[Characteristics of serum bile acids among healthy children in Zhejiang province].

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.

[A clinical challenge of evaluation and management in children with genetic obesity].

Obesity is a growing global public health problem, while 40%-70% of obesity is determined by genetic factors. This article focuses on the classification, disease characteristics, diagnosis and progressive treatment of childhood genetic obesity. The prevention and control of childhood genetic obesity requires early detection of obese individuals and early screening of obesity causes. At the same time, clinicians are advised to propose individualized therapy and intervention measures based on multi-disciplinary opinions to improve the health of genetic obese children.

[Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development].

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].

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.

[The construction of comprehensive stroke prevention and control system requires attention to the precise policies of young stroke].

Youth is the core force of social and economic development, once the occurrence of youth stroke will place a heavy burden on society and family. However, the prevention and control of stroke in China is mainly aimed at middle-aged and elderly patients, the part of young stroke is relatively easy to be ignored. This article focuses on the characteristics, research progress, prevention and control status of young stroke, pointing out the importance of centering on the prevention and treatment of young stroke. At the same time, it hopes that the industry can concentrate on the prevention and treatment of young stroke, making precise policies in the future, and developing secondary prevention guidelines for the causes or risk factors of young stroke, so as to improve comprehensive stroke prevention and control system. On this basis, the health level of the whole population will be improved, and the life expectancy of residents will be extended, thus promoting the realization of the strategic goal of "Healthy China 2030".

[Survey of height and weight of children and adolescents at different Tanner stages in urban China].

Objective: To investigate the status of height and weight of 3-18-year-old children and adolescents in urban China, and to provide a basis for establishing puberty phase specific curves for age-specific height and age-specific weight. Methods: A cross-sectional survey of 218 185 children and adolescents aged 3-18 years in urban China was conducted by using the method of stratified random cluster sampling from January 2017 to December 2019. The sampling areas included 12 provinces municipalities in China and autonomous regions in total. Data were collected on weight, height, waist circumference, hip circumference and secondary sexual characteristics. The generalized additive model for location, scale, and shape (GAMLSS) was employed to establish percentile reference values and growth curves of height and weight for boys and girls aged 3-18 years. Wilcoxon rank sum test was applied to compare the P50 value of height and weight between children of each Tanner stage and children of the same age ignoring the different puberty phase. Results: The 3rd, 50th, and 97th percentile curves for height and weight for age were developed for boys and girls aged 3-18 years. The 3rd, 50th, and 97th percentile curves for age-specific height and age-specific weight for each puberty phase were developed for boys and girls. Compared with all children ignoring the different puberty phase, boys aged 9 and over and girls aged 7 and over who are at Tanner stage 1 showed shorter height and lighter weight than those of the same age group (all P<0.01), the difference ranges of height at P50 are -4.0 to -0.6 cm for boys, and -4.4 to 0.5 cm for girls; the difference ranges of weight are -4.8 to 0.4 kg for boys, and -4.0 to -0.3 kg for girls; children at Tanner stage 2 & 3 initially were taller and heavier than those of the same age group; and later grew shorter and lighter than those of the same age group, the two sets of curves cross over; boys aged 16 and under and girl aged under 14 who are at Tanner stage 4 were taller and heavier than those of the same age group (all P<0.01), the difference ranges of height at P50 are 0.2 to 10.0 cm for boys, and 0.2 to 9.4 cm for girls; the difference ranges of weight at P50 are 0.7 to 10.9 kg for boys, and 1.0 to 11.2 kg for girls, and the differences showed narrowing trend with age. Conclusion: The puberty phase specific growth curves of age-specific height and age-specific weight for boys and girls aged 3-18 years are established, it is useful for clinical work to evaluate physical development of children at different puberty phases.

[Changing prevalence of overweight and obesity among Chinese children aged 6-15 from 2009-2019].

