Nature:清华大学鲁白团队开发出全球全面模拟人类阿尔茨海默症的大鼠模型

2021-11-24 细胞 细胞

目前近乎停滞的AD全球药物临床的成功转化起到一定的促进作用,该研究将为理解AD的发病机制,发现用于AD早期诊断的敏感生物标记物,尤其是创新药物的疗效,提供了不可或缺的工具。

很少有疾病能比阿尔茨海默症(AD)更能引起人们的恐惧和无奈。在过去的一个多世纪,研究人员已经开展了400多项阿尔茨海默症药物临床试验,但迄今为止尚无一个治本(阻止疾病进程)的药物可用。

究其原因,很重要的一条是AD动物模型不能模拟人类AD病人的真实情况;从而导致有很多候选药物在动物模型中有效,但在AD病人的临床试验中则无效。在过去的25年,科学家们相继建立了200多个AD动物模型,但这些模型或者没有神经细胞的死亡,或者缺乏完整的病理特征。

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由于设计或技术方面的缺陷,迄今未能获得一个真正能够全面反映人类AD病理表型和疾病机制的动物模型,这在很大程度上妨碍了对AD的研究和临床药物开发。建立人源化,能够全面模拟人类AD的动物模型,一直是AD领域机制研究和药物开发亟需解决的一大难题。

近日,由著名神经科学家、清华大学药学院教授鲁白领导的团队,在该领域实现了重大突破,成功开发了能够全面模拟阿尔茨海默症的基因敲入大鼠模型,相关成果日前以Article形式在线发表于 Cell Research 期刊。

长期研究表明,大脑中淀粉样蛋白的沉淀(沉淀,俗称老年斑),是AD病人的主要病理表现,也被认为是AD发病的主要原因。而的前体App基因的一些突变,会大大加速沉淀。

因此,以往绝大多数的AD模型,采用各种各样的转基因技术,将不同突变型的App基因表达在小鼠中。在这类App的转基因小鼠中,可以观察到沉淀,但看不到AD的另一特征tau的病理表型,也很少看到神经元的死亡。

另外,转基因技术有一系列不可避免的的缺陷:将人类App突变基因随机插入小鼠的染色体中,可能破坏插入处小鼠自身正常基因的表达;而插入的突变型App基因,也可能表达在错误的脑区,错误的细胞,或者错误的时间;最大的缺陷是导致App蛋白表达水平比正常水平高得多,这些过量的App蛋白会被酶切成和一些非生理的蛋白片段,它们会扰乱小鼠的正常生理功能,导致了与AD无关的表型。

在这项研究中,鲁白教授团队刻意避免使用转基因技术,而采用了CRISPR/Cas9基因敲入技术,在大鼠体内实现了人源App基因的替换,同时携带了Swedish Beyreuther/IberianArctic三个人类家族突变,(AppNL-G-F),而不改变App蛋白及其片段在脑内的时间和空间的表达水平。系统的病理学,细胞生物学和行为学研究表明,该模型与现有其他AD动物模型相比,显示出与人类AD患者更相似的病理和疾病进展。

据该论文的第一作者逄克亮博士介绍,在大鼠中实现人源App基因的替换并同时进行多个家族突变的原位敲入很具挑战。由于上述3个家系突变分布在App基因的两个外显子上,将它们同时准确无误地敲入基因组并实现人源化,其成功率很低。公开文献显示,国际上有诺贝尔奖获得者在内的多个团队曾试图进行类似App突变的敲入,均未成功。而鲁白团队也是在200多个App突变敲入大鼠系中,才筛选到了一个准确的AppNL-G-F敲入大鼠。

研究人员在对该AppNL-G-F大鼠中App蛋白和多个酶切片段进行了详细分析,证实该模型避免了以往转基因模型中普遍存在的多种缺陷。文章显示该大鼠模型在二月龄便显现出的沉积,并随着年龄呈现出多脑区的分布,呈现出非常类似于人类AD大脑中病理的进行性扩展。由此可见,用基因敲入术进行人源App基因的替换,既解决了传统转基因模型常见的过表达和非生理分布缺陷,又避免了基因随机插入对原位基因表达的破坏性导致的死亡,因此更准确地模拟了AD大脑中病理发生机制。 

