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.

ObjectiveTo investigate the possible mechanism of Shenqi Jianxin Formula （参芪健心方） in the treatment of chronic heart failure （CHF） from the perspective of pyroptosis. MethodsFifty-two rats were randomly divided into sham operation group （n=8） and modeling group （n=44）. In the modeling group， the anterior descending branch of the left coronary artery was ligated to construct CHF rat model. Forty successfully-modelled rats were randomly divided into model group， Entresto group， Shenqi Jianxin Formula group， MCC950 group and the combination group （Shenqi Jianxin Formula plus MCC950）， with 8 rats in each group. In Shenqi Jianxin Formula group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， while in Entresto group， 68 mg/（kg·d） of Entresto suspension was given by gavage； in MCC950 group， MCC950 was injected intraperitoneally with 10 mg/kg once every other day， and in the combination group， 7.4 g/（kg·d） of Shenqi Jianxin Formula was given by gavage， and MCC950 was injected intraperitoneally with 10 mg/kg once every other day； 10 ml/（kg·d） of saline was given by gavage in the sham operation group and the model group. After 3 weeks of continuous intervention， serum brain B-type natriuretic peptide （BNP）， creatine kinase isoenzyme MB （CK-MB）， interleukin 1β （IL-1β）， and interleukin 18 （IL-18） levels were detected by ELISA； HE staining and MASSON staining were used to observe pathological changes in rat myocardium. Except for the Entresto group， western blot technique was used to detect the expression of NOD-like receptor protein 3 （NLRP3）， caspase-1， and apoptosis-associated speck-like protein possessing a caspase-recruiting domain （ASC）； RT-PCR was used to detect the expression of NLRP3 and caspase-1 mRNA. ResultsCompared with the sham operation group， HE staining of rats in the model group showed obvious myocardial injury， while MASSON staining showed increased area of collagen fibrosis， and serum BNP， CK-MB， IL-1β， IL-18， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were all elevated （P＜0.05）. Compared with those in the model group， cardiomyocyte injury of rats and collagen fibrosis area were reduced， and serum BNP， CK-MB， IL-1β， and IL-18 contents were all reduced in Shenqi Jianxin Formula group， Entresto group， MCC950 group， and the combination group； except for Entresto group， myocardial tissue NLRP3， caspase-1， ASC protein expression and NLRP3， caspase-1 mRNA expression were reduced in the remaining three medication group （P＜0.05）. Compared with Shenqi Jianxin Formula group， the MCC950 group and the combination group showed decreased serum IL-1β and IL-18 content， collagen fibrosis area， myocardial tissue NLPR3， caspase-1 protein expression， and caspase-1 mRNA expression， and decreased ASC and NLRP3 mRNA expression was shown in the combination group （P＜0.05）. Compared with MCC950 group， collagen fibrosis area was reduced， and serum IL-18 content， NLRP3， caspase-1 mRNA expression were reduced in the combination group （P＜0.05）. ConclusionShenqi Jianxin Formula can effectively improve the myocardial injury and heart failure in rats with CHF， and its mechanism may be related to the inhibition of cardiomyocyte pyroptosis through NLPR3/Caspase-1 pathway to reduce the level of intramyocardial inflammation. The combined use of MCC950 with Shenqi Jianxin Formula could more effectively inhibite myocardial pyroptosis， with better therapeutic result than single use of each part.

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

ObjectiveTo understand the mortality trends among residents of Fuling District， Chongqing， before and after theCOVID-19 outbreak， and to provide references for the government to formulate disease prevention and control policies and measures. MethodsData on mortality and population in Fuling District from 2017 to 2022 were collected to analyze population mortality and standardized mortality rates， and to compare the changes in the causes of death by year and before and after the pandemic. ResultsFrom 2017 to 2022， the crude mortality rate in Fuling District showed an upward trend （APC=3.04%， P<0.05）， while the standardized mortality rate showed a downward trend （APC=-6.47%， P<0.01）. The mortality rate of males was higher than that of females （P<0.05）， with different age groups having different causes of death composition. The highest proportion of deaths in 0-year-old group was from infectious diseases， maternal and neonatal diseases， and nutritional deficiencies， the highest proportion of deaths in the 1‒24 age group， with the exception of those aged 5‒9， was from injuries， and the main cause of death for residents aged 25 and above was chronic diseases. The mortality rate of mental and behavioral disorders rose from the 13th to the 9th place. According to the epidemic situation of COVID-19， there were no changes in the top five causes of death among the entire population. The motility rate of endocrine， nutritional and metabolic diseases rose from the sixth to the fifth place in male population， and the motility rate of malignant tumor rose from the 3rd to the 2nd place in female population. ConclusionThere are no changes in the top five causes of death among the entire population of Fuling District before and after the COVID-19 outbreak. Chronic diseases remain the main cause of death. It is necessary to control the risk factors for cardiovascular and cerebrovascular diseases such as hypertension， diabetes， and dyslipidemia， and to curb the rising trend of mortality rates from strokes and acute myocardial infarction. For deaths caused by accidental injuries， targeted health education should be conducted for different populations.