留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

微小RNA-21在肺动脉高压发病机制中的研究进展

金旗 罗勤 赵智慧 柳志红

金旗, 罗勤, 赵智慧, 柳志红. 微小RNA-21在肺动脉高压发病机制中的研究进展[J]. 协和医学杂志, 2020, 11(4): 430-438. doi: 10.3969/j.issn.1674-9081.2020.04.013
引用本文: 金旗, 罗勤, 赵智慧, 柳志红. 微小RNA-21在肺动脉高压发病机制中的研究进展[J]. 协和医学杂志, 2020, 11(4): 430-438. doi: 10.3969/j.issn.1674-9081.2020.04.013
Qi JIN, Qin LUO, Zhi-hui ZHAO, Zhi-hong LIU. MicroRNA-21 in the Pathogenesis of Pulmonary Hypertension[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(4): 430-438. doi: 10.3969/j.issn.1674-9081.2020.04.013
Citation: Qi JIN, Qin LUO, Zhi-hui ZHAO, Zhi-hong LIU. MicroRNA-21 in the Pathogenesis of Pulmonary Hypertension[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(4): 430-438. doi: 10.3969/j.issn.1674-9081.2020.04.013

微小RNA-21在肺动脉高压发病机制中的研究进展

doi: 10.3969/j.issn.1674-9081.2020.04.013
基金项目: 

国家自然科学基金 81641005

详细信息
    通讯作者:

    柳志红  电话:010-88396985, E-mail:liuzhihong_fw@263.net

  • 中图分类号: R541.5

MicroRNA-21 in the Pathogenesis of Pulmonary Hypertension

More Information
  • 摘要: 微小RNA-21(microRNA-21, miRNA-21)是一种小的内源性非编码RNA, 可广泛表达于多种组织, 在多种疾病的发生和发展中发挥重要作用。近年来, miRNA-21在肺动脉高压中的作用受到广泛关注, 而其在各亚型中的角色不尽相同甚至相互矛盾。本文综述近年来miRNA-21在肺动脉高压中的研究进展, 从miRNA-21参与的病理生理过程、miRNA-21在各种类型肺动脉高压中的作用、当前研究的不足等方面加以综述, 以期明确miRNA-21在肺动脉高压发病机制中的作用, 为未来研究提供参考。
    利益冲突  无
  • 表  1  微小RNA-21在肺动脉高压中的表达及其功能

