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| 1 | Prevalence of Atrial Fibrillation in China and Its Risk Factors显示文摘Objective To study the prevalence of atrial fibrillation(AF)and the relation with its risk factors in China.Methods A total of 19 363 participants(8635 males and 10 728 females) aged ≥35 years in geographically dispersed urban and rural regions of China were included in this cross-sectional survey.All participants received questionnaire,physical and blood examination.Echocardiography were performed for AF patients found in the survey.Results Of the 19 363 participants,199 were diagnosed with AF.The estimated age-standardized prevalence of AF was 0.78% in men and 0.76% in women.The prevalence of AF in participants aged <60 years was 0.41% in men and 0.43% in women,and was 1.83% in both men and women aged ≥60 years.About 19.0% of males and 30.9% of females with AF were diagnosed with valve disease.Age-and sex-adjusted multivariable logistic regression analysis revealed that myocardial infarction,left ventricular hypertrophy(LVH),obesity,and alcohol consumption were associated with a increased risk of AF(P<0.05).Conclusion The age standardized prevalence of AF is 0.77% in the participants enrolled in the present study.The number of AF cases aged ≥35 years is 5.26 million according to 2010 Chinese Census.Most risk factors for AF,identified mainly in Western countries,are also detected in China. | LI Ying WU Yang Feng CHEN Ke Ping LI Xian ZHANG Xing XIE Gao Qiang WANG Fang Zheng ZHANG Shu | 2013 | Biomedical and Environmental Sciences2013，26，9： | 48 |
| 2 | Clinical significance of K-ras and BRAF mutations in Chinese colorectal cancer patients显示文摘AIM:To identify and assess mutations in the K-ras and BRAF genes in a cohort of Chinese patients with colorectal cancer (CRC) for their association with various clinicopathological parameters and prognosis.METHODS:Genomic DNA was isolated from frozen tissues.Pyrosequencing analysis was conducted to detect mutations in the K-ras (codons 12,13,and 61) and BRAF genes (codon 600).Statistical analysis was carried out using SPSS-15.0 software.RESULTS:Among the 118 colorectal cancer patients,we detected 41 (34.7%) mutations in the K-ras gene.Mutation frequencies at codon 12 and codon 13 were 23.7% (28/118) and 10.2% (12/118),respectively.Only one patient harbored a point mutation at codon 61 (0.8%,1/118).Gender was the only factor that showed an obvious relationship with K-ras gene mutation (female 44.7% vs male 28.2%,P=0.037).Other clinicopathological features,such as age,location of the tumor,tumor differentiation,Tumor,Node and Metastases classification,and the Union for International Cancer Control staging,showed no positive relationship with K-ras gene mutations.No significant correlation was observed between the presence of K-ras mutations (codons 12,13,and 61) and the survival of the patients.BRAF mutations were rare,and only two patients (1.7%) harbored a detectable mutation at codon 600.CONCLUSION:K-ras gene mutation is a common event in our 118 Chinese CRC patients,with an obvious relationship with gender.However,it seems not to be an independent prognostic factor in CRC patients.The BRAF gene is rarely mutated in Chinese CRC patients. | Hong Shen Ying Yuan Han-Guang Hu Xiao-Xian Ye Mo- Dan Li Xian Zhong Wei-Jia Fang Shu Zheng | 2011 | World Journal of Gastroenterology2011，17，6： | 29 |
| 3 | 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 |
| 4 | Pneumoconiosis: current status and future prospects显示文摘Pneumoconiosis refers to a spectrum of pulmonary diseases caused by inhalation of mineral dust,usually as the result of certain occupations.The main pathological features include chronic pulmonary inflammation and progressive pulmonary fibrosis,which can eventually lead to death caused by respiratory and/or heart failure.Pneumoconiosis is widespread globally,seriously threatening global public health.Its high incidence and mortality lie in improper occupational protection,and in the lack of early diagnostic methods and effective treatments.This article reviews the epidemiology,safeguard procedures,diagnosis,and treatment of pneumoconiosis,and summarizes recent research advances and future research prospects. | Xian-Mei Qi Ya Luo Mei-Yue Song Ying Liu Ting Shu Ying Liu Jun-Ling Pang Jing Wang Chen Wang | 2021 | Chinese Medical Journal2021，，8： | 22 |
