围妊娠期小鼠胰岛细胞增殖及Survivin表达变化的研究

目的 观察围妊娠期小鼠胰岛β/α细胞量、细胞增殖、Survivin表达变化以及大鼠胰岛细胞瘤细胞株INS-1干扰Survivin表达后催乳素刺激细胞增殖的变化,探讨Survivin与妊娠期胰岛细胞扩增的关系.方法 采用免疫组化染色法检测C57 BL/6雌性小鼠非妊娠对照组（NP）和妊娠10.5、14.5、18.5 d（P10.5、P14.5、P18.5）、产后4、8 d（AP4、AP8）（每组各25只）胰岛β/α细胞量的变化.采用胶原酶消化法分离纯化小鼠胰岛,以流式细胞术检测细胞周期,实时定量聚合酶链反应及Western blotting法检测Survivin mRNA和蛋白的表达.采用脂质体转染siRNA方法干扰INS-1细胞Survivin的表达,催乳素刺激后检测细胞周期.多组数据组间比较采用单因素方差分析,两两比较采用最小差异显著性分析.结果 妊娠期胰岛β/α细胞量均显著增加,高峰在P18.5,与NP组相比,β细胞量增长2.1倍（3.84±0.38比1.81 ±0.09,t =4.75,P＜0.05）,α细胞量增长1.6倍（0.92±0.13比0.56 ±0.08,t =2.69,P＜0.05）,至AP8恢复至NP水平.妊娠期小鼠胰岛细胞增殖显著增加,高峰在P14.5,与NP组相比,增殖指数增长2.7倍（23.07±1.88比7.72±1.12,t=10.89,P＜0.05）,产后恢复正常.Survivin mRNA表达水平在妊娠期明显增高,高峰在P14.5,与NP组相比,增长6.7倍（6.69±1.61比1.00 ±0.00,t =4.57,P＜0.05）,产后恢复正常.P10.5时Survivin蛋白开始表达,高峰在P14.5,与P10.5相比增长3.6倍（3.63±0.26比1.00±0.00,t=9.98,P＜0.05）,P18.5时表达逐渐下降,P20.5时表达消失.催乳素可显著刺激INS-1细胞增殖,而siRNA干扰INS-1细胞Survivin表达后,细胞增殖受阻.结论 妊娠期小鼠胰岛细胞出现明显扩增,并伴有Survivin的动态表达.Survivin介导催乳素刺激的胰岛β细胞扩增作用.     

心肌梗死二级预防生活方式和膳食指南/共识的质量评价与内容分析

背景　健康的生活方式和膳食作为心肌梗死二级预防的重要组成部分,可有效降低再发心肌梗死的危险,改善心肌梗死患者预后。有必要检索相关高质量证据进行总结,以促进心肌梗死二级预防的临床实践。目的　系统检索并筛选当前国内外心肌梗死二级预防生活方式和膳食指南/共识,对纳入指南/共识的质量进行严格评价,提取、分析并综合相关指南推荐意见,为心肌梗死二级预防的生活方式和膳食指导提供最佳干预方案,为促进证据的临床转化提供理论依据。方法　计算机系统检索各专业指南网站和中英文数据库,包括国际指南协作网（GIN）、英国国家卫生与临床优化研究所（NICE）、苏格兰校际指南协作网（SIGN）、美国国立指南库（NGC）、澳大利亚临床实践指南数据库（ACPG）、新西兰指南工作组（NZGG）、世界卫生组织（WHO）、PubMed、中国知网（CNKI）、万方数据知识服务平台（WanFang Data）、维普网（VIP）,有关心肌梗死的指南、规范及专家共识,或内容涉及心肌梗死预防生活方式或膳食指导的相关指南/共识,并请心血管方面专家进行指南推荐及追溯参考文献补充检索相关指南,检索时间为2013-01-01至2018-12-31,并于2019年6月完成检索。采用临床指南研究与评估系统Ⅱ（AGREEⅡ）对指南/共识进行质量评价,归纳总结指南/共识中生活方式和膳食指导的推荐意见。结果　共纳入来自美国、英国、澳大利亚、新西兰、中国的10篇指南/共识,其中A级1篇,B级7篇,C级2篇。汇总49条推荐意见,其中生活方式涵盖戒烟、控制饮酒、体质量管理、睡眠管理、情绪管理、体育锻炼6个方面;膳食推荐涵盖饮食习惯、营养结构、膳食模式及膳食目标等相关内容。结论　纳入指南/共识的总体质量较高,但还需进一步规范指南/共识的制定和报告流程;心肌梗死指南/共识中有关生活方式和膳食推荐的内容涉及范围较广,为临床实践提供了证据支持。临床医护人员在进行证据转化时应基于最佳证据,将研究证据充分整合到卫生保健提供中,在综合考虑证据应用的促进及阻碍因素、患者的价值观和偏好等后,选择最佳证据进行临床实践;患者指南的制定者应进一步考虑患者等利益相关者的意见,并更具针对性地细化推荐意见,以最终改善患者结局。     