AD病人大脑中,除了病理沉积,还有异常高的磷酸化tau蛋白以低聚物纤维形式存在,形成AD的第二个病理特征:神经纤维缠绕。鲁白团队用4种方法证明,该大鼠模型大脑有类似于人类的高磷酸化的tau,以及病理性tau蛋白聚合物,一般在动物模型中很难观察到tau两种病理的同时存在。在以往几乎所有的App小鼠模型中都缺少tau病理表型。该结果揭示了病理和tau病理其潜在关系,只要有突变型在大鼠脑中的表达,就会有tau的病理出现。另外,该研究发现在时间上,tau病理发生在病理之后,这为致病假说提供了强有力的证据,也为继续深入研究其中的机制提供了方向。

人类AD大脑的第三个显著变化是神经细胞的进行性死亡和大脑萎缩(表现为脑室扩张),这也成为临床上用磁共振 (MRI) 诊断AD的主要指征。而在以往的AD动物模型上,都不能模拟大脑萎缩这一关键疾病进展,即使细胞死亡也罕有报道。

鲁白团队在对AppNL-G-F大鼠大脑宏观和微观上的系统研究,发现同时存在程序性凋亡(apoptosis)和程序性坏死(necroptosis)两种发生于AD病人中的主要细胞死亡形式,并随着疾病的进展表现出了脑组织重量减轻和脑室的扩张,这也是科学家首次在人类AD以外的动物模型中观察到脑室的扩张。从AD发现至今100多年,但科学家们却一直没有找到AD患者神经元死亡的确切原因,该AppNL-G-F大鼠为研究这一问题提供了工具。

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用基因敲入的方法建立AD动物模型,并非没有被尝试过。2014年,日本科学家Saido研究组用几乎完全相同的策略,制作了基因敲入型AppNL-G-F小鼠模型。鲁教授团队将其研发的AppNL-G-F大鼠与SaidoAppNL-G-F小鼠做了头对头的比较研究。一个令人惊叹的结果是,尽管AppNL-G-F小鼠展示了与AD比较相关的病理表型,与人类AD的病理特征相类似,但与AppNL-G-F大鼠模型不同,该小鼠模型欠缺AD患者大脑中的最关键的病理表现,即神经细胞的持续性死亡,及其导致的脑萎缩(表现为脑室扩张)。此外,AD的另一个关键特征tau蛋白病理,也没有在Saido小鼠中表现出来。该结果提示AppNL-G-F大鼠是更接近人类AD的动物模型。

此外,研究人员发现在AppNL-G-F大鼠脑中胶质细胞的显著活化。在海马和大脑皮层,小胶质细胞和星形胶质细胞随年龄增长而大量增生。尤为重要的是,小胶质细胞和星形胶质细胞在斑块周围聚集,这反映了与AD患者大脑类似,AppNL-G-F大鼠脑中也有显著的神经炎症。

AD大脑中的毒素(tau)沉积和神经炎症,会造成突触的损伤乃至丢失。突触损伤也被普遍认为AD从病理生理到认知障碍的关键改变点,是与认知状态相关的最具有预测性的病理特征。鲁白团队综合使用生化、免疫组化和三维电镜等技术证明,该大鼠模型大脑有类似人类AD的突触损伤和脑区特征。随着目前针对清除有毒蛋白AD临床治疗绝大部分的失败,修复突触损伤是非常有前景的治疗策略。

鲁白教授早在2013年便在 Nature Reviews Neuroscience 提出了针对神经退行性疾病突触修复和再生的治疗方法,随着越来越多的研究,被科学术界和工业界所公认。该AppNL-G-F大鼠动物模型的建立,将成为验证基于突触修复的新型治疗策略的有效工具。

