生脉散防治心房纤颤的作用机制及网络药理学分析

目的:基于网络药理学方法探讨生脉散治疗心房纤颤的作用靶点和相关信号通路并探讨其作用机制。方法:运用中药系统药理学成分分析平台(bioinformatics analysis tool for molecular mechanism of TCM,BATMAN-TCM)数据库获取生脉散的化学成分及作用靶标基因,通过GeneCards,OMIM,DisGeNET数据库收集心房纤颤的靶标基因。将两者取交集后得到生脉散-心房纤颤靶基因交集,运用STRING构建蛋白质间相互作用网络,并将结果进行网络可视化展示。将药物-疾病交集基因导入DAVID6.8数据库,进行基因本体(gene ontology,GO)分析和基于京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Geomes,KEGG)通路富集分析。结果:生脉散干预房颤的有效活性成分159个,药物靶点与疾病靶点交集后获得206个共有靶点,PPI蛋白互作网络分析发现AKT1,TP53,PRKACA,IL-1B,TNF,INS,PPAR,RXR,F2,CACAN1C,PKC等是生脉散治疗房颤的核心靶点。GO富集分析确定了175个条目(P0.05),其中生物过程主要心脏传导调节心率、动作电位时膜去极化等;分子功能主要包括电压门控钙通道、类固醇激素受体活性、肾上腺素结合等,在细胞组成方面,主要包括钠、钾、钙通道复合物等。KEGG通路富集分析确定了100条相关信号通路,主要有cGMP/PKG信号通路,cAMP信号通路,血清素能突触,肾素分泌,钙信号通路等。结论:生脉散治疗心房纤颤具有多途径、多靶点作用的特点。该研究初步探讨了其作用的关键靶点及涉及的生物学过程和信号通路,为生脉散治疗心房纤颤后续的实验研究提供一定的参考。     

Endovascular deep brain stimulation: Investigating the relationship between vascular structures and deep brain stimulation targets

BackgroundEndovascular delivery of current using ‘stentrodes’ – electrode bearing stents – constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date.ObjectiveTo establish the relationships between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS.MethodsNeuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed.ResultsSix out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0–17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue.ConclusionsWhile several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.     

左金丸抗幽门螺杆菌感染的分子网络调控机制研究

目的基于网络药理学和生物信息学方法探究左金丸抗幽门螺杆菌(Hp)感染的分子网络调控机制。方法通过中药系统药理学数据库和分析平台(TCMSP)检索左金丸化学成分,筛选并预测其入血活性成分和作用靶点,检索疾病数据库中与Hp感染相关的作用靶点,构建左金丸成分靶点与疾病靶点的交互网络,获得左金丸抗Hp的特征性基因;通过DAVID6.8数据库对上述特征性基因进行GO功能富集和KEGG通路富集分析;利用Cytohubba筛选出左金丸抗Hp感染的关键靶点。结果通过TCMSP筛选、预测得到左金丸32个入血活性成分和197个作用靶点。GO分析共得到199条富集结果,其中生物过程包含炎症反应、RNA信号转录、信号传导等152条,细胞组分包含细胞核、细胞外基质、蛋白复合物等19条,分子功能包含细胞因子活性、DNA结合、ATP结合等28条。KEGG分析结果显示,Jak-STAT信号通路、T细胞受体信号通路、细胞周期信号通路、Wnt信号通路等65条通路与左金丸抗Hp感染密切相关。经Cytohubba筛选得到CXCL8、IL10、IL4、VEGFA、MMP9等10个关键基因。结论左金丸抗Hp感染具有多成分、多靶点、多通路协同作用的特点,可为其活性成分研究和抗Hp药效及机制研究提供依据。     

基于网络药理学和分子对接技术的款冬花在清肺排毒汤治疗新型冠状病毒肺炎（COVID-19）中的作用分析

目的采用网络药理学和分子对接法分析款冬花在清肺排毒汤治疗新型冠状病毒肺炎(COVID-19)中发挥的作用。方法基于课题组前期研究,确定款冬花中的主要成分。采用SwissTargetPrediction和BATMAN-TCM数据库对款冬花主要化学成分的潜在靶点进行整理;在GenCLiP 3和GeneCard数据库搜索COVID-19相关靶点,运用Cytoscape 3.7.1软件绘制款冬花成分-靶点-疾病网络图;使用String数据库构建靶点PPI网络;通过DAVID数据库进行GO富集分析和KEGG通路富集分析;将各成分与新型冠状病毒(SARS-CoV-2)3CL水解酶和血管紧张素转化酶II(ACE2)进行分子对接。结果款冬花治疗COVID-19的化合物-靶点-疾病网络包含化合物14个、靶点104个、疾病4个。GO功能富集分析得到GO条目444个(P0.05),其中包括生物过程(BP)条目325个、细胞组成(CC)条目44个、分子功能(MF)条目75个。KEGG通路富集筛选得到94条信号通路(P0.05)。分子对接结果显示异绿原酸B(3,4-dicaffeoylquinicacid)和异绿原酸C(4,5-dicaffeoylquinic acid)与蛋白的亲和力要优于瑞德西韦。结论款冬花中主要化合物能通过与SARS-Co V-2 3CL水解酶和ACE2结合,作用于多靶点调节多条信号通路,从而发挥对COVID-19的防治作用。     

