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.

Autophagy is a highly conserved cellular self-regulatory mechanism， which primarily occurs in the lysosomes or vacuoles of mammalian and yeast cells and plays a critical role in maintaining cellular homeostasis and metabolic balance. When cells encounter stress conditions like nutrient deprivation， physical or chemical stimuli， infections， and oxidative stress， or when damaged or aging organelles accumulate in the cytoplasm， the autophagic process is activated. This process degrades and recycles damaged proteins and organelles， removes potentially harmful substances， in which the degradation products are used for energy supply and macromolecule resynthesis， thereby help maintain the cellular homeostasis. Autophagy activators are compounds or drugs that can promote the cellular self-clearance process （such as mTOR inhibitors， AMPK activators， SIRT1 activators， lysosome enhancers， etc.）. They enhance autophagy activity by acting on autophagy-related signaling pathways or proteins， thereby regulating cellular and metabolic processes， and consequently exerting an impact on the organism. With the deepening of research， more and more small molecule compounds with autophagic activity have been discovered. As autophagy activators， these small molecule compounds have shown great application potential in the treatment of malignant tumors， nervous system diseases， metabolic diseases， etc. Some related drugs have even entered the clinical trial stage and achieved good efficacy. This article discusses the mechanisms of various types of autophagy activators and their potential applications in diseases， aiming to provide a reference for the further development and application of autophagy activators in diseases.

Objective:To investigate the correlations between expression of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1) and their functions on exosome secretion, proliferation and invasion in hepatocellular carcinoma (HCC).Methods:We used small interfering RNA of MALAT1 (si-MALAT1) to knockdown MALAT1 in HuH-7. At the meanwhile, cells which were transfected with si-NC were used as the negative control group. Expression of NEAT1, cell proliferation and invasion function were detected these two groups. HuH-7 cells were transfected with lentivirus NEAT1 over expressing vector (lv-NEAT1) or negative control (lv-control). Expression of exosomes secretion related genes were analyzed between lv-NEAT1 and lv-control groups. Cells of lv-NEAT1 were knockdown MALAT1 expression using si-MALAT1, which could be si-MALAT1+ lv-NEAT1 group. exosomes secretion was detected in si-NC, si-MALAT1 and si-MALAT1+ lv-NEAT1 group. We treated cells (si-MALAT1 group) with exosomes from cells with lv-NEAT1 or lv-control to divide cells as si-MALAT1+ exosomes of lv-NEAT1 cells and si-MALAT1+ exosomes of lv-control groups. Cell proliferation and invasion of cells were detected in two groups.Results:Low expression of NEAT1 were found in MALAT1 knockdown cells compared with si-NC group [(0.72±0.02) vs. (0.98±0.01), P<0.05]. Cells with MALAT1 knockdown shown diminished proliferation [(0.66±0.03) vs. (0.98±0.04), P<0.05)] and invasion [(88.33±7.26) vs. (147.70±13.62), P<0.05)]. Compared with si-NC group, CD9 and CD63 expression were decreased in exosomes of si-MALAT1 group. Compared with si-MALAT1 group, CD9 and CD63 expression was increased in exosomes of si-MALAT1+ lv-NEAT1 group. Compared with si-MALAT1+ exosomes of lv-control group, proliferation [(0.97±0.03) vs. (0.74±0.05), P<0.05)] and invasion [ (132.70±7.36) vs. (98.33±6.01), P<0.05) ] were increased in si-MALAT1+ exosomes of lv-NEAT1 group. Exosomes related genes expression including HSPA8 (5.53±0.31), SLC3A2 (0.32±0.07) and SLC7A5 (0.77±0.45) were changed in lv-NEAT1 group compared with lv-control group [(0.98±0.15), P<0.05]. Conclusion:MALAT1 induced exosomes secretion by NEAT1 and exosomes related genes regulation. This regulation might be related with increased proliferation and invasion function in HCC cells with MALAT1 and NEAT1 abnormal expression.

