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IMpower210:A phase Ⅲ study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer

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Chinese Journal of Cancer Research 2024年第2期36卷 103-113页

作者： Yi-Long Wu Shun Lu Gongyan Chen Jianxing He Jifeng Feng Yiping Zhang Liyan Jiang Hongming Pan Jianhua Chang Jian Fang Amy Cai Lilian Bu Jane Shi Jinjing Xia Guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People's Hospital&Guangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhou 510080China Shanghai Lung Cancer Center Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China department of respiration Harbin Cancer HospitalHarbin Medical UniversityHarbin 150081China department of Thoracic Oncology and Surgery the First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China department of Medical Oncology Jiangsu Cancer HospitalNanjing 210009China department of Medical Oncology Zhejiang Cancer HospitalHangzhou 330022China department of Pulmonary Medicine Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China department of Medical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China department of Medical Oncology Shenzhen HospitalCancer Hospital of Chinese Academy of Medical SciencesShenzhen 518116China department of Thoracic Oncology Beijing Cancer HospitalBeijing 100142China Product Development Shanghai Roche Pharmaceutical LtdShanghai 201203China

Objective: IMpower210(NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs.docetaxel as second-line treatment for advanced non-small cell lung cancer(NSCLC) in East Asian patients.Methods: Key eligibility criteria for this phase Ⅲ, open-label, randomized study included age ≥18 years;histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system(7th edition);Eastern Cooperative Oncology Group performance status of 0 or 1;and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab(1,200 mg) or docetaxel(75 mg/m^(2)). The primary study endpoint was overall survival(OS) in the intention-to-treat(ITT) population with wild-type epidermal growth factor receptor expression(ITT EGFR-WT) and in the overall ITT population.Results: Median OS in the ITT EGFR-WT population(n=467) was 12.3 [95% confidence interval(95% CI),10.3-13.8] months in the atezolizumab arm(n=312) and 9.9(95% CI, 7.8-13.9) months in the docetaxel arm[n=155;stratified hazard ratio(HR), 0.82;95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5(95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1(95% CI, 8.4-14.2) months(n=377) with docetaxel treatment(n=188;stratified HR, 0.87;95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events(TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm.Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade3/4 TRAEs.

关键词： Atezolizumab East Asia non-small cell lung cancer programmed death-ligand 1 inhibitors monoclonal antibody

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Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment:A phase 2 clinical trial(BG01-1801)

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Cancer Pathogenesis and Therapy 2024年第2期2卷 103-111页

作者： Yuankai Shi Gongyan Chen Yanqiu Zhao Jing Zhao Lin Lin department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted DrugsBeijing 100021China department of respiration Harbin Medical University Cancer HospitalHarbinHeilongjiang 150040China Respiratory department of Internal Medicine Henan Provincial Cancer HospitalZhengzhouHenan 450003China department of Pulmonary and Critcal Care Medicine Peking Union Medical College HospitaChinese Academy of Medical Sciences&Peking Union Medical College Beijing100021China

Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents challenges.The aim of this open-label,multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone,a novel genetically engineered epothilone analog and microtubule-stabilizing agent,as a third-or later-line treatment for locally advanced ormetastatic NSCLC.Methods:Patients who had failed standard second-line treatment(including platinum-containing chemotherapy or targeted therapy)received utidelone(40 mg/m?via intravenous injection daily,day 1-5)every 21 days.The primary endpoint was the objective response rate(ORR).Secondary endpoints were the duration of response(DoR),progression-free survival(PFS),overall survival(OS),and safety.Results:From March 12,2019 to January 18,2021,26 pretreated patients with locally advanced or metastatic NSCLC(100%of patients had received prior platinum and 65.4%patients had received prior taxane treatment)were enrolled(80.8%of patients had adenocarcinoma).At baseline,nine(34.6%)patients had received secondline treatment,10(38.5%)patients had received third-line treatment,and seven(26.9%)patients had received fourth-or later-line treatment.By the data cut-off date of August 10,2021,the median follow-up was 7.49 months(range,1.4-26.7 months).The ORR was 15.4%(95%confidence interval[CI],4.4%-34.9%)in the intention-totreat(ITT)cohort(N=26)and 19.0%(95%CI,5.4%-41.9%)in the per-protocol(PP)cohort(N=21).The disease control rate was 69.2%(95%CI,48.2%-85.7%)and 81.0%(95%CI,58.1%-94.6%)in the ITT and PP cohorts,respectively.The median DoR was 4.1 months(95%CI,3.1-5.1 months)in the ITT cohort.The median PFS was 4.37 months(95%CI,2.50-5.29 months)in the ITT cohort and 4.37 months(95%CI,2.50-9.76 months)in the PP cohort.The median OS was not reached,and the 12-month OS rate was 69%(95%CI,45.1%-84.1%).Grade 3/4 treatment-emergent adverse events occurred in 38.5%of patients,and the most common was