| 5 | Adenovirus-mediated gene delivery:Potential applications for gene and cell-based therapies in the new era of personalized medicine显示文摘With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology,it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies.Despite numerous setbacks,efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases.It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies.There has been a long-lasting interest in using viral vectors,especially adenoviral vectors,to deliver therapeutic genes for the past two decades.Among all currently available viral vectors,adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types.The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development.In fact,among over 2000 gene therapy clinical trials approved worldwide since 1989,a significant portion of the trials have utilized adenoviral vectors.This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors,including adenoviral biology,approaches to engineering adenoviral vectors,and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment,vaccination and regenerative medicine.Current challenges and future directions regarding the use of adenoviral vectors are also discussed.It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine. | Cody S.Lee Elliot S.Bishop Ruyi Zhang Xinyi Yu Evan M.Farina Shujuan Yan Chen Zhao Zongyue Zeng Yi Shu Xingye Wu Jiayan Lei Yasha Li Wenwen Zhang Chao Yang Ke Wu Ying Wu Sherwin Ho Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Russell R.Reid Tong-Chuan He | 2017 | Genes & Diseases2017，4，2： | 19 |
| 6 | SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are prognosis-related in colorectal cancer显示文摘AIM: To investigate the expression of markers that are correlated with the prognosis of colorectal cancer (CRC) patients. METHODS: One hundred and fifty-six CRC patientswere followed up for more than 3 years after radical surgery. Immunohistochemical (IHC) analysis was performed to detect the expression of 14 pathway-related markers (p53, APC, p21ras, E-cadherin, endothelin-B receptor, Shp2, ADCY-2, SPARCL1, neuroligin1, hsp27, mmp-9, MAPK, MSH2 and rho) in specimens from these patients. Bioinformatics analysis involving a Support Vector Machine (SVM) was used to determine the best prognostic model from combinations of these markers. RESULTS: Seven markers (SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK) were significantly related to the prognosis and clinical pathological features of the CRC patients (P < 0.05). Prognostic models were established through SVM from combinations of these 7 markers and proved able to differentiate patients with dissimilar survival, especially in stage Ⅱ/Ⅲ patients. According to the best prognostic model, the p53/SPARCL1 model, patients having high p53 and low SPARCL1 expression had about 50% lower 3-year survival than others (P < 0.001). CONCLUSION: SPARCL1, Shp2, MSH2, E-cadherin, p53, ADCY-2 and MAPK are potential prognostic markers in CRC. A p53/SPARCL1 bioinformatics model may be used as a supplement to tumor-nodes-metastasis staging. | Shu-Jing Yu Jie-Kai Yu Wei-Ting Ge Han-Guang Hu Ying Yuan Shu Zheng | 2011 | World Journal of Gastroenterology2011，17，15： | 18 |
| 7 | Relationship of Inflammation and Endothelial Dysfunction with Risks to Cardiovascular Disease among People in Inner Mongolia of China显示文摘Objective To explore the relationship of inflammation and endothelial dysfunction with risks to cardiovascular disease(CVD).Methods Blood pressure,body weight,body height,waist circumference and lifestyle risk factors were measured and studied among 2589 participants in Inner Mongolia of China,and biomarkers of inflammation and endothelial dysfunction including high-sensitivity C-reactive protein(hsCRP),soluble inter-cellular adhesion molecule-1(sICAM-1),soluble E-selectin(sE-selectin),and angiotensin II were investigated.Results Subjects with metabolic risk factors for CVD had higher levels of hsCRP,sE-selectin and sICAM-1 than those without such risk factors(all P<0.05).Levels of all biomarkers positively and significantly increased with aggregation of the