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A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science china(life {2.) 2024年第4期67卷 765-777页

作者： hui Zhao Lin-Lin Liu Jian sun Lian Jin Hai-Bing Xie Jian-Bo Li hui Xu Dong-Dong Wu Xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-Jie sun liang-hu qu Jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping Zhang State Key Laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China Academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China Key Laboratory of Animal Models and human Disease Mechanisms of the Chinese Academy of sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was pre{2.t in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg538 and Gln573)in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2.2.

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Cancer Communications 2024年第1期44卷 127-172页

作者： Feng-hua Wang Xiao-Tian Zhang Lei Tang Qi Wu Mu-yan Cai Yuan-Fang Li Xiu-Juan {2. Hong Qiu Yu-Jing Zhang Jie-Er Ying Jun Zhang Ling-Yu sun Rong-Bo Lin Chang Wang Hao Liu Miao-Zhen Qiu Wen-Long Guan Sheng-Xiang Rao Jia-Fu Ji yan Xin Wei-Qi Sheng hui-Mian Xu Zhi-Wei Zhou Ai-Ping Zhou Jing Jin Xiang-Lin Yuan Feng Bi Tian-Shu Liu Han liang yan-Qiao Zhang Guo-Xin Li Jun liang Bao-Rui Liu Lin Shen Jin Li Rui-hua Xu Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer HospitalBeijingP.R.China Department of Radiology Peking University Cancer HospitalBeijingP.R.China Department of Endoscopy Center Peking University Cancer HospitalBeijingP.R.China Department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center of Cancer MedicineGuangzhouGuangdongP.R.China Department of Gastric Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Medical Oncology The First Hospital of China Medical UniversityShenyangLiaoningP.R.China Department of Medical Oncology Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Radiotherapy Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China Department of Medical Oncology Zhejiang Cancer HospitalHangzhouZhejiangP.R.China Department of Medical Oncology Ruijin HospitalShanghai Jiaotong University School of MedicineShanghaiP.R.China Department of Surgical Oncology The Fourth Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangP.R.China Department of Medical Oncology Fujian Cancer HospitalFuzhouFujianP.R.China Tumor Center The First Hospital of Jilin UniversityChangchunJilinP.R.China Department of General Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China Department of Radiology Zhongshan HospitalFudan UniversityShanghaiP.R.China Department of

The 2.2. update of the Chinese Society of Clinical Oncology(CSCO)Clini-cal Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in china,reflecting the latest advancements in evidence-based medicine,healthcare resource availability,and precision *** updates address the differences in epidemiological characteristics,clinicopatho-logical features,tumor biology,treatment patterns,and drug selections between Eastern and Western gastric cancer *** revisions include a structured template for imaging diagnosis reports,updated standards for molecular marker testing in pathological diagnosis,and an elevated recommendation for neoadju-vant chemotherapy in stage III gastric *** advanced metastatic gastric cancer,the guidelines introduce new recommendations for immunotherapy,anti-angiogenic therapy and targeted drugs,along with updated management strategies for human epidermal growth factor receptor 2.HER2.-positive and deficient DNA mismatch repair(dMMR)/microsatellite instability-high(MSI-H)***,the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric *** 2.2. CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert con{2.sus to enhance their applicability and relevance in clinical practice,particularly in the heterogeneous healthcare landscape of china,while maintaining a commitment to scientific rigor,impartiality,and timely revisions.

关键词： Chinese Society of Clinical Oncology(CSCO) gastric cancer diagnosis surgery neoadjuvant adjuvant radiotherapy chemotherapy targeted therapy immunotherapy

Effect of freeze-thaw cycles on uniaxial mechanical properties of cohesive coarse-grained soils

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Journal of Mountain Science 2019年第9期16卷 2159-2170页

作者： qu Yong-long CHEN Guo-liang NIU Fu-jun NI Wan-kui MU {2.-hu LUO Jing college of Geology Engineering and Geomatics Chang' an University Xi'an 710054 China china Gold Group Tibet Tyrone Mining Development Co. Ltd. Tibet 850000 China State Key Laboratory of Frozen Soil Engineering Northwest Institute of Eco-Environment and Resources Chinese Academy of Sciences Lanzhou 730000 China South china Institute of Geotechnical Engineering School of Civil Engineering and Transportation South China University of Technology Guangzhou 510641 China

