柳叶刀:HPV疫苗真实世界研究结果出来了!宫颈癌发病率下降87%!打不到九价,这样打效果也不差

2021-11-24  Swagpp MedSci原创

近年来,HPV疫苗在国内刮起了很大的风,却出现了“两极分化”的状态。进口九价在国内一针难求,二价库存充足但无人问津。不知道HPV疫苗到底要不要打?什么时候打?要打怎样的?

11月15日,广东省卫生健康委举行新闻发布会,官宣将启动全省适龄女生免费二价HPV疫苗接种工作,这也是全国首个以省为单位进行国产HPV疫苗的免费接种。这一政策的出台,随即在全国范围内引起了轰动。

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广东卫健委召开新闻发布会(图源:南方网)

广东省卫健委副主任、省中医药局局长徐庆锋表示,该项目的实施对象为具有广东省学籍、2022年9月起新进入初中一年级且未接种过HPV疫苗的14周岁以下女生,按照知情、自愿、免费的原则,进行HPV疫苗免费接种。预计到2030年,广东省90%的15岁以下女生将完成HPV预防性疫苗的全程免疫

近年来,HPV疫苗在国内刮起了很大的风,却出现了“两极分化”的状态。进口九价在国内一针难求,二价库存充足但无人问津。很多人还处于观望状态,不知道HPV疫苗到底要不要打?什么时候打?要打怎样的?今日梅斯和大家聊聊HPV疫苗。

HPV疫苗到底要不要接种?

目前唯一可预防的癌症

世界卫生组织国际癌症研究机构(IARC)于2020年发布的数据显示,宫颈癌位列我国第十大癌,2020年发病和死亡人数分别为11.0万和5.9万,呈上升趋势。也就是说每2万多人中便会有1人死于宫颈癌。

 

图片图片

2020年我国癌症发病率与死亡率(图源:IARC)

事实上,宫颈癌是全球目前唯一病因明确且可预防的癌症。正是因为HPV疫苗的出现,使得预防控制、全面消除宫颈癌成为可能。

HPV效果如何?

发病率最高下降87%,9-14岁接种效果最好

11月3日,《柳叶刀》上发布的最新研究显示,在全面接种二价HPV疫苗后,1995年9月1日后出生的英国女性宫颈癌发病率几乎清零。

 

图片

(图源:Lancet  https://doi.org/10.1016/S0140-6736(21)02178-4.)

英国于2008年9月1日开展了二价HPV疫苗接种计划,为12-13岁女孩提供常规疫苗接种,并为14-18岁少女提供疫苗补充计划。由于癌症疫苗的效应并非立竿见影,而需要经过多年的考验。为了验证这一项目的效果,英国盖伊癌症中心的Peter Sasieni教授携其团队历时15年对1370万名女性进行随访调查。

结果发现:与未接种相比,接种疫苗后宫颈癌和宫颈癌前病变发病率显著降低。在8年级(12-13岁;出生日期在1995年9月1日至1996年8月31日之间)就接种二价疫苗的女性中,在之后13年间宫颈癌的发病率降低至3人/百万人,低于未接种疫苗的同龄人(18人/百万人),显示英国HPV疫苗接种计划几乎消除了1995年9月1日后出生的英国女性宫颈癌。

也就是说,HPV疫苗对于接种者有很强的保护效力。

与未接种者相比,16-18岁、14-16岁、12-13岁的接种者宫颈癌发病率分别降低了34%、62%、87%,宫颈上皮内瘤变3级(CIN3)的发病率分别降低了39%、75%、97%。

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宫颈癌及CIN3发病率对比图

这一数据体现,在受调查年龄段的女孩中,随着接种年龄的减小,HPV疫苗对于宫颈癌的预防效果越好。也就是说,越早接种HPV疫苗,保护效力越高。

WHO倡议HPV疫苗的最佳接种年龄是9-14岁。

一是因为,疫苗接种最好在性行为发生之前。HPV主要通过性行为传播,获得感染的高峰为开始性活跃期之后不久。当发生性行为后,HPV的暴露风险很高,而疫苗只是起到预防效果而非治疗,因此在感染后再接种疫苗保护效力很低。

中国流行统计学调查数据显示,我国女性感染高危HPV的第一个高峰年龄为15-24岁。所以,在这个年龄段之前接种HPV疫苗,保护效果最佳。

二是因为,这个年龄段的免疫应答水平高,产生的中和抗体滴度大,也就增强了疫苗的保护效力。

总而言之:HPV疫苗保护效果很好,且要尽量早打,最佳打疫苗年龄为9-14岁

打不上九价咋办?

