部参与社会治理的需求,提出通过党建引领医院离退休干部参与社会治理的“1235”模式,并给出具体的操作路径,以期为推动医院离退休干部积极参与社会治理提供参考。     

胃癌患者术前应用含ω-3不饱和脂肪酸的肠内营养制剂的临床效果观察

目的探讨术前应用含ω-3不饱和脂肪酸的肠内营养制剂对胃癌患者营养状况和炎症因子水平的影响,并对其进行安全性评价。方法前瞻性纳入2014年1~6月期间四川大学华西医院收治的60例胃癌患者,随机分为试验组(30例)和对照组(30例)。试验组术前以含ω-3不饱和脂肪酸的营养制剂(瑞能)作为肠内营养制剂,对照组进食等热卡等氮的均浆膳,术前均连续服用5 d,至术前1 d。检测患者入院时、术前1 d、术后3 d及术后5 d血清中的炎症因子指标和营养相关指标,检测患者入院时和术前1 d的肝肾功能指标以作为安全性评价指标;记录患者呕吐、腹泻等不良反应,以及术后感染相关并发症的发生情况。结果术后3 d试验组患者的白介素-6(IL-6)和α-1酸性糖蛋白(AAG)水平均低于对照组(P<0.05),术后5 d试验组的C反应蛋白(CRP)水平低于对照组(P<0.05),其余各时点2组患者的各指标比较差异均无统计学意义(P>0.05)。在肠内营养支持期间,试验组患者发生腹胀1例,腹泻1例,对照组患者未出现腹胀、腹泻等不适。2组患者的不良反应发生率比较差异无统计学意义(P>0.05)。术后试验组发生切口感染1例(3.3%);对照组发生切口感染3例(10.0%),腹腔感染1例(3.3%),尿路感染1例(3.3%),肺部感染2例(6.7%),共计7例(23.3%)。2组患者的腹腔感染、切口感染、尿路感染及肺部感染发生率比较差异均无统计学意义(P>0.05),但试验组的总并发症发生率低于对照组(P=0.026)。结论术前应用含ω-3不饱和脂肪酸的营养制剂降低了胃癌患者术后的感染并发症发生率,且安全性较高。     

大病保险对我国中老年人家庭灾难性卫生支出影响实证分析

目的:考察大病保险对我国中老年人家庭灾难性卫生支出的影响,为完善我国大病保险制度提供建议。方法:以中国健康与养老追踪调查数据库(2011年与2015年)中45岁及以上的城乡中老年人家庭作为研究对象,利用描述性统计法和两部模型法分析大病保险对我国中老年人家庭灾难性卫生支出的影响。结果:目前的大病保险政策从总体上降低了中老年人家庭灾难性卫生支出的发生率,但没有显著降低其发生强度。结论:目前的大病保险并未达到其预期的效果,只是解决了"面"的问题,从总体上降低了灾难性卫生支出发生的可能性,但并没有解决"点"的问题,没有有效降低其大额的医疗卫生支出进而减少其医疗经济负担。建议各地各级政府相关部门应进一步完善大病保险制度,从而真正有效减轻居民重大疾病医疗经济负担。