Freeze-thaw cycles are closely related to the slope instability in high-altitude mountain regions. In this study, cohesive coarse-grained soils were collected from a high-altitude slope in the Qinghai–Tibet Plateau to study the effect of cyclic freeze-thaw on their uniaxial mechanical properties. The soil specimens were remolded with three dry densities and three moisture contents. Then, after performing a series of freeze-thaw tests in a closed system without water supply, the soil specimens were subjected to a uniaxial compression test. The results showed that the stress-strain curves of the tested soils mainly performed as strain-softening. The softening feature intensified with the increasing dry density but weakened with an increase in freeze-thaw cycles and moisture content. The uniaxial compressive strength, resilient modulus, residual strength and softening modulus decreased considerably with the increase of freeze-thaw cycles. After more than nine freeze-thaw cycles, these four parameters tended to be stable. These parameters increased with the increase of dry density and decreased with the increasing moisture content, except for the residual strength which did not exhibit any clear variation with an increase in moisture content. The residual strength, however, generally increased with an increase in dry density. The soil structural damage caused by frozen water expansion during the freeze-thaw is the major cause for the changes in mechanical behaviors of cohesive coarse-grained soils. With results in this study, the deterioration effect of freeze-thaw cycles on the mechanical properties of soils should be considered during the slope stability analysis in high-altitude mountain regions.

关键词： Freeze thaw cycles Residual strength Resilient modulus Softening modulus Uniaxial compressive strength Slope stability

The genetic load for hereditary hearing impairment in Chinese population and its clinical implication

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Journal of Otology 2009年第2期4卷 98-105页

作者： WANG Qiu-ju 1,2. RAO Shao-qi 1, 3, GUO Yu-fen 4, LI Qing-zhong 5, ZHAO hui 1, ZHAO Li-dong 1, YUAN hu 1, ZONG {2. 1, LIU Qiong 1, ZHAO Ya-li 6, WANG Da-yong 1, HAN Ming-kun 1, JI Yu-bin 1, LI Jian-qiang 1, LAN Lan 1, yanG Wei-yan 1, SHEN yan 2.6, HAN Dong-yi 1 1 Department of Otorhinolaryngology-Head and Neck Surgery, and Institute of Otolaryngology, Chinese People’s Liberation Army General Hospital, Beijing, 100853 china 2.Chinese National human Genome Center, Beijing, 100176 china 3 Department of Medical Statistics and Epidemiology, School of Public Health, sun Yat-sen University, guangzhou, 510080, china 4 Department of Otorhinolaryngology, Head and Neck Surgery, Second Hospital of Lanzhou University, Lanzhou 730030, china 5 Department of Otolaryngology, EYE & ENT hospital of Fudan University, Shanghai, 2.0031,china 6 Institute of Basic Medical sciences, Chinese Academy of Medical sciences and Peking Union Medical college, Beijing, 100005 china Department of Otorhinolaryngology–Head and Neck Surgery and Institute of Otolaryngology Chinese People’s Liberation Army General Hospital Beijing 100853 China Chinese National human Genome Center Beijing 100176 China Department of Medical Statistics and Epidemiology School of Public Health Sun Yat–Sen University Guangzhou 510080 China Department of Otorhinolaryngology Head and Neck Surgery Second Hospital of Lanzhou UniversityLanzhou 730030 China Department of Otolaryngology EYE & ENT hospital of Fudan University Shanghai 200031China Institute of Basic Medical sciences Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100005 China