关键词： Utidelone Locally advanced or metastatic non-small-cell lung cancer Efficacy Platinum-and taxane-refractory

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Obstructive sleep apnea aggravates neuroinflammation and pyroptosis in early brain injury following subarachnoid hemorrhage via ASC/HIF-1α pathway

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Neural Regeneration Research 2022年第11期17卷 2537-2543页

作者： Jun Xu Qian Li Chen-Yu Xu Shan Mao Jia-Jia Jin Wei Gu Ying Shi Chun-Fang Zou Liang Ye department of respiration Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina department of respiration Nanjing Yuhua HospitalYuhua Branch of Nanjing First HospitalNanjingJiangsu ProvinceChina

Obstructive sleep apnea can worsen the prognosis of subarachnoid hemorrhage.Howeve r,the underlying mechanism remains unclear.In this study,we established a mouse model of subarachnoid hemorrhage using the endovascular perforation method and exposed the mice to intermittent hypoxia for 8 hours daily for 2 consecutive days to simulate sleep apnea.We found that sleep apnea aggravated brain edema,increased hippocampal neuron apoptosis,and worsened neurological function in this mouse model of subarachnoid hemorrhage.Then,we established an in vitro HT-22 cell model of hemin-induced subarachnoid hemorrhage/intermittent hypoxia and found that the cells died,and lactate dehydrogenase release increased,after 48 hours.We further investigated the underlying mechanism and found that sleep apnea increased the expression of hippocampal neuroinflammatory factors interleukin-1β,interleukin-18,inte rleukin-6,nuclear factorκB,pyro ptosis-related protein caspase-1,pro-caspase-1,and NLRP3,promoted the prolife ration of astrocytes,and increased the expression of hypoxia-inducible factor 1αand apoptosis-associated speck-like protein containing a CARD,which are the key proteins in the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.We also found that knockdown of hypoxia-inducible factor 1αexpression in vitro greatly reduced the damage to HY22 cells.These findings suggest that sleep apnea aggravates early brain injury after subarachnoid hemorrhage by aggravating neuroinflammation and pyroptosis,at least in part through the hypoxia-inducible factor 1α/apoptosis-associated speck-like protein containing a CARD signaling pathway.

关键词： apoptosis associated speck like protein containing a CARD early brain injury hypoxia-inducible factor 1α nucleotide-binding domain and leucine-rich repeat protein 3 obstructive sleep apnea pyroptosis neuroinflammation subarachnoid hemorrhage

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Modulatory effect of D-pinitol on bleomycin-induced pulmonary fibrosis in rats

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Asian Pacific Journal of Tropical Biomedicine 2023年第5期13卷 205-213页

作者： Yu-Ling Duan Zhi-Hua Wang Yan-Xia Huo Yang Zhang Xiao-Ran Wu Cui-Ke Gong Lin-Lin Bai department of respiration Medicine Xingtai People’s HospitalXingtaiHebei ProvinceChina

