Characteristics of serum bile acids among healthy children in Zhejiang province / 中华儿科杂志

Objective: To characterize the serum bile acid profiles of healthy children in Zhejiang Province. Methods: A cross-sectional study was conducted on 245 healthy children who underwent imaging and laboratory biochemical tests during routine physical examinations at the Children's Hospital of Zhejiang University School of Medicine from January 2020 to July 2022. Overnight fasting venous blood samples were collected, and the concentrations of 18 individual bile acids in the serum were accurately quantitated using tandem mass spectrometry. The concentration difference of bile acid were compared between different genders and to explore the correlation between age and bile acid levels. Used the Mann-Whitney U test for intergroup comparison and Spearman test to correlation analysis. Results: A total of 245 health children with a age of 10 (8, 12) years including 125 boys and 120 girls. There were no significant differences in levels of total bile acids, primary and secondary bile acids, free and conjugated bile acids between the two gender groups (all P>0.05). The serum concentrations of ursodeoxycholic acid and glycoursodeoxycholic acid in girls were significantly higher than those in boys (199.0 (66.9, 276.5) vs. 154.7 (49.3, 205.0) nmol/L, 274.0 (64.8, 308.0) vs. 181.0 (43.8, 209.3) nmol/L, Z=2.06, 2.71, both P<0.05). The serum taurolithocholic acid in both boys and girls were positively correlated with age (r=0.31, 0.32, both P<0.05). The serum chenodeoxycholic acid and glycochenodeoxycholic acid in the boys group were positively correlated with age (r=0.20, 0.23, both P<0.05), whereas the serum tauroursodeoxycholic acid in the girls group was negatively correlated with age (r=-0.27, P<0.05), and the serum cholic acid was positively correlated with age (r=0.34, P<0.05). Conclusions: The total bile acid levels are relatively stable in healthy children in Zhejiang province. However, individual bile acids showed gender differences and were correlated with age.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Relationship between body mass index and sexual development in Chinese children / 中华儿科杂志

Objective: To investigate the relationship between body mass index (BMI) and sexual development in Chinese children. Methods: A nationwide multicenter and population-based large cross-sectional study was conducted in 13 provinces, autonomous regions and municipalities of China from January 2017 to December 2018. Data on sex, age, height, weight were collected, BMI was calculated and sexual characteristics were analyzed. The subjects were divided into four groups based on age, including ages 3-<6 years, 6-<10 years, 10-<15 years and 15-<18 years. Multiple Logistic regression models were used for evaluating the associations of BMI with sexual development in children. Dichotomous Logistic regression was used to compare the differences in the distribution of early and non-early puberty among normal weight, overweight and obese groups. Curves were drawn to analyze the relationship between the percentage of early puberty and BMI distribution in girls and boys at different Tanner stages. Results: A total of 208 179 healthy children (96 471 girls and 111 708 boys) were enrolled in this study. The OR values of B2, B3 and B4+ in overweight girls were 1.72 (95%CI: 1.56-1.89), 3.19 (95%CI: 2.86-3.57), 7.14 (95%CI: 6.33-8.05) and in obese girls were 2.05 (95%CI: 1.88-2.24), 4.98 (95%CI: 4.49-5.53), 11.21 (95%CI: 9.98-12.59), respectively; while the OR values of G2, G3, G4+ in overweight boys were 1.27 (95%CI: 1.17-1.38), 1.52 (95%CI: 1.36-1.70), 1.88 (95%CI: 1.66-2.14) and in obese boys were 1.27 (95%CI: 1.17-1.37), 1.59 (95%CI: 1.43-1.78), and 1.93 (95%CI: 1.70-2.18) (compared with normal weight Tanner 1 group,all P<0.01). Analysis in different age groups found that OR values of obese girls at B2 stage and boys at G2 stage were 2.02 (95%CI: 1.06-3.86) and 2.32 (95%CI:1.05-5.12) in preschool children aged 3-<6 years, respectively (both P<0.05). And in the age group of 6-10 years, overweight girls had a 5.45-fold risk and obese girls had a 12.54-fold risk of B3 stage compared to girls with normal BMI. Compared with normal weight children, the risk of early puberty was 2.67 times higher in overweight girls, 3.63 times higher in obese girls, and 1.22 times higher in overweight boys, 1.35 times higher in obese boys (all P<0.01). Among the children at each Tanner stages, the percentage of early puberty increased with the increase of BMI, from 5.7% (80/1 397), 16.1% (48/299), 13.8% (27/195) to 25.7% (198/769), 65.1% (209/321), 65.4% (157/240) in girls aged 8-<9, 10-<11 and 11-<12 years, and 6.6% (34/513), 18.7% (51/273), 21.6% (57/264) to 13.3% (96/722), 46.4% (140/302), 47.5% (105/221) in boys aged 9-<10, 12-<13 and 13-<14 years, respectively. Conclusions: BMI is positively correlated with sexual development in both Chinese boys and girls, and the correlation is stronger in girls. Obesity is a risk factor for precocious puberty in preschool children aged 3-<6 years, and 6-<10 years of age is a high risk period for early development in obese girls.

