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世界首例猪肾移植到人体，暂未发现排斥反应！异种移植成真了？

2021-10-21 梅斯医学 MedSci原创

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10月19日，美国纽约大学朗格尼医学中心移植外科Montgomery教授团队将经基因改造的猪肾，移植到脑死亡患者中，暂未发现排斥反应，且患者异常的肌酐指标在移植后恢复至正常水平。

10月19日，美国纽约大学朗格尼医学中心移植外科Montgomery教授团队将经基因改造的猪肾，移植到脑死亡患者中，暂未发现排斥反应，且患者异常的肌酐指标在移植后恢复至正常水平。
 
该实验信息止于新闻通稿，尚未经过同行评议及学术出版。患者生前曾希望器官捐赠，但不适合传统的捐赠方式，因而家属在患者亡故后同意了该实验的进行。
 
即便如此，本次实验的成功让移植学界振奋了对“异种移植”的信心。现代医学的进步总是让我们目不暇接。从何时起，我们对“猪肾”打起了主意？又准备走向哪里？
 
图片
图. 供体“猪肾” 来源Joe Carrotta for NYU Langone Health/Handout via REUTERS
 
 
“磨刀霍霍”向猪肾
 
猪和人类有许多共同点，无论是生理上、解剖上，还是基因上，这让猪成为了肾脏移植（KTx）实验研究的最佳动物模型，乃至于距离替代人类肾脏仅一步之遥。
 
1971年，Golby率先对已匹配的猪先进行双侧肾切除术，然后使用左肾进行原位肾移植和肾盂输尿管吻合术，从而制作了一个恒定的、可重复的实验模型。
 
该研究发表之时，参考文献仅一篇。Golby详述了动物模型的解剖结构特征、手术方法，探讨了对猪围术期喂养以及并发症的观察。隔年，相关猪肾移植手术实验喷涌而出。
 
图片
图. 从外科视觉对猪肾移植进行的实验研究
根据Eur Surg Res发布的猪肾移植指南（2012年）的数据统计，自1963年以来，关于“猪肾移植“的研究多达1300多篇，但侧重于手术实践指导的研究仅13项。来源DOI: 10.1159/000343132
 
经过二十年的沉积，Yanaga的猪肾移植模型（1991）更加精细、完善，既可以做到完备的器官保存、免疫抑制，还可以防止氧自由基引起的再灌注损伤。
 
随着围术期管理水平与生命支持技术的提高，猪肾移植技术在经历半个世纪的发展后，已无大忧。
 
图片
图. 猪体解剖结构图
Golby指出猪的解剖结构与人相似，手术难度较小。来源DOI: 10.1159/000343132
 
 
跨越种族的“同化工程”
 
将动物的器官移植到人身上，并非新鲜事。
 
从狗血、羊血、羊胰腺，到黑猩猩的睾丸、卵巢、心脏，医生经过数百年的接力长跑，最终将目标锁定在猪身上。
 
近几十年来，随着猪基因工程和免疫抑制疗法的进步，猪心脏瓣膜也已成功用于人类；血液稀释剂肝素来自猪肠；猪皮移植物用于烧伤，中国外科医生使用猪角膜恢复视力。
 
连猪肾也在“同化”，这是怎么办到的？
 
当人的血液通过猪的血管时，猪的血管内皮细胞将会发生一连串排斥反应。
 
第一个也是最主要的反应是超急性排斥反应（HAR）。人与猪的不同之处在于，猪缺一种蛋白酶，这种蛋白酶可以把“α-Gal”（α-半乳糖）置于存在于细胞表面的分支糖链上。我们的免疫系统可以把“α-Gal”作为攻击的信号。
 
为了消除这个攻击信号，Revivicor公司通过CRISPR基因编辑方法，敲除了在猪细胞表面添加“α-Gal”的蛋白酶，让猪细胞不再表达“α-Gal”，从而克服了超急性排斥反应。
 
转基因猪由此被赋予了“GalSafe猪”的名字。
 
图片
图.GalSafe猪 来源. Revivicor官网
 
2020年12月15日，美国FDA宣布GalSafe猪获批上市。这种家猪可能用于食品或人类治疗。新闻稿指出，这是 FDA批准的首个可以同时用于人类食物消费和作为潜在疗法来源的IGA动物，但尚未评估这些猪用作异种移植产品或植入人类受试者。
  
