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| 1 | Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing,locally advanced or metastatic gastric or gastroesophageal junction cancer:a single-arm phase II study显示文摘Background:Current treatment options for human epidermal growth factor receptor 2(HER2)-overexpressing gastric cancer at third-line have shown limited clinical benefit.Further,there is no specific treatment for HER2 immunohistochemistry(IHC)2+and fluorescence in-situ hybridization-negative patients.Here,we report the efficacy and safety of a novel anti-HER2 antibody RC48 for patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer.Methods:Patients with HER2-overexpressing(IHC 2+or 3+),locally advanced or metastatic gastric or gastroesophageal junction cancer who were under at least second-line therapy were eligible and received RC482.5 mg/kg alone every 2 weeks.The primary endpoint was the objective response rate(ORR)assessed by an independent review committee.Secondary endpoints included progressionfree survival(PFS),overall survival(OS),duration of response,time to progression,disease control rate,and safety.Results:Of 179 patients screened,125 were eligible and received RC48 treatment.The ORR was 24.8%(95%confidence interval[CI]:17.5%-33.3%).The median PFS and OS were 4.1 months(95%CI:3.7-4.9 months)and 7.9 months(95%CI:6.7-9.9 months),respectively.The most frequently reported adverse events were decreased white blood cell count(53.6%),asthenia(53.6%),hair loss(53.6%),decreased neutrophil count(52.0%),anemia(49.6%),and increased aspartate aminotransferase level(43.2%).Serious adverse events(SAEs)occurred in 45(36.0%)patients,and RC48-related SAEs were mainly decreased neutrophil count(3.2%).Seven patients had adverse events that led to death were not RC48-related.Conclusions:RC48 showed promising activity with manageable safety,suggesting potential application in patients with HER2-overexpressing,advanced gastric or gastroesophageal junction cancer who have previously received at least two lines of chemotherapy. | Zhi Peng Tianshu Liu Jia Wei Airong Wang Yifu He Liuzhong Yang Xizhi Zhang Nanfeng Fan Suxia Luo Zhen Li Kangsheng Gu Jianwei Lu Jianming Xu Qingxia Fan Ruihua Xu Liangming Zhang Enxiao Li Yuping Sun Guohua Yu Chunmei Bai Yong Liu Jiangzheng Zeng Jieer Ying Xinjun Liang Nong Xu Chao Gao Yongqian Shu Dong Ma Guanghai Dai Shengmian Li Ting Deng Yuehong Cui Jianmin Fang Yi Ba Lin Shen | 2021 | Cancer Communications2021，41，11： | 29 |
| 2 | Apoptosis and Proinflammatory Cytokine Responses of Primary Mouse Microglia and Astrocytes Induced by Human H1N1 and Avian H5N1 Influenza Viruses显示文摘Patients with an influenza virus infection can be complicated by acute encephalopathy and encephalitis. To investigate the immune reactions involved in the neurocomplication,mouse microglia and astrocytes were isolated,infected with human H1N1 and avian H5N1 influenza viruses,and examined for their immune responses. We observed homogeneously distributed viral receptors,sialic acid (SA)-α2,3-Galactose (Gal) and SA-α2,6-Gal,on microglia and astrocytes. Both viruses were replicative and productive in microglia and astrocytes. Virus-induced apoptosis and cytopathy in infected cells were observed at 24 h post-infection (p.i.). Expression of IL-1β,IL-6 and TNF-α mRNA examined at 6 h and 24 h p.i. was up-regulated,and their expression levels were considerably higher in H5N1 infection. The amounts of secreted proinflammatory IL-1β,IL-6 and TNF-α at 6 h and 24 h p.i. were also induced,with greater induction by H5N1 infection. This study is the first demonstration that both human H1N1 and avian H5N1 influenza viruses can infect mouse microglia and astrocytes and induce apoptosis,cytopathy,and proinflammatory cytokine production in them in vitro. Our results suggest that the direct cellular damage and the consequences of immunopathological injury in the CNS contribute to the influenza viral pathogenesis. | Gefei Wang Juan Zhang Weizhong Li Yun Su Yuanli Gao Heng Zhang Guimei Lin Xiaoyang Jiao Kangsheng Li | 2008 | Cellular & Molecular Immunology2008，5，2： | 28 |
