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 investigate the characteristics of hospitalized injury cases in Huangpu District, Guangzhou City in 2022, so as to provide evidence for optimizing injury prevention interventions. Methods: Data on hospitalized injury cases admitted between January to December 2022 were collected through the hospitalization registry system from 17 healthcare institutions in Huangpu District. The population distribution characteristics, causes of injury, injury sites, duration of hospital stay, and hospitalization costs were descriptively analyzed. Results: A total of 6 729 hospitalized injury cases were reported in Huangpu District in 2022, including 4 277 males and 2 452 females, with a male-to-female ratio of 1.74∶1. The average age was (49.57±19.82) years, with 2 064 cases (30.67%) aged 45 to <60 years and 1 921 cases (28.55%) aged ≥60 years. The median length of hospitalization was 9.00 (interquartile range, 11.00) days, with median hospitalization costs of 15 968.93 (interquartile range, 25 786.69) yuan. In the months of June to August, there were more cases of injury hospitalization,with 1 904 cases accounting for 28.30%. The top three causes of injury were falls (2 895 cases, 43.02%), transportation accidents (1 247 cases, 18.53%) and exposure to inanimate mechanical forces (1 104 cases, 16.41%). The top three injured sites were lower limb injuries (1 850 cases, 27.49%), upper limb injuries (1 596 cases, 23.72%) and other sites (1 178 cases, 17.51%). The three leading causes of injury with longest hospitalization duration were burns and scalds, transport accidents and falls, with the median duration being 12.00 (interquartile range, 8.00) days, 10.00 (interquartile range, 13.00) days and 10.00 (interquartile range, 11.00) days, respectively. The top three injury sites associated with the longest hospitalization duration were others, lower limb injuries, and head and neck injuries, with the median duration being 11.00 (interquartile range, 13.00) days, 11.00 (interquartile range, 11.00) days, and 10.00 (interquartile range, 12.00) days, respectively. The causes of injury associated with higher hospitalization costs were falls and transportation accidents, with the median hospitalization cost being 23 550.13 (interquartile range, 30 087.76) yuan for falls and 20 301.94 (interquartile range, 30 589.86) yuan for transportation accidents. The injury sites associated with higher hospitalization costs were lower limb injuries and upper limb injuries, with the median hospitalization cost being 24 257.32 (interquartile range, 34 145.54) yuan for lower limb injuries and 16 506.33 (interquartile range, 20 052.27) yuan for upper limb injuries. Conclusions In Huangpu District, hospitalized injury mainly occurred among males and individuals aged ≥45 years, with the higher incidence observed between June and August. Fall was the primary cause of injury, while lower limb injuries was the main injury sites. The injury resulted in substantially higher hospitalization costs.

The choice of biopsy method is critical in diagnosing prostate cancer (PCa). This retrospective cohort study compared systematic biopsy (SB) or cognitive fusion-targeted biopsy combined with SB (CB) in detecting PCa and clinically significant prostate cancer (csPCa). Data from 2572 men who underwent either SB or CB in Fudan University Shanghai Cancer Center (Shanghai, China) between January 2019 and December 2023 were analyzed. Propensity score matching (PSM) was used to balance baseline characteristics, and detection rates were compared before and after PSM. Subgroup analyses based on prostate-specific antigen (PSA) levels and Prostate Imaging-Reporting and Data System (PI-RADS) scores were performed. Primary and secondary outcomes were the detection rates of PCa and csPCa, respectively. Of 2572 men, 1778 were included in the PSM analysis. Before PSM, CB had higher detection rates for both PCa (62.9% vs 52.4%, odds ratio [OR]: 1.54, P < 0.001) and csPCa (54.9% vs 43.3%, OR: 1.60, P < 0.001) compared to SB. After PSM, CB remained superior in detecting PCa (63.1% vs 47.9%, OR: 1.86, P < 0.001) and csPCa (55.0% vs 38.2%, OR: 1.98, P < 0.001). In patients with PSA 4-12 ng ml -1 (>4 ng ml -1 and ≤12 ng ml -1 , which is also applicable to the following text), CB detected more PCa (59.8% vs 40.7%, OR: 2.17, P < 0.001) and csPCa (48.1% vs 27.7%, OR: 2.42, P < 0.001). CB also showed superior csPCa detection in those with PI-RADS 3 lesions (32.1% vs 18.0%, OR: 2.15, P = 0.038). Overall, CB significantly improves PCa and csPCa detection, especially in patients with PSA 4-12 ng ml -1 or PI-RADS 3 lesions.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Propensity Score ; Retrospective Studies ; Middle Aged ; Aged ; Image-Guided Biopsy/methods* ; Prostate-Specific Antigen/blood* ; Prostate/diagnostic imaging*

To investigate the clinical utilization of Rituximab biosimilar (Rituximab injection) in order to provide references for evaluating its rationality and economic value in clinical application.

