CRAL:天疱疮治疗指南的比较:全身糖皮质激素、利妥昔单抗和其他免疫抑制疗法

2021-10-14 医路坦克 MedSci原创

天疱疮是包括一组危及生命的自身免疫性大疱性皮肤病,该文从成熟的皮肤病学会和专家共识小组中选择了几个指南进行审查,以呈现相似和不同之处,并进行全面的分析,以更好地指导临床实践。

 

        天疱疮是包括一组危及生命的自身免疫性大疱性皮肤病,主要是皮肤和粘膜的损害。损伤主要由针对表皮角质形成细胞表面桥粒黏附蛋白桥粒蛋白(DSG)的IgG自身抗体介导。

寻常型天疱疮(PV)和落叶型天疱疮(PF)是两种主要的临床变异型。不同的协会制定了许多与天疱疮治疗相关的指南和共识声明。尽管最近公布了一个国际专家小组的建议,但这些指南之间仍存在许多不同之处。该文从成熟的皮肤病学会和专家共识小组中选择了几个指南进行审查,以呈现相似和不同之处,并进行全面的分析,以更好地指导临床实践。该文确定了讨论PV和PF的6个相关指南。审查了以下组织的指南:德国科学医学会协会(ASMSG)、巴西皮肤病学会(BSD)、BAD、中国国际医疗卫生交流与促进协会皮肤病分会(DBC)、欧洲皮肤病和性病学学会(EADV)和法国皮肤病学会(FSD)。

 

皮质类固醇治疗

      皮质类固醇是治疗天疱疮最广泛使用的药物,在大多数指南中被用作轻度和中到重度疾病患者的一线治疗。泼尼松和强的松一般口服,甲基强的松龙(MP)和地塞米松(DXM)主要用于冲击治疗。

      天疱疮的治疗通常包括两个阶段:诱导缓解和维持缓解。在轻度PV中,皮质类固醇的初始剂量通常为0.5-1.0mg/kg/天(泼尼松龙当量)。DBC和BSD指南最初建议仅使用全身性皮质类固醇,但ASMSG和BAD指南从治疗开始就提倡全身性皮质类固醇和免疫抑制剂。轻度PF的治疗建议在指南之间略有不同。ASMSG,BSD,EADV和FSD指南也建议使用系统性皮质类固醇。值得注意的是,皮质类固醇在轻度PF中并不是必不可少的,EADV,BSD和FSD指南建议单独使用其他药物,如氨苯砜和利妥昔单抗。在轻度天疱疮中,冲击疗法通常不优先于每日口服皮质类固醇,但应考虑难治性类型,并作为二线选择引入,仅由ASMSG推荐。

      当PV病变有限或循环抗体水平非常低或为零时,FSD指南建议单独使用局部皮质类固醇作为一线治疗。对于轻度PF,根据EADV,FSD和BSD,局部皮质类固醇单药治疗也可用作一线治疗。ASMSG还提到局部皮质类固醇可被视为局部和轻度疾病患者的单一疗法,但需要更多证据来支持其有效性。

     中重度天疱疮的全身糖皮质激素剂量通常为1.0~1.5 mg/kg/d,从治疗开始就联合辅助剂。与利妥昔单抗联合使用时,全身糖皮质激素的剂量相对较低,平均每天减少0.5毫克/公斤。根据ASMSG、BSD和BAD指南,静脉注射糖皮质激素也被认为是中到重度天疱疮的替代一线治疗方法。

     如果目前的处方不能控制病情,那么就应该增加皮质类固醇的剂量,根据大多数指南,对于单独使用全身皮质类固醇治疗的患者,应该增加辅助药物,或者对于使用全身类固醇和辅助免疫抑制剂治疗的患者,应该改用另一种辅助药物。DBC和ASMSG主张将皮质类固醇的剂量增加到推荐的最大剂量:分别为1.5 mg/kg/天和2.0 mg/kg/天。坏消息是,当水泡持续时,每隔5-7天增加50%-100%的皮质类固醇,直到疾病得到控制。EADV和FSD表明,与未接受利妥昔单抗治疗的患者相比,以前接受过利妥昔单抗治疗的患者每天增加的皮质类固醇剂量应比未接受利妥昔单抗治疗的患者低约0.75-1.0毫克/公斤/天。指南中没有提到当患者单独使用利妥昔单抗治疗时应该采取什么措施。

 