Objective:To assess the effect of D-pinitol on pulmonary fibrosis induced by bleomycin.Methods:Sprague-Dawley rats received intratracheal bleomycin(6 IU/kg)to induce pulmonary fibrosis,followed by administration of either D-pinitol(5,10,or 20 mg/kg)or vehicle or methylprednisolone(10 mg/kg)over 28 days after bleomycin administration.Lung function,biochemical parameters,serum biochemistry,mRNA expressions,and histological features were observed.Results:D-pinitol at 10 and 20 mg/kg significantly(P<0.05)attenuated bleomycin-induced bronchoalveolar lavage fluid,decreased myeloperoxidase,nitric oxide,malondialdehyde levels,and increased glutathione and superoxide dismutase level.D-pinitol also improved lung function(enhanced pause,frequency of breathing,expired volume,and tidal volume).Besides,D-pinitol significantly(P<0.05)upregulated Nrf2 and downregulated mRNA expressions of TGF-β,collagen-1,and Smad-3.Furthermore,considerably less inflammation(peribronchial,perivascular,and total),Ashcroft,and interstitial fibrosis scores were observed in the D-pinitol group.Conclusions:D-pinitol exerts its effect against bleomycin-induced pulmonary fibrosis via antioxidative and anti-fibrotic pathways.

关键词： Antioxidant Bleomycin Collagen-1 D-pinitol Pulmonary fibrosis Smad-3 TGF-β

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Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer’s Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice

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Neuroscience Bulletin 2024年第2期40卷 182-200页

作者： Yang Zhu Hao Huang Zhi Chen Yong Tao Ling-Yi Liao Shi-Hao Gao Yan-Jiang Wang Chang-Yue Gao department of Rehabilitation Medicine Daping HospitalArmy Medical UniversityChongqing 400042China department of Neurology and Center for Clinical Neuroscience Daping HospitalArmy Medical UniversityChongqing 400042China department of Special Medicine Daping HospitalArmy Medical UniversityChongqing 400042China

Intermittent theta burst stimulation(iTBS),a time-saving and cost-effective repetitive transcranial magnetic stimulation regime,has been shown to improve cognition in patients with Alzheimer’s disease(AD).However,the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown.Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation.Here,we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1(ISCA1,an essential regulatory factor for mitochondrial respiration)in the brain of APP/PS1 mice.In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function,which is required for ISCA1.Moreover,iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice.The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD.We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

关键词： Intermittent theta burst stimulation Alzheimer’s disease Iron-sulfur cluster assembly 1 Mitochondrial dysfunction Neurodegeneration

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Electrobiocorrosion by microbes without outer-surface cytochromes

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mLife 2024年第1期3卷 110-118页

作者： Dawn E.Holmes Trevor L.Woodard Jessica A.Smith Florin Musat Derek R.Lovley department of Microbiology University of Massachusetts AmherstAmherstMassachusettsUSA department of Physical and Biological Science Western New England UniversitySpringfieldMassachusettsUSA department of Biomolecular Sciences Central Connecticut State UniversityNew BritainConnecticutUSA department of Biology Section for MicrobiologyAarhus UniversityAarhusDenmark department of Molecular Biology and Biotechnology Facuity of Biology and GeologyBabes-Bolyai UniversityCluj-NapocaRomania

Anaerobic microbial corrosion of iron-containing metals causes extensive economic damage.Some microbes are capable of direct metal-to-microbe electron transfer(electrobiocorrosion),but the prevalence of electrobiocorrosion among diverse methanogens and acetogens is poorly understood because of a lack of tools for their genetic manipulation.Previous studies have suggested that respiration with 316L stainless steel as the electron donor is indicative of electrobiocorrosion,because,unlike pure Fe^(0),316L stainless steel does not abiotically generate H2 as an intermediary electron carrier.Here,we report that all of the methanogens(Methanosarcina vacuolata,Methanothrix soehngenii,and Methanobacterium strain IM1)and acetogens(Sporomusa ovata and Clostridium ljungdahli)evaluated respired with pure Fe^(0)as the electron donor,but only M.vacuolata,Mx.soehngeni,and S.ovata were capable of stainless steel electrobiocorrosion.The electrobiocorrosive methanogens re-quired acetate as an additional energy source in order to produce methane from stainless steel.Cocultures of S.ovata and Mx.soehngeni demonstrated how acetogens can provide acetate to methanogens during corrosion.Not only was Meth-anobacterium strain IM1 not capable of electrobiocorrosion,but it also did not accept electrons from Geobacter metal-lireducens,an effective electron-donating partner for direct interspecies electron transfer to all methanogens that can directly accept electrons from Fe^(0).The finding that M.vacuolata,Mx.soehngeni,and S.ovata are capable of electrobiocorrosion,despite a lack of the outer-surface c-type cytochromes previously found to be important in other electrobiocorrosive microbes,demonstrates that there are multiple microbial strategies for making electrical contact with Fe^(0).

