A random set approach to confidence regions with applications to the effective dose with combinations of agents

The effective dose (ED) is the pharmaceutical dosage required to produce a therapeutic response in a fixed proportion of the patients. When only one drug is considered, the problem is a univariate one and has been well‐studied. However, in the multidimensional setting, that is, in the presence of combinations of agents, estimation of the ED becomes more difficult. This study is focused on the plug‐in logistic regression estimator of the multidimensional ED. We discuss consistency of such estimators and focus on the problem of simultaneous confidence regions. We develop a bootstrap algorithm to estimate confidence regions for the multidimensional ED. Through simulation, we show that the proposed method gives 95% confidence regions, which have better empirical coverage than the previous method for moderate to large sample sizes. The novel approach is illustrated on a cytotoxicity study on the effect of two toxins in the leukemia cell line HL‐60 and a decompression sickness study of the effects of the duration and depth of the dive. Copyright © 2014 John Wiley & Sons, Ltd.     

Review of Low-Frequency Noise Properties of High-Power White LEDs during Long-Term Aging

Low-frequency noise investigation is a highly sensitive and very informative method for characterization of white nitride-based light-emitting diodes (LEDs) as well as for the evaluation of their degradation. We present a review of quality and reliability investigations of high-power (1 W and 3 W) white light-emitting diodes during long-term aging at the maximum permissible forward current at room temperature. The research was centered on the investigation of blue InGaN and AlInGaN quantum wells (QWs) LEDs covered by a YAG:Ce³⁺ phosphor layer for white light emission. The current-voltage, light output power, and low-frequency noise characteristics were measured. A broadband silicon photodetector and two-color (blue and red) selective silicon photodetectors were used for the LED output power detection, which makes it possible to separate physical processes related to the initial blue light radiation and the phosphor luminescence. Particular attention was paid to the measurement and interpretation of the simultaneous cross-correlation coefficient between electrical and optical fluctuations. The presented method enables to determine which part of fluctuations originates in the quantum well layer of the LED. The technique using the two-color selective photodetector enables investigation of changes in the noise properties of the main blue light source and the phosphor layer during the long-term aging.     

Right inferior frontal gyrus: An integrative hub in tonal bilinguals

Right hemispheric dominance in tonal bilingualism is still controversial. In this study, we investigated hemispheric dominance in 30 simultaneous Bai‐Mandarin tonal bilinguals and 28 Mandarin monolinguals using multimodal neuroimaging. Resting‐state functional connectivity (RSFC) analysis was first performed to reveal the changes of functional connections within the language‐related network. Voxel‐based morphology (VBM) and tract‐based spatial statistics (TBSS) analyses were then used to identify bilinguals' alterations in gray matter volume (GMV) and fractional anisotropy (FA) of white matter, respectively. RSFC analyses revealed significantly increased functional connections of the right pars‐orbital part of the inferior frontal gyrus (IFG) with right caudate, right pars‐opercular part of IFG, and left inferior temporal gyrus in Bai‐Mandarin bilinguals compared to monolinguals. VBM and TBSS analyses further identified significantly greater GMV in right pars‐triangular IFG and increased FA in right superior longitudinal fasciculus (SLF) in bilinguals than in monolinguals. Taken together, these results demonstrate the integrative role of the right IFG in tonal language processing of bilinguals. Our findings suggest that the intrinsic language network in simultaneous tonal bilinguals differs from that of monolinguals in terms of both function and structure.     

心血管病继发认知障碍与心脑同治的中医药防治策略

心血管病患者继发认知障碍是老年人群的常见并病,严重危害患者健康,影响长期生存质量,心血管病可导致血管内皮损伤,脑灌注不足,脑部病变,继而引起认知障碍,心血管危险因素也会增加患者继发认知障碍的风险,积极寻求早期诊断及中西医结合防治方法尤为重要。中医基于“整体观念”提出“心脑相通”,心脑相通共主神明,心伤可累及脑,导致神志异常,是心血管病继发认知障碍的病因。后世医家基于“异病同治”和心脑相通,提出“心脑同治”。“心脑同治”包含两种含义,一为不同疾病归同一病因病机,可用同一方法治疗;二为异病共存,针对相同危险因素进行治疗。该文系统探讨了心血管疾病继发认知障碍的中医病因病机及心脑同治的防治策略,认为气血不足是基础,瘀毒互结阻脉、损窍是关键,调畅气血,活血解毒通脉、通窍为其主要治法,以期丰富“心脑同治”的理论内涵,为中医药防治心血管病继发认知障碍提供新的思路。     

