OCC 2020丨羟氯喹在免疫性疾病相关性肺动脉高压中的作用及在新冠肺炎中的价值

2020-06-02 Violet MedSci原创

5月29日,第十四届东方心脏病学会议(OCC2020)上,李梦涛教授就“SLE-PAH基础病的治疗选择”和“羟氯喹在免疫性疾病相关性肺动脉高压中的作用及在新冠肺炎中的价值”的主题与各位专家进行了分享.

 

结缔组织病(CTD)相关肺动脉高压(PAH)是风湿科医师必须面临的挑战之一,中国导致PAH 最常见的CTD是SLE,PAH是SLE常见和严重的并发症[1],SLE相关PAH的患病率在中国系统性红斑狼疮研究协作组( CSTAR)的注册研究中达3.8%[2],SLE相关PAH的患病人数在我国CTD相关PAH中的比例近50%[3]

5月29日,第十四届东方心脏病学会议(OCC2020)上,来自北京协和医院风湿免疫科的李梦涛教授就“SLE-PAH基础病的治疗选择”和“羟氯喹在免疫性疾病相关性肺动脉高压中的作用及在新冠肺炎中的价值”的主题与各位专家进行了分享。

SLE-PAH基础病的治疗选择

李梦涛教授介绍,在SLE-PAH治疗方面,有一个重要的理念是“达标治疗”。相关共识[4]推荐“双重达标”:(1)SLE病情处于临床缓解状态: SLEDAI<4,BILAG各系统评分为C/D/E级,PGA<1分;(2)PAH临床达标需满足下述所有标准[5]:临床方面无右室功能衰竭的表现,无晕厥发作;功能方面,WHO心功能稳定在Ⅰ-Ⅱ级,6分钟步行距离>380-440m,心肺运动试验的VO2max>15ml/min/kg;血清学方面,BNP<50ng/L或NT-proBNP<300ng/L(正常或接近正常);影像学方面,右室结构及功能正常或接近正常;RHC检查,右房压<8 mmHg,心指数(CI)=2.5L/min/m2

 

而治疗达标可改善长期预后,达标治疗的策略是根据危险分层选择相应的靶向治疗。有基础炎症表现(浆膜炎)的患者经过治疗后,比没有基础炎症的表现的患者危险分层改善的比例更多,即该类患者更容易经过强化治疗来实现达标改善预后。

李梦涛教授结合了一个病例(如下图所示)讲解了SLE-PAH基础病的治疗,治疗包括甲强龙冲击的治疗,以及环磷酰胺(CTX)和羟氯喹(HCQ)免疫抑制剂的选择,可见经过4周的治疗,患者肺血管阻力由7.6降为2.5WU。

 

在一项北京协和医院的单中心研究中,共纳入110例经右心导管插入术(RHC)确证的SLE-PAH,71例患者进行联合靶向治疗,其中48例进行强化免疫抑制治疗(IST),23例进行非IST,结果显示强化IST组预后改善更佳。

 

经过基础病+靶向治疗效果较好的患者,持续呈低危状态,与该类患者充分沟通后,减停靶向药物,随访六个月以上,有三分之二的患者仍能保持临床血清学和血流动力学的稳定。

 

日本的一项关于SLE-PAH的研究(如下图),治疗也是大剂量激素治疗,逐渐减量,起到抗炎、免疫抑制的作用,选择CTX进行免疫抑制,患者病情可以得到控制。

 

除CTX外,可供选择的免疫抑制剂还有硫唑嘌呤、吗替麦考酚酯(MMF)、他克莫司等,CTX是诱导阶段的首选免疫抑制剂。除靶向药物以外,一线治疗中,美国风湿病协会(ACR)还推荐CTX和MMF。但后几类药物相关研究及临床证据尚不足。

生物制剂方面,贝利木单抗可选择性识别、阻止血清中游离B淋巴细胞刺激因子,其他小分子药物的治疗也在探索中。

 

