Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeuti...Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.展开更多
Line-commutated converter (LCC)-based high-voltage DC (HVDC) systems have been integrated with bulk AC power grids for interregional transmission of renewable power. The nonlinear LCC model brings additional nonconvex...Line-commutated converter (LCC)-based high-voltage DC (HVDC) systems have been integrated with bulk AC power grids for interregional transmission of renewable power. The nonlinear LCC model brings additional nonconvexity to optimal power flow (OPF) of hybrid AC-DC power grids. A convexification method for the LCC station model could address such nonconvexity but has rarely been discussed. We devise an equivalent reformulation for classical LCC station models that facilitates second-order cone convex relaxation for the OPF of LCC-based AC-DC power grids. We also propose sufficient conditions for exactness of convex relaxation with its proof. Equivalence of the proposed LCC station models and properties, exactness, and effectiveness of convex relaxation are verified using four numerical simulations. Simulation results demonstrate a globally optimal solution of the original OPF can be efficiently obtained from relaxed model.展开更多
Rhodococcus equi is a zoonotic opportunistic pathogen that mainly infects immunodeficient individuals,such as those with HIV infection.In R.equi-infected individuals,serious lung lesions can develop and death may resu...Rhodococcus equi is a zoonotic opportunistic pathogen that mainly infects immunodeficient individuals,such as those with HIV infection.In R.equi-infected individuals,serious lung lesions can develop and death may result without appropriate antiviral treatment.This bacterium is rare in clinic and there is little information regarding its diagnosis and treatment.To improve our understanding,this case report describes the diagnosis and treatment of a patient with HIV complicated with R.equi infection from Ditan Hospital,Beijing,China.展开更多
基金National Natural Science Foundation of China(Grant No.81273297)Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).
文摘Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.
基金supported by the National Natural Science Foundation of China under Grant 52177086the Fundamental Research Funds for the Central Universities under Grant 2023ZYGXZR063the Science and Technology Program of Guizhou Power Grid Coorperation under Grant GZKJXM20222386.
文摘Line-commutated converter (LCC)-based high-voltage DC (HVDC) systems have been integrated with bulk AC power grids for interregional transmission of renewable power. The nonlinear LCC model brings additional nonconvexity to optimal power flow (OPF) of hybrid AC-DC power grids. A convexification method for the LCC station model could address such nonconvexity but has rarely been discussed. We devise an equivalent reformulation for classical LCC station models that facilitates second-order cone convex relaxation for the OPF of LCC-based AC-DC power grids. We also propose sufficient conditions for exactness of convex relaxation with its proof. Equivalence of the proposed LCC station models and properties, exactness, and effectiveness of convex relaxation are verified using four numerical simulations. Simulation results demonstrate a globally optimal solution of the original OPF can be efficiently obtained from relaxed model.
基金supported by the Beijing Municipal Administration of Hospitals’Ascent Plan(DFL20191802)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX202126)Beijing high-level public health technical personnel construction project(2022-2-014).
文摘Rhodococcus equi is a zoonotic opportunistic pathogen that mainly infects immunodeficient individuals,such as those with HIV infection.In R.equi-infected individuals,serious lung lesions can develop and death may result without appropriate antiviral treatment.This bacterium is rare in clinic and there is little information regarding its diagnosis and treatment.To improve our understanding,this case report describes the diagnosis and treatment of a patient with HIV complicated with R.equi infection from Ditan Hospital,Beijing,China.
