The aim of the study was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in distinguishing between benign and malignant cervical lymph nodes (LNs) in patients with papillary thyroid carcinoma (PTC). Two hundred and one cervical LNs (157 metastatic from PTC and 44 benign) were evaluated using conventional ultrasonography (US) and CEUS before biopsy or surgery. Histopathology was used as the gold standard. We evaluated the size, long axis/short axis ratio (L/S), fatty hilum, hyper-echogenicity, calcification, cystic change, peripheral vascularity and CEUS parameters for each lymph nodule. The CEUS parameters included enhancement type, homogeneity, perfusion type, ring enhancement, peak intensity (PI) index and area under the curve (AUC) index. Univariate analysis demonstrated that compared with benign LNs, malignant LNs more frequently had L/S < 2, absence of a fatty hilum, presence of hyper-echogenicity, presence of calcification, peripheral vascularity, hyper-enhancement, heterogeneous enhancement, centripetal perfusion, ring enhancement, PI index > 1 and AUC index > 1 on preoperative US and CEUS. Binary logistic regression analysis demonstrated that hyper-enhancement, centripetal perfusion, and ring enhancement are independent CEUS characteristics related to malignant LNs for their differentiation from benign LNs (all p < 0.05). Our study indicated that preoperative CEUS characteristics may serve as a useful tool to identify malignant cervical LNs from benign cervical LNs.

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Renal 25-hydroxyvitamin D-1α-hydroxylase (1αOHase, CYP27B1) and 24-hydroxylase (24OHase, CYP24A1) are tightly regulated. However, little is known about the regulation of 1α(OH)ase and 24(OH)ase in extrarenal tissue such as the epidermis. This study was to determine the roles of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF 23) in the regulation of 1α(OH)ase and 24(OH)ase in epidermal keratinocytes as well as epidermal keratinocyte proliferation and differentiation. The results showed that PTH increased the protein level of 1α(OH)ase in human epidermal keratinocyte cell line HaCaT, but had no effect on the level of 24(OH)ase. The effect of PTH on 1α(OH)ase was blocked by the PKC inhibitor. Treatment with FGF23 decreased mRNA and protein levels of 1α(OH)ase and increased mRNA and protein levels of 24(OH)ase in HaCaT cells. The effect of FGF23 on 1α(OH)ase and 24(OH)ase was blocked by the mitogen-activated protein kinase/extracellular regulated protein kinase (MAPK/ERK) inhibitor. In addition, treatment with PTH enhanced levels of differentiation markers including keratin 1, involucrin, loricrin, and filaggrin but reduced levels of BrdU incorporation in HaCaT cells. These effects were inhibited by the PKC inhibitor. FGF23 enhanced proliferation of HaCaT cells, but reduced levels of early differentiation markers including keratin 1 and involucrin and enhanced levels of the later differentiation markers including loricrin and filaggrin. These results suggest that PTH stimulates 1α(OH)ase expression and differentiation of HaCaT cells and inhibits proliferation via PKC. The data also suggest that FGF23 inhibits 1α(OH)ase expression and stimulates 24(OH)ase expression via MAPK/ERK. In addition, FGF23 enhances proliferation and late differentiation and inhibits early differentiation of HaCaT keratinocytes.