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Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer:a multicenter,randomized,double-blinded,placebo-controlled,phaseⅡclinical trial

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Chinese Journal of Cancer 2017年第12期36卷 677-685页

作者： Rui-Hua xu Lin Shen Ke-Ming Wang Gang wu Chun-mei Shi Ke-Feng Ding Li-Zhu Lin Jin-Wan Wang Jian-Ping Xiong Chang-Ping wu Jin Li yun-Peng Liu Dong Wang Yi Ba Jue-Ping Feng Yu-Xian Bai jing-Wang Bi Li-wen Ma Jian Lei Qing yang Hao Yu Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060GuangdongP.R.China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteNo 52Fucheng RoadHaidian DistrictBeijing 100142P.R.China Department of Medical Oncology Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011JiangsuP.R.China Cancer Center of Union Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030HubeiP.R.China Department of Medical Oncology Fujian Medical University Union HospitalFuzhou 350001FujianP.R.China Department of Surgical Oncology Second Hospital Affiliated to Zhejiang University School of MedicineHangzhou 310009ZhejiangP.R.China Department of Oncology First Affiliated Hospital of Guangzhou Medical University of Chinese MedicineGuangzhou 510405GuangdongP.R.China Department of Medical Oncology Chinese Academy of Medical Sciences Cancer HospitalBeijing 100021P.R.China Department of Medical Oncology First Affiliated Hospital of Nanchang UniversityNanchang 330006JiangxiP.R.China Department of Medical Oncology First People’s Hospital of ChangzhouChangzhou 213003JiangsuP.R.China Department of Medical Oncology Fudan University Cancer HospitalShanghai 200032P.R.China Department of Medical Oncology First Hospital of China Medical UniversityShenyang 110001LiaoningP.R.China Cancer Center Daping Hospital and Institute of Surgery ResearchThird Military Medical UniversityChongqing 400042P.R.China Department of Gastrointestinal Medical Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060P.R.China Department of Oncology PuAi Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430032HubeiP.R.China Department of Medical Oncology Harbin Medical University Cancer Hospit

Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in ***: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and ***: Between July 18,2012 and Jan 22,2014, a total of 167 patients were screened, and 154 patients were randomized in a 2:1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002) and the ORR was 2.2% and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2 months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable *** registration This study was registered on ***(NCT01762293) and was orally presented in the 2015 ASCO-Gastrointestinal

关键词： Colorectal cancer Famitinib Efficacy Safety

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水泥与减水剂相容性的流变学研究

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华南理工大学学报（自然科学版） 2008年第7期36卷 117-123页

作者：吴笑梅文梓芸樊粤明华南理工大学材料科学与工程学院广东广州510640

通过考察水灰比、减水剂类型、水泥等因素对水泥与减水剂相容性及净浆流变性能的影响,研究相容性与浆体流变性能的关系,阐述了相容性的流变学含义.研究结果表明:掺减水剂的水泥净浆的流变特征符合一般宾汉姆流型或牛顿流型.Marsh筒法检... 详细信息

通过考察水灰比、减水剂类型、水泥等因素对水泥与减水剂相容性及净浆流变性能的影响,研究相容性与浆体流变性能的关系,阐述了相容性的流变学含义.研究结果表明:掺减水剂的水泥净浆的流变特征符合一般宾汉姆流型或牛顿流型.Marsh筒法检测的流速是浆体屈服应力和黏度系数的综合反映;饱和点掺量与饱和点Marsh时间分别代表了浆体屈服应力和黏度系数降低至最小恒定值时对应的减水剂最小掺量,以及最小黏度系数的大小.

关键词：水泥减水剂相容性流变学 Marsh筒法屈服应力黏度系数饱和点

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CD 147 receptor is essential for TFF3-mediated signaling regulating colorectal cancer progression

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Signal Transduction and Targeted Therapy 2021年第8期6卷 2521-2535页