并非一定要选“高价”

国内的九价疫苗“一针难求”,很多人提前一年预约到现在都没打上疫苗,有人为了追求九价甚至跑到国外去接种疫苗,似乎非九价不打。相比之下,国内的二价和四价疫苗很充足,却鲜有人问津。

然而,九价真的会比二价和四价疫苗的保护效益强很多吗?

目前全球范围内运用的二价疫苗,是针对HPV16和HPV18这两种高危型病毒,四价疫苗则比二价增加了两型(即四价可预防HPV6,11,16,18),九价比二价增加了七型(即九价可预防HPV6,11,16,18,31,33,45,52,和58)。

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(图源:Lancet Oncology)

但是在我国国内,84.5%的宫颈癌是由HPV16和HPV18这两型感染引起的,WHO也发文证明过二价、四价、九价在预防HPV16和18具有同等效力。也就是说,在降低宫颈癌患病风险的作用上,二价疫苗是性价比最高的。

一般而言,宫颈癌疫苗都需要接种三针。但近日国际癌症研究机构Partha Basu教授曾在Lancet Oncology上发文,探究了不同剂量(几针)的疫苗在保护效力的区别,发现单剂HPV疫苗与两剂、三剂疫苗对HPV16和18型的持续感染保护效益相似。

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(图源:Lancet Oncology  doi: 10.1016/S1470-2045(21)00453-8. )
 
该研究对14,277名接种过疫苗的女性进行了平均为期9年的随访(IQR 8.2-9.6),其中接种了三针、两针、一针的接种者分别为4348、4980、4949名。结果显示,接种疫苗的十年内,只接种一针四价疫苗对高危型HPV16和HPV18持续感染提供的保护效力为95.4%, 和接种两剂(93.1%)和三剂(93.3%)的保护力相当。
此研究还发现,在接种HPV疫苗后还会对其他基因型有交叉保护效应。也就是说,虽然四价疫苗主要是针对6、11、16、18型HPV,但在接种了四价疫苗后,还会产生对31、33、45型HPV的抗体。只接种一针四价疫苗对预防21种基因型持续感染的效力为35.4%,与两针的36.7%、三针的39.3%相当。
 
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不同剂HPV疫苗保护效力对比图
 
也就是说,不要把眼光局限于九价,能打到啥就打啥,二价疫苗也行,一针或许也行
 
国产疫苗保护效力如何?
不输进口
 
此次,广东省提供免费接种的疫苗是国产二价疫苗“馨可宁”,也是全国首个通过世界卫生组织预认证的国产HPV疫苗。
 
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                                               国产疫苗馨可宁
                                             (图源:WHO
 
馨可宁是由万泰生物全资子公司厦门万泰沧海生物技术有限公司与厦门大学联合研制的。早在去年,厦门就发布了《厦门市国产二价HPV疫苗接种实施方案的通知》,决定在2020-2022年期间为全市13-14岁半的在校女生提供国产二价HPV疫苗并实施自愿免费接种,接种的正是厦门本土疫苗“馨可宁”。
 
作为全国首支国产二价疫苗,国内临床试验显示,馨可宁在预防高危型HPV(16和18)引起的宫颈癌前病变上,该药物效力达到100%(95%CI: 55.7, 100.0),而长期(1年及以上)的保护效力也维持在95.3%(95%CI: 70.7, 99.9)。
 
图片
                          馨可宁的保护效力(图源:馨可宁说明书)
 
二价HPV疫苗馨可宁的覆盖面广,适用于9-45岁女性,其中9-14岁仅需接种两针(0,6月两针),更为方便快捷,而15岁及以上则需要接种3针(0,1,6月三针)。
 
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                                          馨可宁的适用范围
                                      (图源:馨可宁说明书)
 
