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 provide a reference for the early diagnosis， drug treatment and medication monitoring for patients with Lemierre’s syndrome. METHODS The doctors confirmed the diagnosis of the patient as having Lemierre’s syndrome based on the patient’s condition and the results of metagenomic next-generation sequencing （mNGS）， and the clinical pharmacists participated in the treatment process of the patient. During the treatment process， the clinical pharmacists suggested using piperacillin sodium and tazobactam sodium combined with metronidazole for anti-infective treatment against Fusobacterium necrophorum infection； clinical pharmacists recommend anticoagulant treatment with Enoxaparin sodium injection for left internal jugular vein thrombophlebitis. RESULTS The doctors accepted the suggestion of the clinical pharmacists， and the patient’s condition improved after treatment and was allowed to be discharged with medication. CONCLUSIONS By interpreting the results of mNGS， combined with the patient’s condition， the clinical pharmacists assist doctors in formulating individualized anti-infective and anticoagulant plans for the patient and provide medication monitoring， ensuring the safety and effectiveness of the patient’s medication.

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 explore the efficacy and safety of single-incision transobturator bulbourethral sling suspension without skin tunnel puncture in male patients with urinary incontinence.Methods:The clinical data of 6 male patients with urinary incontinence who underwent single-incision transobturator bulbourethral sling suspension without skin tunnel puncture in Beijing Hospital from August 2023 to August 2024 were retrospectively analyzed.The age of the patients ranged from 66 to 76 years old, with an average of 71.7 years old. The disease duration ranged from 18 to 48 months, with an average of 30 months. Six patients used 1 to 3 pads per day, with an average of 2.3 pads. The International Continence Incontinence Questionnaire Short Form (ICI-Q-SF) scored 13 to 19, with an average of 15.8. The Incontinence Quality of Life Questionnaire (I-QOL) scored 5.3 to 30.6, with an average of 18.8. Three patients underwent transurethral resection of the prostate for benign prostatic hyperplasia and three patients underwent radical prostatectomy for prostate cancer. The degree of urinary incontinence was mild in 2 cases and moderate in 4 cases. The technical points are as follows: the puncture method has been changed from the traditional outside-in approach to an inside-out approach. After the puncture needle passes through from beneath the skin at the incision, the sling is guided in, avoiding the need for skin tunneling punctures. Upon completion of the puncture, the ends of the sling on both sides are tied with a certain tension at the midline of the incision, and the incision is then closed layer by layer. The efficacy and safety of surgery were evaluated by recording the number of daily pad use, subjective scoring scale [International Committee on Urinary Incontinence Questionnaire-Short Form (ICI-Q-SF), Incontinence Quality of Life (I-QOL)] and complications at 1 month after surgery. Social continence was defined as 0 to 1 pad use per day. Successful treatment was defined as social continence. Treatment improvement was defined as no social continence, but 50% or more improvement of symptoms compared with that before surgery. Other conditions were defined as treatment failure.Results:All operations were successfully completed. After 1 to 11 months of follow-up, all patients achieved social continence. The patients' postoperative daily use of urinary pads ranged from 0 to 1 piece, with a mean of 0.5 piece. ICI-Q-SF scores ranged from 1 to 7, with a mean of 3. I-QOL scores ranged from 72.1 to 85.2, with a mean of 77.0. All the indicators were significantly improved compared with those before operation. In terms of postoperative complications, one patient had dysuria and urinary retention 2 days after the removal of the catheter, which was improved after symptomatic treatment of anti-inflammatory, detumescence, and indwelling catheter. At the last follow-up, there were no surgical related complications.Conclusions:The single-incision transobturator bulbourethral sling suspension without skin tunnel puncture for the treatment of male urinary incontinence is safe and effective. Compared to the traditional surgical method, it does not increase the difficulty of the procedure and is technically feasible, offering clinicians a new approach and perspective.

