简介：摘要：本文着重介绍了小型燃煤锅炉的脱硝系统的反应机理、系统构成，并以实施环保工艺改造后的35t/h燃煤锅炉为例，着重对影响SNCR-SCR联合脱硝工艺运行的相关因素和造成的部分问题进行了分析，给出了产生影响的原因。

简介：Non-smallcelllungcancer(NSCLC)ranksastheleadingcauseofcancer-relateddeathintheworld.Brainmetastasis(BM)isacommoncomplicationofNSCLC,with25%–40%ofpatientsdevelopingBMduringthecourseofthedisease.Asignificantstrategyoflocaldiseasecontrolinthecentralnervoussystemisradiationtherapy.Withthedevelopmentofprecisionmedicine,theconceptoftreatinglungcancerBMhasgraduallychanged.Inthiscase,weperformedasurgicalproceduretoobtainenoughtumortissueforthedetectionofthetargetgeneandotherrelatedexperimentsafterthepatientwasinformed.Finally,wefoundthatthepatienthadbothhepatocytegrowthfactorreceptor(MET)geneamplificationandkinesinlightchain1-anaplasticlymphomakinasefusion(KLC1-ALK)throughnext-generationsequencingandshowedsensitivitytothetargetedtherapyofcrizotinib.Thepatientexhibitedgoodresponse.Ourcasewassuccessfulandunderwenttargetedtherapywiththeguidanceofprecisediagnosis.

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简介：AbstractBackground:Percutaneous local tumor ablation (LTA) and stereotactic body radiotherapy (SBRT) have been regarded as viable treatments for early-stage lung cancer patients. The purpose of this study was to compare the efficacy and safety of LTA with SBRT for early-stage non-small cell lung cancer (NSCLC).Methods:PubMed, Embase, Cochrane library, Ovid, Google scholar, CNKI, and CBMdisc were searched to identify potential eligible studies comparing the efficacy and safety of LTA with SBRT for early-stage NSCLC published between January 1, 1991, and May 31, 2021. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were applied to estimate the effect size for overall survival (OS), progression-free survival (PFS), locoregional progression (LP), and adverse events.Results:Five studies with 22,231 patients were enrolled, including 1443 patients in the LTA group and 20,788 patients in the SBRT group. The results showed that SBRT was not superior to LTA for OS (HR = 1.03, 95% CI: 0.87-1.22, P = 0.71). Similar results were observed for PFS (HR = 1.09, 95% CI: 0.71-1.67, P = 0.71) and LP (HR = 0.66, 95% CI: 0.25-1.77, P = 0.70). Subgroup analysis showed that the pooled HR for OS favored SBRT in patients with tumors sized >2 cm (HR= 1.32, 95% CI: 1.14-1.53, P = 0.0003), whereas there was no significant difference in patients with tumors sized ≤2 cm (HR = 0.93, 95% CI: 0.64-1.35, P = 0.70). Moreover, no significant differences were observed for the incidence of severe adverse events (≥grade 3) (OR = 1.95, 95% CI: 0.63-6.07, P = 0.25) between the LTA group and SBRT group.Conclusions:Compared with SBRT, LTA appears to have similar OS, PFS, and LP. However, for tumors >2 cm, SBRT is superior to LTA in OS. Prospective randomized controlled trials are required to determine such findings.INPLASY Registration Number:INPLASY202160099

简介：客观：为了探索病理和临床的反应率的变化，为非小的房间肺癌症与MVP政体由neoadjuvant化疗对待。方法：这是在有阶段I-IIIa的病人的使随机化的研究。在他们之中，46个病人在neoadjuvant注册了1鈥对待的化疗吗？功课MVP政体。MMC被给6mg/M2由静脉内(I.V)day1上的注入，VDS2.5鈥吗？day1,8或day15上的mg/M2I.V，day1上的DDP90mg/M2I.V。治疗每28天被再循环。评估与的临床的RR标准。所有外科的样品与病理被分类。结果：在2功课化疗的全面反应率在1堂功课比那好(P<0.01)。有病理等级的病人的数字我在2功课化疗的鈥揑I比那高嗨1堂功课(P<0.01)。但是RR不能完全翻译了成病理等级我鈥揑I。病理等级我鈥揑I仔细与肿瘤参与(T)被联系(P<0.01)然而并非与地区性的淋巴节点转移(N)密切相关。和PCR使用RR判定化疗反应是合理的。NR病人不能作为化疗失败是问候。不服务毒性和外科的死亡被观察。结论：MVP政体是为I-IIIaNSCLC的有效neoadjuvant治疗政体。

