核苷酸还原酶抑制剂抗癌活性与电子结构的关系

用ＣＮＤＯ／２量化方法计算了３２个异羟肟酸化合物、６个酰胺化合物和９个羧甲酯类化合物的电子结构，对其中的４４个化合物的量化指数与其抑制核苷酸还原酶的活性参数ＰＣ进行逐步回归计算，得到关于异羟肟酸化合物、酰胺类化合物和羧甲酯类化合物的二个ＱＳＡＲ，由ＱＳＡＲ表明化合物抑制核苷酸还原酶的机制是络合机制。同时，用模式识别方法研究了其中３５个化合物的结构对治疗患Ｌ１２１０肿瘤小鼠药效的影响，得到满意的分类图，结果表明化合物的抗癌活性是通过抑制核苷酸还原酶所致，但化合物在体内到达受体的过程和难易程度对药效的影响较大。

Impacts of statin and metformin on neuropathy in patients with type 2 diabetes mellitus: Korean Health Insurance data

BACKGROUND Neuropathy is a common chronic complication in type 2 diabetes mellitus(T2DM).Statin and metformin are commonly used medications in T2DM patients,and some studies showed statin-or metformin-induced neuropathy.AIM To evaluate the incidence of neuropathy among patients with T2DM associated with statin and metformin therapies.METHODS Korean Health Insurance Review and Assessment national patient sample data from 2016 and 2017 were used.Patients with T2DM and no complications were divided into statin/metformin/statin+metformin users and non-users.Neuropathy incidence was defined by International Statistical Classification of Diseases and Related Health Problems,10th revision codes and concomitant prescriptions for anticonvulsants or antidepressants.Logistic regression analyses were conducted to examine the associations between statin/metformin/statin+metformin therapies and the incidence of neuropathy.Propensity score(PS)matching was performed on the basis of age,sex and comorbidities.RESULTS Overall,34964 and 35887 patients with T2DM and no complications were included in the Korean Health Insurance Review and Assessment national patient sample datasets from 2016 and 2017,respectively.Statin therapy was associated with increased risks of neuropathy in 2016 and 2017[PS-matched odds ratio(OR)=1.22,95%confidence interval(CI):1.08-1.38;PS-matched OR=1.17,95%CI:1.03-1.33,respectively].Metformin therapy was associated with reduced risks of neuropathy in 2016 and 2017(PS-matched OR=0.30,95%CI:0.21-0.42;PSmatched OR=0.44,95%CI:0.32-0.60,respectively).Combined statin+metformin therapy was not significantly associated with neuropathy in 2016 or 2017(PSmatched OR=0.85,95%CI:0.61-1.19;PS-matched OR=0.95,95%CI:0.66-1.38,respectively).CONCLUSION Statin therapy was associated with enhanced risk of new-onset neuropathy in patients with T2DM,but metformin therapy showed the opposite association.

Effectiveness of statins vs.exercise on reducing postprandial hypertriglyceridemia in dyslipidemic population:A systematic review and network meta-analysis

Background:Individuals at risk of suffering cardiovascular disease(CVD) present with larger increases in blood trigyceride(TG) concentration after a high-fat meal than do healthy individuals.These postprandial hypertriglyceride levels are an independent risk factor for CVD.Prescription of statins and a bout of prolonged exercise are both effective in lowering postprandial hypertriglyceride levels.We aimed to evaluate the comparative effectiveness of statins vs.a bout of aerobic exercise in reducing fasting and postprandial TG(PPTG) concentrations in indiv、duals at high nsk of developing CVD.Methods:Thirty-seven sltudies from a systematic literature search of the PubMed,EMBASE,and Cochrane databases were included in this review.The selected studies conducted trials involving statin therapy(n=20) or a bout of aerobic exercise(n=19) and measured their impact on PPTG levels as the outcome.Two studies analyzed both treatments and were included in duplicate.The meta-analysis was constructed using a random-effects model to calculate the mean difference(MD).The Student t test was used to compare the data sets for statins vs.exercise.Results:Overall,statin and exercise interventions showed similar reductions in PPTG levels,with an MD of-0.65 mmol/L for statins(95% confidence interval(95%CI):-0.54 to-0.77;p <0.001) and-0.46 mmol/L for exercise(95%CI:-0.21 to-0.71;p <0.01).However,statins lowered fasting TG levels more than exercise(MD=-1.54 mmol/L,95%CI:-2.25 to-0.83;p=0.009).Conclusion:Although aerobic exercise is effective in lowering blood TG levels,statins seem to be more efficient,especially in the fasted state.A combination of exercise and statins might reveal a valuable approach to the treatment and prevention of CVD.More studies are required to determine the underlying mechanisms and the possible additive effects of these interventions.