1 H-MRS对低级别和高级别脑胶质瘤鉴别诊断的作用及病理级别相关性的研究

目的 分析脑胶质瘤的氢质子磁共振波谱（proton magnetic resonance spectroscopy，^1H—MRS）表现及其临床意义；探讨脑胶质瘤的^1H—MRS特点与其病理级别相关性。资料与方法 搜集经临床手术、病理证实的脑胶质瘤36例，按照WHO诊断标准分成两组：低级别脑胶质瘤组、高级别脑胶质瘤组。所有患者在术前行^1H—MRS检查。均在MR非增强成像的基础上获得。使用Siemens Sonata 1．5T超导磁共振扫描仪，多体素扫描，点分辨表面线圈法，检测不同区域代谢物变化。结果 脑胶质瘤的^1H—MRS表现：肌酸（Cr）轻度下降，N-乙酰天门冬氨酸（NAA）显著下降。胆碱（Cho）显著增高。低级别、高级别脑胶质瘤的肿瘤组织分别和对侧正常脑组织的NAA／Cr、Cho／Cr、NAA／Cho比值存在非常显著性差异（P〈0．01）；低级别脑胶质瘤和高级别脑胶质瘤的肿瘤组织的NAA／Cr、Cho／Cr、NAA／Cho比值存在显著性差异（P〈0．05）。脑胶质瘤的NAA／Cho、Cho／Cr、NAA／Cr比值与病理级别相关，其中NAA／Cho和Cho／cr比值反映肿瘤级别较稳定；NAA／Cr、NAA／Cho比值存在负相关关系（相关系数rs分别为-0．663，-0．851），Cho／Cr比值存在正相关关系（相关系数rs为0．858）。结论 ^1H—MRS与MRI相结合能提高脑胶质瘤术前诊断的准确性。^1H-MRS可评价脑胶质瘤的分级，反映脑胶质瘤代谢特性以及肿瘤生长潜能。     

脑静脉畸形的MRI表现及其诊断价值

目的 探讨脑静脉畸形的MRI表现，评价各成像序列的诊断价值。资料与方法 搜集经临床手术证实的脑静脉畸形8例进行回顾性分析，所有患者均进行了常规MRI平扫及3D-MOTSA MRA检查。6例行Gd-DTPA增强T1WI，其中3例行3D-MOTSA增强MRA检查。结果 小脑4例，额叶、顶叶、枕叶共4例。5例MRI平扫引流静脉为长T1短T2流空信号，3例呈长T1低信号、长T2高信号。扩张的髓静脉为网状及条状长T1低信号、长T2高信号，增强扫描呈“海蛇头”样改变，即多条髓静脉呈辐射状汇入粗大的引流静脉。3D-MOTSA MRA检查显示部分引流静脉，髓静脉显示较少。3D-MOTSA增强MRA检查引流静脉全程显示，髓静脉显示数目多。结论 MRI能明确诊断脑静脉畸形的合并症，弥补脑血管造影的不足，3D-MOTSA增强MRA检查可取代脑血管造影。     

重型颅脑损伤的手术治疗

目的探讨重型颅脑损伤梯度减压的手术方法对预防术中脑膨出、降低死亡率及致残率的效果。方法对100例重型颅脑损伤患者采用分次减压手术方式及去骨瓣后，硬膜与颞肌筋膜瓣减张缝闭硬膜切口方法。结果40例脑肿胀患者术中脑嘭出6例占15．0％，死亡19例占47．5％；60例脑内血肿病人未发生脑膨出，死亡12例占20％。结论脑外伤后脑血管调节麻痹及血肿压迫继发脑水肿易造成脑膨出.术中分次减压降低了骨窗部位脑组织的顺应性，从而降低了局部的压力梯度，避免脑血管急性扩张，能有效防止脑膨出，降低死亡率及致残率。     

A case of acute heart failure associated with Guillain-Barré syndrome

Abstract Guillain-Barré syndrome (GBS) is a disease of the peripheral nervous system, which is caused by aberrant immune responses directed against some components of peripheral nerves. GBS is rarely accompanied by cardiovascular involvement. We describe a case of acute neuropathy complicated by sudden heart failure and left ventricular dysfunction which had a presumably neurogenic origin. Pathogenesis of acute heart failure is probably due to transitorial stunned myocardium and neurogenic cardiac injury. We show a rare case of transitorial and acute cardiac dysfunction by echocardiography and laboratory markers of heart failure.     

深低温对全脑缺血性损伤的保护作用

国际上把低温划分为轻度低温(33～35℃),中度低温 (28～32℃),深度低温(17～27℃)和超深度低温(2～16℃)。低温已经被大量动物试验和临床实践证实具有脑保护作用,但同时也存在心律失常,凝血功能障碍,免疫抑制等全身多系统副作用,产且温度越低,副作用越明显。日前国内外已经有大量的试验证实深低温对全脑缺血的脑保护作用,它能明显增加脑组织对缺血的耐受性,本文将就深低温对全脑缺血性损