    研究者 条件和物种 样本类型 变化 暴露时间 内参 靶基因 功能
    Sarkar等[2, 49] 3%低氧 正常人PASMC 3倍↑
    2倍↑
    6h
    24h
    U6 PDCD4 ↓Sprouty 2↓
    PPAR-α↓BEST3↓
    促进细胞增殖和迁移
    Caruso等[23-24] 低氧大鼠 - 2/7/21 d U87或RNU-48 NA NA
    常氧和低氧大鼠 PAF/PASMC - 24h
    MCT大鼠 肺组织 2/7/21 d
    IPAH患者 肺和血清 NA
    Parikh等[16, 50] PAH患者 小于200
    μm的肺血管
    NA RNU48 RhoB/Rho激酶活
    性↓
    抑制血管生成,
    促进血管扩张
    低氧 PAEC 1.8倍↑
    MCT大鼠 肺组织 5.2倍↑
    SU5416+10%低氧小鼠 肺组织 2倍↑
    IL-6转基因小鼠 肺组织 4.2倍↓
    Drake等[12, 28-30] BMP刺激 正常人PAEC/
    PASMC
    2~3倍↑ 24h 5S核糖体RNA NA NA
    HPAH患者的
    PAEC/PASMC
    抗增殖
    Yang等[4] 10%低氧小鼠 肺/肺动脉远端 2~3周 NA BMPR2↓, WWP1↓,
    SATB1↓, YOD1↓
    促进增殖,增加
    PCNA,cyclin D1,
    Bcl-xL
    Gubrij等[51-52] MCT大鼠 右心室 5倍↑ 4~6周 NA NA NA
    4倍↑ NA
    肺动脉 6倍↑ NA
    血浆 - miRNA-16
    血浆 2~2.5倍↑ miRNA-103
    Schlosser等[53-55] MCT大鼠 血浆 1.4倍↑ 22d NA NA NA
    肺组织 3.4倍↑
    White等[13] miRNA-21过表达小鼠 肺组织 NA NA U16 PDCD4/caspase-3↓ 减少内皮细胞
    凋亡
    Parikh[34-35] HIV-PAH 血浆 NA miRNA-422b NA NA
    Iannone等[26-27] IPAH 肺组织 NA TBP DDAH1↓ NA
    %10低氧小鼠 肺组织 2周
    %2低氧 PAEC 24h
    %2低氧 PASMC - 24h
    Green等[5-7, 14-15] 10%低氧C57/BL6J
    小鼠
    肺组织 3周 9S PTEN↓ 促进细胞增殖
    %1低氧 PASMC 72h PTEN↓ 促进细胞增殖
    %1低氧 PASMC 48~72h PDCD4↓ 促进细胞增殖和
    凋亡抵抗
    Yuan等[56-57] MCT大鼠 肺和右心室 NA NA Arhgap24↓ 促进细胞增殖
    Joshi等[58] SU5416+10%低氧大鼠 右心室 8/13周 U6 NA NA
    沈丽晓[9] 10%低氧大鼠 肺动脉 8周 U6 NA 促进细胞增殖
    3%低氧 PASMC 24h
    李继中[33] ASD/VSD/PDA/IPAH/
    COPD
    血浆 NA β-actin NA NA
    刘小刚[31] CHD-PAH 肺组织 - NA U6 NA NA
    曹春晖[32] CHD-PAH 血浆 NA cel-mir-39 NA NA
    Zhao等[36] PH-LHD 血清 - NA U6 NA NA
    张灿堂等[40] COPD-PH 血清 NA U6 NA NA
    ↑升高;↓降低;-无显著差异;NA未报道;PASMC:肺动脉平滑肌细胞;PDCD4:程序性细胞死亡因子4;PPAR-α:过氧化物酶体增殖因子活化受体α;BEST3:卵黄状黄斑病蛋白3;PAF:肺动脉成纤维细胞;MCT:野百合碱;IPAH:特发性肺动脉高压;PAH:动脉性肺动脉高压;PAEC:肺动脉内皮细胞;IL-6:白细胞介素-6;VHL:希佩尔-林道蛋白;BMP:骨形成蛋白;HPAH:遗传性肺动脉高压;BMPR2:骨形成蛋白受体2;WWP1:含WW结构域的E3泛素蛋白连接酶1;SATB1:核基质结合区结合蛋白质1;YOD1:泛素硫酯酶OTU1;PCNA:增殖细胞核抗原;HIV-PAH:人类免疫缺陷病毒感染相关性肺动脉高压;TBP:TATA盒结合蛋白;DDAH1:二甲基精氨酸二甲基氨基水解酶1;PTEN:第10号染色体缺失的磷酸酶及张力蛋白同源物基因;Arhgap24:Rho GTP酶激活蛋白24;ASD/VSD/PDA:房间隔缺损/室间隔缺损/动脉导管未闭;COPD:慢性阻塞性肺疾病;CHD-PAH:先天性心脏病相关性肺动脉高压;PH-LHD:左心疾病相关性肺动脉高压;COPD-PH:慢性阻塞性肺疾病相关性肺动脉高压
    下载: 导出CSV

