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| 1 | China National Medical Products Administration approval summary:anlotinib for the treatment of advanced non-small cell lung cancer after two lines of chemotherapy显示文摘Background:On May 8,2018,the China National Medical Products Administration(NMPA)approved anlotinib,an orally administered anti-angiogenesis inhibitor,for the treatment of patients with advanced non-small cell lung can-cer(NSCLC)who have progressed after treatment with two or more lines of prior systemic chemotherapy.Main body of the abstract:China NMPA reviewed and inspected a regional double-blinded,placebo-controlled,Phase III trial comparing the overall survival(OS)of NSCLC patients between the anlotinib and placebo arms.A total of 437 patients were randomized(2:1)to receive either anlotinib(n=294)or placebo(n=143)once daily on a 2-week on and 1-week off schedule.Patients with epidermal growth factor receptor(EGFR)or activating anaplastic lymphoma kinase(ALK)genomic tumor aberrations should have disease progression on NMPA-approved therapy.Anlotinib is the first NMPA-approved drug for patients with advanced NSCLC who have progressed on at least two lines of prior systemic chemotherapies in China.The approval was based on a statistically and clinically significant improvement in median OS with anlotinib(9.46 months)compared with placebo[6.37 months;hazard ratio(HR])=0.70,95%confidence interval(CI)=0.55-0.89;two-sided log-rank P=0.002].The confirmed objective response rate(ORR)was 9.2%in the anlotinib arm and 0.7%in the placebo arm.The median duration of response(DoR)was 4.83 months,with a 95%CI of 3.31-6.97 months.The toxicity profile of anlotinib was consistent with that of known anti-angiogenesis inhibitors.Common adverse drug reactions(ADRs)in anlotinib-treated patients included hypertension(67.4%),hand-foot syndrome(43.9%),hemoptysis(14.0%),thyroid stimulating hormone(TSH)elevation(46.6%),and corrected QT interval(QTc)prolongation(26.2%).Short conclusion:Anlotinib demonstrated a clinically significant OS prolongation as a novel therapeutic option for advanced or metastatic NSCLC following at least two lines of chemotherapy. | Ming Zhou Xiaoyuan Chen Hong Zhang Lin Xia Xin Tong Limin Zou Ruimin Hao Jianhong Pan Xiao Zhao Dongmei Chen Yuanyuan Song Yueli Qi Ling Tang Zhifang Liu Rong Gao Yuankai Shi Zhimin Yang | 2019 | Cancer Communications2019，39，1： | 35 |
| 2 | New incompatible pair of TCM:Epimedii Folium combined with Psoraleae Fructus induces idiosyncratic hepatotoxicity under immunological stress conditions显示文摘Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions. | Yuan Gao Zhilei Wang Jinfa Tang Xiaoyi Liu Wei Shi Nan Qin Xiaoyan Wang Yu Pang Ruisheng Li Yaming Zhang Jiabo Wang Ming Niu Zhaofang Bai Xiaohe Xiao | 2020 | Frontiers of Medicine2020，14，1： | 32 |
| 3 | Transduction of Fas gene or Bcl-2 antisense RNA sensitizes cultured drug resistant gastric cancer cells to chemotherapeutic drugs显示文摘INTRODUCTIONChemotherapyisoneofthemajormethodsintumortreatment,butitoftendoesnotworkduetomultidrugresistance(MDR).Recentstudi... | XIAO Bing, SHI Yong Quan, ZHAO Yan Qiu, YOU Han, WANG Zuo You, LIU Xian Ling, YIN Fang, QIAO Tai Dong and FAN Dai Ming | 1998 | World Journal of Gastroenterology1998，4，5： | 24 |
