Objective:This study aimed to explore the serum levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death-ligand 1 (sPD-L1) in patients with spontaneous intracerebral hemorrhage (ICH) and their clinical value in the prognostic analysis.Methods:This prospective cohort study included patients aged ≥18 years admitted to the department of critical care medicine at the Affiliated Hospital of Zunyi Medical University between January 2022 and October 2024 with a first episode of ICH presenting within 24 hours of onset. Patients with hemorrhage caused by other causes (e.g., tumor, medication and trauma) or incomplete data were excluded. Based on 28-day all-cause mortality, patients were divided into survival group and non-survival group. According to the 60-day neurological outcome, patients were divided into good neurological outcome group and poor neurological outcome group. Clinical and imaging data were collected, along with venous blood samples obtained within 24 hours of admission to measure serum levels of sPD-1 and sPD-L1. Predictive indicators were identified using LASSO-Logistic regression analysis was used to identify predictive indicators, and a nomogram was constructed to visualize the prediction model. Model performances were evaluated using receiver operating characteristic curves, decision curve analysis, calibration curves, and the Hosmer-Lemeshow test.Results:A total of 155 patients were included: 101 in the survival group and 54 in the death group; 56 in the favorable neurological outcome group and 99 in the poor neurological outcome group. Serum sPD-1 concentrations were significantly lower in the death group and poor neurological outcome group compared to the survival group and favorable neurological outcome group, respectively. Conversely, serum sPD-L1 concentrations were significantly higher in the death group and poor neurological outcome group compared to the survival group and favorable neurological outcome group (all P < 0.05). Serum sPD-1 and sPD-L1 were identified as predictors of 28-day mortality risk. A nomogram incorporating seven indicators—brainstem hemorrhage, hemorrhage volume, obstructive hydrocephalus, surgical intervention, admission NIHSS score, and admission serum sPD-1 and sPD-L1 levels—demonstrated superior predictive performance [AUC=0.984 (95% CI: 0.968-1.000)] compared to sPD-1 alone (AUC=0.712) or sPD-L1 alone (AUC=0.753). Serum sPD-1 was a predictor of poor 60-day neurological outcome. A nomogram incorporating obstructive hydrocephalus, admission NIHSS score, and admission serum sPD-1 level [AUC=0.818 (95% CI: 0.754-0.882)] outperformed sPD-1 alone (AUC=0.637) or sPD-L1 alone (AUC=0.602). Conclusions:Serum levels of sPD-1 were significantly lower in the non-survivors and the patients with poor neurological outcomes compared to the survivors and the patients with good neurological outcomes. However, serum levels of sPD-L1 were significantly higher in the non-survivors and the patients with poor neurological outcome. Serum sPD-1 was an independent predictor of 28-day mortality risk and 60-day poor neurological outcome; serum sPD-L1 was an independent predictor of 28-day mortality risk. A nomogram prediction model incorporating sPD-1 and sPD-L1 demonstrated good predictive performance for mortality risk and poor neurological outcome.

Objective: To investigate the differences in enolase and laminin levels in vaginal epithelial tissues between mice successfully infected withGardnerellaand mice not infected with Gardnerella, providing information for further exploration of the correlation between enolase and laminin levels and the incidence of bacterial vaginosis. Methods: Gardnerella strains isolated, purified, and identified from vaginal secretions of patients with bacterial vaginosis were used to infect the vagina of mice and establish a mouse model of bacterial vaginosis. Successful and failed mice was defined as successful and failed groups, respectively. Differential expression of enolase and laminin in the vaginal epithelial tissue of two groups of mice was detected by Western blot. Modeling success rate was statistically analyzed, and the expression differences of enolase and laminin was compared between two groups. Results: One strain of Gardnerella vaginalis infected 10 SPF grade KM mice, 7 mice met the diagnostic criteria for bacterial vaginosis, and 3 mice failed to model, with a success rate of 70%. Western blot was used to detect protein expression levels, and the levels of laminin and enolase in the successfully modeled mouse vaginal epithelial tissue were significantly higher than those in the failed modeling group, with statistical differences between the two groups(P<0.05). Conclusion Enolase and laminin may be involved in the occurrence of bacterial vaginosis, however, further research is needed to determine the mechanisms through which they trigger the occurrence and development of the disease.

Objective:To explore genes related to costimulatory molecule related to the prognosis of bladder cancer,and to construct and evaluate prognosis model based on costimulatory molecule-based signature(CMS).Methods:Gene expression matrix and clinical information of bladder cancer patients were downloaded from TCGA database and GEO database(GSE31684),and costimulatory molecule-related genes were retrieved from the literature.The univariate and multivariate Cox analysis were used to screened prognostic-related genes and constructed prognostic model.Forecast accuracy of model was verified in TCGA training group,TCGA validation data group and GEO group by Kaplan-Meier survival analysis and receiver operating characteristic curve(ROC).Considering risk score and clinical characteristics,we constructed a nomogram and evaluated its performance by consistency analysis and ROC.CIBERSORT algorithm was used to analyze immune cell composition of tumor microenvironment infiltration,and gene set enrichment analysis(GSEA)was performed to explore the potential mechanism.Results:Four prognostic-related CMSs were found:TNFRSF14,CD276,ICOS and TMIGD2,of which three were included in the risk score construction.Multivariate Cox regression results showed that the risk score based on CMS was an independent prognostic factor for bladder cancer patients.Consistency analysis and ROC results showed that the nomogram had ideal prognosis prediction accuracy.Immune infiltration analysis showed that the high risk group was likely to be in immunosuppressive state.GSEA results suggested that genes in high risk group were enriched in extracel-lular matrix(ECM)receptors interaction,cell cycle and other pathways.Conclusion:TNFRSF14,CD276 and ICOS may be potential prognostic biomarkers for bladder cancer patients.CMS-based risk score and nomogram could contribute to early prognosis and choice of personalized treatment.

