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Objective: To study the association between CD40-CD40L system and obesity in children., Methods: A total of 76 obese children were enrolled as the obese group, and 74 healthy children with normal body mass index (BMI) were enrolled as the control group. The two groups were compared in terms of morphological indices, biochemical parameters, and serum levels of CD40 and CD40L. Partial correlation analysis and multivariate linear regression analysis were performed to investigate the correlation of CD40 and CD40L with other clinical indices., Results: Compared with the control group, the obese group had significantly higher BMI, waist circumference/height ratio, systolic pressure, diastolic pressure, alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid, triglyceride, apolipoprotein B, fasting blood glucose, fasting insulin, glycosylated hemoglobin, platelet count, CD40L, and mean carotid intima-media thickness (P<0.05), but significantly lower high-density lipoprotein cholesterol and apolipoprotein A1 (P<0.05). With age and sex as the control factors, the partial correlation analysis showed that CD40L was positively correlated with height, weight, BMI, diastolic pressure, bile acid, triglyceride, total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and platelet count (P<0.05). CD40 was positively correlated with waist circumference/height ratio and platelet count (P<0.05). The multivariate linear regression analysis showed that ALT, AST, total cholesterol, and platelet count were the dependent factors influencing the level of CD40L (R 2 =0.266, P<0.05)., Conclusions: CD40-CD40L system is closely associated with obesity and related hyperlipidemia and hypertension. CD40 and CD40L may be used as new indicators for early warning of metabolic syndrome and provide new ideas for the prevention and treatment of related chronic diseases.

Objective: To compare the therapeutic efficacy of patients with neonatal ABO hemolytic disease treated with introvenous immunoglobin G (IVIG) by different modes of administration., Methods: Ninety-three in patients with neonatal ABO hemolytic disease treated in our hospital were divided into group A (31 cases), B(31 cases) and C (31 cases). Based on basic treatment, the patients in group A were treated by a single high dose of IVIG (1 g/kg), patients in group B were treated by multiple low-dose of IVIG (0.5 g/kg), and the patients in group C treated by placebo without IVIG used as controls. The phototherapy time, jaundice time in 3 groups were observed; the total bilirubin levels in 3 groups were compared before and after treatment; the incidence of anemia, the rate of blood transfusion and the occurrence of bilirubin encephalopathy were compared after treatment between 3 groups., Results: The phototherapy time, jaundice time in group A were statistically significantly shorter than those in the group B and C (P<0.05), but there was not statistical significantly difference between group B and C(P>0.05). Before treatment, serum TBIL level in 3 groups was not significantly different (P>0.05); and after treatment for 24 h and 48 h, the serum TBIL levels in group A were significantly lower than that in group B and C (P<0.05); after treatment for 72 h, the serum TBIL level in group A was all lower than 34.2 µmol/L; before treatment, Hb levels in 3 groups were not significantly different (P>0.05); Hb level in group A was significantly higher than that in group B and C after treatment for 24 h, 48 h and 72 h (P<0.05). The incidence of anemia in group A after treatment was significantly lower than that in group B and C, and that in group B significantly lower than that in group C(P<0.05). The rate of blood transfusion in group A was significantly lower than that in the group B and C (P<0.05); the rate of blood transfusion was not statistically significantly different between group B and C(P>0.05)., Conclusion: The single high dose of IVIG infusion can effectively reduce the serum TBIL level, shorten treatment time and reduce the incidence of anemia and blood transfusion, so the therapeutic efficacy is significantly improved.

