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Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

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Chinese Journal of Cancer Research 2024年第3期36卷 257-276页

作者： Jian Li Ye Xu Aimin Zang Yunong Gao Quanli Gao Yanqiao Zhang Dong Wang Jianming Xu Ying Yuan Haiping Jiang Jieer Ying Chunmei Shi Yanhong Deng Jing Wang tianshu liu Yi Huang Xiaoping Qian Yueyin Pan Ying Cheng Sheng Hu Jin Wang Mengyue Shi Ke Wang Han Hu Lin Shen Department of Medical Oncology the First Affiliated Hospital Zhejiang University School of Medicine Department of Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences Department of Medical Oncology Fujian Medical University Union Hospital Department of Oncology the Sixth Affiliated Hospital Sun Yat-sen University Department of Medical Oncology Hunan Cancer Hospital Department of Medical Oncology Zhongshan HospitalFudan University Department of Immunotherapy Hubei Cancer Hospital Department of Medical Oncology the Affiliated Hospital of Nanjing University Medical School Department of Medical Oncology Anhui Provincial Hospital Department of Medical Oncology Jilin Cancer Hospital State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Department of Gastrointestinal Oncology Peking University Cancer Hospital&Institute Department of Medical Oncology Hubei Cancer Hospital Clinical Development BeiGene(Shanghai)Co. Ltd. Biostatistics BeiGene(Beijing)Co. Ltd. Department of Oncology Fudan University Shanghai Cancer Center Department of Medical Oncology Affiliated Hospital of Hebei University Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gynecology Peking University Cancer Hospital&Institute Department of Immunotherapy Henan Cancer Hospital Department of Gastrointestinal Oncology Affiliated Cancer Hospital of Harbin Medical University Department of Gastrointestinal Oncology Chongqing University Cancer Hospital Department of Gastrointestinal Oncology the Fifth Medical Center Chinese PLA General Hospital Department of Medical Oncology the Second Affiliated Hospital Zhejiang University School of Medicine

Objective: The open-label, phase Ⅱ RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR) tumors.Methods: Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate(ORR; primary endpoint), duration of response(DoR), and progression-free survival(PFS) were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results: Eighty patients were enrolled and treated; 75(93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79; 98.8%). At primary analysis(data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval(95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal(n=46):39.1%(95% CI, 25.1–54.6); gastric/gastroesophageal junction(n=9): 55.6%(95% CI, 21.2-86.3); others(n=20):60.0%(95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five(6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up(data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events(TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs.Conclusions: Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

关键词： Biomarkers DNA mismatch repair immune checkpoint inhibitors microsatellite instability phase II clinical trials programmed cell death 1 receptor

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DeepOCL:A deep neural network for Object Constraint Language generation from unrestricted nature language

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CAAI Transactions on Intelligence Technology 2024年第1期9卷 250-263页

作者： Yilong Yang Yibo liu tianshu Bao Weiru Wang Nan Niu Yongfeng Yin School of Software Beihang UniversityBeijingChina College of Computer Science and Technology Guizhou UniversityGuiyangGuizhouChina Faculty of Information Technology Beijing University of TechnologyBeijingChina Department of Electrical Engineering and Computer Sciences University of CincinnatiCincinnatiOhioUSA

Object Constraint Language(OCL)is one kind of lightweight formal specification,which is widely used for software verification and validation in NASA and Object Management Group projects.Although OCL provides a simple expressive syntax,it is hard for the developers to write correctly due to lacking knowledge of the mathematical foundations of the first-order logic,which is approximately half accurate at the first stage of devel-opment.A deep neural network named DeepOCL is proposed,which takes the unre-stricted natural language as inputs and automatically outputs the best-scored OCL candidates without requiring a domain conceptual model that is compulsively required in existing rule-based generation approaches.To demonstrate the validity of our proposed approach,ablation experiments were conducted on a new sentence-aligned dataset named OCLPairs.The experiments show that the proposed DeepOCL can achieve state of the art for OCL statement generation,scored 74.30 on BLEU,and greatly outperformed experienced developers by 35.19%.The proposed approach is the first deep learning approach to generate the OCL expression from the natural language.It can be further developed as a CASE tool for the software industry.

