Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve ...Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve the progression-free survival(PFS)in the first-line setting but suffers from resistance 7-10 months after treatment initia-tion.Apatinib(YN968D1),a potent vascular endothelial growth factor receptor(VEGFR)2-TKI,specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect.Concurrent inhibition of VEGFR and EGFR path-ways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC.This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.Methods:This multicenter,randomized,double-blind,placebo-controlled phase III study(NCT02824458)has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC.A total of 310 patients with EGFR-mutation(19del or 21L858R),pathological stage IIIB to IV non-squamous NSCLC were to be enrolled.The primary endpoint is investigator assessment of PFS,and the secondary endpoints include independent radiological central(IRC)-confirmed PFS,overall survival(OS),objective response rate(ORR),disease control rate(DCR),time to progressive disease(TTPD),duration of response(DoR),quality of life(QoL)and safety.The patients are randomized in a 1:1 ratio to receive gefitinib(250 mg,p.o.q.d.)plus apatinib(500 mg,p.o.q.d.)or gefitinib plus placebo,given until disease progression or intolerable adverse events.Exploratory biomarker analysis will be performed.This study is being conducted across China and comprises of 30 participating centers.Enrollment commenced in August 2017 and finished in December 2018,most of the patients are in the follow-up period.Anticipated outcomes and significance:The present study will be the first to evaluate the efficacy and safety profile of the combination of apatinib plus gefitinib as a first-line therapy for patients with EGFR-positive advanced non-squamous NSCLC.Importantly,this trial will provide comprehensive evidence on the treatment of EGFR-TKIs combined with antiangiogenic therapy.展开更多
The single crystal scintillating optical fibers acting as the scintillators and light conductors show potential application in scintillating fiber array detectors with high spatial resolution.In this paper we report t...The single crystal scintillating optical fibers acting as the scintillators and light conductors show potential application in scintillating fiber array detectors with high spatial resolution.In this paper we report the growth of 0.2 at%Ce:Y_(3)Al_(5)O_(12) single crystal fiber.The crystalline phase,surface morphology of the axialsection and cro ss-section,optical and scintillation properties of the as-grown fiber were investigated.The Ce:Y_(3)Al_(5)O_(12) single crystal fiber has a pure YAG phase,a uniform distribution of cerium in the axialsection and cross-section surface.Emission spectrum is composed of broad bands ranging from 440 to700 nm.In addition,the single crystal fiber has a high light yield of 26115±2000 photons/MeV,low energy resolution of 9.44%@662 keV and decay time of a fast component of 78 ns and a slow component of 301 ns.The intensity ratio of fast to slow components is roughly 8:1.展开更多
Organic anode materials have attracted considerable interest owing to their high tunability by adopting various active functional groups.However,the interaction mechanisms between the alkali metals and the active func...Organic anode materials have attracted considerable interest owing to their high tunability by adopting various active functional groups.However,the interaction mechanisms between the alkali metals and the active functional groups in host materials have been rarely studied systematically.Here,a widely used organic semiconductor of perylene-3,4,9,10-tetracarboxylic diimide(PTCDI)was selected as a model system to investigate how alkali metals interact with imide functional groups and induce changes in chemical and electronic structures of PTCDI.The interaction at the alkali/PTCDI interface was probed by in-situ X-ray photoelectron spectroscopy(XPS),ultraviolet photoelectron spectroscopy(UPS),synchrotron-based near edge X-ray absorption fine structure(NEXAFS),and corroborated by density functional theory(DFT)calculations.Our results indicate that the alkali metal replaces the hydrogen atoms in the imide group and interact with the imide nitrogen of PTCDI.Electron transfer induced gap states and downward band-bending like effects are identified on the alkali-deposited PTCDI surface.It was found that Na shows a stronger electron transfer effect than Li.Such a model study of alkali insertion/intercalation in PTCDI gives insights for the exploration of the potential host materials for alkali storage applications.展开更多
基金This study was funded by the National Key R&D Program of China(Grant Numbers:2016YFC0905500,2016YFC0905503)the 5010 Clinical Research Foundation of Sun Yat-sen University(Grant Number:2016001)and Hengrui Medicine Co.Ltd