10个月后，首例猪肾移植人体的“转基因猪”正是来自于Revivicor公司的GalSafe猪。
 
United Therapeutics （Revivicor母公司）首席执行官 Martine Rothblatt 在一份声明中表示：“这是实现异种移植承诺的重要一步，在不久的将来，异种移植每年将挽救数千人的生命。”
 
图片
图. 转基因猪异种移植的流程图
为了避免其他免疫排斥反应，Revivicor公司还向猪添加了人类基因，以产生蛋白质CD46，用于调节免疫系统。来源Revivicor官网
 
 
异种移植走向何方？
 
Aaron（2021）研究表示，猪肾异种移植有可能缓解目前人体器官捐赠短缺的问题，并为终末期肾病患者提供更大的长期生存机会和更好的生活质量。人类已经解决了许多阻碍猪肾移植的历史障碍，猪肾异种移植可能很快就会应用于临床。
 
该团队还在研究中启示，“迄今为止，对猪的基因操作都旨在防止先天性免疫反应；不久将来，为降低适应性免疫反应的影响，转基因猪可能会引入CIITA 突变、PD-L1突变等基因操作。”
 
在有限的异种移植治疗方案中，Aaron认为有关生物标志物的鉴定、急性排斥反应的检验与预测这些尖端技术有可能在未来应用于异种移植领域中。
 
随着本次猪肾移植人体实验的成功，医学进步的曙光不断闪烁，我们不乏看到专家对于“养猪成为器官捐赠者”伦理问题的踌躇；以及尿毒症患者的网评—— “早点临床试验，透析太难受了”。
 
【参考文献】
M. Golriz H. Fonouni A. Nickkholgh,et al. Pig Kidney Transplantation: An Up-To-Date Guideline. Eur Surg Res 2012;49:121–129
Golby M, White HJ: The operation of orthotopic renal allografting in the pig and its complications. Br J Surg 1971;58:287–288.
Mazzoni G, Di Martino C, Demofonti A, et al: Simultaneous allografts of both kidneys in pigs with different portal and caval venous drainage. Am J Surg 1972;124:39–42.
Yanaga K, Makowka L, Shimada M, Lebeau G, Kahn D, Mieles LA, et al: Improved method of porcine renal allografting for transplantation research. J Invest Surg 1991; 4: 231–236.
Swindle M: Swine in the Laboratory: Surgery, Anesthesia, Imaging, and Experimental Techniques, ed 2. Boca Raton, CRC Press, 2007. 
CARLA K. JOHNSON. Pig-to-human transplants come a step closer with new test. [OL]Abc NEWS
Lucander ACK, Nguyen H, Foote JB, Cooper DKC, Hara H. Immunological selection and monitoring of patients undergoing pig kidney transplantation. Xenotransplantation. 2021;28:e12686 
Dekel, B., Burakova, T., Arditti, F. et al. Human and porcine early kidney precursors as a new source for transplantation. Nat Med 9, 53–60 (2003).
Eikmans M, Gielis EM, Ledeganck KJ, et al. Non-invasive biomarkers of acute rejection in kidney transplantation: novel targets and strategies. Front Med. 2019;5:358.
撰文 | R.
编辑 | Jennie

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    2022-07-15 sjzlzc007

    #世界首例#

    0

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    2021-11-09 148ccaa6m02暂无昵称

    其实肾要是能移植心脏也不远了，要知道肾脏结构要比心脏复杂的多

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=1968485, encodeId=39871968485bc, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Fri Jul 15 02:13:23 CST 2022, time=2022-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1068790, encodeId=e1921068e90c5, content=其实肾要是能移植心脏也不远了，要知道肾脏结构要比心脏复杂的多, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf435331051, createdName=148ccaa6m02暂无昵称, createdTime=Tue Nov 09 22:45:22 CST 2021, time=2021-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1064364, encodeId=b8901064364d6, content=尿毒症患者的**, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/AyUEibEbicwMicoP7Hq0icpPOnYsfM1FNNpNfK8cNwLs7gEqrbcTXuBVWAsrC55UibRXziaI6H9MrCcEherM1OBeLb9Q/132, createdBy=d8255253397, createdName=冬2651, createdTime=Wed Oct 27 14:10:59 CST 2021, time=2021-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1263008, encodeId=7a7b12630080e, content=<a href='/topic/show?id=3c0f56643cd' target=_blank style='color:#2F92EE;'>#排斥#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56643, encryptionId=3c0f56643cd, topicName=排斥)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=947269, createdName=lvygwyt2781, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1532160, encodeId=0aec153216084, content=<a href='/topic/show?id=54bb56644f5' target=_blank style='color:#2F92EE;'>#排斥反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56644, encryptionId=54bb56644f5, topicName=排斥反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=546412326777, createdName=smallant2006, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555328, encodeId=46af15553288a, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062992, encodeId=49801062992a3, content=厉害，肾脏病患者的曙光。, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=d0d25457511, createdName=ms5000000480932202, createdTime=Fri Oct 22 17:12:30 CST 2021, time=2021-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062573, encodeId=47ce10625e316, content=厉害了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Thu Oct 21 13:14:26 CST 2021, time=2021-10-21, status=1, ipAttribution=)]
    2021-10-27 冬2651