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients / 亚洲男科学杂志(英文版)

Persistent Müllerian duct syndrome (PMDS) is a rare clinically and genetically overlapping disorder caused by mutations in the anti-Müllerian hormone (AMH) gene or the anti-Müllerian hormone receptor type 2 (AMHR2) gene. Affected individuals present uterus and tubes in normally virilized males and are discovered unexpectedly during other surgeries. Since it is rare and complex, a definitive clinical diagnosis can be missed, and there are no guidelines regarding how to deal with the uterus. In the present study, exome sequencing and Sanger verification were performed for causal variants in 12 PMDS patients. Preoperative diagnoses were made by positive exome sequencing in 8 patients. Of them, 7 patients evoked on the basis of ultrasound indicating bilateral testes on the same side of the body. Twelve different AMH variants (2 frameshift/nonsense, 1 deletion, 8 missense, and 1 in-frame) in 9 patients and 6 different AMHR2 variants (5 missense and 1 splicing) in 3 patients were identified. Seven variants were classified as "pathogenic" or "likely pathogenic", and 4 of them were novel. All but two patients with AMH defects showed low serum AMH concentrations, but all patients with AMHR2 defects showed elevated AMH levels. During surgery, an abnormal vas deferens was observed in half of the patients. Eight patients underwent orchidopexy with uterine preservation. Of them, 2 patients presented complications including irreducible cryptorchidism, and 3 patients developed Müllerian remnant cysts. Three patients underwent subtotal hysterectomy. Of them, one patient had complication of injury to the vas deferens, and one had hemorrhage after operation. This is the first report of PMDS involving a large Chinese population. The present study not only expands the variation spectrum but also provides clinical experience about the management of the uterus.

Advances in the diagnosis and hormone replacement treatment of 46, XY disorders of sex development / 中华男科学杂志

Disorders of sex development (DSD) is defined as a congenital condition or atypical development of the chromosomal, gonadal, or anatomic sex. The diagnosis, gender assignment, and treatment of DSD require the guidance from experienced multidisciplinary teams. So far there has been no consensus about it in China. Due to dysgenetic gonads, defects in sex steroid biosynthesis or action, or gonadectomy during the prepubertal years, those with DSD suffer from hypogonadism. The hormone replacement therapy of DSD aims at general physiological health and long-term prognosis as well as the avoidance of unnecessary genital and gonadal surgery. This review focuses on the advances in the studies of the diagnosis and hormone replacement therapy of 46,XY DSD.

Effects of obesity on peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test and obesity-related hormones in girls with central precocious puberty / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the effects of obesity on the peak level of luteinizing hormone (LH) in the gonadotropin-releasing hormone (GnRH) agonist test and obesity-related hormones in girls with central precocious puberty (CPP).</p><p><b>METHODS</b>Three hundred and thirty-three girls with CPP who underwent the GnRH agonist test between 2012 and 2014 were classified into three groups: normal weight (n=123), overweight (n=108), and obesity (n=102), according to body mass index (BMI). The sexual development indices were compared between the three groups. Twenty girls were randomly selected from each group for evaluation of the serum levels of leptin, sex hormone binding globulin (SHBG), neurokinin B, and kisspeptin. The correlation of BMI with the levels of various hormones was assessed using Pearson correlation analysis.</p><p><b>RESULTS</b>There was no significant difference in mean age at diagnosis between the three groups; however, the bone age was significantly higher in the overweight and obesity groups than in the normal weight group (P<0.05). The peak level of LH in the GnRH agonist test and SHBG level in the normal weight group were significantly higher than those in the overweight and the obesity groups, while the serum levels of leptin and neurokinin B were significantly lower in the normal weight group than in the overweight and the obesity groups (P<0.05). BMI was negatively correlated with the peak level of LH in the GnRH agonist test and SHBG level (P<0.05), and positively correlated with the levels of leptin and neurokinin B (P<0.05).</p><p><b>CONCLUSIONS</b>The effects of BMI on the result of the GnRH agonist test and levels of obesity-related hormones should be taken into account in girls with precocious puberty.</p>