羟氯喹在免疫性疾病相关性肺动脉高压中的作用

HCQ的历史要从“奎宁”说起,首次临床报告抗疟药用于SLE治疗距今已有120多年历史;1894年,英国医生 Payne报告用奎宁成功治疗红斑狼疮患者;后来,与天然奎宁化学结构相近的抗疟疾药氯喹被人工合成,在氯喹的基础上进一步研究出HCQ。

HCQ治疗SLE的机制主要为两点:(1)抗炎:干扰T细胞吞噬和抗原呈递功能,对T细胞具有抗增殖作用,减少多种促炎细胞因子的产生(包括INF-γ、TNF、IL-1、IL-6和IL-2)等;(2)免疫调节:阻断Toll样受体(TLRs)与核酸配体的相互作用,减少先天免疫激活。

 

与安慰剂相比,应用HCQ后,SLE复发相对风险下降2.5倍,所有患者新发系统损害风险下降32%(如下图),至于能否降低PAH的风险还需进一步研究。

 

SLE患者死亡的另外一个原因是心脑血管疾病,HCQ通过抗氧化应激、抑制T细胞活性、阻断TLRs与核酸配体的相互作用等减少心血管并发症的出现,是否对PAH也有相应的作用尚无定论。

HCQ在新型冠状病毒肺炎中的价值

HCQ的作用机制还包括抗感染,李梦涛教授复习了HCQ治疗新型冠状病毒肺炎(COVID-19)相关文献,发现很多关于危重症患者的大型临床试验的研究,都认为HCQ对COVID-19的病情没有明显改善作用。5月27日,发表于Ann Intern Med(内科学年鉴)的一篇系统综述[6]也未得出肯定结论。

 

李梦涛教授推测,因为HCQ对SLE的作用起效慢,一般需要三个月,某些COVID-19患者的病情进展较快,7-10天的应用不能得出明显效果。李梦涛教授指出,HCQ对COVID-19能否起到预防作用可以是一个重点研究的方向,比如可以研究对于密切接触的患者,应用HCQ能否减少COVID-19从潜伏感染的状态转变为临床表达的状态,能否产生阻断免疫和炎症风暴的作用。

 

李梦涛教授最后总结道,SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高,如何早期识别进行一级预防仍然是风湿科医师面临的问题,羟氯喹有无可能阻断PAH的出现、对COVID-19能否起到预防作用也需进一步研究。

 

 

参考文献:

[1] 张卓莉. 系统性红斑狼疮相关肺动脉高压[J]. 中国实用内科杂志, 2015, 35(10):807-809.

[2] Li M, Zhang W, Leng X, et al. Chinese SLE Treatment and Research group ( CSTAR ) registry : 1. Major clinical characteristics of Chinese patients with systemic lupus erythematosus[J]. Lupus, 2013, 22( 11 ) : 1192-1199. 

[3] Hao Y J, Jiang X, Zhou W, et al. Connective tissue disease- associated pulmonary arterial hypertension in Chinese patients [ J]. Eur Respir J,2014,44 (4) :963-972. 

[4] 国家风湿病数据中心, 中国系统性红斑狼疮研究协作组. 中国成人系统性红斑狼疮相关肺动脉高压诊治共识[J]. 中华内科杂志, 2015, 054(001):81-86.

[5] McLaughlin VV, Gaine SP, Howard LS, et al. Treatment goals of pulmonary hypertension[ J]. J Am Coil Cardiol, 2013,62 (25 Suppl) : D73-81. 

[6] Hernandez AV, Roman YM, Pasupuleti V, Barboza JJ, White CM. Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review [published online ahead of print, 2020 May 27]. Ann Intern Med. 2020;10.7326/M20-2496. doi:10.7326/M20-2496

