Synthesis of stable-isotope-labeled N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide and N-(3-dimethylaminopropyl)-N′-ethylurea

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) is a carbodiimide coupling reagent commonly used for the preparation of amides from carboxylic acids and amines. Because of initial concerns regarding the genotoxicity of EDC and its use in GMP syntheses at Bristol Myers Squibb, the quantitation of residual EDC and its by-product N-(3-dimethylaminopropyl)-N′-ethylurea (EDU) by liquid chromatography–mass spectrometry (LCMS) impurity analysis was required. These analyses required the use of stable-isotope-labeled EDC and EDU to serve as internal standards. To meet this need, stable-isotope-labeled EDC 9 and EDU 10 were prepared from [1,2-¹³C₂] ethylene glycol and [¹³C,¹⁵N] potassium cyanide in overall yields of 6% and 8%, respectively.     

不同剂量右美托咪定对老年糖尿病足截趾患者全身麻醉苏醒期的影响

目的对比分析不同剂量右美托咪定对老年糖尿病足截趾患者全身麻醉苏醒期的影响。方法选取2017年4月至2018年8月北京市丰台区南苑医院收治的102例拟行截趾术治疗的老年糖尿病足患者作为研究对象,并按照随机数表法将其随机分为低剂量组(51例)和高剂量组(51例),其中低剂量组患者于全身麻醉时静脉缓慢泵注0. 4μg/kg的盐酸右美托咪定注射液,高剂量组患者于全身麻醉时静脉缓慢泵注0. 8μg/kg的盐酸右美托咪定注射液,对比观察两组患者诱导麻醉前、拔管时、拔管后5 min、拔管后10 min的平均动脉压(MAP)、心率(HR)、血氧饱和度(SpO_2),以及苏醒时间及拔管时间。结果诱导麻醉前、拔管时、拔管后5 min、拔管后10 min,两组患者MAP、HR及SpO_2对比,P均0.05,差异无统计学意义;低剂量组患者的苏醒时间为(14. 02±5. 87) min、拔管时间为(16. 55±5. 26) min,明显低于高剂量组患者的苏醒时间(18. 16±6.29) min、拔管时间(22. 73±6.84) min,两组对比,P均0.05,差异具有统计学意义。结论老年糖尿病足患者在截趾术中应用低剂量右美托咪定辅助麻醉,可有效缩短患者苏醒时间及拔管时间,维持患者苏醒期的血流动力学稳定性,安全性较高,具有临床推广价值。     

中国成年双生子高脂血症的分布特征

目的描述中国双生子登记系统(CNTR)成年双生子高脂血症的分布特征, 初步探索遗传和环境因素对高脂血症的影响。方法研究对象来自CNTR在全国11个项目地区募集的双生子, 纳入成年且具有高脂血症信息的69 130名(34 565对)双生子进行分析。采用随机效应模型描述高脂血症的人群、地区分布特征。分别计算不同卵型双生子的高脂血症同病率, 估算遗传度。结果研究对象年龄为(34.2±12.4)岁。双生子人群高脂血症患病率为1.3%(895/69 130)。男性、年长、城镇、已婚、大专及以上文化程度、超重、肥胖、体力活动不足、当前吸烟和曾经吸烟、当前饮酒和曾经饮酒人群中高脂血症患病率较高。双生子对内分析发现, 同卵双生子高脂血症同病率为29.1%(118/405), 高于异卵双生子的18.1%(57/315), 差异有统计学意义(P<0.05)。在不同年龄、地区及性别分层中, 同卵双生子同病率仍呈现高于异卵双生子的趋势。进一步同性别双生子对内分析发现, 在北方组和女性组中, 高脂血症遗传度分别为13.04%(95%CI:2.61%～23.47%)、18.59%(95%CI:4.43%～3...     