相比于进口疫苗,馨可宁的价格更低,每只仅329元,比进口疫苗便宜200多元;生产速度快产量高,供货量每年可达3000万支,所以市场供应相对充足。
 
图片
已上市四种疫苗对比
 
同时,国内的企业也在加紧研发九价HPV疫苗,万泰生物、瑞科生物和康乐卫士这三家企业的疫苗研制均已进入临床三期阶段,有望尽快面世,填补国内HPV疫苗缺口。
 
综上所述:HPV疫苗一定要打!疫苗的最佳接种年龄是9-14岁,早接种效果更好;不一定非“九价”不接种,国产二价疫苗保护效果一样很好。
 
参考资料
[1]IARC中国癌症数据 https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf
[2]厦门万泰官网http://www.innovax.cn/
[3]Milena Falcaro, Alejandra Castañon, Busani Ndlela, Marta Checchi, Kate Soldan, Jamie Lopez-Bernal, Lucy Elliss-Brookes, Peter Sasieni. The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study, The Lancet, 2021, ISSN 0140-6736, https://doi.org/10.1016/S0140-6736(21)02178-4.
[4]Basu P, Malvi SG, Joshi S, Bhatla N, Muwonge R, Lucas E, Verma Y, Esmy PO, Poli URR, Shah A, Zomawia E, Pimple S, Jayant K, Hingmire S, Chiwate A, Divate U, Vashist S, Mishra G, Jadhav R, Siddiqi M, Sankaran S, Prabhu PR, Kannan TPRA, Varghese R, Shastri SS, Anantharaman D, Gheit T, Tommasino M, Sauvaget C, Pillai MR, Sankaranarayanan R. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years after one, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre, prospective, cohort study. Lancet Oncol. 2021 Nov;22(11):1518-1529. doi: 10.1016/S1470-2045(21)00453-8. Epub 2021 Oct 8. PMID: 34634254; PMCID: PMC8560643.
[5]馨可宁说明书file:///D:/Users/shipei.wang/Documents/WeChat%20Files/wxid_zcl0dk9l4tn422/FileStorage/File/2021-11/cecolin.pdf
撰文 | Swagpp
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createdName=智者为医08, createdTime=Sat May 21 10:44:38 CST 2022, time=2022-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075248, encodeId=72d310e524862, content=HPV国产二价广东免费接种,真的是民心所向!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:26:48 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075245, encodeId=6ab710e5245e3, content=受益匪浅!, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:21:17 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1295354, encodeId=40ad1295354d9, content=<a href='/topic/show?id=0425e2636b8' target=_blank style='color:#2F92EE;'>#真实世界#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72636, encryptionId=0425e2636b8, topicName=真实世界)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b34252, createdName=chenshujs, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408319, encodeId=9d41140831901, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
  3. 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createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
  4. 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createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
    2022-05-04 673827243

    早打早受益

    0

  5. 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createdName=智者为医08, createdTime=Sat May 21 10:44:38 CST 2022, time=2022-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075248, encodeId=72d310e524862, content=HPV国产二价广东免费接种,真的是民心所向!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:26:48 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075245, encodeId=6ab710e5245e3, content=受益匪浅!, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:21:17 CST 2021, time=2021-11-29, status=1, ipAttribution=), 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createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
    2022-02-12 ms2000001066939383

