Objective To investigate the association of serum total testosterone(TT),free testosterone(FT),sex hormone-binding globulin(SHBG),and estradiol(E_2)with all-cause mortality rate(AMR)in males and to evaluate their predictive value. Methods Based on data from the National Health and Nutrition Examination Survey(NHANES)cycles(1999—2004 and 2013—2016),the relationships between different sex hormones and AMR was analyzed with Cox proportional hazards regression models. The dose-response relationships between different sex hormones and male AMR were assessed with restricted cubic splines(RCS). The predictive performances of different sex hormones for male AMR were compared with receiver operating characteristic(ROC)curves and the area under the curve(AUC). The survival differences across varying sex hormone levels were evaluated with Kaplan-Meier survival curves and log-rank tests. Results This study involved 3632 adult male participants with a median follow-up of 6.5 years,during which 320 AMR occurred(8.8%). Cox univariate analysis indicated that TT,FT and SHBG were risk factors for AMR(P＜0.001). Cox multivariate analysis revealed that FT and SHBG were independent risk factors for AMR(FT:HR=0.90,95%CI:0.86-0.94; SHBG:HR=1.01,95%CI:1.01-1.02). RCS revealed a U-shaped nonlinear relationship between TT,FT and AMR(P＜0.001); SHBG showed a positive dose-response relationship with AMR(P＜0.001). The AUCs of FT predicting the 5-year,10-year,and 15-year AMR were 0.78(95%CI:0.73-0.82),0.80(95%CI:0.76-0.84),and 0.84(95%CI: 0.80-0.88),respectively,significantly outperforming other indicators. Subgroup analysis revealed that FT was negatively correlated with male AMR,but this association was modulated by age,race,smoking status and diabetes status(P_(interaction)＜0.05). Kaplan-Meier survival analysis showed that different levels of TT and FT(Q1-Q4)were significantly positively correlated with survival rate(P＜0.001),while different levels of SHBG were significantly negatively correlated with survival rate,with patients in the Q4 group having the highest risk of death(P＜0.001). Conclusion Based on US NHANES,studies have shown that the FT and SHBG are independent risk factors for male AMR,and FT demonstrates greater predictive value for male AMR than TT.

Objective:To investigate the interventional and protective effect of low-dose L-carnitine(LC)against reproductive system damage in male Wistar rats during acute exposure to simulated high-altitude environment.Methods:A total of 24 specific pathogen-free male Wistar rats,aged 12 weeks,were randomly divided into control group,high-altitude model group,and LC intervention group[intraperitoneal injection of LC at a dose of 50 mg/(kg·d)],with 8 rats in each group.The rats in the control group were fed under normal conditions(at an altitude of approximately 1 500 m),those in the high-altitude model group,and those in the LC intervention group were fed in a hypobaric oxygen chamber(at a simulated alti-tude of 6 000 m).The rats were sacrificed after 3 days.The testis was collected to calculate testicular index;the semen was collected from the epididymis,and the Weili sperm quality analysis system was used to assess sperm quality;blood samples were collected from the abdominal aorta,and ELISA kits were used to measure the serum levels of testosterone(T),luteinizing hormone(LH),and follicle-stimulating hormone(FSH);testicular tissue samples were collected,and biochemical kits were used to measure the activity of reactive oxygen species(ROS),malondialdehyde(MDA),and superoxide dismutase(SOD);testicular tissue was collected to prepare HE and electron microscopy sections,and a light microscope and a transmission electron microscope were used for observation.Results:Com-pared with the blank control group,the high-altitude model group had significant increases in the levels of T,LH,and FSH(P<0.01),testicular tissue damage under the light microscope,and changes in the morphology of spermatogenic cells,including mitochondrial al-terations,membrane edema,loss of cristae,swelling of the matrix,and local dissolution,as well as significant increases in the levels of ROS and MDA(P<0.01)and a significant reduction in SOD activity(P<0.01).Compared with the high-altitude model group,the LC intervention group had a significant increase in the level of T(P<0.01),significant reductions in the levels of FSH and LH(P<0.01),and significant improvements in the pathological changes of testicular tissue,with no marked mitochondrial injury,and there were sig-nificant reductions in the levels of ROS and MDA(P<0.01)and a significant increase in SOD activity(P<0.01).There was no signifi-cant difference in testicular index between groups(P>0.05).The high-altitude model group had a significantly lower sperm count than the blank control group(P<0.05),while there was no significant difference in sperm count between the LC intervention group and the blank control group(P>0.05);there was no significant difference in sperm motility between groups(P>0.05).Conclusion:Low-dose LC can improve reproductive system damage in rats during acute exposure to simulated high-altitude environment,possibly by alleviat-ing oxidative stress response.

