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| 1 | Structures of EV71 RNA-dependent RNA polymerase in complex with substrate and analogue provide a drug target against the hand-foot-and-mouth disease pandemic in China显示文摘Enterovirus 71(EV71),one of the major causative agents for hand-foot-and-mouth disease(HFMD),has caused more than 100 deaths among Chinese children since March 2008.The EV71 genome encodes an RNAdependent RNA polymerase(RdRp),denoted 3D^(pol),which is central for viral genome replication and is a key target for the discovery of specific antiviral therapeutics.Here we report the crystal structures of EV71 RdRp(3D^(pol))and in complex with substrate guanosine-5'-triphosphate and analog 5-bromouridine-5'-triphosphate best to 2.4Åresolution.The structure of EV71 RdRp(3D^(pol))has a wider open thumb domain compared with the most closely related crystal structure of poliovirus RdRp.And the EV71 RdRp(3D^(pol))complex with GTP or Br-UTP bounded shows two distinct movements of the polymerase by substrate or analogue binding.The model of the complex with the template:primer derived by superimposition with foot-and-mouth disease virus(FMDV)3D/RNA complex reveals the likely recognition and binding of template:primer RNA by the polymerase.These results together provide a molecular basis for EV71 RNA replication and reveal a potential target for anti-EV71 drug discovery. | Yang Wu Zhiyong Lou Yi Miao Yue Yu Hui Dong Wei Peng Mark Bartlam Xuemei Li Zihe Rao | 2010 | Protein & Cell2010，1，5： | 30 |
| 2 | A structural view of the antibiotic degradation enzyme NDM-1 from a superbug显示文摘Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1(NDM-1)are a type of newly discovered antibioticresistant bacteria.The rapid pandemic spread of NDM-1 bacteria worldwide(spreading to India,Pakistan,Europe,America,and Chinese Taiwan)in less than 2 months characterizes these microbes as a potentially major global health problem.The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations.The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics,allowing the bacteria to escape the action of antibiotics.Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues,the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified.Here,we report the threedimensional structure of NDM-1 with two catalytic zinc ions in its active site.Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity.The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases(MBLs)and implicate its role in wide spectrum drug resistance.We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria.Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases. | Yu Guo Jing Wang Guojun Niu Wenqing Shui Yuna Sun Honggang Zhou Yaozhou Zhang Cheng Yang Zhiyong Lou Zihe Rao | 2011 | Protein & Cell2011，2，5： | 16 |
| 3 | Application of next-generation sequencing technology to precision medicine in cancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology显示文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation. | Xuchao Zhang Zhiyong Liang Shengyue Wang Shun Lu Yong Song Ying Cheng Jianming Ying Weiping Liu Yingyong Hou Yangqiu Li Yi Liu Jun Hou Xiufeng Liu Jianyong Shao Yanhong Tai Zheng Wang Li Fu Hui Li Xiaojun Zhou Hua Bai Mengzhao Wang You Lu Jinji Yang Wenzhao Zhong Qing Zhou Xuening Yang Jie Wang Cheng Huang Xiaoqing Liu Xiaoyan Zhou Shirong Zhang Hongxia Tian Yu Chen Ruibao Ren Ning Liao Chunyan Wu Zhongzheng Zhu Hongming Pan Yanhong Gu Liwei Wang Yunpeng Liu Suzhan Zhang Tianshu Liu Gong Chen Zhimin Shao Binghe Xu Qingyuan Zhang Ruihua Xu Lin Shen Yilong Wu | 2019 | Cancer Biology & Medicine2019，16，1： | 14 |
