Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Background/Aims: Liver cirrhosis involves chronic inflammation and progressive fibrosis.Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Objective To explore the value of cuprotosis-related genes in the diagnosis and disease progression of chronic obstructive pulmonary disease(COPD).Methods Differential gene expression related to COPD was identified through gene expression omnibus series(GSE)10006,GSE11784,GSE19407,and GSE8545 datasets,and compared with previously identified cuprotosis-related genes to identify differentially expressed genes.Weighted gene co-expression network analysis(WGCNA)was then performed on GSE8545 and GSE19407 datasets to explore the correlation between cuprotosis-related genes and COPD phenotypes.GSE20257 dataset was introduced to validate the gene's expression level changes and further investigate the impact of smoking on gene expression levels.Subsequently,the effects of smoking cessation on gene expression levels were explored by using the GSE7895 datasets.GSE162635 dataset was then utilized to investigate the impact of differentially expressed cuprotosis-related genes on the severity of COPD.Results The study identified cyclin-dependent kinase inhibitor 2A(CDKN2A)as a potential cuprotosis-related gene associated with COPD,confirming that smoking upregulated CDKN2A expression in lung tissue,which returns to baseline levels after smoking cessation.Finally,the study confirmed that the expression level of CDKN2A was associated with the prognosis of COPD,increasing with severity.Conclusion The study identifies CDKN2A as a cuprotosis-related gene associated with COPD,and shows promising diagnostic potential and correlation with disease severity.

Purpose To investigate the relationships between the genetic variations and clinicopathological fea-tures of thyroid carcinoma in a single-center cohort.Methods The correlation between genetic profiling and clinico-pathologic characteristics of thyroid carcinomas detected by next-generation sequencing was analyzed.Results 93.7％of 238 cases of thyroid cancer had Class Ⅰ or Class Ⅱ variations.Compared with TCGA cohort,the single-center of pa-tients with papillary thyroid cancer(PTC)were younger(44.4±12.4 vs 46.8±15.5,P=0.043),and the rate of lymph node metastasis was higher(57.5％vs 49.2％,P=0.046).The frequency of BRAF gene mutation was signifi-cantly higher(82.4％vs 59.7％,P＜0.001),that of RAS gene mutation(2.3％vs 12.9％,P＜0.001)and TERT promoter mutation was lower(1.8％vs 9.4％,P＜0.001).There were no differences in the incidences of RET fusion(5.4％vs 6.8％,P=0.484)and NTRK fusion(4.1％vs 2.1％,P=0.127).Gene mutations were detected in 210 of 221(95.0％)patients with PTC,including BRAF(182/221,82.4％),RET fusion(12/221,5.4％),NTRK fusion(9/221,4.1％),FGFR amplification(6/221,2.7％),CCND1 amplification(6/221,2.7％),FGFR19 am-plification(6/221,2.7％),RAS(5/221,2.3％),PIK3CA(5/221,2.3％),and TERT(4/221,1.8％).NTRK fusion was associated with younger age(P=0.049)and higher T stage(P=0.005),while TERT promoter mutation was associated with older age(P=0.003)and higher T stage(P=0.001).8.6％(19/221)of thyroid papillary car-cinoma had at least two driver gene variants and tended to occur in patients with older age(P=0.001)and higher T tage(P=0.001).Higher mutation allele fraction(MAF)of BRAF was associated with T stage(P＜0.001)and N stage(P=0.017).Conclusion Chinese patients with papillary thyroid carcinomapatients show unique genetic vari-ant characteristics,and the patients with NTRK fusion,TERT promoter mutation,multiple driver gene variations,or high MAF of BRAF show specific clinicopathologic features.