    再不打,二价也没了

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1823775, encodeId=bbbb1823e75d7, content=<a href='/topic/show?id=b2873e9220e' target=_blank style='color:#2F92EE;'>#发病率#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37922, encryptionId=b2873e9220e, topicName=发病率)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aa0e14, createdName=lifestar, createdTime=Fri Jan 14 16:44:38 CST 2022, time=2022-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079302, encodeId=d39020e930299, content=<a href='/topic/show?id=659ce1280ee' target=_blank style='color:#2F92EE;'>#癌发病率#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71280, encryptionId=659ce1280ee, topicName=癌发病率)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1777154, createdName=chenhongpeng, createdTime=Mon Nov 29 17:44:38 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1799913, encodeId=0e601e99913e4, content=<a href='/topic/show?id=9e3fe127909' target=_blank style='color:#2F92EE;'>#癌发病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71279, encryptionId=9e3fe127909, topicName=癌发病)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e2c92500045, createdName=12498636m49(暂无昵称), createdTime=Fri Apr 08 15:44:38 CST 2022, time=2022-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1216738, encodeId=b8761216e382c, content=早打早受益, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f5223097978, createdName=673827243, createdTime=Wed May 04 11:05:41 CST 2022, time=2022-05-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1192835, encodeId=8f5b1192835f7, content=再不打,二价也没了, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54615714086, createdName=ms2000001066939383, createdTime=Sat Feb 12 23:43:09 CST 2022, time=2022-02-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1739606, encodeId=80381e39606b1, content=<a href='/topic/show?id=8041e343504' target=_blank style='color:#2F92EE;'>#研究结果#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=73435, encryptionId=8041e343504, topicName=研究结果)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=智者为医08, createdTime=Sat May 21 10:44:38 CST 2022, time=2022-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075248, encodeId=72d310e524862, content=HPV国产二价广东免费接种,真的是民心所向!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:26:48 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075245, encodeId=6ab710e5245e3, content=受益匪浅!, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:21:17 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1295354, encodeId=40ad1295354d9, content=<a href='/topic/show?id=0425e2636b8' target=_blank style='color:#2F92EE;'>#真实世界#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72636, encryptionId=0425e2636b8, topicName=真实世界)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b34252, createdName=chenshujs, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408319, encodeId=9d41140831901, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
  7. [GetPortalCommentsPageByObjectIdResponse(id=1823775, encodeId=bbbb1823e75d7, content=<a href='/topic/show?id=b2873e9220e' target=_blank style='color:#2F92EE;'>#发病率#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37922, encryptionId=b2873e9220e, topicName=发病率)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aa0e14, createdName=lifestar, createdTime=Fri Jan 14 16:44:38 CST 2022, time=2022-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079302, encodeId=d39020e930299, content=<a href='/topic/show?id=659ce1280ee' target=_blank style='color:#2F92EE;'>#癌发病率#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71280, encryptionId=659ce1280ee, topicName=癌发病率)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1777154, 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GetPortalCommentsPageByObjectIdResponse(id=1295354, encodeId=40ad1295354d9, content=<a href='/topic/show?id=0425e2636b8' target=_blank style='color:#2F92EE;'>#真实世界#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72636, encryptionId=0425e2636b8, topicName=真实世界)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b34252, createdName=chenshujs, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408319, encodeId=9d41140831901, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
    2021-11-29 ms3000001592172450

    HPV国产二价广东免费接种,真的是民心所向!

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1823775, encodeId=bbbb1823e75d7, content=<a href='/topic/show?id=b2873e9220e' target=_blank style='color:#2F92EE;'>#发病率#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37922, encryptionId=b2873e9220e, topicName=发病率)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aa0e14, createdName=lifestar, createdTime=Fri Jan 14 16:44:38 CST 2022, time=2022-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079302, encodeId=d39020e930299, content=<a href='/topic/show?id=659ce1280ee' target=_blank style='color:#2F92EE;'>#癌发病率#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=71280, encryptionId=659ce1280ee, topicName=癌发病率)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=1777154, 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createdName=智者为医08, createdTime=Sat May 21 10:44:38 CST 2022, time=2022-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075248, encodeId=72d310e524862, content=HPV国产二价广东免费接种,真的是民心所向!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:26:48 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075245, encodeId=6ab710e5245e3, content=受益匪浅!, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:21:17 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1295354, encodeId=40ad1295354d9, content=<a href='/topic/show?id=0425e2636b8' target=_blank style='color:#2F92EE;'>#真实世界#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72636, encryptionId=0425e2636b8, topicName=真实世界)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=5b34252, createdName=chenshujs, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1408319, encodeId=9d41140831901, content=<a href='/topic/show?id=92194628826' target=_blank style='color:#2F92EE;'>#宫颈#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=46288, encryptionId=92194628826, topicName=宫颈)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=11102737131, createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
    2021-11-29 ms3000001592172450

    受益匪浅!

    0

  9. 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createdName=智者为医08, createdTime=Sat May 21 10:44:38 CST 2022, time=2022-05-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075248, encodeId=72d310e524862, content=HPV国产二价广东免费接种,真的是民心所向!, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:26:48 CST 2021, time=2021-11-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1075245, encodeId=6ab710e5245e3, content=受益匪浅!, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ee335603873, createdName=ms3000001592172450, createdTime=Mon Nov 29 23:21:17 CST 2021, time=2021-11-29, status=1, ipAttribution=), 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createdName=一闲, createdTime=Fri Nov 26 00:44:38 CST 2021, time=2021-11-26, status=1, ipAttribution=)]
  10. 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    2021-11-26 一闲

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