缓解期维持中的皮质类固醇减量

      一旦疾病得到控制,缓解期的维持就应该开始,通常定义为大约80%的皮肤和粘膜损伤愈合,至少两周内没有新的病变出现,应该开始逐步减少皮质类固醇。维持疗法的治疗建议在不同的指南之间差别很大。ASMSG、EADV和FSD根据使用或不使用利妥昔单抗的治疗来划分建议,但其他协会不包括这种划分。皮质类固醇的剂量通常在开始时下降得很快,然后下降得更慢。治疗的最终目标是将皮质类固醇降至最低剂量,一般认为该剂量低于10毫克/天。整个过程可能需要几年时间。

     单独使用皮质类固醇的全身维持治疗DBC,EADV,BSD和FSD提到轻度天疱疮可单独使用皮质类固醇治疗。逐渐减少的方案通常基于维持治疗开始时使用的皮质类固醇的剂量来设计。DBC制定的计划似乎更加谨慎,反映在逐渐减少的过程中,这比国际专家和其他欧洲准则的建议要慢。

     使用抗CD20单克隆抗体进行全身维持治疗使用利妥昔单抗的治疗计划中,皮质类固醇的剂量通常比使用其他佐剂的治疗计划中的剂量减少得更快。根据EADV和FSD的时间表,轻度天疱疮患者通常需要4个月的时间,中到重度天疱疮患者需要6个月的时间。

 

复发/复发病例

     复发通常被定义为在1个月内出现3个或3个以上的新病变,并且在1周内不能自然愈合,或者是已经达到疾病控制的患者原有病变的延伸。一些指南,包括ASMSG、EADV和FSD的指南,考虑了使用和不使用利妥昔单抗方案之间的差异。通常的做法是增加皮质类固醇的剂量,但对于确切的剂量没有达成共识。正如BAD和BSD的建议所反映的那样,复发通常比最初的发作要温和,而且可以用较低的剂量进行治疗。如果患者以前接受过利妥昔单抗治疗,在增加皮质类固醇剂量和重新使用利妥昔单抗之间的选择取决于复发的时间。一种新的免疫抑制剂可能会被引入到以前接受过免疫抑制剂治疗的患者中。

抗CD20单克隆抗体

     抗CD20单克隆抗体耗尽外周血中CD20阳性的B淋巴细胞,用于抗体介导的自身免疫性疾病。利妥昔单抗是最常用的抗CD20单克隆抗体。2018年,美国食品和药物管理局(FDA)批准利妥昔单抗作为治疗中重度天疱疮的一线药物。

    利妥昔单抗最初用于严重天疱疮患者的皮质类固醇辅助治疗,但现在,大多数指南建议将其作为治疗中到重度天疱疮的一线疗法,无论是否使用皮质类固醇。值得注意的是,除了EADV的指南外,没有一份指南推荐利妥昔单抗作为治疗包括轻度PF在内的轻度天疱疮的一线治疗。利妥昔单抗应缓慢静脉给药。根据DBC和EADV,虽然天疱疮首次使用4次间隔375毫克/平方米1周的输液,但根据DBC和EADV,2次间隔1000毫克2周的输液更常用。如上所述,在一些指南中,利妥昔单抗作为治疗方案的一部分决定了维持治疗计划和复发后的治疗。EADV建议在以前使用利妥昔单抗治疗的复发患者中增加一个利妥昔单抗周期,特别是在4个月至6个月期间逐渐减少泼尼松治疗期间复发时。DBC和EADV倾向于对以前没有接受过利妥昔单抗治疗的患者添加或替代一种免疫抑制剂,但FSD建议,对于以前接受过免疫抑制剂和皮质类固醇治疗的患者,暂停免疫抑制剂并添加利妥昔单抗比改用另一种免疫抑制剂更有效。由于感染或其他副作用的潜在风险,免疫抑制药物不常与利妥昔单抗一起使用。

 

佐剂免疫抑制剂

     免疫抑制剂被广泛用作类固醇类药物,通常用于中、重度疾病患者的初始治疗。然而,除了ASMSG和BAD之外,我们考虑的所有协会都同意免疫抑制剂对于轻度病例并不是必不可少的。硫唑嘌呤(AZA)和霉酚酸酯(MMF)是纳入指南中最常推荐的免疫抑制剂。所有指南都推荐MMF作为一线佐剂免疫抑制剂。在一些指导方针下,霉酚酸(MPA)也是一种选择。大多数指南都推荐AZA作为一线选择,除了DBC指南,它推荐AZA作为二线选择[9]。ASMSG、EADV和FSD建议将氨苯砜作为治疗轻度PF的一线辅助药物,BSD主张将氨苯砜作为治疗轻度PV的一线辅助药物[10-13]。DBC、BSD和FSD也推荐甲氨蝶呤(MTX)作为一线佐剂[9,10,13]。免疫抑制剂的剂量在指南中略有不同。其他免疫抑制剂,如环孢素A(CsA)和环磷酰胺(CTX),被推荐为二线选择。表5提供了指南中讨论的免疫抑制剂。

