氯吡格雷抵抗基因多态性的研究进展

氯吡格雷是临床上广泛使用的抗血小板药物,其对血小板的抑制具有个体差异性,部分患者在服用常规剂量氯吡格雷后存在抵抗现象而仍有缺血事件的发生,因此明确抵抗的机制将使患者受益。氯吡格雷抵抗可能受多方面因素的影响,目前认为基因多态性是一个重要原因。该文主要从氯吡格雷的吸收、活化和作用受体三方面的基因多态性进行综述。     

Lipotropes from plant-based foods supplied by a standard French diet vs. food guide pyramid recommendations: Grain products are the best sources at lower cost

Lipotropes are compounds that prevent excess hepatic fat deposits. However, although millions of people worldwide suffer from hepatic steatosis, lipotrope consumption has never been investigated. Our objectives were to calculate the amount of lipotropes supplied by a standard French diet vs. food guide pyramid recommendations by using 106 ready-to-eat plant-based foods (PBF) as a basis for comparison, to question whether one can easily increase lipotrope consumption via lipotrope-rich PBFs, and to estimate the lipotrope quantity supplied by €1.00 (one euro) of PBF vs. animal-based foods. Lipotrope potential of PBFs was expressed as the lipotropic capacity (LC) based on the lipotrope densities of 7, 8 or 9 lipotropes (mg/100 kcal), which are identified as betaine, choline, myo-inositol, methionine, magnesium, niacin, pantothenic acid, folates and total polyphenol content. Unrefined/minimally processed PBFs had the highest LC, while energy-dense/refined PBFs had the lowest. A standard French diet fails to provide the lipotrope quantity that should be supplied if food guide pyramid recommendations are followed. Such a difference can be easily compensated by increasing lipotrope-rich PBF consumption. On a €1.00-basis, vegetables and fruits are expensive sources of lipotropes, but grain products, especially legumes, appear to be the best compromise between high LC and low cost.     

阻断CD40／CD40L通道诱导同种胰岛移植免疫耐受的研究

目的：观察阻断CD40／CD40L共刺激通路对同种胰岛移植免疫反应的影响,探讨CD40L单克隆抗体对诱导同种移植免疫耐受的作用。方法：清洁级Wistar大鼠,STZ 60mg／kg诱导1型糖尿病模型,随机分为三组,A组：糖尿病大鼠,B组：糖尿病大鼠＋胰岛细胞＋抗CD40L抗体,C组：糖尿病大鼠＋胰岛细胞。B组在移植前24h注入抗CD40L抗体每只20μg。同种胰岛细胞来自SD大鼠,胶原酶V消化法和Ficoll400密度梯度离心法分离纯化胰岛细胞,收获量为（3．49±0．23）×10^5 IEQ／kg,将同种胰岛细胞按12000IEQ／kg导入受体,移植后每天和每周相同时间点检测血糖和体重变化,3d、7d、15d、22d后检测白介素-2的表达。结果：同种异体胰岛移植可使1型糖尿病大鼠的血糖降至正常并维持一段时间,A组为（23．84±2．74）mmol／L,B组（8．15±1．40）mmol／L,维持（18．12±4．12）d,C组（7．42±2．55）mmol／L,维持（8．00±1．30）d,后两组正常血糖维持天数比较,P〈0．001,有统计学意义。体重变化比较：非移植的A组随着时间的延长,体重不断下降,B、C组至移植后体重有所回升,但移植4周后C组的体重再次下降。移植7d、15d后,IL-2的表达B组和C组比较有显著性差异,B组为（0．1280±0．0104）和（0．1235±0．0073）,C组为（0．1744±0．0096）和（0．1667±0．0098）（P〈0．001）,移植22d后两组比较差异无显著性。结论：CD40L单克隆抗体阻断CD40／CD40L共刺激通路显著延长移植的同种胰岛细胞的存活时间,诱导机体产生针对胰岛移植物的免疫耐受状态。     

氧化应激介导糖原合成酶激酶-3促进D-氨基半乳糖联合脂多糖诱导的急性肝衰竭肝损伤

目的探讨糖原合成酶激酶3(GSK3)在氧化应激促进D-氨基半乳糖联合脂多糖诱导小鼠急性肝衰竭肝损伤中的作用。方法以C57BL/6小鼠为研究对象,腹腔注射D-氨基半乳糖(D-Gal N)联合脂多糖(LPS)建立小鼠急性肝衰竭模型。氧化应激抑制剂N-乙酰半胱氨酸(NAC)或GSK3特异性抑制剂SB216763分别对急性肝衰竭小鼠模型进行干预。检测小鼠血清转氨酶ALT、AST评价肝脏功能,检测肝脏组织中谷胱甘肽(GSH)、超氧化物歧化酶活性(SOD)及丙二醛(MDA)水平评价氧化应激程度,免疫印迹方法检测肝脏组织p-GSK3、p-JNK蛋白表达。结果 D-Gal N/LPS诱导急性肝衰竭引起肝组织GSH和SOD水平降低,肝组织MDA水平上升。NAC干预改善急性肝衰竭损伤(血清ALT、AST水平明显下降),同时增加肝脏组织GSK3β的磷酸化水平(降低GSK3β的活性)。SB216763抑制GSK3β活性增加急性肝衰竭小鼠肝组织GSH和SOD含量,降低肝组织中MDA含量。GSK3β抑制下调肝脏中p-JNK的表达。结论 GSK3β是氧化应激促进急性肝衰竭损伤中的一种重要信号分子,抑制GSK3β活性,减轻氧化应激可以改善急性肝衰竭损伤。     

