TG/HDL-C Ratio for Predicting Insulin Resistance in Obese Children from Beijing, China.

BACKGROUND: International studies have found that the blood triglycerides to highdensity lipoproteins (TG/HDL-C) ratio predicted insulin resistance in children with overweight and obesity. However, there is a lack of such reports on children from China. OBJECTIVE: The objective of this study is to explore the ability of the TG/HDL-C ratio as a blood biomarker for insulin resistance (IR) in obese children in Beijing. METHODS: We evaluated 262 children with obesity from our paediatric outpatient clinic in a cross-sectional study. Detailed medical histories of all children were ascertained, as were clinical examination and laboratory test results, including blood lipids, fasting glucose, insulin, and glycated haemoglobin. We divided them into age groups of 6-9 and 10-13.5 years and then into IR and non-IR groups based on the homeostatic model assessment for IR (HOMA-IR). Analysis was accomplished with SPSS software (version 22.0). RESULTS: The TG/HDL-C ratio was higher in children with IR in the 6-9 and 10-13.5-year age groups (p < 0.001). Univariate and multivariate analyses displayed that the TG/HDL-C ratio and HOMA-IR were correlated in the 6-9 and 10-13.5-year-old groups (p < 0.001). In the 6-9-yearold group, IR identified by a TG/HDL-C ratio ≥ 0.645 had a sensitivity, specificity, and an area under the curve (AUC) of 79.1%, 60.9%, and 0.734, respectively. In the 10-13.5-year-old group, IR identified by a TG/HDL-C ratio ≥ 0.725 had a sensitivity, specificity, and an AUC of 79.4%, 62.9%, and 0.724, respectively. CONCLUSION: We showed the application of the TG/HDL-C ratio to predict insulin resistance in obese children in Beijing with different diagnostic thresholds based on age (6-9-year-old group with TG/HDL-C ≥ 0.645; 10-13.5-year-old group with TG/HDL-C ≥ 0.725), which were lower compared with the diagnostic threshold for insulin resistance in children reported in other countries.

BMI at different childhood age periods associated with cardiometabolic disorders in young adulthood.

OBJECTIVE: The aim of this study was to investigate when the association between childhood obesity and adult cardiometabolic disorders starts to be operative. METHODS: The study cohort included 811 participants who had data on blood pressure, lipid profile, fasting blood glucose, fasting insulin, or alanine aminotransferase in adulthood and had at least one measurement of BMI in childhood. RESULTS: Childhood BMI z score was significantly associated with increased risks of ≥1 cardiometabolic disorders, ≥2 cardiometabolic disorders, and elevated blood pressure in adulthood for age groups of 6 to 9 years, 10 to 12 years, 13 to 15 years, and 16 to 18 years, after adjustment for covariates. For low high-density lipoprotein cholesterol, significant associations were observed for age groups of 10 to 12 years, 13 to 15 years, and 16 to 18 years. For elevated triglyceride and elevated alanine aminotransferase, significant associations were observed for age groups of 13 to 15 years and 16 to 18 years. For insulin resistance, significant associations were observed for age groups of 10 to 12 years and 16 to 18 years. For elevated total cholesterol, elevated low-density lipoprotein cholesterol, or elevated fasting blood glucose, no association was observed in any age group. CONCLUSIONS: The association between childhood BMI and adult cardiometabolic disorders begins to be operative from early life. These results support universal screening of childhood obesity starting at an early age.

[Acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty: a randomized controlled trial].

