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96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients

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Journal of Clinical and Translational Hepatology 2023年第3期11卷 649-660页

作者： Zhihong Liu Qinglong Jin Yuexin Zhang Guozhong Gong Guicheng Wu Lvfeng Yao Xiaofeng Wen Zhiliang Gao Yan Huang Daokun Yang Enqiang Chen Qing Mao Shide Lin Jia Shang Huanyu Gong Lihua Zhong Huafa Yin Fengmei Wang Peng Hu Qiong Wu Chao Pan Wen Jia Chuan Li Chang’an Sun Junqi Niu Jinlin Hou TMF Study Group Department of Infectious Diseases and Hepatology Unit Institutes of Liver Diseases Research of Guangdong ProvinceNan-fang HospitalSouthern Medical UniversityGuangzhouGuangdongChina The First Hospital of Jilin University Chang-chunJilinChina The First Affiliated Hospital of Xinjiang Medical University UrumqiXinjiangChina The Second Xiangya Hospital of Central South University ChangshaHunanChina Chongqing University Three Gorges Hospital ChongqingChina Mengchao Hepatobiliary Hospital of Fujian Medical University FuzhouFujianChina Liuzhou People’s Hospital LiuzhouGuangxiChina The Third Affiliated Hospital of Zhongshan University GuangzhouGuangdongChina Xiangya Hospital of Central South University ChangshaHunanChina The First Affiliated Hospital of Xinxiang Medical University XinxiangHenanChina West China Hospital of Sichuan University ChengduSichuanChina The Southwest Hospi-tal of AMU ChongqingChina Affiliated Hospital of Zunyi Medical University ZunyiGuizhouChina Henan Provincial People’s Hospital ZhengzhouHenanChina The Third Xiangya Hospital of Central South University ChangshaHunanChina The Fourth Affiliated Hospital of Harbin Medical University HarbinHeilongjiangChina The First Affiliated Hospi-tal of Anhui Medical University HefeiAnhuiChina Tianjin Third Central Hospital TianjinChina The Second Affiliated Hospital of Chongqing Medical University ChongqingChina Jiangsu Hansoh Pharmaceutical Group Co. LtdLianyungangJiangsuChina Members listed in the Supplementary File 1

Background and Aims:Tenofovir amibufenamide(TMF)is a novel phosphoramidated prodrug of tenofovir with nonin-ferior efficacy and better bone and renal safety to tenofovir disoproxil fumarate(TDF)in 48 weeks of ***,we update 96-week comparison ***:Patients with chronic hepatitis B were assigned(2:1)to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 *** virological suppression was defined as HBV DNA levels<20 IU/mL at week *** was evaluated thoroughly with focusing on bone,renal,and metabolic ***:Virological suppression rates at week 96 were similar between TMF and TDF group in both HBeAg-positive and HBeAg-negative *** efficacy was maintained in the pooled population,while it was first achieved in patients with HBV DNA≥7 or 8 log10 IU/mL at ***-indexed estimated glomerular filtration rate for renal safety assessment was adopted,while a smaller decline of which was seen in the TMF group than in the TDF group(p=0.01).For bone mineral density,patients receiv-ing TMF displayed significantly lower reduction levels in the densities of spine,hip,and femur neck at week 96 than those receiving *** addition,the lipid parameters were stable after week 48 in all groups while weight change still showed the opposite ***:TMF maintained similar efficacy at week 96 compared with TDF with continued superior bone and renal safety profiles(NCT03903796).

关键词： Hepatitis B Liver function tests Viral hepatitis Liver Osteoporosis

The heterogeneity of islet autoantibodies and the progression of islet failure in type 1 diabetic patients

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Science China(Life Sciences) 2016年第9期59卷 930-939,938-939+932-937页

