Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background Platelet parameters are important indicators of cardiovascular risk, and environmental pollutants such as polychlorinated biphenyls (PCBs) may impair platelet function through oxidative stress. Objective To investigate the differential effects of single and mixed exposure to PCBs on platelet parameters among individuals with normal glucose tolerance (NGT), impaired fasting glucose (IFG), and type 2 diabetes mellitus (T2DM), and to evaluate the potential modifying role of a healthy lifestyle. Methods This study included 2249 participants (including 707 with NGT, 759 with IFG, and 783 with T2DM). Plasma PCB concentrations were measured using triple quadrupole gaschromatography-tandem mass spectrometry. Generalized linear regression was used to assess the associations between individual PCB congeners and platelet parameters. Quantile g-computation (QGC) and Bayesian kernel machine regression (BKMR) models were used to evaluate the overall effects of PCBs mixture exposure on platelet parameters across different glycemic states, as well as its interaction with healthy lifestyle score (HLS). Results Generalized linear regression analyses showed significant differences in the effects of PCBs on platelet parameters across different glycemic states (P<0.05). After adjusting for confounders, PCBs mixture exposure was significantly associated with lower platelet counts (PLT) in individuals with NGT (b=−10.60, 95%CI: −16.48, −4.71) and IFG (b=−12.91, 95%CI: −18.90, −6.92), whereas no significant association was observed in individuals with T2DM (P=0.051). Mean platelet volume (MPV) and platelet-large cell ratio (P-LCR) increased significantly with higher PCBs exposure levels across all three groups (P<0.05). BKMR analysis showed a positive association between PCBs mixture exposure and P-LCR, with the strongest association observed in the NGT group. Furthermore, a significant interaction was observed between HLS and PCBs mixture exposure, and a higher HLS attenuated the effects of PCBs on P-LCR. Conclusion Glycemic glycemic states may modify the effects of PCBs on platelets. Individuals with NGT appear more sensitive to PCBs exposure, whereas the T2DM state may attenuate this effect. Moreover, healthy lifestyles, including not smoking, moderate alcohol consumption, maintaining moderate-to-high physical activity, a healthy diet, and an appropriate body mass index (BMI), may mitigate the adverse effects of most PCBs on platelet parameters.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective:To compare the differences in clinical characteristics among the patients at clinical high risk for bipolar disorder(CHR-BD),the patients with bipolar disorder(BD),and the healthy controls(HC)at low risk,and to provide the basis for the diognasis and treatment of CHR-BD.Methods:For the first time,the BD risk criteria and prospective structured assessment tools were jointly used in outpatients aged 16-30 years,and 43 CHR-BD patients were included to ensure the accuracy of the assessment.Meanwhile,33 BD patients and 32 HC subjects were also enrolled.The clinical symptoms,neurocognitive function,and global functional levels of the subjects in the three groups were evaluated using observer-rated and self-rated tools.The CHR-BD and BD groups were combined,and Logistic regression analysis was used to identify the independent influencing factors related to diagnostic status;Pearson or Spearman correlation analysis was used to analyze the correlations between the global functional levels and the symptoms or neurocognitive characteristics of the patients in CHR-BD and BD groups.Results:There were statistically significant differences in the scores of symptom and global functional level scales among HC,CHR-BD,and BD groups(P<0.05).Compared with HC group,the scores of mood symptoms(anxiety,depression,and mania/hypomania),psychotic symptoms,total affective temperament questionnaire scores,and some dimensions(cyclothymic,depressive,irritable,and anxious temperaments)in CHR-BD and BD groups were significantly increased(P<0.001),while the global functional levels were significantly decreased(P<0.001).Compared with BD group,the lowest global functional level score in the past year in CHR-BD group was significantly increased(P=0.022),while the current global functional level score was significantly decreased(P=0.005).No significant differences were observed in neurocognitive function scores among the three groups(P>0.05).The lowest global functional level score in the past year was an independent influencing factor for BD diagnosis[odds ratio(OR)=0.952,95%confidence interval(CI):0.917-0.988,P=0.010].In both CHR-BD and BD patients,the current global functional levels were negatively correlated with depressive(r=-0.417,P=0.005;r=-0.617,P<0.001)and anxiety symptoms(r=-0.360,P=0.018;r=-0.506,P=0.003).In BD patients,the current global functional level was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.360,P=0.039),psychotic symptoms(r=-0.502,P=0.003),and affective temperament scores(r=-0.479,P=0.005),while the lowest global functional level in the past year was negatively correlated with lifetime manic/hypomanic symptoms(r=-0.391,P=0.024).Conclusion:CHR-BD patients share similar mood symptom characteristics with BD patients,and their global functional levels are negatively correlated with depressive and anxiety symptoms.BD patients exhibit worse lowest global functional levels in the past year,and their global functional levels are negatively correlated with manic/hypomanic symptoms.

