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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

Stabilizing water and regulating interfacial electrostatic interaction with economical supporting salt for stable Zn metal anode

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Journal of Energy Chemistry 2025年第2期101卷 429-436页

作者： yiqun Du Rongkai Kang Boya Zhang han Wang Jianxin Zhang School of Material Science & Engineering University of Jinan Key Laboratory for Liquid-Solid Structural Evolution and Processing of Materials (Ministry of Education) School of Materials Science and Engineering Shandong University

Developing rechargeable aqueous Zn batteries for large-scale energy storage is impeded by inadequate reversibility and stability of the Zn anode,primarily caused by parasitic reactions and heterogeneous *** study proposes an economical electrolyte strategy to address these Zn-related *** addition of a supporting salt enhances the thermodynamic stability of water,reduces the number of highly reactive water molecules,and modulates the interfacial electrostatic *** approach effectively suppresses hydrogen evolution reaction and uncontrolled ***,the rationally proportioned electrolyte allows a high average Coulombic efficiency of 99.93% for 1000 cycles in a Zn‖Cu battery and a prolonged lifespan exceeding 4800 h in Zn‖Zn *** knock-on effect is that Zn‖MnO2pouch cells deliver stable cycling performance,demonstrating the viability of this approach for practical applications.

关键词： Aqueous electrolyte Hydrogen bond Sodium citrate Solvation structure Zn anode

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

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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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

Association of PM_(2.5)Reduction with Improved Kidney Function:A Nationwide Quasiexperiment among Chinese Adults

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Health Data Science 2022年第1期2022卷 115-123页

作者： yiqun han Tao Xue Frank J.Kelly Yixuan Zheng Yao Yao Jiajianghui Li Jiwei Li Chun Fan Pengfei Li Tong Zhu Environmental Research Group MRC Centre for Environment and HealthImperial College LondonLondonUK BIC-ESAT and SKL-ESPC College of Environmental Sciences and EngineeringCenter for Environment and HealthPeking UniversityBeijing 100871China Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health and Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijingChina Center of Air Quality Simulation and System Analysis Chinese Academy of Environmental Planning100012 BeijingChina China Center for Health Development Studies Peking UniversityBeijingChina College of Computer Science and Technology Zhejiang UniversityHangzhouChina Computer Center Peking University and Peng Cheng LaboratoryChina Advanced Institute of Information Technology Peking UniversityChina

*** evidence from human studies has revealed the adverse impact of ambient fine particles(PM_(2.5))on health outcomes related to metabolic disorders and distant *** exposure to ambient PM_(2.5)leads to kidney impairment remains *** rapid air quality improvement driven by the clean air actions in China since 2013 provides an opportunity for a quasiexperiment to investigate the beneficial effect of PM_(2.5)reduction on kidney *** on two repeated nationwide surveys of the same population of 5115 adults in 2011 and 2015,we conducted a difference-indifference *** in long-term exposure to ambient PM_(2.5)were associated with changes in kidney function biomarkers,including estimated glomerular filtration rate by serum creatinine(GFRscr)or cystatin C(GFRcys),blood urea nitrogen(BUN),and uric acid(UA).*** a 10μg/m^(3)reduction in PM_(2.5),a significant improvement was observed for multiple kidney functional biomarkers,including GFRscr,BUN and UA,with a change of 0.42(95%confidence interval[CI]:0.06,0.78)mL/min/1.73m^(2),-0.38(-0.64,-0.12)mg/dL,and-0.06(-0.12,-0.00)mg/dL,respectively.A lower socioeconomic status,indicated by rural residence or low educational level,enhanced the adverse effect of PM_(2.5)on kidney *** results support a significant nephrotoxicity of PM_(2.5)based on multiple serum biomarkers and indicate a beneficial effect of improved air quality on kidney function.