作者： Jin Liu Lingling Bian Li Ji Yang Chen Heng Chen Yong Gu Bingqin Ma Wei Gu Xinyu Xu Yun Shi Jian Wang Dalong Zhu Zilin Sun Jianhua Ma Hui Jin Xing Shi Heng Miao Bing Xin Yan Zhu Zhenwen Zhang Ruifang Bu Lan Xu Guangde Shi Wei Tang Wei Li Dongmei Zhou Jun Liang Xingbo Cheng Bimin Shi Jixiang Dong Ji Hu Chen Fang Shao Zhong Weinan Yu Weiping Lu Chenguang Wu Li Qian Jiancheng Yu Jialin Gao Xiaoqiang Fei Qingqing Zhang Xueqin Wang Shiwei Cui Jinluo Cheng Ning Xu Guofeng Wang Guoqing Han Chunrong Xu Yun Xie Minmin An Wei Zhang Zhixiao Wang Yun Cai Qi Fu Yu Fu Shuai Zheng Fan Yang Qingfang Hu Hao Dai Yu Jin Zheng Zhang Kuanfeng Xu Yifan Li Jie Shen Hongwen Zhou Wei He Xuqin Zheng Xiao Han Liping Yu Jinxiong She Mei Zhang Tao Yang Department of Endocrinology and Metabolism First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China Barbara Davis Center for Childhood Diabetes University of Colorado Denver Aurora Colorado 80045 USA Key Laboratory of Human Functional Genomics of Jiangsu Province Nanjing Medical University Nanjing 210000 China Department of Isotopic Laboratory of Nanjing Medical University Nanjing 210000 China HLA Laboratory of Jiangsu Province People's Hospital Nanjing 210029 China Department of Endocrinology and Metabolism Nanjing General Hospital of Nanjing Military Command Nanjing 210002 China Department of Endocrinology and Metabolism Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing 210008 China Department of Endocrinology and Metabolism Zhongda Hospital Southeast University Nanjing 210009 China Department of Endocrinology and Metabolism Nanjing First Hospital Nanjing 210000 China Department of Endocrinology and Metabolism Nanjing Children's Hospital Nanfing 210008 China Department of Endocrinology and Metabolism The Second Affiliated Hospital of Nanjing Medical University Nanjing 210011 China Department of Endocrinology and Metabolism Nanjing Governmental Hospital Nanjing 210008 China Department of Endocrinology and Metabolism Northern Jiangsu People's Hospital Yangzhou 225001 China Department of Endocrinology and Metabolism Wuxi People's Hospital Wuxi 214023 China Department of Endocrinology and Metabolism Jiangsu Jiangyin People's Hospital Wuxi 214400 China Department of Endocrinology and Metabolism The Affiliated Hospital of Xuzhou Medical College Xuzhou 221006 China Department of Endocrinology and Metabolism Xuzhou Central Hospital Xuzhou 221009 China Department of Endocrinology and Metabolism The First Affiliated Hospital of Soochow University Suzhou 215006 China Department of Endocrinology and Metabolism The Second Affiliated Hospital of Soochow University Suzhou 215004 China Department of Endocri

Type 1 diabetes mellitus is heterogeneous in many facets. The patients suffered from type 1 diabetes present several levels of islet function as well as variable number and type of islet-specific autoantibodies. This study was to investigate prevalence and heterogeneity of the islet autoantibodies and clinical phenotypes of type 1 diabetes mellitus; and also discussed the process of islet failure and its risk factors in Chinese type 1 diabetic patients. A total of 1,291 type 1 diabetic patients were enrolled in this study. Demographic information was collected. Laboratory tests including mixed-meal tolerance test, human leukocyte antigen alleles, hemoglobin A1 c, lipids, thyroid function and islet autoantibodies were conducted. The frequency of islet-specific autoantibody in newly diagnosed T1 DM patients(duration shorter than half year) was 73% in East China. According to binary logistic regressions, autoantibody positivity, longer duration and lower Body Mass Index were the risk factors of islet failure. As the disease developed, autoantibodies against glutamic acid decarboxylase declined as well as the other two autoantibodies against zinc transporter 8 and islet antigen 2. The decrease of autoantibodies was positively correlated with aggressive beta cell destruction. Autoantibodies can facilitate the identification of classic T1 DM from other subtypes and predict the progression of islet failure. As there were obvious heterogeneity in autoantibodies and clinical manifestation in different phenotypes of the disease, we should take more factors into consideration when identifying type 1 diabetes mellitus.

