BACKGROUND Colorectal cancer(CRC)is one of the most prevalent tumors worldwide.Recently,long noncoding RNAs(lncRNAs)have been shown to influence tumorigenesis and tumor progression by acting as competing endogenous RN...BACKGROUND Colorectal cancer(CRC)is one of the most prevalent tumors worldwide.Recently,long noncoding RNAs(lncRNAs)have been shown to influence tumorigenesis and tumor progression by acting as competing endogenous RNAs(ceRNAs).It is difficult to extract prognostic lncRNAs and useful bioinformation from most ceRNA networks constructed previously.AIM To construct a prognostic related ceRNA regulatory network and lncRNA related signature based on risk score in CRC.METHODS RNA transcriptome profile and clinical information of 506 CRC patients were downloaded from the Cancer Genome Atlas database.R packages and Perl program were used for data processing.Cox regression analysis was used for prognostic model construction.Quantitative real-time polymerase chain reaction was used to detect the expression of lncRNAs.RESULTS A prognostic-related ceRNA network was constructed,including 9 lncRNAs,44 mRNAs,and 30 miRNAs.In addition,a four-lncRNA model was constructed using multivariate Cox regression analysis,which could be an independent prognostic model in CRC.The risk score for each patient was calculated,and the 506 patients were divided into high and low-risk groups(253 for each group)based on the median risk score.The results of the survival analysis showed that patients with a high-risk score had a poor survival rate.Furthermore,the predictive value of the four-lncRNA model was evaluated in GSE38832.Patient survival probabilities could be better predicted when combing the risk score and clinical features.Gene Set Enrichment Analysis results verified that a number of cancer-related signaling pathways were enriched with a high-risk score in CRC.Finally,we validated a novel lncRNA(LINC00488)using quantitative real-time polymerase chain reaction in 22 paired CRC patient tumor tissues compared to adjacent non-tumor tissues.CONCLUSION The four-lncRNA model could give better predictive value for CRC patients.Our understanding of the lncRNA-related ceRNA regulatory mechanism could provide a potential diagnostic indicator for CRC patients.展开更多
BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis...BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.展开更多
Cable-type welding wire(CWW)CO2 welding is an innovative process arc welding with high quality,high efficiency and energy saving,in which CWW is used as consumable electrode.The CWW is composed of seven wires with a...Cable-type welding wire(CWW)CO2 welding is an innovative process arc welding with high quality,high efficiency and energy saving,in which CWW is used as consumable electrode.The CWW is composed of seven wires with a diameter of 1.2mm.One is in the center,while others uniformly distribute around it.The diameter of twisted wire is up to 3.6mm,which can increase the deposition rate significantly.With continual wire-feeding and melting of CWW,the formed rotating arc improved welding quality obviously.The arc behavior and droplet transfer were observed by the electrical signal waveforms and corresponding synchronous images,based on the high speed digital camera and electrical signal system.The results showed that the shape of welding arc changed from bell arc to beam arc with the increase of welding parameter.The droplet transfer mode changed from repelled transfer,globular transfer to projected transfer in turn.Droplet transfer frequency increased from 18.17 Hz to 119.05 Hz,while the droplet diameter decreased from 1.5times to 0.3times of the CWW diameter.展开更多
文摘BACKGROUND Colorectal cancer(CRC)is one of the most prevalent tumors worldwide.Recently,long noncoding RNAs(lncRNAs)have been shown to influence tumorigenesis and tumor progression by acting as competing endogenous RNAs(ceRNAs).It is difficult to extract prognostic lncRNAs and useful bioinformation from most ceRNA networks constructed previously.AIM To construct a prognostic related ceRNA regulatory network and lncRNA related signature based on risk score in CRC.METHODS RNA transcriptome profile and clinical information of 506 CRC patients were downloaded from the Cancer Genome Atlas database.R packages and Perl program were used for data processing.Cox regression analysis was used for prognostic model construction.Quantitative real-time polymerase chain reaction was used to detect the expression of lncRNAs.RESULTS A prognostic-related ceRNA network was constructed,including 9 lncRNAs,44 mRNAs,and 30 miRNAs.In addition,a four-lncRNA model was constructed using multivariate Cox regression analysis,which could be an independent prognostic model in CRC.The risk score for each patient was calculated,and the 506 patients were divided into high and low-risk groups(253 for each group)based on the median risk score.The results of the survival analysis showed that patients with a high-risk score had a poor survival rate.Furthermore,the predictive value of the four-lncRNA model was evaluated in GSE38832.Patient survival probabilities could be better predicted when combing the risk score and clinical features.Gene Set Enrichment Analysis results verified that a number of cancer-related signaling pathways were enriched with a high-risk score in CRC.Finally,we validated a novel lncRNA(LINC00488)using quantitative real-time polymerase chain reaction in 22 paired CRC patient tumor tissues compared to adjacent non-tumor tissues.CONCLUSION The four-lncRNA model could give better predictive value for CRC patients.Our understanding of the lncRNA-related ceRNA regulatory mechanism could provide a potential diagnostic indicator for CRC patients.
基金National Natural Science Foundation of China,No.81871723.
文摘BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.
基金Project supported by the National Natural Science Foundation of China(Nos.81774338 and 81674000)the Natural Science Foundation of Guangdong Province(No.2016A030313645)+1 种基金the Science and Technology Projects of Guangdong Province(No.2016A020226006)the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2018),China
基金Item Sponsored by National Natural Science Foundation of China(51275224,51575250,51505200)Prospective Joint Research Project of Jiangsu Province of China(BY2015065-06)Priority Academic Program Development of Jiangsu Higher Education Institutions of China
文摘Cable-type welding wire(CWW)CO2 welding is an innovative process arc welding with high quality,high efficiency and energy saving,in which CWW is used as consumable electrode.The CWW is composed of seven wires with a diameter of 1.2mm.One is in the center,while others uniformly distribute around it.The diameter of twisted wire is up to 3.6mm,which can increase the deposition rate significantly.With continual wire-feeding and melting of CWW,the formed rotating arc improved welding quality obviously.The arc behavior and droplet transfer were observed by the electrical signal waveforms and corresponding synchronous images,based on the high speed digital camera and electrical signal system.The results showed that the shape of welding arc changed from bell arc to beam arc with the increase of welding parameter.The droplet transfer mode changed from repelled transfer,globular transfer to projected transfer in turn.Droplet transfer frequency increased from 18.17 Hz to 119.05 Hz,while the droplet diameter decreased from 1.5times to 0.3times of the CWW diameter.