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Diabetologia：口服组蛋白去乙酰化酶抑制剂与T细胞靶向免疫疗法协同作用可保护β细胞代谢功能并诱导NOD小鼠新发自身免疫糖尿病的缓解

2018-04-24 MedSci MedSci原创

NOD小鼠T细胞靶向免疫疗法
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近日，国际杂志 《Diabetologia》上在线发表一项关于口服组蛋白去乙酰化酶抑制剂与T细胞靶向免疫疗法协同作用可保护β细胞代谢功能并诱导NOD小鼠新发自身免疫糖尿病的缓解。 通过靶向涉及免疫介导的胰腺β细胞破坏的主要因子的联合疗法似乎是有效治疗1型糖尿病的方法。研究人员假设口服活性泛组蛋白脱乙酰酶抑制剂（HDACi：givinostat）与亚治疗剂量的CD3抗体的组合治疗可以提供理想的

近日，国际杂志 《Diabetologia》上在线发表一项关于口服组蛋白去乙酰化酶抑制剂与T细胞靶向免疫疗法协同作用可保护β细胞代谢功能并诱导NOD小鼠新发自身免疫糖尿病的缓解。 通过靶向涉及免疫介导的胰腺β细胞破坏的主要因子的联合疗法似乎是有效治疗1型糖尿病的方法。研究人员假设口服活性泛组蛋白脱乙酰酶抑制剂（HDACi：givinostat）与亚治疗剂量的CD3抗体的组合治疗可以提供理想的协同作用以治疗持续的自身免疫。 给最近发糖尿病的CD3ε（也称为CD3E）链（NOD-huCD3ε）转基因NOD小鼠口服givinostat，亚治疗剂量的人源化CD3抗体（otelixizumab，50微克/天，5天，静脉内）或两种药物的组合。在治疗的小鼠中分析疾病缓解，代谢谱和自身反应性T细胞应答情况。 研究人员证明，givinostat与otelixizumab协同作用，可诱导80％近期患糖尿病的NOD- huCD3ε小鼠获得持久的糖尿病缓解。仅使用otelixizumab治疗的小鼠中只有47％获得缓解。口服givinostat单药治疗并未逆转已确定的糖尿病，但减少了炎症性细胞因子（IL-1β，

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    2018-10-07 ms9608593228839890

    #DIA#

    0

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    2018-11-14 jklm09

    #抑制剂#

    0

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    2018-06-07 般若傻瓜

    #组蛋白去乙酰化酶抑制剂#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1638574, encodeId=34d916385e400, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sun Oct 07 13:08:00 CST 2018, time=2018-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851695, encodeId=d7cd1851695a4, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Nov 14 07:08:00 CST 2018, time=2018-11-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2045496, encodeId=db7c204549648, content=<a href='/topic/show?id=37b4e7743b1' target=_blank style='color:#2F92EE;'>#组蛋白去乙酰化酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77743, encryptionId=37b4e7743b1, topicName=组蛋白去乙酰化酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Thu Jun 07 13:08:00 CST 2018, time=2018-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060512, encodeId=de1c20605128c, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Sat Mar 30 19:08:00 CST 2019, time=2019-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1760656, encodeId=fd071e606565a, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Sep 11 07:08:00 CST 2018, time=2018-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384677, encodeId=c4df13846e75c, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529465, encodeId=bbef1529465f0, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1618893, encodeId=1ca5161889323, content=<a href='/topic/show?id=007419239ca' target=_blank style='color:#2F92EE;'>#β细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19239, encryptionId=007419239ca, topicName=β细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b69919964433, createdName=ms24272190615788285182, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2019-03-30 许安