| 4 | Landscape of DILI-related adverse drug reaction in China Mainland显示文摘Drug-induced liver injury(DILI)is a type of bizarre adverse drug reaction(ADR)damaging liver(L-ADR)which may lead to substantial hospitalizations and mortality.Due to the general low incidence,detection of L-ADR remains an unsolved public health challenge.Therefore,we used the data of 6.673 million of ADR reports from January 1st,2012 to December 31st,2016 in China National ADR Monitoring System to establish a new database of L-ADR reports for future investigation.Results showed that totally 114,357 ADR reports were retrieved by keywords searching of liver-related injuries from the original heterogeneous system.By cleaning and standardizing the data fields by the dictionary of synonyms and English translation,we resulted 94,593 ADR records reported to liver injury and then created a new database ready for computer mining.The reporting status of L-ADR showed a persistent 1.62-fold change over the past five years.The national population-adjusted reporting numbers of L-ADR manifested an upward trend with age increasing and more evident in men.The annual reporting rate of L-ADR in age group over 80 years old strikingly exceeded the annual DILI incidence rate in general population,despite known underreporting situation in spontaneous ADR reporting system.The percentage of herbal and traditional medicines(H/TM)L-ADR reports in the whole number was 4.5%,while 80.60%of the H/TM reports were new findings.There was great geographical disparity of reported agents,i.e.more cardiovascular and antineoplastic agents were reported in higher socio-demographic index(SDI)regions and more antimicrobials,especially antitubercular agents,were reported in lower SDI regions.In conclusion,this study presented a large-scale,unbiased,unified,and computer-minable L-ADR database for further investigation.Age-,sex-and SDI-related risks of L-ADR incidence warrant to emphasize the precise pharmacovigilance policies within China or other regions in the world. | Jiabo Wang Haibo Song Feilin Ge Peng Xiong Jing Jing Tingting He Yuming Guo Zhuo Shi Chao Zhou Zixin Han Yanzhong Han Ming Niu Zhaofang Bai Guangbin Luo Chuanyong Shen Xiaohe Xiao | 2022 | Acta Pharmaceutica Sinica B2022，12，12： | 12 |
| 5 | Four new constituents from Taraxacum mongolicum显示文摘二新黄酮 glycosides ,isoetin-7-O-β- d-glucopyranosyl-2 ′- O -- l-arabinopyranoside ( 1 )和isoetin-7-O-β- d-glucopyranosyl-2 ′- O -- d-glucopyranoside ( 2 ),新 lignan , mongolicumin A ( 3 ),和新 guaianolide , mongolicumin B ( 4 )从薄公英属 mongolicum 的天线部分被孤立。他们的结构被主要阐明光谱分析。 | Shu Yun Shi Qi Zhou Hua Peng Chang Xin Zhou Ming Hui Hu Qiao Feng Tao Xiao Jiang Hao Joachim Stoeckigt Yu Zhao | 2007 | Chinese Chemical Letters2007，18，11： | 11 |
| 6 | The Status and Associated Factors of Successful Aging among Older Adults Residing in Longevity Areas in China显示文摘Objective This study aims to assess the status of successful aging(SA) in longevity areas in China and explore multiple factors associated with SA among the young-old and oldest-old. Methods A total of 2296 elderly people aged 65 and older were interviewed in the longevity areas sub-sample of the Chinese Longitudinal Healthy Longevity Survey(CLHLS) in 2012. Baseline assessments included a researcher-administered questionnaire, physical examination, and laboratory testing. A logistic regression model was used to identify factors associated with SA. Results The prevalence of SA was 38.81% in the CLHLS in 2012. There were significant differences between ages groups, with SA compromising 56.85% among ≥65 years group and 20.31% among ≥100 years group(χtrend2=126.73, P<0.01). The prevalence of SA among females was 33.59%, which was significantly lower than that among males(45.58%)(χ2gender=33.65, P<0.05). In the regression analysis, having anemia(OR=0.744, 95% CI: 0.609-0.910), poor lifestyle(OR=0.697, 95% CI: 0.568-0.854), poor sleep quality(OR=0.558, 95% CI: 0.456-0.682), and central obesity(OR=0.684, 95% CI: 0.556-0.841) were the main factors associated with SA. The promoting SA rate decreased as age increased, and the group of 65-79 years had higher odds than the other age group. Conclusion Preventing central obesity, improving sleep quality and promoting healthy lifestyle may contribute to achieve SA among the elderly. | SHI Wen Hui ZHANG Hong Yan ZHANG Juan LYU Yue Bin Melanie Sereny Brasher YIN Zhao Xue LUO Jie Si HU Dong Sheng FEN Lei SHI Xiao Ming | 2016 | Biomedical and Environmental Sciences2016，29，5： | 10 |