| 4 | Different aspects of cognitive function in adult patients with moyamoya disease and its clinical subtypes显示文摘Objective Although a few reports suggested that cognitive function impairment could be found in adult patients with moyamoya disease(MMD),there were still many aspects that are unclear.The aim of our study was to assess the cognitive function of adult patients with MMD and its clinical subtypes.Methods 49 patients with MMD and 23 healthy controls were asked to take cognitive function tests.Cognitive function tests included IQ,prospective memory(PM),immediate memory(IM),verbal fluency(VF),visual breadth,attention,retrospective memory(RM),Stroop test,Wisconsin Card Sorting Test,Trail-Making Test Part A(TMT-A)and Continuous Performance Test(CPT).Independent t-analysis,one-way analysis of variance and Pearson correlation were used to seek for differences between subgroups and the correlation between cognitive variables.results Compared with healthy controls,adult patients with MMD had a comprehensive cognitive impairment,including IQ,PM,VF,attention,RM,Stroop,CPT and TMT-A,with more serious impairment in PM and attention.PM and RM were separated,indicating that they were independent of each other.Pattern of attention was significantly different from healthy controls.Female patients were better than male patients,where significant differences in PM,IM,Stroop and WCST could be found.The haemorrhagic patients exhibited poorer in the dimension of PM and RM than the ischaemic.The headache subtype exhibited poorer than healthy controls.PM,RM,attention and executive function were moderately correlated with each other.Conclusions Adult patients with MMD had a wide range of cognitive impairment with more serious impairment in memory and attention.Differences in cognitive function existed between the different subtypes of adult MMD. | Zhiyong Shi Yu-Jie Wen Zheng Huang Le-Bao Yu Dong Zhang | 2020 | Stroke & Vascular Neurology2020，5，1： | 12 |
| 5 | The newly emerged SARS-Like coronavirus HCoV-EMC also has an “Achilles’ heel”: current effective inhibitor targeting a 3C-like protease显示文摘From the global outbreak of SARS-CoV caused infection disease in 2003,coronaviruses(CoVs)are known to be a great threat to the human health.Recently,a new SARS-like coronavirus,human betacoronavirus 2c EMC/2012(HCoV-EMC),has been identified and the appearance of this new CoV raises concerns that a new spread of CoV may occurs in the future.By solving the crystal structure of HCoV-EMC main protease with a wide-spectrum anti-CoV inhibitor N3,we confi rmed that that N3 blocks the function of HCoV-EMC main protease through a similar mechanism to other CoVs.Together with the good pharmaceutical features,N3 is conceivable to be effective to HCoV-EMC and other CoVs appearing in the future.These fi ndings make it convincing that CoVs will not be a threat to human health. | Zhilin Ren Liming Yan Ning Zhang Yu Guo Cheng Yang Zhiyong Lou Zihe Rao | 2013 | Protein & Cell2013，4，4： | 10 |
| 6 | Mechanical properties of electron beam welded dissimilar joints of TC17 and Ti60 alloys显示文摘Microstructure, hardness, tensile and high cycle fatigue(HCF) properties of the welded dissimilar joints of Ti60 and TC17 titanium alloys had been investigated in this study. A significant microstructural change was observed to occur after welding, with rod-like α and β phases in the fusion zone(FZ), equiaxed αphases, fine α laths and β phases in the heat-affected zone(HAZ) of TC17 side and acicular martensiteα' phases+ 'ghost' α phases in the HAZ of Ti60 side. The microhardness across the joints exhibited an inhomogeneous distribution with the highest hardness of ~404 HV in FZ and the lowest hardness of^304 HV in base material(BM) of Ti60. All the joints tested in tension fractured at BM of Ti60 side.Fatigue limits of the joints at 107 cycles were 425 MPa at room temperature and 380 MPa at 400℃,respectively. Welding micropores were found to be the main source of fatigue crack initiation. | Chao Cheng Bingbing Yu Zhiyong Chen Jianrong Liu Qingjiang Wang | 2018 | Journal of Materials Science & Technology2018，34，10： | 10 |
