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Disitamab vedotin,a HER2-directed antibody-drug conjugate,in patients with HER2-overexpression and HER2-low advanced breast cancer:a phase I/Ib study

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Cancer Communications 2024年第7期44卷 833-851页

作者： Jiayu Wang Yunjiang Liu Qingyuan Zhang Wei Li Jifeng Feng XiaojiaWang Jianmin Fang yiqun han Binghe Xu Department of Medical Oncology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Breast Center The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebeiP.R.China Department of Breast Medicine Harbin Medical University Cancer HospitalHarbinHeilongjiangP.R.China Department of Medical Oncology The First Hospital of Jilin UniversityChangchunJilinP.R.China Department of Medical Oncology Jiangsu Cancer HospitalNanjingJiangsuP.R.China Department of Breast Medicine Zhejiang Cancer HospitalHangzhouZhejiangP.R.China School of Life Science and Technology Tongji UniversityShanghaiP.R.China

Background:Disitamab vedotin(DV;RC48-ADC)is an antibody-drug conjugate comprising a human epidermal growth factor receptor 2(HER2)-directed antibody,linker and monomethyl auristatin *** studies have shown that DV demonstrated potent antitumor activity in preclinical models of breast,gastric,and ovarian cancers with different levels of HER2 *** this pooled analysis,we report the safety and efficacy of DV in patients with HER2-overexpression and HER2-low advanced breast cancer(ABC).Methods:In the phase I dose-escalation study(C001 CANCER),HER2-overexpression ABC patients received DV at doses of 0.5-2.5 mg/kg once every two weeks(Q2W)until unacceptable toxicity or progressive *** dose range,safety,and pharmacokinetics(PK)were *** phase Ib dose-range and expansion study(C003 CANCER)enrolled two cohorts:HER2-overexpression ABC patients receiving DV at doses of 1.5-2.5 mg/kg Q2W,with the recommended phase 2 dose(RP2D)determined,andHER2-lowABC patients receiving DV at doses of 2.0 mg/kg Q2W to explore the efficacy and safety of DV in HER2-low ***:Twenty-four patients with HER2-overexpression ABC in C001 CANCER,46 patients with HER2-overexpressionABCand 66 patients with HER2-low ABC in C003 CANCER were *** 2.0 mg/kg RP2D Q2W,the confirmed objective response rates were 42.9%(9/21;95%confidence interval[CI]:21.8%-66.0%)and 33.3%(22/66;95%CI:22.2%-46.0%),with median progression-free survival(PFS)of 5.7 months(95%CI:5.3-8.4 months)and 5.1 months(95%CI:4.1-6.6 months)for HER2-overexpression and HER2-low ABC,***(≥5%)grade 3 or higher treatment-emergent adverse events included neutrophil count decreased(17.6%),gamma-glutamyl transferase increased(13.2%),asthenia(11.0%),white blood cell count decreased(9.6%),peripheral neuropathy such as hypoesthesia(5.9%)and neurotoxicity(0.7%),and pain(5.9%).Conclusion:DV demonstrated promising efficacy in HER2-overexpression and HER2-low ABC,with a favorable safety profile at

关键词： antibody-drug conjugate breast cancer clinical trials disitamab vedotin HER2-low HER2-overexpression

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天津大运河活态博物馆系统构建策略与方法研究

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包装工程 2024年第10期45卷 325-331页

作者：曹易韩轶群陈野天津理工大学艺术学院天津300382 合肥工业大学建筑与艺术学院合肥230009 天津工艺美术职业学院天津300250

目的大运河的天津段是其重要组成部分,拥有着丰富的运河文化遗产。利用数字化技术,通过构建“线上+线下”交互一体化的天津大运河活态博物馆系统,丰富大运河天津段文化遗产的保护与利用形式。方法运用地理信息系统(GIS)平台对大运河天... 详细信息

目的大运河的天津段是其重要组成部分,拥有着丰富的运河文化遗产。利用数字化技术,通过构建“线上+线下”交互一体化的天津大运河活态博物馆系统,丰富大运河天津段文化遗产的保护与利用形式。方法运用地理信息系统(GIS)平台对大运河天津段的文化遗产现状与各类文化遗产空间的结构特征进行核密度分析,根据GIS平台的分析结果规划出天津大运河活态博物馆的线下展示空间范围,并对运河文化遗产分布情况进行博物馆式的各主题展区与游览路线的规划设计。基于可视化、数据库与JPS等数字化技术创新构建大运河活态博物馆数字化平台,并针对数字化平台功能模块与数字导览系统的构建方法,分别进行阐释。结论构建天津大运河活态博物馆系统,不仅能够丰富大运河天津段的文化遗产保护与利用形式,还可以为大运河国家文化公园的导览系统设计提供参考范式。

