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NEJM：VX-445-Tezacaftor-Ivacaftor用于治疗Phe508del突变型囊性纤维化

2018-10-25 zhangfan MedSci原创

Phe508del囊性纤维化VX445
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研究认为，VX-445-tezacaftor-ivacaftor三连疗法可显著改善Phe508del CFTR蛋白功能，改善Phe508del-MF或Phe508del-Phe508del突变型囊性纤维化患者呼吸功能

新一代囊性纤维化跨膜电导调节剂(CFTR)VX-445与Tezacaftor和Ivaraftor(Vx-445-Tezacaftor-Ivaraftor)联用的3D疗法可恢复囊性纤维化患者Ph 508 Del CFTR蛋白的功能。近日研究人员利用人支气管上皮细胞评估了该疗法对Phe508del CFTR蛋白功能和患者呼吸功能的影响。

Phe508del-MF或Phe508del-Phe508del突变的CF患者参与研究，接受VX-445-tezacaftor-ivacaftor口服治疗，研究的主要终点为1秒内用力呼气量(FEV1)与基线相比的变化。

研究发现，3D疗法体外可显著改善Phe508del CFTR蛋白功能和氯离子转运。在患者研究中，该疗法具有极高的安全性，大部分不良事件为轻中度事件。治疗29天后，3D疗法对于Phe508del-MF或Phe508del-Phe508del突变患者FEV1分别提高13.8和11.0%。囊性纤维化问卷显示患者氯化物浓度和呼吸域评分均有改善。

研究认为，VX-445-tezacaftor-ivacaftor三连疗法可显著改善Phe508del CFTR蛋白功能，改善Phe508del-MF或Phe508del-Phe508del突变型囊性纤维化患者呼吸功能。

原始出处：


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  1. [GetPortalCommentsPageByObjectIdResponse(id=2007542, encodeId=b9a7200e54265, content=<a href='/topic/show?id=e7a1141e55f' target=_blank style='color:#2F92EE;'>#Phe508del#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14175, encryptionId=e7a1141e55f, topicName=Phe508del)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cdcd18, createdName=bshuang, createdTime=Sat Aug 17 11:47:00 CST 2019, time=2019-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1675880, encodeId=4db716e588083, content=<a href='/topic/show?id=7395403e580' target=_blank style='color:#2F92EE;'>#囊性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40375, encryptionId=7395403e580, topicName=囊性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=926927300775, createdName=wolongzxh, createdTime=Mon Dec 17 01:47:00 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1651935, encodeId=8040165193539, content=<a href='/topic/show?id=3a3e1e9504' target=_blank style='color:#2F92EE;'>#ACA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1795, encryptionId=3a3e1e9504, topicName=ACA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=843c24278901, createdName=lishizhe, createdTime=Mon Dec 03 17:47:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2041379, encodeId=1f4620413e9b7, content=<a href='/topic/show?id=baade55002a' target=_blank style='color:#2F92EE;'>#突变型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75500, encryptionId=baade55002a, topicName=突变型)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Thu Aug 22 08:47:00 CST 2019, time=2019-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970322, encodeId=cf5419e032201, content=<a href='/topic/show?id=d3a7185688b' target=_blank style='color:#2F92EE;'>#VX-445#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18568, encryptionId=d3a7185688b, topicName=VX-445)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Thu Jun 06 11:47:00 CST 2019, time=2019-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007555, encodeId=8338200e55563, content=<a href='/topic/show?id=930139e38e' target=_blank style='color:#2F92EE;'>#CAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3973, encryptionId=930139e38e, topicName=CAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=796422, createdName=lvliquan, createdTime=Fri Apr 05 18:47:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478164, encodeId=835c14e816411, content=<a href='/topic/show?id=54f7e7055b' target=_blank style='color:#2F92EE;'>#FTO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7705, encryptionId=54f7e7055b, topicName=FTO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sat Oct 27 00:47:00 CST 2018, time=2018-10-27, status=1, ipAttribution=)]
    2019-08-17 bshuang