metabolic risk factors among the subjects(all P for trend<0.001).Data from the multivariate analysis showed that participants with high levels of hsCRP [odds ratio(OR): 1.96,95% confidence interval(CI): 1.52-2.53],sE-selectin(OR: 1.35,95% CI: 1.05-1.72),and angiotensin II(OR: 1.81,95% CI: 1.40-2.33) were more likely to develop hypertension; participants with high levels of hsCRP(OR: 2.33,95% CI: 1.85-2.94),sE-selectin(OR: 1.24,95% CI: 1.00-1.54),and sICAM-1(OR: 1.70,95% CI: 1.30-2.22) were more likely to develop dyslipidemia,and those with high levels of hsCRP(OR: 2.95,95% CI: 2.27-3.83) and sICAM-1(OR: 2.80,95% CI: 2.06-3.80) were more likely to develop hyperglycemia.Conclusion Biomarkers of inflammation and endothelial dysfunction were separately associated with relevant metabolic risk factors for CVD.And appropriate measures should be taken to control inflammation and improve endothelial function among individuals with different metabolic risk factors for CVD. | PENG Hao HAN Shu Hai LIU Hai Ying Vasisht CHANDNI CAI Xiao Qing ZHANG Yong Hong | 2013 | Biomedical and Environmental Sciences2013，26，10： | 15 |
| 8 | Changes in count and function of splenic lymphocytes from patients with portal hypertension显示文摘AIM: To investigate changes in numbers and proliferative function of splenic lymphocytes in patients with hypersplenism due to portal hypertension (PH), to provide evidence for further study of immune status of the spleen during PH. METHODS: Twelve spleens from patients with hypersplenism due to PH served as the PH group, and four spleens from cases of traumatic spleen rupture were regarded as the control group. After weighing the spleen, lymphocytes were separated and counted using a cell counting plate to calculate the lymphocyte count per gram of spleen tissue (relative quantity) and total lymphocyte count in whole spleen (absolute quantity). The immunohistochemical SP method was used to observe the density and distribution of lymphocytes in the spleen. The MTT method was used to observe changes in lymphocyte proliferative function. RESULTS: As compared to the control group, the splenic lymphocytes in the PH group showed that: (1) There was no difference in distribution but a significant decreasein density; (2) the number of lymphocytes per gram of spleen (relative quantity) decreased significantly (0.822 ± 0.157) × 108 vs (1.174 ± 0.254) × 108, P < 0.01]; (3) with the significant increase in the weight of the PH spleen (832.6 ± 278.2 g vs 211.7 ± 85.6 g, P < 0.01), the total quantity of lymphocytes (absolute quantity) increased significantly (0.685 ± 0.072) × 1011 vs (0.366 ± 0.057) × 1011, P < 0.01]; and (4) the proliferative function of lymphocytes was enhanced: T lymphocytes, (0.022 ± 0.005 vs 0.015 ± 0.003, P < 0.05), and B lymphocytes (0.034 ± 0.006 vs 0.023 ± 0.001, P < 0.01). CONCLUSION: Although lymphocyte density in the spleen decreased in patients with PH, the total quantity of lymphocytes increased because spleen weight increased greatly, along with the proliferating function. With respect to changes in lymphocytes, PH spleens may still have immune function, although it may be disordered. However, complete evaluation of the immune function of the spleen in PH requires more research. | Zong-Fang Li Shu Zhang Gao-Bo Lv Ying Huang Wei Zhang Song Ren Jun Yang Shuang-Suo Dang | 2008 | World Journal of Gastroenterology2008，14，15： | 13 |
| 9 | Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients显示文摘Objective:The purpose of this study was to determine the unique and universal features of microsatellite instability-high(MSI-H) colorectal cancer(CRC) and MSI-H gastric cancer(GC) in the Chinese population.Methods:A new panel of mononucleotide MSI markers,BAT25,BAT26,NR21,NR24,and MONO-27,was used to define MSI status in 303 CRC and 288 GC subjects.Clinicopathological features of both types of MSI-H tumors were analyzed.Methylation analysis in the hMLH1 promoter region by methylation specific polymerase chain reaction(PCR) and mutation detection of hMSH2/hMLH1 genes by denaturing high-performance liquid chromatography(DHPLC) were carried out simultaneously.Results:MSI-H CRCs and MSI-H GCs account for 11.9% and 8.0% of unselected sporadic CRCs and GCs,respectively.MSI-H CRCs are