Diagnostic value of ultrasonographic examination for hepatic steatosis in obese children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To evaluate the sensitivity and specificity of hepatic ultrasonography (US) for the diagnosis of hepatic steatosis in obese children, using ¹H magnetic resonance spectroscopy (¹H MRS) as the reference standard.</p><p><b>METHODS</b>A total of 162 obese children with age of 10.5 ± 2.2 years and BMI of 28 ± 4 were enrolled in this study. They accepted hepatic US and (1)H MRS examinations. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of US were calculated for the overall presence of hepatic steatosis by comparison with ¹H MRS results.</p><p><b>RESULTS</b>Using quantitative criteria of liver fat content (LFC) >5% determined by (1)H MRS, 95 children(58.6%)were diagnosed as having hepatic steatosis. The sensitivity and specificity of US in diagnosing steatosis were 91.6% (87/95) and 50.7% (34/67) respectively, with PPV of 72.5% (87/120), and NPV of 81.0% (34/42). Considerable overlap in LFC measured by ¹H MRS was observed between different grades from US findings: absent (LFC interquartile range: 1.3%-3.9%), mild (2.4%-10.7%), moderate (7.1%-20.2%) and severe (7.6%-28.8%) steatosis.</p><p><b>CONCLUSIONS</b>The US can yield a high sensitivity and low specificity in the diagnosis of hepatic steatosis in obese children, suggesting it can be used as a screening tool for hepatic steatosis. To improve diagnostics, ¹H MRS is needed to determine LFC.</p>

A clinical follow-up study of premature thelarche in infants under two years of age / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical status and natural course of premature thelarche (PT) in infants under 2 years of age and to analyze the predictive factors for regression of thelarche.</p><p><b>METHODS</b>The clinical and laboratory data of 863 infants under 2 years of age, who visited the department of endocrinology in our hospital due to PT between October 2009 and September 2010, were analyzed. A a longitudinal follow-up study was performed.</p><p><b>RESULTS</b>Of the infants under 2 years of age with isolated PT, 89.3% showed a regression before the age of 3 years (mean 17±5.6 months), 10.7% had recurrent or persistent thelarche, with no regression after the age of 3 years, and some even developed into central precocious puberty. The independent predictive factors for regression of thelarche were Tanner stage at the first visit and whether baseline estradiol level had increased.</p><p><b>CONCLUSIONS</b>PT in infants under 2 years of age is not rare in the clinical setting, and it usually runs a self-limited course, subsiding before the age of 3 years. However, regular follow-ups should be performed for infants aged over 2 years with persistent thelarche.</p>

Non-high-density-cholesterol as a predictor of non-lipid cardiovascular disease risk factors in obese children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the role of non-high density lipoprotein cholesterol (non-HDL-C) in the assessment of cardiovascular disease (CVD) risk factors such as hypertension, pre-diabetes and diabetes in obese children.</p><p><b>METHODS</b>According to the presence of complications (hypertension, pre-diabetes and diabetes), 810 children with central obesity were divided into two groups: one group with complications (n=499) and one group without complications (n=311). One hundred and sixty-four age- and sex-matched children served as the control group. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to analyze the detection of non-lipid CVD risk factors by seven lipid markers.</p><p><b>RESULTS</b>The prevalence rates of hypertension and pre-diabetes were significantly higher in obese children with high non-HDL-C concentrations (≥3.76 mmol/L). After adjusting for waist circumference Z-scores, the area under the ROC curve for non-HDL-C was 0.680 to detect non-lipid CVD risk factors, while the areas for low-density lipoprotein cholesterol, total cholesterol and apoprotein B were 0.659, 0.669 and 0.647 respectively.</p><p><b>CONCLUSIONS</b>Compared with the other lipid markers, non-HDL-C is a better predictor for non-lipid CVD risk factors in obese children. Measurement of non-HDL-C concentations is recommended for obese children.</p>