    #去乙酰化酶#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1638574, encodeId=34d916385e400, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sun Oct 07 13:08:00 CST 2018, time=2018-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851695, encodeId=d7cd1851695a4, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Nov 14 07:08:00 CST 2018, time=2018-11-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2045496, encodeId=db7c204549648, content=<a href='/topic/show?id=37b4e7743b1' target=_blank style='color:#2F92EE;'>#组蛋白去乙酰化酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77743, encryptionId=37b4e7743b1, topicName=组蛋白去乙酰化酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Thu Jun 07 13:08:00 CST 2018, time=2018-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060512, encodeId=de1c20605128c, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Sat Mar 30 19:08:00 CST 2019, time=2019-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1760656, encodeId=fd071e606565a, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Sep 11 07:08:00 CST 2018, time=2018-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384677, encodeId=c4df13846e75c, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529465, encodeId=bbef1529465f0, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1618893, encodeId=1ca5161889323, content=<a href='/topic/show?id=007419239ca' target=_blank style='color:#2F92EE;'>#β细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19239, encryptionId=007419239ca, topicName=β细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b69919964433, createdName=ms24272190615788285182, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2018-09-11 ms5439512287675881

    #BET#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1638574, encodeId=34d916385e400, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sun Oct 07 13:08:00 CST 2018, time=2018-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851695, encodeId=d7cd1851695a4, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Nov 14 07:08:00 CST 2018, time=2018-11-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2045496, encodeId=db7c204549648, content=<a href='/topic/show?id=37b4e7743b1' target=_blank style='color:#2F92EE;'>#组蛋白去乙酰化酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77743, encryptionId=37b4e7743b1, topicName=组蛋白去乙酰化酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Thu Jun 07 13:08:00 CST 2018, time=2018-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060512, encodeId=de1c20605128c, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Sat Mar 30 19:08:00 CST 2019, time=2019-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1760656, encodeId=fd071e606565a, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Sep 11 07:08:00 CST 2018, time=2018-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384677, encodeId=c4df13846e75c, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529465, encodeId=bbef1529465f0, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1618893, encodeId=1ca5161889323, content=<a href='/topic/show?id=007419239ca' target=_blank style='color:#2F92EE;'>#β细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19239, encryptionId=007419239ca, topicName=β细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b69919964433, createdName=ms24272190615788285182, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2018-04-26 xqptu

    #组蛋白#

    0

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    2018-04-26 yangshch

    #细胞代谢#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1638574, encodeId=34d916385e400, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Sun Oct 07 13:08:00 CST 2018, time=2018-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851695, encodeId=d7cd1851695a4, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Nov 14 07:08:00 CST 2018, time=2018-11-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2045496, encodeId=db7c204549648, content=<a href='/topic/show?id=37b4e7743b1' target=_blank style='color:#2F92EE;'>#组蛋白去乙酰化酶抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77743, encryptionId=37b4e7743b1, topicName=组蛋白去乙酰化酶抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ad9f79, createdName=般若傻瓜, createdTime=Thu Jun 07 13:08:00 CST 2018, time=2018-06-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2060512, encodeId=de1c20605128c, content=<a href='/topic/show?id=d4183e22569' target=_blank style='color:#2F92EE;'>#去乙酰化酶#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37225, encryptionId=d4183e22569, topicName=去乙酰化酶)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2dd327, createdName=许安, createdTime=Sat Mar 30 19:08:00 CST 2019, time=2019-03-30, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1760656, encodeId=fd071e606565a, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Tue Sep 11 07:08:00 CST 2018, time=2018-09-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1384677, encodeId=c4df13846e75c, content=<a href='/topic/show?id=5c74e7739f0' target=_blank style='color:#2F92EE;'>#组蛋白#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=67, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77739, encryptionId=5c74e7739f0, topicName=组蛋白)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea13490, createdName=xqptu, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1529465, encodeId=bbef1529465f0, content=<a href='/topic/show?id=ba3be7774b6' target=_blank style='color:#2F92EE;'>#细胞代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=103, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77774, encryptionId=ba3be7774b6, topicName=细胞代谢)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=771d11946860, createdName=yangshch, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1618893, encodeId=1ca5161889323, content=<a href='/topic/show?id=007419239ca' target=_blank style='color:#2F92EE;'>#β细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=69, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=19239, encryptionId=007419239ca, topicName=β细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b69919964433, createdName=ms24272190615788285182, createdTime=Thu Apr 26 06:08:00 CST 2018, time=2018-04-26, status=1, ipAttribution=)]
    2018-04-26 ms24272190615788285182

    #β细胞#

    0

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