strongly characterized by early onset,right-side location,low differentiation,mucinous tumor,less infiltration,less lymphatic metastasis,and more often familial tumor.MSI-H GCs only showed site preference for the antrum and less lymphatic metastasis.Genetic and epigenetic analyses were positive in 6/36 MSI-H CRCs and 0/23 MSI-H GCs with pathological mutation in major mismatch repair genes,and in 7/36 MSI-H CRCs and 18/23 MSI-H GCs with methylated hMLH1 promoter(P<0.01),respectively.Conclusions:Although there are many differences in the genetic basis and clinicopathological features between MSI-H CRC and MSI-H GC,when compared with their microsatellite stable(MSS) counterparts,site preference and lymphatic metastasis are features common to both types of MSI-H tumors. | Yan-qin HUANG Ying YUAN Wei-ting GE Han-guang HU Su-zhan ZHANG Shu ZHENG | 2010 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2010，11，9： | 12 |
| 10 | Diet and gastric cancer:a case-control study in Fujian Province,China显示文摘NTRODUCTIONChangleandFuqingcitiesarelocatedinthesoutheasternpartofFujianProvince,Chinawithahighincidenceofgastriccancer.Howev... | YE Wei Min 1, YI Ying Nan 1, LUO Ren Xia 2, ZHOU Tian Shu 3, LIN Ru Tao 1 and CHEN Gui Dong 3 | 1998 | World Journal of Gastroenterology1998，4，6： | 12 |
| 11 | m^6A Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2显示文摘N6-methyladenosine (m6A),catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14,is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However,the roles and precise mechanisms of m6A modification in regulating neuronal development and adult neurogenesis remain unclear. Here,we examined the function of Mettl3,the key component of the complex,in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced m6A levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neu-ronal development and skewed the differentiation of aNSCs more toward glial lineage,but also affected the morphological maturation of newborn neurons in the adult brain. m6A immunoprecip-itation combined with deep sequencing (MeRIP-seq) revealed that m6A was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically,m6A was present on the transcripts of histone methyltransferase Ezh2,and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively,our results uncover a crosstalk between RNA and histone modifica-tions and indicate that Mettl3-mediated m6A modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2. | Junchen Chen Yi-Chang Zhang Chunmin Huang Hui Shen Baofa Sun Xuejun Cheng Yu-Jie Zhang Yun-Gui Yang Qiang Shu Ying Yang Xuekun Li | 2019 | Genomics, Proteomics & Bioinformatics2019，17，2： | 12 |
| 12 | Association between Chinese Medicine Therapy and Survival Outcomes in Postoperative Patients with NSCLC: A Multicenter, Prospective, Cohort Study显示文摘Objective:To evaluate the association between Chinese medicine(CM)therapy and disease-free survival(DFS)outcomes in postoperative patients with non-small cell lung cancer(NSCLC).Methods:This multiple-center prospective cohort study was conducted in 13 medical centers in China.Patients with stage I,II,or IDA NSCLC who had undergone radical resection and received conventional postoperative treatment according to the National Comprehensive Cancer Network(NCCN)guidelines were recruited.The recruited patients were divided into a CM treatment group and a control group according to their wishes.Patients in the CM treatment group received continuous CM therapy for more than 6 months or until disease progression.Patients in the control group received CM therapy for less than 1 month.Follow-up was 8nducted over 3 years.The primary outcome was DFS,with recurrence/metastasis rates as a secondary outcome.Results:Between May 2013 and August 2016,503 patients were enrolled into the cohort;266 were classified in the CM treatment group and 237 in the control group.Adjusting for covariates,high exposure to CM was associated with better DFS[hazard ratio(HR)=0.417,95%confidential interval(Cl):0.307-0.567)].A longer duration of CM therapy(6-12 months,12-18 months,>24 months)was associated with lower recurrence and metastasis rates(HR=0.225,0.119 and 0.083,respectively).In a subgroup exploratory analysis,CM therapy was also a protective factor of cancer recurrence