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mBio:尿感有救了,科学家制定了尿路感染疫苗策略!

2021-03-02 Dr.neuro MedSci原创

任何曾经发展为泌尿道感染(UTI)的人都知道,尿道感染会很痛苦,令人讨厌且持久。现如今,科学家制定尿路感染疫苗策略,有望减轻医疗负担。

任何曾经发展为泌尿道感染(UTI)的人都知道,尿道感染会很痛苦,令人讨厌且持久。泌尿道感染是人类最常见的细菌感染之一,尿路感染的复发率很高,主要困扰人群为女性,多达50%的女性一生中至少会经历一种尿路感染。

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但是,如果患者可以接种能预防未来尿路感染的疫苗会怎么样呢?现在,这个梦想也许已经实现。在3月1日发表于《美国国家科学院院刊》上的一项研究中,杜克大学的研究人员提出了一种新的疫苗接种策略,他们认为该策略可以对人体进行重新编程,以抵抗引起尿路感染的细菌。

Optimization of an Experimental Vaccine To Prevent Escherichia coli Urinary Tract Infection. mBio, 11(2). doi:10.1128/mbio.00555-20

延谱β-内酰胺酶生产菌株数量的增加,以及尿路感染最常见的致病菌大肠杆菌(UPEC)内潜在的碳青霉烯耐药性,为疫苗的开发带来了迫切的需求。

尽管此前已经在临床试验中研究过几种针对UTI的疫苗,但迄今为止它们取得的成功有限。也就是说,尽管膀胱感染的患病率很高,但目前在美国尚无有效的UTI疫苗可用。但该最新研究描述了一种高效的膀胱疫苗的潜力,该疫苗不仅可以根除残留的膀胱细菌,而且还可以预防将来的感染。

研究人员观察到,当老鼠的膀胱感染了大肠杆菌时,免疫系统会释放修复细胞来修复受损的组织,同时释放很少的免疫细胞来抵抗攻击者。这会导致细菌永远无法完全清除,细菌残存在膀胱中又会再次发作。该小组在小鼠模型中显示出有效的策略,涉及重新编程这种免疫反应不足。

研究者用与霍乱毒素结合的UPEC外膜铁受体FyuA、Hma、IreA和IutA对小鼠进行鼻内免疫,在挑战UPEC菌株CFT073或菌株536的条件下,对膀胱或肾脏提供保护。在这些数据的基础上,研究者试图优化疫苗接种途径(肌内、鼻内或皮下),结合适合人类使用的佐剂,包括氢氧化铝凝胶(alum)、单磷酸脂质A(MPLA)、未甲基化的CpG合成寡核苷酸(CpG)、聚肌苷酸:聚胞苷酸(polyIC)和突变热解大肠杆菌肠毒素(dmLT)。

免疫细胞(绿色)浸润膀胱内膜(红色)以抵抗入侵细菌。蓝色区域是其他膀胱组织细胞的细胞核。

通过给小鼠鼻内接种dmLT-IutA和dmLT-Hma后,膀胱菌落显著减少(分别为86倍和32倍),40%~42%的小鼠检测不到CFU。用CpG-IutA和polyIC-IutA对小鼠进行鼻内接种,分别显著降低了肾脏菌落(131倍)和尿液CFU(22倍)。"dmLT "在鼻内免疫的小鼠中产生的抗体反应最为稳定稳健,而MPLA和明矾在肌肉免疫时产生的抗原特异性血清IgG浓度更高。基于这些结果,得出结论,用dmLT佐剂配制的Hma或IutA的鼻内给药可提供最大的UPEC UTI保护。该报告推进了我们在研制针对不复杂UTI的疫苗方面的进展,这将极大地改善因复发性UTI而负担的妇女的生活质量,并能更好地进行抗生素管理