接种天花疫苗对猴痘病毒感染的保护作用研究进展

2022年,猴痘疫情从区域的地方性流行扩大至全球暴发,并被WHO列为国际关注的突发公共卫生事件。由于正痘病毒之间的基因序列具有高度相似性且正痘病毒可诱发交叉反应型抗体,接种天花疫苗可能会影响猴痘病毒感染诱导的免疫应答水平及感染者的健康结局。分析天花疫苗接种对猴痘病毒感染的保护作用将有助于确定疫情防控策略和措施。因此,本文通过了解既往猴痘疫情中天花疫苗的接种情况及其健康结局,综述天花疫苗接种、免疫应答情况和临床数据之间的关联性,为猴痘疫情的预防控制策略提供科学证据。     

神经内镜经鼻蝶入路切除颅底脊索瘤的临床疗效及其影响因素分析

目的探讨神经内镜经鼻蝶入路切除颅底脊索瘤的手术策略、临床疗效及其影响因素。方法回顾性分析2004年1月至2021年3月首都医科大学附属北京天坛医院神经外科采用神经内镜经鼻蝶入路切除的颅底脊索瘤患者的临床资料,共纳入373例患者(共行500例次手术)。其中2004—2019年为早期手术组,采用以肿瘤为中心的手术策略;2020—2021年为近期手术组,依据肿瘤的起源部位及其沿着颅底骨缝、神经和大血管孔道延伸生长的特点进行顺序探查和切除(探查顺序形似"龟背")。比较两种手术策略切除肿瘤程度的差异。随访患者的无进展生存期(PFS)和总生存期(OS),采用Kaplan-Meier法生存分析,采用log-rank检验分析不同临床特征患者间PFS和OS的差异。结果500例次手术中,413例次为早期手术组,肿瘤的全切除率、次全切除率、部分切除率分别为35.1%(145例次)、36.6%(151例次)、28.3%(117例次);87例次为近期手术组,肿瘤的全切除率、次全切除率、部分切除率分别为52.9%(46例次)、37.9%(33例次)、9.2%(8例次),两组肿瘤的切除率差异有统计学意义(P<0.001)。500例次手术,脑脊液漏的发生率为4.6%(23例次)。373例患者中,术后1例(0.3%)死亡,1例(0.3%)发生大面积脑梗死;共325例(87.1%)患者获得完整的随访资料,中位随访时间为31个月(3~193个月)。182例(56.0%)复发,估计总体患者的中位PFS为24个月(95%CI:17.5~30.5);85例(26.2%)死亡,估计总体患者的中位OS为106个月。生存分析显示,与原发性肿瘤、肿瘤体积小、肿瘤全切除、病理学类型为经典型或软骨型肿瘤及术后放疗的患者比较,复发性肿瘤、肿瘤体积大、肿瘤非全切除、病理学类型为去分化或差分化或肉瘤样型肿瘤及术后未行放疗患者的PFS和OS均短,差异均有统计学意义(均P<0.05)。结论依据颅底脊索瘤生长侵袭特点,采用"龟背"形顺序探查、切除肿瘤的手术策略有利于提高肿瘤的切除程度。肿瘤是否原发、体积大小、切除程度、病理学类型、术后是否放疗可能与颅底脊索瘤患者术后的PFS和OS有关。     

FreeSurfer-based segmentation of hippocampal subfields: A review of methods and applications,with a novel quality control procedure for ENIGMA studies and other collaborative efforts

Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and variation in hippocampal measures is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium, several Disease Working Groups are using the FreeSurfer software to analyze hippocampal subregion (subfield) volumes in patients with neurological and psychiatric conditions along with data from matched controls. In this overview, we explain the algorithm's principles, summarize measurement reliability studies, and demonstrate two additional aspects (subfield autocorrelation and volume/reliability correlation) with illustrative data. We then explain the rationale for a standardized hippocampal subfield segmentation quality control (QC) procedure for improved pipeline harmonization. To guide researchers to make optimal use of the algorithm, we discuss how global size and age effects can be modeled, how QC steps can be incorporated and how subfields may be aggregated into composite volumes. This discussion is based on a synopsis of 162 published neuroimaging studies (01/2013–12/2019) that applied the FreeSurfer hippocampal subfield segmentation in a broad range of domains including cognition and healthy aging, brain development and neurodegeneration, affective disorders, psychosis, stress regulation, neurotoxicity, epilepsy, inflammatory disease, childhood adversity and posttraumatic stress disorder, and candidate and whole genome (epi-)genetics. Finally, we highlight points where FreeSurfer-based hippocampal subfield studies may be optimized.