    表  2  miRNA-21在肺动脉高压患者血液及组织标本中的表达

    研究人群 样本类型 对照组 表达 参考文献
    IPAH 肺组织和
    血清
    无IPAH的对照 [24]
    PAEC 正常人 [25]
    肺组织 健康人 [27]
    HPAH PAEC 正常人 [12]
    CHD-PAH 肺组织 自发性气胸患者 - [31]
    血浆 无PAH的CHD患者 [32]
    血浆 mPAP正常的CHD
    患者
    [33]
    HIV-PAH 血浆 无感染HIV的对照 [34]
    无PAH的HIV患者 - [35]
    PH-LHD 血浆 无PH的瓣膜性心
    脏病患者
    - [36]
    PH-HFpEF 血浆 HFpEF患者和健
    康人
    [37]
    COPD-PH 血清 单纯COPD患者和
    健康人
    [40]
    无PH的COPD患者 [41]
    CTEPH NA NA NA
    ↑升高;↓降低;-无显著差异;NA未报道;IPAH、PAEC、HPAH、CHD-PAH、PAH、HIV-PAH、PH-LHD、COPD-PH、COPD:同表 1;CHD:先天性心脏病;mPAP:平均肺动脉压;HIV:人类免疫缺陷病毒;PH-HFpEF:左心室射血分数保留的心力衰竭相关性肺动脉高压;CTEPH:慢性血栓栓塞性肺动脉高压
    下载: 导出CSV
  • [1] 吴卫华, 胡长平. MicroRNA-21在心血管疾病中的作用[J].中国临床药理学与治疗学, 2012, 17:709-714. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zglcylxyzlx201206021
    [2] Sarkar J, Gou D, Turaka P, et al. MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration[J]. Am J Physiol Lung Cell Mol Physiol, 2010, 299:L861-L871. doi:  10.1152/ajplung.00201.2010
    [3] Sarkar J, Turaka P, Gou D, et al. MiR-21 plays a role in smooth muscle cell proliferation induced by hypoxia[J]. FASEB J, 2009, 23:LB131.
    [4] Yang S, Banerjee S, Freitas A, et al. miR-21 regulates chronic hypoxia-induced pulmonary vascular remodeling[J]. Am J Physiol Lung Cell Mol Physiol, 2012, 302:L521-L529. doi:  10.1152/ajplung.00316.2011
    [5] Green DE, Murphy T, Kang B, et al. PPAR gamma ligands attenuate hypoxia-induced proliferation in vascular smooth muscle cells through modulation of miRNA-21[J]. J Investig Med, 2015, 63:449-450.
    [6] Green DE, Murphy TC, Kang BY, et al. PPARγ ligands attenuate hypoxia-induced proliferation in vascular smooth muscle cells through modulation of miRNA-21[J]. Am J Respir Crit Care Med, 2015, 191:A1982.
    [7] Green DE, Murphy TC, Kang BY, et al. PPARγ ligands attenuate hypoxia-induced proliferation in human pulmonary artery smooth muscle cells through modulation of MicroRNA-21[J]. PLoS One, 2015, 10:e0133391. doi:  10.1371/journal.pone.0133391
    [8] Zhu B, Gong Y, Yan G, et al. Down-regulation of lncRNA MEG3 promotes hypoxia-induced human pulmonary artery smooth muscle cell proliferation and migration via repressing PTEN by sponging miR-21[J]. Biochem Biophys Res Commun, 2018, 495:2125-2132. doi:  10.1016/j.bbrc.2017.11.185
    [9] 沈丽晓. 17β-雌二醇/miRNA-21信号通路抑制低氧性肺动脉高压肺血管重塑的机制研究[D].石家庄: 河北医科大学, 2017.
    [10] 沈丽晓, 袁博云, 王丽, 等. 17β-雌二醇/微小核糖核酸-21信号通路抑制低氧性肺动脉高压肺血管重构的机制研究[J].中国循环杂志, 2018, 33:1118-1123. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgxhzz201811017
    [11] Li F, Wang J, Zhu Y, et al. SphK1/S1P Mediates PDGF-Induced Pulmonary Arterial Smooth Muscle Cell Proliferation via miR-21/BMPRⅡ/Id1 Signaling Pathway[J]. Cell Physiol Biochem, 2018, 51:487-500. doi:  10.1159/000495243
    [12] Drake KM, Zygmunt D, Mavrakis L, et al. Altered MicroRNA processing in heritable pulmonary arterial hypertension:An important role for Smad-8[J]. Am J Respir Crit Care Med, 2011, 184:1400-1408. doi:  10.1164/rccm.201106-1130OC
    [13] White K, Dempsie Y, Caruso P, et al. Endothelial apoptosis in pulmonary hypertension is controlled by a microRNA/program-med cell death 4/caspase-3 axis[J]. Hypertension, 2014, 64:185-194. doi:  10.1161/HYPERTENSIONAHA.113.03037
