Quantitative Metabolomics Reveals Heart Failure With Midrange Ejection Fraction as a Distinct Phenotype of Heart Failure

BackgroundHeart failure with midrange ejection fraction (HFmrEF) has been recently acknowledged as a separate phenotype, but metabolomics evaluation of this subtype remains largely unexamined.MethodsA quantitative metabolomics study on amino acids and acylcarnitines was performed to characterize different states of heart failure (HF) in 628 participants. Both multivariate orthogonal partial least squares- discriminant analysis and univariate Mann-Whitney U test were used to explore reliable metabolic profiles associated with different HF states. The resulting metabolites were further refined to obtain diagnostic metabolite scores (DMSs) with the use of ordinal logistic regression. Lasso-penalized regression was applied to produce a survival-associated prognostic metabolite score (PMS). The Cox proportional hazards model, Kaplan-Meier curves, and time-dependent receiver operating characteristics were used for a comprehensive assessment of prognostic value using PMS versus traditional clinical biomarkers.ResultsThe optimized models identified a panel of 15 differential metabolites that were shared across different HF states, whereas some metabolites were associated with a specific state. PMS consisting of 9 metabolites demonstrated an appreciably better prognostic value (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.25-2.1) vs the natural logarithm of N-terminal pro–B-type natriuretic peptide (Ln[NT-proBNP]; HR 1.23, 95% CI 0.94-1.61; P < 0.001). The overall area under the receiver operating characteristic curve value of PMS was superior to that of Ln(NT-proBNP) in risk prediction for patients with HFmrEF and HF with reduced ejection fraction (HFrEF) subtypes (P < 0.001).ConclusionsTargeted metabolomics has provided a novel understanding of the molecular mechanism underlying HF. Both DMS and PMS clearly demonstrated HFmrEF as a distinct phenotype between a mild HF with preserved ejection fraction state and a severe HFrEF state. PMS exhibited superior prognostic value than Ln(NT-proBNP). Further investigation is needed with independent large-scale validation.     

一种感染性非人灵长类实验装置的生物安全研究

目的 拟设计一种在无操作时能完全隔离感染动物,又能在日常照料动物时形成定向气流的实验装置,保证非人灵长类动物正常生物学特性表达的同时还能有效防止气溶胶感染。方法 使用具有氯霉素抗性的大肠杆菌(Cl+, E.coli, Rosetta菌株)作为指示微生物,观察处于本实验装置中非人灵长类在实验中的生物学特性,并采用气溶胶采集装置及沉降菌采集的方法对本实验装置内外的指示微生物进行监测。结果 在内笼指示菌富集时,本实验安全装置的外笼无论在开启还是关闭状态下,房间内、笼外及外笼均未检测到指示菌及气溶胶。结论 本实验装置能保证非人灵长类正常生物学特性的表达,并可有效防止气溶胶感染。     

经心内和食管快速心房刺激对P波时限及离散度的影响

目的分析快速心房刺激对P波时限及离散度的影响。方法在74例射频消融术经电极导管起搏高位右房及82例经食管心房调搏检查者中,用180次/分的S1S1刺激心房3min,在刺激前后立刻记录12导同步心电图,通过心电图测出刺激前后的最大P波时限(Pmax)、最小P波时限(Pmin)及P波离散度(Pd),然后进行比较。结果:射频消融组Pmax在心房刺激后比刺激前有显著性延长(P<0.01),Pmin及Pd无显著性差异。食管心房调搏组Pmax及Pd在心房刺激后显著性增加(P<0.01),Pmin无显著性差异。结论:快速心房刺激能引起心房传导时间延长,非均质电活动的离散程度增加。     

基于空间分析预测钉螺分布的气温指标研究

目的探讨钉螺分布与气温的定量关系，为全球气候变暖与南水北调钉螺能否北移提供理论基础。方法收集多年来的年平均最低气温、1月平均最低气温、年平均气温、1月平均气温、年平均最高气温，按1km网格匹配气温数据，在GIS支持下，将空间分布的气温数据与中国血吸虫病流行县分布图进行空间统计分析，并比较不同气温与钉螺分布的吻合程度。结果钉螺分布区的累年平均最低气温的95％可信区间为（4．3～18．1℃）、累年1月平均最低气温的为（-4．6～9．2℃）、累年平均气温的为（9．4～21．1℃）、累年1月平均气温的为（0．9～12．4℃）、累年平均最高气温的为（16．2～25．6℃），其中累年1月平均气温与钉螺的分布拟合最好。结论1月平均气温是预测钉螺分布的较好指标。     

