基于网络药理学和实验验证研究柴胡疏肝散治疗慢性萎缩性胃炎的作用机制＊

目的 通过网络药理学的方法进行预测，再深一步进行动物实验验证来研究柴胡疏肝散治疗CAG的作用机制。方法 首先在TCMSP数据库中检索柴胡疏肝散的所有活性成分与药物靶点；通过收集PharmGkb、OMIM、GeneCards和DrugBank数据库中收录的慢性萎缩性胃炎的相关靶点。将药物靶点与疾病靶点进行映射筛选出交集靶点，将得到的交集靶点构建PPI网络与活性成分-共同靶点网络，并对其进行GO和KEGG富集分析。最后利用Vina软件进行分子对接实验验证，并通过免疫印迹法验证柴胡疏肝散对两种受体蛋白EGFR和STAT1的影响。结果 最终筛选得到柴胡疏肝散活性成分104个，潜在靶点238个，与慢性萎缩性胃炎的交集靶点52个；GO与KEGG富集分析分别得到2166条目和148条目，主要涉及到JAK-STAT信号通路、TNF信号通路、HIF-1信号通路等；分子对接结果显示EGFR、STAT1两个靶点能够与核心活性成分能够自发结合成较为稳定的构像；免疫印迹法实验证明柴胡疏肝散能够降低大鼠胃黏膜组织EGFR和STAT1蛋白表达。结论 通过网络药理学和实验验证，发现柴胡疏肝散可能通过调节EGFR和STAT1蛋白表达来共同调控胃黏膜细胞增殖与凋亡，进而发挥着治疗慢性萎缩性胃炎的效果，为深入进行柴胡疏肝散治疗慢性萎缩性胃炎的作用机制研究提供新思路和新方法。     

Quantification of myocardial fibrosis using noninvasive T2-mapping magnetic resonance imaging: Preclinical models of aging and pressure overload

Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T₂-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T₂-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T₂-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T₂ relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T₂ was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T₂ relaxation time was derived (R² = 0.98): T₂ (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T₂-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T₂-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.     

基于网络药理学和分子对接技术探讨黄芪干预腹膜纤维化的机制

目的 运用网络药理学方法及分子对接技术探讨黄芪干预腹膜纤维化的可能机制。方法 利用中药系统药理学数据库及分析平台(TCMSP)检索黄芪的主要化学成分及靶点,并补充文献报道相关药理作用的成分作为潜在活性成分。以"peritoneal fibrosis"为关键词分别在OMIM、Genecards获取目前已知的与腹膜纤维化相关的疾病靶点,后取两者的交集靶点;对交集基因通过STRING数据库与Cytoscape 3.7.2软件构建"药物-成分-靶点-疾病"网络及蛋白互作(PPI)网络并筛选核心网络。基于R软件使用Bioconductor生物信息软件对核心靶点进行GO及KEGG富集分析,最终采用AutoDock软件将主要有效成分与核心靶点进行分子对接,得出其结合能力。结果 筛选出20个黄芪活性成分及文献报道有相关药理作用4个, 457药物作用靶点,与674个腹膜纤维化病靶点取交集,得到86个共同靶点。GO功能富集分析提示黄芪拮抗腹膜纤维化主要参与了蛋白激酶B信号转导的调节、细胞对化学的应激反应、炎症反应的调节等通路; KEGG通路富集分析主要涉及调控肿瘤、磷脂酰肌醇-3-羟激酶-蛋白激酶B(PI3K-Akt)、晚期糖基化终末产物/晚期糖基化终末产物受体(AGE-RAGE)、人类巨细胞病毒感染、HIF-1信号通路等;分子对接结果显示关键靶点与活性成分具有较好的结合能力。结论 黄芪治疗腹膜纤维化的分子机制,可能与抑制炎症及氧化应激反应、调节多种信号通路等相关。     

