中国汉族人群APOB rs10199768及rs1367117基因多态性与HBeAg阳性慢性乙型肝炎患者PEG-IFN-α疗效的相关性

目的 探讨中国汉族人群载脂蛋白B（APOB）rs10199768和rs1367117基因多态性与HBeAg阳性慢性乙型肝炎（CHB）患者聚乙二醇干扰素α（PEG-IFN-α）疗效的相关性。 方法 纳入124例PEG-IFN-α治疗的HBeAg阳性CHB患者进行单核苷酸多态性（SNP）检测和临床指标分析，观察SNP与PEG-IFN-α疗效、临床指标变化的关系，以未经抗病毒治疗患者体外培养外周血单个核细胞（PBMC）为对象，探讨SNP与IFN-α效应的关系。 结果 APOB rs10199768和rs1367117的基因型在PEG-IFN-α完全应答（CR）组和应答不佳（SR）组之间的分布差别具有统计学意义（P=0.036和P=0.021）；SR组中的rs10199768 CC基因型和C等位基因频率显著高于CR组（P=0.036, OR=3.844和P=0.040, OR=3.600）；SR组中的rs1367117 GG基因型和G等位基因频率显著高于CR组（P=0.021, OR=2.647和P=0.017, OR=2.384）。在PEG-IFN-α治疗12和24周时，rs10199768 AC型患者的HBeAg浓度较CC型低（P=0.017和P=0.018）。IFN-α体外刺激实验显示，rs10199768 AA+AC型感染者的信号传导及转录活化因子1（STAT1）和干扰素刺激基因15（ISG15）的mRNA表达水平较CC型高（P=0.005和P=0.018），但在rs1367117 GG/AG基因型中的表达差别均无统计学意义（P>0.05）。 结论 中国汉族人群APOB rs10199768和rs1367117基因多态性与PEG-IFN-α治疗HBeAg阳性CHB患者的疗效有关。rs10199768 A等位基因与PEG-IFN-α应答有关，rs1367117 G等位基因与PEG-IFN-α应答不佳有关。     

安徽地区冠心病人群冠状动脉病变特征与载脂蛋白E基因多态性的研究

目的研究安徽地区冠心病人群冠状动脉病变特征与载脂蛋白E(ApoE)基因多态性的相关性,评估其在冠心病诊疗及预防中的临床应用价值。方法收集2019年9月至2020年9月在合肥市第二人民医院心内科住院行冠状动脉造影检查的患者共199例,根据研究内容不同采用两种分组方式(分别是冠心病组和对照组,ε2、ε3和ε4组),采用PCR-荧光探针法检测ε2、ε3和ε4等位基因以及rs7412和rs429358的基因型。通过比较等位基因ε2、ε3、ε4携带者的冠状动脉病变特征,分析ApoE基因型/亚型与冠心病的发病及严重程度之间的关系。结果ε2、ε3和ε4在样本中的频率分别为13.6%、69.3%和17.1%,ApoE基因多态性与冠心病的发生有相关性(ε2:r=0.160,P<0.05;ε4:r=0.154,P<0.05);ε2、ε3和ε4组Gensini评分差异有统计学意义(P=0.026,0.013,0.001),犯罪血管狭窄程度和病变血管支数与ApoE基因多态性差异无统计学意义(ε2=0.15,ε3=0.822,ε4=0.276;ε2=0.324,ε3=0.849,ε4=0.233);犯罪血管病变类型中ε4携带者以局限性为主,差异有统计学意义(P=0.027)。结论 ApoE基因多态性与冠心病的发生具有良好的相关性,在安徽地区冠心病人群中,冠状动脉病变严重程度及犯罪血管病变类型与其相关。     

Building the evidence for an ecological model of cognitive health

This is a commentary on Besser and colleagues’ article “Associations between neighbourhood built environment and cognition vary by apolipoprotein E genotype: Multi-Ethnic Study on Atherosclerosis” published in Health & Place. Unlike previous studies, the authors found significant environment-cognition associations in apolipoprotein E (APOE) ε2 carriers and no significant associations in ε4 carriers. This commentary discusses the possible reasons for these findings and, in doing so, proposes an ecological model of cognitive health. The model highlights the importance of accounting for multiple environmental influences including the built and natural environment and air and noise pollution indicators. It also stresses the importance of studying the underlying biological mechanisms explaining differences in environment-cognition associations across APOE genotype categories.     

