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The ongoing trends of patient-derived xenograft models in oncology

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Cancer Communications 2020年第11期40卷 559-563页

作者： Jianyong Zhuo renyi su Winyen Tan Zhengxing Lian Di Lu Xiao Xu Department of Hepatobiliary and Pancreatic surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310003P.R.China Department of Hepatobiliary and Pancreatic surgery First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003P.R.China National Health Commission Key Laboratory of Combined Multi-organ Transplantation Institute of Organ TransplantationZhejiang UniversityHangzhouZhejiang 310003P.R.China Department of Hepatobiliary and Pancreatic surgery Li Shui HospitalZhejiang University School of MedicineLishuiZhejiang 323000P.R.China

1 MAIN TEXT Patient-derived xenograft(PDX)models have garnered increasing attention since the last *** models are typically characterized by the implantation of fresh patient-derived tumor tissues into immunodeficient *** models are well recognized in academic laboratories,pharmaceutical institutions,and specialized commercial organizations as having the ability to recapitulate genomics,transcriptomics,proteomics,and metabolomics of the parental tumor tissue[1,2].Recently,these models have been successfully used in preclinical studies to identify potential biomarkers for drug response and resistance,and to measure tumor evolution in response to treatment[3,4].Favorable outcomes demonstrated using PDX models could be used as ideal models for preclinical research and clinical translation studies.

关键词： clinical specialized implantation

Extrahepatic organs in the development of non-alcoholic fatty liver disease in liver transplant patients

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Hepatobiliary surgery and Nutrition 2022年第3期11卷 400-411页

作者： renyi su Xuyong Wei Qiang Wei Di Lu Zuyuan Lin Shuo Wang Chuxiao Shao Xiao Xu Department of Hepatobiliary and Pancreatic surgery Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouChina NHC Key Laboratory of Combined Multi-Organ Transplantation HangzhouChina Department of Hepatobiliary and Pancreatic surgery Shu Lan HospitalShu Lan International Medical College of Zhejiang Shuren UniversityHangzhouChina Department of Hepatobiliary and Pancreatic surgery Affiliated Lishui HospitalZhejiang University School of MedicineLishuiChina

Background and Objective:Non-alcoholic fatty liver disease(NAFLD)is highly prevalent in patients who undergo liver transplantation(LT).Whereas there is huge data on NAFLD,little is known about NAFLD in *** this review,we aim to explore extrahepatic organs and their potential mechanisms in the development of NAFLD in LT patients and discuss current limitations in preclinical and clinical scenarios with suggestions for future ***:The following keywords,such as NAFLD,NASH,liver transplant,therapy,pathogenesis and biomarkers,were set for literature *** articles which were published articles in English till 25th June 2020 in PubMed database were included,and there is no limit for the study design *** Content and Findings:Following LT,there are significant shifts in the microbiota and farnesoid X receptor may be a potential therapeutic target for NAFLD in LT *** roles of probiotics and diet on NALFD remain inconclusive in LT ***,the adipokines and cytokines disorder and local insulin resistance of adipose tissue may contribute to NAFLD *** surgeries are promising in controlling de novo and recurrent NAFLD with significant reduction in abdominal adipose tissue,despite the optimal timing is inconclusive in LT ***,circumstantial evidence indicates that miRNA-33a may function as a mediator bridging sarcopenia and NAFLD of post-LT.β-Hydroxy-β-Methyl-Butyrate treatment could improve muscle status in graft recipients and shows protective potential for NAFLD in LT ***:Gut,adipose tissue and muscle are intricately intertwined in promoting NAFLD in LT *** animal studies are needed to deepen our understanding of mechanisms in multi-organ *** quality clinical trials are warrant for making guidelines and developing management strategies on NAFLD after LT.

