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1.  Cord Blood C-peptide, Insulin, HbA1c, and Lipids Levels in Small- and Large-for-Gestational-Age Newborns 
Small- and large-for-gestational-age (SGA, LGA) newborns are associated with metabolic syndrome in their later life. Cord blood C-peptide, insulin, glycosylated hemoglobin (HbA1c), and lipids levels may be altered in SGA and LGA newborns; however, the results are conflicting. Therefore, this study aimed to determine the effect of cord blood markers on SGA and LGA newborns.
This was a prospective cohort study and included 2873 term newborns of non-diabetic women. Among these newborns, 83 (2.9%) were SGA, 2236 (77.8%) were appropriate-for-gestational-age (AGA), and 554 (19.3%) were LGA newborns. Cord blood C-peptide, insulin, HbA1c, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were measured. The chi-square, Kruskal-Wallis, and Mann-Whitney tests were used to analyze categorical variables and continuous variables, respectively. Multinomial logistic regression analysis was used to determine the independent effect of these variables on SGA and LGA newborns.
Cord serum TG level was significantly higher in the SGA group than in AGA and LGA groups (p<0.05). The LGA group had significantly higher cord serum insulin level than AGA and SGA groups (p<0.05). After adjustment for confounding variables, including maternal age, parity, pre-pregnancy body mass index (BMI), education, annual household income, pregnancy-induced hypertension (PIH), mode of delivery, and newborn sex, high TG and insulin levels remained significantly associated with SGA and LGA newborns, respectively (p<0.05).
High cord serum TG and insulin levels are independently associated with SGA and LGA newborns, respectively.
PMCID: PMC4226317  PMID: 25357084
Lipids; Insulin; Small-For-Gestational Age Newborns; Large-For-Gestational Age Newborns
2.  Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight, renal function and stanozolol administration 
Acta Pharmacologica Sinica  2013;34(7):969-975.
To develop a population pharmacokinetic model for the immunosuppressant ciclosporin in Chinese children with aplastic anemia and to identify covariates influencing ciclosporin pharmacokinetics.
A total of 102 children with either acquired or congenital aplastic anemia aged 8.8±3.6 years (range 0.9–17.6 years) were included. Therapeutic drug monitoring (TDM) data for ciclosporin were collected. The population pharmacokinetic model of ciclosporin was described using the nonlinear mixed-effects modeling (NONMEM) VI software. The final model was validated using bootstrap and normalized prediction distribution errors.
A one-compartment model with first-order absorption and elimination was developed. The estimated CL/F was 15.1, which was lower than those of children receiving stem cell or kidney transplant reported in the West (16.9–29.3). The weight normalized CL/F was 0.45 (range: 0.27–0.70) Lh−1·kg−1. The covariate analysis identified body weight, serum creatinine and concomitant administration of the anabolic steroid stanozolol as individual factors influencing the CL/F of ciclosporin.
Our model could be used to optimize the ciclosporin dosing regimen in Chinese children with aplastic anemia.
PMCID: PMC4002619  PMID: 23624757
ciclosporin; immunosuppressant; aplastic anemia; population pharmacokinetics; stanozolol; serum creatinine; pediatrics
3.  Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China 
Dyslipidemia in pregnancy are associated with gestational diabetes mellitus (GDM), preeclampsia, preterm birth and other adverse outcomes, which has been extensively studied in western countries. However, similar studies have rarely been conducted in Asian countries. Our study was aimed at investigating the associations between maternal dyslipidemia and adverse pregnancy outcomes among Chinese population.
Data were derived from 934 pairs of non-diabetic mothers and neonates between 2010 and 2011. Serum blood samples were assayed for fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) concentrations during the first, second and third trimesters. The present study explored the associations between maternal lipid profile and pregnancy complications and perinatal outcomes. The pregnancy complications included GDM, preeclampsia and intrahepatic cholestasis of pregnancy (ICP); the perinatal outcomes included preterm birth, small/large for gestational age (SGA/LGA) infants and macrosomia. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were calculated and adjusted via stepwise logistic regression analysis. Optimal cut-off points were determined by ROC curve analysis.