Objective: Obese children and adolescents are often complicated with the abnormalities of lipid and glucose metabolism, which are often associated with adulthood hypertension, diabetes and cardiovascular disease. In this study, the blood lipids, blood pressure and carotid arterial intima-media thickness (IMT) in obese children and adolescents were measured to investigate the relationship between the dyslipidemia and early vascular lesions., Method: A total of 580 obese children and adolescents aged from 7 to 17 years of age were enrolled from 3 hospitals from Jan. 2008 to Sept. 2009. They were divided into 2 groups according to their blood lipoid levels. Ortholiposis group included 100 males and 52 females with a mean age of 10.47 years and a mean body mass index (BMI) of 28.28 kg/m(2). Dyslipidemia group included 305 males and 123 females with a mean age of 10.83 years and a mean BMI of 27.60 kg/m(2). Physical examination, and measurement of blood lipid, glucose and liver enzyme were taken. Carotid IMT was measured for 285 subjects., Result: (1) Hypertension was found in 12.5% (19/152) and 20.1% (86/428) patients in ortholiposis and dyslipidemia groups, respectively, with a significant difference (χ(2) = 4.362, P = 0.037). The OR was 1.760 with 95% confidence interval of 1.030 - 3.008. Higher prevalence of hypertension was found in patients with dyslipidemia. (2) The left, right and mean common carotid IMTs of dyslipidemia group were higher than those of ortholiposis group without significant difference (all P > 0.05). The left, right and mean internal carotid IMTs in dyslipidemia group were (0.66 ± 0.15) mm, (0.65 ± 0.15) mm and (0.65 ± 0.15) mm, respectively while these in ortholiposis group were (0.62 ± 0.13) mm, (0.60 ± 0.13) mm and (0.61 ± 0.12) mm, respectively (P < 0.05 for all). (3) Bivariate correlation analysis showed that systolic blood pressure was positively correlated with age, BMI, BMI Z score, waist circumference, hip circumference, uric acid, alanine transaminase, triglyceride, fasting insulin and insulin resistance index (P < 0.05 for all). Moreover, mean carotid and internal carotid IMTs were positively correlated with age, BMI, waist circumference, hip circumference, and triglyceride (all P < 0.05). Multiple linear regression analysis showed that hip circumference and insulin resistance index were independent determinants of systolic pressure. Waist circumference was independent determinant of mean common and internal carotid IMT and triglyceride was independent determinants of mean internal carotid IMT., Conclusion: (1) Vascular lesions, including hypertension and thicker tunica intima are common in obese children and adolescents. (2) Vascular lesions are closely related with dyslipidemia, and waist circumference and hypertriglyceridemia are the risk factors.

Objective: Numerous studies in children with growth hormone deficiency (GHD) show that recombinant human growth hormone (rhGH) treatment results in significant catch-up growth, but some papers reported that the children who underwent rhGH therapy might be at increased risk of diabetes. The aim of this study was to investigate the effects of rhGH treatment on blood glucose and insulin metabolism in children with GHD and the relationship between growth hormone (GH) and glucose homeostasis., Methods: In this study, 44 children with GHD treated with rhGH [0.1 U/(kgxd)] and age- and sex-matched 20 healthy children were enrolled. The GHD group included 28 males and 16 females aged from 4.5 to 16.5 years (mean 10.4 +/- 2.6 years), including 18 cases of complete GHD and 26 cases of partial GHD. The sexual development stage of all subjects was in Tanner I. Oral glucose tolerance tests (OGTT) were done, and body mass index (BMI), serum insulin-like growth factor-1 (IGF-1) level and insulin resistance by homeostasis model (HOMA-IR) were measured at the time of diagnosis and every 3 months after rhGH therapy. Continuous glucose monitoring system (CGMS) was applied for two cases with hyperglycemia., Results: (1) Fasting glucose and IGF-1 levels increased since 3 months of treatment and did not decrease since then. The levels of fasting glucose and IGF-1 at every time points of rhGH therapy were higher than the levels at the time of diagnosis (F = 6.81, P < 0.01; F = 7.31, P < 0.01, respectively). HOMA-IR and fasting insulin levels were increased since 3 and 9 months of treatment (P = 0.001 and P = 0.021, respectively). They decreased after 12 months of therapy and the levels at 18 months of therapy were similar to that at diagnosis. (2) Pearson correlation analysis showed that HOMA-IR was positively correlated with BMI, IGF-1 and the duration of treatment (r = 0.251, 0.437, 0.281, P < 0.01, respectively). The curve between HOMA-IR and duration of therapy was similar with parabola and the quadratic equation obtained was as follows: HOMA-IR = 1.5048 + 0.2177 x duration of therapy (months)-0.0103 x duration of therapy (months)(2) (r(2) = 0.147, F = 14.16, P < 0.01). (3) Two cases had transitory hyperglycemia. Their fasting glucose levels were all higher than 7.1 mmol/L. The glucose levels returned to normal after 1 month and 5 days respectively. OGTT and CGMS showed that their plasma glucose levels were normal after rhGH therapy was applied again., Conclusion: The children who underwent rhGH therapy may be at increased risk of insulin resistance (especially during the first year) and the therapy may even induce transitory glucose metabolic disorder in a very small proportion of patients. Circulating IGF-1 may participate in the control of insulin sensitivity and play an important role in the hormonal balance between GH and insulin. It may be necessary to monitor glucose metabolism and IGF-1 for all children who are treated with rhGH therapy.

