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IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 103-113页

作者： yi-long wu Shun Lu Gongyan Chen Jianxing He Jifeng Feng yiping Zhang Liyan Jiang Hongming Pan Jianhua Chang Jian Fang Amy Cai Lilian Bu Jane Shi Jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China Department of Thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Medical Oncology Jiangsu Cancer HospitalNanjing 210009China Department of Medical Oncology Zhejiang Cancer HospitalHangzhou 330022China Department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Department of Medical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China Department of Thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-Yang Liu Song Dong Xue-Ning Yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji Yang Qing Zhou Hong-Rui Li Ke Liu Wendy wu Si-Yang Maggie Liu Wen-Zhao Zhong yi-long wu Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 expression.Eligible patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK alterations.Patients received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 expression.The primary endpoint was the major pathological response(MPR).Key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and EFS.Fifty-two patients were enrolled,with 46 undergoing surgeries.The MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,respectively.Thirteen(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment.Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–vs.ctDNA+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

Investigations of the mechanical response of dummy HTPB propellant grain under ultrahigh acceleration overload conditions using onboard flight-test measurements

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Defence Technology（防务技术） 2024年第2期32卷 473-484页

作者： yiming Zhang Ningfei Wang Weihua Ma Ran Wang long Bai yi wu School of Aerospace Engineering Beijing Institute of TechnologyBeijing 100081China Beijing System Design Institute of Electro-mechanic Engineering Beijing 100854China Xi'an Changfeng Research Institute of Mechanism and Electricity Xi'an 710065China

In this paper,to study the mechanical responses of a solid propellant subjected to ultrahigh acceleration overload during the gun-launch process,specifically designed projectile flight tests with an onboard measurement system were performed.Two projectiles containing dummy HTPB propellant grains were successfully recovered after the flight tests with an ultrahigh acceleration overload value of 8100 g.The onboard-measured time-resolved axial displacement,contact stress and overload values were successfully obtained and analysed.Uniaxial compression tests of the dummy HTPB propellant used in the gunlaunched tests were carried out at low and intermediate strain rates to characterize the propellant's dynamic properties.A linear viscoelastic constitutive model was employed and applied in finite-element simulations of the projectile-launching process.During the launch process,the dummy propellant grain exhibited large deformation due to the high acceleration overload,possibly leading to friction between the motor case and propellant grain.The calculated contact stress showed good agreement with the experimental results,though discrepancies in the overall displacement of the dummy propellant grain were observed.The dynamic mechanical response process of the dummy propellant grain was analysed in detail.The results can be used to estimate the structural integrity of the analysed dummy propellant grain during the gun-launch process.

关键词： Gun-launched flight test Dummy HTPB propellant Onboard measurements Utrahigh overload Mechanical response

Single-atom Ag-loaded carbon nitride photocatalysts for efficient degradation of acetaminophen:The role of Ag-atom and O_(2)

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Journal of Environmental Sciences 2024年第5期139卷 12-22页

作者： yi Yuan Wen-long Wang Zhi-Wei Wang Jin Wang Qian-Yuan wu Key Laboratory of Microorganism Application and Risk Control of Shenzhen Guangdong Provincial Engineering Research Center for Urban Water Recycling and Environmental SafetyInstitute of Environment and EcologyShenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China Shenzhen Environmental Science and New Energy Technology Engineering Laboratory Tsinghua-Berkeley Shenzhen InstituteShenzhen 518055China College of Materials Science and Engineering Shenzhen UniversityShenzhen 518071China

Carbon nitride has been extensively used as a visible-light photocatalyst,but it has the disadvantages of a low specific surface area,rapid electron-hole recombination,and relatively low light absorbance.In this study,single-atom Ag was successfully anchored on ultrathin carbon nitride(UTCN)via thermal polymerization,the catalyst obtained is called AgUTCN.The Ag hardly changed the carbon nitride's layered and porous physical *** exhibited efficient visible-light photocatalytic performances in the degradation of various recalcitrant pollutants,eliminations of 85% were achieved by visible-light irradiation for 1hr.Doping with Ag improved the photocatalytic performance of UTCN by narrowing the forbidden band gap from 2.49 to 2.36 e V and suppressing electron-hole pair recombination.In addition,Ag doping facilitated O_(2) adsorption on UTCN by decreasing the adsorption energy from -0.2 to -2.22 e V and favored the formation of O_(2)^(·-).Electron spin resonance and radical-quenching experiments showed that O_(2)^(·-)was the major reactive species in the degradation of Acetaminophen(paracetamol,APAP).