OBJECTIVE: To observe the efficacy and safety of acupuncture combined with auricular point sticking for girls aged 3-8 years with incomplete precocious puberty (IPP). METHODS: Sixty girls with IPP were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases were eliminated). The girls in the control group were treated with healthy diet and proper exercise for 12 weeks. On the basis of the treatment in the control group, the girls in the observation group were treated with acupuncture combined with auricular point sticking. The acupuncture was applied at Sanyinjiao (SP 6), Guanyuan (CV 4), Guilai (ST 29), etc., the needles were retained for 20 min, acupuncture was given twice a week (once every 3 days). The auricular point sticking was applied at Luanchao (TF2), Neishengzhiqi (TF2), Neifenmi (CO18), Yuanzhong (AT2,3,4i), etc., twice a week. The treatment was given for 12 weeks. Before treatment, after treatment and in follow-up after 12 weeks of treatment completion, the Tanner stage of breast, serum contents of sex hormone (luteinizing hormone [LH], follicle-stimulating hormone [FSH], estradiol [E2]) were observed. The ovarian volume, the number of follicles with diameter>4 mm, and the uterine volume were measured by abdominal color Doppler ultrasound. In addition, the safety of the observation group was evaluated. RESULTS: Compared with before treatment, the Tanner stage of breast in the observation group was improved after treatment and in follow-up (P<0.05); after treatment and in follow-up, the Tanner stage of breast in the observation group was better than that in the control group (P<0.05). Compared with before treatment, the serum levels of LH and E2 in the observation group were increased (P<0.05), and the volume of bilateral ovaries was larger (P<0.05) in follow-up. Compared with before treatment, the serum contents of LH, FSH and E2 in the control group were increased (P<0.05), the volume of bilateral ovaries was larger (P<0.05), and the number of follicles was increased (P<0.05) after treatment and in follow-up. The serum levels of LH, FSH and E2 in the observation group were lower than those in the control group (P<0.05), the volume of bilateral ovaries was smaller than that in the control group (P<0.05), and the number of follicles was lower than that in the control group (P<0.05). Compared with before treatment, the uterine volume in the two groups was larger in follow-up (P<0.05). There was no statistically significant difference between the two groups after treatment and in follow-up (P>0.05). During the treatment, 3 cases in the observation group had slight abdominal pain and subcutaneous blood stasis, without serious adverse reactions. CONCLUSION: Acupuncture combined with auricular point sticking could improve the Tanner stage of breast, reduce the level of sex hormone, slow down the development and maturation of ovary and follicle, and control the degree and speed of sexual development in girls aged 3-8 years with IPP.

Ovarian juvenile granulosa cell tumors with Ollier's disease in children with IDH1 gene somatic mutation.

Objective: The aim of this study was to explore the symptoms, treatment, and pathogenesis of ovarian juvenile granulosa cell tumors with Ollier's disease in children. Methods: From October 2019 to October 2020, clinical data were retrospectively analyzed for one case of ovarian juvenile granulosa cell tumors with Ollier's disease. Whole-exome sequencing and Sanger sequencing were used to detect gene mutation in ovarian tumor and chondroma tissue. NADP-dependent isocitrate dehydrogenase-1 (IDH1) and S6 ribosomal protein expression levels in cells transfected with wild-type or mutant plasmid were analyzed by Western blot. Results: The 4-year-old female showed multiple skeletal deformities, bilateral breast development with chromatosis, and vulvar discharge. Sex hormone assay suggested that estradiol and prolactin were elevated, and the x-ray of limbs suggested enchondroma. Pelvic ultrasound and abdominal CT revealed a right ovarian solid mass. Pathologic examination of the right ovarian solid mass showed a juvenile granulosa cell type. A c.394C>T (p. Arg132Cys) mutation of the IDH1 gene was detected in both the ovarian juvenile granulosa cell tumors and enchondroma. Transfection of HeLa cells with either WT or Mut plasmid caused 4.46- or 3.77-fold overexpression of IDH1 gene compared to non-transfected control cells, respectively. R132C mutation inhibited the phosphorylation of S6 ribosomal protein, which is central to the mTOR pathway. Postoperatively, estradiol and prolactin levels fell to values normal for her age and bilateral breast gradual retraction. Conclusion: The incidence of ovarian juvenile granulosa cell tumors with Ollier's disease in children may be caused by generalized mesodermal dysplasia; IDH1 gene mutation may play a facilitated role in this process. Surgical operation is the main treatment. We suggest that patients with ovarian juvenile granulosa cell tumors and Ollier's disease should undergo regular investigation.

Differential diagnosis of precocious puberty in girls during the COVID-19 pandemic: a pilot study.