关键词： Non-alcoholic fatty liver disease(NAFLD) liver transplant sarcopenia lipid gut

Targeting a disintegrin and metalloprotease(ADAM)17-CD122 axis enhances CD8^(+)T cell effector differentiation and anti-tumor immunity

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3097-3111页

作者： Lina sun Anjun Jiao Haiyan Liu renyi Ding Ning Yuan Biao Yang Cangang Zhang Xiaoxuan Jia Gang Wang Yanhong su Dan Zhang Lin Shi Chenming sun Aijun Zhang Lianjun Zhang Baojun Zhang Department of Pathogenic Microbiology and Immunology School of Basic Medical SciencesXi’an Jiaotong UniversityXi’anShaanxi 710061China Institute of Infection and Immunity Translational Medicine InstituteXi’an Jiaotong University Health Science CenterXi’anShaanxi 710061China Key Laboratory of Environment and Genes Related to Diseases Ministry of EducationXi’anShaanxi 710061China Xi’an Key Laboratory of Immune Related Diseases Xi’anShannxi 710061China Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy Cancer InstituteXuzhou Medical UniversityXuzhouJiangsuChina Department of Pediatrics Qilu Hospital of Shandong UniversityJinanChina National Key Laboratory of Immunity and Inflammation Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina Key Laboratory of Synthetic Biology Regulatory Elements Suzhou Institute of Systems MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeSuzhou 215123 JiangsuChina

CD8^(+)T cell immune responses are regulated by multi-layer networks,while the post-translational regulation remains largely *** ectodomain shedding is an important post-translational process orchestrating receptor expression and signal transduction through proteolytic cleavage of membrane ***,by targeting the sheddase A Disintegrin and Metalloprotease(ADAM)17,we defined a post-translational regulatory mechanism mediated by the ectodomain shedding in CD8^(+)T *** and proteomic analysis revealed the involvement of post-translational regulation in CD8^(+)T cells.T cellspecific deletion of ADAM17 led to a dramatic increase in effector CD8^(+)T cell differentiation and enhanced cytolytic effects to eliminate pathogens and ***,ADAM17 regulated CD8^(+)T cells through cleavage of membrane ***17 inhibition led to elevated CD122 expression and enhanced response to IL-2 and IL-15 stimulation in both mouse and human CD8^(+)T ***,inhibition of ADAM17 in CD8^(+)T cells improved the efficacy of chimeric antigen receptor(CAR)T cells in solid *** findings reveal a critical post-translational regulation in CD8^(+)T cells,providing a potential therapeutic strategy of targeting ADAM17 for effective anti-tumor immunity.

关键词： immunity stimulation involvement

“机械灌注+”视阈下扩大标准供肝的修复与功能提升

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中华消化外科杂志 2022年第1期21卷 74-78页

作者：汪恺苏仁义王周城徐骁浙江大学医学院附属杭州市第一人民医院肝胆胰外科杭州310006

肝移植是终末期肝病最有效的治疗手段。我国是世界肝移植第二大国,为解决供肝短缺的瓶颈问题,扩大标准供肝的修复和功能提升是目前重要的研究方向。面向未来,基于医工信交叉融合创新平台,探求干细胞命运调控、器官修复与组织再生的基础... 详细信息

肝移植是终末期肝病最有效的治疗手段。我国是世界肝移植第二大国,为解决供肝短缺的瓶颈问题,扩大标准供肝的修复和功能提升是目前重要的研究方向。面向未来,基于医工信交叉融合创新平台,探求干细胞命运调控、器官修复与组织再生的基础理论突破,开展全国多中心、引领性的临床研究至关重要。由此,笔者综合国内外循证医学证据、最新研究成果及临床经验,基于“机械灌注+”的新理念,探索多组学技术、分子生物学技术、信息化技术、自动化技术、纳米靶向递送技术等与传统机械灌注技术相结合的新模式,以期实现实时、无创、智能化的供肝质量评估和检测,建立扩大标准供肝修复与功能提升的技术新体系,安全、有效地拓展供肝来源,降低移植后并发症风险,改善受者预后,从而推动我国肝移植事业更高质量发展。

