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Double-negative T cells:a promising avenue of adoptive cell therapy in transplant oncology

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 387-396页

作者： Zhihang HU Modan YANG Hao CheN chiyu he Zuyuan LIN Xinyu YANG Huigang LI Wei SheN Di LU Xiao XU Zhejiang University School of Medicine Hangzhou 310058China Department of hepatobiliary and Pancreatic Surgery Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Hangzhou 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Department of hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 310004China

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer.In addition to the common mechanisms underlying tumor recurrence,another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis.Transplant oncology is an emerging field that addresses oncological challenges in transplantation.In this context,a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients.Double-negative T cells(DNTs)are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor(TCR)type.Among them,TCRαβ^(+)DNTs are considered to induce immune suppression in immune-mediated diseases,while TCRγδ^(+)DNTs are widely recognized as tumor killers.As a composite cell therapy,healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host.In this work,we summarized the biological characteristics and functions of DNTs in oncology,immunology,and transplantation.Based on the multiple roles of DNTs,we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy(ACT).

关键词： Double-negative T cell(DNT) Adoptive cell therapy(ACT) Liver cancer Liver transplantation Oncology

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Exploration of Related Issues on PK/PD Studies and Bioanalytical Characteristics of Peptides

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Journal of Biosciences and Medicines 2023年第11期11卷 76-93页

作者： chiyu he Yuxi Hu Center for Drug Evaluation National Medical Products Administration Beijing China

Peptides play multiple functions in cellular processes and are considered an attractive paradigm for the development of novel drugs and therapeutic approaches. However, the complexity of their pharmacokinetics/pharmacodynamics and physicochemical properties presents challenges in their development. Currently, there is no single analytical method that fully meets the requirements for studying peptide drug pharmacokinetics. Interdisciplinary teams and multiple technical platforms are required to address these challenges. This article explores the pharmacokinetics, bioanalytical methods, challenges, and strategies in the development of peptide drugs. As our understanding of peptide drug pharmacokinetics and bioanalytical characteristics deepens, it will facilitate their development and provide scientific evidence for rational clinical use.

关键词： Peptides Drugs PK/PD Bioanalytical Characteristics

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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy he Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of Medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou HangzhouZhejiang 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for healthcare Quality Management in Liver Transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum stress.The exact interplay between stress and liver diseases remains unclear.Autophagy plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver diseases.Once the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain homeostasis.In recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much attention.FGF21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to stress.Also,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal role.This review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 Liver diseases mTOR Stress

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TNFR2 is a potent prognostic biomarker for post-transplant lung metastasis in patients with hepatocellular carcinoma

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Chinese Journal of Cancer Research 2023年第1期35卷 66-80页

作者： Huigang Li Zuyuan Lin Jianyong Zhuo Modan Yang Wei Shen Zhihang Hu Yichen Ding Hao Chen chiyu he Xinyu Yang Siyi Dong Xuyong Wei Beicheng Sun Shusen Zheng Ren Lang Di Lu Xiao Xu Zhejiang University School of Medicine Hangzhou 310058China Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China The Institute for Organ Repair and Regenerative Medicine of Hangzhou Hangzhou 310006China Institute of Organ Transplantation Zhejiang UniversityHangzhou 310003China National Center for healthcare Quality Management in Liver Transplant Hangzhou 310003China Department of hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)HospitalHangzhou 311112China NHC Key Laboratory of Combined Multi-organ Transplantation Hangzhou 31003China Department of hepatobiliary Surgery Beijing Chaoyang Hospital Affiliated to Capital Medical UniversityBeijing 100020China

Objective:Lung metastasis is a common and fatal complication of liver transplantation for hepatocellular carcinoma(HCC).The precise prediction of post-transplant lung metastasis in the early phase is of great value.Methods:The mRNA profiles of primary and paired lung metastatic lesions were analyzed to determine key signaling pathways.We enrolled 241 HCC patients who underwent liver transplantation from three centers.Tissue microarrays were used to evaluate the prognostic capacity of tumor necrosis factor(TNF),tumor necrosis factor receptor 1(TNFR1),and TNFR2,particularly for post-transplant lung metastasis.Results:Comparison of primary and lung metastatic lesions revealed that the TNF-dependent signaling pathway was related to lung metastasis of HCC.The expression of TNF was degraded in comparison to that in para-tumor tissues(Phe expression of key receptors in the TNF-dependent signaling pathway,TNFR1 and TNFR2,was higher in HCC tissues than in para-tumor tissues(Phereas elevated TNFR2 in tumor tissue was significantly associated with worse overall survival(OS)and increased recurrence risk(5-year OS rate:31.9%vs.62.5%,Phepatitis B surface antigen were independent risk factors for post-transplant lung metastasis,and a novel nomogram was established accordingly.The nomogram achieved excellent prognostic efficiency(area under time-dependent receiver operating characteristic=0.755,concordance-index=0.779)and was superior to conventional models,such as the Milan criteria.Conclusions:TNFR2 is a potent prognostic biomarker for predicting post-transplant lung metastasis in patients with HCC.A nomogram incorporating TNFR2 deserves to be a helpful prognostic tool in liver transplantation for HCC.