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简介：Objective:Survivalbenefitofadjuvantchemotherapy(AC)ofpatientswithintrapulmonarylymphnode(IPLN)metastasis(level12-14)needsinvestigation.WeevaluatedtheimpactofAConpatientswhosemetastaticnodeswerelimitedtointrapulmonarylevelsaftersystematicdissectionofN1nodes.Methods:First,155consectivecasesoflungcancerconfirmedaspathologicN1werecollectedandevaluated.PatientsreceivedsystematicdissectionofN2andN1nodes.ForpatientswithIPLNmetastasis,survivaloutcomeswerecomparedbetweenthosereceivingACandthosenotreceivingAC.Results:Inthisgroup,112cases(72.3%)hadIPLNmetastasisand55cases(35.5%)hadN1involvementlimitedtolevel13-14withoutfurtherdiseasespreadtohigherlevels.PatientswithIPLNinvolvementhadabetterprognosisthanthatofpatientswithhilar-interlobarinvolvement.FortheintrapulmonaryN1group(level12-14-positive,level10-11-negativeorunknown,n=112),nosurvivalbenefitwasfoundbetweentheACgroupandnonACgroup[5-yearoverallsurvival(OS):54.6±1.6vs.50.4±2.4months,P=0.177].However,76of112casesforwhomharvestingoflevel-10andlevel-11nodeswasdonedidnotshowcancerinvolvementinpathologyreports(level12-14-positive,level10-11bothnegative),oncologicoutcomewasbetterforpatientsreceivingACthanthosenotreceivingACinthissubgroup(5-yearOS:57.3±1.5vs.47.1±3.2months,P=0.002).Conclusions:OncologicoutcomemaybeimprovedbyACforpatientswithinvolvementofN1nodeslimitedtointrapulmonarylevelsaftercompleteexaminationofN1nodes.

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简介：AbstractBackground:Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression.Methods:The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation.Results:CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2.Conclusion:CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.

简介：AbstractBackground:Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as erlotinib and gefitinib, are widely used to treat non-small cell lung cancer (NSCLC). However, acquired resistance is unavoidable, impairing the anti-tumor effects of EGFR-TKIs. It is reported that histone deacetylase (HDAC) inhibitors could enhance the anti-tumor effects of other antineoplastic agents and radiotherapy. However, whether the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) can overcome erlotinib-acquired resistance is not fully clear.Methods:An erlotinib-resistant PC-9/ER cell line was established through cell maintenance in a series of erlotinib-containing cultures. NSCLC cells were co-cultured with SAHA, erlotinib, or their combination, and then the viability of cells was measured by the 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and apoptosis was determined by flow cytometry and western blotting. Finally, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was assessed by western blotting.Results:The half-maximal inhibitory concentration of parental PC-9 cells was significantly lower than the established erlotinib-acquired resistant PC-9/ER cell line. PC-9/ER cells demonstrated reduced expression of PTEN compared with PC-9 and H1975 cells, and the combination of SAHA and erlotinib significantly inhibited cell growth and increased apoptosis in both PC-9/ER and H1975 cells. Furthermore, treating PC-9/ER cells with SAHA or SAHA combined with erlotinib significantly upregulated the expression of PTEN mRNA and protein compared with erlotinib treatment alone.Conclusions:PTEN deletion is closely related to acquired resistance to EGFR-TKIs, and treatment with the combination of SAHA and erlotinib showed a greater inhibitory effect on NSCLC cells than single-drug therapy. SAHA enhances the suppressive effects of erlotinib in lung cancer cells, increasing cellular apoptosis and PTEN expression. SAHA can be a potential adjuvant to erlotinib treatment, and thus, can improve the efficacy of NSCLC therapy.

简介：在答案的膜蛋白质的结构在水晶阶段与那不同。我们在场小角度X光散布的主要结果(萨克斯风管)解决了第一次在净化的答案从光合的bacteriaRhodopseudomonasacidophile收获天线膜蛋白质建筑群LH2的一盏灯的拓扑的结构。我们在答案的LH2建筑群的椭圆的形状清楚地在水晶阶段从它的圆形的结构背离的结果表演由X光衍射决定了。这结果在LH2提供卓见进结构和功能相互影响。

