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.     

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.     

青岛市2018年1例疟疾死亡病例分析

目的 分析青岛市2018年1例输入性恶性疟的死亡原因,为预防疟疾死亡病例发生提供参考。方法 访谈接诊医生及患者家属,对患者病历和流行病学调查资料进行分析。结果 患者刘某,男,35岁,青岛市城阳区人,2018年3月19日到科特迪瓦务工,7月17日回国。25日患者到韩国办事,26日下午出现发冷、发热、出汗、头痛、浑身酸痛等症状,26—27日自服退烧药无好转,28日上午到韩国某医院就诊,未明确诊断,下午出现腹泻、呕吐症状,29日下午回国,14∶59到城阳区人民医院就诊,精神萎靡,经询问患者有非洲出国史可能患疟疾,16∶30将患者转诊至疟疾治疗定点医院,17∶50到达青岛市传染病医院时患者呈深昏迷状态,医生考虑患者病情危重且该院正在改建无ICU病房,建议转至有抢救条件的综合医院抢救。19:40患者转入海慈医疗集团ICU病房,21∶00被确诊为恶性疟,因病情危重,患者于30日14∶15死于多脏器功能衰竭。结论 对于输入性疟疾,根据流行病学史、临床症状和实验室检测结果尽早明确诊断,尽早使用抗疟药治疗,是避免出现死亡病例的关键。