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Science:用微生物做癌症杀手,这些研究让人大开眼界

2016-09-06 佚名 奇点网

导语:日前,Agendia公司宣布该公司检测早期乳腺癌复发风险的基因测试MammaPrint在临床3期试验中可以准确检测出复发风险低的患者。这一结果意味着这些患者可能可以选择不接受辅助化疗,从而避免化疗带来的毒副作用。尽管科学在不停地进步,但是癌症依然是人类难以攻克的一个疾病,不同的治疗办法也是层出不穷。近年来,随着微生物研究的大热,就有科学家把这两者联系到了一起,想看看能不能用这小小的不起眼

导语:日前,Agendia公司宣布该公司检测早期乳腺癌复发风险的基因测试MammaPrint在临床3期试验中可以准确检测出复发风险低的患者。这一结果意味着这些患者可能可以选择不接受辅助化疗,从而避免化疗带来的毒副作用。

尽管科学在不停地进步,但是癌症依然是人类难以攻克的一个疾病,不同的治疗办法也是层出不穷。近年来,随着微生物研究的大热,就有科学家把这两者联系到了一起,想看看能不能用这小小的不起眼的微生物来解决一直困扰人类的疾病。

肠道微生物与抗癌药物的相辅相成

在2013年,就有两个研究同期登上了《科学》杂志。它们共同证明了我们肠道中的菌群可以帮助巩固肿瘤药物的疗效,能够调节免疫系统的反应。其中一项研究是由美国国家癌症研究所的研究员Noriho Iida及其同事发现的,他们培养出癌症小鼠模型,分成2组,其中1组在给药前先服用了3周抗生素,打破了肠道菌群的稳定,再分别给它们服用同等剂量的铂类化疗药物,发现肠道菌群正常的小鼠对药物抗肿瘤的反应明显,治疗效果更好。[1]

另一项实验是由法国的科学家Sophie Viaud领导的,他们利用的是一种叫做环磷酰胺的抗癌药物,它可以刺激免疫细胞产生抗肿瘤免疫反应。研究人员发现,环磷酰胺可以改变肠道微生物的种群构成,驱使种群中的革兰氏阳性菌进入次级淋巴系统,触发一种特殊的辅助T细胞对肿瘤发动攻击,从而达到杀灭肿瘤的治疗效果。而与上一个研究相似的是,在对无菌小鼠或是已经服用抗生素杀死了部分革兰氏阳性菌的小鼠进行实验时,这一抗癌机制就不能够正常启动了。[2]

这两个实验都表明,肠道微生物从某个角度是可以决定药物的抗癌效果如何的,在治疗癌症中少不了它们的存在。除此之外,两项研究也都从侧面提醒我们,在癌症患者的治疗中,使用抗生素可能存在潜在的风险,用药时一定要慎重。

有毒细菌消灭肿瘤

有时候,有些在当时看来很疯狂的疗法,可能往往随着科学的发展在未来还能被人们所启用。注射有毒细菌治疗癌症就是一个例子。2014年,一篇发表在《科学 转化医学》上的文章就证实了直接将细菌注射到肿瘤内能够有效控制肿瘤的生长,甚至能够消灭肿瘤!



诺维氏梭菌的模拟图

这个神奇的细菌叫做诺维氏梭菌,它存在于土壤中,含有毒素,可以感染牛羊等牲畜还有人。研究人员敲掉了细菌中的一部分产毒基因,降低了它的毒性,将诺维氏梭菌改造成了“生物武器”。由于肿瘤生长速度快,往往会导致内部组织缺氧,诺维氏梭菌恰好是厌氧菌,适合在这种低氧环境下生存。随着改造后细菌的分裂繁殖,它们会释放一些毒素可将癌细胞杀死,细菌则利用坏死肿瘤细胞的碎片生存。

实验是在宠物狗身上进行的,研究人员征用了16只患有肿瘤的宠物狗,向它们的肿瘤直接注射诺维氏梭菌的孢子。在21天的治疗后,有6只首先出现了抗肿瘤反应,3只显示肿瘤完全消除,其他3只的肿瘤最长直径缩小了30%。但是麻烦的是,一部分宠物狗都出现了细菌感染的发热和炎症。[3]