| 7 | Impact of Coastal Radar Observability on the Forecast of the Track and Rainfall of Typhoon Morakot(2009)Using WRF-based Ensemble Kalman Filter Data Assimilation显示文摘This study explored the impact of coastal radar observability on the forecast of the track and rainfall of Typhoon Morakot(2009)using a WRF-based ensemble Kalman filter(EnKF)data assimilation(DA)system.The results showed that the performance of radar EnKF DA was quite sensitive to the number of radars being assimilated and the DA timing relative to the landfall of the tropical cyclone(TC).It was found that assimilating radial velocity(Vr)data from all the four operational radars during the 6 h immediately before TC landfall was quite important for the track and rainfall forecasts after the TC made landfall.The TC track forecast error could be decreased by about 43% and the 24-h rainfall forecast skill could be almost tripled.Assimilating Vr data from a single radar outperformed the experiment without DA, though with less improvement compared to the multiple-radar DA experiment.Different forecast performances were obtained by assimilating different radars, which was closely related to the first-time wind analysis increment, the location of moisture transport, the quasi-stationary rainband, and the local convergence line.However, only assimilating Vr data when the TC was farther away from making landfall might worsen TC track and rainfall forecasts.Besides, this work also demonstrated that Vr data from multiple radars, instead of a single radar, should be used for verification to obtain a more reliable assessment of the EnKF performance. | Jian YUE Zhiyong MENG Cheng-Ku YU Lin-Wen CHENG | 2017 | Advances in Atmospheric Sciences2017，34，1： | 8 |
| 8 | Tianshanbeilu and the Isotopic Millet Road: reviewing the late Neolithic/Bronze Age radiation of human millet consumption from north China to Europe显示文摘The westward expansion of human millet consumption from north China has important implications for understanding early interactions between the East and West.However,few studies have focused on the Xinjiang Uyghur Autonomous Region,the vast geographical area directly linking the ancient cultures of the Eurasian Steppe and the Gansu Corridor of China.In this study,we present the largest isotopic investigation of Bronze Age China(n=110)on material from the key site of Tianshanbeilu,in eastern Xinjiang.The large range ofδ13C values(–17.6 to–7.2;–15.5±1.2)provides direct evidence of unique dietary diversity and consumption of significant C4 resources(millets).The highδ15N results(10.3 to 16.7;14.7±0.8)likely reflect sheep/goat and wild game consumption and the arid climate of the Taklamakan Desert.Radiocarbon dates from four individuals indicate Tianshanbeilu was in use between 1940 and1215 cal bc.The Tianshanbeilu results are then analysed with respect to 52 Bronze Age sites from across Eurasia,to investigate the spread and chronology of significant human millet consumption and human migration.This isotopic survey finds novel evidence that the second millennium bc was a dynamic period,with significant dietary interconnectivity occurring between north China,Central Asia and Siberia.Further,we argue that this‘Isotopic Millet Road’extended all the way to the Mediterranean and Central Europe,and conclude that these C4 dietary signatures of millet consumption reflect early links(migration and/or resource transfer)between the Bronze Age inhabitants of modern-day China and Europe. | Tingting Wang Dong Wei Xien Chang Zhiyong Yu Xinyu Zhang Changsui Wang Yaowu Hu Benjamin T.Fuller | 2019 | National Science Review2019，6，5： | 8 |
| 9 | Multi-Agent Reinforcement Learning for Resource Allocation in Io T Networks with Edge Computing显示文摘To support popular Internet of Things(IoT)applications such as virtual reality and mobile games,edge computing provides a front-end distributed computing archetype of centralized cloud computing with low latency and distributed data processing.However,it is challenging for multiple users to offload their computation tasks because they are competing for spectrum and computation as well as Radio Access Technologies(RAT)resources.In this paper,we investigate computation offloading mechanism of multiple selfish users with resource allocation in IoT edge computing networks by formulating it as a stochastic game.Each user is a learning agent observing its