季加孚:肿瘤领域如何实现精准医疗的3R理念

2018-01-07 佚名 北京大学医学部

季加孚理解的精准医学,是指根据个体基因特征、环境以及生活习惯进行疾病干预和治疗的最佳方法,涵盖一个大数据,两个体系,三个精准,四个工具。

根据国家肿瘤防治办公室最新公布的数据,我国的肿瘤5年患病率约为5‰,据此估算我国的肿瘤5年区间患病人数约为778.4万。其中40-60岁的壮年人口比例超过50%,可以说给国家、社会都带来了巨大的疾病负担。

自公元前2500年古埃及伟大的医生印和阗在史密斯莎草纸上首次描述了肿瘤,之后的4000余年时间里,人类一直致力于肿瘤的诊断和治疗,但却基本处于无计可施的状态。直到现代医学的诞生,肿瘤的治疗效果才得到明显改善,在近100年里,肿瘤的治疗经历了从经验医学到循证医学,进而到转化医学和精准医学的变革,肿瘤的长期存活率提高了65%。

季加孚理解的精准医学,是指根据个体基因特征、环境以及生活习惯进行疾病干预和治疗的最佳方法。

他用较为通俗的语言给我们概括了精准医疗:一个大数据,两个体系(微观体系,宏观体系),三个精准(以靶向药物为代表的干预手段精准,以基因测序为代表的疾病信息精准,以临床沟通为代表的医疗需求精准),四个工具(药物研发工具、基因分析工具、系统整合工具、政策引导工具)。

Q精准医学给肿瘤领域带来了什么改变?

季加孚:肿瘤领域精准医学的核心是全方位覆盖,内容包括:高危人群筛选、病因干预、早期诊断、预后判断、治疗决策、复发控制以及疾病康复等多方面。

具体从实现方式上看:首先要采集信息,临床信息资料、生物样本材料、分子分型信息,然后建立精准医疗数据仓库,最后通过分析处理实现三个主要核心功能:临床研究匹配、分子诊断,以及临床决策支持。

这就要求对现有医疗及其支持体系进行全新的研究设计,尤其是医疗信息以及医疗物联网络,从而构建完善的大数据网络。通过构建这样的网络,能促进体系内的快速学习。整合患者内外各项特征数据并进行分析,是精准医疗实现研究、转化、持续发展的核心。通过基因型与表型的关联,识别特定的患者群体。

精准医疗的终极目的是——发展新型的“循证临床决策系统”。通过患者招募、长期随访、样本采集以及分子检测,建立多维数据仓库。从而服务患者、服务医生、服务社会。服务患者,实现个体化医疗,进行健康教育,建立合理的治疗方案;服务医生,主要是为医生提供治疗决策;服务社会,主要是提供动态健康管理、科技动态更新以及建立循证指南予以推广应用。简单来说,就是实现精准医疗的3R理念:RighttreatmentattheRighttimeattheRightplace,即“选择正确的治疗,正确的时间,正确的地点”。

Q目前在肿瘤领域,精准医学取得了哪些初步成效?

季加孚:目前肿瘤领域已经开展的精准医疗研究大致可分为以下4类,包括:1.从基因等多个角度发现肿瘤的个体化差异,形成肿瘤的分子分型。2.建立基于大数据概念的最大范围协同合作平台,测试和验证靶向治疗和干预手段的临床效果。3深入分析个体基因因素、生活方式因素与外环境因素,掌握不同因素间相互作用的机制,系统的评价疾病的风险。4.应用以移动医疗为代表的新一代信息采集技术,实时收集、整合、分析数据,系统的评价健康状况。

肿瘤是一种复杂的多基因病,结肠癌的多阶段发病模型提示一般需要通过多个关键驱动基因异常改变的积累才会最终形成恶变。精准医疗包括精准预测,诊断和治疗几个方面实质上都是要实现肿瘤分子生物学水平的检测筛查,DNA测序技术的不断进步以及成本的不断下降推动了基因检测在临床诊治中的广泛应用。