Objective To investigate the causal relationship between dried fruit intake and color-ectal cancer(CRC)by using a two-sample Mendelian randomization(MR)approach.Methods Two-sample MR analysis was conducted utilizing summary data from genome-wide association studies on dried fruit intake and colorectal cancer.Separate analyses were performed using data for colon cancer and rectal cancer for validation.Genetic variants significantly and independently associated with dried fruit intake were selected as instrumental variables.The inverse variance weighted method,MR-Egger regression,weighted median method,simple mode method,and weighted mode method were employed as the primary analytical approaches.Heterogeneity tests,pleiotropy analysis,and sensitivity analysis were conducted to evaluate the reliability of the study.Results A total of 21 single nucleotide poly-morphisms(SNPs)associated with dried fruit intake were included as instrumental variables.The in-verse variance weighted analysis revealed that increased dried fruit intake was associated with a reduced risk of colorectal cancer(OR=0.55,95％CI,0.32 to 0.96,P=3.53 × 10-2),with consistent results observed for both colon cancer and rectal cancer.The findings of this study were not influenced by plei-otropy or heterogeneity,and the reliability of the results was validated by sensitivity analysis.Conclu-sion Increasing dried fruit intake has potential preventive value against colorectal cancer.

Objective:To investigate the value of myocardium scar area in predicting adverse cardiovascular events (MACEs) after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM).Methods:The first part of this study was a retrospective study. Patients diagnosed with ICM and undergoing CABG surgery at Beijing Anzhen Hospital, Capital Medical University from January 2017 to December 2022 were enrolled as the discovery cohort. All patients underwent cardiac magnetic resonance-late gadolinium enhancement (CMR-LGE) before surgery. According to the occurrence of postoperative MACEs, the patients were divided into MACEs group and MACEs-free group. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. The primary endpoint was postoperative MACEs. Univariate and multifactor regression analyses were used to analyze the risk factors for MACEs. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy and optimal cut-off value of myocardial scar area for endpoint events. The second part of this study was a prospective study. Patients with ICM who received CABG at Beijing Anzhen Hospital, Capital Medical University from January 2023 to June 2023 were enrolled as a validation cohort, and were divided into MACEs group and MACEs-free group according to whether MACEs occurred after surgery. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. Verify the reliability of the cut-off value obtained by ROC curve in the validation cohort.Results:A total of 120 patients with ICM (30 patients in MACEs group and 90 patients in MACEs-free group), aged (61.6±8.7) years, including 93 males, were included in the discovery cohort. A total of 22 ICM patients (5 patients in MACEs group and 17 patients in MACEs-free group), aged (59.5±8.2) years, including 18 males, were included in the validation cohort. Multivariate Cox regression showed that myocardial scar area ( HR=1.258, 95% CI 1.096-1.444, P=0.001) was an independent risk factor for the primary endpoint event. The area under ROC curve of myocardial scar area for predicting postoperative MACEs was 0.90 (95% CI 0.83-0.95), and myocardial scar area≥36.0% was the optimal cut-off value for predicting postoperative MACEs, and its sensitivity, specificity and accuracy were 96.7%, 72.2% and 78.3%, respectively. In the validation cohort, the sensitivity, specificity and accuracy of myocardial scar area in predicting postoperative MACEs in patients with ICM after CABG were 80.0%, 82.4% and 81.8%, respectively. Conclusion:Myocardial scar area is an independent risk factor for MACEs after CABG in patients with ICM, and myocardial scar area≥36.0% is the optimal cut-off value for predicting MACEs after CABG. Myocardial scar area can help to identify patients at high risk of surgery and provide a basis for risk stratification of patients.

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q