十二指肠乳头括约肌切开后球囊扩张术和乳头括约肌切开术治疗巨大胆总管结石效果比较的Meta分析

目的评价两种手术方式十二指肠乳头括约肌切开术(EST)和十二指肠乳头括约肌切开后球囊扩张术(ESBD)处理巨大胆总管结石的疗效差异。方法计算机检索至2019年7月8日的Pubmed、Cochrane Central、Embase等外文数据库及中国知网、万方等中文数据库中的文献,同时检索相关会议论文等,纳入ESBD vs EST治疗巨大胆总管结石的随机对照试验(RCT),提取相关数据,采用RevMan5.3软件进行分析。结果共纳入13项RCT,共计1926例患者,其中ESBD组973例,EST组953例。Meta分析结果显示:ESBD组和EST组结石清除率[比值比(OR)=1.53,95%可信区间(95%CI):1.03~2.29,P=0.04]、一次清除率(OR=1.77,95%CI:1.06~2.93,P=0.03)、机械碎石率(OR=0.40,95%CI:0.25~0.63,P<0.0001)、出血率(OR=0.23,95%CI:0.11~0.50,P<0.001)、胆管炎发生率(OR=0.31,95%CI:0.12~0.78,P=0.01)、早期并发症(OR=0.59,95%CI:0.42~0.84,P=0.003)、手术时间(MD=-8.89,95%CI:-17.56^-0.22,P=0.04)比较,差异均有统计学意义;但在穿孔(OR=0.27,95%CI:0.05~1.30,P=0.10)、内镜后胰腺炎(OR=1.03,95%CI:0.66~1.61,P=0.91)方面二者结果相似。结论在内镜下处理巨大胆总管结石中,ESBD在结石清除率、机械碎石率、出血率、胆管炎发生率、手术时间方面比EST更有优势。     

无义突变的人凝血因子IX小基因稳定细胞株选择性剪接的研究

目的:探讨无义突变的人凝血因子IX小基因稳定细胞株发生选择性剪接的分子机制。方法:将人凝血因子IX小基因(Mini-hF9)及其无义突变体分别转染哺乳动物细胞HeLa,经G418抗性筛选、单克隆化得到稳定细胞株;通过RT-PCR及Western blot分别检测稳定细胞株中Mini-hF9基因mRNA的选择性剪接及蛋白表达情况。结果:成功构建了野生型和无义突变的人凝血因子IX小基因稳定细胞株HeLa-F9-WT、HeLa-F9-M1和HeLa-F9-M2。野生型稳定细胞株HeLa-F9-WT中扩增到正常剪接产物Norm;无义突变稳定细胞株HeLa-F9-M1中扩增到Norm和Alt-S1这两种剪接产物,HeLa-F9-M2中扩增到Norm、Alt-S1和Alt-S2这三种剪接产物。结论:无义突变的凝血因子IX基因可能触发无义相关的选择性剪接(NAS)途径,导致选择性剪接的产生。     

汉防己甲素联合伊马替尼对K562／G01细胞诱导凋亡作用及其相关机制

本研究探讨伊马替尼（imatinib,IM）和汉防己甲素（tetrandrine,Tet）单用和联合应用对K562／G01细胞的凋亡诱导作用及其可能机制。应用M1fr法检测IM和Tet单用及联合用药对细胞增殖抑制的作用,用流式细胞术（FCM）检测细胞周期和凋亡率,用实时荧光定量PCR检测caspase-3、BCL-2mRNA的表达,应用Westernblot分析caspase-3、BCL-2蛋白的表达情况。结果表明,1．0μmol／LIM和／或1．5μmol／L Tet单用及联合作用于K562／G01细胞48h后,对细胞增殖的抑制率分别是（22．74±0．05）％、（20．34±0．57）％、（44．28±0．60）％,两药联合应用较单药抑制作用明显。流式细胞术检测显示,Tet作用后细胞向G,／s期转化;Tet1．5μmol／L、3μmol／L与1．0μmol／LIM联合应用48h的早期凋亡率分别为（7．81±0．16）％、（14．10±0．28）％,诱导凋亡作用比单药组明显增加。FQ—PCR和Westernblot检测均显示单独应用Tet和IM后caspase-3表达上调,BCL-2表达下调,联合用药组作用更显著。结论：单独应用Tet对K562／G01细胞有诱导凋亡的作用,两药联合应用具有明显的协同效应,且具有时间和剂量依赖性,其机制可能与上调caspase-3mRNA及其蛋白表达和下调BCL-2mRNA及其蛋白的表达有关。     

心肌标志物在脓毒症心肌损伤中的临床作用

脓毒症引起的多器官功能衰竭是导致危重病患者的主要死因。心肌损伤在脓毒症中为器官功能障碍的常见表现。本文综述了心肌标志物肌钙蛋白和B型钠尿肽在脓毒症心肌损伤中的产生原理和临床应用,从而为脓毒症心肌损伤的早期诊断、病情监测、疗效观察和预后判断等诸方面提供了依据。     

Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China

ObjectiveSeveral COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.MethodsA retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of the associations between comorbidities (cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.ResultsOverall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30–6.32), type 2 diabetes (T2DM) (3.57, 2.32–5.49), cardiovascular disease (CVD) (3.78, 1.81–7.89), fatty liver disease (7.53, 1.96–28.96), hyperlipidemia (2.15, 1.26–3.67), other lung diseases (6.00, 3.01–11.96), and electrolyte imbalance (10.40, 3.00–26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89–12.75), CVD (8.47, 6.03–11.89), and electrolyte imbalance (19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46–29.64) within two weeks.ConclusionBesides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.