对于精准预测,精准诊断方面,遗传性肿瘤综合征的筛查是最典型的例子,目前多种遗传性肿瘤综合征都找到了主要的治病基因,且经过家系研究得到了印证,这些治病基因的检测可以帮助临床医生综合患者的家系图、临床表现以及基因检测异常对患者做出精准诊断,而对于这些先发病患者的家属进一步进行基因检测,如筛查到同样的基因异常,则可以确定他们是高危易感患者,需要针对易发病脏器进行严密的监查,甚至是采取预防行手术治疗。

最为百姓熟知的例子就是安吉丽娜·朱莉的故事,她通过基因筛查得知自己带有BRCA1基因缺陷,因而预防性切除了乳腺、卵巢及输卵管。胃肠道肿瘤也存在同样的例子,包括家族性腺瘤息肉病(APC基因),Lynch综合征(MLH1,MSH2,MSH6,MSH3,PMS1,PMS2,TACSTD1基因)以及遗传性弥漫性胃癌(CDH基因)都具有比较明确的治病基因,通过基因检测可以早期预测发病风险,从而加强胃肠镜监测筛查,最终达到早期诊断的目的。

精准治疗主要针对某个靶点,对患者进行基因检测,若发现某些突变,可有利于疾病的诊断,并根据肿瘤的分子生物学特征,为患者选择更合适的药物。例如在转移性结直肠癌的治疗中,在KRAS野生型患者中,与单纯化疗相比,化疗联合西妥昔单抗显著延长了患者的PFS和OS。

从发展的角度来看,未来的癌症治疗将全面与基因手段结合,根据基因不同,将患者分为不同亚群,针对个人的主要基因变化进行治疗,实现精准治疗。比如近日FDA官网宣布,免疫药物PD1抑制剂Keytruda被批准用于治疗带有微卫星不稳定性高或错配修复缺陷的不可切除或转移性实体瘤。这种治疗弱化肿瘤的组织来源,按照基因突变信息来治疗肿瘤则是精准医疗的里程碑式突破,体现了真正意义上的精准治疗。

Q请您具体介绍一下北京大学肿瘤医学院在肿瘤的精准医疗方面做了哪些工作?

季加孚:北大肿瘤医院已经在医院内部建立起了完整、干净的数据存储系统;规范化的生物样本采集、存储系统,并辅助以生物信息学分析团队;良好临床及科研能力的临床团队;并有多项同精准医疗相关的临床研究正在进行中。这些体系的建立与完善都是为病人提供更精准的诊断和治疗服务的。

精准医疗的前提是精准诊断,与常规的临床检测相比,精准诊断有助于我们对肿瘤的生物学行为进行更好的预测以及制定更加有效的治疗方案。

我院的多个肿瘤专业都已经开展了不同瘤种的分子生物学诊断研究。

比如针对胃癌的HER2靶点,我们已经开展了大样本的筛查工作,对我国胃癌患者的HER2表达情况及临床特点进行了研究,该项工作对我国胃癌的靶向药物研究起到了很好的示范作用。针对胃癌异质性强的特点,我们也相继开展了VEGFR、免疫检查点等的检测研究,为后续的新靶向治疗、免疫治疗等打下基础。同样地,针对胃肠道间质瘤进行的c-KIT、PDGFRA基因突变检测,黑色素瘤的c-KIT、BRAF等基因突变检测,以及非小细胞肺癌的EGFR、KRAS突变、C-MET扩增、EML4-ALK融合基因检测等诊断均已完成了从临床研究向临床应用的过渡,为患者的后续精准治疗提供了更为详实的依据。

我们对精准医疗的推广不仅限于肿瘤现患者,我们已经着眼于肿瘤的早期预防及高危筛查。我院乳腺中心在国内系统开展了家族性乳腺癌易感基因的研究,在北京地区率先开展了家族性乳腺癌BRCA1/2基因胚系突变的检测。我院分子诊断中心的成立为肿瘤的早期诊断及高危筛查搭建了平台,目前可进行九项肿瘤相关的基因检测。

