Objective:To explore the genes related to renal tubulointerstitial injury in DN and to elucidate their underlying mechanism by using bioinformatics multi-chip joint analysis and machine learning technology,so as to pr...Objective:To explore the genes related to renal tubulointerstitial injury in DN and to elucidate their underlying mechanism by using bioinformatics multi-chip joint analysis and machine learning technology,so as to provide new ideas for the diagnosis and treatment of DN.Methods:Four gene expression datasets of DN tubulointerstitial tissues were retrieved from the GEO database.GSE30122,GSE47185 and GSE99340 were used as the combined microarray datasets,and GSE104954 was used as the independent verification datasets.The differentially expressed genes(DEGs)were identified by R language,and Gene Ontology(GO)enrichment,KEGG pathway enrichment,Gene Set Enrichment Analysis(GSEA)and Immune Cell Infiltration Analysis were performed.Furthermore,LASSO regression,SVM-RFE and RF machine learning algorithm were used to screen core genes,while external validation and Receiver Operating Curve(ROC)analysis as well as the model of prediction nomogram were performed.Finally,the influence of the clinical characteristics of DN patients was explored by Nephroseq.Results:A total of 107 DEGs were obtained,enrichment analysis revealed that the tubulointerstitial injury in DN was mainly involved in adaptive immune response,lymphocyte mediated immunity,regulation of immune effector process and immune-inflammatory pathways such as staphylococcus aureus infection,complement and coagulation cascades,phagosomes,and Th1 and Th2 cell differentiation.In addition,cell adhesion molecule,cytokine-cytokine receptor interaction and ECM-receptor interaction pathways were also significantly enriched.Memory resting CD4 T cells,γδ毮T cells,resting mast cells and neutrophil cells were up-regulated,while CD8 T cells were down-regulated.Machine learning identified MARCKSL1,CX3CR1,FSTL1,AGR2,GADD45B as core genes with good diagnostic and predictive efficacy.Conclusion:The key pathological mechanism of tubulointerstitial injury in DN is immune disorder,inflammatory reaction,cytokine action and extracellular matrix deposition.Moreover,MARCKSL1,CX3CR1,FSTL1 may be the potential biomarkers for the diagnosis and prediction of DN.展开更多
This study aimed to investigate the effects of Sargassum fusiforme polysaccharide(SFPS I,II,and III)on the apoptosis and regulation of human erythroleukemia(HEL)cells.The effect of different doses of SFPS on HEL cell ...This study aimed to investigate the effects of Sargassum fusiforme polysaccharide(SFPS I,II,and III)on the apoptosis and regulation of human erythroleukemia(HEL)cells.The effect of different doses of SFPS on HEL cell growth was detected using the Cell Counting Kit-8 method,and apoptosis was detected by Hoechst staining.Cell cycle distribution and apoptosis were detected using flow cytometry.Expression of the cell cycle gene,p53,antiapoptotic genes,Bcl-xL and Bcl-2,and pro-apoptotic genes,Bax,Bad,and Caspase-3,as well as the expression of the corresponding proteins,were detected using real-time quantitative polymerase chain reaction(qPCR)and Western blot.The results showed that SFPS Ⅱ and Ⅲ decreased HEL cell viability and induced HEL cell apoptosis.Different concentrations of SFPS(Ⅰ,Ⅱ,and Ⅲ)were detected that induced much less toxic effect in normal human embryonic lung(MRC-5)cells,and SFPS Ⅰ increased cell proliferation,indicating its favorable selectivity towards cancer cells.The mechanism by which SFPS induced apoptosis was also found to be related to the induction of cell cycle arrest in the G0/G1 phase and the increased expression of apoptosis-related genes and proteins.We concluded that SFPS induces HEL cell apoptosis,possibly via activation of the Caspase pathway,providing the theoretical basis for the development of SFPS-based anti-tumor drug products.展开更多
Background Acute kidney injury(AKI)was a risk factor for poor outcomes in patients with ST-segment elevation myocardial infarction(STEMI).Whether postoperative serum creatinine(SCr)level measured at early time(24 hour...Background Acute kidney injury(AKI)was a risk factor for poor outcomes in patients with ST-segment elevation myocardial infarction(STEMI).Whether postoperative serum creatinine(SCr)level measured at early time(24 hours)after percutaneous coronary intervention(PCI)had prognostic role in elderly patients with STEMI was unclear.Methods SCr was measured within 24 hours after PCI.A total of 883 elderly patients(≥60 years)with STEMI were finally included and divided into three group according to the tertiles of postoperative SCr level(umol/L):<81(n=283),81-107(n=302)and≥107(n=298).The relationship between postoperative Scr and in-hospital and 1-year adverse events was evaluated.Results In-hospital mortality was 5.4%(48/883),which was significantly higher in patients with a high postoperative SCr level(1.8%vs.3.0%vs.11.4%,P<0.001).Receiver operator characteristic curve analysis indicated that postoperative SCr>120 umol/L had a sensitivity of 66.7%and specificity of 79.2%for predicting in-hospital death[area under the curve(AUC)=0.768,95%CI:0.697-838,P<0.001].Multivariate analysis showed that postoperative Scr>120 umol/L was an independent risk factor for in-hospital mortality even after adjusting for the baseline renal dysfunction[estimated glomerular filtration rate(e GFR)<60 m L/(min·1.73 m2)].Kaplan-Meier analysis showed that patients with postoperative SCr>120 umol/L had a higher one-year mortality than those without(Log-rank test:57.8,P<0.001).Conclusions SCr level measured within 24 hours after PCI could serve as an early and powerful marker for predicting in-hospital and one-year mortality in elderly patients with STEMI.展开更多