关键词：大运河博物馆数字活态展示

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Health effects of fine particles(PM_(2.5)) in ambient air

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Science China(Life Sciences) 2015年第6期58卷 624-626页

作者： han yiqun ZHU Tong State Key Joint Laboratory for Environmental Simulation and Pollution Control College of Environmental Sciences and Engineering Center for Environment and Health Peking University

Air pollutants have serious health effects on human beings. The 2010 Global Burden of Disease study reports that each year, ambient particulate matter （PM2.5, particles with aero- dynamic diameter 〈 2.5 micrometer） is causing 3.2 million premature deaths globally, and 1.2 million in China alone. Ambient PM pollution ranked fourth among all risk factors in China.

关键词：环境空气细颗粒物人类健康 PM2.5 空气污染物空气动力学风险因素中国

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Predictive biomarkers of response and survival following immunotherapy with a PD-L1 inhibitor benmelstobart(TQB2450)and antiangiogenic therapy with a VEGFR inhibitor anlotinib for pretreated advanced triple negative breast cancer

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Signal Transduction and Targeted Therapy 2023年第12期8卷 5944-5953页

作者： yiqun han Jiayu Wang Tao Sun Quchang Ouyang Jianwen Li Jie Yuan Binghe Xu National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Liaoning Cancer Hospital&Institute ShenyangLiaoning 110042China Hunan Cancer Hospital ChangshaHunan 410013China Geneplus-Shenzhen Shenzhen 518118China

In our phase Ib trial(*** Identifier:NCT03855358),benmelstobart(TQB2450),a novel humanized IgG1 antibody against PD-L1,plus antiangiogenic multikinase inhibitor,anlotinib,demonstrated promising antitumor activities in pretreated triple negative breast cancer(TNBC)*** conducted explorative analyses of genomic biomarkers to explore the associations with treatment response and survival *** next generation sequencing(NGS)was undertaken toward circulating tumor DNA(ctDNA)collected from peripheral blood samples prior to the start of treatment and after disease progression.A total of 31 patients received targeted NGS and functional driver mutations in 29 patients were *** most frequent mutations were TP53(72%),MLL3(28%),and PIK3CA(17%).At a blood-based tumor mutational burden(bTMB)cutoff of 6.7 mutations per megabase,patients with low bTMB showed better response to anlotinib plus TQB2450(50%vs.7%,P=0.015)and gained greater PFS benefits(7.3 vs.4.1 months,P=0.012)than those with high *** a maximum somatic allele frequency(MSAF)cutoff of 10%,a low MSAF indicated a better objective response(43%vs.20%)as well as a significantly longer median PFS(7.9 vs.2.7 months,Phan patients with other *** findings support future studes and validation of MSAF and the combined bTMB-MSAF classification as predictive biomarkers of immune checkpoint inhibitor-based regimens in advanced TNBC patients.

关键词： PIK3CA breast cancer

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A prospective study (SCOPE) comparing the cardiometabolic and respiratory effects of air pollution exposure on healthy and pre-diabetic individuals

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Science China(Life Sciences) 2018年第10期61卷 46-56页

作者： Yanwen Wang yiqun han Tong Zhu Weiju Li Hongyin Zhang BIC-ESAT and SKL-ESPC College of Environmental Sciences and Engineering Peking University Peking University Hospital Peking University

Air pollution is known to be a major risk factor for cardiopulmonary disease, but this is unclear for cardiometabolic disease (***). This is of considerable public health importance, given the nationwide epidemic of diabetes, accompanied by severe air pollution, in China. The evidence so far remained inadequate to answer questions of whether individuals with cardiometabolic dysfunctions are susceptible to air pollution and whether air pollution exacerbates diabetes development via certain biological pathways. In this manuscript, we summarize the results and limitations of studies exploring these two topics and elaborate our design of a prospective panel study (SCOPE) as a solution. We assessed and compared the health effect of air pollution among pre-diabetic individuals and matched healthy controls through four repeated clinical visits over 1 year. Comprehensive evaluation was made to both health endpoints and exposure. The primary biomarkers were assessed to reveal the impact on multiple biological pathways, including glycolipid metabolism and insulin resistance, endothelial function, and inflammation. Detailed chemical and size fractional components of particulate matter were measured in this study, along with the application of personal *** work should increase our understanding of how air pollution affects individuals with cardiometabolic dysfunction and the underlying mechanisms.

