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| 1 | Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)显示文摘Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC. | Yuankai Shi Lin Wu Xinmin Yu Puyuan Xing Yan Wang Jianying Zhou Airong Wang Jianhua Shi Yi Hu Ziping Wang Guangyu An Yong Fang Sanyuan Sun Caicun Zhou Changli Wang Feng Ye Xingya Li Junye Wang Mengzhao Wang Yunpeng Liu Yanqiu Zhao Ying Yuan Jifeng Feng Zhendong Chen Jindong Shi Tao Sun Gang Wu Yongqian Shu Qisen Guo Yi Zhang Yong Song Shucai Zhang Yuan Chen Wei Li Hongrui Niu Wenwei Hu Lijun Wang Jianan Huang Yang Zhang Ying Cheng Zhengdong Wu Bo Peng Jiya Sun Christoph Mancao Yanqi Wang Luyao Sun | 2022 | Cancer Communications2022，42，12： | 8 |
| 2 | BUB1B and circBUB1B_544aa aggravate multiple myeloma malignancy through evoking chromosomal instability显示文摘Multiple myeloma(MM)is an incurable plasma cell malignancy in the bone marrow characterized by chromosome instability(CIN),which contributes to the acquisition of heterogeneity,along with MM progression,drug resistance,and relapse.In this study,we elucidated that the expression of BUB1B increased strikingly in MM patients and was closely correlated with poor outcomes.Overexpression of BUB1B facilitated cellular proliferation and induced drug resistance in vitro and in vivo,while genetic targeting BUB1B abrogated this effect.Mechanistic studies unveiled that enforced expression of BUB1B evoked CIN resulting in MM poor outcomes mainly through phosphorylating CEP170.Interestingly,we discovered the existence of circBUB1B_544aa containing the kinase catalytic center of BUB1B,which was translated by a circular RNA of BUB1B.The circBUB1B_544aa elevated in MM peripheral blood samples was closely associated with MM poor outcomes and played a synergistic effect with BUB1B on evoking CIN.In addition,MM cells could secrete circBUB1B_544aa and interfere the MM microenvironmental cells in the same manner as BUB1B full-length protein.Intriguingly,BUB1B siRNA,targeting the kinase catalytic center of both BUB1B and circBUB1B_544aa,significantly inhibited MM malignancy in vitro and in vivo.Collectively,BUB1B and circBUB1B_544aa are promising prognostic and therapeutic targets of MM. | Xiaozhu Tang Mengjie guo Pinggang Ding Zhendong Deng Mengying Ke Yuxia Yuan Yanyan Zhou Zigen Lin Muxi Li Chunyan Gu Xiaosong Gu Ye Yang | 2021 | Signal Transduction and Targeted Therapy2021，6，11： | 2 |
| 3 | Prediction of water table depths under soil water-groundwater interaction and stream water conveyance显示文摘Water table over an arid region can be elevated to a critical level to sustain terrestrial ecosystem along the natural channel by the stream water conveyance. Estimation of water table depth and soil moisture on river channel profile may be reduced to a two-dimensional moving boundary problem with soil water-groundwater interaction. The two-dimensional soil water flow with stream water transferred is divided into an unsaturated vertical soil water flow and a horizontal groundwater flow. Therefore, a prediction model scheme for water table depths under the interaction between soil water and groundwater with stream water transferred is presented, which includes a vertical soil water movement model, a horizontal groundwater movement model, and an interface model. The synthetic experiments are conducted to test the sensitivities of the river elevation, horizontal conductivity, and surface flux, and the results from the experiments show the robustness of the proposed scheme under different conditions. The groundwater horizontal conductivity of the proposed scheme is also calibrated by SCE-UA method and validated by data collected at the Yingsu section in the lower reaches of the Tarim River, which shows that the model can reasonably simulate the water table depths. | DI ZhenHua XIE ZhengHui YUAN Xing TIAN XiangJun LUO ZhenDong CHEN YaNing | 2011 | Science China Earth Sciences2011，54，3： | 1 |
| 4 | Extraction and i- dentification of anthocyanin from purple com显示文摘 | Zhendong Yang Zhijie Chen Shulin Yuan | 2009 | International Jour- nal of Food Science and Technology2009，，44： | 1 |
