Reduced microvascular volume and hemispherically deficient vasoreactivity to hypercapnia in acute ischemia: MRI study using permanent middle cerebral artery occlusion rat model

Vasoreactivity to hypercapnia has been used for assessing cerebrovascular tone and control altered by ischemic stroke. Despite the high prognostic potential, traits of hypercapnia-induced hemodynamic changes have not been fully characterized in relation with baseline vascular states and brain tissue damage. To monitor cerebrovascular responses, T2- and T2*-weighted magnetic resonance imaging (MRI) images were acquired alternatively using spin- and gradient-echo echo plannar imaging (GESE EPI) sequence with 5% CO₂ gas inhalation in normal (n=5) and acute stroke rats (n=10). Dynamic relative changes in cerebrovascular volume (CBV), microvascular volume (MVV), and vascular size index (VSI) were assessed from regions of interest (ROIs) delineated by the percent decrease of apparent diffusion coefficient (ADC). The baseline CBV was not affected by middle cerebral artery occlusion (MCAO) whereas the baseline MVV in ischemic areas was significantly lower than that in the rest of the brain and correlated with ADC. Vasoreactivity to hypercapnic challenge was considerably attenuated in the entire ipsilesional hemisphere including normal ADC regions, in which unsolicited, spreading depression-associated increases of CBV and MVV were observed. The lesion-dependent inhomogeneity in baseline MVV indicates the effective perfusion reserve for accurately delineating the true ischemic damage while the cascade of neuronal depolarization is probably responsible for the hemispherically lateralized changes in overall neurovascular physiology.     

Chemical constituents from the whole herb of Hemiphragma heterophyllum

Phytochemical investigation on Hemiphragma heterophyllum led to the isolation of two new compounds, heterophyllumin A (1) and heterophylliol (3), along with nine known compounds, (?)-sibiricumin A (2), iridolactone (4), jatamanin A (5), dihydrocatalpolgenin (6), 25-hydroperoxycycloart-23-en-3β-ol (7), 24-methylenecycloartanol (8), (+)-pinoresinol (9), hexadec-(4Z)-enoic acid (10), and 9,12, 15-octadecatrienoic acid (11). Their structures were elucidated on the basis of detailed spectroscopic analyses and by comparison with literature data. Further, the structure of compound 3 was unambiguously confirmed by single-crystal X-ray analysis. Some of those compounds showed moderate activity in the α-glucosidase inhibition assay.

     

Cardiovascular events associated with nicorandil administration prior to primary percutaneous coronary intervention in patients with acute ST-segment elevated myocardial infarction: a systematic review and meta-analysis

Introduction: Nicorandil may exert cardioprotective effects in ischemic heart disease. However, its efficacy in combination with early reperfusion is uncertain. The authors performed a meta-analysis of the short- and long-term clinical outcomes of nicorandil administration at the time of primary percutaneous coronary intervention (PCI) in patients with ST-elevated myocardial infarction (STEMI).

Methods: PubMed, MEDLINE, Embase, and the Cochrane Library databases were systematically searched for eligible randomized controlled studies. The primary endpoint was major adverse cardiovascular events (MACE), both in-hospital and post-discharge. The secondary endpoint was the incidence of no-reflow phenomenon.

Results: Ten studies were included (n = 1105). Mean patient age was 63.0 ± 10.0 years; 76.6% of patients were male. Compared with controls who received primary PCI, combined nicorandil/primary PCI significantly reduced in-hospital MACE (pooled odds ratio [OR] 0.16; 95% confidence interval [CI] 0.09–0.27), follow-up MACE (pooled OR 0.53; 95% CI 0.37–0.75), and total MACE (pooled OR 0.27; 95% CI 0.15–0.49). The combined treatment also reduced the incidence of no-reflow phenomenon (pooled OR 0.34; 95% CI 0.23–0.50).

Conclusion: Nicorandil administration at the time of primary PCI is associated with reduced MACE (both short- and long-term) and no-reflow phenomenon in patients with STEMI.     