| 3 | Effects of NS1 variants of H5N1 influenza virus on interferon induction, TNFa response and p53 activity显示文摘Non-structural protein 1(NS1)is an important virulence factor of the highly pathogenic H5N1 avian influenza virus.A five-amino-acid(5 aa)deletion at position 80–84 and an aspartic acid to glutamic acid substitution at position 92(D92E)are two major NS1 mutations that are highly correlated with enhanced virulence.To investigate the effect of these mutations in H5N1 virulence,three H5N1-NS1 variants were constructed:NS51(lacking 5 aa at position 80–84),NS51(I)(carrying a 5-aa insertion at position 80–84)and NS51(IM)(carrying both the 5-aa insertion and the D92E mutation).We examined the effects of these mutations on interferon(IFN)induction,tumor-necrosis factor(TNF)a response,p53 activity and apoptosis.We found that the D92E mutation eliminated NS1’s repressive effect on IFN induction,while the 5-aa deletion resulted in enhanced resistance to TNFa responses.We also observed that all three variants exhibited a similar suppressive effect on p53 transcriptional activity,although none of them significantly influenced apoptosis of host cells.Our findings shed new light on the role of NS1 in the pathogenicity of H5N1 virus. | Weizhong Li Gefei Wang Heng Zhang Gang Xin Dangui Zhang Jun Zeng Xiaoxuan Chen Yanxuan Xu Youhong Cui Kangsheng Li | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 4 | miRNAs targeting CYP6ER1 and CarE1 are involved in nitenpyram resistance in Nilaparvata lugens显示文摘The evolution of nitenpyram resistance has been confirmed to be related to overexpression of two key metabolic enzyme genes, CYP6ER1 and CarE1, in Nilaparvata lugens, a highly destructive rice pest that causes substantial economic losses and has developed insecticide resistance. As microRNAs (miRNAs) are important post-transcriptional regulators of gene expression, whether they are involved in nitenpyram resistance is poorly understood in N. lugens. In this study, knockdown of key genes in the miRNA biogenesis pathway (Dicer1, Drosha, and Argonaute1) changed CYP6ER1 and CarE1 abundance, which confirmed the importance of miRNAs in nitenpyram resistance. Furthermore, global screening of miRNAs associated with nitenpyram resistance in N. lugens was performed, and a total of 42 known and 178 novel miRNAs were identified;of these, 57 were differentially expressed between the susceptible and resistant strains, and two (novel_85 and novel_191) were predicted to target CYP6ER1 and CarE1, respectively. Luciferase reporter assays demonstrated that novel_85 and novel_191 bind to the CYP6ER1 and CarE1 coding regions, respectively, and downregulate their expression. Moreover, modulating novel_85 and novel_191 expression by injection of miRNA inhibitors and mimics significantly altered N. lugens nitenpyram susceptibility. This is the first study to systematically screen and identify miRNAs associated with N. lugens nitenpyram resistance, and provides important information that can be used to develop new miRNA-based targets in insecticide resistance management. | Kaikai Mao Ruoheng Jin Zhijie Ren Junjie Zhang Zhao Li Shun He Kangsheng Ma Hu Wan Jianhong Li | 2022 | Insect Science2022，29，1： | 2 |