Objective:To investigate the prognostic effect of femoral resection on patients with soft tissue sarcoma of the thigh with cortical bone involvement.Methods:This retrospective study included patients with soft tissue sarcoma of the thigh diagnosed and treated in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to December 2021. Patients were divided into two groups based on whether femoral resection and reconstruction were performed with 20 in the resection group and 86 in the non-resection group. Propensity score matching (PSM) was used to control confounding variables. Overall Survival, recurrence free survival, metastasis free survival, and postoperative functional outcomes were compared between groups before and after PSM. Cox proportional hazards regression was used to identify risk factors for death, recurrence, and metastasis.Results:Before PSM, the 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 46.7% and 36.7% in the resection group, compared to 69.7% and 60.3% in the non-resection group without significant differences ( P>0.05). However, the 5-year metastasis-free survival (MFS) rate was significantly lower in the resection group (40.0%) compared to the non-resection group (73.1%) ( P=0.021). After PSM, the 5-year OS, RFS, and MFS in the resection group were 46.7%, 36.7%, and 35.9%, respectively, compared to 45.0%, 39.4%, and 67.7% in the non-resection group, with no significant differences ( P>0.05). The median postoperative MSTS functional score after PSM was significantly lower in the resection group 23(18, 25) points than in the non-resection group 26.5(24.3, 27.8) points ( U=43.000, P=0.007). Multivariate Cox regression analysis identified grade III histology ( HR=3.794, P=0.002) and tumor involvement angle around the femur greater than 180° ( HR=2.729, P=0.030) as independent risk factors for death. Age over 55 years ( HR=4.185, P=0.015), tumor diameter greater than 8 cm ( HR=4.290, P=0.014), and involvement of the intermuscular compartment ( HR=3.794, P=0.017) were associated with increased risk of local recurrence. Grade III histology ( HR=3.848, P=0.006) and involvement of the intermuscular compartment ( HR=2.500, P=0.045) were associated with distant metastasis. Conclusion:For patients with thigh soft tissue sarcoma involving femoral cortex involvement but no medullary cavity invasion, bone resection did not improve survival, recurrence or metastasis compared with patients in non-resection group. A relatively more conservative surgical approach may be advisable to preserve limb function without compromising oncological prognosis.

Sepsis refers to a life-threatening organ dysfunction caused by a dysregulated host response to infection,with persistently high morbidity and mortality,posing a significant healthcare burden.As integral components of innate and adaptive immunity,macrophages exhibit high plasticity and can differentiate into distinct phenotypes(M1 pro-inflammatory and M2 anti-inflammatory)in response to various environmental stimuli,playing crucial roles in both the hyperinflammatory phase and late immunosuppressive phase of sepsis.The metabolic profile of M2 macrophages has gradually become a research focus,and it is regulated by a variety of enzymes and signaling pathways,including adenosine 5'-monophosphate-activated protein kinase,peroxisome proliferator-activated receptor and protein kinase RNA-like ER kinase pathways.These pivotal signaling pathways and enzymes can promote the polarization of M2 macrophages and enhance their anti-inflammatory functions by modulating the metabolism of glucose,lipid,and amino acid,thereby conferring protective effects against sepsis and providing new ideas for the targeted treatment.

BACKGROUND: Post-stroke disability diminishes the physical activity (PA) level of survivors, potentially affecting their long-term prognosis. This study endeavors to explore the correlation between daily PA level and the all-cause mortality in patients with a history of stoke in the United States. METHODS: Data of stroke survivors were sourced from the National Health and Nutritional Examination Survey (NHANES) 2007-2018. The population was stratified into three groups based on their PA level. Kaplan-Meier method with log-rank tests for significance was used for survival analysis. Weighted Cox proportional hazards regression models were employed to estimate the hazard ratios (HRs) for all-cause mortality. Subgroup analysis was conducted to strengthen the results. RESULTS: A total of 1395 participants were recruited, comprising 679 males and 716 females, with a median age of 68 years. Based on their PA levels, 779 individuals were classified as inactive, 156 as insufficiently active, and 460 as sufficiently active. Following a median observation period of 59 months, there were 476 recorded deaths, with 349, 47, and 80 cases in the three respective groups. Compared to the inactive group, the HRs and 95% confidence intervals (CIs) for all-cause mortality in participants who were insufficiently active and sufficiently active were 0.58 (0.40, 0.84) and 0.47 (0.33, 0.67), respectively. The Kaplan-Meier curve revealed a significant difference in overall survival between the three groups, as confirmed by the log-rank test (P < 0.0001). Subgroup analysis further validated our results and demonstrated that the protective impact of PA on stroke prognosis varies according to distinct characteristics. CONCLUSIONS The results indicate that increased levels of PA are associated with a protective effect on long-term mortality among stroke survivors. Further prospective longitudinal studies are necessary to elucidate the optional PA level and special exercise guideline targeting this population.
Humans ; Male ; Female ; Aged ; Exercise ; Middle Aged ; Nutrition Surveys ; Stroke/mortality* ; United States/epidemiology* ; Survivors/statistics & numerical data* ; Aged, 80 and over ; Mortality