| 7 | PandaX: a liquid xenon dark matter experiment at CJPL显示文摘PandaX is a large liquid-xenon detector experiment usable for direct dark-matter detection and 136Xe double-beta decay search.The central vessel was designed to accommodate a staged target volume increase from initially 120 kg(stage I)to 0.5 t(stage II)and eventually to a multi-ton scale.The experiment is located in the Jinping Deep-Underground Laboratory in Sichuan,China.The detector operates in dual-phase mode,allowing detection of both prompt scintillation,and ionization charge through proportional scintillation.In this paper a detailed description of the stage I detector design and performance as well as results established during the commissioning phase are presented. | CAO XiGuang CHEN Xun CHEN YunHua CUI XiangYi FANG DeQing FU ChangBo GIBONI Karl L. GONG HaoWei GUO GuoDong HE Ming HU Jie HUANG XingTao JI XiangDong JU YongLin LI ShaoLi LIN Qing LIU HuaXuan LIU JiangLai LIU Xiang LORENZON Wolfgang MA YuGang MAO YaJun NI KaiXuan PUSHKIN Kirill REN XiangXiang SCHUBNELL Michael SHEN ManBing SHI YuJie STEPHENSON Scott TAN AnDi TARLé Greg WANG HongWei WANG JiMing WANG Meng WANG XuMing WANG Zhou WEI YueHuan WU ShiYong XIAO MengJiao XIAO Xiang XIE PengWei YE Tao YOU YingHui ZEN XiongHui ZHANG Hua ZHANG Tao ZHAO HaiYing ZHAO Li ZHOU XiaoPeng ZHU ZhongHua | 2014 | Science China(Physics,Mechanics & Astronomy)2014，57，8： | 9 |
| 8 | Correlation of An Ultrasonic Scoring System and Intraoperative Blood Loss in Placenta Accreta Spectrum Disorders: A Retrospective Cohort Study显示文摘Objective This study aims to investigate the correlation of an ultrasonic scoring system with intraoperative blood loss(IBL) in placenta accreta spectrum(PAS) disorders.Methods A retrospective cohort study was conducted between January 2015 and November 2019.Clinical data for patients with PAS have been obtained from medical records. Generalized additive models were used to explore the nonlinear relationships between ultrasonic scores and IBL. Logistic regressions were used to determine the differences in the risk of IBL ≥ 1,500 m L among groups with different ultrasonic scores.Results A total of 332 patients participated in the analysis. Generalized additive models showed a significant positive correlation between score and blood loss. The amount of IBL was increased due to the rise in the ultrasonic score. All cases were divided into three groups according to the scores(low score group: ≤ 6 points, n = 147;median score group: 7-9 points, n = 126;and high score group: ≥ 10 points, n = 59). Compared with the low score group, the high score group showed a higher risk of IBL≥ 1,500 m L [odds ratio, 15.09;95% confidence interval(3.85, 59.19);P ≤ 0.001] after a multivariable adjustment.Conclusions The risk of blood loss equal to or greater than 1,500 m L increases further when ultrasonic score greater than or equal to 10 points, the preparation for transfusion and referral mechanism should be considered. | CHEN Lian SHI Hui Feng JIANG Hai SHI Xiao Ming WANG Yuan Yuan ZHANG Ai Qing CHONG Yi Wen ZHAO Yang Yu | 2021 | Biomedical and Environmental Sciences2021，34，2： | 9 |