【Objective】 To investigate the expressions of P53 and Ki-67 in prostate cancer (PCa)and to explore their correlation with the clinicopathological characteristics. 【Methods】 The expressions of P53 and Ki-67 in 90 PCa patients were detected with immunohistochemistry. Patients’ age, preoperative prostate-specific antigen (PSA) level, postoperative Gleason score, pathological stage, and invasion of neurovascular cancer embolus of all patients were recorded. The relationship of P53 expression with the above indexes was evaluated. 【Results】 The positive rates of P53 and Ki-67 were 27.8% (25/90) and 46.7% (42/90), respectively. The positive rate of P53 in pT2 and pT3-T4 stage groups were 19.7% (13/66) and 50.0% (12/24) (P=0.005), and the positive rate of Ki-67 were 36.4% (24/66) and 75.0% (18/24) (P=0.001), respectively. The positive rate of Ki-67 in Gleason score ≤6, ≤7 and ≥8 groups were 30.4%, 53.8% and 66.7%, respectively, with statistical difference. Positive expression of P53 was related to Ki-67 expression, but not to patients’ age, preoperative PSA level, postoperative Gleason score and nerve and invasion of neurovascular cancer embolus. 【Conclusion】 P53 expression is related to tumor stage and Ki-67, while Ki-67 expression is associated with tumor stage ang grade.

Objective:To compare outcomes between standardized and misdiagnosis and mistreatment of osteosarcoma.Methods:A retrospective analysis of patients with high-grade osteosarcoma who received appropriate surgical treatment and chemotherapy (299 cases, control group) and those who were misdiagnosed (benign or infective) and received mistreatment (23 cases, study group) between January 2009 and December 2021. Gender, age, first operation mode, recurrence time, recurrence interval, metastasis time, metastasis interval, total survival time (months), survival status in the two group and tumor site reoperation mode in the study group were statistically analyzed. Further, chi-square test was performed for comparison of the clinical between two groups. The survival analysis was performed using Kaplan-Meier test and Log-rank test.Results:All the 322 patients were followed up. In the control group, the average follow-up time was 42 months (1-137 months), the average age was 24 years (3-80 years), male 184 cases, female 115 cases, and limb salvage rate was 85.3% (255/299). Seven patients underwent amputation, and the amputation rate was 17.7% (44/299). The recurrence rate was 8.4% (25/299), the average recurrence interval was 22.8 months (7-36 months), and the metastasis rate was 28.1% (85/299), the average metastasis time was 32.7 months (0-58 months). In the study group, the average of follow-up time was 30 months (9-117 months), the average age was 36 years (5-67 years), 17 males and 6 females. Among them, eleven patients were treated with limb salvage in the second stage, and the limb salvage rate was 47.8% (11/23). Seven patients underwent amputation, and the amputation rate was 30.4% (7/23). The recurrence rate was 26.1% (6/23), the average recurrence interval was 11 months (1-42 months), and the metastasis rate was 43.4% (10/23), the average metastasis time was 20.3 months (1-44 months). The 5-year survival rate was 50.7% in the study group and 56.1% in the control group. There was no significant difference between the two groups (χ 2=0.09, P=0.760). Conclusion:The overall prognosis of patients with high-grade osteosarcoma who receive active treatment after mistreatment is similar to that of patients with standardized treatment, but the recurrence and metastasis rate is higher, the recurrence time is earlier, and the amputation rate is higher.

Objective:To investigate the clinical features, diagnosis, treatment and prognosis of primary urethral carcinoma.Methods:The clinical and follow-up data of 12 patients with primary urethral carcinoma admitted to Beijing Hospital from July 2016 to December 2020 were retrospectively analyzed.Results:There were four males and eight females, with an average age of 66.3(53~75)years.Nine patients underwent magnetic resonance examination before operation, and eight patients presented with abnormal urethral signals.The clinical stage of female patients was generally later than those of male patients, and all patients received surgical treatment.Four male patients did not receive post-operative adjuvant treatment, and all of them attained disease-free survival.Among the eight female patients, four patients received postoperative adjuvant radiotherapy or chemotherapy, five patients had recurrence or metastasis during follow-up, and two patients died.Conclusions:The clinical stage of female urethral cancer is later than that of male.MRI examination is beneficial to the determination of local invasion of urethral cancer.For female proximal urethral cancer and male posterior urethral cancer, radical resection has a good therapeutic effect.