用外膜铁受体进行鼻内疫苗接种可产生强大的抗原特异性血清IgG反应。

当明矾或MPLA用作佐剂时,用外膜铁受体进行肌内接种可产生强大的抗原特异性血清IgG反应。

研究中显示,新的疫苗策略试图“指导”膀胱以更有效地抵抗攻击细菌。高效疫苗抗原与已知能促进细菌清除细胞募集的佐剂一起直接进入残留细菌的膀胱,其效果要优于传统的肌内疫苗接种。

研究人员报告说,经膀胱免疫的小鼠能有效抵御感染大肠杆菌并消除所有残留的膀胱细菌,这表明给药部位可能是确定疫苗有效性的重要考虑因素。

抗生素耐药性和医疗费用的上升,强调了开发一种针对最常见的UTI病原体--大肠杆菌的疫苗的必要性。用一种解毒热解肠毒素和两种表面暴露的受体Hma或IutA对小鼠进行鼻内接种,可显著降低膀胱内的细菌负担。这项工作突出了用适合人类使用的佐剂和编码限铁尿路感染所需的外膜铁受体的抗原配制的UTI疫苗的开发进展。

原始文献:

Forsyth, V. S., Himpsl, S. D., Smith, S. N., Sarkissian, C. A., Mike, L. A., Stocki, J. A., … Mobley, H. L. T. (2020). Optimization of an Experimental Vaccine To Prevent Escherichia coli Urinary Tract Infection. mBio, 11(2). doi:10.1128/mbio.00555-20 

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createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-07-29 口口王木木

    学习了

    0

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    2021-06-08 口口王木木

    有用,存了

    0

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createdTime=Wed Mar 03 04:27:57 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944892, encodeId=b15e94489255, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 02 19:02:00 CST 2021, time=2021-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944867, encodeId=a1a594486e43, content=尿路感染疫苗也有了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2022-01-03 sunylz
  4. 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createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-03-04 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

  5. 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createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-03-03 80615335422

    期待技术成熟效果稳定

    0

  6. 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createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-03-03 124292adm29暂无昵称

    尿路感染有疫苗了,太好了

    0

  7. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1919218, encodeId=daeb191921864, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Jan 03 11:44:48 CST 2022, time=2022-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=945550, encodeId=7af5945550eb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Mar 04 22:09:16 CST 2021, time=2021-03-04, status=1, ipAttribution=), 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createdTime=Wed Mar 03 06:44:30 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944985, encodeId=7686944985a5, content=<a href='/topic/show?id=1cab4e514e4' target=_blank style='color:#2F92EE;'>#尿路#</a>不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47514, encryptionId=1cab4e514e4, topicName=尿路)], attachment=null, authenticateStatus=null, createdAvatar=/img/user_icon.png, createdBy=8e6d5462230, createdName=鼠叔叔啦啦, createdTime=Wed Mar 03 05:26:56 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944977, encodeId=deb99449e7d4, content=新的启示,, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2db04864507, createdName=996950137, createdTime=Wed Mar 03 04:27:57 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944892, encodeId=b15e94489255, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 02 19:02:00 CST 2021, time=2021-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944867, encodeId=a1a594486e43, content=尿路感染疫苗也有了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-03-03 鼠叔叔啦啦

