Lancet:晚期Duchenne肌营养不良症(HOPE-2)重复静脉注射心肌衍生细胞治疗:一项多中心、随机、双盲、安慰剂对照的2期试验

2022-03-18 Naomi MedSci原创

近日,一项发表在Lancet上的研究评估了HOPE-2试验中重复静脉注射CAP-1002治疗Duchenne肌营养不良症的长期安全性和有效性。研究表明这一疗法在减少患者上肢功能恶化方面似乎安全且有效。

     Duchenne肌营养不良症是一种严重的、进行性的、X连锁的疾病,同时影响骨骼肌和心肌,并严重缩短预期寿命。Duchenne肌营养不良症患者发展为进行性四肢瘫痪、限制性肺病和不断恶化的心肌病;这些因素加在一起,最终导致死亡,通常在第二到第四个十年。超过80%的Duchenne肌营养不良症患者在第一个十年后不能行走,而且这一比例正在增加。Duchenne肌营养不良症的治疗试验很少针对非门诊患者,现在这些患者的数量超过了非门诊患者。

     Duchenne肌营养不良症的肌肉破坏会触发炎症和适应不良的免疫反应,进一步限制固有的肌肉修复能力。心脏球源性细胞(CDCs)是一种基质细胞或前体细胞,已在临床前和临床研究中显示在营养不良和心力衰竭中发挥免疫调节、抗纤维化和再生作用(附录4-12)。CDCs通过分泌称为外泌体的细胞外小泡发挥作用,这些外泌体以巨噬细胞为靶点,改变其表达谱,使其采用愈合表型,而不是促炎表型。CDC分泌的外泌体还对成纤维细胞进行重新编程,使其具有抗纤维化作用。在Duchenne的MDX小鼠模型中在肌营养不良中,CDCs通过减少促炎细胞因子和改变与氧化应激、炎症、线粒体完整性和肌肉再生相关的基因的表达,逆转营养不良的表型,提高行走能力和存活率。

     CAP-1002是人类同种异体CDCs的临床剂型,是治疗Duchenne肌营养不良症的候选药物。尽管临床前研究结果表明,CAP-1002可能在杜氏肌营养不良症的所有阶段都有效,但临床开发工作主要集中在非卧床患者,他们的治疗选择有限,而且有大量未得到满足的需求。在HOP1期临床研究中,CAP-1002显示出可接受的安全性水平,在13名Duchenne肌营养不良症患者一次性注入冠状动脉后,CAP-1002似乎保留了上肢和心脏功能。

      在Duchenne肌营养不良的实验模型中,心肌衍生细胞(CDCs)可以改善骨骼和心肌的恶化。近日,一项发表在Lancet上的研究评估了HOPE-2试验中重复静脉注射CAP-1002治疗Duchenne肌营养不良症的长期安全性和有效性。改变给药途径和多剂量方案都是因为在MDX小鼠身上的临床前研究结果显示冠状动脉内和静脉注射CDC的益处相同,并通过连续给药持续改善功能。HOPE-2的疗效结果包括Duchenne肌营养不良症的上肢功能使用上肢功能(PUL)运动功能量表,心脏MRI成像的心功能,呼吸功能的肺活量测量,以及循环生物标志物。

      在这项多中心、随机、双盲、安慰剂对照的2期多中心试验中,10岁或10岁以上的Duchenne肌营养不良症患者在美国的7个中心登记。患者被随机分配(1:1)使用分层排列块接受CAP1002(1.5×10⁸疾控细胞)或安慰剂静脉注射,每3个月一次,共4次。临床医生、护理人员、患者和临床手术人员对治疗组完全保密。主要结果是在意向治疗人群中评估个月时上肢1.2版(PUL 1.2)评分的中位肘关节功能的变化。对所有接受研究产品的个体进行安全性评估。这项试验在ClinicalTrials.gov注册,NCT03406780。