某高校新生体检结果分析

目的 分析某高校入学新生的体检结果,为制定健康管理措施提供依据。方法 开展某高校入学新生体检(内科、外科、五官科、实验室检查),对血压、肝功与血脂、体质指数、视力、脊柱侧弯等结果进行分析。结果 共调查男生357人,女生641人。高血压患病率1.80%(男2.24%、女1.56%),血脂升高率14.83%(男15.97%、女14.20%),转氨酶升高率4.81%(男8.12%、女2.96%),超重率17.64%(男24.93%、女13.97%),肥胖率7.62%(男12.32%、女4.99%),视力不良率79.36%(男73.67%、女82.53%),脊柱侧弯率1.60%(男1.12%、女1.87%)。不同性别的体质量组构成、血压分型构成、视力不良率差异均有统计学意义(P<0.05);不同体质量组的收缩压升高率、血脂升高率、转氨酶升高率、脊柱侧弯率差异均有统计学意义(P<0.05);超重和肥胖组的收缩压升高率、血脂升高率高于其他组;肥胖组的转氨酶升高率高于其他组;轻体质量组的脊柱侧弯率高于其他组。结论 大学新生的视力不良率和非正常体质量率较高,高血压、血脂异常、肝功异常、脊柱侧弯检出率较低,女生的健康状况优于男生。应重视大学生的健康状况,制定综合干预措施,做好学生健康管理工作。     

Estimation of phase signal change in neuronal current MRI for evoke response of tactile detection with realistic somatosensory laminar network model

Magnetic field generated by neuronal activity could alter magnetic resonance imaging (MRI) signals but detection of such signal is under debate. Previous researches proposed that magnitude signal change is below current detectable level, but phase signal change (PSC) may be measurable with current MRI systems. Optimal imaging parameters like echo time, voxel size and external field direction, could increase the probability of detection of this small signal change. We simulate a voxel of cortical column to determine effect of such parameters on PSC signal. We extended a laminar network model for somatosensory cortex to find neuronal current in each segment of pyramidal neurons (PN). 60,000 PNs of simulated network were positioned randomly in a voxel. Biot–savart law applied to calculate neuronal magnetic field and additional phase. The procedure repeated for eleven neuronal arrangements in the voxel. PSC signal variation with the echo time and voxel size was assessed. The simulated results show that PSC signal increases with echo time, especially 100/80 ms after stimulus for gradient echo/spin echo sequence. It can be up to 0.1 mrad for echo time = 175 ms and voxel size = 1.48 × 1.48 × 2.18 mm³. With echo time less than 25 ms after stimulus, it was just acquired effects of physiological noise on PSC signal. The absolute value of the signal increased with decrease of voxel size, but its components had complex variation. External field orthogonal to local surface of cortex maximizes the signal. Expected PSC signal for tactile detection in the somatosensory cortex increase with echo time and have no oscillation.     

甘肃省和政县农村老年性白内障防盲项目的卫生经济学评价研究

目的 对2014-2016年在甘肃省和政县开展的白内障综合防盲干预项目进行卫生经济学评价。设计 横断面调查。 研究对象 甘肃省和政县2014-2016年老年性白内障手术前407例患者及术后半年109例患者。方法 对所有调查对象进行卫生经济学问卷调查。通过净效益法、成本效益分析法和成本效果分析法评价项目产生的经济效益和总成本。主要指标 直接成本、间接成本、直接经济效益、间接经济效益、总成本、总效益、净效益、成本效益比、成本效果比。结果 2014-2016年项目期间甘肃省和政县白内障所致总体疾病经济负担为2142.28万元。白内障手术产生的总效益为3398424.98元，总成本为2939125.20元，净效益为459299.78元，效益成本比为1.16:1。项目每投入1万元可降低50岁以上白内障患者导致的0.027%的致盲率和0.164%致残率；项目每降低1%的50岁以上白内障患者的盲率，需投入36.47万元；每降低1%50岁以上白内障患者的残率，需投入6.11万元。结论 在甘肃省和政县开展的老年性白内障防盲综合干预项目具有较好的产出回报比和较高的防盲技术效率。（眼科，2020，29： 298-303）     

顶天立地服务需求 注重内涵创建一流——首都医科大学建校60周年教育教学与人才培养成果回顾

首都医科大学通过60年辛勤耕耘、精益求精，秉承“顶天立地”的人才培养理念，为社会培养了大批高水平的学术型与应用型医药卫生人才。回顾学校60年来本专科教育、全科医学教育、国际教育、研究生教育的人才培养成果，以总结经验并鼓舞全体首医人进一步求真务实、凝心聚力、积极进取、追求卓越，努力将学校建设成为国际一流的研究型医科大学。