| 5 | Differential transcription-activating capability of NS1 proteins from different influenza virus subtypes expressed in yeast显示文摘Influenza A virus NS1 protein is an important regulatory factor with multiple functions and contributes greatly to viral pathogenesis.In the present study,transcription-activating potential of NS1 from different influenza A virus subtypes was examined in yeast two-hybrid system.The bait vectors contain-ing different NS1 genes,along with an empty prey vector,were transformed into yeast AH109(for growth assay on QDO plate and α-galactosidase assay),and Y187(for β-galactosidase assay).AH109 transformants with NS1 gene from H1N1,H5N1,and H9N2 viruses grew vigorously on the QDO plate and secreted high level of α-galactosidase.Also,Y187 bearing the above NS1 genes exhibited en-hanced β-galactosidase activity.Nevertheless,H3N2-NS1-transformed AH109 and Y187 yeasts did not grow on QDO plate and secrete β-galactosidase,respectively.These findings denote the remarkable variation in NS1 proteins from different influenza A virus subtypes on the transcription-stimulating capability in yeast. | LI WeiZhong,WANG GeFei,ZENG Jun,ZHANG DanGui,ZHANG Heng,CHEN XiaoXuan,CHEN YouYing & Li KangSheng Department of Microbiology and Immunology,Shantou University Medical College,Shantou 515041,China | 2009 | Science China(Life Sciences)2009，52，6： | 2 |
| 6 | Evidence fusion procedure based on hybrid DSm model显示文摘Dezert-Smarandache(DSm) theory, a new information fusion theory, is widely applied in image processing, multiple targets tracking identification, and other areas for its excellent processing ability of imperfect information. However, earlier research on DSm theory mainly focused on one sort of questions. An evidence fusion procedure is proposed based on the hybrid DSm model to compensate for a lack of research on the entire information procedure of DSm theory. This paper analyzes the evidence fusion procedure, as well as correlative node input and output information. Key steps and detailed procedures of evidence fusion are also discussed. Finally, an experiment illustrates the efficiency of the proposed evidence fusion procedure. | Hongfei Li Hongbin Jin Kangsheng Tian | 2014 | Journal of Systems Engineering and Electronics2014，25，6： | 2 |
| 7 | Prognostic significance of miR-218 in human hepatocellular carcinomaand its role in cell growth显示文摘 | Kangsheng Tu Chao Li Xin Zheng Wei Yang Yingmin Yao Qingguang Liu | 2014 | Oncology Reports2014，，4： | 1 |
| 8 | Paclitaxel liposome for injection (Lipusu) plus cisplatin versus gemcitabine plus cisplatin in the first-line treatment of locally advanced or metastatic lung squamous cell carcinoma: A multicenter, randomized, open-label, parallel controlled clinical study显示文摘Background:Lipusu is the first commercialized liposomal formulation of pacli-taxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma(LSCC)in a small-scale study.Here,we conducted a multicenter,randomized,phase 3 study to compare the efficacy and safety of cis-platin plus Lipusu(LP)versus cisplatin plus gemcitabine(GP)as first-line treat-ment in locally advanced or metastatic LSCC.Methods:Patients enrolled were aged between 18 to 75 years,had locally advanced(clinical stage IIIB,ineligible for concurrent chemoradiation or surgery)or metastatic(Stage IV)LSCC,had no previous systemic chemother-apy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors(version 1.1)before administration of the trial drug.The primary endpoint was progression-free survival(PFS).The secondary endpoints included objective response rate(ORR),disease control rate(DCR),overall survival(OS),and safety profiles.To explore the possible predictive value of plasma cytokines for LP treatment,plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology.The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses.Results:The median duration of follow-up was 15.4 months.237 patients in the LP group and 253 patients in the GP group were included in the per protocol set(PPS).In the PPS,the median PFS was 5.2 months versus 5.5 months in the LP and GP group(hazard