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 diagnostic value of thromboelastography (TEG) combined with conventional coagulation test (CCT) for trauma-induced coagulopathy (TIC) in patients with electric burns in the early stage.Methods:This study was a retrospective case series research. From February 2018 to February 2024, the clinical data of 128 electric burn patients and 118 thermal burn patients who met the inclusion criteria and admitted to the Department of Burn Surgery of the Third Affiliated Hospital of Inner Mongolia Medical University were collected, including 224 males and 22 females, aged (38±14) years. The patients were divided into electric burn group (128 cases) and thermal burn group (118 cases) according to their injuries. The incidence of TIC, the indicators of CCT, including prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen level, D-dimer level, platelet count, and the detection indicators of TEG, including coagulation reaction time, K value, coagulation angle, maximum thrombus amplitude, comprehensive coagulation index, and lysis rate at 30 minutes after maximum amplitude within 8 hours of admission were compared between the two groups of patients. The Kappa test was used to analyze the consistency between CCT and TEG in diagnosing TIC in patients with electric burns in the early stage after burns. The receiver operating characteristic curves of CCT, TEG, and TEG combined with CCT in diagnosing TIC in 128 patients with electric burns were drawn, and the area under the curve (AUC), the maximum Jordan index, and sensitivity and specificity at this time were calculated.Results:The proportion of patients diagnosed with TIC in electric burn group was 19.5% (25/128) within 8 hours of admission, which was significantly higher than 10.2% (12/118) in thermal burn group ( χ2=4.21, P<0.05). Compared with those in thermal burn group, prothrombin time was significantly shortened ( t=-2.32, P<0.05), D-dimer level, fibrinogen level, and platelet count were significantly increased (with Z values of -2.11 and -4.16, respectively, t=4.69, P<0.05), the coagulation reaction time was significantly shortened ( t=-2.51, P<0.05), and the maximum thrombus amplitude and lysis rate at 30 minutes after the maximum amplitude were significantly increased (with t values of 2.50 and 2.10, respectively, P<0.05) in patients in electric burn group within 8 hours of admission. There were no statistically significant differences in the other CCT indicators and TEG detection indicators between the two groups of patients ( P>0.05). The CCT and TEG showed high consistency in the diagnosis of TIC in patients with electric burns in the early stage after burns (Kappa=0.63, P<0.05). The AUCs of TEG combined with CCT, TEG, and CCT in diagnosis of TIC in 128 patients with electric burns were 0.92, 0.84, and 0.77 (with 95% confidence intervals of 0.86-0.97, 0.71-0.97, and 0.71-0.97, respectively), with the maximum Jordan indexes of 0.86, 0.57, and 0.65. At this time, the specificity was 93.7%, 83.2%, and 88.2%, respectively, and the sensitivity was 92.3%, 87.5%, and 76.5%, respectively. Conclusions:Patients with electric burns are in a state of hypercoagulability of coagulation system and hyperfunction of fibrinolysis system in the early stage after burns, and TEG combined with CCT can increase the diagnostic rate of TIC in patients with electric burns.

Objective To investigate the effect of pronunciation organ correction combined with language training on rehabilitation in children with cerebral palsy and language disorder.Methods A total of 120 cases of pe-diatric cerebral palsy and language disorder treated with rehabilitation in our hospital from January 2015 to March 2018 were divided into routine group and study group by a random digital table,with 60 cases in each group.The routine group was given language training alone,while the study group was given pronunciation organ correction combined language training.The assessment results of children with dysarthria and language retardation before and after treatment were compared respectively,and the efficacy and family satisfaction were compared between the two groups.Results There were statistical differences in the assessment results of children with dysarthria and lan-guage retardation in both groups after treatment compared with before treatment(P＜0.05),and there were statis-tical differences between the two groups after treatment(P＜0.05).The overall clinical efficiency was 75％in the study group,which was higher than that of 60％in the routine group(P＜0.05).The total satisfaction rate was 90％in the study group,which was higher than that of 75％in the routine group(P＜0.05).Conclusion Giving pronunciation organ correction combined language training in the rehabilitation treatment of pediatric cerebral palsy and language disorder can improve treatment efficacy and the satisfaction of child family members.