Objective: To analyze the trends of overweight and obesity prevalence in Chinese children, aged from 6 to 15 years old among 4 provinces and cities from 2009 to 2019. Methods: Reviewed the national multi-center epidemiological survey data of children from the National Key Technology R&D Program of China during the Eleventh Five-Year Plan (2009 to 2010) and the National Key Research and Development Program of China during the Thirteenth Five-Year Plan (2017 to 2019). The participants' data were selected from four provinces,municipalities and autonomous region,including Beijing, Tianjin (Northern region), Zhejiang (Eastern region), and Guangxi (Southern region). Totally 14 597 pairs of 6-15 year-old children were surveyed. According to the body mass index (BMI) and standard deviation score (SDS) of children among different genders, ages, and regions, t test or chi-square test was used to evaluate the changes in overweight and obesity over a 10-year span. Results: Totally 7 721 pairs of boys and 6 876 pairs of girls were collectted in this study, whose mean age was (10.7±2.5) years. In the past 10 years, the overall BMISDS were 0.39±1.24 and 0.36±1.31 and the overall obesity rate were 11.8% (n=1 773) anel 12.5% (n=1 813) of children in the 4 administrative regions did not have statistically significant differences (all P>0.05). However, the overall overweight rate rose from 17.1% (n=2 496) to 19.1% (n=2 781) (χ²=18.657, P<0.01), and the average annual growth rate was 0.20%. The BMISDS in the Eastern region increased from 0.10±1.07 to 0.19±1.22 (t=-4.095, P<0.01), and the overweight rate and obesity rate increased by 3.8% (n=202) and 3.1% (n=169) respectively (both P<0.01); the BMISDS in the Northern region and the obesity rate did not have statistically significant differences(all P>0.05), but the overweight rate rose from 20.5% (n=1 233) to 22.8% (n=1 365) significantly (χ²=7.431, P<0.01); BMISDS in the Southern region was significantly decreased from 0.30±1.19 to 0.09±1.25 (t=1.426, P<0.01), and the rate of obesity decreased from 9.8% (n=315) to7.9% (n=256) (χ²=6.46, P<0.05), the overweight rate was not stafistically significant (P=0.10), respectively. The obesity rate of boys had risen from 16.4% (n=1 265) to 18.2% (1 407) (χ²=8.997, P<0.01) in the past 10 years, and the overweight rate had risen from 18.0% (n=1 393) to 20.5% (n=1 579) (χ²=14.26, P<0.01). The overweight+obesity rate rose from 34.4% (n=2 658) to 38.7% (n=2 986) (χ²=29.859, P<0.01), and the weight problem in the age group of 8 to 11 years was particularly severe (all P<0.01). The obesity rate of girls dropped from 6.8% (n=468) to 5.9% (n=406) (χ²=4.546, P<0.05), the overweight rate rose from 16.0% (n=1 103) to 17.5% (n=1 202) (χ²=5.006, P<0.05), and the overall overweight+obesity rate rose from 22.8% (n=1 571) to 23.4% (n=1 608) (χ²=0.53, P>0.05). Conclusions: The growth rate of obesity among children in China had slowed down from 2009 to 2019, but the overweight rate was still on the rise. The overall base of overweight and obesity population continued to expand. The weight problem of peri-adolescent boys was particularly prominent. The current status of obesity epidemics in different regions, ages, and genders are significantly different and had their own characteristics. It is necessary to establish a personalized prevention and control strategy.

[Pseudohypoparathyroidism and GNAS gene defects: clinical evaluation and molecular analysis in 20 children].

Objective: To analyze the patients' clinical and genetic characteristics with pseudohypoparathyroidism (PHP) and investigate the correlation between clinical phenotypes and genotypes. Methods: Twenty PHP patients were ascertained at Children's Hospital Zhejiang University School of Medicine from January 2011 to July 2020. Clinical manifestation, laboratory examination and gene test results were retrospectively analyzed. Results: In these twenty patients, eighteen cases showed resistance to parathyroid hormone (PTH) and thirteen cases had Albright's hereditary osteodystrophy (AHO) phenotype. Gene abnormalities were found in all the twenty PHP patients, which included seven patients with GNAS gene variations (six frameshifts and one missense) and thirteen patients with GNAS gene methylation defects. Moreover, twelve children with both PTH resistance and AHO phenotype were clinically diagnosed as PHP-Ⅰa, meanwhile, seven carried GNAS variations and five had methylation abnormalities with a correct diagnosis of PHP-Ⅰb. Conclusions: Patients with AHO phenotype and PTH resistance may have a high genetic diagnosis rate. Because PHP-Ⅰb clinical phenotype may be similar to PHP-Ⅰa, early genetic detection is required for the differential diagnosis. In addition, children without PTH resistance should also be followed up regularly, which may help the early diagnosis.