Objectives: Metabolic syndrome (MS) in adolescents was reported to be closely associated with cardiovascular diseases in adulthood. However, no unified treatment measure for MS in adolescents is currently available. The aim of this study was to measure the changes of serum adiponectin levels, insulin sensitivity and other biochemical markers after metformin therapy in adolescents with MS, which might provide some information for set up a unified therapeutic measure for MS in adolescents., Methods: In this study, 348 moderately or severely obese adolescents and 24 non-obese healthy adolescents matched in age and sex were enrolled. The obese group included 208 males and 140 females aged from 7 to 16 years (11.5 +/- 2.1 years). Oral glucose tolerance test and biochemical markers measurement were done to all these subjects. Whole body insulin sensitivity index (WBISI), homeostasis model assessment-insulin resistance (HOMA-IR) and fasting serum adiponectin were compared among 36 adolescents with MS (who had two or three abnormalities of hyperglycosemia, hypertension or dyslipidemia), 61 simple obese subjects without abnormality of biochemical markers and 24 healthy controls. Moreover, the changes of WBISI, HOMA-IR and adiponectin levels in 20 cases with MS after metformin therapy for 3 months were measured., Results: (1) HOMA-IR in control group (1.3), simple obese group (2.3) and MS group (4.9) increased by turns (F = 54.08, P < 0.001). WBISI and serum adiponectin in control group, simple obese group and MS group decreased by turns with significant difference [89.6, 22.8 and 10.7, F = 30.06; (7.1 +/- 2.6), (5.9 +/- 1.9), (2.8 +/- 0.9) mg/L, F = 64.93; P < 0.01 for all]. (2) HOMA-IR after metformin therapy decreased [5.7 (1.9-12.4) vs. 2.9 (0.9-7.4), t = 5.05, P < 0.01]; while the serum adiponectin levels increased with significant differences [(3.0 +/- 0.9) mg/L vs. (6.1 +/- 1.9) mg/L, t = 6.19, P < 0.01]. Systolic blood pressure [(132.4 +/- 7.5) mm Hg vs. (116.6 +/- 9.1) mm Hg, t = 8.36, P < 0.01], 2-hour glucose [(8.2 +/- 2.9) mmol/L vs. (5.3 +/- 1.0) mmol/L, t = 3.96, P < 0.01], triglyceride [(2.8 +/- 1.2) mmol/L vs. (1.3 +/- 0.9) mmol/L, t = 4.22, P < 0.01], total cholesterol [(4.9 +/- 0.6) mmol/L vs. (4.0 +/- 0.6) mmol/L, t = 4.72, P < 0.01], alanine aminotransferase [80.5 (29.0-286.0) U/L vs. 56.0 (23.0-163.0) U/L, t = 3.80, P < 0.01]., Conclusion: Insulin sensitivity in adolescents with MS was lower than that of simple obese group. Metformin can improve or ameliorate adiponectin levels, insulin sensitivity and some clinical markers.