BACKGROUND: To investigate the differential diagnosis of girls aged 6 to 8 years with idiopathic premature thelarche (IPT) and central precocious puberty (CPP) during the COVID-19 pandemic. We explored predicted adult height (PAH) discrepancy to guide appropriate diagnosis and treatment. METHODS: From January 2020 to December 2021, Chinese girls aged 6 to 8 years with precocious puberty were recruited. They were divided into IPT and CPP groups. Clinical characteristics, including height, weight, body mass index (BMI), basal luteinizing hormone (LH), oestradiol, uterine length and volume, follicle numbers (d > 4 mm) and bone age (BA) were recorded. We analysed differential diagnosis and PAH discrepancy in both groups. Binary logistic regression analysis was used to explore risk factors for CPP, and receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of related indexes. RESULTS: Sixty patients, including 40 girls with IPT and 20 girls with CPP, were recruited. The prevalence of overweight and obesity in the entire cohort was 25% (15/60) and was significantly higher in IPT than CPP, 32.5% (13/40) vs. 10% (2/20), respectively (P=0.045). There were significant differences in LH, uterine volume, follicle numbers and BA (P<0.05). The impaired PAH of IPT and CPP was 0.01 ± 1.19 SD and 0.62 ± 0.94 SD with significant differences (P=0.047). Logistic regression analysis showed that LH and follicle numbers were independent risk factors for CPP. The ROC curve showed that the area under the curve (AUC) of LH and follicle numbers were 0.823 and 0.697. The sensitivity and specificity of LH with a cut off of 0.285 IU/L were 78.9% and 77.8%. The sensitivity and specificity of follicle numbers with a cut off of 3.5 were 89.5% and 52.8%. CONCLUSION: The prevalence of overweight and obesity in 6- to 8-year-old girls with precocious puberty was high. Auxological data should not be used in the differential diagnosis of IPT and CPP. Basal LH above 0.285 IU/L and follicle numbers greater than 4 were important features suggestive of CPP. PAH was impaired in individuals with CPP, but it was not impaired in individuals with IPT.

[Effect of transcutaneous electrical acupoint stimulation combined with auricular acupressure on sexual hormone level and gonadal development in girls with precocious puberty].

OBJECTIVE: To explore the effect of transcutaneous electrical acupoint stimulation (TEAS) combined with auricular acupressure on serum sexual hormone level, and the ovarian, follicular and uterine development in the girls with precocious puberty. METHODS: Sixty girls with precocious puberty were randomly divided into a control group (30 cases, 2 cases dropped off) and a treatment group (30 cases, 3 cases dropped off). In both the control group and the treatment group, the healthy life-style intervention was provided for 12 weeks. Besides, in the treatment group, TEAS was delivered for 20 minutes each time, twice a week; and bilateral auricular acupressure was combined. The duration of treatment was 12 weeks. The levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E2), as well as ovarian volume, maximum follicular diameter and uterine volume before and after treatment were detected, and the safety was evaluated separately. RESULTS: Compared with before treatment, the contents of serum LH and FSH were increased (P<0.05), and the ovarian volume and the maximum follicle diameter were increased (P<0.05) in the control group after treatment; the contents of serum FSH and E2 were decresed (P<0.05), and the maximum follicular diameter was reduced significantly (P<0.05) in the treatment group after treatment. Compared with the control group, the contents of serum LH, FSH and E2 were decreased (P<0.05), while the ovarian volume and the maximum follicle diameter were decreased (P<0.05) in the treatment group after treatment. CONCLUSION: TEAS combined with auricular acupressure can effectively decrease the level of sex hormone, improve the ovarian and uterine development and retard the gonadal development. Such combined therapy is of high safety and conductive to regulating the development for the girls with precocious puberty.

Simple Method to Predict Insulin Resistance in Children Aged 6-12 Years by Using Machine Learning.

Background: Due to the increasing insulin resistance (IR) in childhood, rates of diabetes and cardiovascular disease may rise in the future and seriously threaten the healthy development of children. Finding an easy way to predict IR in children can help pediatricians to identify these children in time and intervene appropriately, which is particularly important for practitioners in primary health care. Patients and Methods: Seventeen features from 503 children 6-12 years old were collected. We defined IR by HOMA-IR greater than 3.0, thus classifying children with IR and those without IR. Data were preprocessed by multivariate imputation and oversampling to resolve missing values and data imbalances; then, recursive feature elimination was applied to further select features of interest, and 5 machine learning methods-namely, logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), and gradient boosting with categorical features support (CatBoost)-were used for model training. We tested the trained models on an external test set containing information from 133 children, from which performance metrics were extracted and the optimal model was selected. Results: After feature selection, the numbers of chosen features for the LR, SVM, RF, XGBoost, and CatBoost models were 6, 9, 10, 14, and 6, respectively. Among them, glucose, waist circumference, and age were chosen as predictors by most of the models. Finally, all 5 models achieved good performance on the external test set. Both XGBoost and CatBoost had the same AUC (0.85), which was highest among those of all models. Their accuracy, sensitivity, precision, and F1 scores were also close, but the specificity of XGBoost reached 0.79, which was significantly higher than that of CatBoost, so XGBoost was chosen as the optimal model. Conclusion: The model developed herein has a good predictive ability for IR in children 6-12 years old and can be clinically applied to help pediatricians identify children with IR in a simple and inexpensive way.