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    0

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  3. [GetPortalCommentsPageByObjectIdResponse(id=1016825, encodeId=99f51016825c7, content=加积分多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210814/61deb584a399410ca9b720adee4e6850/71825fee35134aee90c3ed9dfe89b69f.jpg, createdBy=3cff5430616, createdName=云舒, createdTime=Sun Sep 12 17:19:29 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925337, encodeId=c436192533ee9, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Jan 27 11:27:01 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1837840, encodeId=02d0183e840b3, content=<a href='/topic/show?id=3f34e253206' target=_blank style='color:#2F92EE;'>#相关性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72532, encryptionId=3f34e253206, topicName=相关性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a9de34, createdName=shenxlcyp, createdTime=Sun Oct 11 12:27:01 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=601719, encodeId=770a601e195c, content=<a href='/topic/show?id=3469e71246f' target=_blank style='color:#2F92EE;'>#红斑狼疮#</a>SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高! 羟氯喹有效,青蒿素也许也有效🐝🐝, beContent=null, objectType=article, channel=null, level=null, likeNumber=169, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77124, encryptionId=3469e71246f, topicName=红斑狼疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Jun 07 10:56:45 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1353123, encodeId=2e541353123fd, content=<a href='/topic/show?id=1d931321816' target=_blank style='color:#2F92EE;'>#OCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13218, encryptionId=1d931321816, topicName=OCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377508, encodeId=1a0c13e75085b, content=<a href='/topic/show?id=55f013219ae' target=_blank style='color:#2F92EE;'>#OCC 2020#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13219, encryptionId=55f013219ae, topicName=OCC 2020)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580168, encodeId=f5441580168ca, content=<a href='/topic/show?id=bd2529020e1' target=_blank style='color:#2F92EE;'>#免疫性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29020, encryptionId=bd2529020e1, topicName=免疫性疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=df0516593209, createdName=124988c7m100暂无昵称, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028113, encodeId=360c1028113e5, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050898, encodeId=836e10508983d, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1016825, encodeId=99f51016825c7, content=加积分多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210814/61deb584a399410ca9b720adee4e6850/71825fee35134aee90c3ed9dfe89b69f.jpg, createdBy=3cff5430616, createdName=云舒, createdTime=Sun Sep 12 17:19:29 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925337, encodeId=c436192533ee9, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Jan 27 11:27:01 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1837840, encodeId=02d0183e840b3, content=<a href='/topic/show?id=3f34e253206' target=_blank style='color:#2F92EE;'>#相关性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72532, encryptionId=3f34e253206, topicName=相关性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a9de34, createdName=shenxlcyp, createdTime=Sun Oct 11 12:27:01 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=601719, encodeId=770a601e195c, content=<a href='/topic/show?id=3469e71246f' target=_blank style='color:#2F92EE;'>#红斑狼疮#</a>SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高! 羟氯喹有效,青蒿素也许也有效🐝🐝, beContent=null, objectType=article, channel=null, level=null, likeNumber=169, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77124, encryptionId=3469e71246f, topicName=红斑狼疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Jun 07 10:56:45 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1353123, encodeId=2e541353123fd, content=<a href='/topic/show?id=1d931321816' target=_blank style='color:#2F92EE;'>#OCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13218, encryptionId=1d931321816, topicName=OCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377508, encodeId=1a0c13e75085b, content=<a href='/topic/show?id=55f013219ae' target=_blank style='color:#2F92EE;'>#OCC 2020#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13219, encryptionId=55f013219ae, topicName=OCC 2020)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580168, encodeId=f5441580168ca, content=<a href='/topic/show?id=bd2529020e1' target=_blank style='color:#2F92EE;'>#免疫性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29020, encryptionId=bd2529020e1, topicName=免疫性疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=df0516593209, createdName=124988c7m100暂无昵称, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028113, encodeId=360c1028113e5, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050898, encodeId=836e10508983d, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=)]
    2020-06-07 lovetcm