After adjustments for confounders, every unit elevation in third-trimester TG concentration was associated with increased risk for GDM (OR = 1.37, 95 % CI: 1.18-1.58), preeclampsia (OR = 1.50, 95 % CI: 1.16-1.93), ICP (OR = 1.28, 95 % CI: 1.09-1.51), LGA (OR = 1.13, 95 % CI: 1.02-1.26), macrosomia (OR = 1.19, 95 % CI: 1.02-1.39) and decreased risk for SGA (OR = 0.63, 95 % CI: 0.40-0.99); every unit increase in HDL-C concentration was associated with decreased risk for GDM and macrosomia, especially during the second trimester (GDM: OR = 0.10, 95 % CI: 0.03-0.31; macrosomia: OR = 0.25, 95 % CI: 0.09-0.73). The optimal cut-off points for third-trimester TG predicting GDM, preeclampsia, ICP, LGA and SGA were separately ≥3.871, 3.528, 3.177, 3.534 and ≤2.530 mmol/L. The optimal cut-off points for third-trimester HDL-C identifying GDM, macrosomia and SGA were respectively ≤1.712, 1.817 and ≥2.238 mmol/L.
Among Chinese population, maternal high TG in late pregnancy was independently associated with increased risk of GDM, preeclampsia, ICP, LGA, macrosomia and decreased risk of SGA. Relative low maternal HDL-C during pregnancy was significantly associated with increased risk of GDM and macrosomia; whereas relative high HDL-C was a protective factor for both of them.
PMCID: PMC4802610  PMID: 27000102
4.  Patent Ductus Arteriosus and Pulmonary Valve Stenosis in A Patient with 18p Deletion Syndrome 
Yonsei Medical Journal  2008;49(3):500-502.
We report on a patient with a partial deletion on the short arm of chromosome 18 (del 18p), who presented with dysmorphic features and delayed developmental milestones as well as with a patent ductus arteriosus (PDA) and pulmonary valve stenosis (PS). Several forms of congenital heart disease (CHD) are found in about 10% of patients with del (18p), but coexisting PDA and PS have not been reported. Del (18p) must be considered in patients with characteristic phenotypic abnormalities and congenital heart disease, including a combination of PDA and PS.
PMCID: PMC2615354  PMID: 18581602
18p deletion syndrome; dysmorphic features; patent ductus arteriosus; pulmonary valve stenosis
5.  Factors associated with fasting plasma ghrelin levels in children and adolescents 
AIM: To measure plasma ghrelin levels in children and adolescents, analyze the associated factors, and investigate the role of ghrelin in obesity, insulin resistance and reproductive physiology.
METHODS: A total of 283 subjects aged 4.8-15.8 year were enrolled. Fasting blood samples were collected and plasma ghrelin levels were measured by radioimmunoassay. Fasting glucose (FG), fasting insulin (FI), baseline testosterone (T), estradiol (E2), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), serum total cholesterol (TC), triglyceride (TG), alanine aminotransferase (ALT) and uric acid (UA) were measured. Body mass index (BMI), insulin resistance by homeostasis model (HOMA-IR) and beta cell function by homeostasis model (HOMA-β) were calculated.
RESULTS: The median ghrelin level was 290 ng/L (15.0-1325.0 ng/L). Bivariate correlation analysis showed that ghrelin levels were inversely correlated with BMI, ALT, TG, UA, LH, FI and HOMA-IR (all P < 0.05). No other significant correlation was found between ghrelin levels and age, gender, TC, E2, FSH, PRL, FG and HOMA-β. Stepwise multiple regression analysis showed that only BMI and FI were independent determinants of plasma ghrelin levels in these children and adolescents (P = 0.018 and P = 0.046, respectively), which explained 25.4% of the variance.
CONCLUSION: These data suggest that the lower ghrelin levels in obese subjects may be the result of obesity and hyperinsulinemia, which is very common in obese subjects. Moreover, ghrelin may regulate human reproductive physiology indirectly.
PMCID: PMC2684010  PMID: 18205273
Ghrelin; Obesity; Body mass index; Insulin
6.  Study on the Social Adaptation of Chinese Children with Down Syndrome 
Yonsei Medical Journal  2007;48(3):412-420.
To evaluate social adjustment and related factors among Chinese children with Down syndrome (DS).
Patients and Methods
A structured interview and Peabody Picture Vocabulary Test (PPVT) were conducted with a group of 36 DS children with a mean age of 106.28 months, a group of 30 normally-developing children matched for mental age (MA) and a group of 40 normally-developing children matched for chronological age (CA). Mean scores of social adjustment were compared between the three groups, and partial correlations and stepwise multiple regression models were used to further explore related factors.