    #Phe508del#

    0

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    2018-12-17 wolongzxh

    #囊性#

    0

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    2018-12-03 lishizhe

    #ACA#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2007542, encodeId=b9a7200e54265, content=<a href='/topic/show?id=e7a1141e55f' target=_blank style='color:#2F92EE;'>#Phe508del#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14175, encryptionId=e7a1141e55f, topicName=Phe508del)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cdcd18, createdName=bshuang, createdTime=Sat Aug 17 11:47:00 CST 2019, time=2019-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1675880, encodeId=4db716e588083, content=<a href='/topic/show?id=7395403e580' target=_blank style='color:#2F92EE;'>#囊性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40375, encryptionId=7395403e580, topicName=囊性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=926927300775, createdName=wolongzxh, createdTime=Mon Dec 17 01:47:00 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1651935, encodeId=8040165193539, content=<a href='/topic/show?id=3a3e1e9504' target=_blank style='color:#2F92EE;'>#ACA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1795, encryptionId=3a3e1e9504, topicName=ACA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=843c24278901, createdName=lishizhe, createdTime=Mon Dec 03 17:47:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2041379, encodeId=1f4620413e9b7, content=<a href='/topic/show?id=baade55002a' target=_blank style='color:#2F92EE;'>#突变型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75500, encryptionId=baade55002a, topicName=突变型)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Thu Aug 22 08:47:00 CST 2019, time=2019-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970322, encodeId=cf5419e032201, content=<a href='/topic/show?id=d3a7185688b' target=_blank style='color:#2F92EE;'>#VX-445#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18568, encryptionId=d3a7185688b, topicName=VX-445)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Thu Jun 06 11:47:00 CST 2019, time=2019-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007555, encodeId=8338200e55563, content=<a href='/topic/show?id=930139e38e' target=_blank style='color:#2F92EE;'>#CAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3973, encryptionId=930139e38e, topicName=CAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=796422, createdName=lvliquan, createdTime=Fri Apr 05 18:47:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478164, encodeId=835c14e816411, content=<a href='/topic/show?id=54f7e7055b' target=_blank style='color:#2F92EE;'>#FTO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7705, encryptionId=54f7e7055b, topicName=FTO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sat Oct 27 00:47:00 CST 2018, time=2018-10-27, status=1, ipAttribution=)]
    2019-08-22 heli0118

    #突变型#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2007542, encodeId=b9a7200e54265, content=<a href='/topic/show?id=e7a1141e55f' target=_blank style='color:#2F92EE;'>#Phe508del#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14175, encryptionId=e7a1141e55f, topicName=Phe508del)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cdcd18, createdName=bshuang, createdTime=Sat Aug 17 11:47:00 CST 2019, time=2019-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1675880, encodeId=4db716e588083, content=<a href='/topic/show?id=7395403e580' target=_blank style='color:#2F92EE;'>#囊性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40375, encryptionId=7395403e580, topicName=囊性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=926927300775, createdName=wolongzxh, createdTime=Mon Dec 17 01:47:00 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1651935, encodeId=8040165193539, content=<a href='/topic/show?id=3a3e1e9504' target=_blank style='color:#2F92EE;'>#ACA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1795, encryptionId=3a3e1e9504, topicName=ACA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=843c24278901, createdName=lishizhe, createdTime=Mon Dec 03 17:47:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2041379, encodeId=1f4620413e9b7, content=<a href='/topic/show?id=baade55002a' target=_blank style='color:#2F92EE;'>#突变型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75500, encryptionId=baade55002a, topicName=突变型)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Thu Aug 22 08:47:00 CST 2019, time=2019-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970322, encodeId=cf5419e032201, content=<a href='/topic/show?id=d3a7185688b' target=_blank style='color:#2F92EE;'>#VX-445#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18568, encryptionId=d3a7185688b, topicName=VX-445)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Thu Jun 06 11:47:00 CST 2019, time=2019-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007555, encodeId=8338200e55563, content=<a href='/topic/show?id=930139e38e' target=_blank style='color:#2F92EE;'>#CAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3973, encryptionId=930139e38e, topicName=CAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=796422, createdName=lvliquan, createdTime=Fri Apr 05 18:47:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478164, encodeId=835c14e816411, content=<a href='/topic/show?id=54f7e7055b' target=_blank style='color:#2F92EE;'>#FTO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7705, encryptionId=54f7e7055b, topicName=FTO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sat Oct 27 00:47:00 CST 2018, time=2018-10-27, status=1, ipAttribution=)]
    2019-06-06 lg.zhao