关键词： autoantibodies heterogeneity islet failure type 1 diabetes

Preliminary molecular epidemiology of the Staphylococcus aureus in lower respiratory tract infections： a multicenter study in China

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Chinese Medical Journal 2011年第5期124卷 687-692页

作者： LI De-zhi CHEN Yu-sheng YANG Jing-ping ZHANG Wei HU Cheng-ping LI Jia-shu MU Lan HU Ying-hui GENG Rong HU Ke CAI Shao-xi WAN Huan-ying WANG Qiu-yue WEI Li-ping DU Juan YU Qin ZHONG Xiao-ning WANG Rui-qin MA Jian-jun TIAN Gui-zhen WANG Si-qin GAO Zhan-cheng Department of Respiratory and Critical Care Medicine Peking University People's Hospital Beijing 100044 China Department of Respiratory Medicine Fujian Provincial Hospital Fuzhou Fujian 350001 China Department of Respiratory Medicine Third Affiliated Hospital of the Inner Mongolia Medical College Baotou Inner Mongolia 014010 China Department of Respiratory Medicine First Affiliated Hospital of Nanchang University Nanchang Jiangxi 330006 China Department of Respiratory Medicine Xiangya Hospital of Central South University Changsha Hunan 410008 China Department of Respiratory Medicine Lianyungang First People's Hospital affiliated of Xuzhou Medical College Lianyungang Jiangsu 222002 China Department of Respiratory Medicine Peking University Space Central Hospital Beijing 100049 China Department of Respiratory Medicine Beijing Children's Hospital affiliated of Capital Medical University Beijing 100045 China Department of Emergency Medicine Beijing Children's Hospital affiliated of Capital Medical University Beijing 100045 China Department of Respiratory Medicine Renmin Hospital of Wuhan University Wuhan Hubei 430060 China Department of Respiratory Medicine Nanfang Hospital affiliated to Southern Medical University Guangzhou Guangdong 510515 China Department of Respiratory Medicine Ruijin Hospital affiliated to Shanghai Jiao Tong University Shanghai 200025 China Institute of Respiratory Disease First Affiliated Hospital of China Medical University Shenyang Liaoning 110001 China Department of Respiratory Medicine Third Affiliated Hospital of Guangzhou Medical College Guangzhou Guangdong 510150 China Department of Respiratory Medicine Affiliated Hospital of Guiyang Medical College Guiyang Guizhou 550004 China Department of Respiratory Medicine First Hospital of Lanzhou University Lanzhou Gansu 730000 China Department of Respiratory Medicine First Affiliated Hospital of Guangxi Medical University Nanning Guangxi 530021 China Department of Respiratory Medicin

Background Staphylococcus aureus （S. aureus） remains as an important microbial pathogen resulting in community and nosocomial acquired infections with significant morbidity and mortality. Few reports for S. aureus in lower respiratory tract infections （LRTIs） have been documented. The aim of this study was to explore the molecular epidemiology of S. aureus in LRTIs in *** A multicenter study of the molecular epidemiology of S. aureus in LRTIs was conducted in 21 hospitals in Beijing, Shanghai and twelve other provinces from November 2007 to February 2009. All the collected S. aureus strains were classified as minimum inhibitory concentration （MIC）, mecA gene, virulence genes Panton-Valentine Leukocidin （PVL） and y-hemolysin （hlg）, staphylococcal cassette chromosome mec （SCCmec） type, agr type, and Multilocus Sequence Typinq （MLST）.Results Totally, nine methicillin-sensitive S. aureus （MSSA） and 29 methicillin-resistant S. aureus （MRSA） strains were isolated after culture from a total of 2829 sputums or bronchoalveolar lavages. The majority of MRSA strains （22/29） had a MIC value of 〉512 μg/ml for cefoxitin. The mecA gene acting as the conservative gene was carried by all MRSA strains. PVL genes were detected in only one S. aureus strain （2.63%, 1/38）. The hlg gene was detected in almost the all S. aureus （100% in MSSA and 96.56% in MRSA strains）. About 75.86% of MRSA strains carried SCCmec Ⅲ. Agr type 1 was predominant （78.95%） among the identified three agr types （agr types 1,2, and 3）. Totally, ten sequence type （ST） of S. aureus strains were detected. A new sequence type （ST1445） was found besides confirming ST239 as the major sequence type （60.53%）. A dendrogram generated from our own MLST database showed all the bootstrap values 〈50%. Conclusion Our preliminary epidemiology data show SCCmec Ⅲ, ST239 and agr type 1 of S. aureus as the predominant strains in LRTIs in Mainland of China.