There was no difference between the DS group and the MA group in terms of communication skills. However, the DS group scored much better than the MA group in self-dependence, locomotion, work skills, socialization and self-management. Children in the CA group achieved significantly higher scores in all aspects of social adjustment than the DS children. Partial correlations indicate a relationship between social adjustment and the PPVT raw score and also between social adjustment and age (significant r ranging between 0.24 and 0.92). A stepwise linear regression analysis showed that family structure was the main predictor of social adjustment. Newborn history was also a predictor of work skills, communication, socialization and self-management. Parental education was found to account for 8% of self-dependence. Maternal education explained 6% of the variation in locomotion.
Although limited by the small sample size, these results indicate that Chinese DS children have better social adjustment skills when compared to their mental-age-matched normally-developing peers, but that the Chinese DS children showed aspects of adaptive development that differed from Western DS children. Analyses of factors related to social adjustment suggest that effective early intervention may improve social adaptability.
PMCID: PMC2628096  PMID: 17594148
Down syndrome; children; social adjustment; cognition
7.  Glycolipid metabolic status of overweight/obese adolescents aged 9- to 15-year-old and the BMI-SDS/BMI cut-off value of predicting dyslipidemiain boys, Shanghai, China: a cross-sectional study 
The prevalence of adolescents’ obesity and overweight has dramatically elevated in China. Obese children were likely to insulin resistance and dyslipidemia, which are risk factors of cardiovascular diseases. However there was no cut-off point of anthropometric values to predict the risk factors in Chinese adolescents. The present study was to investigate glycolipid metabolism status of adolescents in Shanghai and to explore the correlations between body mass index standard deviation score (BMI-SDS) and metabolic indices, determine the best cut-off value of BMI-SDS to predict dyslipidemia.
Fifteen schools in Shanghai’s two districts were chosen by cluster sampling and primary screening was done in children aged 9-15 years old. After screening of bodyweight and height, overweight and obese adolescents and age-matched children with normal body weight were randomly recruited in the study. Anthropometric measurements, biochemical measurements of glycolipid profiles were done. SPSS19.0 was used to analyze the data. Receiver operating characteristic (ROC) curves were made and the best cut-off values of BMI-SDS to predict dyslipidemia were determined while the Youden indices were maximum.
Five hundred and thirty-eight adolescents were enrolled in this research, among which 283 have normal bodyweight, 115 were overweight and 140 were obese. No significant differences of the ages among 3 groups were found. There were significant differences of WC-SDS (p<0.001), triacylglycerol (p<0.05), high and low density lipoprotein cholesterol (p<0.01), fasting insulin (p<0.01) and C-peptide (p<0.001) among 3 groups. Significant difference of fasting glucose was only found between normal weight and overweight group. Significant difference of total cholesterol was found between obese and normal weight group. There was no significant difference of glycated hemoglobin among 3 groups. The same tendency was found in boys but not in girls. Only HDL-C reduced and TG increased while BMI elevated in girls. The best cut-off value of BMI-SDS was 1.22 to predict dyslipidemia in boys. The BMI cut-off was 21.67 in boys.
Overweight and obese youths had reduced insulin sensitivity and high prevalence of dyslipidemia.When BMI-SDS elevated up to 1.22 and BMI was higher than 21.67 in boys, dyslipidemia may happen.
PMCID: PMC3766195  PMID: 23984682
Adolescents; Children; Lipid metabolism; Obesity; Overweight; BMI-SDS; China
8.  Indicators of Child Health, Service Utilization and Mortality in Zhejiang Province of China, 1998–2011 
PLoS ONE  2013;8(4):e62854.
To investigate the levels of primary health care services for children and their changes in Zhejiang Province, China from 1998 to 2011.
The data were drawn from Zhejiang maternal and child health statistics collected under the supervision of the Health Bureau of Zhejiang Province. Primary health care coverage, hospital deliveries, low birth weight, postnatal visits, breastfeeding, underweight, early neonatal (<7 days) mortality, neonatal mortality, infant mortality and under-5 mortality were investigated.
The coverage rates for children under 3 years old and children under 7 years old increased in the last 14 years. The hospital delivery rate was high during the study period, and the overall difference narrowed. There was a significant difference (P<0.001) between the prevalence of low birth weight in 1998 (2.03%) and the prevalence in 2011 (2.71%). The increase in low birth weight was more significant in urban areas than in rural areas. The postnatal visit rate increased from 95.00% to 98.45% with a significant difference (P<0.001). The breastfeeding rate was the highest in 2004 at 74.79% and lowest in 2008 at 53.86%. The prevalence of underweight in children under 5 years old decreased from 1.63% to 0.65%, and the prevalence was higher in rural areas. The early neonatal, neonatal, infant and under-5 mortality rates decreased from 6.66‰, 8.67‰, 11.99‰ and 15.28‰ to 1.69‰, 2.36‰, 3.89‰ and 5.42‰, respectively (P<0.001). The mortality rates in rural areas were slightly higher than those in urban areas each year, and the mortality rates were lower in Ningbo, Wenzhou, and Jiaxing regions and higher in Quzhou and Lishui regions.