  • 在2018年3月1日至2020年3月31日期间,26名男性Duchenne肌营养不良症患者入选,其中8人被随机分配到CAP-1002组,12人被分配到安慰剂组(6人因筛查失败而未被随机分配)。
  • 在接受治疗后PUL1.2评估的患者中(CAP-1002组8例,安慰剂组11例),中位肘部PUL1.2的平均12个月变化倾向于CAP-1002而不是安慰剂(百分位数差异36.2,95%可信区间12.7-59.7;差异2.6分;p=0.014)。
  • 在3名患者中观察到了与输液相关的过敏反应,没有长期的后遗症,其中1名患者因严重的过敏反应而停止治疗。没有注意到其他重大不良反应,也没有发生死亡。

     CAP-1002细胞疗法在减少晚期Duchenne肌营养不良患者上肢功能恶化方面似乎是安全和有效的。与安慰剂组相比,CAP-1002组的心脏功能和结构的各种指标也得到了改善。CAP-1002用于治疗Duchenne肌营养不良症中的骨骼肌病和心肌病12个月以上,需要更长期的扩展研究来证实其治疗的持久性和安全性。

文献来源:McDonald CM, Marbán E, Hendrix S, et al. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2022;399(10329):1049-1058. doi:10.1016/S0140-6736(22)00012-5

 