    [14] Green DE, Murphy T, Kang B, et al. Peroxisome proliferator-activated receptor gamma enhances human pulmonary artery smooth muscle cell apoptosis susceptibility through regulation of microRNA-21 and programmed cell death 4[J]. Am J Respir Crit Care Med, 2017, 195:A2263. doi:  10.1164/ajrccm-conference.2017.195.1_MeetingAbstracts.A2263
    [15] Green DE, Murphy TC, Kang BY, et al. Peroxisome proliferator-activated receptor-γ enhances human pulmonary artery smooth muscle cell apoptosis through microRNA-21 and programmed cell death 4[J]. Am J Physiol Lung Cell Mol Physiol, 2017, 313:L371-L383. doi:  10.1152/ajplung.00532.2016
    [16] Parikh VN, Jin RC, Rabello S, et al. MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension:results of a network bioinformatics approach[J]. Circulation, 2012, 125:1520-1532. doi:  10.1161/CIRCULATIONAHA.111.060269
    [17] Pullamsetti SS, Savai R, Janssen W, et al. Inflammation, immunological reaction and role of infection in pulmonary hypertension[J]. Clin Microbiol Infect, 2011, 17:7-14. doi:  10.1111/j.1469-0691.2010.03285.x
    [18] Steiner MK, Syrkina OL, Kolliputi N, et al. Interleukin-6 overexpression induces pulmonary hypertension[J]. Circ Res, 2009, 104:236-244. doi:  10.1161/CIRCRESAHA.108.182014
    [19] Sheedy FJ. Turning 21:Induction of miR-21 as a Key Switch in the Inflammatory Response[J]. Front Immunol, 2015, 6:19.
    [20] Ranchoux B, Antigny F, Rucker-Martin C, et al. Endothelial-to-mesenchymal transition in pulmonary hypertension[J]. Circulation, 2015, 131:1006-1018. doi:  10.1161/CIRCULATIONAHA.114.008750
    [21] Kim J. MicroRNAs as critical regulators of the endothelial to mesenchymal transition in vascular biology[J]. BMB Rep, 2018, 51:65-72. doi:  10.5483/BMBRep.2018.51.2.011
    [22] 张卫芳, 熊爱珍, 吴卫华, 等.肺动脉高压时肺血管内皮间质转化相关miRNAs网络调控的生物信息学分析[J].中国药理学通报, 2016, 32:1294-1300. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgylxtb201609021
    [23] Caruso P, MacLean MR, Dempsie Y, et al. Dynamic changes in lung MiRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline[J]. Am J Respir Crit Care Med, 2010, 181:A2043.
    [24] Caruso P, MacLean MR, Khanin R, et al. Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline[J]. Arterioscler Thromb Vasc Biol, 2010, 30:716-723. doi:  10.1161/ATVBAHA.109.202028
    [25] Spiekerkoetter E, Alastalo T, Sawada H, et al. Micro RNA 21(miR-21) is a regulator of bone morphogenetic protein receptor Ⅱ in patients with pulmonary hypertension[J]. Am J Respir Crit Care Med, 2010, 181:A5226.
    [26] Iannone L, Leiper J, Zhao L, et al. DDAH1 regulates pulmonary vascular responses to hypoxia via MIR-21[J]. Am J Respir Crit Care Med, 2014, 189:A4805.
    [27] Iannone L, Zhao L, Dubois O, et al. miR-21/DDAH1 pathway regulates pulmonary vascular responses to hypoxia[J]. Biochem J, 2014, 462:103-112. doi:  10.1042/BJ20140486
    [28] Drake KM, Comhair SA, Aldred MA, et al. Microrna processing is dysregulated by mutations associated with pulmonary arterial hypertension[J]. Am J Respir Crit Care Med, 2010, 181:A4019. doi:  10.1513/pats.8.2.205
    [29] Drake KM, Comhair SA, Erzurum SC, et al. MicroRNA processing is dysregulated by mutations associated with pulmonary arterial hypertension[J]. Proc Am Thorac Soc, 2011, 8:205. doi:  10.1513/pats.8.2.205
