Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

目的：观察稀土化合物硝酸钇[Y（NO₃）₃]亚慢性（90 d）暴露对大鼠学习记忆能力的影响，并探究其可能的机制，为全面评估稀土元素钇的健康风险提供科学依据。方法：选用刚离乳（PND21）SD雌性大鼠，根据质量随机分为4组，分别为对照组（ddH₂O），Y（NO₃）₃低剂量组[10 mg/（kg·d）]、中剂量组[40 mg/（kg·d）]和高剂量组[160 mg/（kg·d）]，每组15只。连续灌胃受试物90 d后进行旷场实验、高架十字迷宫实验、转棒实验、Morris水迷宫实验。水迷宫检测后，每组取5只雌鼠心脏原位灌注，进行脑组织病理学检查。每组剩余10只雌鼠摘取脑组织，紫外分光光度计检测雌鼠大脑皮质和海马中谷氨酸（Glu）的含量；Western blot检测海马组织中N-甲基-D-天冬氨酸（NMDA）受体蛋白表达情况。结果：与对照组相比，硝酸钇90 d暴露后，转棒实验中160 mg/（kg·d）剂量组大鼠在棒时间、在棒圈数、掉落速度明显升高（P<0.05）。在Morris水迷宫定位航向实验第4天时，40、160 mg/（kg·d）剂量组大鼠逃避潜伏期明显降低（P<0.05）；Morris水迷宫空间探索实验中，40 mg/（kg·d）剂量组大鼠穿越平台次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组穿越平台次数、进入目标象限次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组大鼠东北、东南、西南象限的逃避潜伏期明显低于西北象限的逃避潜伏期（P<0.05）。160 mg/（kg·d）剂量组大鼠海马中Glu含量和NMDA受体NR1含量均明显低于对照组（P<0.05）。40和160 mg/（kg·d）剂量组大鼠海马中NMDA受体NR2A含量明显低于对照组（P<0.05）。结论：硝酸钇亚慢性（90 d）暴露可以引起雌性大鼠空间学习记忆能力增强；硝酸钇可能通过降低海马组织神经元细胞外Glu含量，抑制NMDA受体激活，增强雌性大鼠的空间学习记忆能力。     

八段锦干预心力衰竭患者疗效的Meta分析

目的:评估八段锦干预心力衰竭的疗效及安全性。方法:搜索中国知网数据库、中国生物医学文献数据库、万方数据库以及维普中文全文数据库；PubMed、Cochrane Library、web of science、EMBASE。检索时间为建库至2019年2月28日。对纳入的随机对照试验（RCT)用Cochrane手册进行偏倚风险评估，用Rev Man 5.3软件进行Meta分析。结果:纳入6篇文献，7个随机对照研究，共计543例心力衰竭患者。与对照组比较，观察组MLHFQ减少[MD=10.88,95%CI=（8.22，13.54）]，6分钟步行试验(6MWT)提高[MD=107.81,95%CI=（75.83，139.78）]，左心室射血分数(LVEF)提高[MD=3.62,95%CI=（2.04，5.19）]，B型利钠肽(BNP)降低[MD=73.32,95%CI=（45.12，101.53）]，临床疗效[OR=4.00,95%CI=（1.35，11.83）]，中医证候评分[OR=4.57,95%CI=（2.03，10.31）]。结论:八段锦可改善心力衰竭患者的心功能，用于稳定期的康复治疗。     

Computational and experimental studies on the interaction between butyrylcholinesterase and fluoxetine: implications in health and disease

1. Butyrylcholinesterase (BChE) is a serine esterase that plays a role in the detoxification of natural as well as synthetic ester-bond-containing compounds. Alterations in BChE activity are associated with a number of diseases. Cholinergic system abnormalities in particular are correlated with the formation of senile plaques in Alzheimer’s disease (AD), and administration of cholinesterase inhibitors is a common therapeutic approach used to treat AD.

2. Here, our aim was to study the interaction between BChE and fluoxetine.

3. Molecular docking simulations revealed that fluoxetine penetrated deep into the active-site gorge of BChE and that it was engaged in stabilizing noncovalent interactions with multiple subsites. In substrate kinetic studies, the V_m, K_m, k_cat and k_cat/K_m values were found to be 20.59?±?0.36?U mg^?1 protein, 194?±?14?µM, 1.3?×?10⁸?s^?1 and 6.7?×?10⁵?µM^?1s^?1, respectively. Based on inhibitory studies, fluoxetine appeared to inhibit BChE competitively, with an IC₅₀ value of 104?µM and a K_i value of 36.3?±?4.7?µM.

4. Overall, both the low K_i value and the high number of BChE–fluoxetine interactions suggest that fluoxetine is a potent inhibitor of BChE, although in vivo mechanisms for the direct effects of BChE inhibition on various pathologies remain to be further investigated.

     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Normative values of the motor competence assessment (MCA) from 3 to 23 years of age

ObjectivesGrowing evidence of the importance of motor competence for developing a healthy lifestyle has been established in the last decade. Nonetheless, no single instrument or observation tool have been able to fully measure this construct, particularly because most were built for the diagnosis of children in risk for motor impairment; are limited to a few years of the developmental span; lack objectivity in the assessment protocols; or do not include the locomotor, stability, and manipulative components. This led to the difficulty of comparing researches, and longitudinally follow children into adulthood. Recently, a novel proposal to assess motor competence was presented - the Motor Competence Assessment (MCA) - and this study aims to present the MCA normative data from 3-to-23 years.Design and methodsTwo thousand and eighty-seven participants (1102 boys) between 3 and 23 years of age were evaluated in the MCA (standing long jump, 10 m shuttle run, throwing velocity, kicking velocity, lateral jumps, shifting platforms). Results for each test were introduced in the LMS Chartmaker 2.3. The best model for test and sex was used, resulting in normative curves and percentile values.ResultsFinal norms showed a good fit to the instrument developmental expectations, allowing to differentiate and classify performances along the age interval.ConclusionsThe MCA age- and sex- normative values allow to assess motor competence from childhood to early adulthood. Future directions will include obtaining a total MCA score and the normative scores for the MCA components (stability, locomotion, object control), and to expand the norms to adulthood and old age.