Detection of thyroid antibodies in children with type 1 diabetes mellitus / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the prevalence of positive thyroid antibodies in children with type 1 diabetes mellitus (T1DM) and its influencing factors.</p><p><b>METHODS</b>The clinical data of T1DM children who were treated in the Children's Hospital of Zhejiang University from May 2005 to April 2011 were retrospectively studied. The relationships of thyroid globulin antibody (TGAb) and thyroid peroxidase antibody (TPOAb) with cytokines IL-2, IL-4, IL-6, IL-10, TNF and IFN-γ were evaluated, and the percentages of CD3+, CD4+ and CD8+ T-lymphocytes in peripheral blood were examined.</p><p><b>RESULTS</b>A total of 186 T1DM children with complete data of both TGAb and TPOAb were included in the study, among whom 143 with normal TGAb and TPOAb levels and 43 (23.1%) presented with positive thyroid antibody (including 21 cases with both positive TGAb and positive TPOAb). Eighteen cases (9.7%) were diagnosed as autoimmune polyglandular syndrome type 3 variant (APS3v). Significantly more patients in the positive thyroid antibody group had a family history of diabetes than in the negative thyroid antibody group (27.9% vs 14.7%; P<0.05). The average age of the positive thyroid antibody group was 10.1±3.2 years, which was significantly greater than that in the negative thyroid antibody group (8.1±4.0 years) (P<0.05). The IL-2 level (4.48 ±1.27 pg/mL vs 2.82 ±0.84 pg/mL, P<0.05) and the percentage of peripheral CD3+ T-lymphocyte[(61±11)% vs (66±11)%; P<0.05] were also different between the positive and negative thyroid antibody groups.</p><p><b>CONCLUSIONS</b>Genetic background and abnormal function of T-lymphocytes (especially higher IL-2 level) may be involved in the elevated prevalence of positive thyroid antibody in T1DM children.</p>

Study on physique index set for Chinese children and adolescents / 中华流行病学杂志

Objective To provide data as age-gender dependent mean,standard deviation and percentile on height,weight.waist circumference (WC),hip circumference (HC).body mass index (BMI),waist hip ratio (WHR),waist to height ratio (WHtR) among 7-16 year-olds Chinese children and adolescents,towards setting up diagnostic criteria on metabolic syndrome for them.Methods A representative sample involvng 22 197 children and adolescence aged 7 to 16 years were randomly surveyed and they were from 6 representative geographical areas,including Beijing.Tianjin? Hangzhou,Shanghai,Chongqing and Nanning.A total of 21858 had available data,with male/female ratio as:11460/10 398.Using the standard methods,we measured height,weight.WC,HC,BMI.WHtR and other data in all age groups.Physique indexes among different geographic regions (North.Mid-west and East) were compared.Results (1) Both male and female showed an inaeasing trend of height.weight,waist circumference,hip circumference and BMI along with the increase of age.WHR of girls decreased gradually from 0.84 to 0.76 went from 7 to 16 years old while WHR of boys changed from 0.87 to 0.81 accordingly.(2) WHtR was rarely affected by age.It fluctuated between 0.42-0.43 in all girls and 0.44-0.45 in boys less than 11 years.WHtR of boys older than 12 years showed a slight decline from 0.45 to 0.42 of WHtR.(3) The average height,weight,BMI of children and adolescents from the northem regions (Beijing,Tianjin) were significantly higher than that of the mid-western (Chongqing,Nanning) and the eastem regions (Shanghai,Hangzhou) (P＜0.001 ),while those from the mid-western region were slightly higher than that of the eastern region (P＜0.05) in each of the age group.Conclusion Reference values and percentile curves for WC and WHtR of Chinese children and adolescents were provided.For the assessment of central obesity.WHtR had the advantages of relative stability and small degree of variation and rarely affected by age and gender,when compared with WC.and could be used as an simple index to reflect the central obesity of children and adolescents.