关键词： Lung metastasis hepatocellular carcinoma liver transplantation nomogram

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重度烧伤的转录组学研究:价值与机遇

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中华烧伤与创面修复杂志 2024年第6期40卷 514-520页

作者：贾赤宇尹斌张泽鑫南华大学衡阳医学院附属第一医院烧伤整形与创面修复中心衡阳421001 厦门大学医学院厦门361100

转录组学技术在多个疾病领域显示出了显著应用效果,但其在重度烧伤尤其是烧伤脓毒症领域的应用还是浅尝止。使用转录组学和大数据的方法,解决重度烧伤尤其是烧伤脓毒症领域一直以来难以攻克的难题,极具前景和意义。该文对转录组学在重... 详细信息

转录组学技术在多个疾病领域显示出了显著应用效果,但其在重度烧伤尤其是烧伤脓毒症领域的应用还是浅尝止。使用转录组学和大数据的方法,解决重度烧伤尤其是烧伤脓毒症领域一直以来难以攻克的难题,极具前景和意义。该文对转录组学在重度烧伤尤其是烧伤脓毒症研究中的应用价值、现状以及未来前景进行全面论述,为重度烧伤的治疗提供新的思路。

关键词：烧伤转录组脓毒症货免疫抑制

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基于向量投影的立体阵定位算法

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电子与信息学报 2024年第1期46卷 31-40页

作者：孙大军蔡珩郑翠娥程驰宇哈尔滨工程大学水声技术全国重点实验室哈尔滨150001 海洋信息获取与安全工信部重点实验室(哈尔滨工程大学)工业和信息化部哈尔滨150001 哈尔滨工程大学水声工程学院哈尔滨150001

传统适配立体阵型的超短基线定位算法计算量大、定位误差难以通过解析式精确表征。针对这些问题,该文提出基于向量投影的立体阵定位算法,从向量投影的角度构建立体阵中各基线向量与目标方位之间的观测方程,实现对传统算法定位模型的简... 详细信息

传统适配立体阵型的超短基线定位算法计算量大、定位误差难以通过解析式精确表征。针对这些问题,该文提出基于向量投影的立体阵定位算法,从向量投影的角度构建立体阵中各基线向量与目标方位之间的观测方程,实现对传统算法定位模型的简化。该文算法通过求解线性方程组即可实现对目标方位的估计,时间复杂度远小于传统算法。此外,基于该文算法简洁的观测方程,给出了适配立体阵的定位误差精确解析表征。仿真结果表明,该文算法消耗的运算时间远小于传统算法,且定位误差变化规律与基于理论解析式得到的结论相符。湖试试验结果表明,该文算法的定位精度与传统算法几乎一致,且计算效率更高。

关键词：超短基线定位立体阵向量投影

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Simultaneous quantification of ginsenoside Rg1 and its metabolites by HPLC–MS/MS:Rg1 excretion in rat bile, urine and feces

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Acta Pharmaceutica Sinica B 2016年第6期6卷 593-599页

作者： chiyu he Ru Feng Yupeng Sun Shifeng Chu Ji Chen Chao Ma Jie Fu Zhenxiong Zhao Min Huang Jiawen Shou Xiaoyang Li Yuzhu Wang Jinfeng Hu Yan Wang Juntian Zhang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences Beijing Analytical Application Center Shimadzu (China) Co. Ltd.

