吸入麻醉药预处理对心肌缺血“第二保护窗”的作用机制

吸入麻醉药预处理对心肌缺血侑罐注损伤具有急性期和“第二保护窗”两个时间段的保护作用。“第二保护窗”起效缓慢而持久,临床上有充分的时间在手术前给予,能更方便有效地预防围术期心肌缺血的并发症。它可诱导一些触发因子如腺苷、一氧化氮的产生,通过信号转导通路蛋白激酶C、核因子-κB等,作用于ATP敏感性钾通道及活性氧族等终末效应离子通道或保护蛋白而发挥迟发性心肌保护。现就近年来关于吸入麻醉药预处理对心肌“第二保护窗”的作用机制作一综述。     

Habitual intakes of sugar-sweetened beverages associated with gut microbiota-related metabolites and metabolic health outcomes in young Chinese adults

Background and aimsReducing consumption of sugar-sweetened beverages (SSBs) is a global public health priority because of their limited nutritional value and associations with increased risk of obesity and metabolic diseases. Gut microbiota-related metabolites emerged as quintessential effectors that may mediate impacts of dietary exposures on the modulation of host commensal microbiome and physiological status.Methods and resultsThis study assessed the associations among SSBs, circulating microbial metabolites, and gut microbiota–host co-metabolites, as well as metabolic health outcomes in young Chinese adults (n = 86), from the Carbohydrate Alternatives and Metabolic Phenotypes study in Shaanxi Province. Five principal component analysis-derived beverage drinking patterns were determined on self-reported SSB intakes, which were to a varying degree associated with 143 plasma levels of gut microbiota-related metabolites profiled by untargeted metabolomics. Moreover, carbonated beverages, fruit juice, energy drinks, and bubble tea exhibited positive associations with obesity-related markers and blood lipids, which were further validated in an independent cohort of 16,851 participants from the Regional Ethnic Cohort Study in Northwest China in Shaanxi Province. In contrast, presweetened coffee was negatively associated with the obesity-related traits. A total of 79 metabolites were associated with both SSBs and metabolic markers, particularly obesity markers. Pathway enrichment analysis identified the branched-chain amino acid catabolism and aminoacyl-tRNA biosynthesis as linking SSB intake with metabolic health outcomes.ConclusionOur findings demonstrate the associations between habitual intakes of SSBs and several metabolic markers relevant to noncommunicable diseases, and highlight the critical involvement of gut microbiota-related metabolites in mediating such associations.     

Cumulative burden of abnormal visceral adiposity index and its components on the risk of hyperuricemia

Background and aimsThe visceral adiposity index (VAI), a gender-specific surrogate maker of adipose tissue distribution and function, is associated with risk of hyperuricemia. However, the impact of time-burden of abnormal VAI and its components on the risk of hyperuricemia remains unknown.Methods and resultsWe included 56,537 participants without hyperuricemia and underwent two health examinations during 2006–2008 from the Kailuan study. Abnormal VAI burdens were evaluated as follows: (1) cumulative number of abnormal VAI presented at each examination (0–2 times); (2) cumulative number of each abnormal VAI component presented at each examination (0–2 times per component); (3) cumulative number of total abnormal VAI components presented at each examination (0–8 times).During a median follow-up of 8.81 years, 10,762 participants were diagnosed with hyperuricemia. The risk of hyperuricemia showed a positive association with cumulative number of abnormal VAI, the adjusted hazard ratio (HR) with 95% confidence interval (CI) of 2 times compared to 0 times was 1.69 (1.58–1.81). All four components of abnormal VAI, when diagnosed repeatedly, were independently associated with an increased risk of hyperuricemia, adjusted HR (95% CI) from 1.15 (1.02–1.28) for low high-density lipoprotein to 1.68 (1.58–1.79) for elevated triglyceride. The risk of hyperuricemia also gradually as abnormal components was accumulated from 0 to 8 counts, reaching an adjusted HR (95% CI) of 3.72 (2.64–5.23). Furthermore, the effect of cumulative abnormal VAI was more pronounced in females than males (P-interaction < 0.0001).ConclusionsCumulative abnormal VAI burdens were positively associated with the risk of hyperuricemia, especially in females.     

阿托西班治疗早产的快速卫生技术评估

目的:基于当前最佳证据,对阿托西班治疗早产的获益与风险进行评价,为临床药物选择和决策提供循证依据。方法:检索 PubMed、the Cochrane library、CNKI、万方等国内外数据库。由2位评价者根据纳入与排除标准独立筛选文献并提取资料。纳入文献进行质量评价后,对有效性、安全性结果进行定量描述,对经济学评价结果进行定性描述。结果:共纳入6篇系统评价/Meta分析和4篇药物经济研究。与硝苯地平相比,阿托西班与硝苯地平治疗早产的疗效相当,阿托西班可显著降低治疗早产过程中发生的心悸、心动过速和头痛等不良反应;与利托君相比,阿托西班与利托君治疗早产的疗效相当,阿托西班产生的孕妇心动过速发生率与因母体不良反应中断治疗率更低,差异具有统计学意义。经济学研究显示,阿托西班在荷兰不具备成本效果优势,在意大利、德国和中国具有成本效果优势。结论:阿托西班治疗早产的有效性与目前的一线治疗药品相当,无明显优势;在安全性方面,与硝苯地平或利托君相比显著降低了心悸、心动过速、头痛等不良反应的发生率;经济学研究显示,阿托西班与非药物治疗相比具有成本效果优势。     