关键词：普通外科肝移植扩大标准供肝机械灌注器官保存

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舟山山海大观养生养老社区及老年公寓

当代建筑 2021年第2期 102-109页

作者：苏仁毅赵强(摄影) 卢凯凯(摄影) 不详

近几年来,由于市场、产品、运营的持续精研改善,商业住宅的设计呈现出趋同的特点。先定成熟户型,由日照推导总图布局,再套用成熟产品体系立面语言——这一整套“由内而外”的“标准动作”,既有合理、科学的一面,呈现出高度产品化的趋势... 详细信息

近几年来,由于市场、产品、运营的持续精研改善,商业住宅的设计呈现出趋同的特点。先定成熟户型,由日照推导总图布局,再套用成熟产品体系立面语言——这一整套“由内而外”的“标准动作”,既有合理、科学的一面,呈现出高度产品化的趋势,但也使得住宅慢慢远离了建筑设计的很多看似“非刚性”要素,而正是这些要素的缺失,导致了居住建筑文化性和地域性特质的弱化。当下,仅提供基本居住功能的产品显然会被日益增加的市场需求所不断推演,很多看似“非刚性”的要素在新的需求下,或许会转变为新的“刚性”需求。这也是未来居住建筑的发展方向,如“未来社区”所倡导的种种。

关键词：老年公寓建筑设计商业住宅居住功能未来居住非刚性产品化户型

幼儿园建筑的空间拓展——南浔镇中心幼儿园新址扩建工程

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城市建筑 2019年第11期16卷 25-26页

作者：王玉平苏仁毅浙江大学建筑设计研究院有限公司

该项目对幼儿园活动空间拓展进行了尝试与研究,旨在从一种新的角度出发,带来全新的幼儿园空间感受。设计师通过建筑形体关系,向外呼应城市和景观产生凹凸变形,向内围合出大尺度的相对封闭安全的内院,打造一个孩子们可以完全自由地奔跑,... 详细信息

该项目对幼儿园活动空间拓展进行了尝试与研究,旨在从一种新的角度出发,带来全新的幼儿园空间感受。设计师通过建筑形体关系,向外呼应城市和景观产生凹凸变形,向内围合出大尺度的相对封闭安全的内院,打造一个孩子们可以完全自由地奔跑,尽情地释放童心童趣的空间。设计团队此次的经验为今后幼儿园空间的拓展提供了新的思路与探索。

关键词：幼儿园空间拓展屋顶绿化立面设计

Three-parameter approximations of sums of locally dependent random variables via Stein's method

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Science China Mathematics 2024年

作者： Zhonggen su Xiaolin Wang School of Mathematical Sciences Zhejiang University

Let,{Xi,i ∈ J} be a family of locally dependent non-negative integer-valued random variables with finite expectations and *** consider the sum W=∑i∈jXiand apply Stein's method to establish general upper error bounds for the total variation distance dTV（W,M）,where M represents a threeparameter random *** a direct consequence,we obtain a discretized normal approximation for *** applications,we study four well-known examples in detail:counting vertices where all edges point inward,the birthday problem,counting monochromatic edges in uniformly colored graphs,and triangles in the Erd?s-renyi random *** delicate analysis and computation,we obtain sharper upper error bounds than existing results.

关键词：

脂肪变性供肝用于肝癌肝移植的预后及影响因素多中心研究

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中华消化外科杂志 2022年第2期21卷 237-248页

作者：杨梦凡王睿潘斌华苏仁义董思依徐骁郑树森魏绪勇浙江大学医学院附属第一医院肝胆胰外科杭州310003 浙江大学医学院附属杭州市第一人民医院肝胆胰外科肿瘤融合研究与精准诊治实验室杭州310006 国家肝脏移植质控中心杭州310003 树兰(杭州)医院肝胆胰外科杭州310022

目的探讨脂肪变性供肝用于肝癌肝移植的预后及影响因素。方法采用回顾性队列研究方法。收集2015年1月至2019年12月2家医学中心收治的152对[树兰(杭州)医院89对、浙江大学医学院附属第一医院63对]脂肪变性供肝用于肝癌肝移植供者和受者... 详细信息