关键词： deep learning OCL software engineering

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Responses of nitrogen cycling and related microorganisms to brackish wetlands formed by evapotranspiration

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Pedosphere 2024年第1期34卷 252-266页

作者： Jiaohui FANG tianshu LU Jian liu Shangbin HE Xiufeng YANG Huashan DOU Honghai ZHANG School of Life Sciences Qufu Normal UniversityQufu 273100China Environment Research Institute Shandong UniversityQingdao 266237China Hulunbuir Academy of Inland Lakes in Northern Cold&Arid Areas Hulunbuir 021000China

Elevated evapotranspiration due to warmer air temperature could raise salinity and nutrient levels of some inland wetlands, potentially impacting nitrogen cycling. To characterize the impact of high evapotranspiration on soil microbial nitrogen cycling in inland wetlands, we compared freshwater and brackish marsh(or non-marsh) wetlands in terms of sediment ammonia-oxidizing rate(AOR), denitrifying rate(DR), and related microbial communities in a typical inland basin, the Hulun Lake basin, in China. Results showed that marsh ecosystems(ME) exhibited 31% higher AOR and 65% higher DR than non-marsh ecosystems(NE). For NE, freshwater non-marsh wetland exhibited 12% higher AOR than brackish non-marsh wetland. This was probably due to the inhibitory effects of high NH_4~+ and salinity levels on ammonia-oxidizing archaea in brackish non-marsh wetland. Conversely, DR in brackish non-marsh wetland was 23% higher than that in freshwater non-marsh wetland, with total organic carbon(TOC) significantly influencing this difference,suggesting that the higher DR in brackish non-marsh wetland was mainly due to its higher TOC level. For ME, due to the direct and indirect interference of salinity, brackish marsh wetland displayed 26% lower AOR and 19% lower DR than freshwater marsh wetland. Besides, brackish wetlands harbored distinct ammonia-oxidizing and denitrifying microbial communities compared to freshwater wetlands. The assembly of these communities was dominated by stochastic processes, while brackish wetlands exhibited more prominent deterministic processes than freshwater wetlands. Overall, high evapotranspiration altered activities and community characteristics of ammonia oxidizers and denitrifiers in inland brackish wetlands by enhancing salinity and nutrient levels,while emergent plants occurring in ME could mitigate the adverse effects of salt stress of inland brackish wetlands on nitrogen cycling.

关键词： ammonia-oxidizing archaea ammonia-oxidizing bacteria aquatic plants denitrifying bacteria nitrogen transformation inland wetlands

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Generalized boundary dilatation flux on a flexible wall

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Theoretical & Applied Mechanics Letters 2022年第6期12卷 445-450页

作者： Tao Chen tianshu liu Department of Mechanics and Aerospace Engineering Southern University of Science and TechnologyShenzhen 518055China Department of Mechanical and Aerospace Engineering Western Michigan UniversityKalamazooMichigan49008USA

In this paper,by applying theoretical method to the governing equations of compressible viscous flow,we derive the theoretical formula of the boundary dilatation flux(BDF)on a flexible wall,which generalizes the most recent work of Mao et al.(Acta Mechanica Sinica 38(2022)321583)for a stationary wall.Different boundary sources of dilatation are explicitly identified,revealing not only the boundary generation mechanisms of vortex sound and entropy sound,but also some additional sources due to the surface vorticity,surface angular velocity,surface acceleration and surface curvature.In particular,the generation mechanism of dilatation at boundary due to the coupled divergence terms is highlighted,namely,the product of the surface velocity divergence(▽_(■B)·U)and the vorticity-induced skin friction divergence(V_(■B)·τ_(ω)).The former is attributed to the surface flexibility while the latter characterizes the footprints of near-wall coherent structures.Therefore,by properly designing the surface velocity distribution,the dilatation generation at the boundary could be controlled for practical purpose in near-wall compressible viscous flows.