Objective: To explore the impact of online sexuality education courses on the sexual knowledge, attitudes and related behaviors of rural girls, so as to provide the practical guidance for promoting sexual health and development. Methods: From February to June 2023, by posting information online and through commonweal organization websites, rural primary schools in 12 provinces were recruited for a semester of online sexuality education courses from October to November 2023. A self compiled sexuality education questionnaire was used to survey the knowledge, attitudes, and behaviors of rural girls before and after the course intervention, with pre tests in September 2023 and post tests in December 2023. The eligible samples were 3 058 and 2 602 , respectively. Independent sample t tests and text frequency and sentiment analysis were used to process the data Results: In terms of sexual knowledge, the scores of rural girls before and after the test were (8.49±3.29) and (9.40±3.35), respectively, with the post test score being higher than the pre test ( t =-10.20, P <0.01). In terms of attitudes, the scores of rural girls before and after the test were (11.50±4.62) and (10.82±4.80), respectively, with a decrease in stigmatization towards physiological development in the post test ( t =5.40, P <0.01). Regarding sexual related behaviors, the frequency of sexualbased bullying among rural girls was (5.12±2.13) before and (4.89±2.18) after, with a statistically significant difference ( t =3.99, P <0.01). The frequency and willingness of rural girls to discuss sexual topics with significant others both increased on post test (pre test:8.45±2.62; post test: 8.73± 2.62) and (pre test:8.90±2.46, post test:9.16±2.46), with a statistically significant difference ( t =-3.91, -4.03, P < 0.01 ). Text analysis revealed that "boys" "girls" and "menstruation" were the most concerned topics among the participants, and compared to before receiving sex education (69.91%), the proportion of negative emotions among rural girls decreased ( 18.59 %). Conclusion Online sexuality education courses can improve the sexual knowledge of rural girls, reduce stigma and negative emotions towards sex, decrease the incidence of sexual based bullying and increase the frequency and willingness to discuss sexual topics with parents, teachers, and peers.

Objective:To investigate the role of RNA m6A methylation in mediating cerebellar dysplasia through analyzing the phenotypes of the mouse cerebella and the expression of several key m6A regulators upon hypobaric hypoxia treatment.Methods:Five-day old C57/BL6 mice were exposed to hypobaric hypoxia for 9 days. The status of mouse cerebellar development was analyzed by comparing the body weights, brain weights and histological features. Immunostaining of cell-type-specific markers was performed to analyze the cerebellar morphology. Real-time PCR, Western blot and immunohistochemical staining were performed to detect the expression of key m6A regulators in the mouse cerebella.Results:Compared with the control, the body weights, brain weights and cerebellar volumes of hypobaric hypoxic mice were significantly reduced ( P<0.01). The expression of specific markers in different cells, including NeuN (mature neuron), Calbindin-D28K (Purkinje cell) and GFAP (astrocyte), was decreased in hypobaric hypoxic mouse cerebella ( P<0.01), accompanied with disorganized cellular structure. The expression of methyltransferase METTL3 was significantly down-regulated in the cerebella of hypobaric hypoxic mice ( P<0.05). Conclusions:Hypobaric hypoxia stimulation causes mouse cerebellar dysplasia, with structural abnormalities in mature granular neurons, Purkinje cells and astrocytes. Expression of METTL3 is decreased in hypobaric hypoxic mice cerebellum compared with that of normobaric normoxic mice, suggesting that its mediated RNA m6A methylation may play an important role in hypobaric hypoxia-induced mouse cerebellar dysplasia.

In magnetic resonance examination,the interaction between implants and the radio frequency(RF)fields induces heating in human tissue and may cause tissue damage.To assess the RF-induced heating of implants,three steps should be executed,including electromagnetic model construction,electromagnetic model validation,and virtual human body simulations.The crucial step of assessing RF-induced heating involves the construction of a test environment for electromagnetic model validation.In this study,a hardware environment,comprised of a RF generation system,electromagnetic field measurement system,and a robotic arm positioning system,was established.Furthermore,an automated control software environment was developed using a Python-based software development platform to enable the creation of a high-precision automated integrated test environment.The results indicate that the electric field generated in this test environment aligns well with the simulated electric field,making it suitable for assessing the RF-induced heating effects of implants.

The NLRP3 inflammasome's core and most specific protein, NLRP3, has a variety of functions in inflammation-driven diseases. Costunolide (COS) is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity, but the principal mechanism and molecular target of COS remain unclear. Here, we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3, altering the ATPase activity and assembly of NLRP3 inflammasome. We declare COS's great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation. We also reveal that the α-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation. Taken together, NLRP3 is identified as a direct target of COS for its anti-inflammasome activity. COS, especially the α-methylene-γ-butyrolactone motif in COS structure, might be used to design and produce novel NLRP3 inhibitors as a lead compound.