简介：Objective:Tocomparetheefficacyandadverseeffectsofpaclitaxel-etoposide-carboplatin/cisplatin(TEP/TCE)regimenwiththoseofetoposide-carboplatin/cisplatin(EP/CE)regimenasfirst-linetreatmentforcombinedsmall-celllungcancer(CSCLC).Methods:Aretrospectivestudywasconductedon62CSCLCpatientswhoweretreatedatTianjinMedicalUniversityCancerInstituteandHospitalfromJuly2000toApril2013andadministeredwithTEP/TCEregimen(n=19)orEP/CEregimen(n=43)asfirst-lineCSCLCtreatment.Allpatientsreceivedmorethantwocyclesofchemotherapy,andtheresponsewasevaluatedeverytwocycles.Theprimaryendpointwasoverallsurvival(OS),andthesecondaryendpointswereprogression-freesurvival(PFS),objectiveresponserate(ORR),diseasecontrolrate(DCR),andadverseeffects.Results:ORRbetweentheTEP/TCEandEP/CEgroupsshowedastatisticaldifference(90%vs.53%,P=0.033).BothgroupsfailedtoreachastatisticaldifferenceinDCR(100%vs.86%,P=0.212).ThemedianPFSandOSoftheTEP/TCEgroupwereslightlylongerthanthoseoftheEP/CEgroup,althoughbothgroupsfailedtoreachastatisticaldifference(10.5vs.8.9months,P=0.484;24.0vs.17.5months,P=0.457).However,stratifiedanalysisindicatedthatthePFSofpatientswithstagesIIIandIVCSCLCshowedmarginallysignificantdifferencebetweentheTEP/TCEandEP/CEgroups(19.5vs.7.6months;P=0.071).BothratesofgradeIVbonemarrowdepressionandterminationofchemotherapyintheTEP/TCEgroupweresignificantlyhigherthanthoseintheEP/CEgroup(26.3%vs.7.0%,P=0.036;31.6%vs.14.7%,P=0.004).Conclusion:TheTEP/TCEregimenmaynotbepreferredforCSCLC,andthisthree-drugregimenrequiresfurtherexplorationandresearch.Todate,theEP/CEregimenremainsthestandardtreatmentforCSCLCpatients.

简介：她出生于一个曾经在美国政坛风光无限的贵族家庭，也是那个百年来被悲剧命运所诅咒的传奇家族。随着她和弟弟特德·肯尼迪在半个月内的相继辞世，辉煌了将近一个世纪的肯尼迪家族似乎走到了风雨飘摇、大厦将倾的前夜。然而，她与自己那些权倾一时的肯尼迪兄弟不同，她把自己毕生的精力都投入到为智障人群奔走呼吁的事业中。作为特奥会的创始人，她的努力不仅为智障人群的生活带来了阳光，更为健全人打开了一扇沟通、了解弱势同胞的窗口。

简介：Objective:Ameta-analysiswasperformedtoaugmenttheinsufficientdataontheimpactofmutativeEGFRdownstreamphosphatidylinositol-3-kinase(PI3K)andmitogen-activatedproteinkinase(MAPK)pathwaysontheclinicalefficiencyofepidermalgrowthfactorreceptortyrosinekinaseinhibitor(EGFR-TKI)treatmentofnon-smallcelllungcancer(NSCLC)patients.Methods:NetworkdatabaseswereexploredinApril,2015.PapersthatinvestigatedtheclinicaloutcomesofNSCLCpatientstreatedwithEGFR-TKIsaccordingtothestatusofK-rasand/orPIK3CAgenemutationwereincluded.Aquantitativemeta-analysiswasconductedusingstandardstatisticalmethods.Oddsratios(ORs)forobjectiveresponserate(ORR)andhazardratios(HRs)forprogression-freesurvival(PFS)andoverallsurvival(OS)werecalculated.Results:MutationinK-rassignificantlypredictedpoorORR[OR=0.22;95%confidenceinterval(CI),0.13-0.35],shorterPFS(HR=1.56;95%CI,1.27-1.92),andshorterOS(HR=1.59;95%CI,1.33-1.91)inNSCLCpatientstreatedwithEGFR-TKIs.MutantPIK3CAsignificantlypredictedshorterOS(HR=1.83;95%CI,1.05-3.20),showedpoorORR(OR=0.70;95%CI,0.22-2.18),andshorterPFS(HR=1.79;95%CI,0.91-3.53)inNSCLCpatientstreatedwithEGFR-TKIs.Conclusion:K-rasmutationadverselyaffectedtheclinicalresponseandsurvivalofNSCLCpatientstreatedwithEGFRTKIs.PIK3CAmutationshowedsimilartrends.InadditiontoEGFR,addingK-rasandPIK3CAasroutinegenebiomarkersinclinicalgeneticanalysisisvaluabletooptimizetheeffectivenessofEGFR-TKIregimensandidentifyoptimalpatientswhowillbenefitfromEGFR-TKItreatment.