作者： Hong-Yong Cui Shi-Jie Wang Fei Song xu Cheng Gang Nan Yu Zhao mei-Rui Qian Xi Chen Jia-yue Li Fen-Ling Liu Yu-Meng Zhu Ruo-Fei Tian Bin Wang Bin wu yang Zhang Xiu-xuan Sun Ting Guo Xiang-Min yang Hai Zhang Ling Li jing xu Hui-Jie Bian Jian-Li Jiang Zhi-Nan Chen National Translational Science Center for Molecular Medicine and Department of Cell Biology Fourth Military Medical UniversityXi'anChina Department of Urology Shenzhen Institute of Translational MedicineThe First Affiliated Hospital of Shenzhen UniversityShenzhen Second People's HospitalShenzhenChina Medical Research Institute School of MedicineWuhan UniversityWuhanChina College of Chemistry and Materials Science Northwest UniversityXi'anChina National Facility for Protein Science Shanghai Zhangjiang LabShanghai Advanced Research InstituteChinese Academy of SciencesShanghaiChina Medical Research Center Southern University of Science and Technology HospitalShenzhenChina

Major gaps in understanding the molecular mechanisms of colorectal cancer(CRC)progression and intestinal mucosal repair have hampered therapeutic development for gastrointestinal *** factor 3(TFF3)has been reported to be involved in CRC progression and intestinal mucosal repair;however,how TFF3 drives tumors to become more aggressive or metastatic and how TFF3 promotes intestinal mucosal repair are still poorly ***,we found that the upregulated TFF3 in CRC predicted a worse overall survival ***3 deficiency impaired mucosal restitution and ***147,a membrane protein,was identified as a binding partner for *** binding to CD147,TFF3 enhanced CD147-CD44s interaction,resulting in signal transducer and activator of transcription 3(STAT3)activation and prostaglandin G/H synthase 2(PTGS2)expression,which were indispensable for TFF3-induced migration,proliferation,and ***2-derived PGE2 bound to prostaglandin E2 receptor EP4 subtype(PTGER4)and contributed to TFF3-stimulated CRC *** NMR studies of the TFF3-CD147 interaction revealed the key residues critical for TFF3 binding and the induction of PTGS2 *** ability of TFF3 to enhance mucosal restitution was weakened by a PTGS2 *** of TFF3-CD147 signaling using competitive inhibitory antibodies or a PTGS2 inhibitor reduced CRC lung metastasis in *** findings bring strong evidence that CD147 is a novel receptor for TFF3 and PTGS2 signaling is critical for TFF3-induced mucosal restitution and CRC progression,which widens and deepens the understanding of the molecular function of trefoil factors.

关键词： TFF3 colorectal impaired

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Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition)

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World Journal of Pediatrics 2018年第5期14卷 437-447页

作者： Xing-Wang Li Xin Ni Su-yun Qian Quan Wang rong-Meng Jiang wen-Bo xu Yu-Cai Zhang Guang-Jun Yu Qiang Chen yun-Xiao Shang Cheng-Song Zhao Hui Yu Ting Zhang Gang Liu Hui-Ling Deng Jie Gao Xian-Gui Ran Qiao-Zhi yang Bian-Li xu xue-Yong Huang Xing-Dong wu Yi-Xiao Bao Yi-Ping Chen Zhi-Hai Chen Qing-Quan Liu Guo-Ping Lu Chun-Feng Liu rong-Bing Wang Guo-Liang Zhang Fang Gu Hong-mei xu Ying Li Tao yang Infectious Disease Diagnosis and Treatment Center Beijing Ditan Hospital Capital Medical UniversityBeijingChina Otorhinolaryngology Head andN eck Surgery Beijing Children’s HospitalCapital Medical UniversityBeijingChina Prediatric Intensive Care Unit Beijing Children’s Hospital of Capit al Medical UniversityBeijingChina National Institute For Viral Disease Control and Prevention Chinese Center for Disease Control and Pre ventionBeijingChina Children’s Hospital ofShanghai Jiaotong University ShanghaiChina Pneumology department Jiangxi Provincial Children’s HospitalNanchangChina Department of P ediatric Pneumology Shengjing Hospital of China Medical UniversityShenyangChina Department of Inf ectious Diseases Beijing Children’s HospitalCapital Medical UniversityBeijingChina Department of Inf ectious Diseases Children’s Hospital of Fudan UniversityShanghaiChina Digestive Department Children’s Hospital of Shanghai Jiaotong UniversityShanghaiChina Department of Inf ectious Diseases The Children’s Hospital of Xi'anXi’anChina Infection Control Offi ce Children’s Hospital ofShanghai Jiaotong UniversityShanghaiChina Department ofR espiratory Medicine People’s Hospital ofFuy ang CityFuyangChina Department of P ediatrics People’s Hospital of Liaoc heng CityLiaochengChina