and metastasis in both stage n-MA(HR=0.50,95%Cl:0.37-0.67)and stage IDA NSCLC postoperative patients(HR=0.48,95%Cl:0.33-0.71),DFS was even longer among CM treatment group patients.Conclusions:Lon ger duration of CM therapy could be 8nsidered a protective factor of cancer recurrence and metastasis.CM treatment is associated with improving survival outcomes of postoperative NSCLC patients in China. | WANG Xue-qian ZHANG Ying HOU Wei WANG Ying-tian ZHENG Jia-bin LI Jie LIN Li-zhu JIANG Yi-lan WANG Shen-yu XIE Ying ZHANG Hong-liang SHU Qi-jin LI Ping WANG Wei YOU Jian-liang LI Ge LIU Jie FAN Hui-ting ZHANG Mei-ying LIN Hong-sheng | 2019 | Chinese Journal of Integrative Medicine2019，25，11： | 12 |
| 13 | CYP11B2 expression in HSCs and its effect on hepatic fibrogenesis显示文摘INTRODUCTIONIt has been reported that renin-angiotensin systemexists in tissue and aldosterone can be synthesizedin extra-adrenal tissue including heart,bloodvessels and brain.Recent studies have broughtrich evidences in favour of aldosterone as a strongstimulator of fibrogenesis and mitogenesis. | Xu Li Ying Meng Xi Shan Yang Ping Sheng Wu Shu Mei Li Wen Yan Lai | 2000 | World Journal of Gastroenterology2000，6，6： | 11 |
| 14 | The enhanced X-ray Timing and Polarimetry mission—eXTP显示文摘In this paper we present the enhanced X-ray Timing and Polarimetry mission—eXTP. eXTP is a space science mission designed to study fundamental physics under extreme conditions of density, gravity and magnetism. The mission aims at determining the equation of state of matter at supra-nuclear density, measuring effects of QED, and understanding the dynamics of matter in strong-field gravity. In addition to investigating fundamental physics, eXTP will be a very powerful observatory for astrophysics that will provide observations of unprecedented quality on a variety of galactic and extragalactic objects. In particular, its wide field monitoring capabilities will be highly instrumental to detect the electro-magnetic counterparts of gravitational wave sources.The paper provides a detailed description of:(1) the technological and technical aspects, and the expected performance of the instruments of the scientific payload;(2) the elements and functions of the mission, from the spacecraft to the ground segment. | ShuangNan Zhang Andrea Santangelo Marco Feroci YuPeng Xu FangJun Lu Yong Chen Hua Feng Shu Zhang Sφren Brandt Margarita Hernanz Luca Baldini Enrico Bozzo Riccardo Campana Alessandra De Rosa YongWei Dong Yuri Evangelista Vladimir Karas Norbert Meidinger Aline Meuris Kirpal Nandra Teng Pan Giovanni Pareschi Piotr Orleanski QiuShi Huang Stephane Schanne Giorgia Sironi Daniele Spiga Jiri Svoboda Gianpiero Tagliaferri Christoph Tenzer Andrea Vacchi Silvia Zane Dave Walton ZhanShan Wang Berend Winter Xin Wu Jean J.M.in't Zand Mahdi Ahangarianabhari Giovanni Ambrosi Filippo Ambrosino Marco Barbera Stefano Basso Jörg Bayer Ronaldo Bellazzini Pierluigi Bellutti Bruna Bertucci Giuseppe Bertuccio Giacomo Borghi XueLei Cao Franck Cadoux Francesco Ceraudo TianXiang Chen Yu Peng Chen Jerome Chevenez Marta Civitani Wei Cui WeiWei Cui Thomas Dauser Ettore Del Monte Sergio Di Cosimo Sebastian Diebold Victor Doroshenko Michal Dovciak YuanYuan Du Lorenzo Ducci QingMei Fan Yannick Favre Fabio Fuschino JoséLuis Ga'lvez Min Gao MingYu Ge Olivier Gevin Marco Grassi QuanYing Gu YuDong Gu DaWei Han Bin Hong Wei Hu Long Ji ShuMei Jia WeiChun Jiang Thomas Kennedy Ingo Kreykenbohm Irfan Kuvvetli Claudio Labanti Luca Latronico Gang Li MaoShun Li Xian Li Wei Li ZhengWei Li Olivier Limousin HongWei Liu XiaoJing Liu Bo Lu Tao Luo Daniele Macera Piero Malcovati Adrian Martindale Malgorzata Michalska Bin Meng Massimo Minuti Alfredo Morbidini Fabio Muleri Stephane Paltani Emanuele Perinati Antonino Picciotto Claudio Piemonte JinLu Qu Alexandre Rachevski Irina Rashevskaya Jerome Rodriguez Thomas Schanz ZhengXiang Shen LiZhi Sheng JiangBo Song LiMing Song Carmelo Sgro Liang Sun Ying Tan Phil Uttley Bo Wang DianLong Wang GuoFeng Wang Juan Wang LangPing Wang YuSa Wang Anna L.Watts XiangYang Wen Jörn Wilms ShaoLin Xiong JiaWei Yang Sheng Yang YanJi Yang Nian Yu WenDa Zhang Gianluigi Zampa Nicola Zampa Andrzej A.Zdziarski AiMei Zhang ChengMo Zhang Fan Zhang Long Zhang Tong Zhang Yi Zhang XiaoLi Zhang ZiLiang Zhang BaoSheng Zhao ShiJie Zheng Yu Peng Zhou Nicola Zorzi J.Frans Zwart | 2019 | Science China(Physics,Mechanics & Astronomy)2019，62，2： | 11 |