Objective To understand the genetic load in the Chinese population for improvement in diagnosis, prevention and rehabilitation of deafness. Methods DNA samples, immortalized cell lines as well as detailed clinical and audiometric data were collected through a national genetic resources collecting network. Two conventional genetic approaches were used in the studies. Linkage analysis in X chromosome and autosomes with microsatellite markers were performed in large families for gene mapping and positional cloning of novel genes. Candidate gene approach was used for screening the mtDNA 12.rRNA, GJB2.and SLC2.A4 mutations in population -based samples. Results A total of 2.572.Chinese hearing loss families or sporadic cases were characterized in the reported studies, including seven X-linked, one Y-linked, 2. large and multiplex autosomal dominant hearing loss families, 607 simplex autosomal recessive hereditary hearing loss families, 100 mitochondrial inheritance families, 147 GJB2.induced hearing loss cases, 2.0 cases with enlarged vestibular aqueduct (EVA) syndrome, 169 sporadic cases with auditory neuropathy, and 1,2.3 sporadic sensorineural hearing loss cases. Through linkage analysis or sequence analysis, two X-linked families were found transmitting two novel mutations in the POU3F4 gene, while another X -linked family was mapped onto a novel locus, nominated as AUNX1 (auditory neuropathy, X-linked locus 1). The only Y-linked family was mapped onto the DFNY1 locus(Y-linked locus 1, DFNY1). Eight of the 2. autosomal dominant families were linked to various autosomal loci. In population genetics studies, 2.567 familial cases and sporadic patients were subjected to mutation screening for three common hearing loss genes: mtDNA 12. rRNA 1555G, GJB2.and SLC2.A4. The auditory neuropathy cases in our samples were screened for OTOF gene mutations. Conclusions These data show that the Chinese population has a genetic load on hereditary hearing loss. Establishing personalize

关键词： Hereditary hea ring loss linkage analysis DFNY1 AUNX1 auditory neuropathy enlarged vestibular aqueduct senserineural hearing loss genetic epidemiology

植物根际促生菌F13的筛选、鉴定及对豆角促生、抗病的效果

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中山大学学报（自然科学版）（中英文） 2024年第2期63卷 150-159页

作者：梁卫驱胡珊黄皓郑伟才喻孟君陈彦陈淑慰徐匆罗华建刘孝龙东莞市农业科学研究中心广东东莞523000 中山大学生命科学学院广东广州510275 中国科学技术大学化学与材料科学学院安徽合肥230026

为获得具有药肥双效的多功能植物根际促生菌,从葡萄根际土壤中分离出同时具有溶磷解钾功能的菌株F13。该菌通过形态学观察、生理生化检测和16S rDNA比对,鉴定为铜绿假单胞菌(Pseudomonas aeruginosa)。经平板对峙法测定菌株F13对8种植... 详细信息

为获得具有药肥双效的多功能植物根际促生菌,从葡萄根际土壤中分离出同时具有溶磷解钾功能的菌株F13。该菌通过形态学观察、生理生化检测和16S rDNA比对,鉴定为铜绿假单胞菌(Pseudomonas aeruginosa)。经平板对峙法测定菌株F13对8种植物病原菌的抑制率为63.2.%~81.53%。田间应用中发现,菌株F13发酵液灌根处理对豆角(Vigna unguiculata ***(L.)Verdc.)生长具有显著的促进作用,其中实验组在株高、叶片数、茎粗方面分别高于对照组2..7%、2..4%、11.9%,产量高于对照组39.68%;在植株吸收磷、钾元素方面分别高于对照组11.5%、46.8%;在豆角果实中维生素C、可溶性蛋白含量方面分别高于对照组2..15%、55.55%。此外,菌株F13对豆角白粉病的相对防效达71.92.。因此,菌株F13是一株具有巨大应用潜力的药肥双效植物根际促生菌。

关键词：植物根际促生菌促生作用拮抗作用

One-year status of hepatic venous pressure gradient measurement from 85 hospitals in china

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Portal Hypertension & Cirrhosis 2024年第2期3卷 116-123页

