AXL表达与乳腺癌预后及临床病理特征关系的Meta分析

目的 探讨受体酪氨酸激酶AXL蛋白的表达对乳腺癌患者预后及临床病理特征的意义。方法 在中国知网(CNKI)、万方医学网(Wanfang Data)、 Cochrane Library、Embase、PubMed和Medline数据库中,搜索国内外公开发表的有关AXL与乳腺癌预后关系的文献,检索时限均为从建库至2019年10月。2位研究者按纳入和排除标准独立筛选文献、提取资料和评价纳入研究的偏倚风险,并进行Meta分析。结果 共纳入7篇文献,包括933例乳腺癌患者。AXL高表达组的乳腺癌患者总生存期(overall survival,OS)明显低于低表达组(HR=2.36,95%CI 1.60~3.46,P<0.000 1),但其表达在无复发生存期(relapse free survival,RFS)和无疾病生存期(disease free survival,DFS)中差异无统计学意义,且与乳腺癌的年龄、临床分期、组织分级、淋巴结转移及受体表达的相关性分析无统计学意义。结论 AXL的阳性表达与乳腺癌患者预后不良有关,是乳腺癌个体化治疗的潜在分子标志物。     

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.     

吗啡依赖和戒断对大鼠杏仁核神经甾体和氨基酸递质水平的影响

目的研究吗啡依赖和戒断时大鼠杏仁核中神经甾体和氨基酸递质水平的变化。方法连续7天给予大鼠盐酸吗啡建立吗啡依赖模型。使用纳洛酮(2mg/kg)催促戒断,观察戒断症状并进行评分。将大鼠断头处死后,剥离大脑并分离出杏仁核,用液-液萃取和固相萃取法提取游离型和结合型神经甾体。神经甾体(包括脱氢表雄酮、孕烯醇酮、别孕烯醇酮、脱氢表雄酮硫酸酯和孕烯醇酮硫酸酯)的含量使用高效液相色谱-质谱法测定。甘氨酸、谷氨酸和γ-氨基丁酸的含量采用柱前OPA衍生-电化学检测-高效液相色谱法测定。结果与盐水对照组相比,吗啡依赖大鼠杏仁核中的脱氢表雄酮水平降低33 %(P<0·01)。与戒断对照组比较,吗啡戒断大鼠杏仁核中的孕烯醇酮和别孕烯醇酮水平分别升高45 %和42 %(P<0·05) ,γ-氨基丁酸水平降低18 %(P<0·01)。与吗啡依赖组比较,吗啡戒断组大鼠杏仁核中的孕烯醇酮和孕烯醇酮硫酸酯水平分别升高60 %和40 %(P<0·05) ,甘氨酸水平降低14 %(P<0·05)。结论吗啡依赖大鼠杏仁核中的脱氢表雄酮可能参与吗啡依赖的形成而与吗啡戒断症状的表达无关。其他神经甾体(包括孕烯醇酮、别孕烯醇酮和孕烯醇酮硫酸酯)则可能参与吗啡的戒断而与依赖的形成无关。纳洛酮催促戒断时,大鼠杏仁核中抑制性氨基酸递质的合成和释放受到抑制。表明大鼠杏仁核中的各种神经甾体和氨基酸递质在吗啡依赖和戒断时发生了不同的变化。     

健康教育个体化对预防急性冠脉综合征的应用研究

目的研究健康教育预防急性冠脉综合征(ACS)的临床治疗效果.方法将62例老年ACS患者分为A组 (常规教育)和B组 (个体化教育),B组通过指导患者制定合适的活动度、掌握缓解疼痛的方式、改善遵医行为、减少冠心病强危险因素以及改变A型行为等方法对患者进行个体化健康教育;A组分小组实施教育.对2组患者康复效果进行对照比较.结果 2组患者的康复有效率:A组低于B组,经统计学分析差异有显著性.结论在ACS患者的诊疗过程中,实施个体化教育对促进患者恢复,减少危险因素的发生具有重要辅助作用.