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噬菌体治疗创面细菌感染研究进展

2016-07-20 中华烧伤杂志 中华烧伤杂志

近年来随着细菌耐药情况的日益严峻,应用噬菌体防控细菌的研究重新受到研究者的重视。噬菌体作为细菌的病毒,其入血后,对机体的影响还不尽清楚,临床上应用噬菌体治疗菌血症尚鲜见报道。应用噬菌体对菌血症等感染的治疗大多停留在动物实验阶段,然而噬菌体在治疗暴露性细菌感染方面取得了较大进展,如在细菌感染性肺炎动物模型、脓肿动物模型和烧伤动物模型中,诸多相关研究显示了噬菌体可以用于细菌感染的防控。引起院内烧伤

近年来随着细菌耐药情况的日益严峻,应用噬菌体防控细菌的研究重新受到研究者的重视。噬菌体作为细菌的病毒,其入血后,对机体的影响还不尽清楚,临床上应用噬菌体治疗菌血症尚鲜见报道。


应用噬菌体对菌血症等感染的治疗大多停留在动物实验阶段,然而噬菌体在治疗暴露性细菌感染方面取得了较大进展,如在细菌感染性肺炎动物模型、脓肿动物模型和烧伤动物模型中,诸多相关研究显示了噬菌体可以用于细菌感染的防控。


引起院内烧伤创面感染的细菌主要有金黄色葡萄球菌和铜绿假单胞菌等,随着它们对抗生素的耐药性日益增加,临床上将面临无抗生素可用的困境。


近年来,研究者在此类院内感染常见细菌的噬菌体分离和特性方面做了大量研究工作,结果显示,噬菌体可以用于创面细菌感染的治疗。本文主要对将噬菌体用于治疗创面细菌感染方面的研究进展进行综述。


1 噬菌体治疗创面金黄色葡萄球菌感染


近年来,抗甲氧西林金黄色葡萄球菌流行,且出现抗万古霉素金黄色葡萄球菌。在有些医院,抗甲氧西林金黄色葡萄球菌的分离率占所有金黄色葡萄球菌的60%,给临床治疗带来极大的困难。


对金黄色葡萄球菌噬菌体的研究显示,金黄色葡萄球菌噬菌体杀菌效果良好,尤其是肌尾科噬菌体,宿主谱广,已显示出良好的应用价值。如通过金黄色葡萄球菌引起的兔皮肤脓肿模型和小鼠菌血症模型的研究显示,噬菌体能用于防控金黄色葡萄球菌引起的感染。


在临床治疗创伤细菌感染研究方面,目前已有金黄色葡萄球菌相关噬菌体制剂用于临床试验研究。2009年,比利时研究者制备了去除LPS的包含有1株金黄色葡萄球菌噬菌体ISP、2株铜绿假单胞菌噬菌体14/1和PNM的制剂,将该噬菌体制剂喷洒于8例烧伤患者感染部位后,其中噬菌体分别对分离自该烧伤中心病房的金黄色葡萄球菌和铜绿假单胞菌有杀菌作用,该噬菌体制剂在使用过程中对患者没有产生可观察到的有害作用。


含有金黄色葡萄球菌和铜绿假单胞菌的噬菌体鸡尾酒制剂BFC-1包含1株肌尾科和1株短尾科铜绿假单胞菌噬菌体以及1株肌尾科金黄色葡萄球菌噬菌体,去除了LPS。有研究者应用该制剂治疗创面感染金黄色葡萄球菌或铜绿假单胞菌的患者,结果显示,噬菌体治疗组和抗生素治疗组细菌量没有差异,噬菌体治疗组没有可观察到的有害作用和临床非正常反应。


上述研究结果显示,应用噬菌体治疗创面感染,不会对机体产生可观察到的有害作用,治疗效果还需进一步临床试验研究评估。


2 噬菌体治疗创面铜绿假单胞菌感染


早在1957年,我国就有成功应用噬菌体控制铜绿假单胞菌感染的病例报道。除上述含铜绿假单胞菌的噬菌体制剂应用于临床的报道外,近年来,应用噬菌体治疗铜绿假单胞菌感染的临床试验研究也见报道。