Survey on the levels of lipids in school-aged children of Beijing, Tianjin, Hangzhou, Shanghai,Chongqing and Nanning cities / 中华流行病学杂志

Objective To investigate the lipid levels of Han ethnicity Chinese children at school-age,to provide objective data for the formulation of prevention and management strategy regarding dyslipidemia among children and adolescents.Methods 20 191 children (with 10 669 boys and 9522 girls) aged 7 to 16 years old from 6 representative geographical areas,including Beijing,Tianjin,Hangzhou,Shanghai,Chongqing and Nanning,were surveyed in a randomly selected clustered sample in China.Data on fasting blood triglyceride (TG),total cholesterol (TC),lowdensity lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were measured.Non-high-density lipoprotein cholesterol (non-HDL-C) levels were calculated with data collection,entry,and collation were under the same criteria.Results (1) In the 7-16 year-old group,TG (P95) fluctuated between 1.26 mmol/L and 1.88 mmol/L,while TC (P95) was between 4.80 mmol/L and 5.46 mmol/L.LDL-C(P95) was between 2.67 mmol/L and 3.27 mmol/L while non-HDL-C (P95) was between 3.36 mmol/L and 3.91mmol/L,sugesting that age did not seem to be an affecting factor for the lipid level (P＞0.05).The level of HDL-C (P5) fluctuated bctwcen 1.08 mmol/L and 0.83 mmol/L,and the dependability analysis on HDL-C and age showed statistically significant difference (P＜0.01,r=-0.274).(2) In the 7-9 year-old group,the levels ofTG,TC,LDL-C and non-HDL-C of boys were lower but the HDL-C level was higher than in girls.However,in the 10-16 year-old group,the levels of five lipids of boys were all lower than in girls,with all the differences statistically significant (P＜0.05).(3) The levels of TG,TC,LDL-C and non-HDL-C in the obese group were significantly higher than those in non-obesity group,as HDL-C was significantly lower than in non-obese group(P＜0.01).Incidence rates of single and multiple dyslipidemia in obese group were significantly higher than in non-obese group (P＜0.01).(4) Grouped by region,the abnormal rates of TG were descending,with the ranking as North (10.4％),Midwest (9.7％) and East (8.3％),while the abnormal rates of TC were descending with the ranking as Midwest (6.0％),North (5.2％)and East (4.8％).The abnormal rates of LDL-C were descending as the ranking of North (3.1％),East (2.6％) and Midwest (0.9％),with the abnormal rates of non-HDL-C were descending as Midwest (6.5％),North(4.2％)and East (3.6％).The abnormal rates of HDL-C were descending as Midwess (14.2％),North(5.7％) and East(5.5％).All the differences in the above-said items were statistically significant (P＜0.05).(5) According to the standards of hyperlipidemia formulated by the American Academy of Pediatrics,the incidence rates of abnormal TG,TC,LDL-C,non-HDL-C,HDL-C were 9.4％,5.4％,2.2％,4.8％,8.6％ respectively.Conclusion (1) Levels of lipids were affected by many factors,but age was not one of them in children and adolescents.However,HDL-C was declining along with the increase of age,to some extent.(2)Girls had a relatively protective tendency through the increasing HDL-C level when they entered the puberty years.(3)Lipids levels in non-obese group were significantly better than the obese group.(4)The lipids levels of children and adolescents in the Eastern region of the country were better than that in the northern and mid-western areas.

Quantitative assessment of intrahepatic fat content in children and adolescents with non-alcoholic fatty liver disease / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To quantitatively evaluate clinical significance of intrahepatic fat (IHF) content in children and adolescents with non-alcoholic fatty liver disease (NAFLD).</p><p><b>METHODS</b>Ninety-three obese children were enrolled in this study. Physical parameters, liver function, serum lipids, glycemic and insulin related parameters were measured. Liver B-mode ultrasound (US) examination was performed. IHF content was quantified by 1H magnetic resonance spectroscopy (1H MRS). Three subgroups were classified according to the conditional diagnostic criteria for obese children: simple obesity (n=31), NAFLD-1 (US fatty liver and normal alanine aminotransterase, n=33) and NAFLD-2 (US fatty liver and elevated alanine aminotransterase, n=29). Twenty healthy age- and sex-matched children served as a control group. IHF content among the four groups was compared. The relationship of IHF content with other common clinical laboratory parameters and independent factors influencing increased IHF content were investigated.</p><p><b>RESULTS</b>IHF content measured by 1H MRS was 0.80% (0.4%-1.0%), 2.9% (1.7%-4.30%), 14.0% (7.2%-17.5%) and 18.8% (14.0%-29.1%) respectively in the control, simple obese, NAFLD-1 and NAFLD-2 groups. There were significant differences in IHF content between the groups. Univariate correlation analysis demonstrated that IHF content was positively correlated with waist circumference, hip circumference, waisttohip ratio, body mass index, systolic blood pressure, diastolic blood pressure, alanine aminotransferase, aspartate aminoreansferase, γ-glutamic acid transtetase, triglyceride, low-density lipoprotein, OGTT 2-hour plasma glucose, fasting insulin, 2-hour insulin and insulin resisfence, and negatively correlated with high-density lipoprotein. Multivariate linear regression analysis demonstrated three independent risk factors for increased IHF content: increased waist circumference, increased 2-hour plasma glucose and decreased high-density lipoprotein levels.</p><p><b>CONCLUSIONS</b>IHF content determined by 1H MRS can reflect early hepatic fatty infiltration and is closely related to the occurrence and progress of NAFLD in obese children and adolescents. There is a significant correlation between most of common clinical laboratory parameters and IHF content, and waist circumference, high-density lipoprotein and OGTT 2-hour plasma glucose are independent factors impacting IHF content.</p>

Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/lysophosphatidylcholine lipoapoptosis pathway in hepatocytes / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the potential preventive effects of metformin on non-alcoholic fatty liver disease (NAFLD) and roles of phospholipase A2/lysophosphatidylcholine pathway in hepatocyte lipoapoptosis in a rat NAFLD model induced by high-fat diet.</p><p><b>METHOD</b>Male SD rats (n = 36) were randomly divided into three groups with 12 rats in each and treated with different diet and drugs: group I: ordinary diet, group II: high-fat diet, group III: high-fat diet and metformin. Ten weeks later, the rats were sacrificed and their body weight and liver weight were obtained, serum lipid metabolic indexes, insulin resistance indexes and secretory phospholipase A2 (sPLA2), lysophosphatidylcholine (LPC) levels and other parameters were measured. Phospholipase A2 mRNA expression levels were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). In addition, the histological changes of liver tissue were analyzed.</p><p><b>RESULT</b>Compared to ordinary diet group, the rat's liver weight (g) (16.92 ± 2.49 vs. 12.16 ± 0.82), hepatic exponent (0.034 ± 0.004 vs. 0.026 ± 0.002), serum alanine aminotransferase (U/L) (45.43 ± 9.73 vs. 29.42 ± 6.73), triglyceride (mmol/L) (1.22 ± 0.24 vs. 0.85 ± 0.19), cholesterol (mmol/L) (2.00 ± 0.37 vs. 1.49 ± 0.33), lipoprotein(a) (mmol/L) (743.86 ± 32.19 vs. 648.42 ± 78.87), low-density lipoprotein (mmol/L) (1.31 ± 0.35 vs. 0.65 ± 0.22), insulin (mmol/L) (22.16 ± 5.16 vs. 16.86 ± 5.35), insulin resistance index(5.10 ± 1.45 vs. 3.59 ± 0.99), free fatty acid (mEq/L) (0.57 ± 0.10 vs. 0.35 ± 0.07), sPLA2 [µmol/(min·ml)] (0.130 ± 0.016 vs. 0.098 ± 0.024), lysophosphatidylcholine (µmol/L) (707.26 ± 92.48 vs. 508.87 ± 96.50), leptin (pg/ml (80.08 ± 17.73 vs. 65.11 ± 14.09), liver triglyceride (mg/g) (13.57 ± 0.65 vs. 12.03 ± 1.14), cholesterol (mg/g) (2.19 ± 0.15 vs. 1.94 ± 0.12) (P < 0.05) were significantly increased in high-fat diet group. Moreover, degree of hepatic steatosis was significantly higher and sPLA2 mRNA expression was also significantly increased. Secondly, in comparison with high-fat diet group, early metformin treatment significantly reduced the rat's body weight (g) (394.40 ± 33.10 vs. 491.86 ± 26.45), liver weight (g) (13.24 ± 1.16 vs. 16.92 ± 2.49), serum alanine aminotransferase (U/L) (30.40 ± 4.50 vs. 45.43 ± 9.73), triglyceride (mmol/L) (0.75 ± 0.19 vs. 1.22 ± 0.24), cholesterol (mmol/L) (1.61 ± 0.38 vs. 2.00 ± 0.37), insulin (mmol/L) (16.96 ± 5.60 vs. 22.16 ± 5.16), insulin resistance index (3.75 ± 1.41 vs. 5.10 ± 1.45), sPLA2 [µmol/(min·ml)] (0.101 ± 0.009 vs. 0.130 ± 0.016), lysophosphatidylcholine (µmol/L) (549.92 ± 90.78 vs. 707.26 ± 92.48), liver triglyceride (mg/g) (11.23 ± 1.70 vs. 13.57 ± 0.65), cholesterol (mg/g) (1.97 ± 0.20 vs. 2.19 ± 0.15) (P < 0.05). Moreover, degree of hepatic steatosis was significantly lower and sPLA2 mRNA expression was also significantly decreased by metformin. Thirdly, when compared to ordinary diet group, metformin could also significantly increase hepatic exponent (0.034 ± 0.004 vs. 0.026 ± 0.002) and low-density lipoprotein level (mmol/L) (0.96 ± 0.34 vs. 0.65 ± 0.22) (P < 0.05). However, it had no impact on hepatic steatosis and sPLA2 expression (P > 0.05).</p><p><b>CONCLUSION</b>It was indicated that metformin has potent effects on improving lipid metabolism and insulin resistance in high-fat diet induced non-alcoholic fatty liver disease rat model. The liver protective mechanisms of metformin in non-alcoholic fatty liver disease may be contributed to down-regulation of secretory phospholipase A2 mRNA expression, decrease in serum secretory phospholipase A2, lysophosphatidylcholine, lower inflammatory response and protect mitochondrial function.</p>