OBJECTIVES: Tiletamine, a veterinary anesthetic, has emerged as a novel psychoactive substance and has been abused in many parts of the world, causing great harm to public health. However, the sensitivity of existing detection methods cannot meet the needs of forensic practice. This study aims to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of tiletamine and its metabolite desethyltiletamine in human biological samples, and to verify its applicability in forensic practice. METHODS: SKF_525A was used as the internal standard. Biological samples were extracted with acetonitrile containing 1 ng/mL SKF_525A, vortexed for 10 min, ultrasonicated for 20 min, centrifuged at 10 000 r/min for 10 min, and 500 μL of the supernatant was filtered through a 0.22 μm membrane. Analyses were performed using an ACQUITY UPLC H-Class PLUS system and an XEVO TQ-S Micro triple quadrupole mass spectrometer. An ACQUITY UPLC^® BEH C18 (1.7 µm, 2.1 mm×100 mm) column at a flow rate of 0.3 mL/min was used, and four mobile phase systems were tested to optimize separation. Detection used positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, with quantifier ion transitions of mass to charge 224.043→179.016 for tiletamine and mass to charge 196.08→151.06 for desethyltiletamine. Calibration curves were established over 0.1-200 ng/mL in spiked blood samples. The linear range, limit of detection (LOD), and limit of quantification (LOQ) were determined. Low (5 ng/mL), medium (20 ng/mL), and high (100 ng/mL) concentrations of tiletamine were spiked into blood, liver, and kidney to evaluate precision, accuracy, matrix effect, recovery, and stability. Finally, actual forensic case samples were tested to validate applicability. RESULTS: The established UPLC-MS/MS method achieved simultaneous detection of tiletamine and desethyltiletamine in human biological samples, with retention times of 3.42 min and 2.82 min, respectively. Using mobile phase A (20 mmol/L ammonium acetate and 0.1% formic acid in water) and mobile phase B (acetonitrile) produced the best separation. In blood, tiletamine showed good linearity from 0.1-200 ng/mL (r=0.992, R²=0.983), LOD 0.03 ng/mL, LOQ 0.1 ng/mL, recovery 92%-107%, and matrix effect 71%-99%. In liver and kidney, recoveries were 91%-98% and 93%-104%, and matrix effects were 69%-96% and 72%-100%, respectively. Intra- and inter-day precision [expressed as relative standard deviation (RSD)] and accuracy [expressed as relative error (RE)] were within 15%, and samples were stable at -20 ℃. Tiletamine was detected in actual case samples at 0.37 μg/mL (blood), 0.15 μg/g (liver), 0.11 μg/g (kidney) in case 1, and 8.75 ng/mL (blood) in case 2; desethyltiletamine was also detected in blood. CONCLUSIONS The UPLC-MS/MS method is efficient, accurate, and sensitive, and is suitable for detecting tiletamine and desethyltiletamine in human biological samples.
Tandem Mass Spectrometry/methods* ; Humans ; Chromatography, High Pressure Liquid/methods* ; Substance Abuse Detection/methods* ; Liquid Chromatography-Mass Spectrometry

Previous studies have found associations between color discrimination deficits and cognitive impairments besides aging. However, investigations into the microstructural pathology of brain white matter (WM) associated with these deficits remain limited. This study aimed to examine the microstructural characteristics of WM in the non-demented population with abnormal color discrimination, utilizing Neurite Orientation Dispersion and Density Imaging (NODDI), and to explore their correlations with cognitive functions and cognition-related plasma biomarkers. The tract-based spatial statistic analysis revealed significant differences in specific brain regions between the abnormal color discrimination group and the healthy controls, characterized by increased isotropic volume fraction and decreased neurite density index and orientation dispersion index. Further analysis of region-of-interest parameters revealed that the isotropic volume fraction in the bilateral anterior thalamic radiation, superior longitudinal fasciculus, cingulum, and forceps minor was significantly correlated with poorer performance on neuropsychological assessments and to varying degrees various cognition-related plasma biomarkers. These findings provide neuroimaging evidence that WM microstructural abnormalities in non-demented individuals with abnormal color discrimination are associated with cognitive dysfunction, potentially serving as early markers for cognitive decline.
Humans ; White Matter/pathology* ; Male ; Female ; Cognitive Dysfunction/physiopathology* ; Middle Aged ; Aged ; Color Perception/physiology* ; Brain/pathology* ; Neuropsychological Tests ; Diffusion Tensor Imaging