| 5 | CREDIBLE SETS FOR SYSTEM PARAMETERS ANDTRANSFER FUNCTIONS显示文摘The credible sets for system parameters and transfer functions are discussedin this paper. The derivations of the credible sets via the Bayesian statistical methods aregiven in various cases and the credible sets of transfer functions are constructed on thebasis of the parameter credible sets. In the small sample case the credible set, which theparameters are in, has minimal volume with given credible probability. In the large samplecaset it is proved that if the critical boundary is taken properly then the probability, withwhich the parameters are in the credible set, will tend to one as the number of data tendsto infinity. The credible set for transfer function is an envelope on the complex plane.Under some assumptions, the envelope tends to the curve of true transfer function. | YUAN Zhendong CHEN Qi DING Sheng DIAO Lianwang(Department of Mathematics, East China Nomal University, Shanghai 200062, China) | 1998 | Systems Science and Mathematical Sciences1998，11，2： | 0 |
| 6 | Identification of Germline Mutations in East‑Asian Young Never‑Smokers with Lung Adenocarcinoma by Whole‑Exome Sequencing显示文摘Recently,an increasing number of young never-smokers are diagnosed with lung cancer.The aim of this study is to investigate the genetic predisposition of lung cancer in these patients and discover candidate pathogenic variants for lung adenocarcinoma in young never-smokers.Peripheral blood was collected from 123 never-smoking east-Asian patients diagnosed with lung adenocarcinoma before the age of 40.Whole-exome sequencing(WES)was conducted on genomic DNA extracted from peripheral blood cells.As a result,3,481 single nucleotide variants were identified.By bioinformatical tools and the published gene list associated with genetic predisposition of cancer,pathogenic variants were detected in ten germline genes:ATR,FANCD2,FANCE,GATA2,HFE,MSH2,PDGFRA,PMS2,SDHB,and WAS.Patients with pathogenic variants were more likely to occur in females(9/10,90.0%)and have stage IV lung adenocarcinoma(4/10,40%).Furthermore,germline muta-tions in 17 genes(ASB18,B3GALT5,CLEC4F,COL6A6,CYP4B1,C6orf132,EXO1,GATA4,HCK,KCP,NPHP4,PIGX,PPIL2,PPP1R3G,RRBP1,SALL4,and TTC28),which occurred in at least two patients,displayed potentially pathogenic effects.Gene ontology analysis further showed that these genes with germline mutations were mainly located in nucleo-plasm and associated with DNA repair-related biological processes.The study provides spectrum of pathogenic variants and functional explanation for genetic predisposition of lung adenocarcinoma in young never-smokers,which sheds a light on prevention and early diagnosis of lung cancer. | Fangqiu Fu Xiaoting Tao Zhonglin Jiang Zhendong Gao Yue Zhao Yuan Li Hong Hu Libing Shen Yihua Sun Yang Zhang | 2023 | Phenomics2023，3，2： | 0 |
| 7 | Effective metal mold method for the production of bionic adhesives based on electrochemical modifications显示文摘Bionic adhesives with tip-expanded microstructural arrays have attracted considerable interest owing to their high adhesive performance at low preloads.Their mainstream manufacturing method is molding.Due to most molds are made of silicon or silicon-based soft templates,and have poor wear resistant or vulnerability to high temperature,limiting their use in large-scale manufacturing.Nickel is widely used as an embossing mold in the micro/nano-imprint industrial process owing to its good mechanical properties.However,the processing of metal molds for the fabrication of tip-expanded microstructural arrays is extremely challenging.In this study,using electrodeposition techniques,the shape of the micropores is modified to obtain end-controlled pores.The effect of the non-uniformity of the electric field on the microporous morphology in the electrodeposition process is systematically investigated.Furthermore,the mechanism of non-uniformity evolution of the microporous morphology is revealed.The optimized microporous metal array is used as a mold to investigate the cavity evolution laws of the elastic cushions under pre-load during the manufacturing process.As a result,typical bionic adhesives with tip-expansion are obtained.Moreover,corresponding adhesion mechanics are analyzed.The results show that electrochemical modifications have broad application prospects in the fabrication of tip-expanded microstructures,providing a new method for the large-scale fabrication of bionic adhesives based on metal molds. | Cong YUAN Keju JI Yiqiang TANG Zizhuo WANG Enhua CUI Jian CHEN Zhendong DAI | 2021 | Chinese Journal of Aeronautics2021，34，4： | 0 |
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