local network environment to learn optimal decisions on either local computing or edge computing with a goal of minimizing long term system cost by choosing its transmit power level,RAT and sub-channel without knowing any information of the other users.Since users’decisions are coupling at the gateway,we define the reward function of each user by considering the aggregated effect of other users.Therefore,a multi-agent reinforcement learning framework is developed to solve the game with the proposed Independent Learners based Multi-Agent Q-learning(IL-based MA-Q)algorithm.Simulations demonstrate that the proposed IL-based MA-Q algorithm is feasible to solve the formulated problem and is more energy efficient without extra cost on channel estimation at the centralized gateway.Finally,compared with the other three benchmark algorithms,it has better system cost performance and achieves distributed computation offloading. | Xiaolan Liu Jiadong Yu Zhiyong Feng Yue Gao | 2020 | China Communications2020，17，9： | 7 |
| 10 | LncRNA NEF is downregulated in triple negative breast cancer and correlated with poor prognosis显示文摘LncRNA NEF has been proved to be a tumor suppressor in liver cancer. In the present study, we found that lncRNA NEF was downregulated and miRNA-155 was upregulated in plasma of triplenegative breast cancer (TNBC) patients compared with those in controls. These two factors were inversely correlated only in TNBC patients but not in controls. Altered expression of lncRNA NEF and miRNA-155 distinguished TNBC patients from healthy controls. Follow-up study showed that low level of lncRNA NEF and high level of miRNA-155 were correlated with poor survival. LncRNA NEF overexpression inhibited the migration and invasion of TNBC cells, while miRNA-155 overexpression promoted the migration and invasion of TNBC cells, but showed no significant effects on cancer cell proliferation. MiRNA-155 overexpression partially rescued the inhibited cell migration and invasion caused by lncRNA NEF overexpression. LncRNA NEF overexpression inhibited miRNA-155 expression, while miRNA-155 overexpression showed no significant effect on lncRNA NEF expression. Therefore, lncRNA NEF may participate in TNBC by negatively regulating miRNA- 155. | Xiang Song Zhaoyun Liu Zhiyong Yu | 2019 | Acta Biochimica et Biophysica Sinica2019，51，4： | 7 |
| 11 | Research into magnetic guidance technology for directional drilling in SAGD horizontal wells显示文摘SAGD horizontal wells are used to enhance oil recovery from heavy oil reservoirs.This technology requires precise separation between the production well and the injection well to ensure the efficient drainage of the reservoir.By studying the attitude of the downhole probe tube and the production well trajectory,an algorithm is proposed for eliminating ferromagnetic interference while drilling injection wells.A high accuracy filter circuit has been designed to correct the detected magnetic signals,which are ultra-weak,frequency-instable,and narrow-band.The directional drilling magnetic guidance system(DD-MGS) has been developed by integrating these advanced techniques.It contains a sub-system for the ranging calculation software,a magnetic source,a downhole probe tube and a sub-system for collecting & processing the detected signals.The DD-MGS has succeeded in oilfield applications.It can guide the directional drilling trajectory not only in the horizontal section but also in the build section of horizontal injection wells.This new technology has broad potential applications. | Gao Deli Diao Binbin Wu Zhiyong Zhu Yu | 2013 | Petroleum Science2013，10，4： | 7 |