尽管如此,科学家们对这个方法的态度仍然是乐观的,论文的通讯作者周世斌说,用细菌来治疗癌症最大的优点在于改造容易,用基因技术可以达到减少毒性等等要求。虽然预计中,临床试验的患者也可能会出现强烈的炎症反应,但是这也有助于研究人员们逐步确定患者耐受范围内的安全剂量。还有一部分研究人员认为,可以将其与其他疗法相结合,可能也能减少副作用,获得更好的治疗效果。

灭活细菌对结肠癌细胞的抑制作用



梭状芽胞杆菌

既然活细菌的不良反应如此之大,灭活的细菌能不能起到作用呢?别说,还真有科学家做了这个研究。2015年年底,来自新加坡的研究人员Teoh Swee Hin在《自然》杂志的子刊《科学报告》上发表文章,他和他的团队使用灭活的梭状芽胞杆菌成功的抑制了结肠癌细胞的生长。

Teoh Swee Hin使用高温对梭状芽胞杆菌进行了灭活,将其分别添加到培养结肠癌细胞的二维和三维细胞培养平台中。二维细胞培养是普通的平板培养,细胞只能沿着培养基的平面生长,而三维细胞培养是将具有三维结构不同材料的载体与细胞在体外进行培养,使细胞能够在三维立体空间结构中迁移、生长。三维细胞培养既能最大程度模拟体内环境,又具有直观和条件可控的优势。

灭活的梭状芽胞杆菌在二维细胞培养平台上经过了72小时,与空白对照组相比,加入了灭活芽孢杆菌的癌细胞生长速度下降到了6.3%。于是研究人员继续使用三维平台来验证,复杂的三维模型更好地模拟了肿瘤以及肿瘤所处的人体内微环境,同样的时间内,抑制作用使得癌细胞的生长速度降低了73.8%。[4]

对于Teoh Swee Hin和他的团队来说,这个结果是令他们感到惊喜的。有了这个结果,他们迅速的开始准备后续的工作,比如对其他癌症模型是否也有同样的抑制作用,以及真正进入人体后,与他们的三维模拟是否会出现偏差,是否还有其他的不良反应等等。

自带“指南针”的磁性细菌成为肿瘤药物的新载体

说了活细菌、灭活细菌,最后还要说一种神奇的“磁性细菌”。这种“奇妙的细菌”是由加拿大蒙特利尔大学理工学院纳米机器人实验室的主任Sylvain Martel发现的,一开始Martel是想利用磁场引导纳米机器人顺着血管游进肿瘤,把治疗癌症的药物送到特定的区域。但是由于纳米机器人的制造技术目前还达不到这个要求,他不得不放弃这个想法。



紧接着Martel在细菌中找到了替代者——趋磁球菌,这种细菌的体内可以合成磁小体,就像一根“指南针”一样,在磁场的作用下,细菌能够准确地到达他的“目的地”。光到达还不够,这种趋磁球菌本身可凭借磁力和自身的氧气传感器向深水缺氧区域移动并生存下来,于是研究人员猜测它们在人体内应该也可以向着低氧的肿瘤区域“进发”。果然,将癌症小鼠放入计算机控制的磁场中,55%的趋磁球菌成功进入了肿瘤区域。[5]

另外利用自身鞭毛的推动力,趋磁球菌的游动速度也比普通细菌要快得多,这使得它们可以迅速的将自己携带的化疗药物准确地投放到肿瘤区域内。化疗药物是对人体有很大的副作用,传统化疗药物就像是找不到路的外卖小哥一样,会把药物留在体内的其他部位,导致药物的效率不高。而这种趋磁球菌则像是自带GPS,听从指挥,直奔目标而去的战士,提高了药物的治疗效率,也降低了副作用。文章刊登在了《自然 纳米技术》杂志上,尽管这只是在理论上证实了可行性,但是依然值得人们期待它在进入临床后的消息。