Primary health care services for children in Zhejiang Province improved from 1998 to 2011. Continued high rates of low birth weight in urban areas and mortality in rural areas may be addressed with improvements in health awareness and medical technology.
PMCID: PMC3636200  PMID: 23638155
9.  Charting the developmental trajectories of attention and executive function in Chinese school-aged children 
Attention is a complex domain that has reawakened research interest in recent years. There are relatively few studies that have examined age-related changes across different attention subcomponents, such as selection, maintenance, and control, using large samples covering a wide age range. The present study assessed performance in 466 participants in order to identify the ages at which mature performance was reached across differing attention subcomponents. Furthermore, we investigated whether the nature of the attentional demands or task difficulty predicted the age at which stable levels of performance were reached. The results supported the former rather than the latter alternative.
PMCID: PMC3483869  PMID: 21218297
Attention; Executive function; Developmental trajectory; Visual search; Vigilance
10.  RNAa-mediated overexpression of WT1 induces apoptosis in HepG2 cells 
Recent studies have reported that double-stranded RNA (dsRNA) can activate gene expression by targeting promoter sequence in a process termed RNA activation. The present study was conducted to evaluate the potential of WT1 induction by small activating RNA targeting the WT1 promoter (dsWT1) in the treatment of hepatocellular carcinoma.
The human hepatocellular carcinoma cell line HepG2 was transfected with dsRNA by liposomes. The expression of mRNA and protein in cells were investigated using real-time reverse real-time quantitative PCR and Western blot, respectively. Cell viability and clonogenicity were determined by MTT assay and clonogenicity assay, respectively. Cell apoptosis was evaluated by flow-cytometric analysis.
Expressions of WT1 mRNA and protein in dsWT1 treated HepG2 cells were significantly elevated. Inhibition of cell viability by dsWT1 was dose-dependent and time-dependent. Reduction of the number and size of colonies formed were found in dsWT1 treated cells. dsWT1 induced significant apoptosis in HepG2 cells. The decreased anti-apoptotic protein Bcl-2 and elevated pro-apoptotic protein Bak expression were detected in dsWT1 treated cells. The level of pro-caspase-3 remarkably decreased and cleaved caspase-3 and PARP fragment were also detected in dsWT1 treated cells.
These data show that RNAa-mediated overexpression of WT1 may have therapeutic potential in the treatment of hepatocellular carcinoma.
PMCID: PMC3268108  PMID: 22244202
WT1; Small activating RNA; dsRNA; Hepatocellular carcinoma; HepG2 cell; Apoptosis
11.  Gram Stain-Specific-Probe-Based Real-Time PCR for Diagnosis and Discrimination of Bacterial Neonatal Sepsis▿  
Journal of Clinical Microbiology  2008;46(8):2613-2619.
Sepsis is a serious disease with high mortality in newborns. It is very important to have a convenient and accurate method for pathogenic diagnosis of neonatal sepsis. We developed a method of simultaneous detection and Gram classification of clinically relevant bacterial pathogens causing sepsis directly from blood samples with Gram stain-specific-probe-based real-time PCR (GSPBRT-PCR). With GSPBRT-PCR, 53 clinically important strains representing 25 gram-positive and 28 gram-negative bacterial species were identified correctly with the corresponding Gram probe. The limits of the GSPBRT-PCR assay in serial dilutions of the bacteria revealed that Staphylococcus aureus could be detected at concentrations of 3 CFU per PCR and Escherichia coli at concentrations as low as 1 CFU per PCR. The GSPBRT-PCR assay was further evaluated on 600 blood specimens from patients with suspicioon of neonatal sepsis and compared to the results obtained from blood cultures. The positive rate of the GSPBRT-PCR array was 50/600 (8.33%), significantly higher than that of blood culture (34/600; 5.67%) (P = 0.00003). When blood culture was used as a control, the sensitivity of GSPBRT-PCR was 100%, the specificity was 97.17%, and the index of accurate diagnosis was 0.972. This study suggests that GSPBRT-PCR is very useful for the rapid and accurate diagnosis of bacterial infection and that it can have an important impact on the current inappropriate and unnecessary use of antibiotics in the treatment of newborns.