Naringenin promotes cell autophagy to improve high-fat-diet-induced atherosclerosis in ApoE-/- mice

Naringenin (NAR) is a major flavanone in citrus fruits that has multiple pharmacological attributes such as anticancer and antiatherogenic. This study aims to investigate the mechanism of NAR in high-fat-diet (HFD)-induced atherosclerosis (AS) in apolipoprotein E-knockout (ApoE^-/-) mice. A HFD-induced AS ApoE^-/- mouse model was established. The mice were treated with HFD, different doses of NAR and simvastatin (Simv). After drug treatment, the levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), and alanine aminotransferase (ALT) were determined. The expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected using qRT-PCR and enzyme-linked immunosorbent assay. The plaque area of the aorta of AS mice was determined using oil red O staining. Western blot analysis was applied to measure the levels of autophagy-related proteins [protein 1 light chain 3B (LC3B), beclin 1, and p62]. The TC, TG, LDL-C, TNF-α, ALT, and MDA levels were significantly increased while the HDL-C, SOD, and GSH-Px levels were decreased in the HFD-induced AS ApoE^-/- mice. NAR treatment reversed the expression of the above indicators in mice. After they were treated with different doses of NAR, the LC3B and beclin 1 levels were improved while the p62 protein level was decreased. This study suggested that NAR could promote cell autophagy to improve HFD-induced AS in ApoE^-/- mice.     

Human serum albumin nanoparticles modified with apolipoprotein A-I cross the blood-brain barrier and enter the rodent brain

Nanoparticles made of human serum albumin (HSA) and modified with apolipoproteins have previously been shown to transport drugs, which normally do not enter the brain, across the blood-brain barrier (BBB). However the precise mechanism by which nanoparticles with different apolipoproteins on their surface can target to the brain, as yet, has not been totally elucidated. In the present study, HSA nanoparticles with covalently bound apolipoprotein A-I (Apo A-I) as a targetor for brain capillary endothelial cells were injected intravenously into SV 129 mice and Wistar rats. The rodents were sacrificed after 15 or 30?min, and their brains were examined by transmission electron microscopy. Apo A-I nanoparticles could be found inside the endothelial cells of brain capillaries as well as within parenchymal brain tissue of both, mice and rats, whereas control particles without Apo A-I on their surface did not cross the BBB during our experiments. The maintenance of tight junction integrity and barrier function during treatment with nanoparticles was demonstrated by perfusion with a fixative containing lanthanum nitrate as an electron dense marker for the permeability of tight junctions.     

颅内外动脉粥样硬化狭窄分布与脂蛋白胆固醇及载脂蛋白的关系

目的评估脂蛋白胆固醇及载脂蛋白在颅内外不同部位动脉粥样硬化狭窄者间是否存在差异及相关性。方法 2011年3月到2012年3月在大连市中心医院颈动脉外科和神经内科住院患者180例,经头-颈CTA/DSA检查证实存在颅内外动脉重度狭窄或闭塞的患者为病例组;以眼动脉及基底动脉起始部位为界,分为颅内动脉狭窄组、颅外动脉狭窄组及颅内外混合动脉狭窄组,每组各60例;对照组选择该时间段在本院住院,经CTA/DSA检查无颅内外动脉狭窄的患者60例。各组间在性别、年龄、吸烟、饮酒史,高血压、糖尿病、冠心病史及家族史方面无差异。检测各组人群血浆中LDL-C、HDL-C、apo B及apo A1水平,计算LDL-C/HDL-C、apo B/apo A1值,并进行比较及进行相关性分析。结果病例组apo A1、HDL-C值较对照组降低,LDL-C、apo B及LDL-C/HDL-C、apo B/apo A1值较对照组增高(P0.05);颅外动脉狭窄组与颅内外混合动脉狭窄组apo A1、HDL-C值较颅内动脉狭窄组降低,LDL-C、apo B及LDL-C/HDL-C、apo B/apo A1值较颅内动脉狭窄组增高(P0.05);颅外动脉狭窄组与混合动脉狭窄组apo A1、HDL-C、LDL-C、apo B及LDL-C/HDL-C、apo B/apo A1值间无差别(P0.05)。Apo B与LDL-C、apo A1与HDL-C及apo B/apo A1与LDL-C/HDL-C的相关系数是分别为0.319、0.507及0.445。结论脂蛋白胆固醇与颅外动脉粥样硬化相关,高LDL-C非颅内动脉粥样硬化狭窄的危险因素;载脂蛋白在脑动脉粥样硬化方面与脂蛋白胆固醇的变化趋势是一致的,并具有相关性。