Comparison between a new platelet count drop method PL-11, light transmission aggregometry,VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals

Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11.     

深圳市制造企业90后新招产线员工心理弹性、应对方式与心理健康间的关系

目的探讨深圳市3家制造企业新招90后产线员工心理弹性、应对方式和心理健康间是否存在某种关系。方法在深圳市3家制造企业选取入职一周的新招90后产线员工,以其入职日期为单位进行整群抽样。应用心理弹性量表CDRISC、简易应对方式问卷SCSQ以及一般健康问卷GHQ-20三个量表分别测量其心理弹性、应对方式以及心理健康,并利用结构方程模型软件Amos 17.0进行路径分析。结果心理弹性与心理健康呈正相关关系(P<0.01);心理弹性和心理健康与积极应对呈正相关关系(P<0.01);心理弹性和心理健康与消极应对呈负相关关系(P<0.01);结构方程模型结果表明:心理弹性既可以直接影响心理健康,又可以通过积极应对和消极应对的中介作用间接影响心理健康。结论深圳市制造企业新招产线员工的心理弹性、应对方式与心理健康间存在线性相关关系,且心理弹性通过积极应对和消极应对对心理健康起着部分间接的作用。     

基于剂量组学预测肺癌患者放射性肺炎发生的研究

目的 探讨剂量组学在预测肺癌根治性放疗患者放射性肺炎发生中的应用潜能。方法 回顾性收集行根治性放疗的314例肺癌患者的临床资料、放疗剂量文件、定位及随访CT图像,根据临床资料及影像学随访资料对放射性肺炎进行分级,提取全肺的剂量组学特征,构建机器学习模型。应用1000次自助抽样法（bootstrap）的最小绝对值收敛和选择算子嵌套逻辑回归（LASSO‐LR）及1000次bootstrap的赤池信息量准则（AIC）向后法筛选与放射性肺炎相关的剂量组学特征,随机按照7∶3划分为训练集及验证集,应用逻辑回归建立预测模型,并应用ROC曲线及校正曲线评价模型的性能。结果 共提取120个剂量组学特征,经LASSO‐LR降维筛选得到12个特征进入“特征池”,再经过AIC向后法筛选,最终筛选出6个剂量组学特征进行模型构建,训练集AUC为0.77（95%CI为0.65~0.87）,独立验证集AUC为0.72（95%CI为0.64~0.81）。结论 利用剂量组学建立的预测模型具有预测放射性肺炎发生的潜力,但仍需继续纳入多中心数据及前瞻性数据进一步挖掘剂量组学的应用潜能。     

Pharmacological doses of melatonin impede cognitive decline in tau‐related Alzheimer models,once tauopathy is initiated,by restoring the autophagic flux

Alterations in autophagy are increasingly being recognized in the pathogenesis of proteinopathies like Alzheimer's disease (AD). This study was conducted to evaluate whether melatonin treatment could provide beneficial effects in an Alzheimer model related to tauopathy by improving the autophagic flux and, thereby, prevent cognitive decline. The injection of AAV‐hTau^P301L viral vectors and treatment/injection with okadaic acid were used to achieve mouse and human ex vivo, and in vivo tau‐related models. Melatonin (10 μmol/L) impeded oxidative stress, tau hyperphosphorylation, and cell death by restoring autophagy flux in the ex vivo models. In the in vivo studies, intracerebroventricular injection of AAV‐hTau^P301L increased oxidative stress, neuroinflammation, and tau hyperphosphorylation in the hippocampus 7 days after the injection, without inducing cognitive impairment; however, when animals were maintained for 28 days, cognitive decline was apparent. Interestingly, late melatonin treatment (10 mg/kg), starting once the alterations mentioned above were established (from day 7 to day 28), reduced oxidative stress, neuroinflammation, tau hyperphosphorylation, and caspase‐3 activation; these observations correlated with restoration of the autophagy flux and memory improvement. This study highlights the importance of autophagic dysregulation in tauopathy and how administration of pharmacological doses of melatonin, once tauopathy is initiated, can restore the autophagy flux, reduce proteinopathy, and prevent cognitive decline. We therefore propose exogenous melatonin supplementation or the development of melatonin derivatives to improve autophagy flux for the treatment of proteinopathies like AD.