关键词： acetogen corrosion Fe^(0) methanogen stainless steel

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Effect of organic mineral supplementation in reducing oxidative stress in Holstein calves during short‑term heat stress and recovery conditions

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Journal of Animal Science and Biotechnology 2024年第2期15卷 812-825页

作者： A-Rang Son Seon-Ho Kim Mahfuzul Islam Michelle Miguel Ye Pyae Naing Sang-Suk Lee Ruminant Nutrition and Anaerobe Laboratory Department of Animal Science and TechnologySunchon National UniversitySuncheon 57922Korea department of Microbiology and Parasitology Sher-e-Bangla Agricultural UniversityDhaka 1207Bangladesh

Background This study investigated the effects of inorganic and organic minerals on physiological responses,oxidative stress reduction,and rumen microbiota in Holstein bull calves(123.81±9.76 kg;5 months old)during short-term heat stress(HS)and recovery periods.Eight Holstein calves were randomly assigned to four treatment groups:no mineral supplementation(Con),inorganic minerals(IM),organic minerals(OM),and high-concentration organic minerals(HOM)and two thermal environments(HS and recovery)using 4×2 factorial arrangement in a crossover design of four periods of 35 d.Calves were maintained in a temperature-controlled barn.The experimental period consisted of 14 d of HS,14 d of recovery condititon,and a 7-d washing period.Results Body temperature and respiration rate were higher in HS than in the recovery conditions(P0.05).The principal coordinate analysis represented that the overall rumen microbiota was not influenced by mineral supplementation;however,temperature-induced microbial structure shifts were indicated(PERMANOVA:P<0.05).At the phylum level,Firmicutes and Actinobacteria decreased,whereas Fibrobacteres,Spirochaetes,and Tenericutes increased(P<0.05),under HS conditions.The genus Treponema increased under HS conditions,while Christensenella was higher in recovery conditions(P<0.05).Conclusion HOM supplementation during HS reduced cor

关键词： Antioxidant status Heat stress Holstein bull calves Organic mineral supplementation Oxidative stress

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Prognostic factors for community-acquired pneumonia in middle-aged and elderly patients treated with integrated medicine

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中医杂志：英文版 2012年第2期32卷 179-186页

作者：李建生侯政昆余学庆李素云孙子凯张伟贾新华郑四平王明航王海峰 Geriatric department Henan College of Traditional Chinese Medicine respiration department First Affiliated Hospital of Henan College of Traditional Chinese Medicine respiration department Jiangsu Province Hospital of Traditional Chinese Medicine respiration department Affiliated Hospital of Shandong University of Chinese Medicine respiration department First Affiliated Hospital of Changchun University of Chinese Medicine

OBJECTIVE:To identify prognostic factors in middle-aged and elderly patients with community-acquired pneumonia(CAP) who underwent integrated interventions involving traditional Chinese medicine(TCM) and modern medicine.METHODS:Patients aged ≥45 years and diagnosed with CAP were divided into a middle-aged cohort(45-59 years) and an elderly cohort(≥60 years),and clinical data comprising 75 predictor variables in seven classes were collected.After replacing missing data,calibrating multicenter differences and classifYing quantitative data,univariate and multivariate analysis were performed.RESULTS:On multivariate analysis,eight independent risk factors-respiration rate,C reactive protein(CRP),cost of hospitalization,anemia,gasping,confusion,moist rales and pneumonia severity index(PSI)-were correlated with the outcome "not cured" in the elderly cohort.Nine factors-neutrophil percentage(Neu%),blood urea nitrogen(BUN),time to clinical stability,appetite,anemia,confusion,being retired or unemployed,Gram-negative bacterial infection and educational level-were correlated with not cured in the middle-aged cohort.CONCLUSION:Independent predictive risk factors correlated with adverse outcomes in elderly patients were higher respiration rate,CRP≥four times the mean or median for the patient's center,cost of hospitalization>11,323 RMB and PSI>II,plus anemia,gasping,confusion and moist rales;those in middle-aged patients were higher Neu%,BUN≥mean or median,loss of appetite,anemia,confusion,being retired or unemployed and lower educational level.Gram-negative bacterial infection and time to clinical stability>9 days were protective factors.

