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Nat Commun:多组学分析鉴定SOX10为胶质母细胞瘤RTK I亚型的主要调节因子

2020-12-24 xiaozeng MedSci原创

胶质母细胞瘤是一种高度恶性的脑癌,尽管目前对于该疾病采取了许多包括手术切除和替莫唑胺相关的放化疗等积极的治疗方案,但患者的预后仍特别差。

胶质母细胞瘤是一种高度恶性的脑癌,尽管目前对于该疾病采取了许多包括手术切除和替莫唑胺相关的放化疗等积极的治疗方案,但患者的预后仍特别差。

近期的一项大规模基因组学研究鉴定了胶质母细胞瘤的四种mRNA表达/DNA甲基化亚型及其标志性遗传病灶:IDH、MES、RTK I、RTK II。 其中,MES、RTK I和RTK II亚型分别对应于间充质、原神经元和经典RNA表达亚型。目前已在患者的治疗过程中观察到这些亚型之间的转换,该作用也可能导致更糟的患者预后。然而,目前尚不清楚这些转变是由于肿瘤细胞的可塑性还是由先前存在的抗性亚群的扩增所引起的。

胶质母细胞瘤亚型的表观基因组的综合数据分析

在该研究中,研究人员通过对60个胶质母细胞瘤原发性肿瘤组织进行多组学分析,并采用染色质和RNA衍生的基因调控网络进行正交分析。研究人员通过分析鉴定了38个亚型的主调控因子,并进一步的将这些因子的细胞群体特异性活性进一步的与已发表的单细胞RNA测序数据进行映射比对。

SOX10缺失诱导间充质表型

这些分析结果发现,少突胶质细胞前体标志物和染色质修饰因子SOX10是RTK I亚型肿瘤的一个主要调节因子。体外功能实验显示,SOX10缺失会导致肿瘤亚型的转换,在患者的转录组学、表观遗传学和表型水平上观察到原神经-间充质的转变。在移植了胶质母细胞瘤的移植瘤小鼠模型中,抑制SOX10的表达能够导致肿瘤侵袭能力的增强,免疫细胞浸润的增加并显著降低存活率。


综上,这些研究结果揭示了SOX10是RTK I亚型的一个主要的调节因子,其能够影响肿瘤细胞以及相关的肿瘤微环境。


原始出处:

Wu, Y., Fletcher, M., Gu, Z. et al. Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype. Nat Commun 11, 6434 (18 December 2020).

 



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beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Sat Dec 26 13:29:20 CST 2020, time=2020-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910906, encodeId=d98b91090636, content=已读,受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Fri Dec 25 16:34:32 CST 2020, time=2020-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910748, encodeId=d82b910e4847, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 24 23:38:53 CST 2020, time=2020-12-24, status=1, ipAttribution=)]
    2021-05-16 liuli5079
  5. [GetPortalCommentsPageByObjectIdResponse(id=1755494, encodeId=54291e55494db, content=<a href='/topic/show?id=186616562dd' target=_blank style='color:#2F92EE;'>#Sox10#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16562, encryptionId=186616562dd, topicName=Sox10)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11c236925356, createdName=周虎, createdTime=Sat Jul 03 16:29:20 CST 2021, time=2021-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772373, encodeId=a2d71e72373b8, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, 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objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Oct 31 11:29:20 CST 2021, time=2021-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911416, encodeId=d6bd9114166c, content=SOX10缺失会导致肿瘤亚型的转换, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Sun Dec 27 21:15:18 CST 2020, time=2020-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476106, encodeId=dcb414e610628, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 24 23:38:53 CST 2020, time=2020-12-24, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1755494, encodeId=54291e55494db, content=<a href='/topic/show?id=186616562dd' target=_blank style='color:#2F92EE;'>#Sox10#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16562, encryptionId=186616562dd, topicName=Sox10)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11c236925356, createdName=周虎, createdTime=Sat Jul 03 16:29:20 CST 2021, time=2021-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772373, encodeId=a2d71e72373b8, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, 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objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Oct 31 11:29:20 CST 2021, time=2021-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911416, encodeId=d6bd9114166c, content=SOX10缺失会导致肿瘤亚型的转换, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Sun Dec 27 21:15:18 CST 2020, time=2020-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476106, encodeId=dcb414e610628, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Sat Dec 26 13:29:20 CST 2020, time=2020-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910906, encodeId=d98b91090636, content=已读,受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Fri Dec 25 16:34:32 CST 2020, time=2020-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910748, encodeId=d82b910e4847, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 24 23:38:53 CST 2020, time=2020-12-24, status=1, ipAttribution=)]
    2021-10-31 liye789132251
  7. 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 24 23:38:53 CST 2020, time=2020-12-24, status=1, ipAttribution=)]
    2020-12-27 oo902

