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。     

Association Study of Matrix Metalloproteinases Gene Polymorphisms with Susceptibility to Rheumatoid Arthritis: A Meta-Analysis

Objective: Association of matrix metalloproteinases (MMPs) gene polymorphisms with rheumatoid arthritis is controversial. We conduct a meta-analysis to clarify this dispute.

Methods: We systematically searched the electronic PUBMED, EMBASE and CNKI databases for research articles about MMPs (MMP-1, MMP-2, MMP-3, MMP-9) gene polymorphisms and rheumatoid arthritis (RA) up to January 2015. According to the heterogeneity, fixed-effects or random-effects models were used to calculate crude odds ratios (ORs) and 95% confidence intervals (95% CIs).

Results: A total of 11 articles involving 2143 cases and 2049 controls were included in this meta-analysis. Overall, no significant associations were observed between MMP-1-1607 1G/2G polymorphism and RA. Stratification by ethnicity, no significant associations were observed in Caucasian populations. Similarly, no significant associations were observed between MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms and RA in overall and Caucasian populations, respectively. However, a weak association was found between MMP-2-1306 C/T polymorphism and RA (C vs. T, OR?=?0.813, 95%CI?=?0.694–0.953, p?=?0.010) in overall populations.

Conclusions: The present meta-analysis suggests that MMP-1-1607 1G/2G, MMP-3-1171 5A/6A, MMP-9-1562 C/T polymorphisms are not associated with the susceptibility of RA, but MMP-2 -1306 C/T is weakly associated with susceptibility to RA. Further studies with more sample size are needed for definitive conclusions.     

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。     

孟鲁司特治疗呼吸道合胞病毒毛细支气管炎症状及反复喘息疗效研究

背景　呼吸道合胞病毒（RSV）毛细支气管炎易出现反复喘息，且下呼吸道分泌物中半胱氨酸白三烯（CysLTs）水平升高。而孟鲁司特是一种白三烯受体拮抗剂，关于其治疗RSV毛细支气管炎症状的研究相对较少。目的　探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法　2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿，随机分为治疗组、对照组。Ⅰ期，治疗组：口服孟鲁司特颗粒（4 mg）12周，1次/d；对照组：口服安慰剂12周，1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月（Ⅱ期），观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析（ITT）原则，应用全分析集（FAS）分析数据。结果　共纳入研究对象186例，治疗组92例，对照组94例。治疗组完成Ⅰ期研究的患儿为89例，对照组为90例；治疗组完成Ⅰ+Ⅱ期的患儿为84例，对照组为86例。治疗组平均依从性为97.8%（7 560/7 728），对照组平均依从性为97.4%（7 690/7 896），两组患儿平均依从性比较，差异无统计学意义（χ2=3.16，P=0.07）。在Ⅰ期研究期间，两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较，差异均无统计学意义（P>0.05）。在整个研究过程中（Ⅰ+Ⅱ期），治疗组RSV毛细支气管炎喘息复发人数少于对照组（P<0.05），治疗组喘息患儿出现2次及以上喘息比例低于对照组（χ2=5.14，P=0.02）。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组（P<0.05）。在事后亚组分析中，治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔（49.7±20.2）、（51.3±20.9）d〕多于对照组〔（36.3±20.4）、（37.8±19.3）d〕（t=2.19，P=0.03；t=2.24，P=0.03）。整个研究过程中没有患儿因不良反应退出研究，两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较，差异均无统计学意义（χ2=0.23，P=0.63；χ2=0.03，P=0.86；χ2=0.15，P=0.69）。结论　口服孟鲁司特（4 mg）12周不能改善RSV毛细支气管炎患儿呼吸道症状，但能降低患儿反复喘息发作次数。口服孟鲁司特（4 mg）有一定效果且安全。     

新型冠状病毒肺炎疫情对天津市无偿献血的影响及其对策

目的 分析新型冠状病毒肺炎(以下简称新冠肺炎)疫情对天津市无偿献血的影响.方法 回顾性分析该市2020年无偿献血人次及献血量,并与2019年献血情况进行对比;分析2020年春节前后及2019年同期的献血情况.结果 2020年捐献全血和单采血小板的总人次较2019年均下降13.03％,献血量分别下降17.60％、10.37％.2020年与2019年春节期间捐献全血和单采血小板的人次和献血量均明显下降,但2020年献血情况持续受疫情影响.2020年1-6月全血和单采血小板的献血情况较2019年同期下降较为明显,2020年7-12月的献血情况好转,与2019年同期差距减小.结论 新冠肺炎疫情对无偿献血工作提出严峻考验.常态化疫情防控期间,分析研判疫情对无偿献血工作的影响,有利于制订更有效的预防措施抗击疫情,保障临床用血.     

护理教学查房在ICU教学中的临床应用效果分析

目的探讨护理教学查房在ICU教学中的临床应用效果。方法选定2018年1月-2019年1月来本院实习的100例学生,按照教学查房方法分为对照组(50例)与观察组(50例),前者采用传统教学查房方法,后者采用针对性教学查房方法。通过出科操作考试及理论考试后,比较2组实习学生的操作考核成绩、理论考核成绩指标。结果教学结束,观察组实习学生的操作考核成绩(94.11±3.54)分、理论考核成绩(85.74±5.39)分均高于对照组实习学生(P<0.05)。结论针对性教学查房方法可有效提高实习学生的操作考核成绩、理论考核成绩,改善其教学质量。