穿拖鞋、浓眼影、爱粉红……这名个性教授有望解决超级细菌难题

2017-06-12 MedSci 药明康德

Janelle Ayres教授是美国最著名的生物研究所之一Salk Institute for Biological Studies(以下简称Salk Institute)的一位科学家。几年前,她父亲因为感染超级细菌引发脓毒症,她守在床边度过整整9天痛苦的日子。父亲最终没有击败超级细菌,使她感到悲伤,继而感到沮丧。从那时起,她一直努力寻找一种更好的方法,来帮助跟父亲一样的不幸患者。

Janelle Ayres教授是美国最著名的生物研究所之一Salk Institute for Biological Studies(以下简称Salk Institute)的一位科学家。几年前,她父亲因为感染超级细菌引发脓毒症,她守在床边度过整整9天痛苦的日子。父亲最终没有击败超级细菌,使她感到悲伤,继而感到沮丧。从那时起,她一直努力寻找一种更好的方法,来帮助跟父亲一样的不幸患者。

事实上,Ayres教授的实验室就是专门研究细菌的。治疗抗感染疾病,科学家几十年来一直关注免疫系统如何与病原体作斗争。她的做法却反其道而行之,不是去研究如何抵抗细菌感染,而是研究如何帮助身体耐受细菌。

Ayres教授正在利用微生物学,遗传学和免疫学领域的各种高科技工具,了解为何有些人会有更好的抗感染能力。她正在开展的研究项目包括寻找有益的细菌,帮助一些患者群体保持健康的食欲,或者在严重疾病发作期间修复损伤的组织。她相信自己的成果能够帮助人们抗击脓毒症,疟疾,霍乱和其他感染疾病。

目前使用抗生素和抗病毒药物作为治疗感染的标准疗法无疑是不够的。这些药物不适用于所有疾病,它们杀伤坏细菌的同时也会杀死好细菌,而且抗生素滥用一旦导致耐药细菌或“超级耐药细菌”,几乎没有医疗手段可以治愈。Ayres的父亲Robert Lamberton先生就是在2015年做常规胆囊手术后发生感染,发展为脓毒症,最后住进ICU,所有抗生素都无效。

“我们只关注于开发新型抗生素,但这其实是一场不会赢的军备竞赛。”

Ayres博士的研究生涯始于斯坦福大学(Stanford University),从处理10000只李斯特菌感染的苍蝇开始,为了给苍蝇注射细菌,她的手伤痕累累。虽然其他免疫学家会寻找具体的免疫反应,Ayres却更关注哪些苍蝇活了下来,她从那些幸存的苍蝇中寻找跟预防、治疗和修复李斯特菌感染有关的基因突变。

她和导师David Schneider教授猜测除了抗原免疫反应,身体还有另外一种抗感染机制——耐受(tolerance),使身体将感染危害降至最小。她后来称为“耐受防御系统”(tolerance defense system)。

他们兴奋地向学术界公布了这一研究发现(相关阅读:Identification of Drosophila Mutants Altering Defense of and Endurance to Listeria monocytogenes Infection.),但是没有得到免疫学家的过多关注。业内人士不太喜欢tolerance这个词,因为它已经有很多其他的专业解释。其实过去一个多世纪,植物学家一直用tolerance描述受感染后仍保有育果能力的植物。

幸运的是,他们的观点受到一位免疫学大牛的注意——拿过几乎每一个主要的生物学大奖、仅仅与2011年诺贝尔奖失之交臂的Ruslan Medzhitov博士。在耶鲁医学院(Yale School of Medicine)工作的Medzhitov博士多年来都有一个困扰,受感染的动物存活率经常出现波动,而这与感染的病原体数量看似无关。如果杀死病原微生物是有效治疗手段,人们就完全无法解释这种存活率的差异。当他第一次读到Ayres和Schneider的文章,马上被这个观点吸引了,这听起来既有逻辑,也是符合生物学的解释。

Schneider教授认为,目前的主流方向——研究如何杀菌是“一种暴力和军国主义的做法”。没人想过“为什么不能和细菌和平共处”?这就是Ayres博士关注的问题。

穿着拖鞋的开拓者

Ayres博士能够有这个开拓性发现,也许与她从小就不因循守旧有关。她的实验室也是十足“粉红”,不仅所有成员都是女性,实验室的凳子、塑胶手套、套头衫、连架子上摆的香槟都是清一色粉红。实验台上还放了一个”科学家芭比“,Ayres嘲笑这个芭比”裙子太短,但确实没有露出脚趾,也戴了护目镜”(这些都是实验室的着装要求)。

