The RTK/ERK signaling pathway has been implicated in prostate cancer progression. However, the genetic relevance of this pathway to aggressive prostate cancer at the SNP level remains undefined. Here we performed a SNP and gene-based association analysis of the RTK/ERK pathway with aggressive prostate cancer in a cohort comprising 956 aggressive and 347 non-aggressive cases. We identified several loci including rs3217869/CCND2 within the pathway shown to be significantly associated with aggressive prostate cancer. Our functional analysis revealed a statistically significant relationship between rs3217869 risk genotype and decreased CCND2 expression levels in a collection of 119 prostate cancer patient samples. Reduced expression of CCND2 promoted cell proliferation and its overexpression inhibited cell growth of prostate cancer. Strikingly, CCND2 downregulation was consistently observed in the advanced prostate cancer in 18 available clinical data sets with a total amount of 1,095 prostate samples. Furthermore, the lower expression levels of CCND2 markedly correlated with prostate tumor progression to high Gleason score and elevated PSA levels, and served as an independent predictor of biochemical relapse and overall survival in a large cohort of prostate cancer patients. Together, we have identified an association of genetic variants and genes in the RTK/ERK pathway with prostate cancer aggressiveness, and highlighted the potential importance of CCND2 in prostate cancer susceptibility and tumor progression to metastasis.

Chronic prostatitis (CP) is a complex disease. Fragmentary evidence suggests that factors such as infection and autoimmunity might be associated with CP. To further elucidate potential risk factors, the current study utilized the Fangchenggang Area Male Health and Examination Survey (FAMHES) project; where 22 inflammatory/immune markers, hormone markers, tumor-related proteins, and nutrition-related variables were investigated. We also performed baseline, regression, discriminant, and receiver operating characteristic (ROC) analyses. According to NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), participants were divided into chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, pain ≥ 4; divided into IIIa and IIIb sub-groups) and non-CPPS (pain = 0; divided into IV and normal sub-groups). Analyses revealed osteocalcin as a consistent protective factor for CP/CPPS, NIH-IIIb, and NIH-IV prostatitis. Further discriminant analysis revealed that ferritin (p = 0.002) and prostate-specific antigen (PSA) (p = 0.010) were significantly associated with NIH-IIIa and NIH-IV prostatitis, respectively. Moreover, ROC analysis suggested that ferritin was the most valuable independent predictor of NIH-IIIa prostatitis (AUC = 0.639, 95% CI = 0.534–0.745, p = 0.006). Together, our study revealed inflammatory/immune markers [immunoglobulin E, Complement (C3, C4), C-reactive protein, anti-streptolysin, and rheumatoid factors], hormone markers (osteocalcin, testosterone, follicle-stimulating hormone, and insulin), tumor-related proteins (carcinoembryonic and PSA), and a nutrition-related variable (ferritin) were significantly associated with CP or one of its subtypes.

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Atropine is a racemic mixture of D-and L-hyoscyamine, but only L-hyoscyamine is the effective ingredient. In this study, a new, sensitive, stable, and selective LC/MS assay was developed for the determination of L-hyoscyamine and applied to a clinical study.The parent-product (m/z) transition pair of L-hyoscyamine was 290.1 ! 124.1. Chromatographic separations were performed using a chiral MZ column (250 mm  4.6 mm, 5.0 μm) by a stepwise gradient elution mode with n-hexane, isopropanol, and diethylamine as mobile phases. L-Hyoscyamine in human plasma was extracted by liquidliquid extraction. This assay displayed a good linearity over a concentration range of 20.0-400 pg/mL for L-hyoscyamine. The accuracy of the validation assay for L-hyoscyamine ranged from À2.7% to 4.5%, and the precision was within 6.3% coefficient of variation. L-Hyoscyamine in human plasma remained stable at different storage conditions. The method has been successfully applied to plasma samples obtained from a safety study in humans.

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