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    2022-11-04 makuansheng
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beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43029, encryptionId=7d454302945, topicName=多中心)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Apr 16 22:49:03 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966873, encodeId=f02a19668e328, content=<a href='/topic/show?id=2d26632280' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6322, encryptionId=2d26632280, topicName=Duchenne肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Thu Jun 16 03:49:03 CST 2022, time=2022-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1729441, encodeId=d6a51e29441b5, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Sat Jul 30 10:49:03 CST 2022, time=2022-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1775629, encodeId=f7bf1e756294d, content=<a href='/topic/show?id=937d46650bf' target=_blank style='color:#2F92EE;'>#对照#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46650, encryptionId=937d46650bf, topicName=对照)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8ae138776909, createdName=amyloid, createdTime=Sat Jun 04 13:49:03 CST 2022, time=2022-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784820, encodeId=a33e1e84820cd, content=<a href='/topic/show?id=303063212d' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6321, encryptionId=303063212d, topicName=Duchenne肌营养不良)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a3a2500014, createdName=fmq_28614553, createdTime=Sat Nov 05 09:49:03 CST 2022, time=2022-11-05, status=1, ipAttribution=)]
    2022-11-14 fusion
  4. [GetPortalCommentsPageByObjectIdResponse(id=2007074, encodeId=a71d200e07453, content=<a href='/topic/show?id=21fe810e29d' target=_blank style='color:#2F92EE;'>#肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81072, encryptionId=21fe810e29d, topicName=肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7482500171, createdName=ms4468361851264128, createdTime=Tue Aug 09 19:49:03 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1783048, encodeId=e3c11e8304800, content=<a href='/topic/show?id=2b3f4623e7' target=_blank style='color:#2F92EE;'>#Chen#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4623, encryptionId=2b3f4623e7, topicName=Chen)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri Nov 04 15:49:03 CST 2022, time=2022-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1698357, encodeId=87be169835ed6, content=<a href='/topic/show?id=f2399910109' target=_blank style='color:#2F92EE;'>#静脉#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99101, encryptionId=f2399910109, topicName=静脉)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0bc129907796, createdName=fusion, createdTime=Mon Nov 14 11:49:03 CST 2022, time=2022-11-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1831503, encodeId=332b183150352, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43029, encryptionId=7d454302945, topicName=多中心)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Apr 16 22:49:03 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966873, encodeId=f02a19668e328, content=<a href='/topic/show?id=2d26632280' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6322, encryptionId=2d26632280, topicName=Duchenne肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Thu Jun 16 03:49:03 CST 2022, time=2022-06-16, status=1, ipAttribution=), 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createdBy=8ae138776909, createdName=amyloid, createdTime=Sat Jun 04 13:49:03 CST 2022, time=2022-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784820, encodeId=a33e1e84820cd, content=<a href='/topic/show?id=303063212d' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6321, encryptionId=303063212d, topicName=Duchenne肌营养不良)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a3a2500014, createdName=fmq_28614553, createdTime=Sat Nov 05 09:49:03 CST 2022, time=2022-11-05, status=1, ipAttribution=)]
    2023-01-22 howi
  5. [GetPortalCommentsPageByObjectIdResponse(id=2007074, encodeId=a71d200e07453, content=<a href='/topic/show?id=21fe810e29d' target=_blank style='color:#2F92EE;'>#肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81072, encryptionId=21fe810e29d, topicName=肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7482500171, createdName=ms4468361851264128, createdTime=Tue Aug 09 19:49:03 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1783048, encodeId=e3c11e8304800, content=<a href='/topic/show?id=2b3f4623e7' target=_blank style='color:#2F92EE;'>#Chen#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4623, encryptionId=2b3f4623e7, topicName=Chen)], attachment=null, authenticateStatus=null, createdAvatar=, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43029, encryptionId=7d454302945, topicName=多中心)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Apr 16 22:49:03 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966873, encodeId=f02a19668e328, content=<a href='/topic/show?id=2d26632280' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6322, encryptionId=2d26632280, topicName=Duchenne肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Thu Jun 16 03:49:03 CST 2022, time=2022-06-16, status=1, ipAttribution=), 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createdBy=8ae138776909, createdName=amyloid, createdTime=Sat Jun 04 13:49:03 CST 2022, time=2022-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784820, encodeId=a33e1e84820cd, content=<a href='/topic/show?id=303063212d' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6321, encryptionId=303063212d, topicName=Duchenne肌营养不良)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a3a2500014, createdName=fmq_28614553, createdTime=Sat Nov 05 09:49:03 CST 2022, time=2022-11-05, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=2007074, encodeId=a71d200e07453, content=<a href='/topic/show?id=21fe810e29d' target=_blank style='color:#2F92EE;'>#肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81072, encryptionId=21fe810e29d, topicName=肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7482500171, createdName=ms4468361851264128, createdTime=Tue Aug 09 19:49:03 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1783048, encodeId=e3c11e8304800, content=<a href='/topic/show?id=2b3f4623e7' target=_blank style='color:#2F92EE;'>#Chen#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4623, encryptionId=2b3f4623e7, topicName=Chen)], attachment=null, authenticateStatus=null, createdAvatar=, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43029, encryptionId=7d454302945, topicName=多中心)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Apr 16 22:49:03 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966873, encodeId=f02a19668e328, content=<a href='/topic/show?id=2d26632280' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6322, encryptionId=2d26632280, topicName=Duchenne肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Thu Jun 16 03:49:03 CST 