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 retrospectively analyze the genetic differences of thalassemia gene mutations among ethnic groups in Hechi, Guangxi. METHODS: A total of 15 595 whole blood samples of residents of Hechi from January 1, 2020 to June 30, 2023 were screened for thalassemia, and the Gap-PCR method and RDB-PCR method were used to perform genetic testing on the positive samples. Gene sequencing was performed on the samples with positive screening results but negative genotyping results. RESULTS: Among the 15 595 samples, 10 501 cases were screened positively, and 8 506 cases were thalassemia gene carriers among the positive samples, with a positive coincidence rate of 81.00%. Among them, there were 5 374 cases of α-thalassemia, 2 531 cases of β-thalassemia, and 601 cases of α+β compound thalassemia. A total of 13 mutant types were detected in α-thalassemia, including --^SEA (48.57%), -α ^3.7 (31.31%), α ^CS (8.57%) and -α ^4.2 (8.07%). A total of 17 mutant types were detected in β-thalassemia, mainly CD17 (48.27%) and CD41-42 (41.24%). The thalassemia gene carriers were mainly from the Zhuang (6 106 cases), Han (969 cases), Yao (793 cases), Mulam (275 cases), and Maonan (228 cases) ethnic groups. The comparison of constituent ratios within the above five ethnic groups demonstrated that there were differences in the proportions of -- ^SEA, -α ^3.7, α ^CS , and -α ^4.2 among the Zhuang, Han, and Yao ethnic groups (P < 0.005). The proportion of α ^CS in the Mulam ethnic group was not significantly different from -α ^3.7 and -α ^4.2. The proportions of -- ^SEA, -α^3.7, and α ^CS in the Maonan ethnic group were not significantly different. There were no significant differences in the proportion of CD17 and CD41-42 among the Han, Yao, Mulam and Maonan ethnic groups. The proportion of --^SEA was the highest in the Mulam ethnic group (56.68%), which was statistically different from 35.92% in the Maonan ethnic group. The proportion of -α ^3.7 was the highest in the Zhuang ethnic group (33.25%), and the difference was statistically significant compared to the Mulam ethnic group which had the lowest proportion (18.72%). The proportion of α ^CS was the highest in the Maonan ethnic group (27.46%), and the differences were statistically significant compared with other ethnic groups. The proportions of CD17 in the Zhuang and Maonan ethnic groups (50.79%, 55.68%) were higher than those in the Han (39.12%), Yao (39.63%) and Mulam (30.00%), and the differences were statistically significant. There was no significant difference in the proportion of CD41-42 among the above five ethnic groups. CONCLUSIONS The mutation type and distribution differences of genes causing thalassemia among main ethnic groups in the minority inhabited areas of Hechi, Guangxi, show the characteristics of ethnic differentiation. The result is helpful to develop a special prevention and control plan for thalassemia in line with the population distribution characteristics, and provide reference for revealing the genetic background and geographical distribution of thalassemia in this area.
Humans ; China ; beta-Thalassemia/genetics* ; Ethnicity/genetics* ; alpha-Thalassemia/genetics* ; Mutation ; Genotype ; Retrospective Studies ; Asian People/genetics* ; Thalassemia/genetics* ; Male

OBJECTIVE To investigate the effect of pharyngeal cavity and genoglossus muscle exercises in patients with mild obstructive sleep apnea syndrome(OSAHS)left over after palatopharyngoplasty with diastolic cardiac dysfunction.METHODS A total of 75 patients with mild OSAHS left after palatopharyngoplasty with diastolic cardiac dysfunction from January 2021 to August 2023 were selected for retrospective study.Among them,37 patients underwent pharyngeal cavity and mentoglossum muscle exercise(observation group),while 38 patients did not(control group).Using postoperative data as baseline value.mean blood oxygen saturation(MSpO2),lowest oxygen saturation(LSpO2),sleep efficiency,apnea index(AI),sleep latency,apnea hypopnea index(AHI),hypopnea index(HI),microarousal index(MAI),rapid eye movement latency,arterial blood pressure of carbon dioxide(PaCO2),pH,arterial partial oxygen pressure(PaO2),left ventricular end-systolic diameter(LVDs),blood lactic acid,left ventricular ejection fraction(LVEF),Tei index,left ventricular end-diastolic diameter(LVDd),daytime Epworth sleepiness scale(ESS)score,Pittsburgh sleep quality index(PSQI)score and incidence of adverse cardiovascular events(MACE)were compared at baseline and 3 months later.RESULTS After 3 months,AHI,HI and AI in observation group were lower than those in control group,and MSpO2 and LSpO2 were higher than those in control group(P<0.05);Sleep efficiency of observation group was higher than control group,daytime ESS score,PSQI score and MAI were lower than control group(P<0.05).There were no significant differences in PaCO2,LVDd,PaO2,blood lactic acid,sleep latency,pH,LVEF,rapid eye movement latency,LVDd,Tei index between the observation group and the control group(P>0.05).The incidence of MACE in the observation group was 5.41%(2/37),compared with 13.16%(5/38)in the control group,there was no significant difference(P>0.05).CONCLUSION In patients with mild OSAHS left after palatopharyngoplasty with diastolic cardiac dysfunction,the exercise of pharyngeal cavity and genoglossus can improve hypopnea,alleviate clinical symptoms and improve sleep quality,but it has limited effect on the improvement of cardiac function.

