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 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.

Objective:To investigate the response of mandibular condylar chondroprogenitors to flow fluid shear stress(FFSS).Methods:Chondroprogenitors were in vitro cultured and stimulated with FFSS that can cause cell degeneration,and treated with sec-ond-generation high-throughput RNA sequencing.Differential gene expression was screened using DESeq2 software for gene ontology(GO)functional enrichment analysis,kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and protein-protein interaction(PPI)network analysis.qRT-PCR was performed to validate the core genes screened by PPI.Results:A total of 1996 differentially expressed genes were obtained,mainly including inflammatory response and cell cycle related molecules.Among them,Actal,Atf3,Ccl2,116,Nfkbia,Ret and Vcaml were identified as the core genes.Conclusion:FFSS stimulation affects chondroprogenitor function by acting on inflammatory responses and cell cycle-related signaling pathways in chondroprogenitors.

Objective To evaluate the efficacy and safety of fluorouracil and leucovorin and oxaliplatin(FOLFOX)regimen hepatic artery infusion chemotherapy(HAIC)combined with lenvatinib(LEN)and immune checkpoint inhibitors(ICIs)in treating patients with hepatocellular carcinoma(HCC)after the occurrence of transcatheter arterial chemoembolization(TACE)refractoriness.Methods The clinical data of 54 HCC patients who developed TACE refractoriness,were admitted to the Jiangsu Provincial Cancer Hospital of China to receive FOLFOX-HAIC combined with LEN and ICIs therapy between January 2019 and December 2022,were retrospectively analyzed.The modified Response Evaluation Criteria in Solid Tumors(mRECIST)was used to statistically analyze the clinical efficacy,the Common Terminology Criteria For Adverse Events version 5.0(CTCAE 5.0)was adopted to record and evaluate the treatment-related adverse events(TRAEs).The primary endpoints were progression-free survival(PFS)and overall survival(OS),the secondary endpoints were objective response rate(ORR),disease control rate(DCR),and safety.Results The median PFS was 11.7 months(95％CI:8.124-15.276 months),the median OS was 23.1 months(95％CI:19.508-26.692 months),the ORR was 46.3％,and the DCR was 87.0％.The most common TRAE at all levels was elevated alanine aminotransferase(51.9％),and the most common TRAE of grade 3/4 was hypertension(9.3％).No treatment-related death occurred.Conclusion For the treatment of HCC patients who developed TACE refractoriness,FOLFOX-HAIC combined LEN and ICIs is clinically safe and effective.(J Intervent Radiol,2024,33:610-615)

Objective To investigate the factors affecting the prognosis of patients with malignant obstructive jaundice(MOJ)after receiving biliary stent placement combined with intraluminal brachytherapy with 125I seed-strip implantation.Methods The clinical data of 52 patients with MOJ,who received biliary stent placement combined with intraluminal brachytherapy with 125I seed-strip implantation at the Jiangsu Provincial Cancer Hospital of China between January 2019 and January 2023,were retrospectively analyzed.The difference value between preoperative and postoperative number of lymphoid immune cells was recorded as△X.X-tile software was used to calculate the optimal cut-off value of △X,based on which the patients were divided into two groups.Univariate and multivariate analysis were used to determine the risk factors for overall survival(OS).Results The mean survival time of the 52 patients was(201.0±32.1)days.Univariate analysis indicated that postoperative TACE,preoperative ALT,preoperative AST,△lymphocyte cell,△CD3+T cell,△CD8+T cell,△natural killer cell(NK)and △regulatory cell(Treg)were significantly associated with OS,the differences were statistically significant(all P＜0.05).Multivariate analysis revealed that △lymphocyte cell(P=0.007)and △Treg(P=0.038)were the independent risk factors for OS.Conclusion For MOJ patients whose△lymphocyte is ≥0.237 or △Treg is ≥0.21,a longer OS can be expected after receiving the treatment of biliary stent placement combined with intraluminal brachytherapy with 125I seed-strip implantation.

Objective It evaluates the high-quality development policies of public hospitals at the provincial level in China,and provides theoretical basis and countermeasures for formulating and optimizing the high-quality develop-ment policies of public hospitals.Methods The ROST CM 6.0 software was used to conduct text mining for 11 sample policies,and the Policy Modeling Consistency(PMC)index model was constructed to evaluate the sample policies quantitatively.Results The average PMC index of 11 sample policies included in the study was 7.16 points,of which 8 were excellent grades and 3 were qualified grades.The first-level variables X5 service system(0.82),X8 Party leadership(0.91)and X6 organization and operation(0.94)scored higher;X2 policy timeliness(0.52),X7 cultural construction(0.68)and X4 service capability(0.71)scored low.Conclusion The content of the high-quality develop-ment policy of public hospitals at the provincial level is basically in line with the national policy,and is relatively excel-lent in the aspects of organization and operation,service system and party leadership,etc.,but there are some weaknesses in the aspects of policy timeliness,cultural construction and service capacity,etc.,which can be op-timized and improved from the aspects of improving service capacity,supplementing long-term policies and strengthening hospital cultural construction.