作为国内负责单位,我院牵头参与了ToGA研究,该研究的成功使得曲妥珠单抗成为迄今为止对HER2阳性胃癌最为有效的靶向治疗方式。目前各瘤种均已开展了针对不同靶点的药物研究。

我们正在发展新型的“询证临床决策系统”,通过患者招募、长期随访、样本留存、分子检测等步骤,建立多位数据仓库,从而更好地服务患者、医生和社会,推动精准医疗的实现。

临床上患者的信息来自于临床、基因、随访等多个方面,甚至还包括个人习惯、家族史这些方面。这些数据过去是分散的、非结构化的,缺乏一个整合的系统来统一呈现。我们积极引入后结构化与数据融合技术,实现了自然语言向结构化数据的自动化转换,以及多类型影像数据的整合共享。目前已经实现在整合数据库里面的融合和展示,从而更精确地去定位患者,这项技术也填补了全国性胃癌整合数据库的空白。

在这个数据库的支持下,我们可以更方便地去获取针对某个特定条件的患者,现有的临床证据是怎样的,过去我们的治疗经验和效果又是怎样,最终给患者制定出真正个体化的诊疗方案。

此外,北京大学肿瘤医院正在和国外的癌症中心及药物研发企业合作,获得每一个患者的基因数据,构建精准医疗数据库,按照不同临床试验所需目标患者的基因类型来匹配临床试验,目的就是为了使国内更多患者参加临床试验,最终让更多患者受益。

Q您认为未来肿瘤精准医学发展方向如何?面临的主要困难是什么?

季加孚:未来,精准医学的理念会更加深入到肿瘤诊断和治疗的方方面面。通过更加准确的诊断方法和标志物,达到早发现、早诊断、早治疗的目的。

对于进展期的肿瘤,能够精确地进行分期、评估和治疗,包括手术、放化疗、靶向治疗、免疫治疗等治疗方式的联合,能够使患者获得更好的预后,增加治疗获益。

与此同时,虽然肿瘤的治疗需要个体化,但是不同类型的肿瘤之间往往具有许多共同点,同病异治,异病也可以同治。利用不同类型的肿瘤的相似特点,可以应用相同的药物进行治疗,达到更好的效果。

例如目前有的新型靶向药物,利用不同肿瘤之间的相似性,应用相同的分子靶向药物治疗,达到了很好的效果。另外,免疫检查点抑制剂应用的相关研究,以及在PD-L1高表达的选择人群应用的PD-1抑制剂的研究,都得到了不错的结果。

精准医学的一大重要支撑是建立一个“大数据平台”,但是目前信息孤岛现象阻碍了上述进程。精准医学的肿瘤研究平台需要成规模、高水平的集团协同。这种协同的前提是具备普遍约束力的规范、便于共享的环境和可靠的质量监管。相应地,现有的激励、管理制度也应随之调整。

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  2. [GetPortalCommentsPageByObjectIdResponse(id=2069871, encodeId=6dc620698e1d5, content=<a href='/topic/show?id=17e78314284' target=_blank style='color:#2F92EE;'>#肿瘤领域#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83142, encryptionId=17e78314284, topicName=肿瘤领域)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c279140, createdName=vividelife, createdTime=Mon Aug 13 19:50:00 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277162, encodeId=e5742e716275, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Jan 10 11:58:42 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277013, encodeId=605e2e7013ac, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Tue Jan 09 23:14:48 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1403277, encodeId=df5014032e700, content=<a href='/topic/show?id=ebbde6353be' target=_blank style='color:#2F92EE;'>#精准#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76353, encryptionId=ebbde6353be, topicName=精准)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epQX9hfEIBiaPg0e9KvLYVBCSGYydH6K6OQxBh3RaOC0TYP9HYy2v0XdHib1LFnZNU5Siak0P8oh8Aqw/132, createdBy=acd92440184, createdName=shijzhiewnjhch, createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578803, encodeId=3ca615e880331, content=<a href='/topic/show?id=7f064540296' target=_blank style='color:#2F92EE;'>#季加孚#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45402, encryptionId=7f064540296, topicName=季加孚)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8ed616431635, createdName=1249862am77(暂无昵称), createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276507, encodeId=10e52e6507d0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Mon Jan 08 05:08:06 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276501, encodeId=67f32e6501eb, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Mon Jan 08 01:17:19 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276476, encodeId=8aa62e64767d, content=很好的文章.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Jan 07 23:40:17 CST 2018, time=2018-01-07, status=1, ipAttribution=)]
    2018-01-10 1ddf0692m34(暂无匿称)