简介：Integrinανβ6isexpressedatanundetectablelevelinnormaltissues,butisremarkablyupregulatedduringmanypathologicalprocesses,especiallyincancerandfibrosis.Noninvasiveimagingofintegrinανβ6expressionusingaradiotracerwithfavorableinvivopharmacokineticswouldfacilitatediseasediagnosisandtherapymonitoring.Throughdisulfide-cyclizedmethod,wesynthesizedinthisstudy,anewintegrinανβ6-targetedcyclicpeptide(denotedascHK),andradiolabeleditwith99mTc.Theabilityoftheresultingradiotracer99mTc-HYNIC-cHKtodetectintegrinανβ6expressioninpancreaticcancerxenograffsandidiopathicpulmonaryfibrosiswasevaluatedusingsmall-animalsingle-photonemissioncomputedtomography(SPECT)/computedtomography(CT).99mTc-HYNIC-cHKshowedsignificantlyimprovedinvivometabolicstabilitycomparedtothelinearpeptide-basedradiotracer99mTc-HYNICHK.99mTc-HYNIC-cHKexhibitedsimilarbiodistributionpropertiesto99mTc-HYNIC-HK,butthetumorto-muscleratiowassignificantlyincreased(2.99±0.87vs.1.82±0.27,P<0.05).High-contrastimagesofintegrinανβ6-positivetumorsandbleomycin-inducedfibroticlungswereobtainedbySPECT/CTimagingusing99mTc-HYNIC-cHK.Overall,ourstudiesdemonstratethat99mTc-HYNIC-cHKisapromisingSPECTradiotracerforthenoninya-siveimagingofintegrinανβ6inlivingsubjects.

简介：AbstractBackground:Emerging evidence indicates that the sineoculis homeobox homolog 1-eyes absent homolog 1 (SIX1-EYA1) transcriptional complex significantly contributes to the pathogenesis of multiple cancers by mediating the expression of genes involved in different biological processes, such as cell-cycle progression and metastasis. However, the roles of the SIX1-EYA1 transcriptional complex and its targets in colorectal cancer (CRC) are still being investigated. This study aimed to investigate the roles of SIX1-EYA1 in the pathogenesis of CRC, to screen inhibitors disrupting the SIX1-EYA1 interaction and to evaluate the efficiency of small molecules in the inhibition of CRC cell growth.Methods:Real-time quantitative polymerase chain reaction and western blotting were performed to examine gene and protein levels in CRC cells and clinical tissues (collected from CRC patients who underwent surgery in the Department of Integrated Traditional and Western Medicine, West China Hospital of Sichuan University, between 2016 and 2018, n = 24). In vivo immunoprecipitation and in vitro pulldown assays were carried out to determine SIX1-EYA1 interaction. Cell proliferation, cell survival, and cell invasion were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, clonogenic assay, and Boyden chamber assay, respectively. The Amplified Luminescent Proximity Homogeneous Assay Screen (AlphaScreen) method was used to obtain small molecules that specifically disrupted SIX1-EYA1 interaction. CRC cells harboring different levels of SIX1/EYA1 were injected into nude mice to establish tumor xenografts, and small molecules were also injected into mice to evaluate their efficiency to inhibit tumor growth.Results:Both SIX1 and EYA1 were overexpressed in CRC cancerous tissues (for SIX1, 7.47 ± 3.54 vs.1.88 ± 0.35, t = 4.92, P = 0.008; for EYA1, 7.61 ± 2.03 vs. 2.22 ± 0.45, t = 6.73, P = 0.005). The SIX1/EYA1 complex could mediate the expression of two important genes including cyclin A1 (CCNA1) and transforming growth factor beta 1 (TGFB1) by binding to the myocyte enhancer factor 3 consensus. Knockdown of both SIX1 and EYA1 could decrease cell proliferation, cell invasion, tumor growth, and in vivo tumor growth (all P < 0.01). Two small molecules, NSC0191 and NSC0933, were obtained using AlphaScreen and they could significantly inhibit the SIX1-EYA1 interaction with a half-maximal inhibitory concentration (IC50) of 12.60 ± 1.15 μmol/L and 83.43 ± 7.24 μmol/L, respectively. Administration of these two compounds could significantly repress the expression of CCNA1 and TGFB1 and inhibit the growth of CRC cells in vitro and in vivo.Conclusions:Overexpression of the SIX1/EYA1 complex transactivated the expression of CCNA1 and TGFB1, causing the pathogenesis of CRC. Pharmacological inhibition of the SIX1-EYA1 interaction with NSC0191 and NSC0933 significantly inhibited CRC cell growth by affecting cell-cycle progression and metastasis.