Ayres博士只有30多岁,她经常穿着白大褂,涂着炫目的眼影,穿着惹眼的拖鞋在社区高中出入,透露出科学家也可以很有个性。她的实验室碰巧过去4年都只有女性。今年秋天会进一位男性博士后,Ayres博士冷酷地说”希望他喜欢粉色”。

熟悉Ayres博士的人都把她的成功发现归结于广泛的兴趣。她阅读涉猎广泛,不仅仅在自己的研究领域。实际上,正是一篇19世纪发表的植物研究论文启发了她关于tolerance的想法。这篇论文讲了感染叶锈病的植物仍然健康生长。“这种现象从来没有在动物中被观察或者描述过,”她用热情如火、滔滔不绝地说:“所以我们要读认知范围以外的东西”。

Ayres博士还对伤寒玛丽(Typhoid Mary)的故事着迷。这个1900年代的女性在做家庭厨师期间,先后感染了雇主家的几十个成员,导致3人死亡,她自己却没有任何症状,是医学鉴定的首例无症状伤寒携带者。

从前人的文献中得到启发后,Ayres博士综合了数学、进化学和生态学等各学科的方法进行研究。她狼吞虎咽地阅读关于其他物种的研究论文,最近感兴趣的是蚂蚁和鳗鱼,这些广泛地阅读会给她从事的tolerance现象研究提供有益启示,带给她培养皿之外的大局思考。如此广泛的涉猎,Ayres博士的确是个工作狂,比起丈夫和以她父亲德文名字称呼的金毛犬宠物,她承认自己把大量时间花在了工作上。她曾说过:“科学家是一种生活方式,而不是一种工作。”

Ayres博士出身平凡,父亲是德国移民的普通农民,母亲是记账员。十几岁时,她就开始给杂货店打工,卖冰淇淋。在伯克利大学(Berkeley University)读大学时,她每天花几小时路程去一个实验室全职做研究,毕业时还是拿到了4.0的平均绩点。2009年,她从斯坦福大学博士毕业,导师对她的评价是“每天花几小时在路上,仍然完成如此大量的研究。她工作相当卖力。”

Ayres博士自己却对于能够在Salk Institute做研究感到非常幸运。这个海边的研究所布满水泥柚木建筑,1960年代,这里是唯一一个实验室之间不设围墙的研究所。正是在这里,她能够和许多神经学和代谢学的专家们自由交流,她自己的研究才会进展得如此顺利。

科研的全身心付出终于换来回报和认可。2014年,Ayres教授作为15个美国年轻科学家之一,被任命为Searle学者。2015年,她获得五角大楼国防高级研究项目署(DARPA)颁发的年轻学者奖。两个奖项总共带来了80万美元的研究经费,使她能够继续做感兴趣的事业。

对付细菌是一场不会赢的战争

世界范围内,耐药感染的发病率不断上升,每年有高达70万人死于耐药感染。2014年,院内采集的大肠杆菌(一种常见的肠道细菌)样本中,青霉素对60%的样本无效,约25%的样本对其他常用的抗生素中的一种或两种产生耐药。最近,世界卫生组织首次发布了12种被列为最高优先级的超级细菌名单。“抗生素耐药不断增强,我们可以用来对付耐药菌的工具差不多用完了,”世卫组织健康体系与研发助理总干事Marie-Paule Kieny博士表示担忧,“抗生素的研发候选物基本枯竭”。



▲世界卫生组织2017年2月公布的优先病原菌新抗生素研发清单(图片来源:straitstimes)

目前,公共卫生机构的做法是是呼吁新的更有效的抗生素。美国和英国在未来三年将投资数千万美元用于新型抗生素开发。今年4月,美国国会提出了一项法案,其中包括20亿美元的新抗生素研究专项资金。

Ayres博士对这些做法感到叹息。她十分了解细菌,尊重细菌甚至爱上细菌。她知道它们永远都会赢。

她认为,社会需要的药物不应该对付细菌,因为细菌可以进化出逃避最好的抗生素的机制。相反,我们可以利用细菌甚至病原体,制作靶向感染者的组织和器官的药物,从而挽救生命。这将是一种全新的治疗方法,可以减少对抗生素的依赖,在某些情况下拯救患者,就像她的父亲。

