简介:摘要目的探讨CYP2C9、CYP2C19基因多态性对心脏瓣膜置换术后患者华法林代谢及个体化用药的影响。方法随机选取2012年1月~2015年1月期间我院收治的风湿性心脏病心脏瓣膜置换术后患者120例,均用PCR-荧光探针法对患者CYP2C9*3(A1075C)基因多态性进行检测,从而辅助临床指导患者个体化华法林的使用;检测CYP2C19*2(G681A)和CYP2C19*3(G636A)基因多态性,通过对患者基因分型检测,判定患者的华法林代谢速率类型,从而合理调整药物剂量,提高药物的有效性。结果CYP2C9、CYP2C19基因多态性对华法林血药浓度具有影响;PM、M与EM标准血药浓度比较,差异明显(P<0.05),具有统计学意义。结论CYP2C9、CYP2C19基因多态性对个体华法林代谢存在一定影响,为提高患者个体用药效果提供参考与借鉴。
简介:摘要目的探讨老年急性冠状动脉综合征(ACS)患者CYP2C19基因中代谢型最佳的抗血小板治疗方案。方法入选2018年1月至2019年3月期间就诊于天津医科大学总医院心内科的ACS老年患者,进行CYP2C19基因检测,对于中代谢型,随机分为2组,替格瑞洛组和氯吡格雷加倍组。随访1年,调查2组患者出血风险和心血管事件发生率。结果本研究入选468例老年患者,CYP2C19基因中代谢214例,占45.7%,分为替格瑞洛组和氯吡格雷加倍组,每组各107例。替格瑞洛组与氯吡格雷加倍组比较小出血发生率为11.2%和22.4%;大出血发生率为2.8%和9.4%;再发心绞痛发生率为4.7%和13.1%;再发急性心肌梗死发生率为3.7%和11.2%,两组比较差异有统计学意义(P<0.05)。氯吡格雷加倍组不仅心血管事件风险更高,而且有更多的出血风险。结论对于CYP2C19基因中间代谢型的老年ACS患者,建议使用标准剂量的替格瑞洛。
简介:摘要目的分析1例表现为全面发育落后患儿的遗传学病因。方法对患儿进行临床和实验室检查,应用二代目标区域捕获测序技术对患儿进行神经系统疾病相关基因的检测,对可疑变异位点进行保守性及致病性预测,并进行患儿及其父母的Sanger测序验证。结果患儿临床表现为发育迟缓,独坐不稳,不能区分生熟人。基因检测示患儿SLC19A3基因存在c.448G>A和c.169C>T,二者均为未见报道的变异,两个变异位置编码的氨基酸为蛋白的保守位点,生物学软件预测具有致病性。结论SLC19A3基因的c.448G>A和c.169C>T复合杂合变异丰富了SLC19A3基因的变异数据库,该基因复合杂合变异引起生物素-硫铵素反应性基底节病,可能导致患儿发病。
简介:摘要目的通过沉默人永生化角质形成细胞HaCaT细胞中nicastrin(NCSTN)基因的表达,研究其下游细胞增殖及分化相关信号通路的改变。方法将HaCaT细胞分为干扰组、阴性对照组和空白对照组:干扰组转染特异性NCSTN-siRNA,阴性对照组转染阴性对照siRNA,空白对照组转染等量转染试剂。实时PCR及Western印迹检测各组NCSTN mRNA和蛋白表达验证转染效率。运用Agilent人类全基因组表达谱芯片技术研究干扰组HaCaT细胞基因表达谱与阴性对照组之间的差异,以表达上调或者下调倍数≥ 2.0且P ≤ 0.05为标准,将差异基因用GO分析进行富集,筛选出表达差异显著且与角质形成细胞增生分化相关的基因,用实时PCR验证结果。结果干扰组HaCaT细胞NCSTN mRNA及蛋白相对表达量分别为0.287 ± 0.090、0.443 ± 0.085,明显低于阴性对照组(0.969 ± 0.127、1.047 ± 0.114)以及空白对照组(1.000 ± 0.151、1.000 ± 0.111),差异均有统计学意义(F值分别为30.787、31.139,P值均为0.001)。表达谱芯片显示,与阴性对照组相比,干扰组表达下调基因605条,上调基因444条。GO分析显示,干扰后差异表达基因富集到上皮发育、上皮细胞分化、角质形成细胞分化、角化4种生物学过程。对表达差异显著且与角质形成细胞增生分化相关的Sprouty相关蛋白2基因、表皮生长因子7基因、胰岛素样生长因子结合蛋白5基因、人Rho关联含卷曲螺旋蛋白激酶2基因和骨形成发生蛋白6基因通过实时PCR验证,验证结果与芯片结果显示的差异趋势一致。结论NCSTN基因功能缺失有可能通过调节其下游细胞增殖及分化相关信号通路的表达,影响角质形成细胞的正常增殖和分化。
简介:基因平等权是指自然人所享有的在基因上被平等对待的人格权利。它的社会根源在于基因歧视,即仅仅基于所谓“缺陷基因”而对携带者作出的不合理的差别对待。基因歧视是对基因平等权的侵害,但基因信息的特殊性使得禁止传统歧视的法律策略不能直接适用。根据“第二次选择”中的基因正义原则,建构基因平等权法律规范是我国应对基因歧视的基本私法政策。基因平等权的边界是基因上差别对待的合理性,要在各种冲突着的利益之间寻求一般禁止与例外的平衡。与欧美相比,我国对基因医学技术的应对机制非常欠缺。虽然在我国目前的法律体系中没有明确、直接的条款能对基因平等权损害提供救济,但基于私法特别是人格权的涵摄力,通过法解释,侵权责任法能够将基因歧视侵权损害纳入救济范围。
简介:AbstractThe novel coronavirus disease 2019 (COVID-19) is the third coronavirus outbreak in the last two decades. Emerging and re-emerging infections like COVID-19 pose serious challenges of the paucity of information and lack of specific cure or vaccines. This leaves utilisation of existing scientific data on related viral infections and repurposing relevant aetiologic and supportive therapies as the best control approach while novel strategies are developed and trialled. Many promising antiviral agents including lopinavir, ritonavir, remdesivir, umifenovir, darunavir, and oseltamivir have been repurposed and are currently trialled for the care for COVID-19 patients. Adjunct therapies for the management of symptoms and to provide support especially in severe and critically ill patients have also been identified. This review provides an appraisal of the current evidence for the rational use of frontline therapeutics in the management of COVID-19. It also includes updates regarding COVID-19 immunotherapy and vaccine development.
简介:AbstractA large-scale vaccination of coronavirus disease-19 (COVID-19) in adults has been conducted for nearly a year, and there is a growing recognition that immunization for children is also essential. It has been months since emergency use of pediatric COVID-19 vaccine was approved, we reviewed the prevalence and transmission of COVID-19 in children. The prevalence of COVID-19 in children is reduced due to vaccination even in a Delta prevalent period, so an increase in the vaccination rate is needed in children. Although the precise role of children in the transmission requires more research to uncover, they likely played a significant role, according to the available literature. We also described four candidate COVID-19 vaccines for children on their safety and immunogenicity and the impact of severe acute respiratory syndrome coronavirus 2 variants on childhood vaccination. Safety issues on pediatric vaccines post-approval, like adverse events following immunization and adverse events of special interest require studies on long-term and effective regulatory mechanisms.