Objective From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient treatments and 0.85±1.15 hospitalizations. Total medical cost was saved by 3 610.21 per capita yuan, including outpatient cost of 241.41 yuan and hospitalization cost of 269.82 yuan; Quality of life was gained by 0.03 QALY gain per capita. The ICER was dominant and CBR was 12.00. Conclusion COPD patients vaccinated with 23-valent pneumococcal polysaccharide vaccine within one year reduced treatments due to acute exacerbation. The vaccination was cost effective and cost saving , and we suggest the vaccine should be covered in the public health program or health insurance scheme in conditional region.

Objective From the perspective of health economics, to evaluate 23 pneumococcal polysaccharide vaccination programme among chronic obstructive pulmonary disease (COPD) patient. Methods In the pilot counties of the project of integrated care pathway for COPD patient (Hanbin district of Hanzhong city in Shanxi Province, Qianjian district of Qingqing city, Huandao district of Qindao city in Shangdong Province, Wen county of Jiaozuo city in Henan Province), information of insurance participants of New Rural Cooperative Medical System (NRCS) was collected by local NRCM information system, which included general information as well as records of medical care and medical fee. Nonprobability sampling method was applied to select a total of 860 objects, who were over 60 years old with local household registration, hospitalized within one recent year due to COPD acute exacerbation, and without vaccination of 23 voluntary pneumococcal polysaccharide vaccine within 3 years. A quasi-experimental design without control group was adopted. Objects were vaccinated with 23-valent pneumococcal polysaccharide vaccine from January to December in 2013, then were followed up from January in 2014 for one year. Data of effectiveness and medical cost was collected by self-designed questionnaire and (Chinese version). Paired rank sum test applied to test the difference of quality of life, number and direct medical cost of treatment (including outpatient treatment and hospitalization) due to COPD acute exacerbation, one year before and after intervention. The incremental cost-effectiveness ratio (ICER) and cost-benefit ratio (CBR) of the programme were calculated. Results By January 2014, eight hundred sixty objects were vaccinated. By January 2015, seven hundred eighty eight objects were followed up, with 72 cases withdrawed (8.4%). On average, COPD patients reduced 1.12±2.51 treatments due to acute exacerbation, including 0.28±2.09 outpatient treatments and 0.85±1.15 hospitalizations. Total medical cost was saved by 3 610.21 per capita yuan, including outpatient cost of 241.41 yuan and hospitalization cost of 269.82 yuan; Quality of life was gained by 0.03 QALY gain per capita. The ICER was dominant and CBR was 12.00. Conclusion COPD patients vaccinated with 23-valent pneumococcal polysaccharide vaccine within one year reduced treatments due to acute exacerbation. The vaccination was cost effective and cost saving , and we suggest the vaccine should be covered in the public health program or health insurance scheme in conditional region.

BACKGROUND:At present, liver transplantation is the only way to cure end-stage liver disease, but the complications after transplantation is stil an important factor of affecting the long-term survival of patients who received orthotopic liver transplantation, therefore it is necessary to establish a stable animal transplantation model. OBJECTIVE:To establish rat models of orthotopic liver transplantation. METHODS:After inhalation anesthesia with ether, 204 SD rats were perfused with 2-4℃ Ringer’s solution through the abdominal aorta. In order to reduce warm ischemia of the liver, the liver was not turned over before perfusion. The suprahepatic inferior vena cava was cut off along the phrenic ring after perfusion. No further trimming was needed when dressing, so as not to damage the vena cava. The donor liver was removed and preserved in 4℃Ringer’s liquid. The receptor liver was cut off and alogeneic orthotopic liver transplantation was performed using modified two-cuff method. After transplantation, rats could automaticaly turn over and drink water. Surviving more than 3 days is regarded as a successful transplantation. RESULTS AND CONCLUSION:102 liver transplantations were performed in 204 rats, with 86 rats surviving more than 3 days. The success rate of transplantation was 84%. The results demonstrate that rat models of orthotropic liver transplantation can be constructed successfuly through improving techniques.