Ginsenoside Rg1(Rg1), the major effective component of ginseng, has been shown to have multiple bioactivities, but low oral bioavailability. The aim of this study was to develop a simple, sensitive and rapid high performance liquid chromatography–tandem mass spectrometry(LC–MS/MS) method, which could be used to validate and quantify the concentrations of Rg1 and its metabolites in Sprague-Dawley rat bile,urine, and feces after oral administration(25 mg/kg). Calibration curves offered satisfactory linearity(r40.995)within the determined ranges. Both intra-day and inter-day variances were less than 15%, and the accuracy was within 80–120%. The excretion recoveries of Rg1, ginsenoside Rh1(Rh1), and protopanaxatriol(Ppt) in bile,urine, and feces combined were all greater than 70%. The fecal excretion recoveries of Rg1, Rh1, and Ppt were40.11%, 22.19%, and 22.88%, respectively, whereas 6.88% of Rg1 and 0.09% of Rh1 were excreted in bile.Urinary excretion accounted for only 0.04% of Rg1. In conclusion, the observed excretion profiles for Rg1 and its metabolites after oral administration are helpful for understanding the poor oral bioavailability of Rg1 and will aid further investigations of Rg1 as a pharmacologically active component.

关键词： Ginsenoside Rg1 Ginsenoside Rh1 Protopanaxatriol Excretion LC–MS/MS

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连续进出料鼓泡流化床停留时间分布的相似准则研究

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化工学报 2024年第2期75卷 543-552页

作者：屠楠刘晓群王驰宇方嘉宾西安工程大学机电工程学院陕西西安710600 西安交通大学化学工程与技术学院陕西西安712000

以连续进出料鼓泡流化床为研究对象,在Glicksman相似准则的基础上引入了扩散准则数,获得了具备颗粒停留时间分布(RTD)相似性的流化床相似放大准则,并明确了颗粒RTD的相似转换关系。对缩尺流化床模型与原型的流动行为及颗粒RTD进行了数... 详细信息

以连续进出料鼓泡流化床为研究对象,在Glicksman相似准则的基础上引入了扩散准则数,获得了具备颗粒停留时间分布(RTD)相似性的流化床相似放大准则,并明确了颗粒RTD的相似转换关系。对缩尺流化床模型与原型的流动行为及颗粒RTD进行了数值模拟分析,发现在给定的几何相似常数范围内(1

关键词：鼓泡流化床停留时间分布相似准则相似转换关系缩尺模型数值模拟

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结合混合注意力的双判别生成对抗网络

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计算机工程与应用 2024年第7期60卷 212-221页

作者：王磊杨军张驰宇代在燕四川师范大学计算机科学学院成都610101

图像生成任务中,如何提升生成图片的质量是一个关键问题。当前,生成对抗网络采用的多层卷积结构存在局部性归纳偏置的问题,无法准确聚焦关键信息,导致图像特征丢失严重,生成图像效果较差。为此,提出了结合混合注意力的双判别生成对抗网... 详细信息

图像生成任务中,如何提升生成图片的质量是一个关键问题。当前,生成对抗网络采用的多层卷积结构存在局部性归纳偏置的问题,无法准确聚焦关键信息,导致图像特征丢失严重,生成图像效果较差。为此,提出了结合混合注意力的双判别生成对抗网络(DDMA-GAN)。设计了一种混合注意力机制,利用通道注意力和空间注意力模块,从两个维度充分捕获图像特征信息;为解决单判别器存在判别误差的问题,提出一种双判别器结构,使用融合系数将判定结果融合,使回传参数更具客观性,并嵌入数据增强模块,进一步提升模型鲁棒性;采用铰链损失作为模型损失函数,最大化真假样本间的距离,明确决策边界。模型在公开数据集LSUN和CelebA上进行验证,实验结果表明,DDMA-GAN生成的图像更加真实,纹理细节更加丰富,其FID和MMD值均显著降低且优于其他常见模型,证明了模型的有效性。

关键词：图像生成卷积神经网络混合注意力双判别器数据增强生成对抗网络

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Erratum to:Bioinformatic analysis for potential biological processes and key targets of heart failure-related stroke

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 359-359页

作者： chiyu LIU Sixu CheN Haifeng ZHANG Yangxin CheN Qingyuan GAO Zhiteng CheN Zhaoyu LIU Jingfeng WANG Department of Cardiology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China Laboratory of Cardiac Electrophysiology and Arrhythmia in Guangdong Province Guangzhou 510120China Guangdong Provincial Key Laboratoryof Malignant Tumor Epigenetics and Gene Regulation Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China

Erratum to:J Zhejiang Univ-Sci B(Biomed&Biotechnol)202122(9):718-732 https:/***/10.1631/jzus.B2000544.The original version of this article(Liu et al.,2021)unfortunately contained a mistake:statement of equal contribution is missing.This correction article shows that chiyu LIU and Sixu CheN contributed equally to this work.The original article has been corrected.

关键词： statement correction potential

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