Wright等应用噬菌体治疗由对抗生素耐药的铜绿假单胞菌引起的24例慢性耳炎患者,治疗后,对感染部位细菌和噬菌体进行定量分析显示,噬菌体治疗有效,患者无可观察到的不良反应。


动物研究也显示,噬菌体可以控制由铜绿假单胞菌引起的感染,包括肺部感染、尿路感染、皮肤感染和烧伤感染。有学者建立小鼠烧伤创面铜绿假单胞菌致死性感染模型,然后采取皮下注射、腹腔注射和肌内注射几种方式给予由3株铜绿假单胞菌噬菌体组成的鸡尾酒制剂。


结果显示噬菌体治疗可以显著降低铜绿假单胞菌感染的致死率,其中腹腔注射效果最好;进一步通过噬菌体在小鼠体内的代谢动力学研究显示,腹腔注射较皮下注射和肌内注射能使噬菌体更快地到达血液、肝脏和脾脏。该研究也说明了给予噬菌体方式不同,会产生不同的治愈效果。


Vieira等研究显示,噬菌体可以显著减少铜绿假单胞菌在离体人体皮肤感染模型中皮肤表面的定植数量,但是高剂量噬菌体组和低剂量噬菌体组所减少的细菌量差异无统计学意义(P>0.05)。以上研究提示在临床上运用噬菌体治疗细菌感染性疾病时,需要评估不同的噬菌体给予途径、频次和剂量,这些可能会影响到噬菌体的最终治疗效果。


3 噬菌体治疗其他创面细菌感染


肺炎克雷伯菌也是院内感染的重要病原菌,对抗生素耐药的肺炎克雷伯菌尤其是产碳青霉烯酶的肺炎克雷伯菌的流行,使得用于治疗该类细菌感染的抗生素也越来越少。


Kumari等研究显示,通过腹腔注射给予肺炎克雷伯菌噬菌体Kpn5,可以降低烧伤小鼠创面肺炎克雷伯菌感染引起的致死率,保护效果和由5株肺炎克雷伯菌噬菌体Kpn5、Kpn12、Kpn13、Kpn17、Kpn22组成的鸡尾酒制剂相似;进一步研究显示一些促炎性细胞因子包括IL-1β、TNF-α和抑炎性细胞因子IL-10在噬菌体治疗组的血液和肺泡灌洗液中的含量要显著低于未治疗组,也进一步说明,噬菌体治疗可以改善机体感染过程中引发的剧烈炎症反应。该研究证明噬菌体在动物感染模型中可以控制由肺炎克雷伯菌引起的烧伤创面感染。


4 展望


噬菌体治疗有很多优点,如能特异性杀死病原菌而不影响正常菌群,可以破坏细菌形成的生物膜。然而,噬菌体治疗也有很多不足,如杀菌谱窄,大规模工业化制备困难。


不过这些不足可以克服:(1)环境中种类多样的噬菌体为噬菌体制剂的制备提供了不竭的资源库,可以制备针对不同宿主菌的噬菌体鸡尾酒制剂来应对不同细菌引起的感染。


(2)抗生素和噬菌体联用能改善噬菌体的杀菌效果,也为噬菌体治疗提供了新的视角。随着生物技术的进步,医用噬菌体的大规模工业化的制备、运输和存储也将不再是难题。


噬菌体作为病毒的一类,其进入机体后的转归还不完全清楚,对机体的影响还不被人们所了解,且不同噬菌体组成成分各异,对机体的影响也不尽相同,这是传统抗生素研究者对噬菌体治疗细菌感染产生怀疑的重要原因之一,也是噬菌体在治疗菌血症等细菌感染性疾病的研究方面进展缓慢的重要原因之一。