关键词： Staphylococcus aureus lower respirato tract infections molecular epidemiology staphylococcal cassette chromosome mec Multilocus Sequence Typing

Research on Multi-Modal Time Series Data Prediction Method Based on Dual-Stage Attention Mechanism

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国际计算机前沿大会会议论文集 2023年第1期 127-144页

作者： Xinyu Liu Yulong Meng Fangwei Liu Lingyu Chen Xinfeng Zhang Junyu Lin Husheng Gou Jiangsu JARI Technology Group Co.Ltd. Lianyungang 222006China Harbin Engineering University Harbin 150001China Modeling and Emulation in E-Government National Engineering Laboratory BeijingChina Institute of Information Engineering Chinese Academy of SciencesBeijingChina China International Engineering Consulting Corporation BeijingChina

The production data in the industrialﬁeld have the characteristics of multimodality,high dimensionality and large correlation differences between *** data prediction methods cannot effectively capture time series and modal features,which leads to prediction hysteresis and poor prediction *** at the above problems,this paper proposes a time-series and modal fea-tureenhancementmethodbasedonadual-stageself-attentionmechanism(DATT),and a time series prediction method based on a gated feedforward recurrent unit(GFRU).On this basis,the DATT-GFRU neural network with a gated feedforward recurrent neural network and dual-stage self-attention mechanism is designed and *** show that the prediction effect of the neural network prediction model based on DATT is signiﬁcantly *** with the traditional prediction model,the DATT-GFRU neural network has a smaller aver-age error of model prediction results,stable prediction performance,and strong generalization ability on the three datasets with different numbers of attributes and different training sample sizes.

关键词： Multi-modal time series data Recurrent neural network Self-attention mechanism

Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection

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Chinese Medical Journal 2010年第18期123卷 2571-2575页

作者： DAI Ning LI De-zhi CHEN Ji-chao CHEN Yu-sheng GENG Rong HU Ying-hui YANG Jing-ping DU Juan HU Cheng-ping ZHANG Wei LI Jia-shu YU Qin WAN Huan-ying MU Lan ZHONG Xiao-ning WEI Li-ping MA Jian-jun WANG Qiu-yue HU Ke TIAN Gui-zhen CAI Shao-xi WANG Rui-qin HE Bei WANG Si-qin WANG Zhan-wei ZHAO Su-rui GAO Zhan-cheng Department of Respiratory and Critical Care Medicine Department of Microbiology Peking University People's Hospital Beijing 100044 China Department of Respiratory Medicine Fujian Provincial Hospital Fuzhou Fujian 350001 China Department of Respiratory Medicine Beijing Children's Hospital Affiliated to Capital Medical University Beijing 100045 China Department of Respiratory Medicine Third Affiliated Hospital of the Inner Mongolia Medical College Baotou Inner Mongolia 014010 China Department of Respiratory Medicine Affiliated Hospital of Guiyang Medical College Guiyang Guizhou 550004 China Department of Respiratory Medicine Xiangya Hospital of Central South University Changsha Hunan 410008 China Department of Respiratory Medicine First Affiliated Hospital of Nanchang University Nanchang Jiangxi 330006 Department of Respiratory Medicine Lianyungang First People's Hospital Affiliated to Xuzhou Medical College Lianyungang Jiangsu 222002 China Department of Respiratory Medicine First Hospital of Lanzhou University Lanzhou Gansu 730000 China Department of Respiratory Medicine Ruijin Hospital Affiliated to Shanghai Jiao Tong University Shanghai 200025 China Department of Respiratory Medicine Aerospace Central Hospital Beijing 100049 China Department of Respiratory Medicine First Affiliated Hospital of Guangxi Medical University Nanning Guangxi 530021 China Department of Respiratory Medicine Third Affiliated Hospital of Guangzhou Medical College Guangzhou Guangdong 510150 China Department of Respiratory Medicine Lanzhou Pulmonary Hospital Lanzhou Gansu 730046 China Institute of Respiratory Disease First Affiliated Hospital of China Medical University Shenyang Liaoning 110001 China Department of Respiratory Medicine Renmin Hospital of Wuhan University Wuhan Hubei 430060 China Department of Respiratory Medicine No.263 Clinical Section of the Military General Hospital of Beijing Beijing 101149 Department of Respiratory Medicine Nanfang Hospital Affiliated to Sout