    尿毒症患者的**

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=1968485, encodeId=39871968485bc, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Fri Jul 15 02:13:23 CST 2022, time=2022-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1068790, encodeId=e1921068e90c5, content=其实肾要是能移植心脏也不远了，要知道肾脏结构要比心脏复杂的多, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf435331051, createdName=148ccaa6m02暂无昵称, createdTime=Tue Nov 09 22:45:22 CST 2021, time=2021-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1064364, encodeId=b8901064364d6, content=尿毒症患者的**, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/AyUEibEbicwMicoP7Hq0icpPOnYsfM1FNNpNfK8cNwLs7gEqrbcTXuBVWAsrC55UibRXziaI6H9MrCcEherM1OBeLb9Q/132, createdBy=d8255253397, createdName=冬2651, createdTime=Wed Oct 27 14:10:59 CST 2021, time=2021-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1263008, encodeId=7a7b12630080e, content=<a href='/topic/show?id=3c0f56643cd' target=_blank style='color:#2F92EE;'>#排斥#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56643, encryptionId=3c0f56643cd, topicName=排斥)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=947269, createdName=lvygwyt2781, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1532160, encodeId=0aec153216084, content=<a href='/topic/show?id=54bb56644f5' target=_blank style='color:#2F92EE;'>#排斥反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56644, encryptionId=54bb56644f5, topicName=排斥反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=546412326777, createdName=smallant2006, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555328, encodeId=46af15553288a, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062992, encodeId=49801062992a3, content=厉害，肾脏病患者的曙光。, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=d0d25457511, createdName=ms5000000480932202, createdTime=Fri Oct 22 17:12:30 CST 2021, time=2021-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062573, encodeId=47ce10625e316, content=厉害了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Thu Oct 21 13:14:26 CST 2021, time=2021-10-21, status=1, ipAttribution=)]
    2021-10-23 lvygwyt2781

    #排斥#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1968485, encodeId=39871968485bc, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Fri Jul 15 02:13:23 CST 2022, time=2022-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1068790, encodeId=e1921068e90c5, content=其实肾要是能移植心脏也不远了，要知道肾脏结构要比心脏复杂的多, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf435331051, createdName=148ccaa6m02暂无昵称, createdTime=Tue Nov 09 22:45:22 CST 2021, time=2021-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1064364, encodeId=b8901064364d6, content=尿毒症患者的**, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/AyUEibEbicwMicoP7Hq0icpPOnYsfM1FNNpNfK8cNwLs7gEqrbcTXuBVWAsrC55UibRXziaI6H9MrCcEherM1OBeLb9Q/132, createdBy=d8255253397, createdName=冬2651, createdTime=Wed Oct 27 14:10:59 CST 2021, time=2021-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1263008, encodeId=7a7b12630080e, content=<a href='/topic/show?id=3c0f56643cd' target=_blank style='color:#2F92EE;'>#排斥#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56643, encryptionId=3c0f56643cd, topicName=排斥)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=947269, createdName=lvygwyt2781, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1532160, encodeId=0aec153216084, content=<a href='/topic/show?id=54bb56644f5' target=_blank style='color:#2F92EE;'>#排斥反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56644, encryptionId=54bb56644f5, topicName=排斥反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=546412326777, createdName=smallant2006, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555328, encodeId=46af15553288a, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062992, encodeId=49801062992a3, content=厉害，肾脏病患者的曙光。, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=d0d25457511, createdName=ms5000000480932202, createdTime=Fri Oct 22 17:12:30 CST 2021, time=2021-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062573, encodeId=47ce10625e316, content=厉害了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Thu Oct 21 13:14:26 CST 2021, time=2021-10-21, status=1, ipAttribution=)]
    2021-10-23 smallant2006