关键词： Ag single atom Carbon nitride Photocatalysis Visible light Adsorption energy Reactive species

Non-adiabatic holonomic quantum operations in continuous variable systems

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 12-19页

作者： Hao-long Zhang yi-Hao Kang Fan wu Zhen-Biao Yang Shi-Biao Zheng Fujian Key Laboratory of Quantum Information and Quantum Optics College of Physics and Information EngineeringFuzhou UniversityFuzhou 350116China

Quantum operations by utilizing the underlying geometric phases produced in physical systems are favoured due to their potential robustness.When a system in a non-degenerate eigenstate undergoes an adiabatically cyclic evolution dominated by its Hamiltonian,it will get a geometric phase,referred to as the Berry Phase.While a non-adiabatically cyclic evolution produces an Aharonov-Anandan geometric phase.The two types of Abelian geometric phases are extended to the non-Abelian cases,where the phase factors become matrix-valued and the transformations associated with different loops are non-commutable.Abelian and non-Abelian(holonomic)operations are prevalent in discrete variable systems,whose limited(say,two)energy levels,form the qubit.While their developments in continuous systems have also been investigated,mainly due to that,bosonic modes(in,such as,cat states)with large Hilbert spaces,provide potential advantages in fault-tolerant quantum computation.Here we propose a feasible scheme to realize non-adiabatic holonomic quantum logic operations in continuous variable systems with cat codes.We construct arbitrary single-qubit(two-qubit)gates with the combination of single-and two-photon drivings applied to a Kerr Parametric Oscillator(KPO)(the coupled KPOs).Our scheme relaxes the requirements of the previously proposed quantum geometric operation strategies in continuous variable systems,providing an effective way for quantum control.

关键词： cat qubit continuous variable systems non-Abelian

Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： yi Zhang Zhi-ying wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

Differential bonding behaviors of sodium/potassium-ion storage in sawdust waste carbon derivatives

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Chinese Chemical Letters 2024年第4期35卷 496-501页

作者： Jun-Ming Cao Kai-Yang Zhang Jia-Lin Yang Zhen-yi Gu Xing-long wu MOE Key Laboratory for UV Light-Emitting Materials and Technology Northeast Normal UniversityChangchun 130024China Department of Chemistry Northeast Normal UniversityChangchun 130024China

Sodium-ion batteries(SIBs) and potassium-ion batteries(PIBs) are the most promising alternatives to lithium-ion batteries, and thus have drawn intensive research attention. Porous carbon materials from different precursors have been widely used as anode materials owing to their compatible storage effectiveness of both larger radii sodium and potassium ions. However, the differential bonding behaviors of Na and K ions with porous carbon-based anode are the significant one worth investigating, which could provide a clean picture of alkali ions storage mechanism. Therefore, in this work, we prepare a porous carbon network derived from sawdust(SDC) wastes, to further analyze the differences on sodium and potassium ions storage behaviors in terms of bond-forming process. It is found that, as-prepared SDC anodes could deliver stable sodium and potassium storage capacities, however, there are notable distinctions in terms of electrochemical behaviors and diffusion processes. By virtue of ex-situ XRD and Raman spectroscopy, the phase transition reaction of potassium ions could be well-observed, and the results shows that the multiple intercalated compounds was formed in SDC network during ions insertion, further resulting in slower diffusion kinetics and larger resistance compared to non-bonded process of sodium ions storage. This study provides more insights into the differences between sodium and potassium ions storage, as well as the energy storage mechanism of porous carbon as anodes for secondary batteries.

关键词： Porous carbon Sodium-ion storage Potassium-ion storage Bonding behaviors Batteries

Almost Periodic Type Group Actions on Compact Quantum Metric Spaces

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Acta Mathematica Sinica,English Series 2024年第2期40卷 568-594页

作者： Bo Tao long Wei wu College of Mathematics MIIT Key Laboratory of Mathematical Modelling and High Performance Computing of Air VehiclesNanjing University of Aeronautics and AstronauticsNanjing 211106P.R.China School of Mathematical Sciences Shanghai Key Laboratory of Pure Mathematics and Mathematical PracticeEast China Normal UniversityShanghai 200241P.R.China

A compact quantum metric space is a complete order unit space A endowed with a Lipnorm L.We give some characterizations of almost periodic type group actions on a compact quantum metric space(A,L)by means of several kinds of subsets of A,its induced equicontinuous actions on several important subsets of the dual Banach space A*,and the Lip-norm L with its induced metric space structures on the state space S(A)of A.

关键词： Lip-norm compact quantum metric space Lipschitz isomorphism almost periodicity Arzela-Ascoli theorem metric set

Early colorectal cancer screening–no time to lose

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World Journal of Gastroenterology 2024年第23期30卷 2959-2963页

作者： ying Wang Zheng-long wu yi-Gang Wang Hui Wang Xiao-Yuan Jia College of Life Sciences and Medicine Zhejiang Sci-Tech UniversityHangzhou 310018Zhejiang ProvinceChina Department of Oncology Zhejiang Xiaoshan HospitalHangzhou 310018Zhejiang ProvinceChina

In this editorial,we comment on the article entitled“Stage at diagnosis of colorectal cancer through diagnostic route:Who should be screened?”by Agatsuma et al.Colorectal cancer(CRC)is emerging as an important health issue as its incidence continues to rise globally,adversely affecting the quality of life.Although the public has become more aware of CRC prevention,most patients lack screening awareness.Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC.However,due to the lack of awareness of the disease,most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.

关键词： Colorectal cancer The immunochemical fecal occult blood test Diagnostic route Cancer screening Stage at diagnosis