Hepatic fibrosis(HF)is a common pathological repair response occurring after liver injury and is a critical stage in the progression of chronic liver diseases towards cirrhosis.The molecular mechanisms of HF occurrence are complex.Liver injury triggers the release of various cytokines by multiple cell types,and initiates the downstream signaling pathways to activate the hepatic stellate cells(HSCs)and transform them into myofibroblasts(MFBs).MFBs can release large quantities of extracellular matrix(ECM),thereby disrupt the normal liver architecture and lead to the occurrence and development of HF.The potential therapeutic targets for HF are still in the experimental animal phase,and there are no clinical applications yet.This review summarizes the signaling pathways and related factors involving HSCs and ECM in HF,such as the transforming growth factor-β(TGF-β)/Smad signaling pathway,platelet-derived growth factor(PDGF),matrix metalloproteinases(MMPs),tissue inhibitors of metalloproteinases(TIMPs),and connective tissue growth factor(CTGF).It also discusses the related therapeutic targets,and provids the theoretical basis for the development of new drugs for HF.

Objective To explore the relationship between serum levels of tyrosine hydroxylase (TH) and the risk of cerebral infarction in Parkinson's patients. Methods A total of 129 patients with confirmed Parkinson's disease who were hospitalized in our hospital were selected, among the 58 patients had Parkinson's disease complicated with cerebral infarction (complicated with cerebral infarction group), and the remaining 71 patients had Parkinson's disease alone (control group). Blood TH levels and other potential related information were collected retrospectively at the time of diagnosis. Comparative analysis of data was performed using SPSS software. Results Comparing the serum TH expression levels in patients with Parkinson's disease and patients with cerebral infarction at admission , the serum TH level in patients with cerebral infarction was lower. Results also showed that the levels of CRP, IL-6, MDA, and Hcy were higher in patients with cerebral infarction, while PON-1 level was lower. In addition, patients with cerebral infarction had lower motor ability (higher UPDRS Ⅲ score). Further regression analysis was carried out with the occurrence of Parkinson's disease complicated with cerebral infarction as the dependent variable and the potential influencing factors as the independent variable. The results indicated that factors such as low expression of TH, high expression of inflammatory factors, and high expression of oxidative stress factors were positively correlated with the risk of complications of the two diseases. Conclusion The low expression of TH, inflammatory state and high oxidative stress state are the potential risk factors for Parkinson's disease complicated with cerebral infarction, which deserves clinical attention.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.
Aneuploidy ; Cost-Benefit Analysis ; Female ; Humans ; Noninvasive Prenatal Testing ; Pregnancy ; Retrospective Studies ; Trisomy 18 Syndrome/genetics*

Dyslipidemia is an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Statins delay the occurrence and development of ASCVD, and reduce the risk of cardiovascular events and death. Due to safety concerns, there exist insufficient use of lipid-lowering agents and a high withdrawal rate of the agents in the elderly. To promote the prevention and treatment of ASCVD, this expert consensus is issued and focuses on the management of dyslipidemia of Chinese elderly basing on the clinical evidence of the use of lipid-lowering drugs by the elderly, and the lipid management guidelines and expert consensus recommendations at home and abroad.

Objective The aims of this study were to determine the expression of CXCR family proteins in various subtypes and adjacent tissues of breast cancer and its relationship with prognosis,and to provide a reference for clinical diagnosis,treatment and prognosis of breast cancer. Methods The mRNA expressive profiles of CXCR family proteins in paracancerous tissues and different subtypes of breast cancer tissues were obtained from the TCGA(The Cancer Genome Atlas)database. The prognostic survival analysis of each differentially expressed protein was obtained using the PRECOG website. Results Except for CXCR1,the expression of CX-CR family proteins in breast cancer tissues and adjacent tissues was statistically different( P<0. 05). CXCR2P1,CXCR3,CXCR4, CXCR5 and CXCR6 were highly expressed in breast cancer tissues,CXCR2 and CXCR7 were lowly expressed in breast cancer tis-sues. The expressive levels of CXCR3,CXCR4 and CXCR7 were associated with the prognosis of patients. Conclusion The expres-sions of CXCR3,CXCR4 and CXCR7 in breast cancer tissues and adjacent tissues is significantly different,and its expression is related to the prognosis of breast cancer patients,which may be a potential target for molecular diagnosis or targeted therapy of breast cancer.