PLOS Pathog:血红素途径作为靶向肝期疟原虫预防药物的潜在靶标

2017-07-16 MedSci MedSci原创

由于抗药性,缺乏有效疫苗以及持续的冲突与贫困这列问题的共同存在,疟疾仍然是全球重大的健康危机。对寄生虫生命各阶段的代谢途径的了解对于优先考虑及研发靶向新型抗寄生虫化合物方面非常重要。啮齿动物疟原虫-伯氏疟原虫异常血红素合成途径需要八种酶,它们分别分布在线粒体,胞浆和细胞质上。

近日,国际杂志 《CLIN CHEM》在线发表一项有关伯氏疟原虫中的一种新型遗传技术能够对蚊期发育所需基因进行肝期分析,并表明从头血红素合成对于疟原虫的肝期发育是至关重要的研究。

由于抗药性,缺乏有效疫苗以及持续的冲突与贫困这列问题的共同存在,疟疾仍然是全球重大的健康危机。对寄生虫生命各阶段的代谢途径的了解对于优先考虑及研发靶向新型抗寄生虫化合物方面非常重要。啮齿动物疟原虫-伯氏疟原虫异常血红素合成途径需要八种酶,它们分别分布在线粒体,胞浆和细胞质上。删除通路中的最后一个酶-铁螯合酶(FC)基因,表明血红素合成在生命周期的红细胞阶段不是必需的,但是在完成蚊子卵囊发育是需要的。在蚊子阶段FC缺失导致的致死率使得难以对这些突变在随后肝期的影响进行研究。为了克服这一点,研究人员将位点特异性荧光团表达与遗传互补方法结合,得到能够同时产生FC表达和FC缺陷子孢子混合物的杂合卵囊。这些子孢子表现出正常的运动能力,并且可以侵入肝细胞,并可以通过荧光和表型鉴别FC缺陷型疟原虫。FC缺陷的疟原虫在肝细胞中表现出严重的生长缺陷,在体外培养时,肝发育早期至中期也会出现发育失败。FC缺陷疟原虫不能在体外完成肝阶段发育,也不能感染小鼠,进一步确认在肝期受阻。

这些结果验证了血红素途径作为靶向肝期疟原虫预防药物的潜在目标。此外,研究人员还证明,简单的遗传方法可以将表型窗口扩展到昆虫阶段之外,对在血细胞期非必须的,但在蚊体内完成发育过程是必须的基因进行进行直接反向遗传分析开创了广阔的前景。

原始出处:

Upeksha L. Rathnapala, Christopher D. Goodman, et al.A novel genetic technique in Plasmodium berghei allows liver stage analysis of genes required for mosquito stage development and demonstrates that de novo heme synthesis is essential for liver stage development in the malaria parasite.

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    2017-07-19 ylzr123

    认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。给点赞啦

    0

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    2017-07-18 zhaojie88
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  4. [GetPortalCommentsPageByObjectIdResponse(id=223810, encodeId=a681223810a3, content=认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。给点赞啦, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Wed Jul 19 08:14:52 CST 2017, time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352767, encodeId=74681352e67b3, content=<a href='/topic/show?id=827d9996311' target=_blank style='color:#2F92EE;'>#靶标#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99963, encryptionId=827d9996311, topicName=靶标)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387848, encodeId=2e11138e84848, content=<a href='/topic/show?id=25ffe04313d' target=_blank style='color:#2F92EE;'>#疟原虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70431, encryptionId=25ffe04313d, topicName=疟原虫)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7e622500011, createdName=12498484m46(暂无昵称), createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512080, encodeId=abd615120809d, content=<a href='/topic/show?id=29b28986491' target=_blank style='color:#2F92EE;'>#血红素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89864, encryptionId=29b28986491, topicName=血红素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ef8a10431556, createdName=ms1692212821629096, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223091, encodeId=cc80223091f5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Mon Jul 17 07:32:37 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223070, encodeId=d0822230e07f, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Jul 17 07:24:29 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223021, encodeId=8415223021e8, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, 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=Mon Jul 17 06:02:36 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223014, encodeId=a65c22301422, content=值得推荐一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLBWOEtiahpXHGVdbFId5PLgK775YNA1ria3lM9KsJT6iczgIhov5sobd1Nr0raUBP58GkUDzvfDic9RCg/0, createdBy=0d021989245, createdName=189****1577, createdTime=Mon Jul 17 05:47:42 CST 2017, time=2017-07-17, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=223810, encodeId=a681223810a3, content=认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。给点赞啦, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Wed Jul 19 08:14:52 CST 2017, time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352767, encodeId=74681352e67b3, content=<a href='/topic/show?id=827d9996311' target=_blank style='color:#2F92EE;'>#靶标#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99963, encryptionId=827d9996311, topicName=靶标)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387848, encodeId=2e11138e84848, content=<a href='/topic/show?id=25ffe04313d' target=_blank style='color:#2F92EE;'>#疟原虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70431, encryptionId=25ffe04313d, topicName=疟原虫)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7e622500011, createdName=12498484m46(暂无昵称), createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512080, encodeId=abd615120809d, content=<a href='/topic/show?id=29b28986491' target=_blank style='color:#2F92EE;'>#血红素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89864, encryptionId=29b28986491, topicName=血红素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ef8a10431556, createdName=ms1692212821629096, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223091, encodeId=cc80223091f5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Mon Jul 17 07:32:37 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223070, encodeId=d0822230e07f, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Jul 17 07:24:29 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223021, encodeId=8415223021e8, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, 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=Mon Jul 17 06:02:36 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223014, encodeId=a65c22301422, content=值得推荐一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLBWOEtiahpXHGVdbFId5PLgK775YNA1ria3lM9KsJT6iczgIhov5sobd1Nr0raUBP58GkUDzvfDic9RCg/0, createdBy=0d021989245, createdName=189****1577, createdTime=Mon Jul 17 05:47:42 CST 2017, time=2017-07-17, status=1, ipAttribution=)]
    2017-07-17 1dd8c52fm63(暂无匿称)

