当药苷调节兴奋-收缩耦联改善心肌缺血再灌注损伤的机制

目的 探索当药苷通过兴奋-收缩耦联信号通路对缺血再灌注损伤后心脏收缩/舒张功能的影响。方法 24只健康雄性SD大鼠随机分为正常组、模型组、10 μmol·L^-1当药苷给药组与1 μmol·L^-1地高辛给药组，并采用Langendorff系统结合左前降支冠状动脉结扎建立缺血再灌注损伤模型（I/R），2，3，5-氯化三苯基四氮唑（TTC）染色检测各组心脏梗死面积，Powerlab生理记录仪检测血流动力学参数，如左心室舒张压（LVDP）、左心室终末舒张压（LVEDP）、左心室终末收缩压（LVESP）、左心室内压最大上升速率（+dp/dt_max）和左心室内压最大下降速率（-dp/dt_max）；提取分离乳鼠原代心肌细胞（NRCMs），建立缺氧/复氧（H/R）损伤模型，随机分为正常组、模型组、1 μmol·L^-1当药苷给药组和10 μmol·L^-1当药苷给药组，多功能成像细胞分析仪和激光共聚焦显微镜测定各组心肌细胞活力、心率、收缩幅度、收缩时程、达峰时程和舒张时程及钙瞬变峰值。根据前期转录组学测序结果及文献调研，利用实时荧光定量聚合酶链式反应（Real-time PCR）检测L型钙通道相关基因（Cacnb2），细胞色素C氧化酶相关基因（Cox6a2），肌钙蛋白（Tnnc1、Tnni3、Tnnt2）、肌动蛋白（Actc1）、肌球蛋白（Myh6、Myl2、Myl4）等兴奋-收缩耦联通路基因的mRNA表达并对差异基因进行聚类分析。结果 与正常组比较，模型组心肌梗死面积显著增加（P<0.01）、LVDP显著降低（P<0.01）、LVEDP显著上升（P<0.01）、LVESP明显下降（P<0.05）、+dp/dt_max有下降趋势和-dp/dt_max上升趋势及心肌细胞活力降低、心率降低、收缩幅度降低、收缩时程升高、达峰时程升高和舒张时程升高（P<0.01），而当药苷可以逆转上述指标（P<0.05）。此外，心肌细胞经H/R损伤后，Cacnb2、Cox6a2、Tnnc1、Tnni3、Tnnt2、Actc1、Myh6、Myl2、Myl4等兴奋-收缩耦联通路的基因表达下降（P<0.05、P<0.01）。而使用当药苷预处理后，可以增强上述基因的表达（P<0.05）。结论 当药苷通过调节兴奋-收缩耦联信号通路，从而调节原代乳鼠心肌细胞内钙离子水平，增强心肌收缩功能，对抗I/R损伤。     

Different clinical features between patients with ROS1-positive and ALK-positive advanced non-small cell lung cancer

ObjectiveTo compare the baseline clinical characteristics between patients with ROS1-positive and ALK-positive advanced non-small cell lung cancer (NSCLC), and the correlations of these subtypes with the distribution of metastases.MethodsWe compared the clinical characteristics and imaging features of patients with ROS1-positive and ALK-positive NSCLC using statistical methods.ResultsData for 232 patients were analyzed. Compared with ALK-positive NSCLC, ROS1-positive NSCLC was more likely to occur in women (71% vs 53%), and primary lesions ≤3 cm were more common in patients with ROS1-positive compared with ALK-positive NSCLC (58% vs 37%). There was no significant difference in the distribution of metastases between the two groups. Subgroup analysis within the ROS1-positive group showed that, compared with primary lesions >3 cm, primary lesions ≤3 cm were more likely to present as peripheral tumors (72% vs 43%) and more likely to exhibit non-solid density (44% vs 4%).ConclusionsAlthough ROS1-positive and ALK-positive NSCLCs show similar clinical features, the differences may help clinicians to identify patients requiring further genotyping at initial diagnosis.     

Meta-analysis of NOD2/CARD15 polymorphisms with psoriasis and psoriatic arthritis

Psoriasis and psoriatic arthritis (PsA) is a complex autoimmune disease. NOD2/CARD15 gene has been suggested to play an important role in the pathogenesis of psoriasis and PsA. This study aims to assess the association between NOD2/CARD15 polymorphisms and the susceptibility to psoriasis/PsA. A meta-analysis was performed to survey studies on the NOD2/CARD15 polymorphisms and psoriasis/PsA using comprehensive PubMed, Embase, and Web of Science citation search. A total of 9 published studies were involved. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed effects models or random effects models were depended on Cochran’s Q-statistic. Potential publication bias was evaluated by Egger’s linear regression test. As for R702W, the pooled ORs were 1.041 (95% CI 0.854–1.268, P?=?0.693; 2,081 patients vs. 2,717 controls) for C allele and 0.886 (95% CI 0.565–1.391. P?=?0.600; 1,222 patients vs. 1,818 controls) for genotype. Then for G908R, the pooled ORs were 1.042 (95% CI, 0.761–1.426, P?=?0.799; 2,053 patients vs. 2,743 controls) for C allele and 0.942 (95% CI 0.708–1.254, P?=?0.683; 1,226 patients vs. 1,824 controls) for the homozygous wild type. Then for Leu1007fsinsC allele polymorphism and genotype, the pooled ORs were 1.160 (95% CI, 0.893–1.507, P?=?0.266; 2,279 patients vs. 3,067 controls) and 1.266 (95% CI 0.897–1.789, P?=?0.180; 1,979 patients vs. 1,607 controls), respectively. No obvious publication bias was shown in the results. The association between NOD2/CARD15 polymorphisms and psoriasis/PsA was not found. Taken together, our results suggest that NOD2/CARD15 might not be a susceptibility gene for psoriasis and psoriatic arthritis.