Background Acinetobacter baumanii （A. baumanii ） remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple 13-1actamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections （LRTIs）. Methods Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods. Results Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanfi strains to ampicillin and first- and second-generation cephalosporins （94.87%, 100% and 97.44%, respectively）, but also to the third-generation cephalosporins （ceftriaxone at 92.31%, ceftazidine at 51.28%） and imipenem （43.59%） as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-1a was found in 23 strains, and the aac-6＂lb gene in 19 strains, aac-3-1a and aac-6＂lb genes hibernated in three A. baumanfi strains that showed no drug-resistant phenotype. Conclusions A. baumanii can carry multiple drug-re

关键词： Acinetobacter baumanii lower respiratory tract infections β-lactamase drug-resistant gene

Genetic Architecture of Childhood Kidney and Urological Diseases in China

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Phenomics 2021年第3期1卷 91-104页

作者： Ye Fang Hua Shi Tianchao Xiang Jiaojiao Liu Jialu Liu Xiaoshan Tang Xiaoyan Fang Jing Chen Yihui Zhai Qian Shen Guomin Li Li Sun Yunli Bi Xiang Wang Yanyan Qian Bingbing Wu Huijun Wang Wenhao Zhou Duan Ma Jianhua Mao Xiaoyun Jiang Shuzhen Sun Ying Shen Xiaorong Liu Aihua Zhang Xiaowen Wang Wenyan Huang Qiu Li Mo Wang Xiaojie Gao Yubin Wu Fang Deng Ruifeng Zhang Cuihua Liu Li Yu Jieqiu Zhuang Qing Sun Xiqiang Dang Haitao Bai Ying Zhu Siguang Lu Bili Zhang Xiaoshan Shao Xuemei Liu Mei Han Lijun Zhao Yuling Liu Jian Gao Ying Bao Dongfeng Zhang Qingshan Ma Liping Zhao Zhengkun Xia Biao Lu Yulong Wang Mengzhun Zhao Jianjiang Zhang Shan Jian Guohua He Huifeng Zhang Bo Zhao Xiaohua LI Feiyan Wang Yufeng Li Hongtao Zhu Xinhui Luo Jinghai Li Jia Rao Hong Xu Department of Nephrology Children’s Hospital of Fudan UniversityNational Pediatric Medical Center of CHINA399 Wanyuan RoadShanghaiChina Shanghai Kidney Development and Pediatric Kidney Disease Research Center ShanghaiChina Shanghai Key Lab of Birth Defect Children’s Hospital of Fudan UniversityShanghai 201102China Department of Rheumatology Children’s Hospital of Fudan UniversityShanghaiChina Department of Urology Children’s Hospital of Fudan UniversityShanghaiChina Clinical Genetic Center Children’s Hospital of Fudan UniversityShanghaiChina Key Laboratory of Metabolism and Molecular Medicine Ministry of EducationDepartment of Biochemistry and Molecular BiologyInstitutes of Biomedical SciencesSchool of Basic Medical SciencesFudan UniversityShanghaiChina The Children Hospital of Zhejiang University School of Medicine HangzhouChina The First Affiliated Hospital of Sun Yat-Sen University GuangzhouChina Shandong Provincial Hospital JinanChina Bejing Children’s Hospital Affiliated to Capital University of Medical Science BeijingChina Children’s Hospital of Nanjing Medical University NanjingChina Wuhan Children’s Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Shanghai Children’s Medical Centre Shanghai Jiaotong University School of MedicineShanghaiChina Children’s Hospital of Chongqing Medical University ChongqingChina Shenzhen Children’s Hospital ShenzhengChina Shengjing Hospital of China Medical University ShenyangLiaoningChina Anhui Provincial Children’s Hospital HefeiChina Xuzhou Children’s Hospital XuzhouChina Henan Children’s Hospital ZhengzhouChina Guangzhou First People’s Hospital GuangzhouChina The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University WenzhouChina Qingdao Women and Children’s Hospital QingdaoChina Xiangya Hospital Central South University ChangshaHunanChina The First Affiliated Hospital of Xiamen University XiamenChina First Affiliated Hospital of Anhui Medical University HefeiC