    学习了.涨知识

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2069871, encodeId=6dc620698e1d5, content=<a href='/topic/show?id=17e78314284' target=_blank style='color:#2F92EE;'>#肿瘤领域#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83142, encryptionId=17e78314284, topicName=肿瘤领域)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c279140, createdName=vividelife, createdTime=Mon Aug 13 19:50:00 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277162, encodeId=e5742e716275, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Jan 10 11:58:42 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277013, encodeId=605e2e7013ac, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Tue Jan 09 23:14:48 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1403277, encodeId=df5014032e700, content=<a href='/topic/show?id=ebbde6353be' target=_blank style='color:#2F92EE;'>#精准#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76353, encryptionId=ebbde6353be, topicName=精准)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epQX9hfEIBiaPg0e9KvLYVBCSGYydH6K6OQxBh3RaOC0TYP9HYy2v0XdHib1LFnZNU5Siak0P8oh8Aqw/132, createdBy=acd92440184, createdName=shijzhiewnjhch, createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578803, encodeId=3ca615e880331, content=<a href='/topic/show?id=7f064540296' target=_blank style='color:#2F92EE;'>#季加孚#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45402, encryptionId=7f064540296, topicName=季加孚)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8ed616431635, createdName=1249862am77(暂无昵称), createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276507, encodeId=10e52e6507d0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Mon Jan 08 05:08:06 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276501, encodeId=67f32e6501eb, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Mon Jan 08 01:17:19 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276476, encodeId=8aa62e64767d, content=很好的文章.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Jan 07 23:40:17 CST 2018, time=2018-01-07, status=1, ipAttribution=)]
    2018-01-09 131****2916

    不错的文章值得推荐

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2069871, encodeId=6dc620698e1d5, content=<a href='/topic/show?id=17e78314284' target=_blank style='color:#2F92EE;'>#肿瘤领域#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83142, encryptionId=17e78314284, topicName=肿瘤领域)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c279140, createdName=vividelife, createdTime=Mon Aug 13 19:50:00 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277162, encodeId=e5742e716275, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Jan 10 11:58:42 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277013, encodeId=605e2e7013ac, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Tue Jan 09 23:14:48 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1403277, encodeId=df5014032e700, content=<a href='/topic/show?id=ebbde6353be' target=_blank style='color:#2F92EE;'>#精准#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76353, encryptionId=ebbde6353be, topicName=精准)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epQX9hfEIBiaPg0e9KvLYVBCSGYydH6K6OQxBh3RaOC0TYP9HYy2v0XdHib1LFnZNU5Siak0P8oh8Aqw/132, createdBy=acd92440184, createdName=shijzhiewnjhch, createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578803, encodeId=3ca615e880331, content=<a href='/topic/show?id=7f064540296' target=_blank style='color:#2F92EE;'>#季加孚#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45402, encryptionId=7f064540296, topicName=季加孚)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8ed616431635, createdName=1249862am77(暂无昵称), createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276507, encodeId=10e52e6507d0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Mon Jan 08 05:08:06 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276501, encodeId=67f32e6501eb, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Mon Jan 08 01:17:19 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276476, encodeId=8aa62e64767d, content=很好的文章.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Jan 07 23:40:17 CST 2018, time=2018-01-07, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=2069871, encodeId=6dc620698e1d5, content=<a href='/topic/show?id=17e78314284' target=_blank style='color:#2F92EE;'>#肿瘤领域#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83142, encryptionId=17e78314284, topicName=肿瘤领域)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c279140, createdName=vividelife, createdTime=Mon Aug 13 19:50:00 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277162, encodeId=e5742e716275, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Jan 10 11:58:42 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277013, encodeId=605e2e7013ac, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Tue Jan 09 23:14:48 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1403277, encodeId=df5014032e700, content=<a href='/topic/show?id=ebbde6353be' target=_blank style='color:#2F92EE;'>#精准#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76353, encryptionId=ebbde6353be, topicName=精准)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epQX9hfEIBiaPg0e9KvLYVBCSGYydH6K6OQxBh3RaOC0TYP9HYy2v0XdHib1LFnZNU5Siak0P8oh8Aqw/132, createdBy=acd92440184, createdName=shijzhiewnjhch, createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578803, encodeId=3ca615e880331, content=<a href='/topic/show?id=7f064540296' target=_blank style='color:#2F92EE;'>#季加孚#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45402, encryptionId=7f064540296, topicName=季加孚)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8ed616431635, createdName=1249862am77(暂无昵称), createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276507, encodeId=10e52e6507d0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Mon Jan 08 05:08:06 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276501, encodeId=67f32e6501eb, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Mon Jan 08 01:17:19 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276476, encodeId=8aa62e64767d, content=很好的文章.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Jan 07 23:40:17 CST 2018, time=2018-01-07, status=1, ipAttribution=)]
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    2018-01-08 yjs木玉

