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.

Objectives To investigate the clinical efficacy on combined application of ear canal injected administration dispenser and triamcinolone acetonide econazole nitrate cream in the treatment of mycosis externa.Methods Clinical data of 130 patients(166 ears)diagnosed with mycosis externa from January 2023 to December 2023 were collected and randomly divided into two groups.In the observation group,65 cases(86 ears)were treated with ear canal injected administration dispenser combined with triamcinolone acetonide econazole nitrate cream,while in the control group,65 cases(80 ears)applied clean cotton swabs with triamcinolone acetonide econazole nitrate cream to the external auditory canal by themselves to treat mycosis externa.All the patients were treated for 4 weeks and followed up for half a year.The clinical efficacy,recurrence rate and adverse reactions were statistically analyzed and compared.Results The total effective rate of the observation group was 97.67%,which was significantly higher than that of the control group was 73.75%,there was a significant difference between the two groups(P<0.05).There were no obvious adverse reactions in either group.No obvious recurrence was observed in the recovered patients of both groups during the follow-up period.Conclusion The efficacy of combined of ear canal injected administration dispenser and triamcinolone acetonide econazole nitrate cream in the treatment of mycosis externa is significant.Compared with the traditional way of medicine application,the adverse reactions are less.It can improve the cure rate and reduce the recurrence rate,which is worthy in clinical application.

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.

Objectives To investigate the clinical efficacy on combined application of ear canal injected administration dispenser and triamcinolone acetonide econazole nitrate cream in the treatment of mycosis externa.Methods Clinical data of 130 patients(166 ears)diagnosed with mycosis externa from January 2023 to December 2023 were collected and randomly divided into two groups.In the observation group,65 cases(86 ears)were treated with ear canal injected administration dispenser combined with triamcinolone acetonide econazole nitrate cream,while in the control group,65 cases(80 ears)applied clean cotton swabs with triamcinolone acetonide econazole nitrate cream to the external auditory canal by themselves to treat mycosis externa.All the patients were treated for 4 weeks and followed up for half a year.The clinical efficacy,recurrence rate and adverse reactions were statistically analyzed and compared.Results The total effective rate of the observation group was 97.67%,which was significantly higher than that of the control group was 73.75%,there was a significant difference between the two groups(P<0.05).There were no obvious adverse reactions in either group.No obvious recurrence was observed in the recovered patients of both groups during the follow-up period.Conclusion The efficacy of combined of ear canal injected administration dispenser and triamcinolone acetonide econazole nitrate cream in the treatment of mycosis externa is significant.Compared with the traditional way of medicine application,the adverse reactions are less.It can improve the cure rate and reduce the recurrence rate,which is worthy in clinical application.

Objective:To investigate the levels and clinical significances of miRNA-155-5p (miR-155-5p) and hypoxia inducible factor-1α (HIF-1α) in the bone marrow of patients with acute myeloid leukemia (AML)-M 5. Methods:A cross sectional study was conducted. The bone marrow samples were collected from 32 AML-M 5 patients who were admitted to the First Affiliated Hospital of Hebei North University from November 2023 to December 2024, and the bone marrow samples collected from 11 patients with megaloblastic anemia from November 2023 to May 2025 were used as controls. Reverse transcription real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to determine relative expression of miR-155-5p at the transcription level in bone marrow mononuclear cells, and enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of HIF-1α protein in bone marrow supernatant. The levels of miR-155-5p and HIF-1α in bone marrow were compared between AML patients and control group, as well as among AML patients with different prognostic risks. Spearman method was used to analyze the relationship between miR-155-5p level and HIF-1α level in bone marrow of AML patients and their levels with bone marrow and peripheral blood cell indicators. Results:Among the 32 AML-M 5 patients, 20 patients (62.5%) were male and 12 patients (37.5%) were female, with a median age [ M ( Q1, Q3)] of 63 (51, 70) years; according to the clinical response criteria recommended by the European Leukemia Network (ELN) in 2022, there were 12 cases (37.5%) of complete response (CR) and 8 cases (25.0%) of non-complete response (NCR); according to the risk stratification criteria recommended by ELN in 2022, there were 8 cases (25.0%) with good prognosis, 13 cases (40.6%) with moderate prognosis and 11 cases (34.4%) with poor prognosis. In the control group, there were 5 males and 6 females, with a median age of 68 (63, 72) years. There was no statistically significant difference in gender and age between the two groups (both P > 0.05). The transcription level relative expression of miR-155-5p in the bone marrow mononuclear cells of AML-M 5 patients [5.13 (2.83, 8.84) vs. 0.87 (0.56, 1.69)] and the concentration of HIF-1α protein in the bone marrow supernatant of AML-M 5 patients [(116±32) pg/ml vs. (58±22) pg/ml] were higher than those in the control group, and the differences were statistically significant (both P < 0.001). The relative expression of miR-155-5p at the transcription level in the initial diagnosis group and NCR group and the concentration of HIF-1α in the initial diagnosis group, NCR group and CR group were higher than those in the control group (all P < 0.01), the relative expression of miR-155-5p at the transcription level in the CR group was higher than that in the control group, but the difference was not statistically significant ( P > 0.05); the relative expression of miR-155-5p at the transcription level in the newly diagnosis group was higher than that in the CR group, and the difference was statistically significant ( P < 0.01). However, there was no statistically significant difference between the newly diagnosis group and the NCR group or between the NCR group and the CR group (all P > 0.05). The concentration of HIF-1α in the newly diagnosis group and NCR group was higher than that in the CR group, and the differences were statistically significant (both P < 0.05). However, there was no statistically significant difference between the newly diagnosis group and the NCR group ( P > 0.05). There was no statistically significant difference in the relative expression of miR-155-5p at the transcription level and HIF-1α concentration in bone marrow among AML-M 5 patients with poor prognosis, moderate prognosis and good prognosis (both P > 0.05). The level of miR-155-5p in the bone marrow of AML-M 5 patients was positively correlated with the level of HIF-1α ( r = 0.446, P = 0.010); the level of miR-155-5p in bone marrow was positively correlated with the proportion of bone marrow primitive cells ( r = 0.583, P < 0.001), peripheral blood leukocyte count ( r = 0.464, P = 0.008), peripheral blood monocyte count ( r = 0.464, P = 0.007), and peripheral blood monocyte-to-leukocyte ratio ( r = 0.457, P = 0.009). The concentration of HIF-1α in the bone marrow of AML-M 5 patients was positively correlated with the proportion of bone marrow primitive cells ( r = 0.568, P = 0.001) and peripheral blood mononuclear cells-to-white blood cells ratio ( r = 0.375, P = 0.034), but not with peripheral blood white blood cell count ( r = 0.159, P = 0.385) or peripheral blood mononuclear cell count ( r = 0.300, P = 0.095). Conclusions:The levels of miR-155-5p and HIF-1α in the bone marrow of AML-M 5 patients are relatively high, and the levels of both are lower in patients with remission. However, the levels of both may not be related to the risk of prognosis. The levels of miR-155-5p and HIF-1α in the bone marrow of AML-M 5 patients are positively correlated, and their levels are also positively correlated with major hematological indicators in the bone marrow and peripheral blood.