作者： Jitao Wang Ting Cui Linpeng Zhang Zhiping yan Lei Li Jinjun Chen Junhui {2. hua Xiang He Zhu Hao Wu Jiancuo Gengzang Feng Zhang Wei Wu Guohong Cao Wuhua Guo Haibin Shi hui Xue Guangjun huang Qiang Yu Meng Niu huiling Xiang Derun Kong Wei Gou Xuefeng Luo Fuliang He Min Yuan Wei Liu Yong Wang Hongjie hu Xiaoli Zhu Tao Yu Qinxue {2. Wei qu Ting Lu Deqiang Ma Li Zhang Jun Ma Jun yang Ketao Mu Xiaoliang Zhu Kai Xiong huiguo Ding Shengjuan Yao Mingsheng huang Fang Wang Zexin Wang Yong huang Jianan Li Hongfeng Yi Birun huang Zhongwei Zhao Duiping Feng yanming Lei Changlong Hou Wenbo Guo Shirong Liu Gaojun Teng Kangshun Zhu Fan Wu Xiaogang hu Wenfeng Zhang Shaoqi yang Zhouchao hu Pengfei Pang Shaowu Zhuang Weidong Wang Qingliang Zhu Kunpeng Zhang Chengyu Liu Dongliang Li Chao Ma Hong Jiang Xingong Zhao Weixin Ren Zhiwei Wang Lei Yu Fuhuang Lin Chaoguang yan Feng Wang Lei Yu hui huan Wenyong Shen Shaofei He Chengda Zhang Jinlun Bao Jiangtao Liu Jun Wu Jianbo Zhao Jian Zhang Xiaolong Qi Hebei Provincial Key Laboratory of Cirrhosis&Portal Hypertension Xingtai People's HospitalXingtaiHebeiChina Center of Portal Hypertension Department of RadiologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsuChina Department of Interventional Therapy Beijing Shijitan Hospital Affiliated to Capital Medical UniversityBeijingChina Department of Intervention Taiyuan Third People's HospitalTaiyuanShanxiChina Department of Intervention Zhongshan Hospital Affiliated to Fudan UniversityShanghaiChina Department of Interventional Medicine The First Hospital of Lanzhou UniversityLanzhouGansuChina Department of Infectious Diseases Nanfang Hospital of Southern Medical UniversityGuangzhouGuangdongChina Hepatobiliary and Pancreatic Intervention Center The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangChina Interventional Vascular Surgery Hunan Provincial People's HospitalChangshaHunanChina Department of Intervention Sixth People's Hospital of ShenyangShenyangLiaoningChina Department of Gastroenterology West China Hospital of Sichuan UniversityChengduSichuanChina Department of Intervention The Fourth People's Hospital of Qinghai ProvinceXiningQinghaiChina Department of Gastroenterology Nanjing Drum Tower HospitalNanjingJiangsuChina Department of Gastroenterology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Department of Radiology Shulan(Hangzhou)HospitalHangzhouZhejiangChina Department of Intervention Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouFujianChina Department of Interventional Radiology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina Department of Gastroenterology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina Department of Interventional Radiology Fifth Medical Center

Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in *** article aimed to investigate the status of hepatic venous pressure gradient measurement in china in ***:We investigated the overall status of HVPG technology in china-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online *** counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in ***:According to the survey,85 hospitals in china used HVPG technology in 2.2. distributed across 2. provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2.2.,of which 2.13 cases(56.4%)were measured *** average cost of HVPG measurement was 5646.8±2.2..9 *** the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82.87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy ***:This survey clarified the clinical application status of HVPG in china and confirmed that some medical institutions in china have established a foundation for this *** is still necessary to continue promoting and popularizing this technology in the future.

关键词： application status hepatic vein pressure gradient questionnaire survey

Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing chemotherapy:china Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study

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Frontiers of Medicine 2019年第3期13卷 365-377页

作者： Ling Wang Ying Wang Jiong hu Yuqian sun He huang Jing Chen Jianyong Li Jun Ma Juan Li Yingmin liang Jianmin Wang yan Li Kang Yu Jianda hu Jie Jin Chun Wang Depei Wu yang Xiao Xiaojun huang Blood & Marrow Transplantation Center Department of HematologyCollaborative Innovation Center of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Hematology The First Affiliated Hospital of China Medical UniversityShenyang 110001China Department of Hematology The First Affiliated Hospital of Wenzhou Medical CollegeWenzhou 325000China Department of Hematology Fujian Medical University Union HospitalFuzhou 350001China Department of Hematology The First People's Hospital of ShanghaiShanghai 200080China Department of Hematology The First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Hematology The General Hospital of Guangzhou Military Command of PLAGuangzhou 510010China Peking University Institute of Hematology Peking UniversityPeople's HospitalBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Department of Hematology The First Affiliated Hospital of Medical School of Zhejiang UniversityHangzhou 310003China Department of Hematology-Oncology Shanghai Children's Medical CenterShanghai 200127China Department of Hematology Jiangsu Province HospitalNanjing 210029China Harbin Hematologic Tumor Institution Harbin 150010China Department of Hematology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Hematology Tangdu HospitalFourth Military Medical UniversityXi'an 710032China Department of Hematology Changhai Hospital of the Second Military Medical UniversityShanghai 200082China

