OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

The incidence of metabolic rheumatism gout has been increasing with a trend of more younger patients and atypical symptoms. Typical gout is easy to be diagnosed, but it is difficult for atypical cases. Finding uric acid crystal in articular fluid by polarizing light microscope is a gold standard of diagnosis, but it is an invasive diagnostic method and difficult to be widely used. The patients need further imaging examination for assistance of diagnosis and guide of follow-up treatment. This article reviews the research progress of different imaging methods used for diagnosis of gouty arthritis.

A novel protein encoded by the open reading frame 4 (ORF4) was recently discovered in porcine circovirus type 2 (PCV2). However, little is known about the interaction proteins of ORF4 which hindered better understanding the biological functions of ORF4 in the life cycle of PCV2. In the present study, the ORF4 was inserted into the multiple cloning site of pCMV-N-Flag-GST, yielding recombinant plasmid pCMV-N-Flag-GST-ORF4. The recombinant plasmid was transfected into 293T cells and the intracellular interaction complex of ORF4 were enriched and separated by GST pull-down and SDS-PAGE, sequentially. The potential interacting proteins of PCV2 ORF4 were stained with silver and identified by mass spectrometry (MS). Finally, five candidate ORF4-interacting proteins, including Serine/threonine-protein phosphatase 6 catalytic subunit, alpha cardiac muscle 1, actin, SEC14-like protein 5 and myosin 9 were identified. These results would benefit a better understanding of the biological function of ORF4 in PCV2 infected cells.
Animals ; Circoviridae Infections ; Circovirus ; HEK293 Cells ; Humans ; Mass Spectrometry ; Open Reading Frames ; Swine ; Viral Proteins

To investigate the effect of a novel EZH2 inhibitor GSK126 on cell growth, apoptosis and migration of prostate cancer cells.Prostate cancer PC-3 and DU145 cells were treated with GSK126 at different doses. Cell growth was detected by sulforhodamine assay. Cell apoptosis was assayed by Annexin V-/PI kit. Transwell chamber and wound healing assays were conducted to detect cell migration. The mRNA level was detected by quantitative PCR, and protein expression was detected by Western blot analysis.GSK126 showed significant effect on cell growth and apoptosis when the dose was higher than 50 μmol/L. Wound healing assay revealed that scratch space in PC-3 cells was significantly increased in a dose-dependent manner in GSK126-treated groups[(247.2±24.4),(347.2±19.2) and (410.5±18.1) μm in low, medium and high dose (5.0, 20.0, 50.0 μmol/L), respectively] as compared with the control group[(171.3±17.8) μm](all<0.05). Transwell assay showed that migrated PC-3 cells in control group was 322.0±17.9,while those in GSK126-treated groups were 198.3±15.4 (low),82.7±6.2 (medium) and 30.2±4.1 (high), and the differences between the control group and GSK126-treated groups were significant(all<0.05). In addition, GSK126 up-regulated E-cadherin mRNA expression and down-regulated N-cadherin and Vimentin mRNA expression, whereas had no significant effect on Snail, Fibronectin and VEGF-A mRNA expression. The protein expression of E-cadherin was elevated but VEGF-A protein did not change in GSK126-treated groups. Similar results were exhibited in DU145 cell.GSK126 can significantly inhibit cell migration and invasion in prostate cancer PC-3 and DU145 cells, which may be resulted from its effect on epithelial-mesenchymal transition. GSK126 may be used as a potential anti-prostate cancer dug in clinic.
Apoptosis ; drug effects ; Cadherins ; analysis ; drug effects ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Down-Regulation ; drug effects ; Drug Screening Assays, Antitumor ; methods ; Enhancer of Zeste Homolog 2 Protein ; analysis ; drug effects ; metabolism ; Fibronectins ; analysis ; drug effects ; metabolism ; Humans ; Indoles ; pharmacology ; Male ; Prostatic Neoplasms ; chemistry ; genetics ; physiopathology ; Pyridones ; pharmacology ; RNA, Messenger ; Up-Regulation ; drug effects ; Vascular Endothelial Growth Factor A ; analysis ; drug effects ; Vimentin ; analysis ; drug effects ; metabolism

Objective To explore the correlation between the family care and the hope level in maintenance hemodialysis ( MHD) patients in grassroots hospital. Methods A total of 280 MHD patients were questionnaired by Herth Hope Scale and the Family APGAR Index. Pearson correlation analysis and hierarchical regression analysis were used to explore the effect of family care on the hope level in MHD patients. Results The total score of hope level in MHD patients was (29. 04 ± 4. 23) staying in medium level, and 15. 00% (42/280) of them in the low level, 62. 86% (176/280) of them in the medium level, and 22. 14%(62/280) of them in the high level. The total score of family care in MHD patients was (6. 45 ± 1. 51), and 61. 07% ( 171/280 ) of them suffered the family care disability, among them, 22. 86% ( 64/280 ) MHD patients′family care was serious disability, and 38. 21% (107/280) MHD patients′family care were moderate disability. Pearson correlation analysis shew that the reality, positive attitude ( T ) in the future, positive behavior ( P) , intimate relations with others ( I) and total hope score had positive correlation with family care of adaptive level, cooperation, growing level, emotional level, intimate level and total score (P<0. 05). There were significant difference of hope level in the patients with different gender, culture level, occupation, marital status, medical payment (P<0. 05), and the hope level was significantly positively correlated with age (r=0. 312, P<0. 05) and family income(r=0. 387,P<0. 05), and was significantly negatively correlated with the receiving care time (r= -0. 298,P<0. 05), the length of MHD (r= -0. 304,P<0. 05) and the number of complication incidences (r= -0. 364,P<0. 05). Hierarchical regression analysis shew that adaptive level, intimate level and emotional level could explained 30. 50% of the total variance of the hope level in MHD patients (△R2 =0. 305,P<0. 05). Conclusions The hope level in MHD patients is in the medium level, and family care is poor. Family function may be the important influence factor of the hope level in MHD patients.