Objective To explore the regulatory effect of corilagin(COR)on Nod-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome activation and chondrocyte pyroptosis induced by lipopolysaccharide(LPS)combined with nigericin(NIG).Methods Primary chondrocytes isolated from C57BL/6J mice were cultured to passage 3 for experiments.Cells were divided into control group,LPS group,LPS+NIG group,and LPS+NIG+COR(low-,medium-,and high-dose)groups.The chondrocytes were pre-sensitized with LPS for 4 h.Then the cells were treated with COR at different concentrations(10,20,and 40 μmol/L)for 30 min,and finally NIG(10 μmol/L)was supplemented for 1 h.Control cells were cultured in DMEM/F-12 medium supplemented with 1%FBS.Cell counting kit 8(CCK-8)was used to detect the effect of COR at different concentrations(10,20,40 μmol/L)on chondrocyte viability.Propidium iodide(PI)and Hoechst 33342 staining and lactate dehydrogenase(LDH)release assay were used to analyze the effect of COR on chondrocyte death induced by LPS and NIG.Western blotting was used to detect the expression of the NLRP3 inflammasome activation marker cysteine aspartic acid specific protease 1(caspase 1)p20 in the cell supernatant and NLRP3,apoptosis-associated speck-like protein(ASC),caspase 1,interleukin-1β precursor(pro-IL-1β),and pyroptosis execution protein gasdermin D(GSDMD)in the cell lysate.Enzyme-linked immunosorbent assay was used to detect the level of IL-1β in cell culture supernatant.Reactive oxygen species(ROS)fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate(H2DCFDA)staining was used to observe the effect of COR on ROS production,and Western blotting was used to detect the expression of intracellular glycolysis-related proteins hexokinase 2(HK2),glucose transporter 1(GLUT1),and lactate dehydrogenase A(LDHA).Results COR exhibited slight effect on chondrocyte viability at the concentration≤40 μmol/L.COR(10-40 μmol/L)reduced the proportion of PI-positive cells(all P＜0.05)and the release of LDH(all P＜0.01)stimulated by LPS and NIG,inhibited the expression of GSDMD N-terminus domain in chondrocytes,and reduced the release of caspase 1 p20 and IL-1β from chondrocytes(all P＜0.01).Furthermore,COR(40 μmol/L)reduced the production of ROS(compared with the control group,P＜0.01)and inhibited the expression of glycolysis-related proteins HK2,GLUT1,and LDHA(all P＜0.05).Conclusion COR can inhibit NIG-induced glycolysis/ROS/NLRP3 signaling,thereby preventing NLRP3 inflammasome activation and chondrocyte pyroptosis.

Objective To determine the acute effects of blood flow restriction(BFR)running warm-up on Achilles tendon morphology and function in basketball players in order to provide a theoretical basis for optimizing warm-up protocols for military personnel and athletes susceptible to Achilles tendon injuries.Methods Twenty-seven male basketball players were subjected and asked to participate in 3 different running warm-up protocols:low-speed running(LSR),high-speed running(HSR),and BFR combined with LSR(BFR-LSR).The acute changes in Achilles tendon morphology,mechanical properties,and functional performance across the 3 testing sessions were analyzed and compared.Results Immediately after training,both HSR warm-up and BFR-LSR warm-up significantly improved Achilles tendon thickness,blood flow,stiffness,and gastrocnemius maximal voluntary isometric contraction(MVIC)when compared with LSR warm-up(P<0.05).No statistical differences were observed in above indicators between the BFR-LSR and HSR warm-ups(P>0.05).24 hours after training,compared with LSR warm-up,HSR warm-up still significantly improved Achilles tendon thickness,blood flow,stiffness,and gastrocnemius MVIC(P<0.05).Although BFR-LSR warm-up did not show statistically significant differences in these parameters compared to LSR warm-up,it still demonstrated positive trends.Immediately and 24 h after training,no obvious difference were found in jump performance among the 3 warm-up protocols(P>0.05),but,both BFR-LSR and HSR warm-ups exhibited superior performance than LSR warm-up.Conclusion Immediately after training,BFR-LSR warm-up demonstrates comparable effects to the HSR warm-up on improving Achilles tendon morphology and performance,as well as enhancing jump performance.However,its sustained and long-term effects require further investigation.

High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.