关键词： Boundary dilatation flux Surface deformation Boundary vorticity dynamics Near-wall flow

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Evolutionary understanding of airfoil lift

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Advances in Aerodynamics 2021年第1期3卷 649-672页

作者： tianshu liu Department of Mechanical and Aerospace Engineering Western Michigan UniversityKalamazooMI 49008USA

This review attempts to elucidate the physical origin of aerodynamic lift of an airfoil using simple formulations and notations,particularly focusing on the critical effect of the fluid viscosity.The evolutionary development of the lift problem of a flat-plate airfoil is reviewed as a canonical case from the classical inviscid circulation theory to the viscous-flow model.In particular,the physical aspects of the analytical expressions for the lift coefficient of the plate-plate airfoil are discussed,including Newton’s sine-squared law,Rayleigh’s lift formula,thin-airfoil theory and viscous-flow lift formula.The vortex-force theory is described to provide a solid foundation for consistent treatment of lift,form drag,Kutta condition,and downwash.The formation of the circulation and generation of lift are discussed based on numerical simulations of a viscous starting flow over an airfoil,and the evolution of the flow topology near the trailing edge is well correlated with the realization of the Kutta condition.The presented contents are valuable for the pedagogical purposes in aerodynamics and fluid mechanics.

关键词： Lift Drag Airfoil Circulation Kutta condition Taylor-Sears condition Viscosity Boundary layer Vorticity Vortex Lamb vector Boundary enstrophy flux

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基于电场传感器阵列的输电线路电压非接触式测量方法

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高电压技术 2024年第1期50卷 292-301页

作者：冯迪刘灏李嘉贤毕天姝华北电力大学新能源电力系统国家重点实验室北京102206 国网冀北电力有限公司电力科学研究院北京100054

电压作为表征线路运行状态的重要参量,实现其灵活准确的测量对保证电力系统稳定运行至关重要。传统的接触式电压测量方法,因电压互感器体积较大、会产生电磁谐振和高频振荡、额外测量需断电安装等问题,对于海量化测量并不便利。相比较而... 详细信息

电压作为表征线路运行状态的重要参量,实现其灵活准确的测量对保证电力系统稳定运行至关重要。传统的接触式电压测量方法,因电压互感器体积较大、会产生电磁谐振和高频振荡、额外测量需断电安装等问题,对于海量化测量并不便利。相比较而言,非接触式测量不接触导线,更加安全和便捷,将成为未来电压测量的发展方向。文中提出了基于电场传感器阵列的输电线路电压非接触式测量方法,该方法为了解决导线位置信息未知的问题,设计了与导线方向垂直排列的电场传感器阵列;求解了含导线未知信息量的方程组;构建了比例系数矩阵,反推出导线电压瞬时值;分析了电场传感器对测量的影响;最后,进行了10 kV电压等级电压瞬时值仿真验证,结果显示最大测量误差为2.219%。

关键词：非接触式电压测量电压瞬时值模拟电荷法电场传感器阵列比例系数矩阵

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风电接入海上换流站的交流汇集出线高速保护

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中国电机工程学报 2024年第12期44卷 4775-4787,I0014页

作者：温志文刘昊霖贾科张旸毕天姝新能源电力系统国家重点实验室(华北电力大学) 北京市昌平区102206

风电接入海上换流站的交流汇集出线双端均是电力电子电源,短路电流均呈现幅值受限和相角受控的特征,导致差动保护动作性能下降,存在拒动的风险。针对上述问题,分析了柔直换流站和风机变流器在故障暂态期间的故障特性,证实了区内故障线... 详细信息

风电接入海上换流站的交流汇集出线双端均是电力电子电源,短路电流均呈现幅值受限和相角受控的特征,导致差动保护动作性能下降,存在拒动的风险。针对上述问题,分析了柔直换流站和风机变流器在故障暂态期间的故障特性,证实了区内故障线路两侧短路电流频谱特征存在很大的差异,基于此,利用时频能量系数衡量线路两侧短路电流的时频特性差异,提出适用于风电接入海上换流站交流汇集出线的高速保护原理。该时频能量系数综合幅值、频率和相角差异,具有较强的耐受过渡电阻和系统噪声的能力。所提保护衡量故障暂态的故障特性差异,理论上可以在5 ms内快速可靠识别区内外故障,硬件在环实验结果验证了所提保护的有效性。

