Jinan City People's Hospital

To investigate the association between monounsaturated fatty acids (MUFAs) intake and the prevalence of Parkinson’s disease (PD) among US adults using data from the National Health and Nutrition Examination Survey (NHANES) database. Cross-sectional data from the NHANES 2001–2018 were selected. PD cases were identified through self-reported PD medications. MUFAs intake was determined from dietary interview data for two 24-hour periods. To address severe outcome imbalance and improve covariate comparability, we conducted survey-weighted propensity score matching (PSM) incorporating NHANES sampling weights. In the matched sample, survey-weighted logistic regression was used to evaluate the association between MUFAs intake (quartiles) and PD prevalence, and a trend test was performed. Restricted cubic spline (RCS) models were applied to examine potential non-linear associations. A total of 12,122 participants were included, consisting of 84 PD patients and 12,038 participants without PD. MUFAs intake was significantly lower in the PD group than in matched controls after PSM (P = 0.010). Exploratory subgroup analyses suggested heterogeneity across some subpopulations. RCS analyses did not indicate a significant non-linear relationship between MUFAs intake and the prevalence of PD. Higher MUFAs intake was inversely associated with PD prevalence in this cross-sectional analysis. Given the study design, causality cannot be inferred; prospective studies are warranted to confirm these findings and clarify underlying mechanisms.

Vessels encapsulating tumor clusters (VETC) serve as a crucial adverse prognostic indicator in hepatocellular carcinoma (HCC). This study aimed to develop and validate a Delta radiomics-based nomogram model on dynamic contrast-enhanced CT (DCE-CT) to predict VETC status and patient prognosis in HCC. A cohort of 222 patients from two centers with HCC undergoing DCE-CT scans and CD34 immunochemical staining was enrolled. Each liver lesion was segmented on intratumoral and peritumoral regions in the arterial phase (AP) and portal vein phase (PP) CT images. A total of 10,128 (1,688*6) radiomics features, including absolute and relative delta radiomics features, were extracted. Using four machine-learning algorithms, the features were trained and optimized (training set), and validated (internal and external test sets) to classify VETC patterns. Multivariable logistic regression incorporating signature scores and clinical predictors generated the nomogram. Model performance was evaluated through area under the curves (AUC) analysis, calibration curves, and decision curve analysis (DCA). The Kaplan-Meier survival analysis was used to assess recurrence-free survival (RFS) in the VETC+ and VETC- patients. The logistic regression-based nomogram incorporating three radiomic signatures and two clinical factors showed powerful predictive ability in internal and external test sets with AUCs of 0.854 and 0.803, respectively. The calibration curves, DCA showed favorable predictive performance of the nomogram. Patients classified as high-risk by the nomogram exhibited significantly shorter RFS compared to low-risk counterparts (P < 0.001). The developed nomogram demonstrated clinical translatability in preoperative VETC prediction and recurrence risk stratification, providing a potential imaging biomarker for guiding personalized therapeutic strategies in HCC management.

Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD) undergoing maintenance dialysis. To further clarify this critical relationship, we conducted a prospective study to evaluate the prognostic significance of calcification in different segments of the thoracic aortafor all-cause mortality in this patient population. This prospective study enrolled stable adult patients who were undergoing maintenance hemodialysis (MHD) at our center between July 2019 and December 2020 and who had available chest X-rays or computed tomography (CT) scans. Thoracic aortic calcification (TAC) was assessed via chest CT or X-ray imaging. Cox proportional hazards models and Kaplan‒Meier curves were used to describe the risk factors for mortality. At a mean follow-up of 3.95years, 18 of 62 patients had died. Cox proportional hazards regression models demonstrated that elevated systolic blood pressure (HR 1.029), aortic arch calcification (AAC) (HR 1.104), and descending thoracic aortic calcification (DTAC) (HR 1.066) were independent risk factors for all-cause mortality in patients with MHD (allP < 0.05). Additionally, the presence of severe DTAC or severe AAC emerged as an independent risk factor for death in this patient population (log-ranktest, P < 0.05). AAC and DTAC are important predictors of all-causemortality among patients undergoing maintenance hemodialysis.