| 9 | Prevalence and Correlates of Elevated Blood Pressure in Chinese Children Aged 6-13 Years: a Nationwide School-Based Survey显示文摘Objective To estimate the prevalence of elevated blood pressure(EBP) in Chinese children and identify individual and family factors associated with EBP. Methods A nationwide cross-sectional study was conducted in 2010 using stratified cluster sampling. Participants' blood pressure was measured, and their parents completed a questionnaire on personal and family characteristics. Prevalence and correlates of EBP were assessed. Results Among a total of 24,333 participants, 20.2% of boys and 16.3% of girls had EBP. The prevalence of EBP increased with the ascending trend of waist circumference, Waist-to-height ratio, and body mass index. The adjusted prevalence ratios(aP Rs) for obese boys and girls were 2.50 and 2.97, respectively. Fewer urban boys(16.2%) had EBP than rural boys(21.7%). Boys with a family history of hypertension were 12% more likely to have EBP. Children whose mothers received a college education tended to have lower likelihood of EBP; with an aP R was 0.85 among boys and 0.78 among girls. Conclusion EBP is common among obese students and those who have a family history of hypertension. A negative association between mothers' education levels and EBP risk in children was found. | ZHAI Yi LI Wei Rong SHEN Chong Frank QIAN SHI Xiao Ming | 2015 | Biomedical and Environmental Sciences2015，28，6： | 8 |
| 10 | Laboratory Evaluation of the Molluscicidal Activity of Pulsatilla Chinensis(Bunge)Regel Saponins against the Snail Oncomelania Hupensis显示文摘Objective To observe the toxicity of Pulsatilla chinensis(Bunge) Regel saponins(PRS) against Oncomelania hupensis(O.hupensis).Methods O.hupensis snails were exposed to 40% and 80% of 24 h LC50 of PRS for 24 h,and then choline esterase(CHE),alanine aminotransferase(ALT),alkaline phosphatase(ALP),lactate dehydrogenase(LDH) activities in cephalopodium and liver of snails were determined.Niclosamide(NIC) was used as the reference molluscicide.Zebra fish lethality test was evaluated to non-target aquatic species of PRS.Results The molluscicidal activity of PRS(LC50 at 24 h:0.48 mg/L) was similar to that of NIC(LC50 at 24 h:0.16 mg/L).Significant alterations about CHE,ALP,and ALT activities both in the cephalopodium and the liver of snails were observed when O.hupensis was exposed to 40% and 80% LC50 of PRS or NIC for 24 h.PRS and NIC could not affect LDH activity in the cephalopodium and the liver.Lower toxicity to fish of PRS was observed up to the highest concentration tested than NIC.Conclusion PRS,as compared with the reference molluscicide NIC,is thought to be used for the control of harmful vector snails safely. | CHEN Yan Qin XU Qiong Ming LIU Yan Li LI Xiao Ran YANG Shi Lin ZHUGE Hong Xiang | 2012 | Biomedical and Environmental Sciences2012，25，2： | 8 |
| 11 | Allele-defined genome reveals biallelic differentiation during cassava evolution显示文摘Dear Editor,Generation of heterozygous genomes by hybridization between or within species can help maintain plant diversity and serve as a potential source of new species(Baek et al.,2018).Moreover,genomic heterozygosity is associated with genomic coadaptation,developmental stability,and heterosis.Accurate definition of alleles in haplotypes is necessary to precisely characterize allelic variation controlling agriculturally important traits(Shi et al.,2019).Currently,most released genomes have mosaic assembly of haplotypes due to random selection or collapse of alleles during genome assembly(Shi et al.,2019),which masked allelic variation and functional differentiation of divergent alleles in heterozygous species. | Wei Hu Changmian Ji Haitao shi Zhe Liang Zehong Ding Jianqiu Ye Wenjun Ou Gang Zhou Weiwei Tie Yan Yan Jinghao Yang Xiaoying Yang Yunxie Wei Zhiqiang Jin Jianghui Xie Ming Peng Wenquan Wang Anping Guo Biyu Xu Jianchun Guo Songbi Chen Liming Ma Mingcheng Wang Yang Zhou Xiaolong Li Ruoxi Li Siyi Guo Xinhui Xiao Zhongqing Wan Feifei An Jie Zhang Qingyun Leng Yin Li Ray Ming Kaimian Li | 2021 | Molecular Plant2021，14，6： | 8 |