关键词：海上风电故障特征时频能量系数高速保护

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考虑PMU数据质量问题的电力系统扰动检测方法

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中国电机工程学报 2024年第2期44卷 451-463,I0002页

作者：李子康刘灏毕天姝杨奇逊国网上海市区供电公司上海市虹口区200080 新能源电力系统国家重点实验室(华北电力大学) 北京市昌平区102206

快速准确的电力系统扰动检测能够为后续扰动分析提供有效的指导信息,而广域测量系统(wide area measurement system,WAMS)的广泛应用为扰动检测提供了有力的数据基础。基于PMU量测数据,该文提出一种考虑PMU不良数据的扰动事件检测方法... 详细信息

快速准确的电力系统扰动检测能够为后续扰动分析提供有效的指导信息,而广域测量系统(wide area measurement system,WAMS)的广泛应用为扰动检测提供了有力的数据基础。基于PMU量测数据,该文提出一种考虑PMU不良数据的扰动事件检测方法。首先分析PMU异常数据行为特性,揭示扰动事件与不良数据的差异性特征。进一步,提出一种基于差分Teager-Kaiser能量算子与3Sigma准则相结合的PMU异常数据初筛方法,避免了低强度扰动漏检和扰动的重复检测问题。接着,利用动态时间规整和最大互信息系数分别计算不同PMU间的时空相似性,以及同一台PMU内不同量测间的相关性,并以此作为表征扰动事件和不良数据差异的特征。最后,通过局部离群概率算法对得到的综合度量指标进行分析,可实现在含有不良数据场景下的扰动事件准确检测。基于IEEE39系统,实际电网模型以及PMU实测数据,验证所提方法具有较好准确性、实时性以及泛化能力。

关键词：同步相量测量扰动检测数据质量问题不良数据

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China enters CAR-T cell therapy era

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The Innovation 2022年第1期3卷 93-94页

作者： Xin Cao Wei Li Yiyi Yu tianshu liu Yuhong Zhou Institute of Clinical Science Zhongshan HospitalFudan UniversityShanghai 200032China Department of Medical Oncology Zhongshan Hospital Fudan UniversityShanghai 200032China Cancer Center Zhongshan HospitalFudan UniversityShanghai 200032China Cell Therapy Center Zhongshan HospitalFudan UniversityShanghai 200032China Clinical Trial Center Zhongshan HospitalFudan UniversityShanghai 200032China

The emerging individualized and living-cell-based genetic engineering chimeric antigen receptor T(CAR-T)therapy demonstrates great curative effects in some hematological tumor treatments,thus it is turning out to be a star immunotherapy method of the world.1 Recently,the China NationalMedical Products Administration(NMPA)approved launching applications of two CAR-T cell cancer products,Axicabtagene Ciloleucel(FKC876)and Relmacabtagene Autoleucel(Carteyva),which marked the beginning of the of CAR-T cell therapy era in China(Figure 1).

关键词： CAR curative Figure

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Immune Checkpoint Inhibitor-associated Myocarditis with Myasthenia Gravis:A Case Report

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Clinical Cancer Bulletin 2022年第3期1卷 182-184页

作者： Qing liu Jinyi LIN tianshu liu Yiyi YU Department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China Cancer Center Zhongshan Hospital180 Fenglin RoadShanghai 200032China Department of Cardiology Zhongshan HospitalFudan UniversityShanghai 200032China

Immune checkpoint inhibitors(ICIs)have revolutionized the management of various cancers.However,myocarditis is a rare but severe complication associated with ICI use.We describe the case of a 62-year-old woman who presented with ICI-associated myocarditis alongside myasthenia gravis.Consequently,the patient was treated with initial high doses of corticosteroids combined with immunosuppressive therapy,and improved outcomes and clinical remission were observed.The overlap of myocarditis with myasthenia gravis is associated with high morbidity and mortality.The early administration of high dose of corticosteroids combined with immunosuppressive therapy was associated with improved outcomes in our patient.

关键词： corticosteroid immune checkpoint inhibitors myocarditis myasthenia gravis

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