非对称PCR-FP技术同步检测HSV-1/-2、CMV和EBV

目的应用非对称PCR-荧光偏振(FP)技术建立一种同步检测全血中4种主要疱疹病毒(单纯疱疹病毒1/2型,巨细胞病毒、EB病毒)的新方法。方法以人疱疹病毒属通用引物行非对称PCR,扩增从179例样本中抽提的DNA。PCR扩增产物与特异性单纯疱疹病毒1/2型(HSV-1/-2)、巨细胞病毒(CMV)和EB病毒(EBV)寡核苷酸探针混合物温育杂交,荧光偏振检测技术检测杂交液荧光偏振值,据荧光偏振值判断病毒感染类型,并以DNA序列测定结果为参照。结果与DNA序列测定的阳性检测符合率为100%,但DNA序列测定检测均未检出多重混合感染。非对称PCR-FP方法对HSV-1/-2检测的灵敏度达到1.0×10~3拷贝/ml,对EBV和CMV检测的灵敏度达到2.0×10~3拷贝/ml。结论本法对于4种主要疱疹病毒感染的筛查及预防、预后判断具重要价值。     

脑心通胶囊“心脑同治”的免疫和炎症标志物研究

目的 探讨脑心通胶囊“心脑同治”的免疫和炎症标志物。方法 采用结扎左前降支冠状动脉（left anterior descending coronary artery ligation,LAD）模型为心肌缺血模型,大脑中动脉阻塞（middle cerebral artery occlusion,MCAO）模型为脑缺血模型。雄性SD大鼠随机分为8组,包括用于心肌缺血研究的假手术组、LAD模型组、脑心通（110 mg/kg）组和卡托普利（10.125 mg/kg）组,以及用于脑缺血研究的假手术组、MCAO模型组、脑心通（220 mg/kg）组和银杏提取物（50 mg/kg）组,每组15只。药效学指标选择心电图、心肌酶谱、透射电镜等;生物信息学和蛋白质组学预测并筛选免疫炎症标志物;利用qRT-PCR和Western blotting验证关键备选标志物靶点的mRNA和蛋白相对表达量。结果 脑心通胶囊不仅降低LAD大鼠的心梗死率、心肌酶活性（P＜0.01）,改善心肌损伤,还能降低LAD大鼠的脑海马组织损伤和脑水肿（P＜0.05）。对于MCAO大鼠,脑心通胶囊显著降低脑梗死率、神经功能评分和脑组织含水率（P＜0.05、0.01）,同时减轻心肌组织和细胞损伤,降低心肌酶活性（P＜0.01）。根据生物信息学和蛋白质组学结果,Toll受体信号通路的相关靶点是“心脑同治”的关键所在,有成为标志物的潜力。在心肌缺血和脑缺血2种状态下,α-干扰素（interferon-α,IFN-α）、Toll样受体4（Toll-like receptor 4,TLR4）、TLR7、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）共4个靶点的mRNA和蛋白相对表达量显著变化（P＜0.05、0.01）,表明LAD大鼠和MCAO大鼠的海马中出现炎症因子风暴和免疫反应瀑布。结论 IFN-α、TLR4、TLR7、TNF-α能够作为海马中“心脑互损”“心脑同治”的免疫和炎症标志物。     

Development of a Novel UPLC-MS/MS Method for the Simultaneous Determination of 16 Mycotoxins in Different Tea Categories

The contamination of potential mycotoxins in tea production and consumption has always been a concern. However, the risk monitoring on multiple mycotoxins remains a challenge by existing methods due to the high cost and complex operation in tea matrices. This research has developed a simple ultra-performance liquid chromatography-tandem mass spectrometry strategy based on our homemade purification column, which can be applied in the detections of mycotoxins in complex tea matrices with high-effectively purifying and removing pigment capacity for 16 mycotoxins. The limits of detection and the limits of quantification were in the ranges of 0.015~15.00 and 0.03~30.00 µg·kg⁻¹ for 16 mycotoxins, respectively. Recoveries from mycotoxin-fortified tea samples (0.13~1200 µg·kg⁻¹) in different tea matrices ranged from 61.27 to 118.46%, with their relative standard deviations below 20%. Moreover, this method has been successfully applied to the analysis and investigation of the levels of 16 mycotoxins in major categories of tea and the monitoring of multiple mycotoxins in processed samples of ripened Pu-erh. In conclusion, the proposed strategy is simple, effective, time-saving, and low-cost for the determination of a large number of tea samples.     

上颌窦底微创提升的短期临床疗效评价

目的：通过临床试验评估一种上颌窦底微创提升技术的疗效。方法试验组11例患者的上颌后牙区行上颌窦底微创提升技术并同期植入短种植体14枚。对照组10例患者进行了使用扩孔钻的上颌窦冲顶技术并同期植入短种植体13枚。两组患者术后6个月行暂冠修复,进行咬合训练及软组织塑形,3个月后永久修复。术后定期复诊,检查患者的上颌窦、种植体骨结合情况,并使用锥形束CT（CBCT）测量骨增量水平。结果试验组及对照组均无种植体松动、脱落及上颌窦炎发生,CBCT显示种植体与周围组织形成良好的骨性结合。经2~28个月随访观察,临床效果良好。试验组和对照组平均窦底垂直骨增量分别为5.87和5.45 mm。结论上颌窦底微创提升联合短种植体同期植入是一种创伤小、操作简单、行之有效的上颌后牙区种植外科技术,可用于上颌窦底垂直骨量严重不足,余留牙槽骨高度不足4 mm的病例。