Assessing the practice of data quality evaluation in a national clinical data research network through a systematic scoping review in the era of real-world data

ObjectiveTo synthesize data quality (DQ) dimensions and assessment methods of real-world data, especially electronic health records, through a systematic scoping review and to assess the practice of DQ assessment in the national Patient-centered Clinical Research Network (PCORnet).Materials and MethodsWe started with 3 widely cited DQ literature—2 reviews from Chan et al (2010) and Weiskopf et al (2013a) and 1 DQ framework from Kahn et al (2016)—and expanded our review systematically to cover relevant articles published up to February 2020. We extracted DQ dimensions and assessment methods from these studies, mapped their relationships, and organized a synthesized summarization of existing DQ dimensions and assessment methods. We reviewed the data checks employed by the PCORnet and mapped them to the synthesized DQ dimensions and methods.ResultsWe analyzed a total of 3 reviews, 20 DQ frameworks, and 226 DQ studies and extracted 14 DQ dimensions and 10 assessment methods. We found that completeness, concordance, and correctness/accuracy were commonly assessed. Element presence, validity check, and conformance were commonly used DQ assessment methods and were the main focuses of the PCORnet data checks.DiscussionDefinitions of DQ dimensions and methods were not consistent in the literature, and the DQ assessment practice was not evenly distributed (eg, usability and ease-of-use were rarely discussed). Challenges in DQ assessments, given the complex and heterogeneous nature of real-world data, exist.ConclusionThe practice of DQ assessment is still limited in scope. Future work is warranted to generate understandable, executable, and reusable DQ measures.     

王念孙释《广雅》医学词汇

三国时代魏张揖编著的《广雅》中收录有医学词汇,清代训诂大家王念孙所著的《广雅疏证》是《广雅》最好的注本,最注重以声音通训诂、系联同源词,以此对词义进行训释,沟通词际关系。以《广雅》中收录的医学词汇为语料,挖掘王念孙在《广雅疏证》中训释医词时所使用的破通假、系同源、沟通普通词汇与医学词汇等理论、方法,并结合王念孙在校勘《广雅》文本中存在的误字、脱文、衍文等问题时采用的校勘学方法,从中探索当今医学词汇研究可以借鉴的释词方法。     

