Ginsenoside Rg1 prevents acetaminophen-induced oxidative stress and apoptosis via Nrf2/ARE signaling pathway

Inappropriate use of acetaminophen (APAP) can lead to morbidity and mortality secondary to hepatic necrosis. Ginsenoside Rg1 is a major active ingredient in processed Panax ginseng, which is proved to elicit biological effects. We hypothesized the beneficial effect of Rg1 on APAP-mediated hepatotoxicity was through Nrf2/ARE pathway. The study was conducted in cells and mice, comparing the actions of Rg1. Rg1 significantly improved cell survival rates and promoted the expression of antioxidant proteins. Meanwhile, Rg1 reduced the excessive ROS and the occurrence of cell apoptosis, which were related to Nrf2/ARE pathway. Expression of Nrf2 has a certain cell specificity.

     

Innovative Thinking on Endpoint Selection in Clinical Trials

ABSTRACT

In clinical trials, selection of appropriate study endpoints is critical for an accurate and reliable evaluation of safety and effectiveness of a test treatment under investigation. In practice, however, there are usually multiple endpoints available for measurement of disease status and/or therapeutic effect of the test treatment under study. For example, in cancer clinical trials, overall survival, response rate, and/or time to disease progression are usually considered as primary clinical endpoints for evaluation of safety and effectiveness of the test treatment under investigation. Once the study endpoints have been selected, sample size required for achieving a desired power is then determined. It, however, should be noted that different study endpoints may result in different sample sizes. In practice, it is usually not clear which study endpoint can best inform the disease status and measure the treatment effect. Moreover, different study endpoints may not translate one another although they may be highly correlated one another. In this article, we intend to develop an innovative endpoint namely therapeutic index based on a utility function to combine and utilize information collected from all study endpoints. Statistical properties and performances of the proposed therapeutic index are evaluated theoretically. A numerical example concerning a cancer clinical trial is given to illustrate the use of the proposed therapeutic index.     

中医健康状态辨识模式的研究现状与展望

健康状态的辨识是把握健康的前提。当前学界已存在专家辨识模式、标准辨识模式、数字辨识模式、智能辨识模式以及微观辨识模式等。联合多种辨识方法,构建健康状态辨识体系,形成常态与动态结合、主观与客观结合、人机互参的中医健康状态个体化辨识方法是研究的趋势所在。文章对未来的研究方向进行展望,探讨了多元辨识模式、远程辨识模式、终身辨识模式、自动辨识模式的思路方法,以期促进全民健康事业,助力"健康中国"战略。     

Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

Specific alterations in plasma proteins during depressed,manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.     

Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio

BackgroundDual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI).ObjectiveThe present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI).MethodsWe designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant.ResultsCompared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05).ConclusionTAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

BCAN基因在肾透明细胞癌中的表达及临床意义

目的以基因表达数据集资料为研究对象,分析BCAN基因在肾透明细胞癌中的表达情况以及对患者预后的影响。方法在Oncomine数据库中挖掘BCAN在肾透明细胞癌(ccRCC)中的表达情况。从TCGA数据库中获取ccRCC患者临床资料和目的基因的表达信息并进行统计分析。利用GEO数据库中GSE73731数据集的ccRCC样本进行基因富集分析。利用String数据库分析与BCAN相关的蛋白。结果BCAN低表达组的ccRCC患者在病理分期及T分期方面低于高表达组(P<0.001;P=0.001);N分期及M分期差异无统计学意义(P>0.05)。BCAN低表达组患者的总生存期优于高表达组(P=0.033)。BCAN基因高表达组的样本主要富集在KRAS信号通路。结论BCAN可以通过多种途径来促进肿瘤细胞的侵袭能力,有望成为ccRCC不良预后的重要生物标志物之一。