    SOX10缺失会导致肿瘤亚型的转换

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1755494, encodeId=54291e55494db, content=<a href='/topic/show?id=186616562dd' target=_blank style='color:#2F92EE;'>#Sox10#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16562, encryptionId=186616562dd, topicName=Sox10)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11c236925356, createdName=周虎, createdTime=Sat Jul 03 16:29:20 CST 2021, time=2021-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772373, encodeId=a2d71e72373b8, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, 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objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Oct 31 11:29:20 CST 2021, time=2021-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911416, encodeId=d6bd9114166c, content=SOX10缺失会导致肿瘤亚型的转换, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Sun Dec 27 21:15:18 CST 2020, time=2020-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476106, encodeId=dcb414e610628, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Sat Dec 26 13:29:20 CST 2020, time=2020-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910906, encodeId=d98b91090636, content=已读,受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Fri Dec 25 16:34:32 CST 2020, time=2020-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910748, encodeId=d82b910e4847, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 24 23:38:53 CST 2020, time=2020-12-24, status=1, ipAttribution=)]
  9. [GetPortalCommentsPageByObjectIdResponse(id=1755494, encodeId=54291e55494db, content=<a href='/topic/show?id=186616562dd' target=_blank style='color:#2F92EE;'>#Sox10#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16562, encryptionId=186616562dd, topicName=Sox10)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11c236925356, createdName=周虎, createdTime=Sat Jul 03 16:29:20 CST 2021, time=2021-07-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1772373, encodeId=a2d71e72373b8, content=<a href='/topic/show?id=c38963544cc' target=_blank style='color:#2F92EE;'>#母细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=63544, encryptionId=c38963544cc, topicName=母细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b07438375157, createdName=huperzia, createdTime=Fri Jun 04 22:29:20 CST 2021, time=2021-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2052938, encodeId=5e062052938a6, content=<a href='/topic/show?id=ae848406335' target=_blank style='color:#2F92EE;'>#胶质母细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84063, encryptionId=ae848406335, topicName=胶质母细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a691420, createdName=30397604, createdTime=Tue Nov 23 22:29:20 CST 2021, time=2021-11-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087860, encodeId=1675208e860ad, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Sun May 16 17:29:20 CST 2021, time=2021-05-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1969277, encodeId=dc4c19692e76e, content=<a href='/topic/show?id=10e09205572' target=_blank style='color:#2F92EE;'>#调节因子#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=92055, encryptionId=10e09205572, topicName=调节因子)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Wed Apr 07 08:29:20 CST 2021, time=2021-04-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1884863, encodeId=746c188486394, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Oct 31 11:29:20 CST 2021, time=2021-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911416, encodeId=d6bd9114166c, content=SOX10缺失会导致肿瘤亚型的转换, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Sun Dec 27 21:15:18 CST 2020, time=2020-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476106, encodeId=dcb414e610628, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77977, encryptionId=2bcee797732, topicName=细胞瘤)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf5e7252474, createdName=spoonycyy, createdTime=Sat Dec 26 13:29:20 CST 2020, time=2020-12-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910906, encodeId=d98b91090636, content=已读,受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f03a5433387, createdName=ms5000000518166734, createdTime=Fri Dec 25 16:34:32 CST 2020, time=2020-12-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=910748, encodeId=d82b910e4847, content=了解, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 24 23:38:53 CST 2020, time=2020-12-24, status=1, ipAttribution=)]
    2020-12-25 ms5000000518166734

    已读,受益匪浅

    0

  10. 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objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Oct 31 11:29:20 CST 2021, time=2021-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=911416, encodeId=d6bd9114166c, content=SOX10缺失会导致肿瘤亚型的转换, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=a37a1710612, createdName=oo902, createdTime=Sun Dec 27 21:15:18 CST 2020, time=2020-12-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1476106, encodeId=dcb414e610628, content=<a href='/topic/show?id=2bcee797732' target=_blank style='color:#2F92EE;'>#细胞瘤#</a>, 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topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6KcicAVC1MwuOgo3iaicb1Imgk1yIfnvr6oXzibcAFB6puAyNJXbzWhNuLqaFYBVRWjh7rghkvFLPxMAfD5ib3nXwVD/0, createdBy=bed21972958, createdName=wxl882001, createdTime=Thu Dec 24 23:38:53 CST 2020, time=2020-12-24, status=1, ipAttribution=)]
    2020-12-24 wxl882001

    了解

    0

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