| 12 | Association of Overlapped and Un-overlapped Comorbidities with COVID-19 Severity and Treatment Outcomes: A Retrospective Cohort Study from Nine Provinces in China显示文摘Objective Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear.Methods A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients’ medical records. Multivariable logistic regression models were used to estimate the odds ratio(OR) and 95% confidence interval(95% CI) of the associations between comorbidities(cardiometabolic or non-cardiometabolic diseases), clinical severity, and treatment outcomes of COVID-19.Results Overall, 158(13.6%) patients were diagnosed with severe illness and 32(2.7%) had unfavorable outcomes. Hypertension(2.87, 1.30–6.32), type 2 diabetes(T2 DM)(3.57, 2.32–5.49),cardiovascular disease(CVD)(3.78, 1.81–7.89), fatty liver disease(7.53, 1.96–28.96), hyperlipidemia(2.15, 1.26–3.67), other lung diseases(6.00, 3.01–11.96), and electrolyte imbalance(10.40, 3.00–26.10)were independently linked to increased odds of being severely ill. T2 DM(6.07, 2.89–12.75), CVD(8.47,6.03–11.89), and electrolyte imbalance(19.44, 11.47–32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission(5.46,3.25–9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes(6.58, 1.46–29.64) within two weeks.Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes. | MA Yan ZHU Dong Shan CHEN Ren Bo SHI Nan Nan LIU Si Hong FAN Yi Pin WU Gui Hui YANG Pu Ye BAI Jiang Feng CHEN Hong CHEN Li Ying FENG Qiao GUO Tuan Mao HOU Yong HU Gui Fen HU Xiao Mei HU Yun Hong HUANG Jin HUANG Qiu Hua HUANG Shao Zhen JI Liang JIN Hai Hao LEI Xiao LI Chun Yan LI Min Qing LI Qun Tang LI Xian Yong LIU Hong De LIU Jin Ping LIU Zhang MA Yu Ting MAO Ya MO Liu Fen NA Hui WANG Jing Wei SONG Fang Li SUN Sheng WANG Dong Ting WANG Ming Xuan WANG Xiao Yan WANG Yin Zhen WANG Yu Dong WU Wei WU Lan Ping XIAO Yan Hua XIE Hai Jun XU Hong Ming XU Shou Fang XUE Rui Xia YANG Chun YANG Kai Jun YUAN Sheng Li ZHANG Gong Qi ZHANG Jin Bo ZHANG Lin Song ZHAO Shu Sen ZHAO Wan Ying ZHENG Kai ZHOU Ying Chun ZHU Jun Teng ZHU Tian Qing ZHANG Hua Min WANG Yan Ping WANG Yong Yan 无 | 2020 | Biomedical and Environmental Sciences2020，33，12： | 8 |
| 13 | Convergent genomic signatures of high-altitude adaptation among domestic mammals显示文摘Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence.Here,we used 327 genomes from horses,sheep,goats,cattle,pigs and dogs living at both high and low altitudes,including 73 genomes generated for this study,to disentangle the genetic mechanisms underlying local adaptation of domestic mammals.Although molecular convergence is comparatively rare at the DNA sequence level,we found convergent signature of positive selection at the gene level,particularly the EPAS1 gene in these Tibetan domestic mammals.We also reported a potential function in response to hypoxia for the gene C10 orf67,which underwent positive selection in three of the domestic mammals.Our data provide an insight into adaptive evolution of high-altitude domestic mammals,and should facilitate the search for additional novel genes involved in the hypoxia response pathway. | Dong-Dong Wu Cui-Ping Yang Ming-Shan Wang Kun-Zhe Dong Da-Wei Yan Zi-Qian Hao Song-Qing Fan Shu-Zhou Chu Qiu-Shuo Shen Li-Ping Jiang Yan Li Lin Zeng He-Qun Liu Hai-Bing Xie Yun-Fei Ma Xiao-Yan Kong Shu-Li Yang Xin-Xing Dong Ali Esmailizadeh David M Irwin Xiao Xiao Ming Li Yang Dong Wen Wang Peng Shi Hai-Peng Li Yue-Hui Ma Xiao Gou Yong-Bin Chen Ya-Ping Zhang | 2020 | National Science Review2020，7，6： | 7 |