    #红斑狼疮#SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高! 羟氯喹有效,青蒿素也许也有效🐝🐝

    0

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    2020-06-03 zhaojie88
  6. [GetPortalCommentsPageByObjectIdResponse(id=1016825, encodeId=99f51016825c7, content=加积分多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210814/61deb584a399410ca9b720adee4e6850/71825fee35134aee90c3ed9dfe89b69f.jpg, createdBy=3cff5430616, createdName=云舒, createdTime=Sun Sep 12 17:19:29 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925337, encodeId=c436192533ee9, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Jan 27 11:27:01 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1837840, encodeId=02d0183e840b3, content=<a href='/topic/show?id=3f34e253206' target=_blank style='color:#2F92EE;'>#相关性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72532, encryptionId=3f34e253206, topicName=相关性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a9de34, createdName=shenxlcyp, createdTime=Sun Oct 11 12:27:01 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=601719, encodeId=770a601e195c, content=<a href='/topic/show?id=3469e71246f' target=_blank style='color:#2F92EE;'>#红斑狼疮#</a>SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高! 羟氯喹有效,青蒿素也许也有效🐝🐝, beContent=null, objectType=article, channel=null, level=null, likeNumber=169, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77124, encryptionId=3469e71246f, topicName=红斑狼疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Jun 07 10:56:45 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1353123, encodeId=2e541353123fd, content=<a href='/topic/show?id=1d931321816' target=_blank style='color:#2F92EE;'>#OCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13218, encryptionId=1d931321816, topicName=OCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377508, encodeId=1a0c13e75085b, content=<a href='/topic/show?id=55f013219ae' target=_blank style='color:#2F92EE;'>#OCC 2020#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13219, encryptionId=55f013219ae, topicName=OCC 2020)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580168, encodeId=f5441580168ca, content=<a href='/topic/show?id=bd2529020e1' target=_blank style='color:#2F92EE;'>#免疫性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29020, encryptionId=bd2529020e1, topicName=免疫性疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=df0516593209, createdName=124988c7m100暂无昵称, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028113, encodeId=360c1028113e5, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050898, encodeId=836e10508983d, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=)]
    2020-06-03 hmwwww
  7. [GetPortalCommentsPageByObjectIdResponse(id=1016825, encodeId=99f51016825c7, content=加积分多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210814/61deb584a399410ca9b720adee4e6850/71825fee35134aee90c3ed9dfe89b69f.jpg, createdBy=3cff5430616, createdName=云舒, createdTime=Sun Sep 12 17:19:29 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925337, encodeId=c436192533ee9, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Jan 27 11:27:01 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1837840, encodeId=02d0183e840b3, content=<a href='/topic/show?id=3f34e253206' target=_blank style='color:#2F92EE;'>#相关性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72532, encryptionId=3f34e253206, topicName=相关性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a9de34, createdName=shenxlcyp, createdTime=Sun Oct 11 12:27:01 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=601719, encodeId=770a601e195c, content=<a href='/topic/show?id=3469e71246f' target=_blank style='color:#2F92EE;'>#红斑狼疮#</a>SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高! 羟氯喹有效,青蒿素也许也有效🐝🐝, beContent=null, objectType=article, channel=null, level=null, likeNumber=169, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77124, encryptionId=3469e71246f, topicName=红斑狼疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Jun 07 10:56:45 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1353123, encodeId=2e541353123fd, content=<a href='/topic/show?id=1d931321816' target=_blank style='color:#2F92EE;'>#OCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13218, encryptionId=1d931321816, topicName=OCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377508, encodeId=1a0c13e75085b, content=<a href='/topic/show?id=55f013219ae' target=_blank style='color:#2F92EE;'>#OCC 2020#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13219, encryptionId=55f013219ae, topicName=OCC 2020)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580168, encodeId=f5441580168ca, content=<a href='/topic/show?id=bd2529020e1' target=_blank style='color:#2F92EE;'>#免疫性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29020, encryptionId=bd2529020e1, topicName=免疫性疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=df0516593209, createdName=124988c7m100暂无昵称, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028113, encodeId=360c1028113e5, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050898, encodeId=836e10508983d, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1016825, encodeId=99f51016825c7, content=加积分多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210814/61deb584a399410ca9b720adee4e6850/71825fee35134aee90c3ed9dfe89b69f.jpg, createdBy=3cff5430616, createdName=云舒, createdTime=Sun Sep 12 17:19:29 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925337, encodeId=c436192533ee9, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Jan 27 11:27:01 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1837840, encodeId=02d0183e840b3, content=<a href='/topic/show?id=3f34e253206' target=_blank style='color:#2F92EE;'>#相关性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72532, encryptionId=3f34e253206, topicName=相关性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a9de34, createdName=shenxlcyp, createdTime=Sun Oct 11 12:27:01 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=601719, encodeId=770a601e195c, content=<a href='/topic/show?id=3469e71246f' target=_blank style='color:#2F92EE;'>#红斑狼疮#</a>SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高! 羟氯喹有效,青蒿素也许也有效🐝🐝, beContent=null, objectType=article, channel=null, level=null, likeNumber=169, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77124, encryptionId=3469e71246f, topicName=红斑狼疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Jun 07 10:56:45 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1353123, encodeId=2e541353123fd, content=<a href='/topic/show?id=1d931321816' target=_blank style='color:#2F92EE;'>#OCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13218, encryptionId=1d931321816, topicName=OCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377508, encodeId=1a0c13e75085b, content=<a href='/topic/show?id=55f013219ae' target=_blank style='color:#2F92EE;'>#OCC 2020#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13219, encryptionId=55f013219ae, topicName=OCC 2020)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580168, encodeId=f5441580168ca, content=<a href='/topic/show?id=bd2529020e1' target=_blank style='color:#2F92EE;'>#免疫性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29020, encryptionId=bd2529020e1, topicName=免疫性疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=df0516593209, createdName=124988c7m100暂无昵称, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028113, encodeId=360c1028113e5, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050898, encodeId=836e10508983d, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=)]
    2020-06-01 公卫新人