    [30] Drake KM, Comhair SAA, Erzurum SC, et al. Dysregulated microrna processing in pulmonary arterial hypertension contributes to endothelial and smooth muscle cell hyperprolifera-tion[J]. Am J Respir Crit Care Med, 2011, 183:A2523.
    [31] 刘小刚. miR-19a下调BMPR2促PAEC增殖在CHD-PAH血管重构中的作用机制研究[D].上海: 第二军医大学, 2013.
    [32] 曹春辉.血浆miRNA在先天性心脏病继发性肺动脉高压的差异表达的筛选及其功能研究[D].广州: 南方医科大学, 2016.
    [33] 李继中. MicroRNA-21与肺动脉高压的相关性研究[D].南宁: 广西医科大学, 2017.
    [34] Parikh VN, Park J, De Marco T, et al. Plasma expression of miR-21 is increased in HIV-infection and HIV-related pulmonary arterial hypertension[J]. J Am Coll Cardiol, 2014, 63:A1486. doi:  10.1016/S0735-1097(14)61487-X
    [35] Parikh VN, Park J, Nikolic I, et al. Coordinated modulation of circulating miR-21 in HIV, HIV-associated pulmonary arterial hypertension, and HIV/hepatitis C virus coinfection[J]. J Acquir Immune Defic Syndr, 2015, 70:236-241. doi:  10.1097/QAI.0000000000000741
    [36] Zhao Z, Zhou Y. Circulating miR-21 and miR-423-5p as biomarkers for heart failure in heart valve disease patients[J]. Int J Clin Exp Pathol, 2017, 10:5703-5711.
    [37] 吴美华, 曾建斌, 熊向阳.血浆microRNA-21水平与左室射血分数保留的心力衰竭相关性肺高压的关系[J].中国病理生理杂志, 2018, 34:1784-1789. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgblslzz201810010
    [38] Kim R, Sunkara K, Jarnicki A, et al. Microrna-21 drives experimental chronic obstructive pulmonary disease through a SATB1/S100A9/NF-κB axis[J]. Respirology, 2017, 22:71.
    [39] Zeng Z, He S, Lu J, et al. MicroRNA-21 aggravates chronic obstructive pulmonary disease by promoting autophagy[J]. Exp Lung Res, 2018, 44:89-97. doi:  10.1080/01902148.2018.1439548
    [40] 张灿堂, 朱述阳. MicroRNA-21在慢性阻塞性肺疾病并发肺动脉高压患者的表达及临床意义[J].江苏医药, 2015, 10:1170-1173.
    [41] 妥亚军, 侯滨, 张方, 等. miR-21在COPD患者肺动脉高压形成及病情判断中的作用[J].山东医药, 2018, 58:66-68. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=shandyy201836018
    [42] Chang WT, Hsu CH, Huang TL, et al. MicroRNA-21 is Associated with the Severity of Right Ventricular Dysfunction in Patients with Hypoxia-Induced Pulmonary Hypertension[J]. Acta Cardiol Sin, 2018, 34:511-517. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236563/
    [43] Chang WT. Smoking May Contribute to an Increase of miR-21 and a Worse Outcome in Pulmonary Hypertension[J]. Acta Cardiol Sin, 2019, 35:350.
    [44] Pullamsetti S, Doebele C, Fischer A, et al. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension[J]. Eur Respir J, 2011, 38:412. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=1d78dded67354ddf60880075724d1988
    [45] Pullamsetti SS, Doebele C, Fischer A, et al. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension[J]. Am J Respir Crit Care Med, 2012, 185:A2617. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=1d78dded67354ddf60880075724d1988
    [46] Pullamsetti SS, Doebele C, Fischer A, et al. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension[J]. Am J Respir Crit Care Med, 2012, 185:409-419. doi:  10.1164/rccm.201106-1093OC
    [47] Pullamsetti S, Doebele C, Fischer A, et al. Role of microRNA 17/92 cluster and microRNA 21 in the patho-genesis of pulmonary hypertension-novel therapeutic targets[J]. Eur Respir J, 2013, 42:5160.
