Biomed Pharmacother:白藜芦醇苷可用于治疗糖皮质激素诱导的骨坏死

2019-08-09 sunshine 译 MedSci原创

类固醇诱导的股骨头坏死(SONFH)是由糖皮质激素诱导的难治性疾病。骨髓间充质干细胞(MSC)分化成多个骨基质细胞并且已经用作基于细胞的疗法来治疗ONFH。然而,从患有SONFH的患者分离的MSC的成骨明显降低。白藜芦醇苷因其多种药理作用而被广泛用于中药。如我们之前的研究所示,白藜芦醇苷可以防止氧化应激并促进BMSC迁移。然而,关于它在BMSC(骨髓间充质干细胞)成骨中的作用知之甚少;因此,我们进

类固醇诱导的股骨头坏死(SONFH)是由糖皮质激素诱导的难治性疾病。骨髓间充质干细胞(MSC)分化成多个骨基质细胞并且已经用作基于细胞的疗法来治疗ONFH。然而,从患有SONFH的患者分离的MSC的成骨明显降低。白藜芦醇苷因其多种药理作用而被广泛用于中药。如我们之前的研究所示,白藜芦醇苷可以防止氧化应激并促进BMSC迁移。然而,关于它在BMSC(骨髓间充质干细胞)成骨中的作用知之甚少;因此,我们进一步研究了白藜芦醇苷在hBMSC成骨中的作用和机制。

使用MTT测定,ALP染色和ALP活性测定确定白藜芦醇苷促进hBMSC的增殖和成骨分化的能力。接下来,进行qPCR和蛋白质印迹以测量与hBMSC的成骨相关的基因和蛋白质的水平。然后,用免疫荧光染色测定白藜芦醇苷对β-连环蛋白核转位的影响。

结果显示,白藜芦醇苷(30μM)明显增强hBMSCs的增殖和碱性磷酸酶(ALP)活性。此外,它还可显著上调成骨基因(Runx2,骨桥蛋白,DLX5,骨钙蛋白,I型和BMP2胶原)和Wnt信号通路的组分(β-catenin,Lef1,TCF7,c-jun,c-myc和细胞周期蛋白D)的表达。白藜芦醇苷的这些成骨作用增强作用被BMP通路的抑制剂Noggin和Wnt /β-连环蛋白途径的抑制剂DKK1阻断。然而,DKK1不影响白藜芦醇苷诱导的BMP2表达。

综上所述,该研究结果表明,白藜芦醇苷通过BMP2-Wnt/β-连环蛋白信号传导通路促进hBMSCs的增殖和成骨分化。

原始出处:

Chen XJ, Shen YS, et al., Polydatin promotes the osteogenic differentiation of human bone mesenchymal stem cells by activating the BMP2-Wnt/β-catenin signaling pathway. Biomed Pharmacother. 2019 Apr;112:108746. doi: 10.1016/j.biopha.2019.108746. Epub 2019 Mar 2.