关键词： Kidney organs ambient

Docetaxel plus S-1 versus docetaxel plus capecitabine as first-line treatment for advanced breast cancer patients:a prospective randomized phase II study

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Journal of the National Cancer Center 2023年第2期3卷 115-120页

作者： Nilupai Abudureheiyimu Yun Wu Qing Li Pin Zhang Fei Ma Peng Yuan Yang Luo Ying Fan Shanshan Chen Ruigang Cai Qiao Li yiqun han hangcheng Xu Yan Wang Jiayu Wang Binghe Xu Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of VIP Medical Services National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Background:This study was conducted to evaluate the efficacy and safety of docetaxel/S-1(TS)compared with docetaxel/capecitabine(TX)as a first-line treatment for advanced breast ***:Patients with advanced metastatic breast cancer were randomly divided into the TS group(n=54)and the TX group(n=57)for first-line chemotherapy from August 2015 to April 2019(*** registration ***02947061).Following the completion of combination therapy,patients without progression received S-1 or capecitabine maintenance *** primary end point was progression-free survival(PFS).Results:Among 111 enrolled patients,the median PFS did not differ significantly between the TS group and the TX group(TS ***,9.0 vs.7.4 months,P=0.365,95%confidence interval[CI]:0.50-1.11,hazard ratio[HR]:0.75).There was also no statistically significant difference in median overall survival(OS)between the two groups(TS ***,40.2 vs.41.3 months,P=0.976).In addition,visceral metastasis and metastasis sites,such as the liver or lung,did not lead to a significant effect on PFS and *** two regimens showed no significant difference in adverse events,except hand-foot syndrome,which predominated in the TX group(38.6%vs.7.4%,P=0.001),and diarrhea(24.1%vs.3.6%,P=0.003)and elevation of aspartate aminotransferase(AST)/alanine aminotransferase(ALT)levels(14.8%vs.3.5%,P=0.049),which were more frequent in the TS ***:The TS and TX regimens demonstrated similar efficacy and safety for the first-line treatment of advanced breast *** TS regimen had fewer cases of severe hand-foot syndrome than the TX regimen,representing an effective alternative option to the TX *** studies are warranted to define the efficacy and safety of this strategy in real-world settings.

关键词： Advanced breast cancer Maintenance therapy Docetaxel Capecitabine S-1

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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环境流行病学研究中全血长期保存与RNA提取方法

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环境科学学报 2019年第12期39卷 4301-4308页

作者：姚媛陈悟陈曦韩逸群朱彤北京大学工程科学与新兴技术高精尖创新中心北京大学环境科学与工程学院环境模拟与污染控制国家重点联合实验室北京100871 深圳市建筑科学研究院股份有限公司研创中心深圳518049 MRC-PHE Centre for Environment and Health School of Population Health&Environmental SciencesKing′s College LondonLondon SE19NH

RNA是在基因表达层面探究分子生物学机制的重要研究对象.由于RNA化学性质活泼、结构不稳定,并且内外源RNA酶无处不在,如何从环境流行病学研究收集到的全血样本中提取出高质量的总RNA是困扰研究人员的一大难题.本研究旨在建立一种能长期... 详细信息

RNA是在基因表达层面探究分子生物学机制的重要研究对象.由于RNA化学性质活泼、结构不稳定,并且内外源RNA酶无处不在,如何从环境流行病学研究收集到的全血样本中提取出高质量的总RNA是困扰研究人员的一大难题.本研究旨在建立一种能长期保存全血样本并从中提取出高质量总RNA的方法.通过将环境流行病学研究中采集到的少量新鲜全血立即与10倍体积的TRIzol试剂混匀后置于-80℃冰箱中,可保护RNA在长期保存过程中不发生降解.针对长期保存的全血-TRIzol混合体系,在经典的TRIzol一步法基础上,无需将全血样本分装至不含RNA酶的1.5 mL离心管,直接在较大操作空间(不含RNA酶的15 mL离心管)中进行总RNA相分离、沉淀、洗涤等操作,并在总RNA晾干前再增加离心并吸取少量残留液体操作,缩短自然晾干时间.本方法无需离心、分离血浆、裂解红细胞等繁杂的前处理步骤,极大地简化了操作步骤,减少了采样工作量,实现了对全血样本的低成本长期保存.通过增大操作空间、改进晾干操作,本方法显著提高了总RNA样本的完整性和纯度.使用本方法提取出保存一年的全血总RNA产率为(9.18±2.10)μg·mL^-1,完整性指标RIN值和28S/18S分别为8.98±0.18和1.08±0.08,纯度指标OD260/OD280和OD260/OD230分别为2.18±0.04和1.70±0.00.保存两年的全血提取出总RNA的产率、完整性及纯度仍然可以满足下游实验要求.

关键词：环境流行病学全血长期保存 RNA提取产率完整性纯度