| 14 | 中国国家药品监督管理局批准安罗替尼用于经两种系统化疗后疾病进展的晚期非小细胞肺癌的治疗显示文摘背景2018年5月8日,中国国家药品监督管理局(National Medical Products Administration,NMPA)批准了小分子多靶点抗血管抑制剂盐酸安罗替尼,用于既往经过至少两种系统化疗后疾病进展的晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的治疗。概要中国NMPA审查了一项随机双盲、安慰剂对照的III期临床试验,该临床试验的主要终点为总生存期(overall survival,OS)。试验共纳入437例患者随机分组(2∶1)接受安罗替尼(n=294)或安慰剂(n=143)治疗,每日1次,连服2周,停药1周。表皮生长因子受体(epidermal growth factor receptor,EGFR)基因敏感突变或间变性淋巴瘤激酶(activating anaplasticlymphomakinase,ALK)阳性的患者须经过NMPA已批准的药物治疗后出现疾病进展。安罗替尼为中国NMPA批准的用于治疗既往经过两种及以上系统化疗后疾病进展的晚期NSCLC患者的首个药物。安罗替尼组的中位OS(9.46个月)较安慰剂组[6.37个月;风险比(hazard ratio,HR)=0.70,95%置信区间(confidence Interval,CI):0.55–0.89;双侧log-rank P=0.002]显著延长。安罗替尼组的客观缓解率(objective responserate,ORR)为9.2%,安慰剂组为0.7%。安罗替尼组的中位缓解持续时间(durationofresponse,DoR)为4.83个月,95%CI为3.31–6.97个月。安罗替尼的常见不良反应(adverse drug reactions,ADRs)包括高血压(67.4%)、手足综合征(43.9%)、咳血(14.0%)、促甲状腺激素(thyroid stimulating hormone,TSH)升高(46.6%)、心电图QT间期(corrected QT Interval,QTc)延长(26.2%)。结论安罗替尼显著延长了患者的OS,可作为经二线及以上化疗后晚期或转移性非小细胞肺癌的一种新的治疗方案。 | Ming Zhou Xiaoyuan Chen Hong Zhang Lin Xia Xin Tong Limin Zou Ruimin Hao Jianhong Pan Xiao Zhao Dongmei Chen Yuanyuan Song Yueli Qi Ling Tang Zhifang Liu Rong Gao Yuankai Shi Zhimin Yang | 2019 | 癌症2019，38，12： | 7 |
| 15 | Melatonin enhances radiofrequency-induced NK antitumor immunity,causing cancer metabolism reprogramming and inhibition of multiple pulmonary tumor development显示文摘Surgery is the comm on treatme nt for early lung cancer with multiple pulm onary no dules,but it is often accompanied by the problem of significant malignancy of other nodules in non-therapeutic areas.In this study,we found that a combined treatment of local rad iofreq ue ncy ablati on(RFA)and melatonin(MLT)greatly improved clinical outcomes for early lung cancer patie nts with multiple pulmonary nodules by minimizing lung function injury and reducing the probability of malignant transformation or enlargement of nodules in non-ablated areas.Mechanically,as demonstrated in an associated mouse lung tumor model,RFA not only effectively remove treated tumors but also stimulate antitumor immunity,which could inhibit tumor growth in non-ablated areas.MLT enhanced RFA-stimulated NK activity and exerted synergistic antitumor effects with RFA.Transcriptomics and proteomics analyses of residual tumor tissues revealed enhanced oxidative phosphorylation and reduced acidification as well as hypoxia in the tumor microenvironment,which suggests reprogrammed tumor metabolism after combined treatment with RFA and MLT.Analysis of residual tumor further revealed the depressed activity of MAPK,NF-kappa B,Wnt,and Hedgehog pathways and upregulated P53 pathway in tumors,which was in line with the inhibited tumor growth.Combined RFA and MLT treatment also reversed the Warburg effect and decreased tumor malignancy.These findings thus demonstrated that combined treatment of RFA and MLT effectively inhibited the malignancy of non-ablated nodules and provided an innovative non-invasive strategy for treating early lung tumors with multiple pulmonary nodules.Trial registration:www.chictr.org.cn,identifier ChiCTR2100042695,http://gffzz62a03ee25e6f4a77huqwvpovcbucc6xkf.ffgz.tsg.suse.edu.cn/showproj.aspx?proj=120931. | Ming Li Bingjie Hao Menghuan Zhang Russel J.Reiter Shumeng Lin Tiansheng Zheng Xiangyun Chen Yanbei Ren Liduo Yue Baigenzhin Abay Guojie Chen Xiao Xu Yufeng Shi Lihong Fan | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 6 |