    好好好好好好好好

    0

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    2018-01-08 jihuaijun1112

    学习学习学习

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=2069871, encodeId=6dc620698e1d5, content=<a href='/topic/show?id=17e78314284' target=_blank style='color:#2F92EE;'>#肿瘤领域#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=83142, encryptionId=17e78314284, topicName=肿瘤领域)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c279140, createdName=vividelife, createdTime=Mon Aug 13 19:50:00 CST 2018, time=2018-08-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277162, encodeId=e5742e716275, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Wed Jan 10 11:58:42 CST 2018, time=2018-01-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=277013, encodeId=605e2e7013ac, content=不错的文章值得推荐, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=04f22055142, createdName=131****2916, createdTime=Tue Jan 09 23:14:48 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1403277, encodeId=df5014032e700, content=<a href='/topic/show?id=ebbde6353be' target=_blank style='color:#2F92EE;'>#精准#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76353, encryptionId=ebbde6353be, topicName=精准)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83epQX9hfEIBiaPg0e9KvLYVBCSGYydH6K6OQxBh3RaOC0TYP9HYy2v0XdHib1LFnZNU5Siak0P8oh8Aqw/132, createdBy=acd92440184, createdName=shijzhiewnjhch, createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1578803, encodeId=3ca615e880331, content=<a href='/topic/show?id=7f064540296' target=_blank style='color:#2F92EE;'>#季加孚#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=45402, encryptionId=7f064540296, topicName=季加孚)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8ed616431635, createdName=1249862am77(暂无昵称), createdTime=Tue Jan 09 13:50:00 CST 2018, time=2018-01-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276507, encodeId=10e52e6507d0, content=好好好好好好好好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/29/bbc5cc0eed9b8d17623d2fd49dbdf19a.jpg, createdBy=79522135794, createdName=yjs木玉, createdTime=Mon Jan 08 05:08:06 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276501, encodeId=67f32e6501eb, content=学习学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzR8ylhYfiaoAUx2BsaYHVia1IKhG3Cg8CT84rBrn6iaVRkyAibJxBcLEXabOQ5p19vWgDe34ib5ErxNgx/0, createdBy=8a701629084, createdName=jihuaijun1112, createdTime=Mon Jan 08 01:17:19 CST 2018, time=2018-01-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=276476, encodeId=8aa62e64767d, content=很好的文章.谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Sun Jan 07 23:40:17 CST 2018, time=2018-01-07, status=1, ipAttribution=)]
    2018-01-07 清风拂面

    很好的文章.谢谢分享

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