文摘Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve the progression-free survival(PFS)in the first-line setting but suffers from resistance 7-10 months after treatment initia-tion.Apatinib(YN968D1),a potent vascular endothelial growth factor receptor(VEGFR)2-TKI,specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect.Concurrent inhibition of VEGFR and EGFR path-ways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC.This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.Methods:This multicenter,randomized,double-blind,placebo-controlled phase III study(NCT02824458)has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC.A total of 310 patients with EGFR-mutation(19del or 21L858R),pathological stage IIIB to IV non-squamous NSCLC were to be enrolled.The primary endpoint is investigator assessment of PFS,and the secondary endpoints include independent radiological central(IRC)-confirmed PFS,overall survival(OS),objective response rate(ORR),disease control rate(DCR),time to progressive disease(TTPD),duration of response(DoR),quality of life(QoL)and safety.The patients are randomized in a 1:1 ratio to receive gefitinib(250 mg,p.o.q.d.)plus apatinib(500 mg,p.o.q.d.)or gefitinib plus placebo,given until disease progression or intolerable adverse events.Exploratory biomarker analysis will be performed.This study is being conducted across China and comprises of 30 participating centers.Enrollment commenced in August 2017 and finished in December 2018,most of the patients are in the follow-up period.Anticipated outcomes and significance:The present study will be the first to evaluate the efficacy and safety profile of the combination of apatinib plus gefitinib as a first-line therapy for patients with EGFR-positive advanced non-squamous NSCLC.Importantly,this trial will provide comprehensive evidence on the treatment of EGFR-TKIs combined with antiangiogenic therapy.
基金Project supported by the Instrument Developing Project of the Chinese Academy of Sciences(YJKYYQ20170019)International Partnership Program of Chinese Academy of Sciences(121631KYSB20180045)+2 种基金National Natural Science Foundation of China(51872309,U1832106,62005302)Science and Technology Commission of Shanghai Municipality(20511107400,ZJ2020-ZD-005)Science Foundation for Youth Scholar of State Key Laboratory of High Performance Ceramics and Superfine Micro structures(SKL201904)。
文摘The single crystal scintillating optical fibers acting as the scintillators and light conductors show potential application in scintillating fiber array detectors with high spatial resolution.In this paper we report the growth of 0.2 at%Ce:Y_(3)Al_(5)O_(12) single crystal fiber.The crystalline phase,surface morphology of the axialsection and cro ss-section,optical and scintillation properties of the as-grown fiber were investigated.The Ce:Y_(3)Al_(5)O_(12) single crystal fiber has a pure YAG phase,a uniform distribution of cerium in the axialsection and cross-section surface.Emission spectrum is composed of broad bands ranging from 440 to700 nm.In addition,the single crystal fiber has a high light yield of 26115±2000 photons/MeV,low energy resolution of 9.44%@662 keV and decay time of a fast component of 78 ns and a slow component of 301 ns.The intensity ratio of fast to slow components is roughly 8:1.
基金The authors acknowledge the financial support from Singapore MOE Tier II grant R143-000-A29-112,Academic Research Fund Tie I grant RG104/18,and the National Research Foundation under the grant of NRF2017NRF-NSFC001-007the computing resources from National Supercomputing Centre Singapore.
文摘Organic anode materials have attracted considerable interest owing to their high tunability by adopting various active functional groups.However,the interaction mechanisms between the alkali metals and the active functional groups in host materials have been rarely studied systematically.Here,a widely used organic semiconductor of perylene-3,4,9,10-tetracarboxylic diimide(PTCDI)was selected as a model system to investigate how alkali metals interact with imide functional groups and induce changes in chemical and electronic structures of PTCDI.The interaction at the alkali/PTCDI interface was probed by in-situ X-ray photoelectron spectroscopy(XPS),ultraviolet photoelectron spectroscopy(UPS),synchrotron-based near edge X-ray absorption fine structure(NEXAFS),and corroborated by density functional theory(DFT)calculations.Our results indicate that the alkali metal replaces the hydrogen atoms in the imide group and interact with the imide nitrogen of PTCDI.Electron transfer induced gap states and downward band-bending like effects are identified on the alkali-deposited PTCDI surface.It was found that Na shows a stronger electron transfer effect than Li.Such a model study of alkali insertion/intercalation in PTCDI gives insights for the exploration of the potential host materials for alkali storage applications.