Invasive fungal disease (IFD) is a major infectious complication in patients with hematological *** this study,we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n=3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression,which included the following variables: male patients,induction chemotherapy for newly diagnosed or relapsed disease,neutropenia,neutropenia longer than 10 days,hypoalbuminemia,central-venous catheter,and history of *** patients were classified into three groups,which had low (0-10,~1.2.),intermediate (11-15,6.4%),and high risk (> 15,17.5%) of *** the validation set (n=1389),the IFD incidences of the groups were ~1.4%,5.0%,and 2..4%.In addition,we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients,whereas benefits were documented in intermediate (2.1% vs.6.6%,P=0.007) and high-risk patients (8.4% vs.2..3%,P=0.007).To make the risk score applicable for clinical settings,a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established,and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of *** conclusion,an objective,weighted risk score for IFD was developed,and it may be useful in guiding antifungal prophylaxis.

关键词： invasive fungal diseases hematological malignancies chemotherapy risk score prophylaxis

Entinostat,a classⅠselective histone deacetylase inhibitor,plus exemestane for Chinese patients with hormone receptor-positive advanced breast cancer:A multicenter,randomized,double-blind,placebo-controlled,phase 3 trial

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Acta Pharmaceutica Sinica B 2023年第5期13卷 2250-2258页

作者： Binghe Xu Qingyuan Zhang Xichun hu Qing Li Tao {2. Wei Li quchang Ouyang Jingfen Wang Zhongsheng Tong Min yan huiping Li Xiaohua Zeng Changping Shan Xian Wang Xi yan Jian Zhang Yue Zhang Jiani Wang liang Zhang Ying Lin Jifeng Feng Qianjun Chen Jian huang Lu Zhang Lisong yang Ying Tian Hongyan Shang Department of Medical Oncology and State Key Laboratory of Molecular Oncology National Cancer Cener/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Medical Oncology Harbin Medical University Cancer HospitalHarbin 150000China Department of Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200000China Department of Galactophore Liaoning Cancer Hospital&InstituteShenyang 110801China Department of Oncology the First Hospital of Jilin UniversityChangchun 130061China Department of Galactophore Hunan Cancer HospitalChangsha 410000China Department of Galactophore Linyi Cancer HospitalLinyi 276000China Department of Breast Medical Oncology Tianjin Medical University Cancer Institute&HospitalTianjin 300000China Department of Breast Disease Henan Breast Cancer Centerthe Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhou 450008China Department of Breast Oncology Beijing Cancer HospitalBeijing 100000China Breast Cancer Center Chongqing University Cancer HospitalChongqing 400000China Department of Breast and Thyroid Oncology Affiliated Hospital of Jining Medical UniversityChangchun 130021China Department of Medical Oncology Run Run Shaw HospitalAffiliated Hospital of Zhejiang UniversityHangzhou 310003China Department of Head and Heck Oncology West China HospitalSichuan UniversityChengdu 610000China Department of Thyroid&Breast Surgery the First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510000China Department of Medical Oncology Jiangsu Cancer HospitalNanjing 210000China Department of Galactophore Guangdong Hospital of Traditional Chinese MedicineGuangzhou 510000China Department of Oncological Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Taizhou EOC Pharma Co. Ltd.Taizhou 318000China