Objective: To evaluate the viral pathogen of pneumonia in children., Methods: A total of 13 642 cases of children pneumonia in 3 years were enrolled in this study. Antigens of viral pathogen in respiratory excretion, including respiratory syncytial virus (RSV), type 1, 2 and 3 parainfluenza virus, type A and B influenza virus, and adenovirus were detected by direct immunofluorescence method., Results: Viral pneumonia accounted for 34.3% of all cases, including 25.8% cases of RSV, 4.7% of parainfluenza virus, 2.4% of type A influenza virus, 0.2% of type B influenza virus and 1.3% of adenovirus. Coinfection was found in 20 cases, in which 17 cases (85%) were infected with RSV and another virus. Positive rates of RSV in children < or = 1 year, 1 to 3 years, and >3 years were 33.1%, 19.7% and 5.1% with a significant difference (chi(2)(trend)=763.4, P < 0.001). The positive rate of adenovirus in children < or =1 year (0.7%) was significantly lower than that in children aged 1 to 3 years and in children >3 years (2.3% and 2.5%) (all P<0.01). The positive rate of type A influenza virus in children aged 1 to 3 years was higher than that in children < or =1 year (chi(2)=18.2, P<0.01). Type 1 parainfluenza virus was found in 1.2% children aged 1 to 3 years with most prevalence (P<0.05). Infection rates of type 3 parainfluenza in children < or =1 year, 1 to 3 years, and >3 years were 4.7%, 3.2% and 1.4% respectively with a significant difference (chi(2)(trend)=52.4, P<0.01). Although there were some differences of infection rate of RSV in different years, it tended to increase from November to next April with a highest rate of 62.8%. Type 3 parainfluenza virus and Type A influenza virus were almost sporadic while type A influenza virus was epidemic in August 2003 with an infection rate of 15.7%., Conclusion: The highest infection rate of viral pathogen of pneumonia in children is RSV and the follows are parainfluenza, influenza and adenovirus in turn.

Objective: To study the epidemiolgy of respiratory syncytial virus (RSV) infection in children and its relations to climate factors in Hangzhou., Methods: Monthly positive rate of RSV in pneumonia inpatients and climate factor including mean air temperature, mean relative humidity and rainy days per month were continuously observed for 3 years. Correlation analysis for RSV positive rate and these three climate factors were performed using partial correlation, and regression methods between the positive rate and significant factor was done., Results: 13 642 cases were detected and 25.8% showed positive of RSV. The positive rate of RSV in children < or =1 years old, 1-3 years old, > 3 years old were 33.1%, 19.7% and 5.1% respectively with significant difference (chi2 = 763.7, P = 0.000). Rate of RSV infection was increased from December and kept in high level until May or April next year, but were varied at different years. Partial correlations between positive rate and rainy days, mean relative humidity, and mean air temperature per month were 0.32 (P= 0.066), -0.27 (P = 0.117) and -0.83 (P = 0.000) respectively. The regression equation of RSV positive rate and mean air temperature was: RSV positive rate (%) = 52.933 - 1.914 x mean air temperature (degrees C)., Conclusion: RSV was one of the main factors causing of pneumonia in children while the highest infectious rate was in children < or =1 year old and infectious rate reduced along with the increase of age. Low air temperature was the main factor affecting the epidemiology of RSV. RSV was prevalent both in spring and winter in Hangzhou area.

