鼠巨细胞病毒感染C57BL/6小鼠急性肝炎动物模型的建立与鉴定

目的：建立鼠巨细胞病毒（MCMV）感染C57BL/6小鼠急性肝炎模型并对其感染特点进行分析及鉴定。方法：将24 只C57BL/6小鼠随机分为阴性对照组（n =12）及病毒感染组（n =12），病毒感染组腹腔注射1.0×106 PFU（200 μL）MCMV悬液，阴性对照组注射等体积小鼠胚胎成纤维细胞（MEF）悬液。于感染后第3天和第7天取外周血分离血清检测谷丙转氨酶（ALT）及谷草转氨酶（AST）。同时进行肝组织病毒分离、组织病理学及MCMV IE和M55基因、细胞因子白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子α（TNF-α）的检测。结果：病毒感染组肝组织匀浆病毒分离均为阳性，肝炎发生率为100%。在感染后第3天即发生肝炎病理改变，病毒感染组血清ALT及AST较阴性对照组明显升高（P ＜0.01）；病毒感染组肝脏HE染色第3天可见局灶性炎性细胞浸润及肝脏点灶状坏死，持续至第7天，Ishak评分较阴性对照组明显升高（P ＜0.01）；在感染后第3天病毒感染组肝组织内可检测到MCMV IE及M55基因，且在感染后第7天仍可测得IE基因；感染后第3天及第7天病毒感染组炎性细胞因子IL-6、TNF-α及IL-1β mRNA表达水平明显升高（P ＜0.05）。 结论：成功建立MCMV感染C57BL/6小鼠急性动物肝炎模型，其感染表现主要集中在急性感染前期。     

Adeno-associated virus (AAV)-mediated neuroprotective effects on the degenerative retina: the therapeutic potential of erythropoietin

Retinal degeneration (RD) results in photoreceptor loss and irreversible visual impairments. This study sought to alleviate the photoreceptor degeneration via the adeno-associated virus (AAV)-mediated erythropoietin (EPO) therapy. AAV-2/2-mCMV-EPO vectors were constructed and delivered into the subretinal space of a RD model. The retinal morphology, optokinetic behaviour and electrophysiological function of the treated animals were analysed. The subretinal delivery of AAV-2/2 vectors induced robust EPO gene expressions in the retinas. AAV2/2-mediated EPO therapy ameliorated the photoreceptor degeneration and visual impairments of the RD animal model. Furthermore, the multi-electrodes array (MEA) was used to detect the firing activities of retinal ganglion cells. MEA recording showed that the EPO therapy could restrain the spontaneous firing response, enhance the light-induced firing response and preserve the basic configurations of visual signal pathway in RD model. Our MEA assay provided an example to evaluate the potency of pharmacological compounds on retinal plasticity. In conclusion, AAV2/2-mediated EPO therapy can ameliorate the photoreceptor degeneration and rectify the abnormities in visual signal transmission. These beneficial results suggest the AAV vector is a viable therapeutic option for retinopathies with rapidly degenerating kinetics and lay the groundwork for future development of EPO gene therapy.     

基于全-精细指纹图谱与多元统计分析的栀子炒制前后差异评价

目的比较栀子炒制前后化学成分差异,明确其差异标志物,为栀子与炒栀子质量标准的制定提供参考。方法采用全-精细指纹图谱和多指标含量同时测定对栀子炒制前后样品进行分析,采用层次聚类分析(HCA)、主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA)等多元统计分析对栀子与炒栀子指纹图谱进行比较,筛选出导致差异的特征性成分。结果栀子炒制前后指纹图谱中共有15个峰,其中12个峰为两者所共有,栀子与炒栀子对照指纹图谱的全指纹图谱相似度为0.991,而去除栀子苷积分后建立的精细指纹图谱相似度为0.880,低于0.90,可基本实现两者区分;多元统计分析结果表明栀子与炒栀子可明显分为2类,并筛选得到贡献度较大的4个差异标志物,分别为峰3、5、9(栀子苷)、11(西红花苷I);含量测定结果表明栀子炒制后栀子苷、西红花苷I、西红花苷II含量显著降低,而去乙酰车叶草酸甲酯含量显著升高。结论栀子炒制前后成分差异显著,建立的精细指纹图谱结合多成分含量测定方法可有效区分栀子与炒栀子,筛选得到的差异标志物可为其质量标志物的选择提供参考。     

Clinical effectiveness and radial artery remodeling assessment via very-high-frequency ultrasound/ultra biomicroscopy after applying slender 7Fr sheath for transradial approach in left main bifurcation disease

Abstract

Objective

To explore the clinical effect and radial remodeling of transradial slender 7?Fr sheath for left main bifurcation disease (LM bifurcation).     