Objective:To investigate the influencing factors for dysphagia in the elderly,to construct a predictive model for dysphagia,and to provide a theoretical basis for clinical practice.Methods:In this case-control study,the patients with dysphagia who attended Department of Geriatrics in the first affiliated hospital of Chongqing Medical University from March 2016 to June 2023 were enrolled as case group,and the patients without dysphagia who attended the same department during the same period of time were enrolled as con-trol group.The correlation analysis,least absolute shrinkage and selection operator(LASSO)regression,and multivariate logistic re-gression analysis were used to investigate the influencing factors for dysphagia;the 10-fold cross-validation Extreme Gradient Boosting(XGBoost)model was used to predict dysphagia,and the SHapley additive exPlanations(SHAP)method was used for model visualiza-tion.Results:There were 1009 cases in the case group and 2125 cases in the control group.The correlation analysis and LASSO re-gression analysis identified 12 factors for the multivariate logistic re-gression analysis,and the results showed that sarcopenia,increasing age,children or caretakers as caregivers,frail health,poor oral health,poor self-care ability,depression,and cognitive impairment were risk factors for dysphagia(odds ratio[OR]>1,P<0.05),and fe-male sex and participation in community activities were protective factors against dysphagia(OR<1,P<0.05).The XGBoost model had a good predictive efficacy,with an accuracy rate of 0.795,a preci-sion rate of 0.711,a sensitivity of 0.613,a specificity of 0.881,an F1 value of 0.661,and an area under the ROC curve of 0.855.The SHAP plot showed that the top five important characteristics were caregiver,oral score,frail health condition,activities of daily living,and cognitive function.Conclusion:There are various influencing factors for dysphagia in the elderly,and the elderly patients with poor oral health,frailty,dependence on others for daily life,and cognitive impairment should be taken seriously in clinical practice.The XGBoost model has a good performance in predicting dysphagia in the elderly,which can provide a reference for clinical practice.

Objective:To investigate the influencing factors for sarcopenia in hospitalized patients,to construct a risk prediction model for sarcopenia in elderly hospitalized patients,and to provide a quantitative tool for early screening and intervention of sarcopenia based on the integration of multi-dimensional indicators.Methods:A retrospective analysis was performed for the data of 2105 elderly patients who were hospitalized in The First Affiliated Hospital of Chongqing Medical University from March 2016 to June 2023.The least absolute shrinkage and selection operator analysis was used for the screening of variables,and the logistic regression analysis was used to investigate the influencing factors for sarcopenia.A predictive model was constructed,and internal and external validation was performed.The Shapley additive explanations model was used to analyze feature contributions,and a nomogram model was constructed to visualize and interpret the results.Results:The 1259 patients from March 2016 to December 2020 were randomly divided into a training set with 882 patients and an internal test set with 377 patients at a ratio of 7∶3,and the 846 patients from January 2021 to June 2023 were established as the external validation set.A total of 489 cases of sarcopenia(55.44%)were detected in the training set.The logistic regression analysis based on the training set showed that asthenia,dependence on Activity of Daily Living,malnutrition,and in-creasing age were risk factors for sarcopenia(odds ratio[OR]>1,P<0.05),and male sex,normal body mass index,and overweight were protective factors against sarcopenia(OR<1,P<0.05).The model had an AUC of 0.876(95%CI=0.854-0.899)in the training set,0.883(95%CI=0.849-0.918)in the internal test set,and 0.750(95%CI=0.717-0.783)in the external validation set,suggesting that the model had good performance.The decision curve analysis showed that the nomogram model had a good clinical value.Conclu-sion:The predictive model for sarcopenia has good performance and holds promise for clinical application.

