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.     

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。     

Rho蛋白与动脉粥样硬化

Rho蛋白作为信号分子,联系细胞表面受体和肌动蛋白细胞骨架的组建,在细胞代谢进程中起重要作用.在动脉血管中,Rho信号途径参与调节平滑肌细胞收缩、迁移、增殖、分化,内皮功能改变,巨噬细胞功能改变,血栓形成,氧化应激与细胞外基质合成等多种动脉粥样硬化的病理生理过程.     

子宫腔碘水加压法输卵管再通术的临床研究

目的寻求一种简便快速、安全有效、经济实用,将造影诊断与输卵管再通治疗结合起来的新方法。方法应用双腔球囊胶管插入子宫腔,充盈球囊堵塞子宫颈内口,用助推器注入碘海醇充盈子宫腔及输卵管,电视动态观察实时点片,完成造影诊断。当发现输卵管阻塞时,用手助推加压,逐渐增高宫腔内压力,使阻塞输卵管被造影剂压力钝性开通。结果本组2698例,插管成功2685例。其中,原发不孕806例,继发不孕1868例,其他24例,输卵管阻塞3082支(右1561支、左1521支),占实有输卵管的59%,加压开通率为77.8%(2397/3082);通而不畅343支(右175支、左168支),加压开通率:93.9%(322/343),出现静脉逆流27例。除局部疼痛及少量阴道流血外,无严重并发症病及病死率。结论该法简便快速,安全有效,经济实用,将造影诊断与输卵管再通相结合,深受患者欢迎,值得推广应用。     

Histomorphologic Characterization of Noncarious and Caries-Affected Dentin/Adhesive Interfaces

PURPOSE: The purpose of this study was to compare the dentin/adhesive interfacial characteristics when bonding to noncarious as well as caries-affected dentin. MATERIALS AND METHODS: Seven extracted, unerupted, third molars were sectioned into halves. Artificial caries was created on one-half of each tooth, leaving the other half as a control. Dentin surfaces were treated with UNO adhesive according to the manufacturer's instructions for the wet-bonding technique and under environmental conditions present in the oral cavity. Dentin/adhesive interface sections of each half-tooth were stained with Goldner's trichrome, a classic bone stain, and examined using light microscopy. The width of exposed collagen was measured directly from photomicrographs, and adhesive penetration was analyzed qualitatively. RESULTS: The degree and extent to which the adhesive encapsulated the demineralized dentin matrix were reflected in the color difference in the stained sections with the noncarious dentin sections showing a degree of collagen encapsulation superior to that of the caries-affected dentin sections. The overall mean widths of exposed collagen were significantly (p < or = .05) greater at the caries-affected dentin/adhesive interface, 8.6 (1.7) microm, as compared with those at the noncarious dentin/adhesive interface, 6.0 (1.5) microm. CONCLUSIONS: The morphologic characteristics of the caries-affected dentin/interface suggest an increase in the exposed collagen zone and a decrease in the quality of the adhesive infiltration when compared with noncarious dentin. The evidence suggests that dentin substrate characteristics have a significant effect on the dentin/adhesive interface structure.     

周围神经因素与骨和组织工程骨

随着对正常骨组织中神经支配的研究,周围神经对骨的作用日益受到重视.目前对支配骨组织的周围神经的类型和功能已进行多方面的研究,发现了多种神经肽,揭示了其对骨组织的重要作用,并在组织工程化骨的构建过程中进行探索,使神经因素参与到骨组织工程研究中来.