The prevalence of type 2 diabetes mellitus and prediabetes in children / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the incident and prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in obese children in the last ten years.</p><p><b>METHODS</b>The clinical data of hospitalized children with newly diagnosed diabetes mellitus (DM) or obesity between October 2000 and September 2011 were retrospectively studied.</p><p><b>RESULTS</b>A total of 503 newly onset cases were diagnosed as DM in the past ten years, of which 31 were diagnosed as T2DM. The prevalence of T2DM in the second five-year duration increased significantly compared with that in the first five-year duration (0.18‰ vs 0.05‰; P<0.01). The number of cases of type 1 diabetes mellitus (T1DM) and T2DM increased by 1.35 fold and 4.20 fold, respectively in the second five-year duration. A total of 1301 obese patients received oral glucose tolerance tests, and 29 cases were diagnosed with T2DM and 255 cases with prediabetes. Of the 255 cases of prediabetes, 133 had dyslipidemia, 138 had non-alcoholic fatty liver disease and 53 had hypertension.</p><p><b>CONCLUSIONS</b>The prevalence rates of T1DM and T2DM increased significantly in the last 5 years. The prevalence of T2DM increased more significantly than T1DM. There was a higher prevalence of prediabetes in obese children. Childhood obesity predicts a higher risk of T2DM and cardiovascular disease in the future.</p>

Relationship between dyslipidemia and early vascular lesions in obese children and adolescents / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>(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.</p><p><b>CONCLUSION</b>(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.</p>

Relationship between sleep duration and metabolic syndrome in obese children / 中华流行病学杂志

Objective To investigate the relationship between sleep duration and metabolic syndrome in obese children.Methods Sleep time was recorded and metabolic syndrome (MS) diagnostic criteria as blood pressure,body mass index (BMI) were measured among 311 obese children.The children were divided into 4 groups by sleep time while normal-weight children served as the control group.A disorderly multi-classification logistic regression method was used.Results Statistically,significant differences were found in the levels of BMI,blood pressure,fasting blood glucose and postprandial 2 h glucose and the incidence rates of abnormality on MS,blood pressure,fasting insulin,and BMI≥30 kg/m2 between the group with daily sleep time less than 8 h and the group with daily sleep time no less than 10 h (P＜0.05).Date from logistic regression analysis revealed that the reduction of sleep time was the risk factor of MS in obese children.Conclusion Insufficient sleep could greatly contribute to the occurrence of MS in obese children.