| 15 | BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis显示文摘B cell activating factor of TNF family(BAFF)is a member of TNF ligand superfamily and plays a key role in B cell homeostasis,proliferation,maturation,and survival.In this study,we detected BAFF level,the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis(RA)patients and analyzed the correlation between BAFF level and clinical variables,laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA.A total of 50 RA patients and 50 healthy controls(HCs)were enrolled.We showed that the serum BAFF level in RA patients was significantly higher than that of HCs,and the percentages of B cell subsets(CD19^(+)B cells,CD19^(+)CD27^(+)B cells,CD19^(+)CD20^(+)CD27^(+)B cells,and CD19^(+)CD20−CD27^(+)B cells)in the serum of RA patients were significantly increased compared with those of HCs.The percentages of CD19^(+)BAFFR^(+)B cells,CD19^(+)BCMA^(+)B cells,and CD19^(+)TACI^(+)B cells in RA patients were significantly increased compared with those in HCs.The expression of important molecules in the NF-κB pathway(MKK3,MKK6,p-P38,p-P65,TRAF2,and p52)was significantly higher in RA patients than in HCs,but p100 level in RA patients was lower than that in HCs.The serum BAFF level was positively correlated with C-reactive protein,rheumatoid factor,disease activity score(in 28 joints),swollen joint counts,tender joint counts,and X-ray scores.When normal B cells were treated with BAFF in vitro,the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated.BAFF also promoted the expression of MKK3,MKK6,p-P38,p-P65,TRAF2,and p52.In conclusion,this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA.BAFF is involved in the differentiation,proliferation,and activation of B cells in RA through NF-κB signaling pathway,suggesting that BAFF might be an ideal therapeutic target for RA. | Ling-ling Zhang Hui Xiao Feng Zhang Yu-jing Wu Jin-ling Shu Ying Li Yu Tai Sheng-qian Xu Jian-hua Xu Wei Wei | 2021 | Acta Pharmacologica Sinica2021，42，10： | 9 |
| 16 | Atorvastatin combined with low-dose dexamethasone for vascular endothelial cell dysfunction induced by chronic subdural hematoma显示文摘Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma.However,treatment with atorvastatin is not effective in some patients,who must undergo further surgical treatment.Dexamethasone has anti-inflammatory and immunomodulatory effects,and low dosages are safe and effective for the treatment of many diseases,such as ankylosing spondylitis and community-acquired pneumonia.However,the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood.Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group.Atorvastatin,dexamethasone,or their combination was added to the culture medium.The main results were as follows:hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1μM atorvastatin and 0.1μM dexamethasone.Atorvastatin,dexamethasone,or their combination could markedly improve the recovery of injured endothelial cells.Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin,dexamethasone,or their combination exhibited varying levels of rescue of endothelial cell function.Hopping probe ion conductance microscopy,western blot assay,and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin,dexamethasone,or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid.Moreover,the curative effect of the combined treatment was significantly better than that of either single treatment.Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased,as was expression of the tight junction protein and vascular permeability marker vascular endothelial cadherin in each treatment group compared with the hematoma stimulation group.Hematoma fluid in patients with chronic subdural hematoma may damage vascular endothelial cells.However,atorvastatin combined with low-dose dexamethasone could rescue endothelial cell dysfunction by increasing the expression of tight junction proteins after hematoma injury.The effect of combining atorvastatin with low-dose dexamethasone was better than that of atorvastatin alone.Increased expression of Krüppel-like factor 2 may play an important role in the treatment of chronic subdural hematoma.The animal protocols were approved by the Animal Care and Use Committee of Tianjin Medical University of China on July 31,2016(approval No.IRB2016-YX-036).The study regarding human hematoma samples was approved by the Ethics Committee of Tianjin Medical University of China on July 31,2018(approval No.IRB2018-088-01). | Yue-Shan Fan Bo Wang Dong Wang Xin Xu Chuang Gao Ying Li Shu Zhang Gui-Li Yang Xiao Liu Rong-Cai Jiang Jian-Ning Zhang | 2021 | Neural Regeneration Research2021，16，3： | 9 |