| 16 | Compression-related EMIC waves drive relativistic electron precipitation显示文摘With coordinated observations of the NOAA 15 satellite and OUL magnetometer station in Finland, we report that the electromagnetic ion cyclotron(EMIC) waves which were stimulated by the compression of the magnetosphere drive relativistic electron precipitation in geoquiescence on 1 Jan 2007. After an enhancement of solar wind dynamic pressure(SWDP), a dayside Pc1 pulsation was observed by the OUL station. Such a Pc1 pulsation is caused by an EMIC wave which propagates from the generation source to lower altitudes. Simultaneously, the NOAA 15 satellite registered an enhancement of precipitating electron count rates with energies >3 Me V within the anisotropic zone of protons. This phenomenon is coincident with the quasi-linear theoretical calculation presented in this paper. Our observations suggest that after a positive impulse of solar wind, the compression-related EMIC waves can drive relativistic electrons precipitation and play a pivotal role in the dynamic of radiation belts. | WANG De Dong YUAN Zhi Gang DENG Xiao Hua ZHOU Meng HUANG Shi Yong LI Ming LI Hui Min LI Hai Meng RAITA Tero PANG Ye | 2014 | Science China(Technological Sciences)2014，57，12： | 6 |
| 17 | Promoter methylation of Wnt/β-Catenin signal inhibitor TMEM88 is associated with unfavorable prognosis of nonsmall cell lung cancer显示文摘Objective:Recent research has indicated that altered promoter methylation of oncogenes and tumor suppressor genes is an important mechanism in lung cancer development and progression.In this study,we investigated the association between promoter methylation of TMEM88,a possible inhibitor of the Wnt/β-Catenin signaling,and the survival of patients with nonsmall cell lung cancer(NSCLC).Methods:Twelve pairs of tumor and adjacent non-tumor samples were used for microarray analyses of DNA methylation and gene expression.For validation,more than two hundred additional samples were analyzed for methylation using bisulfite pyrosequencing and for gene expression using q RT-PCR.Then the cell function were tested by wound healing,transwell,CCK8 and cell cycle assay.Results:Our analysis of patient specimens showed that TMEM88 methylation was higher in NSCLC tumors(82.2%±10.3,P<0.01)compared with the adjacent normal tissues(65.9%±7.2).The survival analysis revealed that patients with high TMEM88methylation had a shorter overall survival(46 months)compared with patients with low TMEM88 methylation(>56 months;P=0.021).In addition,we found that demethylation treatment could inhibit tumor cell proliferation,migration,and invasion,which was supportive of an association between methylation and survival.Conclusions:Based on these consistent observations,we concluded that TMEM88 may play an important role in NSCLC progression and that promoter methylation of TMEM88 may serve as a biomarker for NSCLC prognosis and treatment. | Rongna Ma Nannan Feng Xiao Yu Hongyan Lin Xiaohong Zhang Oumin Shi Huan Zhang Shuo Zhang Lei Li Min Zheng Ming Gao Herbert Yu Biyun Qian | 2017 | Cancer Biology & Medicine2017，14，4： | 6 |
| 18 | A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats显示文摘INTRODUCTIONLongtermtotalparenteralnutrition(TPN)canfrequentlyleadtothedevelopmentofhepaticsteatosis.Althoughitsincidencehas... | LIANG Li Jian, YIN Xiao Yu, LUO Shi Min, ZHENG Jin Fang, LU Ming De and HUANG Jie Fu | 1999 | World Journal of Gastroenterology1999，5，4： | 6 |