Esophageal Cancer (EC) is a commonly occurring cancer of the digestive tract. The bismuth compounds from thiosemicarbazones have been observed to be active against cancer cells. However, a synthetic nine-coordinate bismuth (III) complex (complex 1) has never been assessed so far for its anticancer in the esophageal squamous cell carcinoma cell line (EC109). This study aimed to investigate the apoptosis effect of a complex1 in the EC109 cells. EC109 cells were treated with complex1. The MTT assay was employed to assess the viability of EC109 cells; the changes in apoptotic and morphological characteristics, reactive oxygen species (ROS) generation, and mitochondrial membrane potential (MMP) were examined. The expression levels of proteins associated with apoptosis were assessed using western blotting. Complex1 was found to inhibit the growth of EC109 cells, exhibiting an IC50 of 0.654 μM through apoptosis depends upon complexation with bismuth(III). In addition, cells exposed to complex1 exhibited a significant increase in the level of intracellular ROS through the suppression of the antioxidant system and caused a reduction in mitochondrial membrane potential(MMP). Co-treatment with N-acetyl-Lcysteine( NAC), an antioxidant agent prevented accumulation of ROS and cell death. Complex1 also led to enhanced Bax expression, and reduced Bcl-2 expression in EC109 cells, thereby enhancing caspase-3/9 activity. Our study confirmed that complex1 induced apoptosis via enhancing the generation of ROS along with a decline in levels of antioxidant enzymes, subsequently causing MMP loss.

Lung adenocarcinoma (LUAD), the most prevalent and aggressive form of non-small cell lung cancer. Natural compounds have gained increasing attention as potential anti-cancer agents. The therapeutic potential of chebulagic acid (CA)-a hydrolysable tannin with documented anti-proliferative properties-has not been investigated in LUAD. In the present study, functional experiments revealed that CA treatment markedly suppressed proliferation and induced mitochondrial-dependent apoptosis of LUAD cells. In addition, CA augments natural killer (NK) cell migration by enhancing LUAD CCL5 production. Quantitative proteomics identified FBXO38 as the most significantly upregulated protein following CA treatment. FBXO38 silencing abrogated CA-induced CCL5 production and NK cell migration in LUAD cells. The in vivo experiments showed that CA significantly inhibited tumor growth and enhanced NK cell infiltration in mice, accompanied by decreased Ki67+ proliferating cells, increased cleaved caspase-3+ apoptotic cells, and upregulated FBXO38 expression. Collectively, our findings demonstrate that CA may be exert anti-LUAD effects through FBXO38/CCL5-mediated NK cell recruitment.

In recent years, probiotics have become one of the research hotspots in the scientific community, and its potential role in intestinal health, immune regulation, and the relationship with the brain has attracted much attention. However, the improvement of cognitive function by probiotics shows different effects in different stages of the human life cycle. Therefore, we conducted a meta-analysis of randomized controlled trials to examine the specific effects of probiotics on cognitive function in different age groups. We searched four databases from creation to December 2023. A meta-analysis of 21 randomized controlled clinical trials was conducted, using random effect Meta analysis combined with standardized mean difference (SMD) (95% confidence interval [CI]). Our meta-analysis found that the effects of probiotics on cognitive performance were primarily seen in older age groups, with significant effects on overall cognitive performance, processing speed, memory, and spatial ability (SMD = 0.40, 95% CI [0.13, 0.67], P = 0.004), (SMD = 0.37, 95% CI [0.11, 0.63], P = 0.006), (SMD = 0. 51, 95% CI [0.25, 0.78], P = 0.0002), (SMD = 0.35, 95% CI [0.09, 0.62], P = 0.008). In addition, probiotics improved executive function in infants and children (SMD = 0.30, 95% CI [0.04, 0.56], P = 0.03). In young adults, the effects of probiotics were mainly seen in verbal ability (SMD = 0.43, 95% CI [0.15, 0.71], p = 0.003). Probiotic supplements primarily improve overall cognitive function, information processing speed, memory, and spatial ability in older adults, with the best results observed after 12 weeks of daily intake of approximately 2 × 10¹⁰ CFU.

Prolonged door-to-needle time (DNT) in stroke treatment has been associated with adverse clinical outcomes. However, its impact on post-stroke cognitive impairment (PSCI) remains underexplored. This study investigates the association between DNT and PSCI and evaluates the predictive value of DNT for cognitive dysfunction after acute ischemic stroke (AIS). This retrospective single-center study included 176 patients with AIS who received intravenous thrombolysis (IVT) between January 2021 and December 2024. The relationship between DNT and PSCI was assessed using multivariate logistic regression analysis, adjusting for stroke severity, infarct volume, stroke laterality, stroke circulation type, and vascular risk factors. Additionally, receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of DNT for PSCI. Patients who developed PSCI had a significantly longer DNT compared to those without PSCI (63.7 ± 8.9 minutes vs 51.2 ± 12.3 minutes, P < .001). Logistic regression analysis confirmed that DNT was an independent predictor of PSCI (odds ratio = 1.125, 95% confidence interval: 1.071–1.182, P < .001). ROC curve analysis demonstrated that a DNT threshold of 52.5 minutes yielded a sensitivity of 89.0% and a specificity of 59.3% for predicting PSCI. Prolonged DNT is independently associated with an increased risk of PSCI within 6 months after stroke. Despite its high sensitivity, the predictive specificity of DNT remains limited, necessitating further studies incorporating additional risk factors to enhance predictive accuracy. These findings emphasize the importance of minimizing DNT delays in stroke management to improve long-term cognitive outcomes.

