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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 257-269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 State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Department of Medical Oncology Affiliated Hospital of Hebei UniversityBaoding 071000China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of GynecologyPeking University Cancer Hospital&InstituteBeijing 100142China Department of Immunotherapy Henan Cancer HospitalZhengzhou 450001China Department of Gastrointestinal Oncology Affiliated Cancer Hospital of Harbin Medical UniversityHarbin 150086China Department of Gastrointestinal Oncology Chongqing University Cancer HospitalChongqing 400030China Department of Gastrointestinal Oncology the Fifth Medical CenterChinese PLA General HospitalBeijing 100048China Department of Medical Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Medical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Medical Oncology Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China Department of Medical Oncology Fujian Medical University Union HospitalFuzhou 350001China Department of Oncology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China Department of Medical Oncology Hunan Cancer HospitalChangsha 410013China Department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Immunotherapy Hubei Cancer HospitalWuhan 430079China Department of Medical Oncology the Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Medical Oncology Anhui Provincial HospitalHefei 230001China Department of Medical Oncology Jilin Cancer Hospital

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)***:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were *** received tislelizumab 200 mg intravenously every 3 *** 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 *** 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 *** 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 ***-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to ***: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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晚期胃癌Claudin-18.2靶向治疗临床研究新进展

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肿瘤 2024年第1期44卷 34-43页

作者：余一祎王晓刘天舒复旦大学附属中山医院肿瘤内科上海200032 复旦大学附属中山医院肿瘤防治中心上海200032

胃癌是消化系统最常见的恶性肿瘤之一,多数胃癌患者在确诊时已为晚期。晚期胃癌预后差,既往以化疗为基础的治疗效果有限。近年来,随着分子生物学技术的发展,寻找影响胃癌发生与发展的关键分子、预后指标及相关治疗靶点已成为晚期胃癌治... 详细信息

胃癌是消化系统最常见的恶性肿瘤之一,多数胃癌患者在确诊时已为晚期。晚期胃癌预后差,既往以化疗为基础的治疗效果有限。近年来,随着分子生物学技术的发展,寻找影响胃癌发生与发展的关键分子、预后指标及相关治疗靶点已成为晚期胃癌治疗领域的研究热点。Claudin-18剪接变异体2(Claudin-18 isoform 2,Claudin-18.2)是极具潜力的新兴肿瘤治疗靶点,为胃癌的靶向治疗带来新的希望。靶向Claudin-18.2的药物或治疗方法种类多样,包括单克隆抗体、双特异性抗体(bispecific antibody,Bs Ab)、抗体偶联药物(antibody-drug conjugate,ADC)和嵌合抗原受体T细胞(chimeric antigen receptor T cell,CAR-T)免疫治疗等,目前已有多项临床研究项目正在进行并取得了良好的结果。本文总结Claudin-18.2靶向治疗的临床研究进展,以期为改善晚期胃癌患者的预后提供临床依据。

关键词：晚期胃癌 Claudin-18.2 靶向治疗 CAR-T

Reconstruction of skin friction topology in complex separated flows

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Advances in Aerodynamics 2023年第1期5卷 579-613页

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

This paper describes a theoretical method for reconstruction of the skin friction topology in complex separated flows,which is developed based on the exact relation between skin friction and surface pressure through the boundary enstrophy flux(BEF).The key of this method is that a skin friction field is reconstructed from a surface pressure field as an inverse problem by applying a variational *** applications,the approximate method is proposed,where the composite surface pressure field is given by a linear superposition of the base-flow surface pressure field and the surface pressure variation field and the base-flow BEF field is used as the first-order *** approximate method is constructive in a mathematical sense since a complex skin friction field in separated flows can be reconstructed from some elemental skin friction structures(skin friction source/sink,vortex and their combinations)by a linear superposition of some simple surface pressure *** distinct topological features,such as critical points,separation lines and attachment lines,naturally occur as a result of such *** examples,some elemental skin friction structures in separated flows are reconstructed in simulations,and the skin friction fields in shock-wave/boundary-layer interactions(SWBLIs)are reconstructed from pressure sensitive paint(PSP)images obtained in wind tunnel experiments.

关键词： Skin friction Surface pressure Boundary enstrophy flux Flow separation Topology Inverse problem Variational method Euler-Lagrange equation Taylor-series-expansion solution Navier-Stokes equations Poincare-Bendixson index formula Shock-wave/boundary-layer interaction Pressure sensitive paint Aerodynamics

Can lift be generated in a steady inviscid flow?