Objective: To investigate the relationship of serum dehydroepiandrosterone (DHEA) levels and female precocious puberty., Methods: The serum levels of DHEA and dehydroepiandrosterone sulfate (DHEAS) were measured by ELISA in 60 idiopathic central precocious puberty (ICPP) girls, 62 premature thelarche (PT) girls and 31 age-matched health prepuberty girls. Bone age,volume of uterus and ovary, DHEA and DHEAS were re-measured in 3, 12 months after treatment with Diphereline in ICPP girls., Result: (1) The Log(DHEA) and Log(DHEAS) were (0.81 +/-0.36)microg/L and (2.31 +/-0.31)microg/L in ICPP group, (0.72 +/-0.30)microg/L and (2.31 +/-0.28)mg/L in PT group, and (0.32 +/-0.26)microg/L and (2.16+/-0.27)microg/L in controls (P <0.05). However, no significant differences were found between ICPP and PT group (P >0.05). Moreover, the serum levels of DHEA and DHEAS in precocious puberty girls with Tanner III stage were significant higher than those with Tanner II stage (P <0.05). (2) With bivariate correlation analysis, Log(DHEA) was positively correlated with height, bone age, volume of uterus and ovary (r=0.429, 0.339, 0.217, 0.282; all P<0.05), while no significant correlation with Log(LH peak), Log(FSH peak) and BMI (r=0.135, -0.165, 0.059). Log(DHEAS) was positively correlated with height,bone age and volume of ovary (r=0.319, 0.210, 0.181; P <0.05), while no correlated with Log(LH peak), Log(FSH peak), volume of uterus and BMI (r=0.012, -0.173, 0.146 and 0.081 respectively). (3) Serum Log (DHEA) and Log(DHEAS) of 32 ICPP were decreased from (0.83 +/-0.35) microg/L and (2.27 +/-0.30)microg/L to (0.68 +/-0.44)microg/L and (2.11 +/-0.43)microg/L (P<0.05) 3 months after treatment. The serum Log(DHEA) and Log(DHEAS) in 12 months after treatment were (0.78 +/-0.30)microg/L and (2.40+/-0.34)microg/L, which was not significantly different with that before treatment (P>0.05). However, the volume of uterus and ovary, bone age/age in 12 months after treatment were significantly different with those before treatment (2.82 +/-1.52 compared with 1.09 +/-0.50 ml, 3.15 +/-1.13 compared with 1.18 +/-0.42 ml, 1.43 +/-0.23 compared with 1.25 +/-0.12, all P<0.05)., Conclusion: (1) The serum levels of DHEA and DHEAS are increased in precocious puberty girls with the development of Tanner stage. (2) Serum levels of DHEA and DHEAS are declined transiently when the hypothalamic-pituitary-gonadal axis is inhibited. (3) Serum DHEA is associated with the acceleration of growth and bone age in precocious puberty girls.

Objective: To analyze factors relevant to retarded intellectual development in infants born to mothers with autoimmune disease of thyroid., Methods: All the term newborns born to mothers with autoimmune thyroid disease (selection criteria) without asphyxia in all county, city, and provincial hospitals in Zhejiang province (except for Ningbo City) from July 2001 to June 2003 were enrolled through Zhejiang provincial neonatal disease screening network system. The control group was consisted of the neonates who were born to mothers without thyroid disease in these hospitals during the same period. Heel capillary blood samples were collected from the neonates older than 3 days in local hospitals and sent to the center of Zhejiang provincial neonatal disease screening network system. TSH levels were measured by Time Difference Fluorescent Analysis Device (1420 II type, EGG Company, US). If the level of TSH was higher than 9 mU/L, their mothers were called back to the center with their infants within 3 days. If the level of TSH was normal, they were called back to hospitals at age of 28 - 35 days of infants. The pattern of maternal thyroid disease, duration, thyroid function, the history of maternal drug administration, maternal age, gestational age and body weight of the neonates were recorded. The neonatal and maternal serum thyroid function tests were re-performed and the serum TPOAb, TGAb, TRAb and TSAb levels in both neonates and their mothers were measured as well. A 1-year follow-up study was done and all these subjects were investigated by means of Gesell development schedules by special investigators at the age of 1, 3, 6 and 12 months. The results were expressed as developmental quotient. Case-sectional study was performed. Statistical analyses were conducted using SPSS software. The multiple logistic regression analysis was used to analyze factors which might have effect on infantile personal-social ability, adaptive ability, gross motor ability or the fine-motor ability. One-way ANOVA was used to compare those five subfields ability followed by LSD multiple