目的探讨脂肪变性供肝用于肝癌肝移植的预后及影响因素。方法采用回顾性队列研究方法。收集2015年1月至2019年12月2家医学中心收治的152对[树兰(杭州)医院89对、浙江大学医学院附属第一医院63对]脂肪变性供肝用于肝癌肝移植供者和受者的临床病理资料;152例供者, 男131例, 女21例;年龄为(48±12)岁, 供肝轻度脂肪变性130例、中度脂肪变性22例。152例受者, 男138例, 女14例;年龄为(52±9)岁。观察指标:(1)受者随访、总生存和肿瘤无复发生存情况。(2)受者总生存和肿瘤无复发生存影响因素分析。(3)受者总生存和肿瘤无复发生存列线图预测模型构建及评价。采用门诊和电话方式进行随访, 了解受者生存和肿瘤复发情况。随访时间截至2020年12月。正态分布的计量资料以x±s表示, 偏态分布的计量资料以M(IQR)表示。计数资料以绝对数表示。采用Kaplan-Meier法计算生存率和绘制生存曲线, 采用Log-Rank检验进行生存分析。单因素及多因素分析采用COX回归模型。将独立危险因素引入R 3.6.2软件, 构建列线图预测模型, 绘制受试者工作特征曲线(ROC)并以曲线下面积(AUC)和校准曲线评价模型准确度与区分度。结果 (1)受者随访、总生存和肿瘤无复发生存情况:152例脂肪变性供肝用于肝癌肝移植受者均获得随访, 随访时间为45.8(27.6)个月。随访期间, 152例受者总生存时间为36.5(32.3)个月, 肿瘤无复发生存时间为30.4(34.6)个月, 1、3年总生存率和肿瘤无复发生存率分别为73.4%、55.8%和62.2%、43.4%。(2)受者总生存和肿瘤无复发生存影响因素分析。单因素分析结果显示:供肝冷缺血时间、供肝热缺血时间、移植物受者体重比率(GRWR)、ABO血型相容情况、受者体质量指数(BMI)、受者肿瘤长径、受者肿瘤数目、受者肿瘤分化程度、受者术前甲胎蛋白(AFP)是影响受者总生存的相关因素(风险比=6.26, 1.90, 2.47, 4.08, 0.55, 5.16, 3.62, 5.28, 2.65, 95%可信区间为3.01~13.03, 1.07~3.38, 1.36~4.49, 2.07~8.03, 0.31~0.98, 2.56~10.42, 1.95~6.72, 1.60~17.42, 1.48~5.01, P<0.05)。供肝冷缺血时间、GRWR、ABO血型相容情况、受者肿瘤长径、受者肿瘤数目、受者肿瘤分化程度、受者术前AFP是影响受者肿瘤无复发生存的相关因素(风险比=4.24, 2.53, 4.05, 3.39, 3.10, 5.19, 2.63, 95%可信区间为2.50~7.21, 1.54~4.17, 2.12~7.72, 2.04~5.62, 1.91~5.03, 2.04~13.18, 1.61~4.30, P<0.05)。多因素分析结果显示:供肝冷缺血时间≥8 h、GRWR≥2.5%、受者肿瘤长径≥8 cm、受者术前AFP≥400 μg/L是影响受者总生存的独立危险因素(风险比=4.21, 2.58, 4.10, 2.27, 95%可信区间为1.98~8.96, 1.24~5.35, 1.35~12.43, 1.13~4.56, P<0.05)。供肝冷缺血时间≥8 h、GRWR≥2.5%、受者肿瘤长径≥8 cm、受者肿瘤数目≥3个、受者术前AFP≥400 μg/L是影响受者肿瘤无复发生存的独立危险因素(风险比=3.37, 2.63, 2.42, 2.12, 2.22, 95%可信区间为1.70~6.67, 1.40~4.96, 1.04~5.66, 1.08~4.18, 1.26~3.90, P<0.05)。(3)受者总生存和肿瘤无复发生存列线图预测模型构建及评价。纳入供肝冷缺血时间、GRWR、受者肿瘤长径、受者术前AFP构建受者总生存列线图预测模型;纳入供肝冷缺血时间、GRWR、受者肿瘤长径、受者肿瘤数目、受者术前AFP构建受者肿瘤无复发生存列线图预测模型。ROC显示:受者总生存列线图预测模型AUC=0.84(95%可信区间为0.76~0.92, P<0.05), 诊断最佳临界值为7.3, 特异度、灵敏度分别为87.6%、70.0%。受者肿瘤无复发生存列线图预测模型AUC=0.79(95%可信区间为0.71~0.87, P<0.05), 诊断最佳临界值为5.8, 特异度、灵敏度分别为97.4%、52.5%。校准曲线显示:列线图预测模型对受者总生存和肿瘤无复发生存高危人群具有良好区分度。结论供肝冷缺血时间≥8 h、GRWR≥2.5%、受者肿瘤长径≥8 cm、受者术前AFP≥400 μg/L是影响脂肪变性供肝用于肝癌肝移植受者总生存的独立危险因素;供肝