不同临床分型的新型冠状病毒肺炎患者影像学表现

目的 探讨不同临床分型的新型冠状病毒肺炎（COVID-19）的影像学表现。方法 回顾性分析71例COVID-19患者的电子计算机断层扫描（computed tomography,CT）影像资料,分析普通型与重型及危重型患者的临床特点、影像学特点、优势分布以及出现好转时间,并进行统计学分析。结果 71例患者中,轻型12例,普通型45例,重型及危重型14例。临床表现方面,重型及危重型（6/14,42.9%;4/14,28.6%）伴乏力、胸闷及呼吸困难较轻型（0;0）及普通型（2/45,4.4%;0）明显,差异有统计学意义（P值分别为0.001,0.002）;普通型（30/45,66.7%）、重型及危重型（9/14,64.3%）C反应蛋白升高较轻型（2/12,16.7%）明显,差异有统计学意义（P=0.005）。CT表现,病变累及范围超过3个肺叶数：重型及危重型（13/14,92.9%）明显高于普通型（26/45,57.8%）;重型及危重型（12/14,85.7%）病变分布于两肺外周及中心多于普通型（20/45,44.4%）;病变表现为实变、病变内伴小叶间隔增厚,重型及危重型均多于普通型;以上表现两组相比,差异均有统计学意义（P值分别为0.036、0.007、0.004、0.002）。对22例患者进行随访,CT表现达高峰及病情出现好转多发生在发病10 d后（40.9%,45.5%）。结论 普通型与重型及危重型COVID-19患者胸部CT在发病部位、病变密度、实变程度等方面具有不同特征,多数COVID-19患者多在发病10 d后好转。     

牙周基础治疗对2型糖尿病相关性牙周炎患者血糖控制的Meta分析

目的系统评价牙周基础治疗对2型糖尿病相关性牙周炎患者血糖控制的影响,探讨牙周基础治疗在糖尿病治疗中的具体作用。方法计算机检索Cochrane图书馆对照试验注册中心、Medline、EMbase、SIGLE、GreyNet、NTIS、中国生物医学文献数据库、中文科技期刊全文数据库、中国期刊全文数据库和万方数据库,查找有关牙周基础治疗对糖尿病血糖控制影响的研究。检索时限均为1991-2011年4月31日。均由2名评价者独立选择试验、提取资料和评估方法学质量,然后采用RevMan 5．1软件对资料进行Meta分析。纳入7个研究,共计471例受试患者。结果牙周基础治疗能明显降低2型糖尿病相关性牙周炎患者糖化血红蛋白的水平,组间差异有统计学意义（95％CI：-0．94—0．22,P=0．001）。治疗组牙周袋探诊深度低于对照组,组间差异也有统计学意义（95％CI：-2．26～0．69,P=0．0002）。结论牙周基础治疗有利于2型糖尿病相关性牙周炎患者总体血糖水平的控制。     

MiR-195 inhibits proliferation and growth and induces apoptosis of endometrial stromal cells by targeting FKN

MiR-195, which exhibits a proliferation-inhibiting role in different tumors, has been reported to be down-regulated in the ectopic endometrium. The aim of this study was to determine the impact of miR-195 on the biological characteristic of the endometrial stromal cells (ESCs). MiR-195 has been presumed to target the 3’-untranslated regions (3’-UTR) of Fractalkine (FKN), which also plays important roles in endometriosis. Fluorescence reporter assays showed that miR-195 effectively binds to the 3’-UTR of FKN. The normal ESCs showed a significant higher miR-195 expression than that of eutopic and ectopic ESCs associated with endometriosis, while the FKN expression showed opposite results. MiR-195 mimics inhibited proliferation and growth and induced apoptosis of eutopic ESCs, and these effects were abolished by FKN-siRNA. miR-195 could decrease the expression of survivin, matrix metalloproteinase-9 (MMP9) and up-regulate the expression of CD82, tissue inhibitor of metalloproteinase 1 (TIMP1) and TIMP2 of eutopic ESCs by targeting FKN. Our study has demonstrated for the first time that miR-195 plays important roles in regulating the functions of ESCs through targeting FKN. The information may be useful for developing a new therapeutic strategy for endometriosis.     

Role of adenosine A2A receptor in organ-specific vascular reactivity following hemorrhagic shock in rats

Background

Previous studies have demonstrated differences among organs in terms of shock-induced vascular reactivity and a role for adenosine A2A receptors (A2ARs) in protection against ischemia/reperfusion injury. However, the contributions of A2ARs to organ-specific vascular reactivity and the protection of vascular responsiveness following shock are currently unknown.