PMCID: PMC2519463  PMID: 18550744
12.  Treatment and follow-up of children with transient congenital hypothyroidism*  
Objective: To study the clinical therapy and prognosis in children with transient congenital hypothyroidism (CH). Methods: Fifty-seven children with CH diagnosed after neonatal screening were treated with low-dosage levothyroxine (L-T4). Follow-up evaluation included the determination of TT3, TT4 and TSH serum levels and the assessment of thyroid gland morphology, bone age, growth development and development quotients (DQ). A full check-up was performed at age 2, when the affected children first discontinued the L-T4 treatment for 1 month, and one year later. Development quotients were compared with a control group of 29 healthy peers. Results: The initial L-T4 dosage administered was 3.21~5.81 μg/(kg·d) with an average of (16.25±3.87) μg/d. Mean duration of therapy was (28.09±9.56) months. No significant difference was found between study group and control group in the DQ test (average score (106.58±14.40) vs (102.4±8.6), P>0.05) and 96.49% of the CH children achieved a test score above 85. Bone age, 99mTc scans and ultrasonographic findings were all normal, and evaluation of physical development was normal too, as were the serum levels of TT3, TT4 and TSH after one year of follow-up. Conclusion: A L-T4 dosage of 3.21~5.81 μg/(kg·d) was found sufficient for the treatment of transient CH. The treated children showed satisfactory overall mental and physical development at age 2. So it is possible for CH children to stop taking medicine if their laboratory findings and physical development are all normal after regular treatment and 2~3 years of follow-up.
PMCID: PMC1390645  PMID: 16358380
Transient congenital hypothyroidism; Levothyroxine; Development quotient; Follow-up
13.  Study on the neurotoxic effects of low-level lead exposure in rats*  
Objective: To investigate effects of developmental lead exposure on nitric oxide synthase (NOS) activity in different brain regions and on N-methyl-D-aspartate (NMDA) receptor mRNA expression in the hippocampus of rats. On the basis of these observations, we explored possible mechanisms by which lead exposure leads to impaired learning and memorizing abilities in children. Methods: A series of rat animal models exposed to low levels of lead during the developing period was established (drinking water containing 0.025%, 0.05% and 0.075% lead acetate). NOS activities in the hippocampus, the cerebral cortex, the cerebellum and the brain stem were determined with fluorescence measurement and levels of mRNA expression of the NMDA receptor 2A (NR2A) subunit and NMDA receptor 2B (NR2B) subunit in the rat hippocampus were measured with Retro-translation (RT-PCR). Results: There were no differences in the body weight of rat pups between any of the groups at any given time (P>0.05). The blood lead level of Pb-exposed rat pups showed a systematic pattern of change: at 14 d of age, it was lower than that at 7 d of age, then rising to the peak level at 21 d and finally falling to lower levels at 28 d. The hippocampal NOS activities of lead-exposed groups were all lower than that of the control group on the 21st and 28th day (P<0.01). NOS activities in the cerebellum of lead-exposed groups were all lower than that of the control group on the 21st and 28th day (P<0.001) and the NOS activity of the 0.025% group was significantly lower than that of the 0.05% and 0.075% groups on the 28th day (P<0.05). NOS activity in the cerebral cortex of the 0.075% group was significantly lower than that of the control, 0.025% and 0.05% groups on the four day spans (P<0.001). There was no significant difference of NOS activity in the brain stem between any lead-exposed group and the control group on the four day spans. In the 0.05% and the 0.075% groups, the level of NR2A mRNA expression was higher than that in the control group at 7 d and 14 d of age (P<0.05). In the 0.025% group, the level of NR2A was found to be higher than that in the control group at 7 d of age only (P<0.05). No significant differences were found for the levels of NR2B mRNA expression between any of the groups at any given time. Conclusions: NOS activity in the hippocampus, the cerebral cortex and the cerebellum are inhibited by lead exposure. The degree of the inhibitory effect depends on the time span of exposure and the lead concentration. Developmental low-level lead exposure was found to raise the level of NR2A mRNA expression in the hippocampus of rats. Developmental low-level lead exposure does not affect the level of NR2B mRNA expression in the hippocampus.
PMCID: PMC1389806  PMID: 15973774
Lead exposure; Rat pups; Nitric oxide synthase (NOS); Fluorescence; Hippocampus; mRNA; Retro-translation (RT-PCR); N-methyl-D-aspartate receptor (NMDAR)

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