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Advances in Aerodynamics 2023年第1期5卷 108-125页

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

This paper presents a critical evaluation of the physical aspects of lift generation to prove that no lift can be generated in a steady inviscid ***,the answer to the recurring question in the paper title is *** other words,the fluid viscosity is necessary in lift *** relevant topics include D’Alembert’s paradox of lift and drag,the Kutta condition,the force expression based on the boundary enstrophy flux(BEF),the vortex lift,and the generation of the vorticity and *** physi-cal meanings of the variational formulations to determine the circulation and lift are *** particular,in the variational formulation based on the continuity equation with the first-order Tikhonov regularization functional,an incompressible flow with the artificial viscosity(the Lagrange multiplier)is simulated,elucidating the role of the artifi-cial viscosity in lift *** presented contents are valuable for the pedagogical purposes in aerodynamics and fluid mechanics.

关键词： Lift Drag Airfoil Circulation Viscosity Vorticity Vortex Lamb vector Vortex lift Boundary enstrophy flux D’Alembert’s paradox Kutta-Joukowski theorem Kutta condition Variational formulation

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 *** 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 *** 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 *** vortex-force theory is described to provide a solid foundation for consistent treatment of lift,form drag,Kutta condition,and *** 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 *** 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

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 *** 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 *** 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 ***,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

Robust,fluorine-free and superhydrophobic composite melamine sponge modified with dual silanized SiO_(2) microspheres for oil-water separation

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Chinese Journal of Chemical Engineering 2021年第5期34卷 50-60页

作者： Ruilong Zhang Zhiping Zhou Wenna Ge Yi Lu tianshu liu Wenming Yang Jiangdong Dai School of Material Science and Engineering Jiangsu UniversityZhenjiang 212013China Institute of Green Chemistry and Chemical Technology School of Chemistry and Chemical EngineeringJiangsu UniversityZhenjiang 212013China School of Mechanical Engineering Dalian University of TechnologyDalian 116023China Entry-Exit Inspection Quarantine Bureau Zhenjiang 212008China

Massive oily wastewater discharged from industrial production and human daily life have been an urgent environmental and ecological *** materials have attracted tremendous attention due to their unique properties and potential applications in the treatment of *** this study,a novel superhydrophobic/superoleophilic composite melamine sponge modified with dual silanized SiO_(2) microspheres was fabricated simply by a two-step sol-gel method using vinyltriethoxysilane and hexadecyltrimethoxysilane as functional agent,which exhibited a water contact angle of 153.2°and a water sliding contact angle of 4.8°.Furthermore,the composite sponge showed the excellent oil adsorption performance and the compressive elasticity reaching up to 130 g·g^(-1) of dichloromethane and 33.1 kPa of compressive *** was worth noting that the composite sponge presented the excellent separation efficiency(up to 99.5%)in the processes of continuous oil/water *** robust superhydrophobic composite melamine sponge provided the possibility with the practical application for oil-water separation.

关键词： Superhydrophobic sponge Two-step sol-gel method Oil-water separation Dual silanized SiO_(2) microspheres

Scattering Center Modeling Using Adaptive Segmental Compressive Sampling

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Journal of Beijing Institute of Technology 2017年第4期26卷 484-493页

作者： Qifeng Li Kunyi Guo Jiaxin Wang Xinqing Sheng tianshu liu Center for Electromagnetic Simulation School of Information and ElectronicsBeijing Institute of Technology Science and Technology on Special System Simulation Laboratory Beijing Simulation Center

In order to deal with aliasing distortions of Doppler frequencies shown in time-frequency representation（ TFR） with aspect undersampling,an approach using adaptive segmental compressive sampling according to the aspect dependencies of the scattering centers is proposed. The random noise problem induced by compressive sampling is solved by employing a series of signal processing techniques of filtering,image transformation and Hough Transform. Three examples are presented to verify the effectiveness of this approach. The comparisons between the built models and the precise scattered fields computed by a well-validated full-wave numerical method are investigated,and the results showgood agreements between each other.

关键词： scattering center undersampling compressive sensing time-frequency representation parameter estimation

Numerical simulation of unsteady flows over a slow-flying bat

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Theoretical & Applied Mechanics Letters 2015年第1期5卷 5-8页

作者： Shizhao Wang Xing Zhang Guowei He tianshu liu The State Key Laboratory of Nonlinear Mechanics Institute of MechanicsChinese Academy of Sciences Department of Mechanical and Aerospace Engineering Western Michigan University

This letter describes numerical simulation of the unsteady flow over a slow-flying bat by using the immersed boundary method based on the measured bat wing geometry and kinematics. The main vortical structures around the bat flapping wings are identified, illuminating the lift-generating role of the leading- edge vortices generated mainly in the downstroke. Furthermore, the lift decomposition indicates that the vortex lift has the dominant contribution to the time-averaged lift and the lift associated with the fluid acceleration has the relatively moderate effect.

关键词： Flapping flightBatLiftLeading-edge vortexVortex liftNumerical simulation