二叶式主动脉瓣主动脉病变相关基因突变患者的影像学特征与遗传学相关性研究

摘要 目的：研究主动脉病变相关基因在二叶式主动脉瓣（Bicuspid aortic valve，BAV）相关性主动脉病变中的作用。 方法：纳入2014年4月至2016年6月于北京安贞医院行Bentall手术并检测到主动脉病变相关基因的突变的BAV患者8例。并排除具有主动脉病变家族史的BAV患者。收集患者外周血并针对已报道的主动脉疾病相关基因进行筛查。将基因突变的结果在多个数据库中进行检索，排除其为单核苷酸多肽性（SNPs）。通过多个突变评价软件对变异进行致病性预测。记录患者的一般临床参数及实验室检查结果，利用超声心动图评估其BAV分型、瓣膜功能及升主动脉内径等指标。 结果：8例检测到主动脉病变相关基因的突变的BAV患者男性7例，女性1例，平均年龄50.25岁（28-71岁）。8例患者均。其中4例患者FBN1基因突变（c.2926C>Tp.Arg976Cys，c.2374T>Cp.Cys792Arg，c.2639G>Ap.Gly880Asp，c.6700G>Ap.Val2234Met），2例COL3A1基因突变（c.2190A>Tp.GLU730Asp，c.2181G>Ap.Met727Ile），1例MYLK基因突变（c.1414C>Tp.Leu472Phe），1例TGFBR1基因突变（c.134A >Gp.Asn45Ser）。8例患者中1例FBN1基因突变患者为Sievers 0型，余7例均为Sievers I型BAV，其中RL型6例，RN型1例。8例患者中5例患者主动脉最宽处位于升主动脉管部，3例位于主动脉窦部。2例以主动脉瓣狭窄表现为主，5例以主动脉瓣关闭不全表现为主，1例主动脉瓣狭窄与关闭不全程度相当。3例FBN1基因突变（c.2926C>Tp.Arg976Cys，c.2374T>Cp.Cys792Arg，c.2639G>Ap.Gly880Asp）经3个突变评价软件预测均为可能致病性突变，该3例患者胸主动脉最宽处内径显著高于其它基因突变患者。 结论：主动脉病变相关基因可能参与BAV相关性主动脉病变的发生发展。基因变异相关的解剖结构异常所引起的血流动力学改变可能最终导致了BAV患者不同类型的主动脉病变。     

Risk factors for asthma in schoolchildren in Southern Brazil

BackgroundDue to the high prevalence of recurrent wheezing in the pediatric population, it is important to be able to identify environmental risk factors that may affect the etiology of asthma in several regions.Objective: to identify possible risk factors associated with asthma in children (9–12 years old) in Passo Fundo, Rio Grande do Sul, Brazil.Material and MethodsA total of 1003 school-age children were selected for the cross-sectional study by applying a standardized written questionnaire from the International Study of Asthma and Allergy, and a supplementary questionnaire (ISAAC phase II) was added to address personal, family and environmental factors. Of these, 125 children were excluded because they did not accept to do the skin prick test, resulting in a sample of 878.ResultsIndependent risk factors associated with asthma were bronchiolitis before two years old [OR] = 3.11; 2.23–4.33, current rhinitis [0R] = 2.07; 1.43–3.0; sharing bedroom during the first year of life [OR] = 2.03; 1.36–3.04; atopy [OR] = 1,82; 1.26–2.50; use of paracetamol more than 12 times a year [OR] = 1.68; 1.20–2.31; use of antibiotics in the first six months of life [OR] = 1,57 1;13–2.17; maternal asthma [OR] = 1.75; 1.05–2.78, having an indoor cat during the first year of life [OR] = 1.73, 1.07–2.78; premature birth [OR] = 1.60,1.02–2.50.Conclusionour results show that genetic backgrounds, environmental factors, premature birth, use of antibiotics before six months of life, using paracetamol once per month and the presence of co-morbidities such as rhinitis are the risk factors associated with asthma in Brazilian children.     

Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation

The circadian nature of melatonin has a protective effect on the progression of female reproductive cancers, including breast and ovarian cancers. However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub-G1 phase and increased DNA condensation in ELT3 cells. Melatonin-induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up-regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down-regulated the Akt-ERK1/2-NFκB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.