comparisons and Dunnet's C test was used when variances were not equal. Correlation analysis was used to compare the anti-thyroid antibody between neonates and their mothers., Results: Poor personal-social ability, adaptive ability, gross motor ability and fine motor ability of infants born to mothers with autoimmune thyroid diseases were found as compared to the infants born to healthy mothers (P < 0.01). Moreover, the infants born to mothers with Hashimoto's thyroiditis had significantly poorer fine motor ability and adaptive ability than those born to mothers with Grave's disease (P < 0.05). The Spearman correlation coefficients of TPOAb, TGAb, TRAb and TSAb were 0.636, 0.574, 0.619 and 0.473, respectively, and all the P values were lower than 0.01.The multifactor logistic regression analysis showed that infantile TPOAb levels and maternal TRAb levels were associated with infantile personal-social ability, adaptive ability, and gross motor; while maternal TPOAb levels and thyroid function during gestation were associated with infantile fine-motor ability (P < 0.05)., Conclusion: Maternal autoimmune thyroid diseases during pregnancy had adverse effects on intellectual development of infants. The maternal levels of TPOAb, TRAb and thyroid status were associated with the infantile personal-social ability, adaptive ability, gross motor and fine motor development. In order to reduce the effect on infant, it is necessary to treat adequately the maternal autoimmune thyroid diseases during pregnancy.

Objective: The prevalence of obesity and of type 2 diabetes mellitus in children have increased in the Chinese population over the past two decades, and thus diabetes prevention has become a major concern of public health agencies. Identification of individuals at risk for diabetes is an essential first step in designing and implementing intervention programs. Insulin resistance is the hallmark of the pathophysiology of type 2 diabetes mellitus. Subjects with hyperinsulinemia and impaired glucose tolerance are well accepted as being at high risk for diabetes. Acanthosis nigricans (AN) has been proposed as a reliable marker of hyperinsulinemia, but its utility for predicting hyperinsulinemia has not been systematically evaluated in obese children. In order to further explore the relationship between obese childhood with benign acanthosis nigricans and insulin resistance and type 2 diabetes mellitus, we examined 19 obese children with benign acanthosis nigricans., Methods: Nineteen of seventy six obese children (25%) with BMI over 25 enrolled in the Children' Hospital of Zhejiang University School of Medicine fromJune 1st to September 1st in 2003 were studied. Skin biopsies were performed in these 19 obese children with acanthosis nigricans for final diagnosis. Levels of glucose, insulin, and glucose/insulin ratio were measured on fasting blood specimens and anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index were examined. Oral glucose tolerance tests were also performed in these 19 children with benign acanthosis nigricans., Results: Anthropometric parameters including waist/hip ratio, fat mass, body fat percentage and body mass index as well as fasting insulin level in acanthosis nigricans group were significantly higher than that of healthy controls (P < 0.01). Fasting glucose to insulin ratio (FGIR) of these 19 obese children with benign acanthosis nigricans was 4.27 +/- 0.53, indicating apparent insulin resistance. One of them was diagnosed as type 2 diabetes mellitus and ten of them showed impaired oral glucose tolerance., Conclusion: Childhood benign acanthosis nigricans is tightly associated with obesity, hyperinsulinemia, insuline resistance and type 2 diabetes mellitus, and may be used as a reliable index of insulin resistance.

Objective: To evaluate the association between the methylenetetrahydrofolate reductase C/T polymorphism and the prevalence and course of asthma., Method: Genotypes were determined in 433 asthmatic patients and 1 249 healthy subjects by the polymerase chain reaction and restriction fragment length polymorphism method., Results: The frequencies of the three genotypes were 40.27% for CC, 48.44% for CT, 11.29% for TT and the frequency of allelic T was 35.51% in controls. The frequency of TT genotype in atopic asthmatic patients was significantly higher than that in controls (P = 0.026). The OR for the TT genotype compared with all CC and CT genotypes was 1.61 (95% CI 1.06 approximately 2.47)., Conclusion: These results imply that homozygosity for this common mutation significantly increases the risk of atopic asthma.