Background Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treat-ments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. Methods National Health Commission of China assembled an expert committee for a revision of the guidelines. The com-mittee included 33 members who are specialized in diagnosis and treatment of HFMD. Results Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia;(2) involvement of nervous system;(3) worsening respiratory rate and rhythm;(4) circulatory dysfunction;(5) elevated peripheral WBC count;(6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. Conclusion The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

关键词： Diagnosis Guidelines HFMD Treatment

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Associations of Gonadotropin-Releasing Hormone Receptor (GnRHR) and Neuropeptide Y(NPY) Genes’Polymorphisms with Egg-Laying Traits in wenchang Chicken

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Agricultural Sciences in China 2007年第4期6卷 499-504页

作者： wu xu LI Hui-fang YAN mei-jiao TANG Qing-ping CHEN Kuan-wei WANG Jin-yu GAO Yu- shi TU yun-jie YU Ya-bo ZHU wen-qi Institute of Poultry Science Chinese Academy of Agricultural Sciences Yangzhou 225003 P.R.China College of Animal Science and Technology Yangzhou University Yangzhou 225009 P.R.China

Single nucleotide polymorphisms （SNP） of chicken gonadotropin-releasing hormone receptor （GnRHR） and neuropeptide Y （NPY） were selected to identify the genotypes of wenchang （Chinese indigenous breed） chicken with restricton fragment length polymorphisms. The associations of the SNPs with the total egg production （NE）, average days of continual laying （ADCL）, and number of double-yolked eggs （DYE） traits were analyzed. The frequency of restriction enzyme A/a alleles in the population was for GnRHR 0.69 （Bpu1102 Ⅰ A） and 0.31 （Bpu1102 Ⅰ a） and for NPY 0.46 （Dra Ⅰ B） and 0.54 （Dra Ⅰ b）. Trait data from a total of 120 hens, which were purebred introduced from Hainan Province, China from one generation were recorded. Two significant effects of genes＇ marker were found： for GnRHR and number of eggs （dominant; t= 2.67, df= 116） and NPY and number of eggs （additive; t= 1.97, df= 116）. The current research supports the effects of GnRHR and NPY genes on egg-laying traits of chickens.

关键词： chicken gonadotropin-releasing hormone receptor (GnRHR) neuropeptide Y (NPY) egg-laying traits single nucleotide polymorphisms (SNP)

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Low WT1 transcript levels at diagnosis predicted poor outcomes of acute myeloid leukemia patients with t(8;21) who received chemotherapy or allogeneic hematopoietic stem cell transplantation

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Chinese Journal of Cancer 2016年第7期35卷 350-358页

作者： Ya-zhen Qin Yu Wang Hong-Hu Zhu Robert Peter Gale mei-Jie Zhang Qian Jiang Hao Jiang Lan-Ping xu Huan Chen Xiao-Hui Zhang Yan-rong Liu yue-yun Lai Bin Jiang Kai-Yan Liu Xiao-Jun Huang Peking University People's Hospital Peking University Institute of HematologyBeijing Key Laboratory of Hematopoietic Stem Cell Transplantation No.11 Xizhimen South Street Beijing P.R. China Haematology Research Center Division of Experimental MedicineDepartment of MedicineImperial College London London SW72AZUK Biostatistics Division Medical College of Wisconsin Milwaukee WI53226USA Peking-Tsinghua Center for Life Sciences Beijing 100871P.R. China