| 12 | Simultaneous quantification of fifty-one odor-causing compounds in drinking water using gas chromatography-triple quadrupole tandem mass spectrometry显示文摘A wide range of compounds with various structural features can cause taste and odor(T&O)problems in drinking water. It would be desirable to determine all of these compounds using a simple analytical method. In this paper, a sensitive method combining liquid–liquid extraction(LLE) with gas chromatography-triple quadrupole tandem mass spectrometry(GC–MS/MS)was established to simultaneously analyze 51 odor-causing compounds in drinking water,including organic sulfides, aldehydes, benzenes, phenols, ethers, esters, ketones, nitrogenous heterocyclic compounds, 2-methylisoborneol and geosmin. Three deuterated analogs of target analytes, dimethyl disulfide-d6, benzaldehyde-d6 and o-cresol-3,4,5,6-d4,were used to correct the variations in recovery, and five isotope-labeled internal standards(4-chlorotoluene-d4, 1, 4-dichlorobenzene-d4, naphthalene-d8, acenaphthene-d10, phenanthrene-d10 respectively) were used prior to analysis to correct the variations arising from instrument fluctuations and injection errors. The calibration curves of the target compounds showed good linearity(R2> 0.99, level = 7),and method detection limits(MDLs) below 1/10 of the odor threshold concentrations were achieved for most of the odorants(0.10–20.55 ng/L). The average recoveries of most of the analytes in tap water samples were between 70% and 120%, and the method was reproducible(RSD < 20%, n = 7). Additionally, concentrations of odor-causing compounds in water samples collected from three drinking water treatment plants(DWTPs) were analyzed by this method.According to the results, dimethyl trisulfide, dimethyl disulfide and indole were considered to be the key odorants responsible for the swampy/septic odor. 2-Methylisoborneol and geosmin were detected as the main odor-causing compounds for musty/earthy odor in DWTP B. | Chunmiao Wang Jianwei Yu Qingyuan Guo Yu Zhao Nan Cao Zhiyong Yu Min Yang | 2019 | Journal of Environmental Sciences2019，31，5： | 7 |
| 13 | Remarkably enhanced water splitting activity of nickel foam due to simple immersion in a ferric nitrate solution显示文摘到一个高效的电极具有到碱的水电解的申请的首要的重要性的构造的一个灵巧的方法的发展。这里,我们报导向氧进化反应(OER ) 的镍泡沫(NF ) 的活动能在铁的硝酸盐通过简单沉浸显著地被提高(Fe (在房间温度的没有 3)3) 溶液。在这个沉浸过程期间,由没有 3 离子的 NF 表面的氧化增加近表面的集中哦导致的 和 Ni 2+, 在里面高度活跃的非结晶的 Ni-Fe 氢氧化物的 situ 免职(a-NiFeO x H y ) 层。明确地, NF 电极的 OER 过电位从 371 mV (赤裸的 NF )减少到 270 mV (@ 10 妈眭瑡牥獡楳瑳摥???????????????????慮潮畴敢?????????????? 鞤 吗?? | Huajie Yin Lixue Jiang Porun Liu Mohammad AI-Mamun Yun Wang Yu Lin Zhong Huagui Yang Dan Wang Zhiyong Tang Huijun Zhao | 2018 | Nano Research2018，11，8： | 6 |
| 14 | The effect of 2,4-diamino-6-hydroxy-pyrimidine on PoStburn Staphylococcus aureus sepsis in rats显示文摘Objective;GTP-cyclohydrolase I (GTP-CHI) is the first and rate-limiting enzyme for the de novo bio-synthesis of biopterin.The present study was to observe the effect of 2,4-diamino-6-hydroxy-pyrimidine (DAHP),an inbibtor of GTP-CHI,on the development of postburn Staphylococcus aureus sepsis.Methods;56 male Wistarrats were randomly divided into four groups as follows;normal control group (n=10),scald control group(n=10),postburn sepsis group (n=20) and DAHP treatment group (n=16).In the scald control gro... | Li Hongyun Yao Yongming Shi ZhiGuo Dong Ning Yu Yan Lu Lianrong Sheng Zhiyong (C.Y.Sheng) Research Department of Burn Institute,304th Hospital of PLA,Beijing 100037 | 2002 | 感染.炎症.修复2002，3，1： | 6 |
| 15 | Insight into the Ebola virus nucleocapsid assembly mechanism: crystal structure of Ebola virus nucleoprotein core domain at 1.8 A resolution显示文摘 | Shishang Dong Peng Yang Guobang Li Baocheng Liu Wenming Wang Xiang Liu Boran Xia Cheng Yang Zhiyong Lou Yu Guo Zihe Rao | 2015 | Protein & Cell2015，6，5： | 6 |
| 16 | Construction of plasmid vector pAFP-HSVtk-IRES2-EGFP and its effect on the cytotoxicity of ganciclovir to hepatocellular carcinoma显示文摘 | Lai Zhiyong Qin Qin Yu Baofeng Xie Jun Gao Ranpeng Zhang Tiantian Li Chunfeng Niu Kai Xu Jun | 2014 | Chinese Medical Journal2014，，12： | 6 |
| 17 | Realization of low contact resistance close to theoretical limit in graphene transistors显示文摘认识到在 graphene 和金属电极之间的低接触抵抗为造高效的 graphene 设备仍然是著名挑战。在这个工作,我们试图在 graphene 晶体管减少接触抵抗并且进一步探索在 graphene 和金属接触之间的抵抗限制。在房间温度的 Pd/graphene 接触抵抗在 100 ?? 下面被减少 ? ?? 汣獡 ? 愢瀭畬 ? 汰獵?? 猯'T ￣慮潮慰瑲捩敬 ? 敤潣慲整 ? 湯吠佩猼'T 挠慬獳∽ ? 汰獵瀭畬 ? 资 ? ?? 渠湡景扩牥 ? 湥 'L 敬 ? 桴 ? ?捣獥晳汵椠瑮来慲楴湯漠 ? 桴 ? 楢慮祲挠浯潰楳整椠瑮 ? 慢瑴牥敩 ? 潴愠摤敲獳猠牴 ' 壮霊 `? 瑳 'L 汩瑩 ? 湡 ? 潬 ? 慣慰楣吗? | Hua Zhong Zhiyong Zhang Bingyan Chen Haitao Xu Dangming Yu Le Huang Lianmao Peng | 2015 | Nano Research2015，8，5： | 5 |
