Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT,and RASSF1A methylations in Vietnamese lung adenocarcinomas

Genetic and epigenetic alterations importantly contribute to the pathogenesis of lung cancer. In the study, we measured the frequency and distribution of molecular abnormalities of EGFR as well as the aberrant promoter methylations of BRCA1, MGMT, MLH1, and RASSF1A in Vietnamese lung adenocarcinomas. We investigated the association between genetic and epigenetic alteration, and between each abnormality with clinicopathologic parameters. Somatic EGFR mutation that was found in 49/139 (35.3%) lung adenocarcinomas showed a significant association with young age, female gender, and non-smokers. EGFR overexpression was identified in 82 tumors (59.0%) and statistical relationships with EGFR or BRCA1 methylation but not EGFR mutation. In addition, EGFR, BRCA1, MGMT, MLH1, and RASSF1A methylations were found in 33 (23.7%), 41 (29.5%), 46 (33.1%), 28 (20.1%), and 41 (29.5%) cases of a total of 139 lung adenocarcinomas, respectively. The RASSF1A methylation was found to be linked to the smoking habit. Methylations in MGMT and RASSF1A were also found to correlate with metastasis status. Furthermore, the distribution of EGFR mutation and that of BRCA1, MGMT or RASSF1A methylation were significantly exclusive in lung adenocarcinomas. The main finding of our study demonstrate that epigenetic abnormalities might play a critical role for the lung tumorigenesis in patients with smoking history and metastasis, and partly affect the predictive value of EGFR mutations through blocking expression due to promoter EGFR hypermethylation. Mutually exclusive distribution of genetic and epigenetic alterations reflects differently biological characteristics in the etiology of lung adenocarcinomas.     

Pump Speed Optimization in Patients Implanted With the HeartMate 3 Device

Background

Pump speed optimization in patients implanted with a ventricular assist device represents a major challenge during the follow-up period. We present our findings on whether combined invasive hemodynamic ramp tests and cardiopulmonary exercise testing (CPX) can help optimize patient management.

Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

Coronary Artery Disease Manifestations in HIV: What,How, and Why

Understanding why persons with human immunodeficiency virus (HIV) have accelerated atherosclerosis and its sequelae, including coronary artery disease (CAD) and myocardial infarction, is necessary to provide appropriate care to a large and aging population with HIV. In this review, we delineate the diverse pathophysiologies underlying HIV-associated CAD and discuss how these are implicated in the clinical manifestations of CAD among persons with HIV. Several factors contribute to HIV-associated CAD, with chronic inflammation and immune activation likely representing the primary drivers. Increased monocyte activation, inflammation, and hyperlipidemia present in chronic HIV infection also mirror the pathophysiology of plaque rupture. Furthermore, mechanisms central to plaque erosion, such as activation of toll-like receptor 2 and formation of neutrophil extracellular traps, are also abundant in HIV. In addition to inflammation and immune activation in general, persons with HIV have a higher prevalence than uninfected persons of traditional cardiovascular risk factors, including dyslipidemia, hypertension, insulin resistance, and tobacco use. Antiretroviral therapies, although clearly necessary for HIV treatment and survival, have had varied effects on CAD, but newer generation regimens have reduced cardiovascular toxicities. From a clinical standpoint, this mix of risk factors is implicated in earlier CAD among persons with HIV than uninfected persons; whether the distribution and underlying plaque content of CAD for persons with HIV differs considerably from uninfected persons has not been definitively studied. Furthermore, the role of cardiovascular risk estimators in HIV remains unclear, as does the role of traditional and emerging therapies; no trials of CAD therapies powered to detect clinical events have been completed among persons with HIV.     

中医院校预防医学课程思政的教学改革和实践

“课程思政”是当前高等教学中加强大学生思想政治教育的主要途径之一。本文通过探索中医院校“预防医学”课程思政的建设,从教学内容、教学方法、教学团队建设、考核方式四个方面论述了专业知识传授和思政教育育人的有机融合,在教学中实施“知识传授”与“价值引领”同向同行,培养德术兼备的“卓越医生”。     

Trade-offs between acquired and innate immune defenses in humans

Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.     

Rural–urban disparities in knowledge,behaviors, and mental health during COVID-19 pandemic: A community-based cross-sectional survey

To examine the knowledge level, behaviors, and psychological status of the Chinese population during the COVID-19 pandemic, and to explore the differences between urban and rural areas.We carried out a cross-sectional survey of the knowledge, behaviors related to COVID-19, and mental health in a probability sample of 3001 community residents in 30 provinces or districts across China from February 16–23, 2020. Convenience sampling and a snowball sampling were adopted. We used General Anxiety Disorder (GAD), the 9-item Patient Health Questionnaire (PHQ-9), and knowledge and behaviors questionnaire of community residents regarding COVID-19 designed by us to investigate the psychological status, disease-related knowledge, and the behavior of Chinese urban and rural residents during the pandemic.The average score of anxiety and depression among urban residents was 9.15 and 11.25, respectively, while the figures in rural areas were 8.69 and 10.57, respectively. There was a statistically significant difference in the levels of anxiety (P < .01) and depression (P < .01). Urban participants reported significantly higher levels of knowledge regarding COVID-19 in all aspects (transmission, prevention measures, symptoms of infection, treatment, and prognosis) (P < .01), compared to their rural counterparts. While a majority of respondents in urban areas obtained knowledge through WeChat, other apps, and the Internet (P < .01), residents in rural areas accessed information through interactions with the community (P < .01). Urban residents fared well in exchanging knowledge about COVID-19 and advising others to take preventive measures (P < .01), but fared poorly in advising people to visit a hospital if they displayed symptoms of the disease, compared to rural residents (P < .01). Regression analysis with behavior showed that being female (OR = 2.106, 95%CI = 1.259–3.522), aged 18 ≤ age < 65 (OR = 4.059, 95%CI = 2.166–7.607), being satisfied with the precautions taken by the community (OR = 2.594, 95%CI = 1.485–4.530), disinfecting public facilities in the community (OR = 2.342, 95%CI = 1.206–4.547), having knowledge of transmission modes (OR = 3.987, 95%CI: 2.039, 7.798), symptoms (OR = 2.045, 95%CI = 1.054–4.003), and outcomes (OR = 2.740, 95%CI = 1.513–4.962) of COVID-19, and not having anxiety symptoms (OR = 2.578, 95%CI = 1.127–5.901) were positively associated with affirmative behavior in urban areas. Being married (OR = 4.960, 95%CI = 2.608–9.434), being satisfied with the precautions taken by the community (OR = 2.484, 95%CI = 1.315–4.691), screening to ensure face mask wearing before entering the community (OR = 8.809, 95%CI = 2.649–19.294), and having knowledge about precautions (OR = 4.886, 95%CI = 2.604–9.167) and outcomes (OR = 2.657, 95%CI = 1.309–5.391) were positively associated with acceptable conduct in rural areas.The status of anxiety and depression among urban residents was more severe compared to those living in rural areas. There was a difference in being positively associated with constructive behaviors between rural and urban areas.