基金National Natural Science Foundation of China(No.81774273)。
文摘Objective:To explore the genes related to renal tubulointerstitial injury in DN and to elucidate their underlying mechanism by using bioinformatics multi-chip joint analysis and machine learning technology,so as to provide new ideas for the diagnosis and treatment of DN.Methods:Four gene expression datasets of DN tubulointerstitial tissues were retrieved from the GEO database.GSE30122,GSE47185 and GSE99340 were used as the combined microarray datasets,and GSE104954 was used as the independent verification datasets.The differentially expressed genes(DEGs)were identified by R language,and Gene Ontology(GO)enrichment,KEGG pathway enrichment,Gene Set Enrichment Analysis(GSEA)and Immune Cell Infiltration Analysis were performed.Furthermore,LASSO regression,SVM-RFE and RF machine learning algorithm were used to screen core genes,while external validation and Receiver Operating Curve(ROC)analysis as well as the model of prediction nomogram were performed.Finally,the influence of the clinical characteristics of DN patients was explored by Nephroseq.Results:A total of 107 DEGs were obtained,enrichment analysis revealed that the tubulointerstitial injury in DN was mainly involved in adaptive immune response,lymphocyte mediated immunity,regulation of immune effector process and immune-inflammatory pathways such as staphylococcus aureus infection,complement and coagulation cascades,phagosomes,and Th1 and Th2 cell differentiation.In addition,cell adhesion molecule,cytokine-cytokine receptor interaction and ECM-receptor interaction pathways were also significantly enriched.Memory resting CD4 T cells,γδ毮T cells,resting mast cells and neutrophil cells were up-regulated,while CD8 T cells were down-regulated.Machine learning identified MARCKSL1,CX3CR1,FSTL1,AGR2,GADD45B as core genes with good diagnostic and predictive efficacy.Conclusion:The key pathological mechanism of tubulointerstitial injury in DN is immune disorder,inflammatory reaction,cytokine action and extracellular matrix deposition.Moreover,MARCKSL1,CX3CR1,FSTL1 may be the potential biomarkers for the diagnosis and prediction of DN.
基金Zhejiang Province Focuses on“Biological Engineering”Innovation Projects(No.CX2017001)the Autonomous Research Project of FSEKDNB(No.2020FSEKDNB001)。
文摘This study aimed to investigate the effects of Sargassum fusiforme polysaccharide(SFPS I,II,and III)on the apoptosis and regulation of human erythroleukemia(HEL)cells.The effect of different doses of SFPS on HEL cell growth was detected using the Cell Counting Kit-8 method,and apoptosis was detected by Hoechst staining.Cell cycle distribution and apoptosis were detected using flow cytometry.Expression of the cell cycle gene,p53,antiapoptotic genes,Bcl-xL and Bcl-2,and pro-apoptotic genes,Bax,Bad,and Caspase-3,as well as the expression of the corresponding proteins,were detected using real-time quantitative polymerase chain reaction(qPCR)and Western blot.The results showed that SFPS Ⅱ and Ⅲ decreased HEL cell viability and induced HEL cell apoptosis.Different concentrations of SFPS(Ⅰ,Ⅱ,and Ⅲ)were detected that induced much less toxic effect in normal human embryonic lung(MRC-5)cells,and SFPS Ⅰ increased cell proliferation,indicating its favorable selectivity towards cancer cells.The mechanism by which SFPS induced apoptosis was also found to be related to the induction of cell cycle arrest in the G0/G1 phase and the increased expression of apoptosis-related genes and proteins.We concluded that SFPS induces HEL cell apoptosis,possibly via activation of the Caspase pathway,providing the theoretical basis for the development of SFPS-based anti-tumor drug products.
文摘Background Acute kidney injury(AKI)was a risk factor for poor outcomes in patients with ST-segment elevation myocardial infarction(STEMI).Whether postoperative serum creatinine(SCr)level measured at early time(24 hours)after percutaneous coronary intervention(PCI)had prognostic role in elderly patients with STEMI was unclear.Methods SCr was measured within 24 hours after PCI.A total of 883 elderly patients(≥60 years)with STEMI were finally included and divided into three group according to the tertiles of postoperative SCr level(umol/L):<81(n=283),81-107(n=302)and≥107(n=298).The relationship between postoperative Scr and in-hospital and 1-year adverse events was evaluated.Results In-hospital mortality was 5.4%(48/883),which was significantly higher in patients with a high postoperative SCr level(1.8%vs.3.0%vs.11.4%,P<0.001).Receiver operator characteristic curve analysis indicated that postoperative SCr>120 umol/L had a sensitivity of 66.7%and specificity of 79.2%for predicting in-hospital death[area under the curve(AUC)=0.768,95%CI:0.697-838,P<0.001].Multivariate analysis showed that postoperative Scr>120 umol/L was an independent risk factor for in-hospital mortality even after adjusting for the baseline renal dysfunction[estimated glomerular filtration rate(e GFR)<60 m L/(min·1.73 m2)].Kaplan-Meier analysis showed that patients with postoperative SCr>120 umol/L had a higher one-year mortality than those without(Log-rank test:57.8,P<0.001).Conclusions SCr level measured within 24 hours after PCI could serve as an early and powerful marker for predicting in-hospital and one-year mortality in elderly patients with STEMI.