Association between vitiligo and subsequent risk of dementia: A population‐based cohort study

Increasing evidence suggests a positive association between autoimmune disorders and the subsequent risk of dementia, supporting the idea that neuroinflammation is a major contributor to dementia. However, whether or not adults with vitiligo have an increased risk of dementia remains unclear. We aimed to investigate the association between vitiligo and the subsequent risk of dementia. A total of 1320 patients with vitiligo and 5280 matched controls were identified from the Taiwan National Health Insurance Research Database between 1998 and 2011. Dementia was diagnosed by board‐certificated psychiatrists or neurologists in the follow‐up period. Cox proportional hazards models were used to estimate the adjusted hazard ratios (aHR) after controlling for age, sex, income‐related monthly premium, residence and comorbidities associated with dementia. The incidence rate of dementia (per 100 000 person‐years) was 502.8 among patients with vitiligo and 101.9 among the controls. Patients with vitiligo were more likely to develop any type of dementia (aHR, 5.30; 95% confidence interval [CI], 3.30–8.51), Alzheimer’s disease (aHR, 12.22; 95% CI, 3.71–40.28) and vascular dementia (aHR, 3.99; 95% CI, 1.31–12.15) compared with the controls. In conclusion, middle‐aged and old patients with vitiligo are more likely to develop dementia compared with those without vitiligo. This novel finding reminds physicians to be more careful about signs of dementia when managing patients with vitiligo and provides the basis for further investigations that clarify the underlying mechanisms.     

铜绿假单胞菌注射液对肺癌A549细胞自噬及PI3K/Akt通路的影响

目的探究铜绿假单胞菌注射液(PA-MSHA)对肺癌A549细胞自噬及磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)通路的影响。方法体外培养人肺癌A549细胞,随机分为空白对照组、LY294002组(加入20μmol/L LY294002),PA-MSHA干预组(加入0.5×10^9/mL、1.0×10^9/mL、2.0×10^9/mL PA-MSHA)。干预培养48 h后,MTT法检测各组细胞活性,平板克隆形成实验检测各组细胞增殖能力,透射电子显微镜观察各组细胞自噬情况,Western blot检测各组细胞中自噬相关蛋白p62、LC3Ⅰ、LC3Ⅱ及PI3K/Akt通路相关蛋白PI3K、Akt、p-PI3K、p-Akt表达。结果与空白对照组相比,LY294002组、0.5×10^9/mL、1.0×10^9/mL、2.0×10^9/mL PA-MSHA组细胞增殖抑制率、LC3Ⅱ/LC3Ⅰ蛋白表达显著升高(P<0.05),自噬体个数增加,细胞克隆形成率、p62、p-PI3K/PI3K、p-Akt/Akt蛋白表达显著降低(P<0.05);与LY294002组相比,0.5×10^9/mL、1.0×10^9/mL PA-MSHA组细胞增殖抑制率、LC3Ⅱ/LC3Ⅰ蛋白表达显著降低(P<0.05),自噬体个数减少,细胞克隆形成率、p62、p-PI3K/PI3K、p-Akt/Akt蛋白表达显著升高(P<0.05);与0.5×10^9/mL、1.0×10^9/mL PA-MSHA组相比,2.0×10^9/mL PA-MSHA组细胞增殖抑制率、LC3Ⅱ/LC3Ⅰ蛋白表达显著升高(P<0.05),自噬体个数增加,细胞克隆形成率、p62、p-PI3K/PI3K、p-Akt/Akt蛋白表达显著降低(P<0.05)。结论PA-MSHA可能通过调控PI3K/Akt信号通路,促进肺癌A549细胞自噬,抑制细胞增殖。     