Objective To investigate the influencing factors of disease progression and prognosis in patients with large artery atherosclerotic(LAA)cerebral infarction and analyze the value of plasma cyclin-dependent kinase 9(CDK9)level in the diagnosis and treatment of LAA cerebral infarction.Methods Patients with acute cerebral infarction admitted to the Department of Neurology of the Affili-ated Hospital of Yangzhou University between March 1,2022,and November 20,2023,were select-ed.According to the diagnostic criteria,98 patients with acute LAA(LAA group)and 33 patients with acute small artery occlusion(SAO)cerebral infarction(SAO group)were selected.Additionally,40 healthy individuals matched for age and gender from the Health Examination Center were included as control group.Based on whether the condition of LAA cerebral infarction patients progressing,they were divided into progressive cerebral infarction(PCI)group(39 patients)and the non-pro-gressive cerebral infarction(NPCI)group(59 patients).During the 3-month follow-up period,6 patients from the 98 LAA cerebral infarction patients were lost.According to the modified Rankin Scale(mRS)score at 90 days of follow-up,patients were divided into good prognosis group(mRS score≤2,59 patients)and poor prognosis group(mRS score＞2,33 patients).Fasting lipid in-dices[total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),glucose(GLU),glycated hemoglobin(HbA1c),and homocysteine(Hey)]were collected on the second day after admission.The National Institutes of Health Stroke Scale(NIHSS)was used to assess the degree of neurological impairment in cerebral infarction patients.Enzyme-linked immunosorbent assay(ELISA)was used to measure plasma CDK9 levels in different groups;factors influencing disease progression in patients with acute LAA cerebral infarction were explored;and receiver operating characteristic curves were plotted to evalu-ate the predictive value of CDK9 in patients with acute LAA cerebral infarction.Results Compared with the control group,the LAA group had lower HDL-C level and higher CDK9 level(P＜0.05).The LAA group had a higher proportion of diabetes history,larger infarction volume,higher NIHSS score at admission,and higher CDK9 level compared with the SAO group(P＜0.05).Binary Logistic regression analysis showed that diabetes history and plasma CDK9 levels were influencing factors for LAA cerebral infarction.There were statistically significant differences in the proportion of diabetes history,HbA1c,random GLU,and CDK9 levels between the NPCI and PCI groups(P＜0.05).Diabetes history and plasma CDK9 levels were influencing factors for disease progression in patients with acute LAA cerebral infarction.The area under the ROC curve for CDK9 in predicting acute LAA cerebral infarction was 0.854 5(95％CI,0.794 1 to 0.9148).When the CDK9 level was 602.1 ng/L,the Youden index was maximum(0.604),with a corresponding sensitivity of 0.849 and specificity of 0.755.The NIHSS score,infarction volume,and plasma CDK9 level were higher in the poor prognosis group compared with the good prognosis group(P＜0.01).Correlation analysis showed a positive correlation between mRS scores and CDK9 levels(r=0.485,P＜0.01).Conclusion Plasma CDK9 levels are significantly elevated,and is an influencing factor.It is positively correlated with disease progression and poor prognosis in acute cerebral infarction and has certain predictive value for the progression of LAA cerebral infarction.

Objective To analyze the application trends and research hotspots of brain-computer interface(BCI)technology in stroke rehabilitation over the past five years.Methods Relevant literatures on the use of BCI in stroke rehabilitation published between January,2021 and August,2025 were retrieved from the Web of Science Core Collection database.CiteSpace 6.4.R1 was used for visualiza-tion analysis.Results A total of 458 papers were included.The annual number of publications remained at a high level.China was the leading country in publication output,with Fudan University and Aalborg University as the top institutions.The most prolific author was Mads R.Jochumsen,while G.Pfurtscheller had the highest citation frequency.The key-words and burst terms with the highest frequency in this field were brain-computer interface,motor imagery,up-per limb and deep learning.Conclusion Over the past five years,research on BCI in stroke rehabilitation has maintained a high publication volume.The research hotspots focus on innovations in BCI algorithm technology and multidimensional validation of neu-ral mechanisms and rehabilitation efficacy.

A local context fusion based segmentation model which uses a local context attention mechanism to filter out irrelevant feature information and enhance the attention to important regions is presented for accurate polyp segmentation. The features at different scales are captured by multi-kernel dilated convolution for improving the accuracy of polyp boundary segmentation. Pyramid context selection module utilizes shallow encoder features to compensate for the low-level information lost by the deeper encoder,enabling the model to adapt to polyps of various sizes. The proposed model achieves accuracies of 97.67％,97.19％ and 99.23％ on Kvasir-SEG,EndoScene and CVC-ClinicDB datasets,respectively,with mIoU of 91.20％,88.31％ and 94.75％,respectively,exhibiting higher accuracy and generalizability than the existing classical methods and validating its superior performance in polyp segmentation. The proposed model can improve polyp segmentation accuracy and provide a more accurate aid for polyp segmentation.