    继续关注

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=223810, encodeId=a681223810a3, content=认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。给点赞啦, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Wed Jul 19 08:14:52 CST 2017, time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352767, encodeId=74681352e67b3, content=<a href='/topic/show?id=827d9996311' target=_blank style='color:#2F92EE;'>#靶标#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99963, encryptionId=827d9996311, topicName=靶标)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387848, encodeId=2e11138e84848, content=<a href='/topic/show?id=25ffe04313d' target=_blank style='color:#2F92EE;'>#疟原虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70431, encryptionId=25ffe04313d, topicName=疟原虫)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7e622500011, createdName=12498484m46(暂无昵称), createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512080, encodeId=abd615120809d, content=<a href='/topic/show?id=29b28986491' target=_blank style='color:#2F92EE;'>#血红素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89864, encryptionId=29b28986491, topicName=血红素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ef8a10431556, createdName=ms1692212821629096, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223091, encodeId=cc80223091f5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Mon Jul 17 07:32:37 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223070, encodeId=d0822230e07f, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Jul 17 07:24:29 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223021, encodeId=8415223021e8, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, 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=Mon Jul 17 06:02:36 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223014, encodeId=a65c22301422, content=值得推荐一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLBWOEtiahpXHGVdbFId5PLgK775YNA1ria3lM9KsJT6iczgIhov5sobd1Nr0raUBP58GkUDzvfDic9RCg/0, createdBy=0d021989245, createdName=189****1577, createdTime=Mon Jul 17 05:47:42 CST 2017, time=2017-07-17, status=1, ipAttribution=)]
    2017-07-17 清风拂面

    谢谢分享学习了

    0

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    2017-07-17 刘煜

    学习了谢谢分享

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=223810, encodeId=a681223810a3, content=认真学习,把间接经验应用到临床实践中去,然后再总结出新思路。给点赞啦, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Wed Jul 19 08:14:52 CST 2017, time=2017-07-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1352767, encodeId=74681352e67b3, content=<a href='/topic/show?id=827d9996311' target=_blank style='color:#2F92EE;'>#靶标#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=99963, encryptionId=827d9996311, topicName=靶标)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1387848, encodeId=2e11138e84848, content=<a href='/topic/show?id=25ffe04313d' target=_blank style='color:#2F92EE;'>#疟原虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70431, encryptionId=25ffe04313d, topicName=疟原虫)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7e622500011, createdName=12498484m46(暂无昵称), createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1512080, encodeId=abd615120809d, content=<a href='/topic/show?id=29b28986491' target=_blank style='color:#2F92EE;'>#血红素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89864, encryptionId=29b28986491, topicName=血红素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ef8a10431556, createdName=ms1692212821629096, createdTime=Tue Jul 18 13:29:00 CST 2017, time=2017-07-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223091, encodeId=cc80223091f5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Mon Jul 17 07:32:37 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223070, encodeId=d0822230e07f, content=谢谢分享学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Mon Jul 17 07:24:29 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223021, encodeId=8415223021e8, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, 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=Mon Jul 17 06:02:36 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223014, encodeId=a65c22301422, content=值得推荐一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLBWOEtiahpXHGVdbFId5PLgK775YNA1ria3lM9KsJT6iczgIhov5sobd1Nr0raUBP58GkUDzvfDic9RCg/0, createdBy=0d021989245, createdName=189****1577, createdTime=Mon Jul 17 05:47:42 CST 2017, time=2017-07-17, status=1, ipAttribution=)]
    2017-07-17 189****1577

    值得推荐一下

    0