| 18 | Leaching behavior of enrofloxacin in three different soils and the influence of a surfactant on its mobility显示文摘The leaching behaviors of enrofloxacin (ENR), a fluoroquinolone group antibiotic, in three different standard soils, namely sandy, loamy sand and sandy loam were investigated according to OECD guideline 312. In addition, the effects of tenside, sodium dodecylbenzenesulfonate (DBS) on the mobility of ENR in two different soils were studied. The mobility of ENR in all three standard soils was very similar and was mostly (98%) concentrated on the top 0-5 cm segment of the soils at pH 5.7. The DBS can enhance the mobility of ENR in soils but the impact was in general negligible under the studied conditions. | Zhiyong Yu Ayfer Yediler Min Yang Sigurd Schulte-Hostede | 2012 | Journal of Environmental Sciences2012，24，3： | 5 |
| 19 | Mechanism and technology study of collaborative support with long and short bolts in large-deformation roadways显示文摘Common short bolts of equal length are widely used to support the roofs of roadways in coal mines.However, they are insufficient to keep the roof stable against large deformations, so docking long bolts with high levels of elongation that can adapt to large deformations of the surrounding rock have been adopted. This paper proposes a collaborative support method that uses long and short bolts. In this study,the mechanism of docking long bolts and collaborative support was studied. Numerical simulation, similarity simulation, and field testing were used to analyze the distribution law of the displacement, stress,and plastic failure in the surrounding rock under different support schemes. Compared with the equal-length short bolt support, the collaborative support changed the maximum principal stress of the shallow roof from tensile stress to compressive stress, and the minimum principal stress of the roof significantly increased. The stress concentration degree of the anchorage zone clearly increased. The deformation of the roof and the two sides was greatly reduced, and the subsidence shape of the shallow roof changed from serrated to a smooth curve. The roof integrity was enhanced, and the roof moved down as a whole. Plastic failure significantly decreased, and the plastic zone of the roof was within the anchorage range. The similarity simulation results showed that, under the maximum mining stress,the roof collapsed with the equal-length short bolt support but remained stable with the collaborative support. The collaborative support method was successfully applied in the field and clearly improved the stability of the surrounding rock for a large deformation roadway. | Yu Hui Niu Zhiyong Kong Linggen Hao Caicheng Cao Peng | 2015 | International Journal of Mining Science and Technology2015，25，4： | 5 |
| 20 | Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial显示文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting. | Yuankai Shi Kaijian Lei Yuming Jia Bingqiang Ni Zhiyong He Minghong Bi Xicheng Wang Jianhua Shi Ming Zhou Qian Sun Guolei Wang Dongji Chen Yongqian Shu Lianke Liu Zhongliang Guo Yong Liu Junquan Yang Ke Wang Ke Xiao LinWu Tienan Yi Debin Sun Mafei Kang Tianjiang Ma Yimin Mao Jinsheng Shi Tiegang Tang Yan Wang Puyuan Xing Dongqing Lv Wangjun Liao Zhiguo Luo Bin Wang Xiaohong Wu Xiaoli Zhu Shuhua Han Qisen Guo Rongyu Liu Zhiwei Lu Jianyong Zhang Jian Fang Changlu Hu Yinghua Ji Guolong Liu Hong Lu Dedong Wu Junhong Zhang Shuyang Zhu Zheng Liu Wensheng Qiu Feng Ye Yan Yu Yanqiu Zhao Qinhong Zheng Jun Chen Zhanyu Pan Yiping Zhang Wenjuan Lian Bo Jiang Bo Qiu Guojun Zhang Hua Zhang Yanju Chen Yuan Chen Hongbing Duan Manxiang Li Shengming Liu Lijun Ma Hongming Pan Xia Yuan Xueli Yuan Yulong Zheng Emei Gao Li Zhao Shumin Wang Can Wu | 2021 | Cancer Communications2021，41，9： | 5 |
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