Inhibition of phosphodiesterase-4 suppresses HMGB1/RAGE signaling pathway and NLRP3 inflammasome activation in mice exposed to chronic unpredictable mild stress

Inhibition of phosphodiesterase-4 (PDE4) produces robust anti-inflammatory and antidepressant-like effects in multiple animal models. However, the detailed mechanisms have not been well studied. Receptor for advanced glycation endproducts (RAGE) and inflammasome activation are implicated in the etiology of depression. Here, we aimed to investigate the involvement of RAGE and nucleotide-binding domain (NOD)–like receptor protein 3 (NLRP3) inflammasome in the antidepressant-like effects of PDE4 inhibition in mice. We found that inhibition of PDE4 by roflupram (ROF, 0.5, and 1.0 mg/kg, i.g.) exerted antidepressant-like effects in mice subjected to chronic unpredictable mild stress (CUMS). Simultaneously, ROF inhibited CUMS-induced microglial activation and restored the morphology of microglial cells in the hippocampus, as evidenced by reduced total process length, area, volume, number of branching points, number of terminal points and total sholl intersections of microglia. ROF also decreased the expression of ionized calcium-binding adapter molecule-1 and the level of interleukin-1β. Western blot analysis showed that PDE4 inhibition suppressed the high-mobility group box 1 protein (HMGB1)/RAGE signaling pathway, as the levels of HMGB1, RAGE, toll-like receptor 4, phosphorylated p38 mitogen-activated protein kinase, and nuclear factor κ-B were decreased in both hippocampus and cortex in mice after treatment with ROF. Moreover, ROF also attenuated the protein levels of NLRP3, the apoptosis-associated speck-like protein containing (ASC), and cysteine-requiring aspartate protease-1 (Caspase-1), which are key proteins in the NLRP3-mediated inflammasome signaling pathway. In summary, these results demonstrate that the down-regulation of HMGB1/RAGE signaling pathway and inflammasome suppression possibly contribute to the antidepressant-like effects of PDE4 inhibitors. And, ROF has potential as a candidate drug in the treatment of depression.     

IL-8、MIP-1a和TNF-a在细菌性脑膜炎患者脑脊液中的表达

目的通过研究白细胞介素-8（IL-8）、巨噬细胞炎症蛋白-1a（MIP-1a）和肿瘤坏死因子-a（TNF-a）在细菌性脑膜炎患者脑脊液中的表达水平，探讨其在细菌性脑膜炎发病过程中的发病机制。方法采用双抗体夹心酶联免疫吸附试验（ELISA）检测45例细菌性脑膜炎患者和40例无中枢神经系统炎症性疾病儿童脑脊液中IL-8、MIP-1a和TNF-a的浓度。结果细菌性脑膜炎患者脑脊液中IL-8浓度明显高于对照组（P〈0．05），且其水平与脑脊液中TNF-a水平、蛋白质含量相关；而MIP-1a水平在两组间差异无统计学意义（P〉0．05）。结论趋化因子IL-8、TNF-a在细菌性脑膜炎中起着显著上调作用，即参与了细菌性脑膜炎患者的局部炎性应答，而MIP-1a的调节作用不明显。     

帕金森病与阿尔茨海默病患者的经颅超声图像分析

目的 对比分析帕金森病（PD）和阿尔茨海默病（AD）患者的经颅超声（TCS）图像变化特点。方法 对38例PD、28例AD及26名健康志愿者行TCS检查,分析其黑质回声、3脑室宽度及大脑中动脉血流参数变化特点。结果 黑质异常强回声比例PD组（31/38,81.58%）高于AD组（8/28,28.57%）和对照组（3/26,11.54%）,差异均有统计学意义（χ²=18.74、30.41,P均<0.001）,而AD组和对照组间无明显差异（χ²=2.41,P=0.120）;3脑室宽度AD组[（0.82±0.14）cm]大于PD组[（0.63±0.16）cm]和对照组[（0.56±0.16）cm],差异均有统计学意义（P均<0.001）,而PD组和对照组间差异无统计学意义（P=0.098）;双侧大脑中动脉平均流速AD组均低于PD组和对照组,右侧大脑中动脉搏动指数AD组高于PD组和对照组,差异均有统计学意义（P均<0.05）。结论 通过TCS检查,联合黑质回声、3脑室宽度及大脑中动脉血流变化,可为PD及AD的诊断提供有价值的神经影像学信息。