细胞凋亡通路激活对实验性1型糖尿病树胰岛β细胞死亡的作用

树 2 6只分为正常对照组和 1型糖尿病组。小量、多次链脲佐菌素注射可诱导树产生 1型糖尿病 ,其 β细胞损伤与胰岛中细胞凋亡通路激活有关。     

多巴丝肼联合盐酸普拉克索治疗帕金森病对运动功能的影响研究

目的探究帕金森病患者应用多巴丝肼联合盐酸普拉克索治疗对运动功能的影响。方法100例帕金森病患者,随机分为对照组与观察组,各50例。对照组患者给予多巴丝肼治疗,观察组患者给予多巴丝肼联合盐酸普拉克索治疗。比较两组患者的运动功能和不良反应发生情况。结果观察组患者左手运动、右手运动、起立、转弯、10 m折返运动时间分别为(94.06±5.23)、(98.64±8.03)、(3.03±0.25)、(4.44±0.84)、(13.48±0.72)min,均长于对照组的(86.13±4.02)、(88.65±5.46)、(2.23±0.12)、(2.98±0.48)、(13.94±0.62)min,差异有统计学意义(P<0.05)。治疗前及治疗4周,两组帕金森病综合评分量表(UPDRS)评分比较差异无统计学意义(P>0.05);观察组治疗8、12周UPDRS评分均低于对照组,差异有统计学意义(P<0.05)。两组不良反应发生率比较差异无统计学意义(χ2=3.053,P>0.05)。结论应用多巴丝肼联合盐酸普拉克索治疗帕金森病患者效果显著,可有效改善运动功能,临床价值高。     

Enhancing Social Initiations Using Naturalistic Behavioral Intervention: Outcomes from a Randomized Controlled Trial for Children with Autism

Deficits in social skills are common in children with Autism Spectrum Disorder (ASD), and there is an urgent need for effective social skills interventions, especially for improving interactions with typically developing peers. This study examined the effects of a naturalistic behavioral social skills intervention in improving social initiations to peers through a randomized controlled trial. Analyses of multimethod, multi-informant measures indicated that children in the active group (SIMI) demonstrated greater improvement in the types of initiations which were systematically prompted and reinforced during treatment (i.e., behavior regulation). Generalization to joint attention and social interaction initiation types, as well as collateral gains in broader social functioning on clinician- and parent-rated standardized measures were also observed.

     

Brainstem atrophy in the early stage of Alzheimer’s disease: a voxel-based morphometry study

Brain Imaging and Behavior - Postmortem studies on patients with Alzheimer’s disease (AD) have confirmed that the dorsal raphe nucleus (DRN) in the brainstem is the first brain structure...     

舌静脉畸形的DSA分型及治疗—132例临床分析

目的:探讨舌静脉畸形(venous malformations,VM)的数字减影血管造影（digital substraction angiography, DSA）分型及治疗策略。方法:总结2016年2月—2019年2月收治的132例舌VM患者的DSA表现,根据影像学特征将其分为4型,Ⅰ型为无回流型、Ⅱ型为低回流型、Ⅲ型为高回流型、Ⅳ型为广泛型,依据分型选择不同的治疗方案。无回流型单纯采用平阳霉素进行硬化治疗,低回流型单纯采用聚桂醇泡沫硬化剂进行硬化治疗,高回流型采用无水乙醇结合聚桂醇泡沫硬化剂进行硬化治疗,广泛型先按高回流型进行硬化治疗后再结合整形手术切除。统计各组病例的治疗效果及不良反应。结果:本组132例病例获得12~41个月随访,平均15.8个月,所有患者术后舌VM明显缩小甚至消失。Ⅰ型8例,有效率100%;Ⅱ型17例,有效率100 %;Ⅲ型98 例,有效率90.8 %;Ⅳ型 9例,有效率77.8%。不良反应主要为组织溃烂、坏死,Ⅰ型0例;Ⅱ型1例,发生率5.88%; Ⅲ型16例,发生率16.33%;Ⅳ型7例,发生率77.78%。结论:基于DSA的舌VM分型对临床治疗具有重要指导意义。舌VM中大部分为Ⅲ型病例,Ⅰ型比例最小。经黏膜注射无水乙醇是治疗高回流型和广泛型舌VM的有效方法。