简介：AbstractBackground:There is limited information about thymosin α1 (Tα1) as adjuvant immunomodulatory therapy, either used alone or combined with other treatments, in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free (R0)-resected stage IA-IIIA NSCLC patients.Methods:A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were included. The patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not. A propensity score matching (PSM) analysis was performed to reduce bias, resulting in 1027 pairs of patients.Results:After PSM, the baseline clinicopathological characteristics were similar between the two groups. The 5-year disease-free survival (DFS) and overall survival (OS) rates were significantly higher in the Tα1 group compared with the control group. The multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis. A longer duration of Tα1 treatment was associated with improved OS and DFS. The subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age, sex, Charlson Comorbidity Index (CCI), smoking status, and pathological tumor-node-metastasis (TNM) stage, especially for patients with non-squamous cell NSCLC and without targeted therapy.Conclusion:Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection, except for patients with squamous cell carcinoma and those receiving targeted therapy. The duration of Tα1 treatment is recommended to be >24 months.

简介：Objective:Weinvestigatedthecorrelationbetweenthenumberofcirculatingtumorcells(CTCs)andwholebodymetabolictumorvolume(WBMTV)measuredby18F-fluorodeoxyglucose(FDG)positronemissiontomography/computedtomography(PET/CT).TheaimwastoevaluatethevalueoftheincorporationofCTCnumberandWBMTVintheprognosticpredictionofstageIIIsmall-celllungcancer(SCLC).Methods:Onehundredandtwenty-ninepatientswereenrolledinthisstudy.Allpatientsweretreatedwithfourcyclesofaplatinum-basedregimenandconcurrentchestirradiation,followedbyprophylacticcranialirradiation.BloodsamplesforCTCanalysiswereobtainedfrom112patientsbeforetheinitiationofchemotherapy(asabaseline),aftercycle1andaftercycle4.CTCsweremeasuredusingtheCELLSEARCH?system.ThepatientsunderwentpretreatmentFDGPET/CTWBMTV,whichincludedallmalignantlesions.TheSpearmanranktestwasusedtodeterminethecorrelationamongCTCcounts,WBMTVanddiseasestage.Overallsurvival(OS)andprogression-freesurvival(PFS)curveswereproducedusingtheKaplan-Meiermethod,andsurvivaldifferencesbetweengroupswereassessedbythelog-ranktest.Results:ThenumberofCTCsatbaselinedidnotcorrelatewithWBMTVbeforetheinitiationoftherapy(P=0.241).ThenumberofCTCsatbaselineandtheWBMTVbeforetheinitiationoftherapywereindependentrelevantfactorsforPFSandOS.Thesubgroupanalysis(GroupA:CTCcount>19.5andaWBMTV>266.5cm^3;GroupB:CTCcount>19.5andaWBMTV≤266.5cm^3;GroupC:CTCcount≤19.5andaWBMTV>266.5cm^3;GroupD:CTCcount≤19.5andaWBMTV≤266.5cm^3)showedthatthedifferenceswerestatisticallysignificantinthemedianPFS(GroupAvs.D,P<0.001;GroupBvs.D,P=0.018;GroupCvs.D,P=0.029)andinthemedianOS(GroupAvs.D,P<0.001;GroupBvs.D,P=0.012).Conclusions:CTCnumberandWBMTVarerelatedtoprogressionanddeathinpatientswithSCLC.TheincorporationofCTCnumberandWBMTVscanscanprovideadetailedprognosticpredictionforSCLC.