rtio[HR]:1.03,P=0.742)respectively.The median OS was 14.6 months versus 12.5 months in the LP and GP group(HR:0.83,P=0.215).The ORR(41.8%versus 45.9%,P=0.412)and DCR(90.3%versus 88.1%,P=0.443)were also similar between the LP and GP group.A significantly lower proportion of patients in the LP group experienced adverse events(AEs)leading to treatment interruptions(10.9%versus 26.4%,P<0.001)or treatment termination(14.3%versus 23.1%,P=0.011).The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR,and 15 cytokines were associated with improved PFS,with 14 cytokines,including TNF-a,IFN-y,IL-6,and IL-8,demonstrating an overlapping trend.Conclusion:The LP regimen demonstrated similar PFS,OS,ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles.The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen. | Jie Zhang Yueyin Pan Qin Shi Guojun Zhang Liyan Jiang Xiaorong Dong Kangsheng Gu Huijuan Wang Xiaochun Zhang Nong Yang Yuping Li Jianping Xiong Tienan Yi Min Peng Yong Song Yun Fan Jiuwei Cui Gongyan Chen Wei Tan Aimin Zang Qisen Guo Guangqiang Zhao Ziping Wang Jianxing He Wenxiu Yao Xiaohong Wu Kai Chen Xiaohua Hu Chunhong Hu Lu Yue Da Jiang Guangfa Wang Junfeng Liu Guohua Yu Junling Li Jianling Bai Wenmin Xie Weihong Zhao Lihong Wu Caicun Zhou | 2022 | Cancer Communications2022，42，1： | 1 |
| 9 | High performance genetic algorithm based text clustering using parts of speech and outlier elimination 显示文摘 | Shi Kangsheng Li Lerming | 2012 | Applied Intelligence2012，7，8： | 1 |
| 10 | Heterologous interactions between NS1 proteins from different influenza A virus subtypes/strains显示文摘Non-structural protein 1(NS1) of the influenza virus plays a crucial role in modulating the host immune response and facilitating virus replication.The formation of a homodimer or an oligomer is necessary for NS1 to exert its function efficiently.In the present study,the NS1 protein from the A/Shantou/602/06(H3N2) virus(herein abbreviated as NS32) was found to interact with NS1 from A/Shantou/169/06(H1N1),A/Chicken/Guangdong/1/05(H5N1) and A/Quail/Hong Kong/G1/97(H9N2)(abbreviated as NS11,NS51 and NS92,respectively) viruses,although NS32 shares 17.4% 20.9% sequence diversity with NS11,NS51 and NS92.This indicates that the heterologous interactions between NS1 proteins from different influenza A virus subtypes/strains may be a common event during co-infection. | LI WeiZhong ZHANG Heng WANG GeFei ZHANG Chi ZENG XiangXing LIU Hui CHEN XiaoXuan XU YanXuan LI KangSheng | 2012 | Science China(Life Sciences)2012，55，6： | 0 |
| 11 | Decoy Nanozymes Enable Multitarget Blockade of Proinflammatory Cascades for the Treatment of Multi-Drug- Resistant Bacterial Sepsis显示文摘Sepsis is a life-threatening organ dysfunction characterized by severe systemic inflammatory response to infection.Effective treatment of bacterial sepsis remains a paramount clinical challenge,due to its astonishingly rapid progression and the prevalence of bacterial drug resistance. | Xuancheng Du Mingzhen Zhang Huiting Zhou Weijie Wang Chengmei Zhang Lei Zhang Yuanyuan Qu Weifeng Li Xiangdong Liu Mingwen Zhao Kangsheng Tu Yong-Qiang Li | 2023 | Research2023，，2： | 0 |
| 12 | Safety and activity of WX-0593(Iruplinalkib)in patients with ALK-or ROS1-rearranged advanced non-small cell lung cancer:a phase 1 dose-escalation and dose-expansion trial显示文摘WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement. | Yuankai Shi Jian Fang Xuezhi Hao Shucai Zhang Yunpeng Liu Lin Wang Jianhua Chen Yi Hu Xiaosheng Hang Juan Li Chunling Liu Yiping Zhang Zhehai Wang Yanping Hu Kangsheng Gu Jian’an Huang Liangming Zhang Jinlu Shan Weiwei Ouyang Yanqiu Zhao Wu Zhuang Yan Yu Jun Zhao Helong Zhang Pei Lu Weidong Li Meimei Si Mingjing Ge Huaize Geng | 2022 | Signal Transduction and Targeted Therapy2022，7，2： | 0 |
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