 

其他疗法

    静脉注射免疫球蛋白(IVIG)、血浆置换、免疫吸附和其他治疗方法在上述治疗方法不可行的情况下也被推荐用于严重或难治性天疱疮的治疗。

     随着我们对疾病和技术发展的更好理解,越来越多的新型疗法正在出现。除静脉注射外,利妥昔单抗可用于病灶内,因为发现病灶内给药可有效治疗天疱疮难治性口腔病变[48]。布鲁顿酪氨酸激酶抑制剂通过下调各种B细胞活性来抑制抗体产生,最近已被FDA批准为孤儿药,但未来需要更多证据来支持它们用于治疗天疱疮。通常用于治疗肿瘤的嵌合抗原受体疗法也可以设计用于靶向天疱疮中致病性B细胞的增殖并且已经在体外显示出功效,并且预期将来会进行临床研究[25,49-53]。最近发现T滤泡辅助细胞与天疱疮中B细胞的发育有关[53,54]。白细胞介素-21(IL-21)是T滤泡辅助细胞分泌的细胞因子,对T滤泡辅助细胞的活化以及这些细胞与B细胞的相互作用至关重要,这会影响记忆B和浆细胞的产生。[55]。IL-21的分泌与Janus家族的酪氨酸激酶(Janus Kinases或JAKs)有关,尤其是JAK1和JAK3。托法替尼是JAK1和/或JAK3的选择性抑制剂,可能干扰DSG特异性T滤泡辅助细胞的激活及其与B细胞的相互作用。因此,托法替尼在未来也可能成为治疗天疱疮的有效药物[49]。FcRN是一种受体,介导IgG从母亲到胎儿的转运和IgG的稳态;因此,从理论上讲,拮抗FcRN在允许自身抗体更快降解方面是有效的[49]。几种针对FcRN的药物正在进行临床试验。许多新疗法在理论上可能是可行的,但在这些药物用于临床实践之前,还有很长的路要走。

文献来源:Zhao W,  Wang J,  Zhu H,Comparison of Guidelines for Management of Pemphigus: a Review of Systemic Corticosteroids, Rituximab, and Other Immunosuppressive Therapies.Clin Rev Allergy Immunol 2021 Aug 04

 

 

 