[Effects of electroacupuncture on sexual development and ovarian estrogen receptor ß expression in female adolescent obese rats].

OBJECTIVE: To observe the effect of electroacupuncture on sexual development and ovarian estrogen receptor ß(ER-ß) expression in female adolescent obese rats induced by high-fat diet, so as to explore its underlying mechanisms of improving adolescent obesity. METHODS: Female SD rats (age of 21 days) were randomly divided into control, model and acupuncture groups, with 6 rats in each group. The obese model was established by feeding high-fat diet for 6 weeks. Rats of the acupuncture group received electroacupuncture(2 Hz, 0.5-1.2 mA)stimulation at bilateral "Sanyinjiao"(SP6), "Fenglong"(ST40) and "Zusanli"(ST36) for 30 min, once a day for 14 days. The body mass and abdominal circumference of rats were measured before and after treatment. The contents of serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were detected by ELISA. The number of corpus luteum and follicle were observed by HE staining. The expression levels of ER-ß mRNA and protein in ovary were detected by fluorescence quantitative PCR and Western blot, respectively. RESULTS: Compared with the control group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-ß mRNA and protein in ovary were significantly increased (P<0.05)in the model group, while the number of mature follicles and corpus luteum increased significantly. Compared with the model group, the body mass and abdominal circumference, the contents of serum FSH and E2, and the expression levels of ER-ß mRNA and protein in ovary were significantly decreased (P<0.05) in the acupuncture group, while the number of mature follicles and corpus luteum decreased significantly. CONCLUSION: Electroacupuncture can effectively improve the levels of sex hormone and the development of ovary, down-regulate the expression levels of ER-ß mRNA and protein in ovary, so as to regulate the process of sexual development of female adolescent obese rats induced by high-fat diet.

Associations between body mass index in different childhood age periods and hyperuricemia in young adulthood: the China Health and Nutrition Survey cohort study.

BACKGROUND: Few studies have evaluated the specific age period in childhood when the association of body mass index with adult hyperuricemia begins to be operative. This study aimed to examine the associations between body mass index in different childhood age periods and the risk of adult hyperuricemia in China. METHODS: The study cohort from the China Health and Nutrition Survey included 676 participants who were aged ≥ 18 years and had data on uric acid in 2009 with at least one measurement of body mass index in childhood surveys before 2009. There were 357, 365, 358, 427, and 432 observations in childhood age groups of ≤ 5 years, 6-9 years, 10-12 years, 13-15 years, and 16-18 years, respectively. Body mass index Z score was calculated based on 2000 Center for Disease Control and Prevention growth charts for the United States. RESULTS: Childhood body mass index Z scores measured at age ≤ 5 years, 6-9 years, 10-12 years, and 13-15 years had no statistical association with adult uric acid. In comparison, childhood body mass index Z scores measured at age 16-18 years were significantly associated with adult uric acid (ß = 11.539, P = 0.007), and the strength of association was stronger in girls (ß = 18.565, P = 0.002) than in boys (ß = 9.209, P = 0.087). In addition, childhood body mass index Z scores measured at age 16-18 years were significantly associated with an increased risk of adult hyperuricemia (odds ratio = 1.323, 95% confidence interval = 1.003-1.746, P = 0.048), but not for other age groups. CONCLUSION: The association between childhood body mass index and young adulthood hyperuricemia was influenced by childhood age.

Circular RNA has Circ 001372-Reduced Inflammation in Ovalbumin-Induced Asthma Through Sirt1/NFAT5 Signaling Pathway by miRNA-128-3p.