    #尿路#不错

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1003531, encodeId=0272100353141, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20230114/bc8f9e242ba04619a889c6a2e67ce2c1/f4da081d14584973854d77cd79b42c5b.jpg, createdBy=41181970428, createdName=口口王木木, createdTime=Thu Jul 29 09:38:30 CST 2021, time=2021-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971914, encodeId=c40b9e191480, content=有用,存了, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20230114/bc8f9e242ba04619a889c6a2e67ce2c1/f4da081d14584973854d77cd79b42c5b.jpg, createdBy=41181970428, createdName=口口王木木, createdTime=Tue Jun 08 17:46:25 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1919218, encodeId=daeb191921864, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Jan 03 11:44:48 CST 2022, time=2022-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=945550, encodeId=7af5945550eb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Mar 04 22:09:16 CST 2021, time=2021-03-04, status=1, ipAttribution=), 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createdTime=Wed Mar 03 06:44:30 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944985, encodeId=7686944985a5, content=<a href='/topic/show?id=1cab4e514e4' target=_blank style='color:#2F92EE;'>#尿路#</a>不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47514, encryptionId=1cab4e514e4, topicName=尿路)], attachment=null, authenticateStatus=null, createdAvatar=/img/user_icon.png, createdBy=8e6d5462230, createdName=鼠叔叔啦啦, createdTime=Wed Mar 03 05:26:56 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944977, encodeId=deb99449e7d4, content=新的启示,, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2db04864507, createdName=996950137, createdTime=Wed Mar 03 04:27:57 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944892, encodeId=b15e94489255, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 02 19:02:00 CST 2021, time=2021-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944867, encodeId=a1a594486e43, content=尿路感染疫苗也有了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-03-03 996950137

    新的启示,

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1003531, encodeId=0272100353141, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20230114/bc8f9e242ba04619a889c6a2e67ce2c1/f4da081d14584973854d77cd79b42c5b.jpg, createdBy=41181970428, createdName=口口王木木, createdTime=Thu Jul 29 09:38:30 CST 2021, time=2021-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=971914, encodeId=c40b9e191480, content=有用,存了, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20230114/bc8f9e242ba04619a889c6a2e67ce2c1/f4da081d14584973854d77cd79b42c5b.jpg, createdBy=41181970428, createdName=口口王木木, createdTime=Tue Jun 08 17:46:25 CST 2021, time=2021-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1919218, encodeId=daeb191921864, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Jan 03 11:44:48 CST 2022, time=2022-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=945550, encodeId=7af5945550eb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Mar 04 22:09:16 CST 2021, time=2021-03-04, status=1, ipAttribution=), 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createdTime=Wed Mar 03 06:44:30 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944985, encodeId=7686944985a5, content=<a href='/topic/show?id=1cab4e514e4' target=_blank style='color:#2F92EE;'>#尿路#</a>不错, beContent=null, objectType=article, channel=null, level=null, likeNumber=136, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47514, encryptionId=1cab4e514e4, topicName=尿路)], attachment=null, authenticateStatus=null, createdAvatar=/img/user_icon.png, createdBy=8e6d5462230, createdName=鼠叔叔啦啦, createdTime=Wed Mar 03 05:26:56 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944977, encodeId=deb99449e7d4, content=新的启示,, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2db04864507, createdName=996950137, createdTime=Wed Mar 03 04:27:57 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944892, encodeId=b15e94489255, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 02 19:02:00 CST 2021, time=2021-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944867, encodeId=a1a594486e43, content=尿路感染疫苗也有了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-03-02 jyzxjiangqin

    好文章!

    0

  10. 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status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1919218, encodeId=daeb191921864, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Mon Jan 03 11:44:48 CST 2022, time=2022-01-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=945550, encodeId=7af5945550eb, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=107, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Thu Mar 04 22:09:16 CST 2021, time=2021-03-04, status=1, ipAttribution=), 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createdTime=Wed Mar 03 04:27:57 CST 2021, time=2021-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944892, encodeId=b15e94489255, content=好文章!, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160806/IMG57A5698BDB0244113.jpg, createdBy=32a91358059, createdName=jyzxjiangqin, createdTime=Tue Mar 02 19:02:00 CST 2021, time=2021-03-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=944867, encodeId=a1a594486e43, content=尿路感染疫苗也有了!!!, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210110/e6124a4b19bc40ce8afaae096d21126b/dd778ac260c9416eb87e7d08139507f5.jpg, createdBy=4d2f5079605, createdName=科研科研科研, createdTime=Tue Mar 02 18:14:20 CST 2021, time=2021-03-02, status=1, ipAttribution=)]
    2021-03-02 科研科研科研

    尿路感染疫苗也有了!!!

    0

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