Objective To establish a mouse model treated with busulfan and to investigate its effects on the metabo-lism of spermatogonial stem cells(SSCs)of mouse testis.Methods C57BL/6J male mice with age of 8 weeks were injected with 10 mg/kg of busulfan intraperitoneally,then Thy1 positive cells were selected by immunomagnetic beads on day 0,day 5 and day 10 and followed by identification for purity and metabolomic analysis.Results The testis weight ratio decreased and the tissue structure of testis was damaged(P＜0.05).Based on the results of principal component analysis(PCA)and partial least squares discriminant analysis(PLS-DA),there were signifi-cant metabolic differences between the sample groups treated for 0 d,5 d and 10 d.A total of 89 differential metabolites were identified including glutathione(GSH),arginine and unsaturatedfatty acids(UFAs),and their important metabolic pathways involved glycerophospholipid metabolism,arginine and proline metabolism.Conclu-sions Affecting the specific metabolic pathway may result in obvious reproductive toxicity and lead to decrease of testicular weight as well as tissue structure damage in mice.Metabolomic analysis showed that the potential repro-ductive toxicity mechanism of SSCs may be related to the metabolic pathways such as lipid metabolism,arginine and proline metabolism.

OBJECTIVE: To explore the effect of femoral neck cortical fragments and surfacial area on avascular necrosis(AVN) after internal fixation of femoral neck fractures based on CT imaging in young adult. METHODS: From January 2011 to January 2021, 218 young and middle-aged patients with femoral neck fractures were reverse triangle fixed with three cannulated lag screws, including 104 males and 114 females;aged 19 to 60 years old with a mean of (48.22±10.58) years old. The preoperative waiting time≤48 h was 155 cases, and the preoperative waiting time> 48 h was 63 cases; 68 cases were comminuted cortex of the femoral neck, 32 of them with superficial area of the comminuted cortex>25 mm². All patients were followed up for at least 2 years, the age, gender, injury side, body mass index, injury mechanism, preoperative waiting time, operation time, Garden classification, whether femoral neck cortex fracture and size by CT analysis and complications were analyzed the correlation to the definite occurrence of AVN. The AVN group and the non-AVN group were divided according to the final efficacy results.Univariate analysis yielded significant independent variables, Multiple Logistic regression analysis was further performed to identify the independent risk factors for AVN. RESULTS: By univariate analysis, the AVN and non-AVN groups were significant in injury mechanism(χ²=18.552, P=0.000), preoperative waiting time( χ²=2.065, P=0.033), Garden classification (χ²=12.598, P=0.006), comminuted cortex (χ²=16.357, P=0.000), and the superficial area of the comminuted cortex(χ²=23.371, 0.000, P=0.000). Multiple Logistic regression indicated injury mechanism high energy injury[Exp(B)=3.487, 95%CI(1.583, 10.464), P=0.002], comminuted cortex of the femoral neck[Exp(B)=2.494, 95%CI(1.315, 10.861), P=0.002];the superficial area of the comminuted cortex>25 mm²[Exp(B)=22.161, 95%CI(3.922, 1242.828), P=0.001] were independent risk factors for AVN after internal fixation of femoral neck fractures. CONCLUSION High energy injury mechanism, with comminuted cortex of the femoral neck and the superficial area of the comminuted cortex> 25 mm² were independent risk factors for AVN.The larger the superficial area of the cortex fragment may suggest more complicated injury mechanism and worse outcome.
Humans ; Male ; Female ; Adult ; Femoral Neck Fractures/diagnostic imaging* ; Tomography, X-Ray Computed ; Middle Aged ; Femur Head Necrosis/etiology* ; Young Adult ; Fracture Fixation, Internal/methods*

OBJECTIVE: To investigate the mechanism of self-efficacy between self-management ability and self-management behavior and its differences among patients with different disease courses through mediation tests. METHODS: In the study, 489 patients with type 2 diabetes who attended the endocrinology departments of four hospitals in Shanxi Province and Inner Mongolia Autonomous Region from July to September 2022 were enrolled as the study population. They were investigated by General Information Questionnaire, Diabetes Self-Management Scale, Chinese version of Diabetes Empowerment Simplified Scale, and Diabetes Self-Efficacy Scale. Mediation analyses were performed using the linear regression model, Sobel test, and Bootstrap test in the software Stata version 15.0 and divided the patients into different disease course groups for subgroup analysis according to whether the disease course was > 5 years. RESULTS: In this study, the score of self-management behavior in the patients with type 2 diabetes was 6.16±1.41, the score of self-management ability was 3.99±0.74, and the score of self-efficacy was 7.05±1.90. The results of the study showed that self-efficacy was positively correlated with self-management ability (r=0.33) as well as self-management behavior (r=0.47) in the patients with type 2 diabetes (P < 0.01). The mediating effect of self-efficacy accounted for 38.28% of the total effect of self-management ability on self-management behaviors and was higher in the behaviors of blood glucose monitoring (43.45%) and diet control (52.63%). The mediating effect of self-efficacy accounted for approximately 40.99% of the total effect for the patients with disease course ≤ 5 years, while for the patients with disease course > 5 years, the mediating effect accounted for 39.20% of the total effect. CONCLUSION Self-efficacy enhanced the effect of self-management ability on the behavior of the patients with type 2 diabetes, and this positive effect was more significant for the patients with shorter disease course. Targeted health education should be carried out to enhance patients' self-efficacy and self-management ability according to their disease characteristics, to stimulate their inner action, to promote the development of their self-management behaviors, and to form a more stable and long-term mechanism for disease management.
Humans ; Diabetes Mellitus, Type 2/therapy* ; Self Efficacy ; Self-Management ; Blood Glucose Self-Monitoring ; Blood Glucose ; Self Care

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.