传播这个新的思想并不容易,很多业内科学家对这个新的领域不甚了解。但是情况正在逐渐转好。

除了细菌感染,这个新思路对开发其他疾病领域的治疗药物也有帮助,比如病毒感染,甚至癌症。Schneider教授注意到,有些患者在肿瘤负荷很大的情况下依然生存良好,有些患者却会被很小的肿瘤打垮,帮助患者从放化疗中恢复食欲和力气的药物对提高生存率似乎有效。

业界有一些小型生物技术公司已经在从事这类药物的研发。Ayres博士仍然在自己的实验室里孜孜不倦地进行基础科研,通过一系列研究发现若干新药靶标。她的关注点是微生物组,这是居住在我们体内但却不会导致感染的数万亿细菌的组合。Ayres博士猜测微生物组可能在“耐受防御系统”中发挥关键作用。

但是,如果细菌确实有助于增加疾病耐受性,那究竟是什么样的菌株在发挥作用呢?

Ayres博士和研究人员正在寻求答案。他们研究小鼠对肠道感染和沙门氏菌引起的肺炎的反应。

肠道感染的研究采用的小鼠在遗传特性完全相同,但是由于生长环境不同,所以它们体内具有不同的微生物组。结果发现,尽管所有小鼠感染的病原体数量一样,有一组小鼠没有出现肌肉萎缩,这表明其体内微生物组中的某些物质正在促进疾病耐受性。

研究人员将这些耐受性小鼠的微生物组与普通小鼠进行比较,发现只有耐受性小鼠携带了特异性的大肠杆菌菌株,Ayres博士称之为“超级英雄菌”。当他们把“英雄菌株”输给普通小鼠时,竟然也能使这些小鼠避免肌肉萎缩。

通过进一步研究,Ayres博士的研究团队还揭示了大肠杆菌滋养肌肉的机制。大肠杆菌可以离开肠道并迁移到脂肪组织,在那里激活免疫系统的炎性体,后者可以刺激炎症反应来对抗微生物感染。

这项研究成果2015年发表在《科学》杂志(相关阅读:Disease tolerance mediated by microbiome E. coli involves inflammasome and IGF-1 signaling. Science.)。在小鼠实验中获得新发现之后,Ayres博士现在着手研究人体内发挥类似作用的细菌,希望可以用于肌肉萎缩治疗。



▲Ayres博士及团队发现一种“超级英雄菌”——大肠杆菌菌株(左),能够阻止感染鼠伤寒沙门氏菌(右)和泰国伯克霍尔德氏菌(中)的小鼠肌肉萎缩。(图片来源:Salk Institute官网)

在另一项研究中,Ayres博士发现一种称为SlrP的细菌蛋白可以防止小鼠死于沙门氏菌感染。研究先通过基因突变获得不含SlrP蛋白的沙门氏菌突变菌株,然后用野生菌株和突变菌株同时去感染小鼠。结果发现,跟感染野生菌株的小鼠相比,感染突变菌株的小鼠吃得更少,体重减轻,死亡更快。

同样, Ayres博士的团队通过进一步研究揭示了野生沙门氏菌中的SlrP蛋白的作用机制,它能够阻断肠道向大脑发送停止进食的信号,使得已经感染沙门氏菌的小鼠能够良好进食 。

研究人员解释说:“沙门氏菌实际上已经进化出了保持人体健康的方法。细菌这样做的既得利益是:只要人类继续吃饭和活动,细菌就能继续繁殖并传播给其他宿主。”

这项研究成果2017年发表在《细胞》杂志(相关阅读:Pathogen-Mediated Inhibition of Anorexia Promotes Host Survival and Transmission. Cell.)。Ayres博士希望这个新发现能够开发成提高化疗患者食欲的SlrP靶点药物。