多年以来,科学家们对癌症进行了大量的研究,但是在治疗方面,可以说只取得了微小的进步。在与癌症的战斗中,我们还有很多的工作要做,而且也还有不同类型、不同阶段的肿瘤需要歼灭,这全部的问题不是一种药物或者一种疗法就能解决的,所以希望在未来,我们能看到更多的、更好的新技术来治疗顽固的癌症。

原始出处:

Iida N1, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, Molina DA, Salcedo R, Back T, Cramer S, Dai RM, Kiu H, Cardone M, Naik S, Patri AK, Wang E, Marincola FM, Frank KM, Belkaid Y, Trinchieri G, Goldszmid RS.Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.Science. 2013 Nov 22

Viaud S1, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ, Schlitzer A, Ginhoux F, Apetoh L, Chachaty E, Woerther PL, Eberl G, Bérard M, Ecobichon C, Clermont D, Bizet C, Gaboriau-Routhiau V, Cerf-Bensussan N, Opolon P, Yessaad N, Vivier E, Ryffel B, Elson CO, Doré J, Kroemer G, Lepage P, Boneca IG, Ghiringhelli F, Zitvogel L.The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide.Science. 2013 Nov 22

Roberts NJ1, Zhang L2, Janku F3, Collins A2, Bai RY4, Staedtke V5, Rusk AW6, Tung D2, Miller M2, Roix J2, Khanna KV6, Murthy R7, Benjamin RS8, Helgason T3, Szvalb AD9, Bird JE10, Roy-Chowdhuri S11, Zhang HH2, Qiao Y1, Karim B12, McDaniel J13, Elpiner A14, Sahora A15, Lachowicz J16, Phillips B17, Turner A18, Klein MK19, Post G13, Diaz LA Jr20, Riggins GJ4, Papadopoulos N1, Kinzler KW1, Vogelstein B1, Bettegowda C21, Huso DL12, Varterasian M2, Saha S22, Zhou S1.Intratumoral injection of Clostridium novyi-NT spores induces antitumor responses.Sci Transl Med. 2014 Aug 13


Felfoul O1, Mohammadi M1, Taherkhani S1,2, de Lanauze D1, Zhong Xu Y3, Loghin D1, Essa S2,4, Jancik S3, Houle D3, Lafleur M4, Gaboury L5, Tabrizian M2,6, Kaou N1, Atkin M1, Vuong T7, Batist G7, Beauchemin N8, Radzioch D3, Martel S1.Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions.Nat Nanotechnol. 2016 Aug 15

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#插入话题
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  2. [GetPortalCommentsPageByObjectIdResponse(id=1824691, encodeId=e3e01824691cc, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, createdName=wjcjjian, createdTime=Wed Dec 28 17:30:00 CST 2016, time=2016-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=144466, encodeId=38241444661c, content=好文章,受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Tue Oct 11 15:14:09 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127868, encodeId=3ca212e86825, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127869, encodeId=969c12e869b5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375330, encodeId=f49513e533019, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Sep 08 06:30:00 CST 2016, time=2016-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112903, encodeId=04f811290362, content=希望早日成功!早日应用到一线治疗当中!希望有更多的人,更多的科学家去关注!让患者们早日获得治疗带来的益处!, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Wed Sep 07 09:23:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112840, encodeId=142911284051, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Sep 07 06:38:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112685, encodeId=3e3311268511, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112686, encodeId=03e01126865f, content=继续关注, 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/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=)]
    2016-10-11 1e10c84am36(暂无匿称)

    好文章,受益

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1824691, encodeId=e3e01824691cc, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, createdName=wjcjjian, createdTime=Wed Dec 28 17:30:00 CST 2016, time=2016-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=144466, encodeId=38241444661c, content=好文章,受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Tue Oct 11 15:14:09 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127868, encodeId=3ca212e86825, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127869, encodeId=969c12e869b5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375330, encodeId=f49513e533019, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Sep 08 06:30:00 CST 2016, time=2016-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112903, encodeId=04f811290362, content=希望早日成功!早日应用到一线治疗当中!希望有更多的人,更多的科学家去关注!让患者们早日获得治疗带来的益处!, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Wed Sep 07 09:23:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112840, encodeId=142911284051, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Sep 07 06:38:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112685, encodeId=3e3311268511, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112686, encodeId=03e01126865f, content=继续关注, 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/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=)]
    2016-09-15 doctorJiangchao