但是其在治疗暴露性细菌感染尤其是创面感染方面显示出很大的潜能,在治疗暴露性细菌感染过程中,可以避免噬菌体直接进入血液而引起不必要的争议。


随着基因组测序技术的发展,近年来越来越多的噬菌体基因组被报道,使得研究者可从基因组水平深入了解噬菌体的杀菌机制,噬菌体基因组上通常编码有裂解酶类基因,这类基因产物能破坏细菌细胞壁结构进而杀死细菌。


根据作用底物化学键的不同,噬菌体裂解酶可以分为5个大类:N-乙酰葡糖胺酶、乙酰胞壁质酶、肽链内切酶、裂解性转糖基酶和酰胺水解酶。


越来越多的研究也证实,这类酶也可以用于细菌感染的治疗,并可通过改造这些酶类使其具有更强杀菌活性。进而可开发出成分更加单一的噬菌体衍生制剂用于防控细菌感染。


中华烧伤杂志 2015年5月31卷5期

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    2016-10-04 榄枷檬

    噬菌体真的能用于创面细菌感染的治疗嘛?

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=140168, encodeId=331214016813, content=噬菌体真的能用于创面细菌感染的治疗嘛?, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Tue Oct 04 23:35:20 CST 2016, time=2016-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134565, encodeId=c4411345656a, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Sat Sep 24 21:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100330, encodeId=d8b910033076, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100331, encodeId=61301003316f, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631982, encodeId=6dc5163198202, content=<a href='/topic/show?id=b88a321e6b2' target=_blank style='color:#2F92EE;'>#创面#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32176, encryptionId=b88a321e6b2, topicName=创面)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6fda21837820, createdName=qindq, createdTime=Fri Oct 07 14:40:00 CST 2016, time=2016-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1280653, encodeId=3324128065317, content=<a href='/topic/show?id=beefe810798' target=_blank style='color:#2F92EE;'>#细菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78107, encryptionId=beefe810798, topicName=细菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6779163, createdName=liuhuangbo, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1341378, encodeId=d17213413e8f2, content=<a href='/topic/show?id=a9d940353d8' target=_blank style='color:#2F92EE;'>#噬菌体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40353, encryptionId=a9d940353d8, topicName=噬菌体)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLIQxicGuURvblbKDmmdLreAdrFKYA57y7viabog6mfk8dXQpQzYCf0ibcgoMnFrQ2MiaV8Iic4ocdhEfw/132, createdBy=0e3a2500177, createdName=ms1692810954239974, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380525, encodeId=36dd1380525d0, content=<a href='/topic/show?id=9281e34519b' target=_blank style='color:#2F92EE;'>#研究进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73451, encryptionId=9281e34519b, topicName=研究进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f13d475, createdName=mashirong, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=)]
    2016-09-24 1dd8c52fm63(暂无匿称)

    了解一下

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=140168, encodeId=331214016813, content=噬菌体真的能用于创面细菌感染的治疗嘛?, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Tue Oct 04 23:35:20 CST 2016, time=2016-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134565, encodeId=c4411345656a, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Sat Sep 24 21:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100330, encodeId=d8b910033076, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100331, encodeId=61301003316f, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631982, encodeId=6dc5163198202, content=<a href='/topic/show?id=b88a321e6b2' target=_blank style='color:#2F92EE;'>#创面#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32176, encryptionId=b88a321e6b2, topicName=创面)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6fda21837820, createdName=qindq, createdTime=Fri Oct 07 14:40:00 CST 2016, time=2016-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1280653, encodeId=3324128065317, content=<a href='/topic/show?id=beefe810798' target=_blank style='color:#2F92EE;'>#细菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78107, encryptionId=beefe810798, topicName=细菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6779163, createdName=liuhuangbo, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1341378, encodeId=d17213413e8f2, content=<a href='/topic/show?id=a9d940353d8' target=_blank style='color:#2F92EE;'>#噬菌体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40353, encryptionId=a9d940353d8, topicName=噬菌体)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLIQxicGuURvblbKDmmdLreAdrFKYA57y7viabog6mfk8dXQpQzYCf0ibcgoMnFrQ2MiaV8Iic4ocdhEfw/132, createdBy=0e3a2500177, createdName=ms1692810954239974, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380525, encodeId=36dd1380525d0, content=<a href='/topic/show?id=9281e34519b' target=_blank style='color:#2F92EE;'>#研究进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73451, encryptionId=9281e34519b, topicName=研究进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f13d475, createdName=mashirong, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=)]
    2016-08-18 doctorJiangchao