Ayres博士正在努力推动细菌耐受性的基础科学研究,她坚信这会带来新的治疗方法,可以治愈她父亲的细菌感染。

她父亲已经等不到答案揭晓了。但对其他人来说可能不算太晚。

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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xwU6047w4GQZHmaJMe3cGxCqPS0x43a9R04dN3HrAn5diaR2N4pEwoibqiaiaA3m6ia3g3XbZXadIomlRa5WAvjSUHb/0, createdBy=93aa1715091, createdName=为啥子, createdTime=Tue Jun 13 07:11:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210072, encodeId=51772100e266, content=学习了,关于抗感染的治疗,也许可以从另一角度研究。, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Tue Jun 13 07:08:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210042, encodeId=5c8121004258, content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
  2. 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time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210141, encodeId=e5352101414b, content=这篇咨询不错哦,值得学习,对于临床工作和科研思路都很有帮助。, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Tue Jun 13 08:32:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210129, encodeId=84bf210129c6, content=谢谢分享,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Tue Jun 13 08:12:37 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210117, encodeId=c20f21011e9c, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=15, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Tue Jun 13 07:59:26 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210083, encodeId=7e38210083b9, content=另辟蹊径……, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xwU6047w4GQZHmaJMe3cGxCqPS0x43a9R04dN3HrAn5diaR2N4pEwoibqiaiaA3m6ia3g3XbZXadIomlRa5WAvjSUHb/0, createdBy=93aa1715091, createdName=为啥子, createdTime=Tue Jun 13 07:11:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210072, encodeId=51772100e266, content=学习了,关于抗感染的治疗,也许可以从另一角度研究。, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Tue Jun 13 07:08:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210042, encodeId=5c8121004258, content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-14 stupidox

    学习了,谢谢。

    0

  3. 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xwU6047w4GQZHmaJMe3cGxCqPS0x43a9R04dN3HrAn5diaR2N4pEwoibqiaiaA3m6ia3g3XbZXadIomlRa5WAvjSUHb/0, createdBy=93aa1715091, createdName=为啥子, createdTime=Tue Jun 13 07:11:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210072, encodeId=51772100e266, content=学习了,关于抗感染的治疗,也许可以从另一角度研究。, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Tue Jun 13 07:08:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210042, encodeId=5c8121004258, content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 xxx2501

    反向思维,腻害!

    0

  4. 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xwU6047w4GQZHmaJMe3cGxCqPS0x43a9R04dN3HrAn5diaR2N4pEwoibqiaiaA3m6ia3g3XbZXadIomlRa5WAvjSUHb/0, createdBy=93aa1715091, createdName=为啥子, createdTime=Tue Jun 13 07:11:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210072, encodeId=51772100e266, content=学习了,关于抗感染的治疗,也许可以从另一角度研究。, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Tue Jun 13 07:08:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210042, encodeId=5c8121004258, content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 131****1460

    学习了,受益匪浅。

    0

  5. 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createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6Nx0VGA4QMDzOP8oAgnV4h51EjSfehJ9QxyiaSmw8PB56BhY8KXFSxHCibXrzcy4abrzSibXQPxJ9kzrLcJyhhB8a/0, createdBy=1d3b1672603, createdName=明月清辉, createdTime=Tue Jun 13 08:12:37 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210117, encodeId=c20f21011e9c, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=15, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Tue Jun 13 07:59:26 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210083, encodeId=7e38210083b9, content=另辟蹊径……, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xwU6047w4GQZHmaJMe3cGxCqPS0x43a9R04dN3HrAn5diaR2N4pEwoibqiaiaA3m6ia3g3XbZXadIomlRa5WAvjSUHb/0, createdBy=93aa1715091, createdName=为啥子, createdTime=Tue Jun 13 07:11:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210072, encodeId=51772100e266, content=学习了,关于抗感染的治疗,也许可以从另一角度研究。, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Tue Jun 13 07:08:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210042, encodeId=5c8121004258, content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 李东泽

    这篇咨询不错哦,值得学习,对于临床工作和科研思路都很有帮助。

    0

  6. 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3xwU6047w4GQZHmaJMe3cGxCqPS0x43a9R04dN3HrAn5diaR2N4pEwoibqiaiaA3m6ia3g3XbZXadIomlRa5WAvjSUHb/0, createdBy=93aa1715091, createdName=为啥子, createdTime=Tue Jun 13 07:11:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210072, encodeId=51772100e266, content=学习了,关于抗感染的治疗,也许可以从另一角度研究。, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/xkvRjYnJzzRJ2R0y7VhicibvkjPWHjIMmu4ZpKnE9cWAu4lVicS3uDUCfF4M4JWvrkrYfpb2KehPV0Ee29tPqyPEebBUibiaKhnvD/0, createdBy=f8412001184, createdName=惠映实验室, createdTime=Tue Jun 13 07:08:45 CST 2017, time=2017-06-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=210042, encodeId=5c8121004258, content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 明月清辉

    谢谢分享,学习了

    0

  7. 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content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 龙胆草

    学习谢谢分享

    0

  8. 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content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 为啥子

    另辟蹊径……

    0

  9. 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content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 惠映实验室

    学习了,关于抗感染的治疗,也许可以从另一角度研究。

    0

  10. 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content=阅读了谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, 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=Tue Jun 13 06:30:28 CST 2017, time=2017-06-13, status=1, ipAttribution=)]
    2017-06-13 刘煜

    阅读了谢谢分享。

    0

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