Methods

We investigated the role of A2ARs in different arteries, including the left femoral artery (LFA), thoracic aorta (TA), superior mesenteric artery (SMA), right renal artery (RRA), pulmonary artery (PA), and middle cerebral artery (MCA), in hemorrhagic-shock rats.

Results

The vascular reactivities of the LFA, SMA, RRA, and MCA increased slightly during early shock and then gradually decreased, whereas those of the PA and TA decreased from the start of shock. Different blood vessels lost vascular reactivity at different rates compared with controls; the LFA had the highest rate of loss (64.51%), followed by the SMA (44.69%), TA (36.06%), PA (37.83%), and RRA (32.33%), whereas the MCA had the lowest rate (18.45%). The rate of loss of vascular reactivity in the different vessels was negatively correlated with A2AR expression levels in normal and shock conditions. The highly selective A2AR agonist CGS 21680 significantly improved vascular reactivity, hemodynamic parameters, and animal survival, whereas the specific antagonist SCH58261 further decreased the shock-induced reduction in vascular reactivity and hemodynamic parameters.

Conclusions

A2ARs are involved in the regulation and protection of vascular reactivity following shock. A2AR activation may have a beneficial effect on hemorrhagic shock by improving vascular reactivity and hemodynamic parameters.     

长链非编码RNA 母系表达基因3调控miR-34a对糖尿病视网膜病变Müller细胞活化及炎症因子分泌的影响

目的　探讨母系表达基因3（maternally expressed gene 3,MEG3）对糖尿病视网膜病变（DR）Müller细胞的活化及炎症因子分泌的影响及机制。方法　高脂饮食联合链脲佐菌素腹腔注射构建小鼠DR体内模型。高糖刺激人视网膜Müller细胞株MIO-M1构建DR体外模型。免疫荧光化学染色及Western blot检测小鼠视网膜及Müller细胞中胶质纤维酸性蛋白（GFAP）的表达。Western blot及酶联免疫吸附实验（ELISA）检测小鼠视网膜及细胞培养基上清中血管内皮生长因子（VEGF）蛋白的表达。ELISA检测小鼠视网膜及细胞培养基上清中IL-1β蛋白的表达。分别或同时向Müller细胞中转染pcDNA-MEG3及miR-34a mimic对其表达进行干预。qRT-PCR检测MEG3 mRNA及miR-34a表达。结果　与正常对照组小鼠比较,DR组小鼠视网膜中GFAP、VEGF及IL-1β蛋白表达均增多（均为P<0.05）,MEG3 mRNA表达降低(P<0.01)。与对照组比较,高糖组Müller细胞中MEG3 mRNA表达降低(P<0.01),而GFAP、VEGF及IL-1β蛋白表达均升高（均为P<0.05）。与高糖组比较,高糖+pcDNA-MEG3组中GFAP、VEGF及IL-1β蛋白表达均降低（均为P<0.05）。与正常对照组比较,DR组小鼠视网膜及高糖刺激的Müller细胞中miR-34a表达均升高(均为P<0.05)。与pcDNA组比较,pcDNA-MEG3组中miR-34a表达减少(P<0.01)。与pcDNA+NC mimic组比较,pcDNA+miR-34a mimic组中GFAP、VEGF及IL-1β蛋白表达均升高（均为P<0.05）,而pcDNA-MEG3+NC mimic组中GFAP、VEGF及IL-1β蛋白表达均减少（均为P<0.05）。与pcDNA-MEG3+miR-34a mimic组比较,GFAP、VEGF及IL-1β蛋白表达水平均升高（均为P<0.05）。结论　MEG3在DR小鼠视网膜及高糖刺激的Müller细胞中表达均降低,其可通过负向调控miR-34a抑制Müller细胞活化及炎症因子的分泌。过表达MEG3可能成为DR治疗的新靶点。