Background:Acute myeloid leukemia(AML) with t(8;21) is a heterogeneous *** AML patients with t(8;21) who have a poor prognosis despite achieving remission is important for determining the best subsequent *** study aimed to evaluate the impact of Wilm tumor gene-1(WT1) transcript levels and cellular homolog of the viral oncogene v-KIT receptor tyrosine kinase(C-KIT) mutations at diagnosis,and RUNXTRUNX1T1 transcript levels after the second consolidation chemotherapy cycle on ***:Eighty-eight AML patients with t(8;21) who received chemotherapy only or allogeneic hematopoietic stem cell transplantation(allo-HSCT) were *** who achieved remission,received two or more cycles of consolidation chemotherapy,and had a positive measureable residual disease(MRD) test result(defined as <3-log reduction in RUNX1-RUNX1T1 transcript levels compared to baseline) after 2-8 cycles of consolidation chemotherapy were recommended to receive *** who had a negative MRD test result were recommended to receive further chemotherapy up to only 8 ***1 transcript levels and C-KIT mutations at diagnosis,and RUNX1-RUNX1T1 transcript levels after the second consolidation chemotherapy cycle were ***:Patients who had a C-KIT mutation had significantly lower WTl transcript levels than patients who did not have a C-KIT mutation(6.7%± 10.6%vs.19.5%± 19.9%,P < 0.001).Low WTl transcript levels(<5.0%) but not C-KIT mutation at diagnosis,a positive MRD test result after the second cycle of consolidation chemotherapy,and receiving only chemotherapy were independently associated with high cumulative incidence of relapse in all patients(hazard ratio[HR]= 3.53,2.30,and 11.49;95%confidence interval[CI]1.64-7.62,1.82-7.56,and 4.43-29.82;P = 0.002,0.034,and <0.001,respectively);these conditions were also independently associated with low leukemia-free survival(HR =3.71,2.33,and 5.85;95%CI 1.82-7.56,1.17-4.64,and 2.75-12.44;P < 0.00

关键词：异基因造血干细胞移植转录水平白血病 WT1 患者化疗诊断预后

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Plasma biomarkers and plaque strain predict long-term cardiovascular events in patients with acute coronary syndrome

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Science China(Life Sciences) 2020年第2期63卷 269-278页

作者： Mingjun xu Xiaobo Hu Lin Wang Wei Zhang Lindi wu Jifu Li Yuguo Chen Pengfei Zhang Haijun Su Yaling Han Cheng Zhang mei Zhang yun Zhang The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesThe State and Shandong Province Joint Key Laboratory of Translational Cardiovascular MedicineDepartment of CardiologyQilu Hospital of Shandong UniversityJinan 250012China Department of Intensive Care Unit Shandong Provincial Hospital affiliated to Shandong UniversityJinan 250012China School of Mathematics Shandong UniversityJinan 250012China Department of Cardiology Shenyang Military Region General HospitalShenyang 110016China

To test whether circulating and intracoronary biomarkers and coronary plaque strain have additive values to Global Registry of Acute Coronary Events(GRACE) score for predicting long-term cardiovascular events in ACS patients. One hundred ACS patients were enrolled and the GRACE score and plasma levels and intracoronary gradients of a number of biomarkers were measured. Coronary plaque burden and morphology in non-critical stenotic plaques were determined by intravascular ultrasound(IVUS) technique, and the maximal shear strain(SSmax) and maximal area strain(ASmax) were determined by intravascular ultrasound elastography(IVUSE) technique. Patients were followed for cardiovascular events and the predictive values of clinical characteristics, plasma biomarkers and plaque parameters were compared with GRACE score, and the incremental values of these measurements to the GRACE score were assessed. GRACE score, plasma biomarkers and plaque strain were independent predictors of cardiovascular events. Combination of GRACE score, plasma biomarkers and plaque strains significantly improved the predictive value of the GRACE score alone with the receiver-operating characteristic area increased from0.457 to 0.667(P=0.014). The combination of circulating and intracoronary biomarkers, plaque strain and GRACE score provides a better predictive tool than GRACE score alone in patients with ACS.

关键词： plasma biomarker plaque strain GRACE score cardiovascular events acute coronary syndrome

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Structure modification,antialgal,antiplasmodial,and toxic evaluations of a series of new marine-derived 14-membered resorcylic acid lactone derivatives

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Marine Life Science & Technology 2022年第1期4卷 88-97页

作者： Wei-Feng xu Na-Na wu Yan-Wei wu yue-xuan Qi mei-Yan Wei Laura M.Pineda Michelle G.Ng Carmenza Spadafora Ji-Yong zheng Ling Lu Chang-yun Wang Yu-Cheng Gu Chang-Lun Shao Key Laboratory of Marine Drugs the Ministry of Education of ChinaSchool of Medicine and PharmacyOcean University of ChinaQingdao266003China Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and TechnologyQingdao266237China State Key Laboratory for Marine Corrosion and Protection Luoyang Ship Material Research Institute(LSMRI)Qingdao266237China Center of Cellular and Molecular Biology of Diseases Instituto de Investigaciones Científcas y Servicios de Alta TecnologíaCity of KnowledgeClaytonApartado0816-02852Panama Syngenta Jealott’s Hill International Research Centre BracknellBerkshireRG426EYUK