    [48] Ding F, You T, Hou XD, et al. MiR-21 regulates pulmonary hypertension in rats via TGF-beta1/Smad 2 signaling pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23:3984-3992.
    [49] Sarkar J, Gou D, Ramchandran R, et al. MicroRNA-21 plays a role in hypoxia-mediated pulmonary artery smooth muscle cell proliferation and migration[J]. Am J Physiol Lung Cell Mol Physiol, 2010, 299:L861-L871. doi:  10.1152/ajplung.00201.2010
    [50] Parikh VN, Jin RC, Rabello S, et al. A systems-biology approach reveals that microRNA-21 integrates diverse patho-genic signaling to control pulmonary hypertension[J]. Circulation, 2011, 124:A13395.
    [51] Gubrij IB, Pangle AK, Pang L, et al. Micrornas as potential targets for therapy of pulmonary hypertension[J]. Mol Ther, 2013, 21:S169.
    [52] Johnson LG, Gubrij IB, Pangle AK, et al. Upregulation of MicroRNAs 21 and 223 in an animal model of pulmonary hypertension[J]. Am J Respir Crit Care Med, 2013, 187:A4644.
    [53] Schlosser K, Deng Y, Stewart DJ. Circulating extracellular microRNA-21 is a powerful biomarker for disease activity in experimental pulmonary arterial hypertension[J]. Am J Respir Crit Care Med, 2013, 187:A2098.
    [54] Schlosser K, Deng Y, Stewart DJ. Circulating extracellular microRNA-21 is a biomarker for disease activity in the monocrotaline rat model of pulmonary arterial hypertension[J]. Can J Cardiol, 2013, 29:S174.
    [55] Schlosser K, Deng Y, Stewart DJ. Increased circulating levels of miRNA-21 mirrors disease activity in rats with monocrotaline-induced pulmonary arterial hypertension[J]. Circulation, 2013, 128:A16844.
    [56] Zhang S, Yuan P, Chen TX, et al. Inhibition of miR-21 suppresses miR-223 in estrogen-treated experimental pulmonary hypertension[J]. Am J Respir Crit Care Med, 2017, 195:A4473.
    [57] Yuan P, Hu QH, Liu J, et al. Inhibition of miR-21/Arhgap24 axis and prevention of pulmonary arterial hypertension by estrogen[J]. Am J Respir Crit Care Med, 2015, 191:A4097.
    [58] Joshi SR, Dhagia V, Gairhe S, et al. Microrna-140 is elevated and mitofusin-1 is downregulated in the right ventricle of the sugen5416/hypoxia/normoxia model of pulmonary arterial hypertension[J]. Am J Physiol Heart Circ Physiol, 2016, 311:H689-H698. doi:  10.1152/ajpheart.00264.2016
    [59] Schlosser K, Taha M, Deng Y, et al. Discordant regulation of microRNA between multiple experimental models and human pulmonary hypertension[J]. Chest, 2015, 148:481-490. doi:  10.1378/chest.14-2169
    [60] Blissenbach B, Nakas CT, Kronke M, et al. Hypoxia-induced changes in plasma micro-RNAs correlate with pulmonary artery pressure at high altitude[J]. Am J Physiol Lung Cell Mol Physiol, 2018, 314:L157-L164. doi:  10.1152/ajplung.00146.2017
    [61] Wang F, Long G, Zhao C, et al. Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction[J]. PLoS One, 2014, 9:e105734. doi:  10.1371/journal.pone.0105734
  • 加载中
表(2)
计量
  • 文章访问数:  357
  • HTML全文浏览量:  31
  • PDF下载量:  108
  • 被引次数: 0
出版历程
  • 收稿日期:  2018-04-16
  • 刊出日期:  2020-07-30

目录

    /

    返回文章
    返回

    【温馨提醒】近日,《协和医学杂志》编辑部接到作者反映,有多名不法人员冒充期刊编辑发送见刊通知,鼓动作者添加微信,从而骗取版面费的行为。特提醒您,本刊与作者联系的方式均为邮件通知或电话,稿件进度通知邮箱为:mjpumch@126.com,编辑部电话为:010-69154261,请提高警惕,谨防上当受骗!如有任何疑问,请致电编辑部核实。谢谢!