最后,研究人员通过多种行为实验范式,发现该模型大鼠全方位地出现了人类AD的空间记忆障碍、工作记忆障碍,等等。尤为重要的是,研究人员用一种精巧的更接近于人类行为的触屏技术,证明AppNL-G-F大鼠具有明显的情景记忆障碍。情景记忆的缺失是AD患者最早也是最为常见的行为表现,但在小鼠模型中应用触屏技术却很难。因此,该研究结果也展示了大鼠AD模型的另一优越性。

这项研究由清华大学鲁白教授的研究生/博士后逄克亮为第一作者,鲁白团队副研究员郭炜博士为共同通讯作者,联合瑞典卡洛琳斯卡医学院 Per Nilsson 研究组,中科院心理学研究所王玮文研究组,中科院自动化研究所蒋田仔研究组和韩华研究组等多个科学家团队通力合作,历时数载,才成功地建立了全世界领先的阿尔茨海默症模型。

鲁白教授指出,此次构建的AD大鼠模型全面展现出AD的病理特征,将对目前近乎停滞的AD全球药物临床的成功转化起到一定的促进作用,它将为理解AD的发病机制,发现用于AD早期诊断的敏感生物标记物,尤其是创新药物的疗效,提供了不可或缺的工具。

论文链接:

https://www.nature.com/articles/s41422-021-00582-x

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#插入话题
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  2. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
    2022-09-24 liye789132251
  3. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
    2021-11-26 医生2397
  6. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
    2021-11-25 50277

    临床研究

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
    2021-11-25 ms5000000353966274

    太好了,这能够促进相关基础研究的发展

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
    2021-11-25 lyb5810215

    很棒的模型

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1817139, encodeId=d17a181e139ae, content=<a href='/topic/show?id=17b59e77626' target=_blank style='color:#2F92EE;'>#阿尔茨#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97776, encryptionId=17b59e77626, topicName=阿尔茨)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Bnia2EtH2IvyBtniaWHPQOYAicsN3IAL1ZuPV7qyALcdCiawRJdEiafMxWTxzERQW7eeKg8HfCKCRK2CJicy073C4RJg/132, createdBy=464b2500186, createdName=ms1948154235210413, createdTime=Thu Jun 09 22:24:29 CST 2022, time=2022-06-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885511, encodeId=8c9218855113f, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sat Sep 24 22:24:29 CST 2022, time=2022-09-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1818162, encodeId=100d1818162bd, content=<a href='/topic/show?id=4c9f9e777ac' target=_blank style='color:#2F92EE;'>#阿尔茨海#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97777, encryptionId=4c9f9e777ac, topicName=阿尔茨海)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=636e2500187, createdName=12498da4m32(暂无昵称), createdTime=Mon Apr 04 23:24:29 CST 2022, time=2022-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1470516, encodeId=57f514e0516f9, content=<a href='/topic/show?id=45a79e7788c' target=_blank style='color:#2F92EE;'>#阿尔茨海默#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97778, encryptionId=45a79e7788c, topicName=阿尔茨海默)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c5917090900, createdName=yhj-time, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500174, encodeId=6ee215001e4b8, content=<a href='/topic/show?id=9e6866216d7' target=_blank style='color:#2F92EE;'>#清华#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=66216, encryptionId=9e6866216d7, topicName=清华)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=10f29422809, createdName=医生2397, createdTime=Fri Nov 26 14:24:29 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073758, encodeId=791c10e375820, content=临床研究, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0d7c1341677, createdName=50277, createdTime=Thu Nov 25 09:12:20 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073730, encodeId=eb3610e3730b3, content=太好了,这能够促进相关基础研究的发展, beContent=null, objectType=article, channel=null, level=null, likeNumber=63, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=96425723286, createdName=ms5000000353966274, createdTime=Thu Nov 25 07:58:25 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073710, encodeId=0e1510e3710a9, content=很棒的模型, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f36c1992001, createdName=lyb5810215, createdTime=Thu Nov 25 05:20:38 CST 2021, time=2021-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1073682, encodeId=454210e368210, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=71, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Wed Nov 24 23:55:00 CST 2021, time=2021-11-24, status=1, ipAttribution=)]
    2021-11-24 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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