Objective To assess the exposure levels of heavy metals,including lead,arsenic,mercury,and cadmium,in the local population in Sichuan and Chongqing,China,to compare and analyze the differences in reference intervals(RIs)obtained from direct and indirect sampling methods,and to explore the interchangeability and limitations of these two sampling methods.Methods RIs were obtained by the direct sampling method and the indirect sampling method.In the direct sample method,the levels of blood arsenic,urinary cadmium,urinary mercury,and blood lead levels of 5562 healthy participants aged 22-50 years in Sichuan and Chongqing,China were measured by atomic absorption spectrometry and inductively coupled plasma-mass spectrometry.Using the human biomonitoring(HBM)data,we established RIs for the population by a nonparametric method.On the other hand,in the indirect sampling method,RIs were established via a nonparametric method based on data from the laboratory information system(LIS)of a local hospital after stratifying healthy individuals using a Gaussian mixture model(GMM).Comparative analysis of the RIs derived from the two sampling methods were then conducted.Results The RI for blood arsenic was 0.11-1.3 μmol/L.The RI for urinary cadmium was 0.51-2.80 μmol/mol creatine for adults aged 22 to under 43 years and 0.66-2.96 μmol/mol creatine for adults aged 43-50 years.The RI for urinary mercury was 0.12-1.10 μmol/mol creatine.The RI for blood lead was 14.00-47.00 pg/L for adults aged 22 to under 41 year,16.00-53.38 pg/L for males aged 41-50 year,and 15.00-51.02 pg/L for females aged 41-50 year.Most of the RIs established by the direct sampling method had a narrower range compared to those established by the indirect sampling method,and the RIs established by both sampling methods were partially biased.Conclusions The RIs for blood arsenic,urine cadmium,urine mercury,and blood lead in healthy individuals aged 22-50 years in Sichuan and Chongqing,China were established using both direct and indirect sampling methods,which contributes to a better understanding of environmental exposure to metals in the general population and provides a reference for metal poisoning.For data from the same lab,the GMM-based indirect sampling method demonstrated relatively consistent performance in establishing RIs compared with the direct sampling method.

Animals ; Coronary Vessels ; Diabetes Mellitus ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Rats

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.

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.

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.

Arrhythmias, Cardiac ; Humans ; Large-Conductance Calcium-Activated Potassium Channels ; Small-Conductance Calcium-Activated Potassium Channels