ABSTRACT
PTPN11 is the most common mutation gene of RAS disease, which is located in the upstream of RAS/MAPK pathway and participates in signal transduction. Because the molecular mechanism of RAS's disease involves the same pathway, it may present a certain commonality in clinic, but the different genotypes with PTPN11 mutation may also express different phenotypes. Therefore, it is not easy to identify and diagnose this disease early in clinic. The present article aims to analyze the correlation between the clinical phenotype and genotype of 4 patients with RAS disease.
ABSTRACT
Objective · To observe effect of 17β estrodial (17β E2) with different concentrations on C type natriuretic peptide (CNP), insulin like growth factor 1 (IGF1), and natriuretic peptide receptor B (NPR-B) expression and proliferation of growth plate chondrocytes of rats in vitro. Methods · Eight Wistar rats were sacrificed and their epiphyseal cartilages of the upper tibias were separated to obtain chondrocytes on the 14th day after birth. Then chondrocytes were cultured with 17β E2 in different concentrations (10-4、10-6、10-8、10-10 and 10-12 mol/L) for 48 h, while control group was cultured without 17β E2. CCK8 method, ELISA and qRT-PCR were used to analyze the proliferation of chondrocytes, the levels of CNP and IGF1 in culture medium and mRNA levels of CNP, NPR-B and IGF1, respectively. Results · 17β E2 in different concentrations affected the proliferation of growth plate chondrocytes significantly. When the concentration of 17β E2 was 10-8 mol/L, it had the strongest effect on the cell proliferation. When the concentration increased to 10-4 mol/L, the proliferation of chondrocytes was inhibited. With the increasement of 17β E2 concentration, the levels of CNP in the culture medium and the mRNA levels of CNP in the chondrocytes were significantly different. The highest levels of CNP protein and mRNA both appeared in 10-8 mol/L group, while the lowest levels both appeared in 10-4 mol/L group. IGF1 and its mRNA also reached the highest levels in 10-8 mol/L group,but the lowest concentration and mRNA level were in 10-10 mol/L group and 10-12 mol/L, respectively. Both CNP mRNA and protein levels were positive correlated with the proliferation of chondrocytes (P=0.000). Nevertheless, there was no significant correlation between the proliferation of chondrocytes and IGF1 mRNA or protein levels (P>0.05). Conclusion · 17β E2 modulates proliferation of rat growth plate chondrocytes in a dose-effect manner. It enhances proliferation at relatively low concentrations (10-10-10-8 mol/L) and inhibits proliferation at high concentration. This effect is positively related to CNP expression in chondrocytes.
ABSTRACT
Objective To study the early diagnostic predictors and key follow-up parameters for girls with rapidly progressive central precocious puberty (RP-CPP). Methods A total of 260 girls with CPP participated in a prospective, nonrandomized, multi-center, nested case control study. After follow-up six months without any therapy, 114 girls were divided into RP-CPP (n=70) and slowly progressive CPP (SP-CPP) (n=44) groups. Results The basal serum LH and insulin-like growth factor Ⅰstandard deviation score (IGF-ⅠSDS) were the important risk factors of RP-CPP (OR 4.04, 1.578), especially the former. The receiver operating characteristic (ROC) curve revealed that the areas under the ROC curve of basal LH and IGF-ⅠSDS were 0.83 and 0.807, respectively. The levels of basal LH and IGF-ⅠSDS were at 0.52 mIU/ml and 0.35 respectively for the accuracy diagnosis of RP-CPP with the maximum Youden indexs. After follow-up for six months, the change levels of height, breast stages, bone age/chronological age ratio, serum LH, uterine and ovarian volume in RP-CPP group were significantly higher than those in SP-CPP group (all P<0.05). Conclusions The level of basal serum LH and IGF-ⅠSDS may be used as the risk predictors for early diagnosis for girls with RP-CPP. The change levels of basal LH, progress rates of gonad and sex character, height, and impaired growth potential seem to be the key follow-up parameters for CPP progress.