Objective:To explore the aperiodic components(1/f slopes)and their associations with cognitive impairment in patients with schizophrenia.Methods:Nineteen patients with schizophrenia according to the Interna-tional Statistical Classification of Diseases and Related Health Problem,Tenth Revision(ICD-10)and 21 normal controls were administrated the total Brief Assessment of Cognition in Schizophrenia(BACS)to measure the cogni-tive performance.The 5-minute eyes-closed and eyes-open resting EEG signals were collected and parameterized in-to aperiodic components(1/f slope).Finally,Pearson correlation was used to examine the relationships between the 1/f slope and cognition assessment scores.Results:The patients with schizophrenia had higher 1/f slope compared to HC on central location of scalp(P＜0.05).The vocal memory scores showed a significantly positive relation with 1/f slopes in patients with schizophrenia(anterior location:r=-0.68,P＜0.05;central location:r=-0.44,P＜0.05),but a significantly negative relation in normal controls(anterior location:r=0.57,P＜0.05;posterior lo-cation:r=0.54,P＜0.05).Conclusion:The 1/f slopes of EEG in schizophrenia were steeper than normal control,suggesting its strong cognitive functional significance and complex mechanisms in schizophrenia.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Metastasis serves as an indicator of malignancy and is a biological characteristic of carcinomas. Epithelial-mesenchymal transition (EMT) plays a key role in the promotion of tumor invasion and metastasis and in the enhancement of tumor cell aggressiveness. Prostaglandin E synthase 3 (p23) is a cochaperone for heat shock protein 90 (HSP90). Our previous study showed that p23 is an HSP90-independent transcription factor in cancer-associated inflammation. The effect and mechanism of action of p23 on lung cancer metastasis are tested in this study. By utilizing cell models in vitro and mouse tail vein metastasis models in vivo, the results provide solid evidence that p23 is critical for promoting lung cancer metastases by regulating downstream CXCL1 expression. Rather than acting independently, p23 forms a complex with RNA-binding motif protein 14 (RBM14) to facilitate EMT progression in lung cancer. Therefore, our study provides evidence for the potential role of the RBM14-p23-CXCL1-EMT axis in the metastasis of lung cancer.

Long-term exposure to particulate matter has been increasingly implicated in the progression of chronic kidney disease (CKD). However, its impact on IgA nephropathy (IgAN), a leading cause of end-stage renal disease (ESRD), remains unclear. A total of 1768 IgAN patients, confirmed by renal biopsy were included in this cohort study. Long-term exposure to PM_2.5 and PM₁₀ was assessed using high-resolution satellite-based data from the China High Air Pollutants (CHAP) dataset. Cox proportional hazards models were used to estimate the associations between PM_2.5 or PM₁₀ and ESRD risk, adjusting for demographic, clinical, and biochemical covariates. Over a median follow-up of 3.63 years, 209 participants progressed to ESRD. Higher exposure to both PM_2.5 and PM₁₀ was significantly associated with an increased risk, with hazard ratios of 1.62 and 1.36 per 10 µg/m³ increase, respectively. A nonlinear dose-response relationship was observed, with risk increasing markedly beyond threshold levels. Trajectory modeling of prebaseline exposure identified a subgroup with persistently high and fluctuating particulate matter exposure that showed the highest risk. This study provides strong evidence that prolonged exposure to ambient particulate matter contributes to renal disease progression in individuals with IgAN.
Humans ; Glomerulonephritis, IGA/pathology* ; Particulate Matter/adverse effects* ; Male ; Female ; Kidney Failure, Chronic/epidemiology* ; Adult ; China/epidemiology* ; Disease Progression ; Environmental Exposure/adverse effects* ; Middle Aged ; Proportional Hazards Models ; Risk Factors ; Air Pollutants/adverse effects* ; Cohort Studies