Bone morphogenetic proteins (BMPs) belong to TGF-β superfamily and are a group of important cytokines involved in cell differentiation, proliferation and embryonic development. Multiple BMPs play important roles in several functions of vertebrates. Signaling pathway of BMPs is known to be mediated by Smad proteins, which include 8 members while Smad1, Smad5 and Smad8 are involved in BMPs signal transduction while Smad2 and Smad3 are mediated TGF-β signal transduction. Although several BMPs such as BMP4 and BMP9 have been documented in the liver, BMP13 has not been examined in the liver. BMP13 also known as growth differentiation factor (GDF)-6 or cartilage-derived morphogenetic protein (CDMP)-2 is one of the BMPs family members. Function of BMP13 has been investigated in bone and tendon repair. It can stimulate tendon-like cell proliferation. However, our recent findings revealed that there was expression of BMP13 in the liver and its expression was modulated during metabolic disorders. The current article is to understand biological function of BMP13 especially in the liver.
Bone Morphogenetic Proteins ; metabolism ; physiology ; Growth Differentiation Factor 6 ; metabolism ; physiology ; Humans ; Liver ; metabolism ; Liver Diseases ; metabolism ; Smad Proteins ; metabolism

PURPOSE: Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer. METHODS: We searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets. RESULTS: We found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p<0.001), advanced tumor grade (p<0.001), and poor tumor differentiation (p<0.001). GSEA revealed that UCK2-high breast cancers were enriched for gene sets associated with metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox proportional hazards regression analyses of microarray datasets verified that high UCK2 gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of UCK2 was superior to that of TNM staging and comparable to that of multiple gene signatures. CONCLUSION: These findings suggest that UCK2 may be a promising prognostic biomarker for patients with breast cancer.
Biomarkers ; Breast Neoplasms* ; Breast* ; Dataset ; Estrogens ; Gene Expression ; Humans ; Neoplasm Metastasis ; Neoplasm Staging ; Phenotype ; Prodrugs ; Prognosis* ; RNA, Messenger ; Uridine Kinase*

BACKGROUNDMost indices for evaluating a diagnostic test can be expressed as functions of sensitivity (SEN) and specificity (SPE). Practically, all existing methods suffer from the inability to weight sensitivity and specificity relative to their importance. In this paper, we developed a novel index, the weighted Youden index, that allows Youden index to be a combination of sensitivity and specificity with user-defined weights.

METHODSThe weighted Youden index Jw is defined as Jw = 2(w×SEN + (1-w)SPE)-1 (0 ≤ w ≤ 1). It has three properties: (1) the sum of the weights which are attached to sensitivity and specificity should be equal to 1; (2) the range of Jw should be within [-1, 1], which is the range of the Youden index J; (3) Jw should be equal to J when sensitivity and specificity have equal weights. According to the central limit theorem, we obtain the standard error of Jw, and propose a statistical inference method to compare two weighted Youden indices. The monotonicity of the test statistic was discussed.

RESULTSAn example of comparing two diagnostic tests for pheochromocytoma was used to demonstrate the weighted Youden index method. Weighted Youden index, the confidence interval for each test and the hypothesis test of comparing two independent diagnostic tests were presented. Assigning the weights is essential to the weighted Youden index approach.

CONCLUSIONThe weighted Youden index can broaden its applications in diagnostic test development and motivate further research in weighting sensitivity and specificity explicitly.

Diagnostic Tests, Routine ; Humans ; Models, Theoretical ; Sensitivity and Specificity

OBJECTIVETo estimate the prevalence of elevated blood pressure (EBP) in Chinese children and identify individual and family factors associated with EBP.

METHODSA nationwide cross-sectional study was conducted in 2010 using stratified cluster sampling. Participants' blood pressure was measured, and their parents completed a questionnaire on personal and family characteristics. Prevalence and correlates of EBP were assessed.

RESULTSAmong a total of 24,333 participants, 20.2% of boys and 16.3% of girls had EBP. The prevalence of EBP increased with the ascending trend of waist circumference, Waist-to-height ratio, and body mass index. The adjusted prevalence ratios (aPRs) for obese boys and girls were 2.50 and 2.97, respectively. Fewer urban boys (16.2%) had EBP than rural boys (21.7%). Boys with a family history of hypertension were 12% more likely to have EBP. Children whose mothers received a college education tended to have lower likelihood of EBP; with an aPR was 0.85 among boys and 0.78 among girls.

CONCLUSIONEBP is common among obese students and those who have a family history of hypertension. A negative association between mothers' education levels and EBP risk in children was found.

Adolescent ; Blood Pressure ; Body Mass Index ; Child ; China ; epidemiology ; Cluster Analysis ; Cross-Sectional Studies ; Female ; Humans ; Hypertension ; epidemiology ; Male ; Pedigree ; Prevalence ; Schools ; statistics & numerical data ; Surveys and Questionnaires ; Waist Circumference ; Waist-Height Ratio