    新冠肺炎,疫情何时才能消失

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1016825, encodeId=99f51016825c7, content=加积分多学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210814/61deb584a399410ca9b720adee4e6850/71825fee35134aee90c3ed9dfe89b69f.jpg, createdBy=3cff5430616, createdName=云舒, createdTime=Sun Sep 12 17:19:29 CST 2021, time=2021-09-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1925337, encodeId=c436192533ee9, content=<a href='/topic/show?id=26d633354c9' target=_blank style='color:#2F92EE;'>#动脉高压#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33354, encryptionId=26d633354c9, topicName=动脉高压)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Jan 27 11:27:01 CST 2021, time=2021-01-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1837840, encodeId=02d0183e840b3, content=<a href='/topic/show?id=3f34e253206' target=_blank style='color:#2F92EE;'>#相关性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72532, encryptionId=3f34e253206, topicName=相关性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a9de34, createdName=shenxlcyp, createdTime=Sun Oct 11 12:27:01 CST 2020, time=2020-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=601719, encodeId=770a601e195c, content=<a href='/topic/show?id=3469e71246f' target=_blank style='color:#2F92EE;'>#红斑狼疮#</a>SLE的脏器受累方面,PAH超过了神经精神性狼疮,比例仍在升高! 羟氯喹有效,青蒿素也许也有效🐝🐝, beContent=null, objectType=article, channel=null, level=null, likeNumber=169, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77124, encryptionId=3469e71246f, topicName=红斑狼疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Sun Jun 07 10:56:45 CST 2020, time=2020-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1353123, encodeId=2e541353123fd, content=<a href='/topic/show?id=1d931321816' target=_blank style='color:#2F92EE;'>#OCC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13218, encryptionId=1d931321816, topicName=OCC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1377508, encodeId=1a0c13e75085b, content=<a href='/topic/show?id=55f013219ae' target=_blank style='color:#2F92EE;'>#OCC 2020#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13219, encryptionId=55f013219ae, topicName=OCC 2020)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c859411, createdName=hmwwww, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1580168, encodeId=f5441580168ca, content=<a href='/topic/show?id=bd2529020e1' target=_blank style='color:#2F92EE;'>#免疫性疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29020, encryptionId=bd2529020e1, topicName=免疫性疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=df0516593209, createdName=124988c7m100暂无昵称, createdTime=Wed Jun 03 08:27:01 CST 2020, time=2020-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1028113, encodeId=360c1028113e5, content=新冠肺炎,疫情何时才能消失, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=公卫新人, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1050898, encodeId=836e10508983d, content=肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=明天jing, createdTime=Mon Jun 01 20:27:01 CST 2020, time=2020-06-01, status=1, ipAttribution=)]
    2020-06-01 明天jing

    肺动脉高压表面是罕见病,事实上临床上并不少见,治疗药物虽然有一些,但是整体仍然不理解,可能未来需要采用综合治疗措施。

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