    #排斥反应#

    0

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    2021-10-23 muzishouyi

    #猪#

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1968485, encodeId=39871968485bc, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Fri Jul 15 02:13:23 CST 2022, time=2022-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1068790, encodeId=e1921068e90c5, content=其实肾要是能移植心脏也不远了，要知道肾脏结构要比心脏复杂的多, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf435331051, createdName=148ccaa6m02暂无昵称, createdTime=Tue Nov 09 22:45:22 CST 2021, time=2021-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1064364, encodeId=b8901064364d6, content=尿毒症患者的**, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/AyUEibEbicwMicoP7Hq0icpPOnYsfM1FNNpNfK8cNwLs7gEqrbcTXuBVWAsrC55UibRXziaI6H9MrCcEherM1OBeLb9Q/132, createdBy=d8255253397, createdName=冬2651, createdTime=Wed Oct 27 14:10:59 CST 2021, time=2021-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1263008, encodeId=7a7b12630080e, content=<a href='/topic/show?id=3c0f56643cd' target=_blank style='color:#2F92EE;'>#排斥#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56643, encryptionId=3c0f56643cd, topicName=排斥)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=947269, createdName=lvygwyt2781, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1532160, encodeId=0aec153216084, content=<a href='/topic/show?id=54bb56644f5' target=_blank style='color:#2F92EE;'>#排斥反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56644, encryptionId=54bb56644f5, topicName=排斥反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=546412326777, createdName=smallant2006, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555328, encodeId=46af15553288a, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062992, encodeId=49801062992a3, content=厉害，肾脏病患者的曙光。, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=d0d25457511, createdName=ms5000000480932202, createdTime=Fri Oct 22 17:12:30 CST 2021, time=2021-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062573, encodeId=47ce10625e316, content=厉害了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Thu Oct 21 13:14:26 CST 2021, time=2021-10-21, status=1, ipAttribution=)]
    2021-10-22 ms5000000480932202

    厉害，肾脏病患者的曙光。

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1968485, encodeId=39871968485bc, content=<a href='/topic/show?id=a57f208660f' target=_blank style='color:#2F92EE;'>#世界首例#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20866, encryptionId=a57f208660f, topicName=世界首例)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=917c196, createdName=sjzlzc007, createdTime=Fri Jul 15 02:13:23 CST 2022, time=2022-07-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1068790, encodeId=e1921068e90c5, content=其实肾要是能移植心脏也不远了，要知道肾脏结构要比心脏复杂的多, beContent=null, objectType=article, channel=null, level=null, likeNumber=91, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf435331051, createdName=148ccaa6m02暂无昵称, createdTime=Tue Nov 09 22:45:22 CST 2021, time=2021-11-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1064364, encodeId=b8901064364d6, content=尿毒症患者的**, beContent=null, objectType=article, channel=null, level=null, likeNumber=100, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/AyUEibEbicwMicoP7Hq0icpPOnYsfM1FNNpNfK8cNwLs7gEqrbcTXuBVWAsrC55UibRXziaI6H9MrCcEherM1OBeLb9Q/132, createdBy=d8255253397, createdName=冬2651, createdTime=Wed Oct 27 14:10:59 CST 2021, time=2021-10-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1263008, encodeId=7a7b12630080e, content=<a href='/topic/show?id=3c0f56643cd' target=_blank style='color:#2F92EE;'>#排斥#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=88, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56643, encryptionId=3c0f56643cd, topicName=排斥)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=947269, createdName=lvygwyt2781, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1532160, encodeId=0aec153216084, content=<a href='/topic/show?id=54bb56644f5' target=_blank style='color:#2F92EE;'>#排斥反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=87, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=56644, encryptionId=54bb56644f5, topicName=排斥反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=546412326777, createdName=smallant2006, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555328, encodeId=46af15553288a, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Sat Oct 23 00:13:23 CST 2021, time=2021-10-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062992, encodeId=49801062992a3, content=厉害，肾脏病患者的曙光。, beContent=null, objectType=article, channel=null, level=null, likeNumber=114, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=d0d25457511, createdName=ms5000000480932202, createdTime=Fri Oct 22 17:12:30 CST 2021, time=2021-10-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1062573, encodeId=47ce10625e316, content=厉害了！, beContent=null, objectType=article, channel=null, level=null, likeNumber=121, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=c4a44885671, createdName=419040982, createdTime=Thu Oct 21 13:14:26 CST 2021, time=2021-10-21, status=1, ipAttribution=)]
    2021-10-21 419040982

    厉害了！

    0

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