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Cell Metab:糖真的有毒!高血糖环境下,胰腺细胞中致癌的KRAS突变暴增,或为导致胰腺癌的罪魁祸首之一

2019-03-26 奇点糕 奇点网

近日,中国台湾中央研究院的胡春美和李文华等研究发现,胰腺癌中极为常见的KRAS突变,竟与高血糖关系密切!高血糖引起的一系列代谢变化,让胰腺细胞缺乏合成修复DNA的原料dNTP,KRAS突变频率翻着倍的往上长。相关研究发表在Cell Metabolism上。

近日,中国台湾中央研究院的胡春美和李文华等研究发现,胰腺癌中极为常见的KRAS突变,竟与高血糖关系密切!高血糖引起的一系列代谢变化,让胰腺细胞缺乏合成修复DNA的原料dNTP,KRAS突变频率翻着倍的往上长。相关研究发表在Cell Metabolism上。

癌中之王胰腺癌,相比其它肿瘤,那可是专一的很,90%以上都带有KRAS突变。而这个KRAS突变,也正是驱动胰腺细胞走上癌变这条不归路的主力。不过为何胰腺癌跟KRAS这么亲密?

除了几乎全都携带KRAS突变外,胰腺癌跟糖尿病的关系也极为密切。据统计,胰腺癌患者中68%都有糖尿病,相比之下肺癌乳腺癌、前列腺癌和直肠癌的患者中,只有20%左右有糖尿病。或许高血糖等代谢紊乱和KRAS突变间存在着什么联系?

研究人员对比了有无糖尿病的胰腺癌患者中,未癌变的胰腺组织和小肠组织,发现糖尿病患者的胰腺组织中,DNA的损伤明显要多于无糖尿病者的,不过两者小肠组织中的DNA损伤数量却是相似的。

而在高脂高糖饮食诱导代谢紊乱的小鼠中,同样发现了胰腺中DNA损伤的增加,但其它器官中却不存在这一现象。进一步在高糖、高谷氨酰胺或高脂环境中培养胰腺细胞的试验显示,只有高糖条件下,胰腺细胞中的DNA损伤才会增多,而高谷氨酰胺和高脂环境都不会损伤胰腺细胞DNA。

正是高糖造成了胰腺细胞中的DNA损伤!

高糖让胰腺细胞中KRAS突变增多(绿色的是KRAS突变)

不仅如此,由于KRAS致癌突变会让细胞具有生存优势,高糖条件下,胰腺细胞中KRAS致癌突变频率增加的更多。

不过高糖又是怎么造成DNA损伤的?研究人员测试了两种最常见的DNA损伤途径:活性氧(ROS)介导的氧化应激和核苷酸失衡造成的复制应激。

试验发现,高糖条件下,胰腺细胞中ROS水平没有显着的变化,而脱氧核苷三磷酸(dNTP)的水平显着下降了,但核苷三磷酸(NTP)的水平没有变化。向培养基中补充dNTP也能减弱高糖诱导的DNA损伤。

这个dNTP正是合成和修复DNA的原料。如果细胞中缺乏dNTP,不只DNA的合成受影响,还会有本来用于合成RNA的NTP浑水摸鱼,掺入DNA中,进而造成基因组不稳定。

高糖下,细胞内dNTP浓度下降

进一步研究发现,高糖处理下,胰腺细胞中糖酵解中间物果糖-6-磷酸(F-6-P)的浓度升高了。而F-6-P浓度的升高,促进了乙酰葡糖胺的合成,进而让细胞中许多蛋白质都被O-乙酰葡糖胺化修饰了。

这些被O-乙酰葡糖胺化的蛋白中就包括负责脱氧核苷酸合成的核糖核苷酸还原酶(RNR)。RNR被O-乙酰葡糖胺化修饰后,活性下降,造成细胞中dNTP浓度的下降。

除此外,胰腺细胞中整体活性本就不强的磷酸果糖激酶(催化F-6-P磷酸化成果糖-1,6-二磷酸,糖酵解中的关键限速酶)也被O-乙酰葡糖胺化了,造成它的活性进一步下降,抑制糖酵解,让更多的葡萄糖去合成乙酰葡糖胺,形成了正反馈。

不过在其它细胞中,由于本身磷酸果糖激酶的活性较高,在高糖环境下并没有出现类似的现象。

“当胰腺细胞中有过多的葡萄糖时,就会开始糖基化过程,影响细胞基因的修复。”论文第一作者胡春美总结到,“即使在被诊断为糖尿病之前,当血糖浓度很高时,胰腺细胞也有可能受到这样的损害。”

糖的危害这么多,也难怪含糖饮料会增加21%的死亡风险了。

原始出处:Hu C M, Tien S C, Hsieh P K, et al. High Glucose Triggers Nucleotide Imbalance through O-GlcNAcylation of Key Enzymes and Induces KRAS Mutation in Pancreatic Cells[J]. Cell Metab, 2019.