Kidney disease is manifested in a wide variety of phenotypes,many of which have an important hereditary *** delineate the genotypic and phenotypic spectrum of pediatric nephropathy,a multicenter registration system is being imple-mented based on the Chinese Children Genetic Kidney Disease Database(CCGKDD).In this study,all the patients with kidney and urological diseases were recruited from 2014 to *** analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal *** genetic diagnosis was confirmed in 883 of 2256(39.1%)patients from 23 provinces in *** profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome(SRNS,23.5%),glomerulonephritis(GN,32.2%),congenital anomalies of the kidney and urinary tract(CAKUT,21.2%),cystic renal disease(3.9%),renal calcinosis/stone(3.6%),tubulopathy(9.7%),and chronic kidney disease of unknown etiology(CKDu,5.8%).The pathogenic variants of 105 monogenetic disorders were *** distinct genomic disorders were identified as pathogenic copy number variants(CNVs)in 11 *** diagnostic yield differed by subgroups,and was highest in those with cystic renal disease(66.3%),followed by tubulopathy(58.4%),GN(57.7%),CKDu(43.5%),SRNS(29.2%),renal calcinosis/stone(29.3%)and CAKUT(8.6%).Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic *** present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was *** data demonstrate the utility of family-based exome sequencing,and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.

关键词： Chronic kidney disease(CKD) Exome sequencing(ES) Steroid-resistant nephrotic syndrome(SRNS) Congenital anomalies of the kidney and urinary tract(CAKUT) Nephronophthisis(NPHP) Polycystic kidney disease(PKD)

Simultaneous determination of gallic acid and p-coumaric acid in rat plasma by UPLC-MS/MS and its application to a comparative pharmacokinetic study after oral administration of monomer compound and red wine extract

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Journal of Polyphenols 2019年第1期1卷 1-11页

作者： Huijie Lv Mengyu Zou Weichao Yu Baoshan Sun Yan Cui School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China Jiangsu Hengrui Pharmaceutical Co. LtdLianyungang 222002China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Functional Food and Wine Shenyang Pharmaceutical UniversityShenyang 110016China Pólo Dois Portos Instituto National de Investigação Agrária e VeterináriaI.P.Quinta da AlmoinhaDois Portos 2565-191Portugal

A rapid,sensitive and selective ultra high performance liquid chromatography-tandem mass spectrometry(UPLCMS/MS)method was developed and validated for simultaneous determination of gallic acid(GA)and p-coumaric acid(CA)in rat *** samples were extracted by methanol and separated on an ACQUITY UPLC BEH C18 column(1.7μm,100 mm×2.1 mm)using gradient elution consisting of acetonitrile–0.2%formic acid within a runtime of 4.0 *** detection was performed in multiple reaction monitoring(MRM)mode with negative *** linear range was 20–20000 ng/mL for both GA and CA,with lower limits of quantification of 20 ng/***-day and inter-day precisions were within 5.4%and 10.0%,respectively and the accuracy(relative error,RE,%)was less than 7.2%and–4.9%,*** mean absolute extraction recoveries of both analytes and IS from rat plasma were all more than 82.6%.The validated method was successfully applied to the comparative pharmacokinetic study of GA and CA in rat plasma after oral administration of GA and CA monomers and red wine extract,*** was found that both the area under the curve(AUC)and t1/2 of the two constituents were remarkably increased for red wine extract group than that in monomer group,indicating the priority of intake of red wine to active component monomer.

关键词： gallic acid p-coumaric acid red wine extract UPLC-MS/MS pharmacokinetics

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