    继续学习

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1824691, encodeId=e3e01824691cc, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, createdName=wjcjjian, createdTime=Wed Dec 28 17:30:00 CST 2016, time=2016-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=144466, encodeId=38241444661c, content=好文章,受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Tue Oct 11 15:14:09 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127868, encodeId=3ca212e86825, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127869, encodeId=969c12e869b5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375330, encodeId=f49513e533019, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Sep 08 06:30:00 CST 2016, time=2016-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112903, encodeId=04f811290362, content=希望早日成功!早日应用到一线治疗当中!希望有更多的人,更多的科学家去关注!让患者们早日获得治疗带来的益处!, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Wed Sep 07 09:23:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112840, encodeId=142911284051, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Sep 07 06:38:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112685, encodeId=3e3311268511, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112686, encodeId=03e01126865f, content=继续关注, 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/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=)]
    2016-09-15 doctorJiangchao

    继续关注

    0

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    2016-09-08 jichang
  6. [GetPortalCommentsPageByObjectIdResponse(id=1824691, encodeId=e3e01824691cc, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, createdName=wjcjjian, createdTime=Wed Dec 28 17:30:00 CST 2016, time=2016-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=144466, encodeId=38241444661c, content=好文章,受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Tue Oct 11 15:14:09 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127868, encodeId=3ca212e86825, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127869, encodeId=969c12e869b5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375330, encodeId=f49513e533019, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Sep 08 06:30:00 CST 2016, time=2016-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112903, encodeId=04f811290362, content=希望早日成功!早日应用到一线治疗当中!希望有更多的人,更多的科学家去关注!让患者们早日获得治疗带来的益处!, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Wed Sep 07 09:23:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112840, encodeId=142911284051, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Sep 07 06:38:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112685, encodeId=3e3311268511, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112686, encodeId=03e01126865f, content=继续关注, 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/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=)]
    2016-09-07 明天会更好!

    希望早日成功!早日应用到一线治疗当中!希望有更多的人,更多的科学家去关注!让患者们早日获得治疗带来的益处!

    0

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    2016-09-07 忠诚向上

    好好学习一下

    0

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    2016-09-06 doctorJiangchao

    继续学习

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1824691, encodeId=e3e01824691cc, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, createdName=wjcjjian, createdTime=Wed Dec 28 17:30:00 CST 2016, time=2016-12-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=144466, encodeId=38241444661c, content=好文章,受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=80, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzdAIB7UwTkHt6fQkBP8ictliaXtc5gCUmYdAW1sAETC2nhO3q6YjRHkUibyOCtP8ibmXNObTyd63A076/0, createdBy=d4111948983, createdName=1e10c84am36(暂无匿称), createdTime=Tue Oct 11 15:14:09 CST 2016, time=2016-10-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127868, encodeId=3ca212e86825, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=127869, encodeId=969c12e869b5, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=101, 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 Sep 15 16:07:00 CST 2016, time=2016-09-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375330, encodeId=f49513e533019, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Thu Sep 08 06:30:00 CST 2016, time=2016-09-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112903, encodeId=04f811290362, content=希望早日成功!早日应用到一线治疗当中!希望有更多的人,更多的科学家去关注!让患者们早日获得治疗带来的益处!, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160914/IMG57D82E721DB581755.jpg, createdBy=4fc81933929, createdName=明天会更好!, createdTime=Wed Sep 07 09:23:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112840, encodeId=142911284051, content=好好学习一下, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=45101626056, createdName=忠诚向上, createdTime=Wed Sep 07 06:38:00 CST 2016, time=2016-09-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112685, encodeId=3e3311268511, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=112686, encodeId=03e01126865f, content=继续关注, 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/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Tue Sep 06 21:32:00 CST 2016, time=2016-09-06, status=1, ipAttribution=)]
    2016-09-06 doctorJiangchao

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