| 19 | Bevacizumab biosimilar LY01008 compared with bevacizumab(Avastin)as first-line treatment for Chinese patients with unresectable,metastatic,or recurrent non-squamous non-small-cell lung cancer:A multicenter,randomized,double-blinded,phase Ⅲ trial显示文摘Background:Previous studies have demonstrated the preclinical pharmacological and toxicological consistency,and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab(Avastin).This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer(NSCLC).Methods:StageⅢB-ⅣNSCLC patients with evaluable lesions,good physical status,and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin(combined treatment)for 4-6 cycles,followed by maintenance monotherapy with LY01008 until disease progression,intolerable toxicity,or death.The primary endpoint was objective response rate(ORR)in accordance with Response Evaluation Criteria in Solid Tumors(RECIST)version 1.1 confirmed by independent radiological review committees(IRRC).Secondary endpoints included disease control rate(DCR),duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.This study was registered in Clinical Trials.gov(NCT03533127).Results:Between December 15^(th),2017,and May 15^(th),2019,a total of 649 patients were randomized to the LY01008(n=324)or Avastin(n=325)group.As of September 25th,2019 for primary endpoint analysis,589 patients received ORR evaluation,with a median number of combined treatment cycles of 5(range 1-6)andmedian duration of treatment of 3.0(range 0.0-5.1)months.ORRof responseevaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%,respectively.The stratified ORR ratio was 0.91(90%CI 0.80-1.04,within the prespecified equivalence margin of 0.75-1.33).Up to May 15^(th),2020,with a median follow-up of 13.6(range 0.8-28.4)months,no notable differences in DCR,median DoR,median PFS,median OS,and 1-year OS rate were observed between the LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,LY01008 and Avastin groups.There were no clinically meaningful differences in safety and immunogenicity across treatment groups.Conclusions:LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC.LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable,metastatic,or recurrent non-squamous NSCLC patients in the first-line setting. | Yuankai Shi Kaijian Lei Yuming Jia Bingqiang Ni Zhiyong He Minghong Bi Xicheng Wang Jianhua Shi Ming Zhou Qian Sun Guolei Wang Dongji Chen Yongqian Shu Lianke Liu Zhongliang Guo Yong Liu Junquan Yang Ke Wang Ke Xiao LinWu Tienan Yi Debin Sun Mafei Kang Tianjiang Ma Yimin Mao Jinsheng Shi Tiegang Tang Yan Wang Puyuan Xing Dongqing Lv Wangjun Liao Zhiguo Luo Bin Wang Xiaohong Wu Xiaoli Zhu Shuhua Han Qisen Guo Rongyu Liu Zhiwei Lu Jianyong Zhang Jian Fang Changlu Hu Yinghua Ji Guolong Liu Hong Lu Dedong Wu Junhong Zhang Shuyang Zhu Zheng Liu Wensheng Qiu Feng Ye Yan Yu Yanqiu Zhao Qinhong Zheng Jun Chen Zhanyu Pan Yiping Zhang Wenjuan Lian Bo Jiang Bo Qiu Guojun Zhang Hua Zhang Yanju Chen Yuan Chen Hongbing Duan Manxiang Li Shengming Liu Lijun Ma Hongming Pan Xia Yuan Xueli Yuan Yulong Zheng Emei Gao Li Zhao Shumin Wang Can Wu | 2021 | Cancer Communications2021，41，9： | 5 |
| 20 | Effect of devazepide reversed antagonism of CCK-8 against morphineon electrical and mechanical activities of rat duodenum in vitro显示文摘INTRODUCTIONCholecystokininoctapeptide(CCK8)isatypicalbraingutpeptide.ManydatashowthatCCK8hasbeenthestrongestendogenousant... | XU Man Ying 1, LU Hui Ming 1, WANG Shu Zhen 1, SHI Wen Yan 2, WANG Xin Chun 2, YANG Dong Xiao 3, YANG Chun Xiao 3 and YANG Li Zhuang 3 | 1998 | World Journal of Gastroenterology1998，4，6： | 4 |
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