关键词： panel study air pollution diabetes susceptibility cardiometabolic effect

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Possibility and stabilizing effect of Mo clusters in the Ni-based single-crystal superalloy

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Communications in Theoretical Physics 2024年第8期76卷 187-192页

作者： yiqun Du Huixin Jin Rongkai Kang Boya Zhang han Wang Jianxin Zhang Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials(Ministry of Education) School of Materials Science and EngineeringShandong UniversityJinan 250061China Department of Materials Science and Technology Tokyo University of ScienceTokyo 1258585Japan

Nickel-based single-crystal superalloys are crucial materials for the preparation of aero-engine turbine blades. Many solute elements are added to superalloys for strengthening. However, the relationship between the clustering behavior of solute atoms and the properties of nickel-based single-crystal superalloys is still unclear. Herein, we conduct first-principles calculations onγ phases with Mo-Mo and Mo-Mo-Ru clusters to reveal the possibility and stabilizing mechanism of solute clusters. Introducing Mo lowers the total energy, binding energy, and formation energy of the γ phase due to the replacement of weak Ni-Ni interaction with strong Mo-Ni bonding. Note that the γ phase containing the Mo-Mo cluster is more stable than that containing a Mo single atom, possibly owing to a wide affecting range. The Ru atom added to the γ phase can further boost system stability, and it tends to form a Mo-Mo-Ru cluster. The stabilizing impact of the Mo-Mo-Ru cluster is demonstrated to be the replacement of weak Ni-Mo interaction by the strong Ru-Mo interaction, which may be derived from the enhanced d-orbital hybridization.

关键词： density functional theory superalloys solute cluster

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Bioinspired Tactile Sensation Based on Synergistic Microcrack-Bristle Structure Design toward High Mechanical Sensitivity and Direction-Resolving Capability

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Research 2024年第1期2023卷 611-624页

作者： yiqun Zhang Qi Liu Wenjuan Ren Yangyang Song Hua Luo Yangyang han Liang He Xiaodong Wu Zhuqing Wang School of Mechanical Engineering Sichuan UniversityChengdu 610065China Med+X Center for Manufacturing West China HospitalSichuan UniversityChengdu 610041China State Key Laboratory of Polymer Materials Engineering Polymer Research Institute of Sichuan UniversityChengdu 610065China

Natural tactile sensation is complex,which involves not only contact force intensity detection but also the perception of the force direction,the surface texture,and other mechanical ***,the vast majority of the developed tactile sensors can only detect the normal force,but usually cannot resolve shear force or even distinguish the directions of the ***,we present a new paradigm of bioinspired tactile sensors for resolving both the intensity and the directions of mechanical stimulations via synergistic microcrack-bristle structure design and cross-shaped configuration *** microcrack sensing structure gives high mechanical sensitivity to the tactile sensors,and the synergistic bristle structure further amplifies the sensitivity of the *** cross-shaped configuration engineering of the synergistic microcrack-bristle structure further endows the tactile sensors with good capability to detect and distinguish the directions of the applied mechanical *** as-fabricated tactile sensors exhibit a high sensitivity(25.76 N^(−1)),low detection limit(5.4 mN),desirable stability(over 2,500 cycles),and good capability to resolve both mechanical intensity and directional *** promising application scenarios,surface texture recognition and biomimetic path explorations are successfully demonstrated with these tactile *** newly proposed tactile sensation strategy and technology have great potential applications in ingenious tactile sensation and construction of various robotic and bionic prostheses with high operational dexterity.

关键词： crack sensation directions

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Interfacial Oxygen Octahedral Coupling-Driven Robust Ferroelectricity in Epitaxial Na_(0.5)Bi_(0.5)TiO_(3)Thin Films

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Research 2024年第2期2023卷 149-157页

作者： Haojie han Qinghua Zhang Wei Li yiqun Liu Jiasheng Guo Yue Wang Qian Li Lin Gu Ce-Wen Nan Jing Ma State Key Laboratory of New Ceramics and Fine Processing Schoolof Materials Science and EngineeringTsinghua UniversityBeijing 100084China Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China

The oxygen octahedral rotation(OOR)forms fundamental atomic distortions and symmetries in perovskite oxides and definitely determines their properties and ***,epitaxial strain and interfacial structural coupling engineering have been developed to modulate the OOR patterns and explore novel properties,but it is difficult to distinguish the 2 ***,different symmetries are induced in Na_(0.5)Bi_(0.5)TiO_(3)(NBT)epitaxial films by interfacial oxygen octahedral coupling rather than epitaxial *** NBT film grown on the Nb:SrTiO_(3)substrate exhibits a paraelectric tetragonal phase,while with La_(0.5)Sr_(0.5)MnO_(3)as a buffer layer,a monoclinic phase and robust ferroelectricity are obtained,with a remanent polarization of 42μC cm^(-2)and a breakdown strength of 7.89 MV cm^(-1),which are the highest record among NBT-based ***,the interfacial oxygen octahedral coupling effect is demonstrated to propagate to the entire thickness of the film,suggesting an intriguing long-range *** work provides a deep insight into understanding the structure modulation in perovskite heterostructures and an important avenue for achieving unique functionalities.