简介：AbstractBackground:As erythropoietin (EPO) has been used to treat anemia in cancer patients, negative controversy has continued. Unfortunately, its effects on non-small-cell lung carcinoma (NSCLC) cell lines are uncertain and the phenomenon of inducing immune escape of tumor cells remains to be explored. This study aimed to provide an important basis for the application of exogenous EPO in the treatment of tumor-associated anemia.Methods:Cells were cultured in 1% O2, 5% CO2, and 94% N2 to simulate a hypoxic environment of the tumor. A549 cell line (lower expression EPOR) and NCI-H838 cell line (higher expression EPOR) were treated with 2 and 8 U/ml recombinant human EPO (rhEPO). CCK-8 method was used to determine the logarithmic growth phase of the cells and to detect cell proliferation. The expression levels of VEGF, HIF-1α, and PD-L1 were determined by western blot. One-way ANOVA was used for statistical analysis between groups, with p < 0.05 indicating a significant difference.Results:Hypoxia itself could decrease the survival rate of NSCLC cells. Under the hypoxic condition, rhEPO induced tumor cells proliferation, especially in the NCI-H838 cell line, where 2 U/ml rhEPO increased the total number of surviving cells (Hypoxia + rhEPO 2 U/ml vs. Hypoxia, p < 0.05). Western blot analysis showed that hypoxia upregulated the expression of VEGF, HIF-1α, and PD-L1 in NSCLC cell lines (Normoxia vs. Hypoxia, p < 0.05), but may not be dependent on the expression levels of EPOR. RhEPO decreased the expression levels of VEGF and HIF-1α. In the A549 cell line, it depended on the concentration of rhEPO and was particularly obvious in HIF-1α (Hypoxia vs. Hypoxia + rhEPO 2 U/ml vs. Hypoxia + rhEPO 8 U/ml, p < 0.05). A low concentration of rhEPO may not reduce VEGF expression. In the NCI-H838 cell line, the effect of rhEPO on VEGF was more obvious, but it may be independent of rhEPO concentrations. The downregulation of PD-L1 expression by rhEPO was only presented in the A549 cell line and required higher rhEPO concentrations (Hypoxia + rhEPO 8 U/ml vs. Hypoxia&Hypoxia + rhEPO 2 U/ml, p < 0.05).Conclusion:The effect of prolonged high concentrations of rhEPO under hypoxic conditions resulted in accelerated cells proliferation of non-small-cell lung cancer and was independent of EPOR expression levels on the cell lines surface. Hypoxia resulted in increased expression of VEGF, HIF-1α, and PD-L1 on the NSCLC cell lines. Under normoxic conditions, rhEPO did not affect the expression of VEGF, HIF-1α, and PD-L1; but under hypoxic conditions, the application of rhEPO reduced the expression of VEGF, HIF-1α, and PD-L1, producing an impact on the biological behavior of tumor cells.

简介：AbstractBackground:Pancreatic cancer (PC) is a highly deadly malignancy with few effective therapies. We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) plays in PC cells by targeting far upstream element binding protein 1 (FUBP1) via microRNA-26a-5p (miR-26a-5p).Methods:SNHG6 expression was predicted by bioinformatics, followed by verification via reverse transcription quantitative polymerase chain reaction. Then, the interactions among SNHG6, miR-26a-5p, and FUBP1 were detected through online software analysis, dual luciferase reporter assay and RNA pull-down. After that, cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6, miR-26a-5p, and FUBP1 and their roles in PC cells. Finally, the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice. A t-test, one-way and two-way analysis of variance were used for data analysis.Results:Compared with that in normal tissues, SNHG6 was highly expressed in PC tissues (1.00 ± 0.05 vs. 1.56 ± 0.06, t= 16.03, P < 0.001). Compared with that in human pancreatic duct epithelial cells (HPDE6-C7), SNHG6 showed the highest expression in PANC-1 cells (1.00 ± 0.06 vs. 3.87 ± 0.13, t= 34.72, P < 0.001) and the lowest expression in human pancreatic cancer cells (MIAPaCa-2) (1.00 ± 0.06 vs. 1.41 ± 0.07, t= 7.70, P= 0.0015). Compared with the levels in the si-negative control group, SNHG6 (0.97 ± 0.05 vs. 0.21 ± 0.06, t = 16.85, P < 0.001), N-cadherin (0.74 ± 0.05 vs. 0.41 ± 0.04, t= 8.93, P < 0.001), Vimentin (0.55 ± 0.04 vs. 0.25 ± 0.03, t= 10.39, P < 0.001), and β-catenin (0.62 ± 0.05 vs . 0.32 ± 0.03, t= 8.91, P < 0.001) were decreased, while E-cadherin (0.65 ± 0.06 vs. 1.36 ± 0.07, t= 13.34, P < 0.001) was increased after SNHG6 knockdown or miR-26a-5p overexpression, accompanied by inhibited cell proliferation, migration, and invasion. SNHG6 overexpression exerted the opposite effects. SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p. Silencing SNHG6 blocked the growth of PC in vivo.Conclusion:Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p, thus providing further supporting evidence for its use in PC treatment.