某高校临床医学“5+3”专业医学统计学试卷分析

目的 通过分析某高校临床医学“5+3”专业学生《医学统计学》考试试卷，了解学生学习情况，改善试卷质量，为进一步教学改革提供依据。方法 采用教育测量学的原理与方法对试卷的难度、区分度、信度（Cronbach α 系数）和覆盖度及考试成绩进行分析。结果 147 名八年制临床医学学生《医学统计学》试卷的平均成绩为78.25±11.70 分，最低分为42.5 分，最高分为98.5 分，及格率为91.2%；选择题平均得分率85%，名词解释题平均得分率87.2%，填空题平均得分率78%，简答题平均得分率74.1%，计算题平均得分率76.3%；试卷难度系数为0.22，区分度为0.28,；试卷的Cronbach α 系数为0.846，题目间的相关系数＜ 0.2的占89%。结论 本次考试学生成绩优良；试卷难度稍显偏低，总体区分度一般，信度良好，试题覆盖面较广，试卷整体质量优良，能够反映学生掌握知识的水平，今后的教学中应开展多元统计相关知识及统计软件的操作，提高学生的科研素质。     

The quality of spontaneous adverse drug reaction reports from the pharmacovigilance centre in western China

Background: High-quality adverse drug reaction (ADR) reports are essential for conducting drug safety monitoring in pharmacovigilance. The study aim was to assess the current quality of ADR reports in western China, and to identify problems with ADR report quality.

Research design and methods: A sample of 1139 reports received by the Shaanxi ADR Monitoring Center from January 2015 to December 2017 was selected. ADR report quality was evaluated using an ADR report quality evaluation system.

Results: None of the reports were rated as excellent and 1.40% (n = 16) as good. Report quality was better for new and serious reports than for general reports. Medical institutions generated higher quality reports than pharmaceutical manufacturers. Nurses generated higher quality reports than doctors, pharmacists, and other professionals. Reporters of different occupations showed significant differences in the quality of the indicators Reporting time limit, Intervention ADR time, ADR termination time, ADR intervention measures, Original disease, and Cause of medication (P = 0.000).

Conclusions: The ADR data quality was poor in western China, and of lower quality than reported data from previous research in other regions. Improvements in the quality and availability of ADR reports are urgently needed.     

小胶质细胞极化在热损伤介导的早期神经损伤中的相关研究

目的观察小胶质细胞在热损伤介导的早期神经损伤中的极化状态并探讨其可能机制。 方法通过建立Beagle犬热射病动物模型，按随机数字表法将18只Beagle犬分为正常对照组（A组）9只，根据热损伤后不同时间点（1、6、24 h）分为B、C、D组各3只，B~D组置于动物体温维持仪的电热毯上，温度设置为40℃±0.5℃，每5 min监测1次直肠温度直至达到40℃。建模成功后转移到26℃±0.5℃温度和60%±0.5%湿度的环境。4组18只Beagle犬均取下丘脑进行Western blot检测，检测小胶质细胞特异性标志物CD45、iNOS及Arginase、CD206分别在4组小胶质细胞中的表达。进一步免疫组织荧光共定位观察CD45、Arginase表达。 结果A组检测出少许CD45及iNOS蛋白，B、C组两种蛋白标志物均显著高于A组（P<0.05），而D组较A组差异无统计学意义（P>0.05）；A组检测出少许Arginase及CD206蛋白，B、C、D组两种蛋白标志物均高于A组，差异有统计学意义（P<0.05）。免疫组织荧光共定位CD45、Arginase，分别在热损伤后6 h和24 h荧光光密度显著增强，差异有统计学意义（P<0.001）。 结论热射病后Beagle犬脑组织可见小胶质细胞极化活跃，中枢神经系统损伤早期1~6 h小胶质细胞活化主要以M1型为主，6 h后则转化为M2为主，热射病后24 h M2型占优势。M1/M2极化趋势与热射病早期脑损伤的相互关系可能成为热射病中枢神经损伤关键。     

Rapamycin prevents thoracic aortic aneurysm and dissection in mice

Objective

The purpose of this study was to investigate whether rapamycin inhibits the development of thoracic aortic aneurysm and dissection (TAAD) in mice.

A novel DDC gene deletion mutation in two Chinese mainland siblings with aromatic l-amino acid decarboxylase deficiency

Background

Aromatic l-amino acid decarboxylase (AADC) deficiency (OMIM #608643) is a rare and severe disorder of biogenic amine synthesis caused by mutations in the DDC gene. The phenomenology of the movement disorder includes intermittent oculogyric crises and limb dystonia, generalized athetosis, and impaired voluntary movement.