IntroductionGrowing evidence suggests that increased matrix stiffness can significantly enhance the malignant characteristics of glioma cells. However, the mechanisms by which increased matrix stiffness regulates the tumorigenesis of glioma cells remain largely unknown. A growing number of studies show that carcinogenesis in various human cancers is linked to cell membrane glycoproteins and their corresponding receptors. Among these, synaptic vesicle glycoprotein 2 isoforms B (SV2B) has emerged as a transmembrane glycoprotein with significant functional implications. However, whether SV2B is involved in matrix-stiffness-mediated glioma tumorigenesis and its related mechanisms remains to be elucidated.MethodsIn this study, we aimed to investigate whether SV2B mediates the effects of matrix stiffness on the focal adhesion kinase (FAK)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. To examine the expression of SV2B in patients with glioma, we analyzed data from bioinformatics databases. Furthermore, we assessed SV2B variation in glioma and its impact on overall survival. In vitro experiments included Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analyses to determine protein and messenger RNA (mRNA) expression in glioma cell lines. Cell viability and DNA replication capacity were evaluated using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), and colony formation assays. Migration ability was assessed through Transwell and wound healing assays. Flow cytometry was employed to analyze apoptotic rates in glioma cells. Additionally, an orthotopic tumorigenesis model was established to investigate the in vivo effects of SV2B.ResultsOur results demonstrated low expression of SV2B in glioma tissues. Overexpression of SV2B was found to inhibit proliferation and migration and induce apoptosis of glioblastoma cells, while knockdown of SV2B promoted these processes. Furthermore, we observed that SV2B overexpression suppressed the epithelial–mesenchymal transition (EMT) process and inhibited the activation of the FAK/PI3K/AKT signaling pathway in glioma cells, with similar effects observed in vivo. Finally, we demonstrated that increased matrix stiffness can promote glioma tumor growth through FAK/PI3K/AKT pathway, while overexpression of SV2B can inhibit this effect.ConclusionsOur study provides insights into the functional role of SV2B in matrix-stiffness-driven glioma progression, elucidating its molecular mechanisms and highlighting its potential as a therapeutic target.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40487-025-00410-x.

Objective:Motor decline is a hallmark of Parkinson’s disease (PD) and biological aging. While epigenetic clocks measure systemic biological aging, their specific relationship with neuromotor function in the context of aging and neurodegeneration remains under-characterized. This study utilized data from the Parkinson’s Progression Markers Initiative (PPMI) to examine the relationships between multiple DNA methylation-based epigenetic aging measures and motor impairment across distinct domains.Methods:We utilized longitudinal phenotype and whole-blood DNA methylation data from the PPMI cohort. Seven epigenetic aging measures were calculated, including first-generation clocks (Horvath v1, Hannum), risk-optimized second-generation clocks (PhenoAge, GrimAge v1 and v2), a deep-learning estimator (AltumAge), and a pace-of-aging biomarker (DunedinPACE). Motor function was assessed using the MDS-UPDRS, which captures patient-reported disability, global staging (Hoehn & Yahr), and specific motor signs, including tremor, bradykinesia, and postural instability. Cross-sectional associations were evaluated using binary or ordinal logistic regression, while longitudinal repeated measures were analyzed using generalized estimating equations (GEE) and cumulative link mixed models (CLMM), with adjustments for multiple comparisons made using the false discovery rate (FDR).Results:Cross-sectional analyses yielded limited evidence, identifying only a specific association between Horvath v1 acceleration and postural tremor in males (PFDR < 0.1). Repeated-measures analyses in the overall sample revealed robust associations between accelerated epigenetic aging and worsening tremor phenotypes (postural and kinetic), while associations with gait, rigidity, and bradykinesia were largely non-significant or inversely related. Sex-stratified analyses revealed distinct sexual dimorphism: males exhibited a broad, multi-clock phenotype (involving Horvath v1, PhenoAge, and GrimAge), where accelerated aging was associated with worsening tremor, gait, and rigidity. Females showed restricted associations, primarily linking the Hannum clock to tremor and global staging, and DunedinPACE to rigidity.Conclusions:Accelerated epigenetic aging is robustly associated with the longitudinal progression of tremor impairment in PD, with associations being particularly consistent and multi-dimensional in men. These findings suggest that systemic biological aging, as captured by both first- and second-generation clocks, disproportionately exacerbates tremor circuitry distinct from the dopaminergic pathways that drive bradykinesia. Epigenetic clocks may serve as valuable biomarkers for monitoring progression and risk stratification, particularly for tremor-dominant phenotypes.