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    2019-09-20 维他命
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    2019-10-31 guojianrong
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level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102726, encryptionId=30c6102e2607, topicName=高血糖)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332862, encodeId=0b3b133286231, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369006, encodeId=54a013690062a, content=<a href='/topic/show?id=13cb1056e20' target=_blank style='color:#2F92EE;'>#KRAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10567, encryptionId=13cb1056e20, topicName=KRAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370973, encodeId=13b113e0973a9, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
    2019-12-23 一闲
  4. [GetPortalCommentsPageByObjectIdResponse(id=1961480, encodeId=89761961480b2, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Sep 20 19:21:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888002, encodeId=02a318880029a, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Thu Oct 31 17:21:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896473, encodeId=bed318964e319, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 23 17:21:00 CST 2019, time=2019-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871201, encodeId=2b2618e1201ca, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 31 15:21:00 CST 2019, time=2019-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704037, encodeId=f2111e04037e5, content=<a href='/topic/show?id=14e0839919f' target=_blank style='color:#2F92EE;'>#胰腺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83991, encryptionId=14e0839919f, topicName=胰腺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d39330628330, createdName=fzwish20010, createdTime=Thu Oct 17 07:21:00 CST 2019, time=2019-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1261176, encodeId=a44612611e68c, content=<a href='/topic/show?id=30c6102e2607' target=_blank style='color:#2F92EE;'>#高血糖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102726, encryptionId=30c6102e2607, topicName=高血糖)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332862, encodeId=0b3b133286231, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), 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createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1961480, encodeId=89761961480b2, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Sep 20 19:21:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888002, encodeId=02a318880029a, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Thu Oct 31 17:21:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896473, encodeId=bed318964e319, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 23 17:21:00 CST 2019, time=2019-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871201, encodeId=2b2618e1201ca, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 31 15:21:00 CST 2019, time=2019-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704037, encodeId=f2111e04037e5, content=<a href='/topic/show?id=14e0839919f' target=_blank style='color:#2F92EE;'>#胰腺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83991, encryptionId=14e0839919f, topicName=胰腺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d39330628330, createdName=fzwish20010, createdTime=Thu Oct 17 07:21:00 CST 2019, time=2019-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1261176, encodeId=a44612611e68c, content=<a href='/topic/show?id=30c6102e2607' target=_blank style='color:#2F92EE;'>#高血糖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102726, encryptionId=30c6102e2607, topicName=高血糖)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332862, encodeId=0b3b133286231, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369006, encodeId=54a013690062a, content=<a href='/topic/show?id=13cb1056e20' target=_blank style='color:#2F92EE;'>#KRAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10567, encryptionId=13cb1056e20, topicName=KRAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370973, encodeId=13b113e0973a9, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1961480, encodeId=89761961480b2, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Sep 20 19:21:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888002, encodeId=02a318880029a, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Thu Oct 31 17:21:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896473, encodeId=bed318964e319, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 23 17:21:00 CST 2019, time=2019-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871201, encodeId=2b2618e1201ca, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 31 15:21:00 CST 2019, time=2019-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704037, encodeId=f2111e04037e5, content=<a href='/topic/show?id=14e0839919f' target=_blank style='color:#2F92EE;'>#胰腺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83991, encryptionId=14e0839919f, topicName=胰腺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d39330628330, createdName=fzwish20010, createdTime=Thu Oct 17 07:21:00 CST 2019, time=2019-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1261176, encodeId=a44612611e68c, content=<a href='/topic/show?id=30c6102e2607' target=_blank style='color:#2F92EE;'>#高血糖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102726, encryptionId=30c6102e2607, topicName=高血糖)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332862, encodeId=0b3b133286231, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369006, encodeId=54a013690062a, content=<a href='/topic/show?id=13cb1056e20' target=_blank style='color:#2F92EE;'>#KRAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10567, encryptionId=13cb1056e20, topicName=KRAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370973, encodeId=13b113e0973a9, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
    2019-03-28 hbwxf