In this study, we sought to investigate the prospective role of circ 001372 in modifying inflammation in ovalbumin-induced asthma. In the vivo model of asthma, the serum of circ 001372 was reduced. Down-regulation of circ 001372 increased inflammation reaction (TNF-α, IL-1ß, IL-6, and IL-18) and induced COX-2 and iNOS protein expression in vitro model through activation of NFAT5 and suppression of Sirt1. Up-regulation of circ 001372 decreased inflammation reaction (TNF-α, IL-1ß, IL-6, and IL-18) in vitro model through inactivation of NFAT5 and induction of Sirt1 by miRNA-128-3p. The miRNA-128-3p lowered the effects of circ 001372 on inflammation in vitro model. The Sirt1 inhibitor reduced the effects of circ 001372 on inflammation in vitro model. Our results revealed the serum of circ 001372 against inflammation in ovalbumin-induced asthma through Sirt1/NFAT5 by miRNA-128-3p.

Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

Context: Long-acting recombinant human growth hormone (rhGH) has transformed growth hormone deficiency (GHD) treatment. However, the possibility and rationality for flexible time regimen are pending. Objective: We studied the efficacy of biweekly versus weekly PEGylated rhGH (PEG-rhGH) therapy in GHD children. Design Setting and Patients: This multicenter, phase IV trial with a non-inferiority threshold ≥20% enrolled 585 Tanner stage I GHD children. Intervention: Subjects randomly received 0.20 mg/kg once-weekly or biweekly PEG-rhGH, or 0.25 mg/kg.w rhGH once daily for 26 weeks. Main Outcome Measure: The primary outcome was height SD scores for chronological age (HtSDSCA) at week 26 and safety measurements including adverse events (AEs), IGF-2, and IGFBP-2 changes. Results: At week 26, the median HtSDSCA changed from -2.75, -2.82, and -2.78 to -2.31, -2.43, and -2.28 with weekly and biweekly PEG-rhGH, and daily rhGH, respectively. The difference in HtSDSCA was 0.17 ± 0.28 between weekly and biweekly PEG-rhGH, and 0.17 ± 0.27 between daily rhGH and biweekly PEG-rhGH, failing the non-inferiority threshold. Nevertheless, the height velocity of children receiving biweekly PEG-rhGH reached 76.42%-90.34% and 76.08%-90.60% that of children receiving weekly PEG-rhGH and daily rhGH, respectively. The rate of AEs was comparable among the groups. No statistical difference was observed in IGF-2 and IGFBP-2 levels among the groups. IGFBP-2 levels decreased over time in all groups, with no notable difference in IGF-2 and IGFBP-2 changes among the three treatment groups. Conclusions: Although notably promoted height velocity, biweekly PEG-rhGH failed the non-inferiority threshold as compared with either weekly PEG-rhGH or daily rhGH. Compared with short-term rhGH, long-acting PEG-rhGH did not significantly increase tumor-associated IGF-2 and IGFBP-2 expressions. Clinical Trial Registration: clinicaltrials.gov, identifier NCT02976675.

Molecular genetic analysis and growth hormone response in patients with syndromic short stature.

BACKGROUND: Syndromic short stature is a genetic and phenotypic heterogeneous disorder with multiple causes. This study aims to identify genetic causes in patients with syndromic short stature of unknown cause and evaluate the efficacy of the growth hormone response. METHODS: Trio-whole-exome sequencing was applied to identify pathogenic gene mutations in seven patents with short stature, multiple malformations, and/or intellectual disability. Whole-genome low-coverage sequencing was also performed to identify copy number variants in three patients with concurrent intellectual disability. Recombinant human growth hormone was administered to improve height in patients with an identified cause of syndromic short stature. RESULTS: Of the seven patients, three pathogenic/likely pathogenic gene mutations, including one FGFR3 mutation (c.1620C>A p.N540K), one novel GNAS mutation (c.2288C>T p.A763V), and one novel TRPS1 mutation (c.2527_c.2528dupTA p.S843fsX72), were identified in three patients. No copy number variants were identified in the three patients with concurrent intellectual disability. The proband with an FGFR3 mutation, a female 4 and 3/12 years of age, was diagnosed with hypochondroplasia. Long-acting growth hormone improved her height from 85.8 cm [- 5.05 standard deviation (SD)] to 100.4 cm (- 4.02 SD), and her increased height SD score (SDS) was 1.03 after 25 months of treatment. The proband with a GNAS mutation, a female 12 and 9/12 years of age, was diagnosed with pseudohypoparathyroidism Ia. After 14 months of treatment with short-acting growth hormone, her height improved from 139.3 cm (- 2.69 SD) to 145.0 cm (- 2.36 SD), and her increased height SDS was 0.33. CONCLUSIONS: Trio-whole-exome sequencing was an important approach to confirm genetic disorders in patients with syndromic short stature of unknown etiology. Short-term growth hormone was effective in improving height in patients with hypochondroplasia and pseudohypoparathyroidism Ia.