Purpose To investigate the relationships between the genetic variations and clinicopathological fea-tures of thyroid carcinoma in a single-center cohort.Methods The correlation between genetic profiling and clinico-pathologic characteristics of thyroid carcinomas detected by next-generation sequencing was analyzed.Results 93.7％of 238 cases of thyroid cancer had Class Ⅰ or Class Ⅱ variations.Compared with TCGA cohort,the single-center of pa-tients with papillary thyroid cancer(PTC)were younger(44.4±12.4 vs 46.8±15.5,P=0.043),and the rate of lymph node metastasis was higher(57.5％vs 49.2％,P=0.046).The frequency of BRAF gene mutation was signifi-cantly higher(82.4％vs 59.7％,P＜0.001),that of RAS gene mutation(2.3％vs 12.9％,P＜0.001)and TERT promoter mutation was lower(1.8％vs 9.4％,P＜0.001).There were no differences in the incidences of RET fusion(5.4％vs 6.8％,P=0.484)and NTRK fusion(4.1％vs 2.1％,P=0.127).Gene mutations were detected in 210 of 221(95.0％)patients with PTC,including BRAF(182/221,82.4％),RET fusion(12/221,5.4％),NTRK fusion(9/221,4.1％),FGFR amplification(6/221,2.7％),CCND1 amplification(6/221,2.7％),FGFR19 am-plification(6/221,2.7％),RAS(5/221,2.3％),PIK3CA(5/221,2.3％),and TERT(4/221,1.8％).NTRK fusion was associated with younger age(P=0.049)and higher T stage(P=0.005),while TERT promoter mutation was associated with older age(P=0.003)and higher T stage(P=0.001).8.6％(19/221)of thyroid papillary car-cinoma had at least two driver gene variants and tended to occur in patients with older age(P=0.001)and higher T tage(P=0.001).Higher mutation allele fraction(MAF)of BRAF was associated with T stage(P＜0.001)and N stage(P=0.017).Conclusion Chinese patients with papillary thyroid carcinomapatients show unique genetic vari-ant characteristics,and the patients with NTRK fusion,TERT promoter mutation,multiple driver gene variations,or high MAF of BRAF show specific clinicopathologic features.

Objective To explore the value of cuprotosis-related genes in the diagnosis and disease progression of chronic obstructive pulmonary disease(COPD).Methods Differential gene expression related to COPD was identified through gene expression omnibus series(GSE)10006,GSE11784,GSE19407,and GSE8545 datasets,and compared with previously identified cuprotosis-related genes to identify differentially expressed genes.Weighted gene co-expression network analysis(WGCNA)was then performed on GSE8545 and GSE19407 datasets to explore the correlation between cuprotosis-related genes and COPD phenotypes.GSE20257 dataset was introduced to validate the gene's expression level changes and further investigate the impact of smoking on gene expression levels.Subsequently,the effects of smoking cessation on gene expression levels were explored by using the GSE7895 datasets.GSE162635 dataset was then utilized to investigate the impact of differentially expressed cuprotosis-related genes on the severity of COPD.Results The study identified cyclin-dependent kinase inhibitor 2A(CDKN2A)as a potential cuprotosis-related gene associated with COPD,confirming that smoking upregulated CDKN2A expression in lung tissue,which returns to baseline levels after smoking cessation.Finally,the study confirmed that the expression level of CDKN2A was associated with the prognosis of COPD,increasing with severity.Conclusion The study identifies CDKN2A as a cuprotosis-related gene associated with COPD,and shows promising diagnostic potential and correlation with disease severity.

Objective:To study the potential mechanism of Ganwei Baihe Decoction in the treatment of gastric ulcer (GU) based on bioinformatics and validate it through animal experiments.Methods:TCMSP, DisGeNET, and GeneCards databases were used to retrieved active components and action targets of Ganwei Baihe Decoction. After obtaining the intersection, protein interaction data of the intersection genes were obtained through the STRING database. A PPI network was constructed by Cytoscape 3.10.0 software and the key genes and key components were obtained. DAVID online analysis database was used for GO functional enrichment and KEGG pathway enrichment analysis of key targets. Animal experiments were used for verification. Totally 36 SD rats were divided into blank group, model group, Omeprazole group and Ganwei Baihe Decoction group according to the random number table method, with 9 rats in each group. After 7 days of gavage of the corresponding drugs to each group of rats, they fasted and but with water for 24 hours, and then re-gavaged once. After 1 hour of administration, a gastric ulcer rat model was prepared by gavage of 80 mg/kg of indomethacin. After 3 hours of administration, anesthesia was used to extract the sample. The expression level of Caspase-3 protein in the gastric tissue of rats was to be determined by Western blot method.Results:There were 234 effective active components with 290 targets in Ganwei Baihe Decoction, and 6 496 therapeutic targets for GU. 213 potential targets for GU were screened out. There were 437 GO function and 153 KEGG pathway enriched entries. Compared with the model group, the protein expression of Caspase-3 in the Ganwei Baihe Decoction group and Omeprazole group decreased ( P<0.05). Conclusion:The mechanism of Ganwei Baihe Decoction in treating GU may be through key components such as quercetin and β-sitosterol acting on key targets such as AKT1 and CASP3, regulating the Apoptosis pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, etc. to exert inhibitory effects on apoptosis.