  7. [GetPortalCommentsPageByObjectIdResponse(id=1961480, encodeId=89761961480b2, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Sep 20 19:21:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888002, encodeId=02a318880029a, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Thu Oct 31 17:21:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896473, encodeId=bed318964e319, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 23 17:21:00 CST 2019, time=2019-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871201, encodeId=2b2618e1201ca, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 31 15:21:00 CST 2019, time=2019-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704037, encodeId=f2111e04037e5, content=<a href='/topic/show?id=14e0839919f' target=_blank style='color:#2F92EE;'>#胰腺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83991, encryptionId=14e0839919f, topicName=胰腺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d39330628330, createdName=fzwish20010, createdTime=Thu Oct 17 07:21:00 CST 2019, time=2019-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1261176, encodeId=a44612611e68c, content=<a href='/topic/show?id=30c6102e2607' target=_blank style='color:#2F92EE;'>#高血糖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102726, encryptionId=30c6102e2607, topicName=高血糖)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332862, encodeId=0b3b133286231, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), 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createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=1961480, encodeId=89761961480b2, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Sep 20 19:21:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888002, encodeId=02a318880029a, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Thu Oct 31 17:21:00 CST 2019, time=2019-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896473, encodeId=bed318964e319, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Mon Dec 23 17:21:00 CST 2019, time=2019-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871201, encodeId=2b2618e1201ca, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 31 15:21:00 CST 2019, time=2019-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704037, encodeId=f2111e04037e5, content=<a href='/topic/show?id=14e0839919f' target=_blank style='color:#2F92EE;'>#胰腺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83991, encryptionId=14e0839919f, topicName=胰腺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d39330628330, createdName=fzwish20010, createdTime=Thu Oct 17 07:21:00 CST 2019, time=2019-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1261176, encodeId=a44612611e68c, content=<a href='/topic/show?id=30c6102e2607' target=_blank style='color:#2F92EE;'>#高血糖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102726, encryptionId=30c6102e2607, topicName=高血糖)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332862, encodeId=0b3b133286231, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1369006, encodeId=54a013690062a, content=<a href='/topic/show?id=13cb1056e20' target=_blank style='color:#2F92EE;'>#KRAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10567, encryptionId=13cb1056e20, topicName=KRAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370973, encodeId=13b113e0973a9, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
    2019-03-28 yinhl1978
  9. [GetPortalCommentsPageByObjectIdResponse(id=1961480, encodeId=89761961480b2, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Fri Sep 20 19:21:00 CST 2019, time=2019-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1888002, encodeId=02a318880029a, content=<a href='/topic/show?id=d56611584ec' target=_blank style='color:#2F92EE;'>#Meta#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11584, encryptionId=d56611584ec, topicName=Meta)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, 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topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Tue Dec 31 15:21:00 CST 2019, time=2019-12-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1704037, encodeId=f2111e04037e5, content=<a href='/topic/show?id=14e0839919f' target=_blank style='color:#2F92EE;'>#胰腺细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=72, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83991, encryptionId=14e0839919f, topicName=胰腺细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d39330628330, createdName=fzwish20010, createdTime=Thu Oct 17 07:21:00 CST 2019, time=2019-10-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1261176, encodeId=a44612611e68c, content=<a href='/topic/show?id=30c6102e2607' target=_blank style='color:#2F92EE;'>#高血糖#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=102726, encryptionId=30c6102e2607, topicName=高血糖)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1332862, encodeId=0b3b133286231, content=<a href='/topic/show?id=e070105e2bb' target=_blank style='color:#2F92EE;'>#KRAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10572, encryptionId=e070105e2bb, topicName=KRAS突变)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/17F844FBE270B8196CB4C53EC9493C57/100, createdBy=9d712500079, createdName=ms5906905816781247, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), 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createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
    2019-03-28 jambiya
  10. 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GetPortalCommentsPageByObjectIdResponse(id=1369006, encodeId=54a013690062a, content=<a href='/topic/show?id=13cb1056e20' target=_blank style='color:#2F92EE;'>#KRAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10567, encryptionId=13cb1056e20, topicName=KRAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8217292, createdName=yinhl1978, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1370973, encodeId=13b113e0973a9, content=<a href='/topic/show?id=9c39864991e' target=_blank style='color:#2F92EE;'>#致癌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=85, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86499, encryptionId=9c39864991e, topicName=致癌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2c25323, createdName=jambiya, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1585316, encodeId=568e1585316b2, content=<a href='/topic/show?id=792b15145a6' target=_blank style='color:#2F92EE;'>#RAS突变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15145, encryptionId=792b15145a6, topicName=RAS突变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6f2c17156536, createdName=bioon7, createdTime=Thu Mar 28 14:21:00 CST 2019, time=2019-03-28, status=1, ipAttribution=)]
    2019-03-28 bioon7

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