Entinostat plus exemestane in hormone receptor-positive(HR+)advanced breast cancer(ABC)previously showed encouraging *** multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR+ABC that relapsed/progressed after≥1 endocrine *** were randomized(2.1)to oral exemestane 2. mg/day plus entinostat(n=2.5)or placebo(n=119)5 mg/week in 2.-day *** primary endpoint was the independent radiographic committee(IRC)-assessed progression-free survival(PFS).The median age was 52.range,2.—75)years and 2.2.62.7%)patients were ***4/6 inhibitors and fulvestrant were previously used in 2.(6.5%)and 92.2..0%)patients,*** baseline characteristics were comparable between the entinostat and placebo *** median PFS was 6.32.95%CI,5.30—9.11)and 3.72.95%CI,1.91—5.49)months in the entinostat and placebo groups(HR,0.76;95%CI,0.58—0.98;P=0.046),***≥3 adverse events(AEs)occurred in 154(65.5%)patients in the entinostat group versus 2.(19.3%)in the placebo group,and the most common grade≥3 treatment-related AEs were neutropenia[103(43.8%)],thrombocytopenia[2.(8.5%)],and leucopenia[15(6.4%)].Entinostat plus exemestane significantly improved PFS compared with exemestane,with generally manageable toxicities in HR+ABC(***#NCT03538171).

关键词： Advanced breast cancer Hormone receptor-positive Histone deacetylase inhibitors Phase 3 clinical trial

CEPC Technical Design Report

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Radiation Detection Technology and Methods 2024年第1期8卷 I0003-I0016,1-1091页

作者： Waleed Abdallah Tiago Carlos Adorno de Freitas Konstantin Afanaciev Shakeel Ahmad Ijaz Ahmed Xiaocong Ai Abid Aleem Wolfgang Altmannshofer Fabio Alves Weiming An Rui An Daniele Paolo Anderle Stefan Antusch Yasuo Arai Andrej Arbuzov Abdesslam Arhrib Mustafa Ashry Sha Bai Yu Bai yang Bai Vipul Bairathi Csaba Balazs Philip Bambade Yong Ban Tripamo Bandyopadhyay Shou-Shan Bao Desmond P.Barber Ayse Bat Varvara Batozskaya Subash Chandra Behera Alexander Belyaev Michele Bertucci Xiao-Jun Bi Yuanjie Bi Tianjian Bian Fabrizio Bianchi Thomas Biekotter Michela Biglietti Shalva Bilanishvili Deng Binglin Denis Bodrov Anton Bogomyagkov Serge Bondarenko Stewart Boogert Maarten Boonekamp Marcello Borri Angelo Bosotti Vincent Boudry Mohammed Boukidi Igor Boyko Ivanka Bozovic Giuseppe Bozzi Jean-Claude Brient Anastasiia Budzinskaya Masroor Bukhari Vladimir Bytev Giacomo Cacciapaglia hua Cai Wenyong Cai Wujun Cai Yijian Cai Yizhou Cai Yuchen Cai Haiying Cai huacheng Cai Lorenzo Calibbi Junsong Cang Guofu Cao Jianshe Cao Antoine Chance Xuejun Chang Yue Chang Zhe Chang Xinyuan Chang Wei Chao Auttakit Chatrabhuti Yimin Che Yuzhi Che Bin Chen Danping Chen Fuqing Chen Fusan Chen Gang Chen Guoming Chen hua-Xing Chen huirun Chen Jinhui Chen Ji-Yuan Chen Kai Chen Mali Chen Mingjun Chen Mingshui Chen Ning Chen Shanhong Chen Shanzhen Chen Shao-Long Chen Shaomin Chen Shiqiang Chen Tianlu Chen Wei Chen Xiang Chen Xiaoyu Chen Xin Chen Xun Chen Xurong Chen Ye Chen Ying Chen Yukai Chen Zelin Chen Zilin Chen Gang Chen Boping Chen Chunhui Chen Hok Chuen Cheng huajie Cheng Shan Cheng Tongguang Cheng Yunlong Chi Pietro Chimenti Wen Han Chiu Guk Cho Ming-Chung Chu Xiaotong Chu Ziliang Chu Guglielmo Coloretti Andreas Crivellin Hanhua Cui Xiaohao Cui Zhaoyuan Cui Brunella D'Anzi Ling-Yun Dai Xinchen Dai Xuwen Dai Antonio De Maria Nicola De Filippis Christophe De La Taille Francesca De Mori Chiara De Sio Elisa Del Core Shuangxue Deng Wei-Tian Deng Zhi Deng Ziyan Deng Bhupal Dev Tang Dewen Biagio Di Micco Ran Ding Siqin Dingl Yadong Ding Haiyi Dong Jianin AGH University of Science and Technology Faculty of Physics and Applied Computer ScienceKrakow Anhui University HefeiAnhui Applied Physics Department Federal Urdu University of ArtsScience and TechnologyIslamabad Banaras Hindu University Institute of ScienceVaranasi Bandirma Onyedi Eylul University Bandirma Beihang University Beijing Beijing Computational Science Research Center Beijing Beijing Conveyi LTD Beijing Beijing Glass Research Institute Co. LtdBeijing Beijing Institute of Technology Beijing Beijing Normal University Beijing Brown University ProvidenceRI Budker Institute of Nuclear Physics Novosibirsk Cadi Ayyad University Laboratory of Fundamental and Applied PhysicsPolydisciplinary FacultyMarrakech Cairo University Giza Center for Theory and Computation National Tsing Hua UniversityHsinchu Central china Normal University WuhanHubei Central South University ChangshaHunan Centro de Fisica Teorica de Particulas Universidade Tecnica de LisboaLisboa Chengdu KaitengSifang Digital Radio&TV Equipment Co. LtdChengduSichuan china academy of engineering physics MianyangSichuan china building materials academy Beijing china Center of Advanced Science and Technology Beijing china Institute of Atomic Energy Beijing china Jiliang University HangzhouZhejiang china Nuclear Instrument CO. LTDBeijing china University of Geosciences Beijing china University of Geosciences WuhanHubei china University of Mining and Technology XuzhouJiangsu china West Normal University NanchongSichuan Chongqing University Department of PhysicsChongqing Chulalongkorn University Bangkok City University of Hong Kong Department of PhysicsHong Kong Cockcroft Institute Daresbury Cornell University IthacaNY CPPM(AMU/IPhu&CNRS/INP) Marseille Dalian Minzu University DalianLiaoning Dalian University of Technology Department of PhysicsDalian Deutsches Elektronen-Synchrotron DESY Hamburg Dzhelepov Laboratory of Nuclear Problems of Joint Institute for Nuclear Research(DLNP JINR) Dubna East china University Of Science And Technol

