十问十答,轻松掌握磺脲类降糖药!

2022-05-15 王维波 医学界内分泌频道

磺脲类降糖药,属于促进胰岛素分泌剂,是治疗2型糖尿病的一线药物,在我国2型糖尿病治疗中占有重要地位。

磺脲类降糖药,属于促进胰岛素分泌剂,是治疗2型糖尿病的一线药物,在我国2型糖尿病治疗中占有重要地位。磺脲类降糖药种类多,临床应用广,患者需求量大,在临床使用中常见问题有哪些?我们应该如何合理用药?


问:临床常见的磺脲类品种有哪些、有何不同?


常见的磺脲类降糖药包括格列本脲、格列吡嗪、格列齐特等,主要特点见下表:



(注:药物品种限普通剂型)


问:磺脲类的药理作用及适应证是什么?


磺脲类的主要药理作用是通过与胰岛β细胞膜 ATP敏感性钾通道KATP的磺脲类受体(SUR)-l 结合,促使KATP关闭,从而刺激内源性胰岛素分泌。此外部分药物也具有改善外周胰岛素抵抗降糖的作用,适用于有一定β细胞功能、无使用禁忌的2型糖尿病患者的治疗。


问:磺脲类的用药原则?


①以餐后血糖升高为主者,宜选择格列吡嗪等短效磺脲类;


②以空腹血糖升高或餐后和空腹血糖均升高者,宜选择依从性好、低血糖发生风险低的中长效磺脲类(如格列美脲、格列吡嗪控释片等);


③若磺脲类单药治疗血糖控制不佳,应与其他降糖药物如双胍类、α-糖苷酶抑制剂或TZDs类药物联用。


问:磺脲类与其他药物相互作用有哪些?


①某些药物可增强磺脲类药物的降血糖作用,包括非甾体类抗炎药物和其它具有高蛋白质结合力的药物、单胺氧化酶抑制剂等。同时服用这些药物时,应严密监测低血糖的发生;


②某些药物具有升血糖的作用,包括噻嗪类利尿剂、皮质类固醇、甲状腺激素制剂、雌激素等,同时服这些药物时,应密切观察患者的血糖控制情况。


问:磺脲类常见不良反应有哪些?


常见不良反应有低血糖、体重增加、胃肠道不适、皮疹、头痛等;另外,该类药物有继发性失效不良反应,是与其他降糖药的不同之处。


问:磺脲类继发性失效的原因?


①糖尿病患者饮食、运动控制差;


②胰岛素抵抗加重;


③机体对药物快速耐药;


④胰岛β细胞功能减退(主要原因)。


问:如何治疗磺脲类失效?


①生活方式干预:严格饮食控制、适当运动,控制体重;


②联合用药:选择不同作用机制降糖药,与双胍类、α-糖苷酶抑制剂、TZDs类等联合治疗;


③换用另一种磺脲类:需在血糖控制良好基础上,进行更换;


④胰岛素治疗:尽快消除高糖毒性。


问:磺脲类禁忌有哪些?


禁用于药物过敏、1 型糖尿病、糖尿病酮症酸中毒或昏迷、严重肝或肾损伤等患者。


问:磺脲类在特殊人群中如何使用?


①格列奎酮仅5%经过肾脏排泄,严重肾功能不全(CKD4期)患者慎用。



(注:√√表示无需减量;√√表示减量;√表示用药经验有限)


②对于妊娠期妇女,格列苯脲极少通过胎盘屏障,有随机对照试验支持的有效性和短期安全性,但用药后有发生子痫前期和新生儿黄疸的风险。其他磺脲类不建议用于妊娠期妇女。


问:除了降糖,磺脲类还有哪些作用?


英国糖尿病前瞻性研究(UKPDS)等相关研究显示,磺脲类可减少微血管并发症的发生,早期使用还可减少大血管并发症和全因死亡的发生。


参考资料:

[1]中华医学会内分泌学分会.中国成人2型糖尿病胰岛素促泌剂应用的专家共识[J].2012;

[2]中国医师协会内分泌代谢科医师分会. 2型糖尿病合并慢性肾脏病口服降糖药用药原则中国专家共识(2015年更新版)[J].2016;

[3]中华医学会妇产科学分会产科学组. 妊娠合并糖尿病诊治指南(2014)[J].2014;

[4]中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2013年版)[J]. 2014;

[5]American Diabetes Association.Cardiovascular disease and risk management [J]. 2015;

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GetPortalCommentsPageByObjectIdResponse(id=127630, encodeId=15c812e6304e, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:47:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127577, encodeId=8c2912e57773, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, 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    2016-09-24 李东泽

    很好,不错,以后会多学习

    0

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createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 21:27:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=128006, encodeId=2787128006d1, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 17:35:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127826, encodeId=4ce712e826e5, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 15:55:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127729, encodeId=061612e729d4, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 15:00:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127630, encodeId=15c812e6304e, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:47:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127577, encodeId=8c2912e57773, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, 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  4. 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createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 21:27:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=128006, encodeId=2787128006d1, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 17:35:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127826, encodeId=4ce712e826e5, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, 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createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:37:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127336, encodeId=5c3a12e3363f, content=学习谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 15 09:49:00 CST 2016, time=2016-09-15, status=1, ipAttribution=)]
    2016-09-15 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

    0

  5. 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likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 15:55:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127729, encodeId=061612e729d4, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 15:00:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127630, encodeId=15c812e6304e, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:47:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127577, encodeId=8c2912e57773, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:37:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127336, encodeId=5c3a12e3363f, content=学习谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 15 09:49:00 CST 2016, time=2016-09-15, status=1, ipAttribution=)]
    2016-09-15 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

    0

  6. 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createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 21:27:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=128006, encodeId=2787128006d1, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 17:35:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127826, encodeId=4ce712e826e5, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, 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createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:37:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127336, encodeId=5c3a12e3363f, content=学习谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 15 09:49:00 CST 2016, time=2016-09-15, status=1, ipAttribution=)]
    2016-09-15 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

    0

  7. 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createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 21:27:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=128006, encodeId=2787128006d1, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 17:35:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127826, encodeId=4ce712e826e5, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, 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createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:37:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127336, encodeId=5c3a12e3363f, content=学习谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 15 09:49:00 CST 2016, time=2016-09-15, status=1, ipAttribution=)]
    2016-09-15 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

    0

  8. 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createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:37:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127336, encodeId=5c3a12e3363f, content=学习谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 15 09:49:00 CST 2016, time=2016-09-15, status=1, ipAttribution=)]
    2016-09-15 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

    0

  9. 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createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 21:27:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=128006, encodeId=2787128006d1, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 17:35:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127826, encodeId=4ce712e826e5, content=学习了,赞一个!!!, beContent=null, objectType=article, channel=null, level=null, 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createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:37:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127336, encodeId=5c3a12e3363f, content=学习谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 15 09:49:00 CST 2016, time=2016-09-15, status=1, ipAttribution=)]
    2016-09-15 1dd8a7c5m95(暂无匿称)

    学习了,赞一个!!!

    0

  10. 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createdName=1dd8a7c5m95(暂无匿称), createdTime=Thu Sep 15 14:37:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127336, encodeId=5c3a12e3363f, content=学习谢谢。, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cdnapi.center.medsci.cn/medsci/head/2017/04/21/72142930668371951a41ef4ea4b233e6.jpg, createdBy=dcbc1715228, createdName=刘煜, createdTime=Thu Sep 15 09:49:00 CST 2016, time=2016-09-15, status=1, ipAttribution=)]
    2016-09-15 刘煜

    学习谢谢。

    0

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