关键词：中西医结合治疗老年人患者中年预后肺炎社区革兰氏阴性

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Yinyanghuo(Herba Epimedii Brevicornus) and its components for chronic obstructive pulmonary disease:preclinical evidence and possible mechanisms

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Journal of Traditional Chinese Medicine 2023年第2期43卷 386-396页

作者： WANG Yide GAO Zhen department of respiration Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical UniversityUrumqi 830000China department of Integrative Medicine Huashan hospital of Fudan UniversityShanghai 200040China

OBJECTIVE:To integrate Meta-analysis and bioinformatics strategies in the preliminary exploration of the potential mechanism of Yinyanghuo(Herba Epimedii Brevicornus) and its extract in treating chronic obstructive pulmonary disease(COPD).METHODS:First,Meta-analysis was carried out.The Chinese and English literature of Yinyanghuo(Herba Epimedii Brevicornus) in treating COPD was searched using the systematic strategy of combining subject words with free words.The included studies were evaluated by the SYRCLE risk bias assessment tool,after which the review manager software was used to combine the effect quantities for statistical analysis.Then,based on bioinformatics technology,the active ingredients and their targets of Yinyanghuo(Herba Epimedii Brevicornus) were screened,and the intersection genes were obtained by mapping and comparing with the targets of COPD.The "medicinal materials-compounds-targets model" was constructed,and the key pathways were annotated.Finally,the core target was docked with important compounds.RESULTS:A total of 8 studies were included in the Metaanalysis.The results showed that the Yinyanghuo(Herba Epimedii Brevicornus) group could significantly downregulate pro-inflammatory factors such as tumor necrosis factor-α(TNF-α) and interleukin(IL)-8 and increase the expression of anti-inflammatory factors and antioxidant factors such as IL-10 and phospho-protein kinase B(pAKT) in the COPD model(all P < 0.05).A total of 23 active components and 102 corresponding target genes of Yinyanghuo(Herba Epimedii Brevicornus) were obtained by bioinformatics technology,among which 17 compounds and 63 targets were closely related to COPD.The results of enrichment analysis mainly included TNF signaling pathway,phosphoinositide 3-kinase(PI3K)/Akt signaling pathway,cancer signaling pathway,and other inflammatory reactions,oxidative stress,and tumorrelated pathways.The molecular docking results showed that the binding energy fractions of the top five components of 24-epicampesterol with 10 core targets such a

关键词： Yinyanghuo(Herba Epimedii Brevicornus) pulmonary disease chronic obstructive Meta-analysis computational biology

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Evaluation of serum and pleural levels of endostatin and vascular epithelial growth factor in lung cancer patients with pleural effusion

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Asian Pacific Journal of Tropical Medicine 2012年第3期5卷 239-242页

作者： Yu Zhang Li-Ke Yu Ning Xia department of respiration Nanjing Chest Hospital

Objective:To evaluate the diagnostic value of endostatin(ES),vascular endothelial growth factor (VEGF) and careinoembryonie antigen(CEA) in both serum and pleural effusion of lung cancer patients.Methods:Levels of ES,VEGF and CEA in 52 malignant pleural effusion due to lung cancer and 50 patients with non-malignant disease were measured by using sandwich enzymelinked immunosorbent assay and microparticle enzyme immunoassay.Results:The ES.VEGF and CEA levels in pleural effusion and serum,and their ratio(F/S) were higher in lung cancer group than that in benign group,and the differences were statistically significant(P<0.05).The diagnostic efficiency of ES+VEGF for lung cancer was superior to either single detection.The diagnostic efficiency of ES+VEGK+CEA was superior to either ES+VEGF or ES+CEA.Conclusions: The results suggest that ES,VEGF and CEA might be useful in the differentiation between benign and malignant pleural effusion due to lung cancer.In comparison with either single determination of concentration in serum or pleural fluid,the couiljined detection of two or three markers is of important clinical significance in the diagnosis of lung cancer.

关键词： Pleural effusion Serum Endostatin Lung cancer Vascular endothelial growth factor

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