| 17 | Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)显示文摘Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC. | Yuankai Shi Lin Wu Xinmin Yu Puyuan Xing Yan Wang Jianying Zhou Airong Wang Jianhua Shi Yi Hu Ziping Wang Guangyu An Yong Fang Sanyuan Sun Caicun Zhou Changli Wang Feng Ye Xingya Li Junye Wang Mengzhao Wang Yunpeng Liu Yanqiu Zhao Ying Yuan Jifeng Feng Zhendong Chen Jindong Shi Tao Sun Gang Wu Yongqian Shu Qisen Guo Yi Zhang Yong Song Shucai Zhang Yuan Chen Wei Li Hongrui Niu Wenwei Hu Lijun Wang Jianan Huang Yang Zhang Ying Cheng Zhengdong Wu Bo Peng Jiya Sun Christoph Mancao Yanqi Wang Luyao Sun | 2022 | Cancer Communications2022，42，12： | 8 |
| 18 | Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission显示文摘Objective To investigate the relationship between maternal peripheral blood mononuclear cells (PBMC) hepatitis B virus(HBV) covalenty closed circular deoxyribonucleic acid(cccDNA) and other HBV serological markers and its effects on HBV intrauterine transmission. Methods We enrolled 290 newborns and their hepatitis B surface antigen(HBsAg) positive mothers. HBV cccDNA in PBMC and HBV DNA in serum were detected by a real‐time PCR‐TaqM an probe while HBV serological markers were detected with an electrochemiluminescence immunoassay. Results There was a positive correlation between the levels of PBMC HBV cccD NA and serum HBV DNA and HBeA g(r = 0.436 and 0.403, P < 0.001). The detection rate of pattern A [‘HBsA g(+), HBeA g(+), and anti‐HBc(+)’] was significantly higher in the PBMC HBV cccD NA positive group than in the control group(χ^2 = 48.48, P < 0.001). There was a significant association between HBV intrauterine transmission and PBMC HBV cccD NA(χ^2 = 9.28, P = 0.002). In the presence of serum HBV DNA, HBeA g, and PBMC HBV cccD NA, the risk of HBV intrauterine transmission was three times higher(OR = 3.69, 95% CI: 1.30‐10.42) than that observed in their absence. The risk of HBV intrauterine transmission was the greatest(OR = 5.89, 95% CI: 2.35‐14.72) when both PBMC HBV cccD NA and pattern A were present. A Bayesian network model showed that maternal PBMC HBV cccD NA was directly related to HBV intrauterine transmission. Conclusion PBMC HBV cccDNA may be a direct risk factor for HBV intrauterine transmission. Our study suggests that serological markers could be combined with PBMC‐related markers in prenatal testing. | WANG Dan Dan YI Lin Zhu WU Li Na YANG Zhi Qing HAO Hai Yun SHI Xiao Hong WANG Bo FENG Shu Ying FENG Yong Liang WANG Su Ping | 2019 | Biomedical and Environmental Sciences2019，32，5： | 8 |
| 19 | Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer(ESWN 01):a prospective randomized,multicenter,open-labeled phase 3 trial显示文摘Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC. | Jing Huang Binghe Xu Ying Liu Junxing Huang Ping Lu Yi Ba Lin Wu Yuxian Bai Shu Zhang Jifeng Feng Ying Cheng Jie Li Lu Wen Xianglin Yuan Changwu Ma Chunhong Hu Qingxia Fan Xi Wang | 2019 | Cancer Communications2019，39，1： | 8 |
| 20 | Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms显示文摘刺激干扰素的基因 56 (ISG56 ) 家庭成员在堵住病毒的复制并且然而,调整细胞的功能起重要作用他们的内在的分子的机制大部分是不清楚的。这里,我们在场 ISG54 的水晶结构,有新奇 RNA 有约束力的结构的 ISG56 家庭蛋白质。结构证明 ISG54 单体有 9 tetratricopeptide 像重复的主题和伙伴到形成交换域的 dimers。C 终端部分合拢进超级螺旋状的结构并且在它的内部表面上有一条广泛地断然控告的核苷酸绑定隧道。EMSA 结果证明 ISG54 明确地绑在一些 RNA,例如 adenylate uridylate (AU ) 富有的 RNA,与或没有 5 ′triphosphorylation。Mutagenesis 和功能的研究证明这个 RNA 有约束力的能力对它的抗病毒的活动重要。我们的结果建议位于这干扰素可诱导的基因的抗病毒的活动下面的新机制 56 家庭成员。 | Zhenlin Yang Huanhuan Liang Qian Zhou Ying Li Haiwei Chen Wen Ye Danying Chen Joy Fleming Hongbing Shu Yingfang Liu | 2012 | Cell Research2012，22，9： | 8 |
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