Clinical analysis of 13 cases with growth hormone deficiency combined with pituitary stalk interruption / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics of the patients with pituitary stalk interruption syndrome (PSIS), and to achieve better comprehension of this disease.</p><p><b>METHOD</b>Data of 13 patients with PSIS were retrospectively analyzed for the clinical, laboratory and imaging features.</p><p><b>RESULT</b>All the 13 patients (9 male, 4 female) had the chief complaint of growth retardation, 81.5 - 135.0 cm in body height, which were minus two standard deviations below the average of the normal children of same age and same sex. GH stimulated peak levels were all below 5 microg/L; Among them, one was accompanied by delayed sexual development, one by central diabetes insipidus, one was complicated with central hypothyroidism and one was accompanied by central adrenocortical hypofunction.</p><p><b>CONCLUSION</b>The most remarkable clinical manifestations of patients with PSIS were growth retardation, partial or complete adenohypophyseal dysfunction. MRI revealed absence of pituitary stalk or anterior pituitary hypoplasia with ectopic posterior pituitary gland.</p>

A 10-year review of childhood type 1 diabetes mellitus and the clinical value of interleukin-10 in diabetic ketoacidosis / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To review the incident status of childhood type 1 diabetes mellitus hospitalized in the Children's Hospital of Zhejiang University School of Medicine from 1999 to 2009 and to explore the clinical value of IL-10 in diabetic ketoacidosis.</p><p><b>METHODS</b>The clinical data of 263 children with type 1 diabetes mellitus hospitalized in the Children's Hospital of Zhejiang University School of Medicine from January 1999 to February 2009 were retrospectively reviewed. Serum lipid levels were measured in 48 children with type 1 diabetes mellitus and in 24 healthy children. The diabetic children were classified into two subgroups, with or without ketoacidosis. Serum lipid and cytokines levels were compared.</p><p><b>RESULTS</b>Childhood type 1 diabetes mellitus was common in females (56.3%). The peak incident age of the disease was between 6 and 11.9 years. Diabetic ketoacidosis was as the presenting symptom for the first visit in 86 cases (32.7%). The levels of serum lipid, blood glucose and HbA1c in diabetic children with ketoacidosis were significantly higher than those without ketoacidosis (P<0.05). Logistic analysis demonstrated that the increased levels of blood glucose, serum lipid and HbA1c were risk factors for diabetic ketoacidosis. The level of serum IL-10 in diabetic children with ketoacidosis was significantly higher than that in patients without ketoacidosis (P<0.01), while there were no differences in serum levels IL-2, IL4, IL-6, TNF-α and IFN-γ between them. Serum levels IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in diabetic children were significantly higher than those in healthy children (P<0.01).</p><p><b>CONCLUSIONS</b>Ketoacidosis is a common acute complication of type 1 diabetes mellitus. The disorders of glucose and lipid metabolism are the risk factors for ketoacidosis in diabetic children. IL-10 may be a sensitive index of diabetic ketoacidosis in children with type 1 diabetes mellitus.</p>

Relationship between nonalcoholic fatty liver disease and cardiovascular disease in children with obesity / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the relationship between nonalcoholic fatty liver disease (NAFLD) and the development of cardiovascular disease (CVD) in children with obesity.</p><p><b>METHODS</b>Two hundred and thirty-one obese children and 24 non-obese children as control were enrolled. Body mass index (BMI), serum triglyceride, blood pressure, liver function, and carotid artery intima-media thickness (IMT) were examined. The obese children were classified into two subgroups according to the diagnosis criteria: group 1 without liver disorder (OCWLD group, n=75) and group 2 with NAFLD (NAFLD group, n=156). The incidences of hyperlipidemia and hypertension, carotid artery intima-media thickness (IMT) and biochemical indicators were compared in the three groups.</p><p><b>RESULTS</b>The NAFLD group showed significantly greater carotid IMT (0.066+/-0.021 cm) than the OCWLD (0.060+/-0.011 cm) and control groups (0.037+/-0.007 cm) (P<0.05). The OCWLD group had also thicker IMT than the control group (P<0.05). The incidences of hyperlipidemia and hypertension were 39.7% and 40.4%, respectively in the NAFLD group, which were significantly higher than those in the OCWLD (22.7% and 29.3% respectively)and control groups (4.2% and 12.6% respectively) (P<0.05). The liner stepwise regression analysis showed that the IMT was positively correlated with BMI, NAFLD and ALT (adjusted R2=0.316, P<0.01).</p><p><b>CONCLUSIONS</b>NAFLD may be not only an early marker but also an early state of CVD in obese children. Early diagnosis and treatment of NAFLD is crucial for the prevention of the occurrence and development of CVD.</p>