Marine natural products play critical roles in the chemical defense of many marine organisms and are essential,reputable sources of successful drug ***-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol(1)isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination,acylation,esterification,and acetalization in one to three *** structures of these new derivatives were established by HRESIMS and NMR *** the compounds(1–71)were evaluated for their antialgal and antiplasmodial *** them,14 compounds displayed antifouling activities against adhesion of the fouling *** particular,9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua(EC50=6.67 and 8.55μmol/L),respectively,which were similar in efficacy to those of the positive control SeaNine 211(EC50=2.90 and 9.74μmol/L).More importantly,38,39,and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72μmol/*** interestingly,the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model,thus,representing potential promising antiplasmodial drug *** preliminary structure–activity relationships indicated that biphenyl substituent at C-2,acetonide at positions C-5′and C-6′,and tri-or tetra-substituted of acyl groups increased the antiplasmodial ***,combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy,not only for environmentally friendly antifoulants but also for structurally novel drugs.

关键词： Marine natural product 14-Membered resorcylic acid lactone Zeaenol Semisynthesis Antialgal activity Antiplasmodial activity

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A Novel Reassortant H3N8 Influenza Virus Isolated from Drinking Water for Duck in a Domestic Duck Farm in Poyang Lake Area

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Biomedical and Environmental Sciences 2013年第7期26卷 546-551页

作者： DONG Bei Bei xu Cui Ling DONG Li Bo CHENG Hui Jian yang Lei ZOU Shu mei CHEN Min BAI Tian ZHANG Ye GAO rong Bao LI Xiao Dan SHI jing Hong YUAN Hui yang jing CHEN Tao ZHU yun XIONG Ying yang Shuai SHU yue Long Chinese National Influenza Center National Institute for Viral Disease Control and Prevention China CDC School of Public Health Chinese Academy of Medical Sciences & Peking Union Medical College Jiangxi Province Center for Disease Control and Prevention

Objective To conduct a full genome sequence analysis for genetic characterization of an H3N8 influenza virus isolated from drinking water of a domestic duck farm in Poyang Lake area in 2011. Methods The virus was cultivated by specific pathogen free （SPF） chicken embryo eggs and was subtyped into hemagglutinin （HA） and neuraminidase （NA） by real-time PCR method. Eight gene segments were sequenced and phylogenetic analysis was conducted. Results The NA gene of this virus belongs to North American lineage; other seven genes belong to Eurasian lineage. Compared with the viruses containing NA gene, the PB2 and PB2 gene came from different clades. And this indicates that the virus was a novel reassortant genotype. The HA receptor binding preference was avian-like and the cleavage site sequence showed a low pathogenic feature. There was no drug resistance mutation of M2 protein. The mutations of Asn30Asp, and Thr225Ala of the M1 protein implied the potential of pathogenicity increase in mice. Conclusion The finding of novel genotype of H3N8 virus in drinking water in this duck farm near Poyang Lake highlighted the importance of strengthening the surveillance of avian influenza in this region, which could contribute to pinpointing the influenza ecological relations among avian, swine, and human.

关键词： Avian influenza H3N8 Sequence analysis

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某汽车涂装线机械设备的CE认证分析与总结

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现代涂料与涂装 2024年第4期27卷 40-42+49页

作者：刘聪王建凯岳丽霞何小伍崔建光许昀初吴谦中国汽车工业工程有限公司

以某汽车涂装生产线上机械设备CE认证的过程为例，梳理了CE认证的工作流程，介绍了产品认证过程中的相关指令和协调标准，总结了CE认证的模式，举例阐述了风险分析的过程，汇总了技术文件及符合性声明文件的主要构成，供后续类似项目中... 详细信息

以某汽车涂装生产线上机械设备CE认证的过程为例，梳理了CE认证的工作流程，介绍了产品认证过程中的相关指令和协调标准，总结了CE认证的模式，举例阐述了风险分析的过程，汇总了技术文件及符合性声明文件的主要构成，供后续类似项目中相关机械进行CE认证时做参考。

关键词：汽车涂装线机械设备 CE认证

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