关键词：肝肿瘤肝移植脂肪变性供肝预后肿瘤复发列线图

丹参酮ⅡA注射液对缺血缺氧性脑损伤新生大鼠皮质神经元自噬及Akt-mTOR通路的影响

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中国中医急症 2019年第2期28卷 204-208页

作者：朱波杨艳苏仁意许细平孙乾朕湖北医药学院附属襄阳市第一人民医院湖北襄阳441000

目的观察丹参酮ⅡA注射液对缺血缺氧性脑损伤新生大鼠皮质神经元自噬及Akt-mTOR通路影响并探讨其机制。方法 7日龄SD新生大鼠80只,随机平均分为5组,分别为假手术组、模型组及经丹参酮ⅡA处理的高剂量组(0.1 mg/g)、中剂量组(0.05 mg/g)... 详细信息

目的观察丹参酮ⅡA注射液对缺血缺氧性脑损伤新生大鼠皮质神经元自噬及Akt-mTOR通路影响并探讨其机制。方法 7日龄SD新生大鼠80只,随机平均分为5组,分别为假手术组、模型组及经丹参酮ⅡA处理的高剂量组(0.1 mg/g)、中剂量组(0.05 mg/g)、低剂量组(0.02 mg/g)。Rice法造模,透射电镜观察新生大鼠大脑皮质神经元变化情况,TTC染色检测脑梗死情况,蛋白免疫印迹检测脑组织LC3-Ⅰ、LC3-Ⅱ、Beclin-1、p-Akt、p-mTOR、p-S6蛋白表达情况。结果假手术组神经元结构正常,模型组中观察到皮质神经元中存在大量的自噬体和自噬溶酶体,其中泡状自噬体中包裹有可见的细胞质结构。相较于模型组,高剂量组、中剂量组、低剂量组中自噬体数量明显减少,且呈一定的剂量依赖性(P <0.05)。与假手术组相比,模型组中幼鼠脑梗死面积显著增加(P <0.05)。与模型组相比,高剂量组、中剂量组、低剂量组中脑梗死面积显著减小,且呈一定的剂量依赖性(P <0.05)。与假手术组相比,模型组中LC3-Ⅰ/(LC3-Ⅰ+LC3-Ⅱ)的比值与Beclin-1蛋白表达水平显著增高(P <0.05)。与模型组相比,高剂量组、中剂量组、低剂量组中LC3-Ⅰ/(LC3-Ⅰ+LC3-Ⅱ)的比值与Beclin-1蛋白表达水平显著降低,且呈剂量依赖性(P <0.05)。与假手术组相比,模型组中pAkt、p-mTOR、p-S6蛋白表达水平均显著降低(P <0.05)。与模型组相比,高剂量组、中剂量组、低剂量组中pAkt、p-mTOR、p-S6蛋白表达水平均显著增加,且呈剂量依赖性(P <0.05)。结论丹参酮ⅡA对新生大鼠缺血缺氧性脑损伤大脑皮质神经元自噬具有显著的抑制作用,推测其机制可能为通过激活Akt-mTOR信号转导通路实现的。

关键词：缺血缺氧性脑损伤丹参酮ⅡA 皮质神经元自噬 Akt-mTOR通路