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    2020-04-18 sunylz
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    2020-07-12 yb6560
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createdName=yb6560, createdTime=Sun Jul 12 01:39:00 CST 2020, time=2020-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908560, encodeId=6b811908560a2, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Mon Oct 14 12:39:00 CST 2019, time=2019-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1701263, encodeId=20471e0126391, content=<a href='/topic/show?id=b5f6e6827fb' target=_blank style='color:#2F92EE;'>#糖皮质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76827, encryptionId=b5f6e6827fb, topicName=糖皮质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0f4230340116, createdName=Tommy1959, createdTime=Mon May 11 16:39:00 CST 2020, time=2020-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787629, encodeId=c49b1e87629c3, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Mon Jun 29 16:39:00 CST 2020, time=2020-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680012, encodeId=692f16800120d, content=<a href='/topic/show?id=f0061016322a' target=_blank style='color:#2F92EE;'>#骨坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101632, encryptionId=f0061016322a, topicName=骨坏死)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ef27829166, createdName=zll0634, createdTime=Thu Mar 26 00:39:00 CST 2020, time=2020-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1362956, encodeId=6fc01362956ff, content=<a href='/topic/show?id=b723414321c' target=_blank style='color:#2F92EE;'>#坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41432, encryptionId=b723414321c, topicName=坏死)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600387, encodeId=9129160038ead, content=<a 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time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=371038, encodeId=e10e3e10382d, content=骨坏死新观点!, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4BC357ED6E1444.jpg, createdBy=9f231612624, createdName=liushui8012, createdTime=Sat Aug 10 08:08:45 CST 2019, time=2019-08-10, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1918816, encodeId=119f191881677, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Sat Apr 18 00:39:00 CST 2020, time=2020-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996311, encodeId=445b1996311cc, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sun Jul 12 01:39:00 CST 2020, time=2020-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908560, encodeId=6b811908560a2, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Mon Oct 14 12:39:00 CST 2019, time=2019-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1701263, encodeId=20471e0126391, content=<a href='/topic/show?id=b5f6e6827fb' target=_blank style='color:#2F92EE;'>#糖皮质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76827, encryptionId=b5f6e6827fb, topicName=糖皮质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0f4230340116, createdName=Tommy1959, createdTime=Mon May 11 16:39:00 CST 2020, time=2020-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787629, encodeId=c49b1e87629c3, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Mon Jun 29 16:39:00 CST 2020, time=2020-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680012, encodeId=692f16800120d, content=<a href='/topic/show?id=f0061016322a' target=_blank style='color:#2F92EE;'>#骨坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101632, encryptionId=f0061016322a, topicName=骨坏死)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ef27829166, createdName=zll0634, createdTime=Thu Mar 26 00:39:00 CST 2020, time=2020-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1362956, encodeId=6fc01362956ff, content=<a href='/topic/show?id=b723414321c' target=_blank style='color:#2F92EE;'>#坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41432, encryptionId=b723414321c, topicName=坏死)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600387, encodeId=9129160038ead, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1609928, encodeId=c8a01609928b9, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=371038, encodeId=e10e3e10382d, content=骨坏死新观点!, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4BC357ED6E1444.jpg, createdBy=9f231612624, createdName=liushui8012, createdTime=Sat Aug 10 08:08:45 CST 2019, time=2019-08-10, status=1, ipAttribution=)]
    2020-06-29 jj000001
  6. [GetPortalCommentsPageByObjectIdResponse(id=1918816, encodeId=119f191881677, content=<a href='/topic/show?id=4f26341994' target=_blank style='color:#2F92EE;'>#Bio#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3419, encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Sat Apr 18 00:39:00 CST 2020, time=2020-04-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1996311, encodeId=445b1996311cc, content=<a href='/topic/show?id=ed881120ec8' target=_blank style='color:#2F92EE;'>#MAC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11207, encryptionId=ed881120ec8, topicName=MAC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sun Jul 12 01:39:00 CST 2020, time=2020-07-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1908560, encodeId=6b811908560a2, content=<a href='/topic/show?id=a8d0141605e' target=_blank style='color:#2F92EE;'>#pharma#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14160, encryptionId=a8d0141605e, topicName=pharma)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Mon Oct 14 12:39:00 CST 2019, time=2019-10-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1701263, encodeId=20471e0126391, content=<a href='/topic/show?id=b5f6e6827fb' target=_blank style='color:#2F92EE;'>#糖皮质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76827, encryptionId=b5f6e6827fb, topicName=糖皮质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0f4230340116, createdName=Tommy1959, createdTime=Mon May 11 16:39:00 CST 2020, time=2020-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787629, encodeId=c49b1e87629c3, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Mon Jun 29 16:39:00 CST 2020, time=2020-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680012, encodeId=692f16800120d, content=<a href='/topic/show?id=f0061016322a' target=_blank style='color:#2F92EE;'>#骨坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101632, encryptionId=f0061016322a, topicName=骨坏死)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ef27829166, createdName=zll0634, createdTime=Thu Mar 26 00:39:00 CST 2020, time=2020-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1362956, encodeId=6fc01362956ff, content=<a href='/topic/show?id=b723414321c' target=_blank style='color:#2F92EE;'>#坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41432, encryptionId=b723414321c, topicName=坏死)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600387, encodeId=9129160038ead, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1609928, encodeId=c8a01609928b9, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=371038, encodeId=e10e3e10382d, content=骨坏死新观点!, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4BC357ED6E1444.jpg, createdBy=9f231612624, createdName=liushui8012, createdTime=Sat Aug 10 08:08:45 CST 2019, time=2019-08-10, status=1, ipAttribution=)]
    2020-03-26 zll0634
  7. 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encryptionId=b5f6e6827fb, topicName=糖皮质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0f4230340116, createdName=Tommy1959, createdTime=Mon May 11 16:39:00 CST 2020, time=2020-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1787629, encodeId=c49b1e87629c3, content=<a href='/topic/show?id=fa03141591e' target=_blank style='color:#2F92EE;'>#Pharm#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14159, encryptionId=fa03141591e, topicName=Pharm)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8942242, createdName=jj000001, createdTime=Mon Jun 29 16:39:00 CST 2020, time=2020-06-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1680012, encodeId=692f16800120d, content=<a href='/topic/show?id=f0061016322a' target=_blank style='color:#2F92EE;'>#骨坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101632, encryptionId=f0061016322a, topicName=骨坏死)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=63ef27829166, createdName=zll0634, createdTime=Thu Mar 26 00:39:00 CST 2020, time=2020-03-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1362956, encodeId=6fc01362956ff, content=<a href='/topic/show?id=b723414321c' target=_blank style='color:#2F92EE;'>#坏死#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=41432, encryptionId=b723414321c, topicName=坏死)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c0e3195, createdName=millore, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1600387, encodeId=9129160038ead, content=<a href='/topic/show?id=3565e21649e' target=_blank style='color:#2F92EE;'>#皮质激素#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72164, encryptionId=3565e21649e, topicName=皮质激素)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb1a18781011, createdName=bbwznl, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1609928, encodeId=c8a01609928b9, content=<a href='/topic/show?id=eb6b1145939' target=_blank style='color:#2F92EE;'>#Med#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=19, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11459, encryptionId=eb6b1145939, topicName=Med)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a19396740, createdName=ms3994565386320060, createdTime=Sun Aug 11 05:39:00 CST 2019, time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=371038, encodeId=e10e3e10382d, content=骨坏死新观点!, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4BC357ED6E1444.jpg, createdBy=9f231612624, createdName=liushui8012, createdTime=Sat Aug 10 08:08:45 CST 2019, time=2019-08-10, status=1, ipAttribution=)]
    2019-08-11 millore
  8. 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  9. 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  10. 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time=2019-08-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=371038, encodeId=e10e3e10382d, content=骨坏死新观点!, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20150714/IMG55A4BC357ED6E1444.jpg, createdBy=9f231612624, createdName=liushui8012, createdTime=Sat Aug 10 08:08:45 CST 2019, time=2019-08-10, status=1, ipAttribution=)]
    2019-08-10 liushui8012

    骨坏死新观点!

    0