    继续关注

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=140168, encodeId=331214016813, content=噬菌体真的能用于创面细菌感染的治疗嘛?, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Tue Oct 04 23:35:20 CST 2016, time=2016-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134565, encodeId=c4411345656a, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Sat Sep 24 21:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100330, encodeId=d8b910033076, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100331, encodeId=61301003316f, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631982, encodeId=6dc5163198202, content=<a href='/topic/show?id=b88a321e6b2' target=_blank style='color:#2F92EE;'>#创面#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32176, encryptionId=b88a321e6b2, topicName=创面)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6fda21837820, createdName=qindq, createdTime=Fri Oct 07 14:40:00 CST 2016, time=2016-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1280653, encodeId=3324128065317, content=<a href='/topic/show?id=beefe810798' target=_blank style='color:#2F92EE;'>#细菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78107, encryptionId=beefe810798, topicName=细菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6779163, createdName=liuhuangbo, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1341378, encodeId=d17213413e8f2, content=<a href='/topic/show?id=a9d940353d8' target=_blank style='color:#2F92EE;'>#噬菌体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40353, encryptionId=a9d940353d8, topicName=噬菌体)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLIQxicGuURvblbKDmmdLreAdrFKYA57y7viabog6mfk8dXQpQzYCf0ibcgoMnFrQ2MiaV8Iic4ocdhEfw/132, createdBy=0e3a2500177, createdName=ms1692810954239974, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380525, encodeId=36dd1380525d0, content=<a href='/topic/show?id=9281e34519b' target=_blank style='color:#2F92EE;'>#研究进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73451, encryptionId=9281e34519b, topicName=研究进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f13d475, createdName=mashirong, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=)]
    2016-08-18 doctorJiangchao