脂必泰胶囊临床应用进展

血脂异常是动脉粥样硬化发生和发展的病理基础,是高血压、冠心病和脑血管疾病的主要独立危险因素。调脂治疗对于降低心脑血管疾病的发生具有非常重要的临床意义。脂必泰胶囊是具有他汀类药物作用的中药调脂药物。该研究通过搜索中国知网数据库查看关于脂必泰的动物实验、临床试验和综述,分析总结脂必泰胶囊的应用价值和作用优势。

Atorvastatin induces autophagy of mesenchymal stem cells underhypoxia and serum deprivation conditions by activating the mitogen-activated protein kinase/extracellular signal-regulatedkinase pathway

Background The survival ratio of implanted mesenchymal stem cells （MSCs） in the infarcted myocardium is low.Autophagy is a complex self-eating process and can be utilized for cell survival. We have found that atorvastatin （ATV）can effectively activate autophagy to enhance MSCs survival during hypoxia and serum deprivation （H/SD）. The mitogen-activated protein kinase/extracellular signal-regulated kinase （MEK/ERK） pathway is a non-canonical autophagy pathway.We hypothesized that the MEK/ERK pathway mediated ATV-induced autophagy of MSCs under H/SD.

Underuse of statins in patients with atherosclerotic ischemic stroke in China

Background Well designed randomized trials and meta-analyses have clearly shown that statins reduce the risk of major vascular events, including ischemic stroke, in a wide range of patients and their routine use is recommended for patients at an increased cardiovascular risk. Survivors of a first ischemic stroke are at a risk of recurrence and of other vascular events and statins are generally recommended to reduce this risk. This study investigated how widely statins were being used for such patients in China. Methods Totally 6422 patients with a history of ischemic stroke were identified by reviewing medical records at 51 highest-ranking hospitals in 14 cities in China, and invited to attend a screening clinic to assess eligibility for a randomized trial. Their current statin and other drug uses were recorded alongside clinical and demographic characteristics. Univariate chi-square test and multivariate Logistic regression were used to determine the factors associated with treatment. Results Only 24% of these patients reported currently taking a statin. The most important predictor of statin use among these patients was prior history of coronary heart disease. History of diabetes or hypertension, as well as treated in university affiliated hospitals is related to increased use. The status had improved significantly during a 2-year period. Atorvastatin （40%） and simvastatin （39%） were the most commonly used. Conclusions In China, statins are still underused for secondary prevention among survivors of ischemic stroke. Reasons for this Door use need to be understood in order to increase use of these evidence based therapies.

阿托伐他汀通过下调核因子-κB减轻载脂蛋白E基因缺陷小鼠颈总动脉粥样硬化

目的探讨阿托伐他汀抗颈总动脉粥样硬化形成作用及其可能机制。方法36只雄性载脂蛋白E（apolipoprotein E，ApoE）基因敲除（ApoE^-/-）小鼠随机分为对照组、模型组和阿托伐他汀组。对照组饲以普通饲料做假手术，模型组和阿托伐他汀组均给予高脂饮食并做右侧颈总动脉套管术，术后第5周开始分别予生理盐水和阿托伐他汀（10mg／kg，1次／d）灌胃。术后第8周末经股动脉取血进行生化检测，并取右侧颈总动脉进行组织病理学检查。实时荧光定量聚合酶链反应（polymerase chain reaction，PCR）检测斑块内NF—κB mRNA表达，蛋白质印迹法检测磷酸化NF-κBp65蛋白表达。结果模型组和阿托伐他汀组血脂水平均显著高于对照组（P均〈0．05），阿托伐他汀组血脂水平低于模型组，但差异无统计学意义。组织病理学观察显示，模型组可见明显斑块形成，斑块内可见坏死核心区和新生微血管；阿托伐他汀组血管内膜明显增厚，但管壁可见较完整的内皮细胞。模型组和阿托伐他汀组斑块负荷均显著高于对照组（P均〈0．001），而阿托伐他汀组斑块负荷显著小于模型组（P〈0．001）。实时荧光定量PCR检测显示，模型组和阿托伐他汀组NF—κB mRNA表达水平均显著高于对照组（P均〈0．001），阿托伐他汀组NF—κB mRNA表达水平显著低于模型组（P=0．022）。蛋白质印迹分析显示，模型组磷酸化NF—κBp65表达水平显著高于对照组（P〈0．001），阿托伐他汀组磷酸化NF-κBp65表达水平显著低于模型组（P〈0．001）。结论阿托伐他汀可通过下调核因子-κB减轻颈总动脉粥样硬化。