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  2. [GetPortalCommentsPageByObjectIdResponse(id=1701315, encodeId=80ba1e01315d2, content=<a href='/topic/show?id=b5f6e6827fb' target=_blank style='color:#2F92EE;'>#糖皮质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76827, encryptionId=b5f6e6827fb, topicName=糖皮质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0f4230340116, createdName=Tommy1959, createdTime=Mon Aug 22 12:10:34 CST 2022, time=2022-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1220368, encodeId=a33c1220368bf, content=<a href='/topic/show?id=dc4644189eb' target=_blank style='color:#2F92EE;'>#天疱疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44189, encryptionId=dc4644189eb, topicName=天疱疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=赛华佗, createdTime=Tue May 17 16:28:40 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1934933, encodeId=83111934933f3, content=<a href='/topic/show?id=1072646328c' target=_blank style='color:#2F92EE;'>#治疗指南#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64632, encryptionId=1072646328c, topicName=治疗指南)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6732482, createdName=w984445tii, createdTime=Wed Jul 20 09:10:34 CST 2022, time=2022-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191214, encodeId=efc3119121448, content=新治疗方法,值得推广, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 20:54:29 CST 2022, time=2022-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660515, encodeId=ab0a1660515e6, content=<a href='/topic/show?id=c0de32285a1' target=_blank style='color:#2F92EE;'>#利妥昔#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32285, encryptionId=c0de32285a1, topicName=利妥昔)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a58d25117340, createdName=花花1374, createdTime=Thu Feb 03 00:10:34 CST 2022, time=2022-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070740, encodeId=309110e074059, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56095714142, createdName=ms5000000753978789, createdTime=Tue Nov 16 12:40:39 CST 2021, time=2021-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067439, encodeId=f833106e43957, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=145, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/15/7274ed1be4747d648e4e2f7f62fae403.jpg, createdBy=d8d65273314, createdName=1482963am12暂无昵称, createdTime=Fri Nov 05 23:34:22 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600449, encodeId=cf0e1600449ff, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Oct 16 14:10:34 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=1701315, encodeId=80ba1e01315d2, content=<a href='/topic/show?id=b5f6e6827fb' target=_blank style='color:#2F92EE;'>#糖皮质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76827, encryptionId=b5f6e6827fb, topicName=糖皮质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0f4230340116, createdName=Tommy1959, createdTime=Mon Aug 22 12:10:34 CST 2022, time=2022-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1220368, encodeId=a33c1220368bf, content=<a href='/topic/show?id=dc4644189eb' target=_blank style='color:#2F92EE;'>#天疱疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44189, encryptionId=dc4644189eb, topicName=天疱疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=赛华佗, createdTime=Tue May 17 16:28:40 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1934933, encodeId=83111934933f3, content=<a href='/topic/show?id=1072646328c' target=_blank style='color:#2F92EE;'>#治疗指南#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64632, encryptionId=1072646328c, topicName=治疗指南)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6732482, createdName=w984445tii, createdTime=Wed Jul 20 09:10:34 CST 2022, time=2022-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191214, encodeId=efc3119121448, content=新治疗方法,值得推广, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 20:54:29 CST 2022, time=2022-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660515, encodeId=ab0a1660515e6, content=<a href='/topic/show?id=c0de32285a1' target=_blank style='color:#2F92EE;'>#利妥昔#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32285, encryptionId=c0de32285a1, topicName=利妥昔)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a58d25117340, createdName=花花1374, createdTime=Thu Feb 03 00:10:34 CST 2022, time=2022-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070740, encodeId=309110e074059, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56095714142, createdName=ms5000000753978789, createdTime=Tue Nov 16 12:40:39 CST 2021, time=2021-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067439, encodeId=f833106e43957, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=145, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/15/7274ed1be4747d648e4e2f7f62fae403.jpg, createdBy=d8d65273314, createdName=1482963am12暂无昵称, createdTime=Fri Nov 05 23:34:22 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600449, encodeId=cf0e1600449ff, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Oct 16 14:10:34 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1701315, encodeId=80ba1e01315d2, content=<a href='/topic/show?id=b5f6e6827fb' target=_blank style='color:#2F92EE;'>#糖皮质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76827, encryptionId=b5f6e6827fb, topicName=糖皮质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0f4230340116, createdName=Tommy1959, createdTime=Mon Aug 22 12:10:34 CST 2022, time=2022-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1220368, encodeId=a33c1220368bf, content=<a href='/topic/show?id=dc4644189eb' target=_blank style='color:#2F92EE;'>#天疱疮#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=44189, encryptionId=dc4644189eb, topicName=天疱疮)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=赛华佗, createdTime=Tue May 17 16:28:40 CST 2022, time=2022-05-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1934933, encodeId=83111934933f3, content=<a href='/topic/show?id=1072646328c' target=_blank style='color:#2F92EE;'>#治疗指南#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64632, encryptionId=1072646328c, topicName=治疗指南)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6732482, createdName=w984445tii, createdTime=Wed Jul 20 09:10:34 CST 2022, time=2022-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1191214, encodeId=efc3119121448, content=新治疗方法,值得推广, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=89ae6481716, createdName=ms3000000637975859, createdTime=Tue Feb 08 20:54:29 CST 2022, time=2022-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1660515, encodeId=ab0a1660515e6, content=<a href='/topic/show?id=c0de32285a1' target=_blank style='color:#2F92EE;'>#利妥昔#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32285, encryptionId=c0de32285a1, topicName=利妥昔)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a58d25117340, createdName=花花1374, createdTime=Thu Feb 03 00:10:34 CST 2022, time=2022-02-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1070740, encodeId=309110e074059, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=134, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56095714142, createdName=ms5000000753978789, createdTime=Tue Nov 16 12:40:39 CST 2021, time=2021-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1067439, encodeId=f833106e43957, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=145, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2020/02/15/7274ed1be4747d648e4e2f7f62fae403.jpg, createdBy=d8d65273314, createdName=1482963am12暂无昵称, createdTime=Fri Nov 05 23:34:22 CST 2021, time=2021-11-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600449, encodeId=cf0e1600449ff, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sat Oct 16 14:10:34 CST 2021, time=2021-10-16, status=1, ipAttribution=)]
    2022-02-08 ms3000000637975859

    新治疗方法,值得推广

    0

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    2021-11-16 ms5000000753978789

    学习

    0

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    2021-11-05 1482963am12暂无昵称

    学习了,谢谢分享

    0

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