2022, time=2022-06-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1729441, encodeId=d6a51e29441b5, content=<a href='/topic/show?id=986913980dd' target=_blank style='color:#2F92EE;'>#PE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13980, encryptionId=986913980dd, topicName=PE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f06c33759375, createdName=feather89, createdTime=Sat Jul 30 10:49:03 CST 2022, time=2022-07-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1775629, encodeId=f7bf1e756294d, content=<a href='/topic/show?id=937d46650bf' target=_blank style='color:#2F92EE;'>#对照#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46650, encryptionId=937d46650bf, topicName=对照)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8ae138776909, createdName=amyloid, createdTime=Sat Jun 04 13:49:03 CST 2022, time=2022-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784820, encodeId=a33e1e84820cd, content=<a href='/topic/show?id=303063212d' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6321, encryptionId=303063212d, topicName=Duchenne肌营养不良)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a3a2500014, createdName=fmq_28614553, createdTime=Sat Nov 05 09:49:03 CST 2022, time=2022-11-05, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=2007074, encodeId=a71d200e07453, content=<a href='/topic/show?id=21fe810e29d' target=_blank style='color:#2F92EE;'>#肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81072, encryptionId=21fe810e29d, topicName=肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7482500171, createdName=ms4468361851264128, createdTime=Tue Aug 09 19:49:03 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1783048, encodeId=e3c11e8304800, content=<a href='/topic/show?id=2b3f4623e7' target=_blank style='color:#2F92EE;'>#Chen#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4623, encryptionId=2b3f4623e7, topicName=Chen)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2ba9118, createdName=makuansheng, createdTime=Fri Nov 04 15:49:03 CST 2022, time=2022-11-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1698357, encodeId=87be169835ed6, content=<a href='/topic/show?id=f2399910109' target=_blank style='color:#2F92EE;'>#静脉#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99101, encryptionId=f2399910109, topicName=静脉)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0bc129907796, createdName=fusion, createdTime=Mon Nov 14 11:49:03 CST 2022, time=2022-11-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1831503, encodeId=332b183150352, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43029, encryptionId=7d454302945, topicName=多中心)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Apr 16 22:49:03 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966873, encodeId=f02a19668e328, content=<a href='/topic/show?id=2d26632280' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6322, encryptionId=2d26632280, topicName=Duchenne肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Thu Jun 16 03:49:03 CST 2022, time=2022-06-16, status=1, ipAttribution=), 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  8. [GetPortalCommentsPageByObjectIdResponse(id=2007074, encodeId=a71d200e07453, content=<a href='/topic/show?id=21fe810e29d' target=_blank style='color:#2F92EE;'>#肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81072, encryptionId=21fe810e29d, topicName=肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7482500171, createdName=ms4468361851264128, createdTime=Tue Aug 09 19:49:03 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1783048, encodeId=e3c11e8304800, content=<a href='/topic/show?id=2b3f4623e7' target=_blank style='color:#2F92EE;'>#Chen#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4623, encryptionId=2b3f4623e7, topicName=Chen)], attachment=null, authenticateStatus=null, createdAvatar=, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43029, encryptionId=7d454302945, topicName=多中心)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Apr 16 22:49:03 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966873, encodeId=f02a19668e328, content=<a href='/topic/show?id=2d26632280' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6322, encryptionId=2d26632280, topicName=Duchenne肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Thu Jun 16 03:49:03 CST 2022, time=2022-06-16, status=1, ipAttribution=), 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createdBy=8ae138776909, createdName=amyloid, createdTime=Sat Jun 04 13:49:03 CST 2022, time=2022-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784820, encodeId=a33e1e84820cd, content=<a href='/topic/show?id=303063212d' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6321, encryptionId=303063212d, topicName=Duchenne肌营养不良)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a3a2500014, createdName=fmq_28614553, createdTime=Sat Nov 05 09:49:03 CST 2022, time=2022-11-05, status=1, ipAttribution=)]
    2022-07-30 feather89
  9. [GetPortalCommentsPageByObjectIdResponse(id=2007074, encodeId=a71d200e07453, content=<a href='/topic/show?id=21fe810e29d' target=_blank style='color:#2F92EE;'>#肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81072, encryptionId=21fe810e29d, topicName=肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7482500171, createdName=ms4468361851264128, createdTime=Tue Aug 09 19:49:03 CST 2022, time=2022-08-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1783048, encodeId=e3c11e8304800, content=<a href='/topic/show?id=2b3f4623e7' target=_blank style='color:#2F92EE;'>#Chen#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4623, encryptionId=2b3f4623e7, topicName=Chen)], attachment=null, authenticateStatus=null, createdAvatar=, 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beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=43029, encryptionId=7d454302945, topicName=多中心)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Sat Apr 16 22:49:03 CST 2022, time=2022-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1966873, encodeId=f02a19668e328, content=<a href='/topic/show?id=2d26632280' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良症#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6322, encryptionId=2d26632280, topicName=Duchenne肌营养不良症)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=87f580, createdName=yilong5287542, createdTime=Thu Jun 16 03:49:03 CST 2022, time=2022-06-16, status=1, ipAttribution=), 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createdBy=8ae138776909, createdName=amyloid, createdTime=Sat Jun 04 13:49:03 CST 2022, time=2022-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1784820, encodeId=a33e1e84820cd, content=<a href='/topic/show?id=303063212d' target=_blank style='color:#2F92EE;'>#Duchenne肌营养不良#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6321, encryptionId=303063212d, topicName=Duchenne肌营养不良)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0a3a2500014, createdName=fmq_28614553, createdTime=Sat Nov 05 09:49:03 CST 2022, time=2022-11-05, status=1, ipAttribution=)]
    2022-06-04 amyloid
  10. 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