膝关节骨关节炎治疗的研究进展

骨关节炎（osteoarthritis，OA）是一种以关节软骨退行性改变和继发性骨增生为特征的慢性关节疾病，其中以膝关节骨关节炎（knee osteoarthritis，KOA）最为常见。目前针对KOA的非手术治疗仅能达到缓解疼痛、改善功能的目的。积极的手术治疗效果虽好，但假体定位困难，手术难度高，因此急需新的治疗方式以改善患者预后。基于KOA的最新临床研究，本文对膝神经射频消融术、机器人辅助膝关节置换术、生物治疗和激光治疗等4种新的治疗方式开展评述。     

Partitioning heritability analyses unveil the genetic architecture of human brain multidimensional functional connectivity patterns

Resting‐state functional connectivity profiles have been increasingly shown to be important endophenotypes that are tightly linked to human cognitive functions and psychiatric diseases, yet the genetic architecture of this multidimensional trait is barely understood. Using a unique sample of 1,704 unrelated, young and healthy Chinese Han individuals, we revealed a significant heritability of functional connectivity patterns in the whole brain and several subnetworks. We further proposed a partitioned heritability analysis for multidimensional functional connectivity patterns, which revealed the common and unique enrichment patterns of the genetic contributions to brain connectivity patterns for several gene sets linked to brain functions, including the genes expressed preferentially in the central nervous system and those associated with intelligence, educational attainment, attention‐deficit/hyperactivity disorder, and schizophrenia. These results for the first time reveal the genetic architecture of multidimensional brain connectivity patterns across different networks and advance our understanding of the complex relationship between gene sets, neural networks, and behaviors.     

Hypertension is a risk factor for adverse outcomes in patients with coronavirus disease 2019: a cohort study

Abstract

Background

Comorbidities are commonly seen in patients with coronavirus disease 2019 (COVID-19), but the clinical implication is not yet well-delineated. We aim to characterize the prevalence and clinical implications of comorbidities in patients with COVID-19.     

消化道恶性肿瘤住院患者的能量消耗研究

目的评估消化道恶性肿瘤患者的能量消耗，探讨最佳计算公式及能量消耗的影响因素。方法采用连续入组法，纳入2016年3月至2016年12月在陆军军医大学第一附属医院肿瘤科住院治疗患者，运用代谢车测定其静息代谢能量（REE），使用Harris-Benedict公式和30kcal/（kg·d） 公式预测患者的一日总能量消耗（TEE）。收集研究对象的相关指标如年龄、身高、体重、病程、原位癌部位、是否荷瘤等。结果共纳入26例患者，其中包括食管癌11例，胃癌8例，结直肠癌7例，73%的患者处于高代谢状态，约69%的患者处于肿瘤Ⅳ期；其中不同病程和原位癌位置与静息能量消耗有差异，差异具有统计学意义；用30kcal/（kg·d）×体重估算TEE可能并不适用于消瘦的消化道肿瘤患者。结论消化道恶性肿瘤患者大多存在营养不良且处于高代谢状态，在给消化道恶性肿瘤患者提供能量时应适当考虑病程长短、肿瘤分期以及肿瘤部位等因素。尽量使用代谢车估算恶性肿瘤患者的TEE，若没有代谢车条件时，对于能下床活动的消化道恶性肿瘤患者，体质指数（BMI）≥18.5kg/m2者推荐使用30kcal/（kg·d）×实际体重的方法估算TEE，BMI<18.5kg/m2者推荐使用30kcal/（kg·d）×标准体重的方法估算TEE。     

小剂量丙戊酸联合拉莫三嗪治疗癫痫的疗效

目的探索小剂量的丙戊酸联合拉莫三嗪治疗癫痫的临床治疗效果。方法进行分组研究,对照组和观察组所选取的研究对象是本院在2018年2月-2019年2月收治的90例癫痫患者,每组患者各45例,观察组采用小剂量的丙戊酸联合拉莫三嗪进行治疗,对照组采用丙戊酸进行治疗,分析两组患者的癫痫发作次数、癫痫持续时间、临床症状好转时间及总有效率。结果观察组患者癫痫发作次数、癫痫持续时间和临床症状好转时间明显均优于对照组,观察组患者比对照组患者总有效率高,观察组总有效率为84.4%,对照组总有效率为62.2%,差异有统计学意义(P <0.05)。结论对癫痫患者的治疗,小剂量的丙戊酸联合拉莫三嗪提高了癫痫患者的治疗总有效率,具有显著疗效。