    继续关注

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=140168, encodeId=331214016813, content=噬菌体真的能用于创面细菌感染的治疗嘛?, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Tue Oct 04 23:35:20 CST 2016, time=2016-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134565, encodeId=c4411345656a, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Sat Sep 24 21:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100330, encodeId=d8b910033076, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100331, encodeId=61301003316f, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631982, encodeId=6dc5163198202, content=<a href='/topic/show?id=b88a321e6b2' target=_blank style='color:#2F92EE;'>#创面#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32176, encryptionId=b88a321e6b2, topicName=创面)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6fda21837820, createdName=qindq, createdTime=Fri Oct 07 14:40:00 CST 2016, time=2016-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1280653, encodeId=3324128065317, content=<a href='/topic/show?id=beefe810798' target=_blank style='color:#2F92EE;'>#细菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78107, encryptionId=beefe810798, topicName=细菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6779163, createdName=liuhuangbo, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1341378, encodeId=d17213413e8f2, content=<a href='/topic/show?id=a9d940353d8' target=_blank style='color:#2F92EE;'>#噬菌体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40353, encryptionId=a9d940353d8, topicName=噬菌体)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLIQxicGuURvblbKDmmdLreAdrFKYA57y7viabog6mfk8dXQpQzYCf0ibcgoMnFrQ2MiaV8Iic4ocdhEfw/132, createdBy=0e3a2500177, createdName=ms1692810954239974, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380525, encodeId=36dd1380525d0, content=<a href='/topic/show?id=9281e34519b' target=_blank style='color:#2F92EE;'>#研究进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73451, encryptionId=9281e34519b, topicName=研究进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f13d475, createdName=mashirong, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=)]
    2016-10-07 qindq
  6. [GetPortalCommentsPageByObjectIdResponse(id=140168, encodeId=331214016813, content=噬菌体真的能用于创面细菌感染的治疗嘛?, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Tue Oct 04 23:35:20 CST 2016, time=2016-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134565, encodeId=c4411345656a, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Sat Sep 24 21:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100330, encodeId=d8b910033076, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100331, encodeId=61301003316f, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631982, encodeId=6dc5163198202, content=<a href='/topic/show?id=b88a321e6b2' target=_blank style='color:#2F92EE;'>#创面#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32176, encryptionId=b88a321e6b2, topicName=创面)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6fda21837820, createdName=qindq, createdTime=Fri Oct 07 14:40:00 CST 2016, time=2016-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1280653, encodeId=3324128065317, content=<a href='/topic/show?id=beefe810798' target=_blank style='color:#2F92EE;'>#细菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78107, encryptionId=beefe810798, topicName=细菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6779163, createdName=liuhuangbo, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1341378, encodeId=d17213413e8f2, content=<a href='/topic/show?id=a9d940353d8' target=_blank style='color:#2F92EE;'>#噬菌体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40353, encryptionId=a9d940353d8, topicName=噬菌体)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLIQxicGuURvblbKDmmdLreAdrFKYA57y7viabog6mfk8dXQpQzYCf0ibcgoMnFrQ2MiaV8Iic4ocdhEfw/132, createdBy=0e3a2500177, createdName=ms1692810954239974, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380525, encodeId=36dd1380525d0, content=<a href='/topic/show?id=9281e34519b' target=_blank style='color:#2F92EE;'>#研究进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73451, encryptionId=9281e34519b, topicName=研究进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f13d475, createdName=mashirong, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=140168, encodeId=331214016813, content=噬菌体真的能用于创面细菌感染的治疗嘛?, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Pw2csslt7CukWiabqiblnQAXaDEiaxhu025c3P0XshccTrbvGWBjKvnHIxbK3vqa80P7WGIFuicCFet97TicrNKpgB3TdabxP1vMh/0, createdBy=28851960965, createdName=榄枷檬, createdTime=Tue Oct 04 23:35:20 CST 2016, time=2016-10-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=134565, encodeId=c4411345656a, content=了解一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=93f31631454, createdName=1dd8c52fm63(暂无匿称), createdTime=Sat Sep 24 21:28:00 CST 2016, time=2016-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100330, encodeId=d8b910033076, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=92, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=100331, encodeId=61301003316f, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=78, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Thu Aug 18 14:51:00 CST 2016, time=2016-08-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1631982, encodeId=6dc5163198202, content=<a href='/topic/show?id=b88a321e6b2' target=_blank style='color:#2F92EE;'>#创面#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=90, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=32176, encryptionId=b88a321e6b2, topicName=创面)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6fda21837820, createdName=qindq, createdTime=Fri Oct 07 14:40:00 CST 2016, time=2016-10-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1280653, encodeId=3324128065317, content=<a href='/topic/show?id=beefe810798' target=_blank style='color:#2F92EE;'>#细菌感染#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78107, encryptionId=beefe810798, topicName=细菌感染)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6779163, createdName=liuhuangbo, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1341378, encodeId=d17213413e8f2, content=<a href='/topic/show?id=a9d940353d8' target=_blank style='color:#2F92EE;'>#噬菌体#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=40353, encryptionId=a9d940353d8, topicName=噬菌体)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLIQxicGuURvblbKDmmdLreAdrFKYA57y7viabog6mfk8dXQpQzYCf0ibcgoMnFrQ2MiaV8Iic4ocdhEfw/132, createdBy=0e3a2500177, createdName=ms1692810954239974, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1380525, encodeId=36dd1380525d0, content=<a href='/topic/show?id=9281e34519b' target=_blank style='color:#2F92EE;'>#研究进展#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73451, encryptionId=9281e34519b, topicName=研究进展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f13d475, createdName=mashirong, createdTime=Fri Jul 22 13:40:00 CST 2016, time=2016-07-22, status=1, ipAttribution=)]
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