    #VX-445#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2007542, encodeId=b9a7200e54265, content=<a href='/topic/show?id=e7a1141e55f' target=_blank style='color:#2F92EE;'>#Phe508del#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14175, encryptionId=e7a1141e55f, topicName=Phe508del)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cdcd18, createdName=bshuang, createdTime=Sat Aug 17 11:47:00 CST 2019, time=2019-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1675880, encodeId=4db716e588083, content=<a href='/topic/show?id=7395403e580' target=_blank style='color:#2F92EE;'>#囊性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40375, encryptionId=7395403e580, topicName=囊性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=926927300775, createdName=wolongzxh, createdTime=Mon Dec 17 01:47:00 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1651935, encodeId=8040165193539, content=<a href='/topic/show?id=3a3e1e9504' target=_blank style='color:#2F92EE;'>#ACA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1795, encryptionId=3a3e1e9504, topicName=ACA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=843c24278901, createdName=lishizhe, createdTime=Mon Dec 03 17:47:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2041379, encodeId=1f4620413e9b7, content=<a href='/topic/show?id=baade55002a' target=_blank style='color:#2F92EE;'>#突变型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75500, encryptionId=baade55002a, topicName=突变型)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Thu Aug 22 08:47:00 CST 2019, time=2019-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970322, encodeId=cf5419e032201, content=<a href='/topic/show?id=d3a7185688b' target=_blank style='color:#2F92EE;'>#VX-445#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18568, encryptionId=d3a7185688b, topicName=VX-445)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Thu Jun 06 11:47:00 CST 2019, time=2019-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007555, encodeId=8338200e55563, content=<a href='/topic/show?id=930139e38e' target=_blank style='color:#2F92EE;'>#CAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3973, encryptionId=930139e38e, topicName=CAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=796422, createdName=lvliquan, createdTime=Fri Apr 05 18:47:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478164, encodeId=835c14e816411, content=<a href='/topic/show?id=54f7e7055b' target=_blank style='color:#2F92EE;'>#FTO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7705, encryptionId=54f7e7055b, topicName=FTO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sat Oct 27 00:47:00 CST 2018, time=2018-10-27, status=1, ipAttribution=)]
    2019-04-05 lvliquan

    #CAF#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=2007542, encodeId=b9a7200e54265, content=<a href='/topic/show?id=e7a1141e55f' target=_blank style='color:#2F92EE;'>#Phe508del#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14175, encryptionId=e7a1141e55f, topicName=Phe508del)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=cdcd18, createdName=bshuang, createdTime=Sat Aug 17 11:47:00 CST 2019, time=2019-08-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1675880, encodeId=4db716e588083, content=<a href='/topic/show?id=7395403e580' target=_blank style='color:#2F92EE;'>#囊性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40375, encryptionId=7395403e580, topicName=囊性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=926927300775, createdName=wolongzxh, createdTime=Mon Dec 17 01:47:00 CST 2018, time=2018-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1651935, encodeId=8040165193539, content=<a href='/topic/show?id=3a3e1e9504' target=_blank style='color:#2F92EE;'>#ACA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1795, encryptionId=3a3e1e9504, topicName=ACA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=843c24278901, createdName=lishizhe, createdTime=Mon Dec 03 17:47:00 CST 2018, time=2018-12-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2041379, encodeId=1f4620413e9b7, content=<a href='/topic/show?id=baade55002a' target=_blank style='color:#2F92EE;'>#突变型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75500, encryptionId=baade55002a, topicName=突变型)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Thu Aug 22 08:47:00 CST 2019, time=2019-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970322, encodeId=cf5419e032201, content=<a href='/topic/show?id=d3a7185688b' target=_blank style='color:#2F92EE;'>#VX-445#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18568, encryptionId=d3a7185688b, topicName=VX-445)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c737344, createdName=lg.zhao, createdTime=Thu Jun 06 11:47:00 CST 2019, time=2019-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2007555, encodeId=8338200e55563, content=<a href='/topic/show?id=930139e38e' target=_blank style='color:#2F92EE;'>#CAF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3973, encryptionId=930139e38e, topicName=CAF)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=796422, createdName=lvliquan, createdTime=Fri Apr 05 18:47:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1478164, encodeId=835c14e816411, content=<a href='/topic/show?id=54f7e7055b' target=_blank style='color:#2F92EE;'>#FTO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7705, encryptionId=54f7e7055b, topicName=FTO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Sat Oct 27 00:47:00 CST 2018, time=2018-10-27, status=1, ipAttribution=)]
    2018-10-27 仁者大医

    #FTO#

    0

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