关键词： effect. interfacial coupling

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Susceptibility of patients with chronic obstructive pulmonary disease to heart rate difference associated with the short-term exposure to metals in ambient fine particles:A panel study in Beijing,China

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Science China(Life Sciences) 2022年第2期65卷 387-397页

作者： Ke Gao Xi Chen Xiaoying Li hanxiyue Zhang Mengxiao Luan Yuan Yao Yifan Xu Teng Wang yiqun han Tao Xue Junxia Wang Mei Zheng Xinghua Qiu Tong Zhu State Key Joint Laboratory for Environmental Simulation and Pollution Control and Beijing Innovation Center for Engineering Science and Advanced Technology College of Environmental Sciences and EngineeringPeking UniversityBeijing 100871China Green Research Inspection and Certification Co. Ltd.Institute of Building Research Co.Ltd.in ShenzhenShenzhen 518071China Medical Research Council Centre for Environment and HealthImperial College LondonDepartment of Epidemiology and BiostatisticsLondon W21PGUK Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health and Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China

Susceptibility of patients with chronic obstructive pulmonary disease(COPD)to cardiovascular autonomic dysfunction asso-ciated with exposure to metals in ambient fine particles(PM2.5,particulate matter with aerodynamic diameter≤2.5µm)remains poorly *** on the COPDB(COPD in Beijing)panel study,we aimed to compare the associations of heart rate(HR,an indicator of cardiovascular autonomic function)and exposure to metals in PM2.5 between 53 patients with COPD and 82 healthy controls by using linear mixed-effects *** all participants,the HR levels were significantly associated with interquartile range increases in the average concentrations of Cr,Zn,and Pb,but the strength of the associations differed by exposure time(from 1.4%for an average 9 days(d)Cr exposure to 3.5%for an average 9 d Zn exposure).HR was positively associated with the average concentrations of PM2.5 and certain metals only in patients with *** between HR and exposure to PM2.5,K,Cr,Mn,Ni,Cu,Zn,As,and Se in patients with COPD significantly differed from those in health ***,association between HR and Cr exposure was robust in COPD *** conclusion,our findings indicate that COPD could exacerbate difference in HR following exposure to metals in PM2.5.

关键词： metal in fine particles chronic obstructive pulmonary disease(COPD) susceptibility heart rate cardiovascular auto-nomic function

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Wind-Vortex-Induced Vibrations of a Deepwater Jacket Pipe and Vibration Suppression Using a Nonlinear Energy Sink

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Journal of Ocean University of China 2024年第3期23卷 633-642页

作者： LIU Liqin YU Yongjun CHEN yiqun State Key Laboratory of Hydraulic Engineering Simulation and Safety Tianjin UniversityTianjin 300072China China Classification Society Haikou 570102China

The purpose of this study is to investigate the suppression effect of a nonlinear energy sink(NES)on the wind-vortex-induced pipe vibration and explore the influence of damping,stiffness,and NES installation position on the suppression *** this work,the wind-vortex-induced vibration of an elastic pipe of a deepwater jacket was studied,and vibrations were suppressed by using an NES.A van der Pol wake oscillator was used to simulate vortex-induced force,and the dynamic equation of the pipe considering the NES was *** Galerkin method was applied to discretize the motion equation,and the vortex-induced vibration(VIV)of the pipe at reduced wind speeds was numerically *** novelty of this research is that particle swarm optimization was used to optimize the parameters of the NES to improve vibration *** influence of the installation position,nonlinear stiffness,and damping parameters of the NES on vibration suppression was *** showed that the optimized parameter combinations of the NES can effectively reduce wind-vortex-induced pipe *** installation position of the NES had a significant effect on vibration suppression,and the midpoint of the pipe was the optimal NES installation *** increase in stiffness or a 10% decrease in damping may cause vibration suppression *** results of this study provide some guidance for VIV suppression in deepwater jacket pipes.

关键词： deepwater jacket wind-vortex-induced vibration NES PSO vibration suppression effect analysis

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