The Circular Electron Positron Collider(CEPC)is a large scientific project initiated and hosted by china,fostered through extensive collaboration with international *** complex comprises four accelerators:a 30 GeV Linac,a 1.1 GeV Damping Ring,a Booster capable of achieving energies up to 180 GeV,and a Collider operating at varying energy modes(Z,W,H,and tt).The Linac and Damping Ring are situated on the surface,while the subterranean Booster and Collider are housed in a 100 km circumference underground tunnel,strategically accommodating future expansion with provisions for a potential Super Proton Proton Collider(SPPC).The CEPC primarily serves as a Higgs *** its baseline design with synchrotron radiation(SR)power of 30 MW per beam,it can achieve a luminosity of 5×10^(34)cm^(-2.s^(-1)per interaction point(IP),resulting in an integrated luminosity of 13 ab^(-1)for two IPs over a decade,producing 2.6 million Higgs *** the SR power to 50 MW per beam expands the CEPC's capability to generate 4.3 million Higgs bosons,facilitating precise measurements of Higgs coupling at sub-percent levels,exceeding the precision expected from the HL-LHC by an order of *** Technical Design Report(TDR)follows the Preliminary Conceptual Design Report(Pre-CDR,2.15)and the Conceptual Design Report(CDR,2.18),comprehensively detailing the machine's layout,performance metrics,physical design and analysis,technical systems design,R&D and prototyping efforts,and associated civil engineering ***,it includes a cost estimate and a preliminary construction timeline,establishing a framework for forthcoming engineering design phase and site selection *** is anticipated to begin around 2.2.-2.2.,pending government approval,with an estimated duration of 8 *** commencement of experiments and data collection could potentially be initiated in the mid-2.30s.

关键词： initiated exceeding precise