Genotype-Phenotype Analysis of 8q24.3 Duplication and 21q22.3 Deletion in a Chinese Patient and Literature Review.

INTRODUCTION: Copy number variants (CNVs) are responsible for many patients with short stature of unknown etiology. This study aims to analyze clinical phenotypes and identify pathogenic CNVs in a patient with short stature, intellectual disability, craniofacial deformities, and anal imperforation. METHODS: G-banded karyotyping and chromosomal microarray analysis (CMA) was used on the patient to identify pathogenic causes. Fluorescence in situ hybridization (FISH) was applied to explore the abnormal genetic origin. Literatures were searched using identified CNVs as keywords in the PubMed database to perform genotype-phenotype analysis. RESULTS: Cytogenetic analysis revealed a normal karyotype 46,XY. CMA detected a 6.1 Mb duplication at 8q24.3 and a 3.6 Mb deletion at 21q22.3. FISH confirmed that the abnormal chromosomes were inherited from paternal balanced translocation. We compared phenotypes of our patient with 6 patients with 8q24.3 duplication and 7 cases with 21q22.3 deletion respectively. CONCLUSIONS: A novel 8q24.3 duplication and 21q22.3 deletion was identified in a Chinese patient. Genotype-phenotype analysis demonstrated that patients with 8q24.3 duplication and 21q22.3 deletion had specific facial features, intellectual disability, short stature, and multiple malformations.

Corrigendum: Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial.

[This corrects the article DOI: 10.3389/fendo.2021.779365.].

Acupuncture Improving Early Sexual Development of Girls with Peripheral Precocious Puberty: A Prospective Cohort Study.

OBJECTIVE: To study primarily on the effect of acupuncture on breast Tanner stage, serum sex hormone level, and TCM symptom scores in girls with peripheral precocious puberty (PPP). METHODS: 19 eligible patients diagnosed with PPP received acupuncture intervention for 12 weeks, twice a week for 12 weeks, 24 sessions of acupuncture treatment in all, and then follow-up for 12 weeks. The primary outcome was the change in serum luteinizing hormone (LH) level, follicle-stimulating hormone (FSH) level, and breast Tanner stage at 12-week treatment and 12-week follow-up. Serum estradiol (E2) level and TCM symptom scores were also assessed. RESULTS: Nineteen patients with peripheral precocious puberty were treated with acupuncture. After the 12-week acupuncture intervention, the serum LH level, breast Tanner stage, and TCM symptom scores decreased significantly compared with baseline (P < 0.05); the serum FSH and E2 level did not change significantly after the 12-week treatment (P > 0.05). After the 12-week follow-up, breast Tanner stage and TCM symptom scores decreased significantly compared with baseline (P < 0.05), and there was no statistical difference between serum sex hormone (LH, FSH, and E2) level and baseline level (P > 0.05). During the period of acupuncture treatment, no side effects or serious adverse events occurred. CONCLUSIONS: Acupuncture is effective in regulating the hormone level and controlling early development process. It may be a viable alternative to the treatment of peripheral precocious puberty in girls. However, further randomized controlled trials are needed.

[Analysis of clinical phenotypes and KCNJ2 gene mutations in a Chinese pedigree affected with Andersen-Tawil syndrome].

OBJECTIVE: To analyze the clinical phenotypes of a pedigree affected with periodic paralysis and explore its molecular basis. METHODS: Clinical data and peripheral blood samples of the pedigree were collected. The proband and his father both complained of periodic paralysis and dysmorphic features. The exome of the proband was screened using Roche NimbleGen probes, and the results were confirmed by Sanger sequencing. Suspected mutations were subjected to bioinformatic and gene-disease correlation analysis. RESULTS: A c.653G>A (p.R218Q) mutation of the KCNJ2 gene was detected in both the proband and his father. Bioinformatics analysis suggested it to be pathogenic. CONCLUSION: The clinical manifestation of the pedigree was suggestive of Andersen-Tawil syndrome. KCNJ2 c.653G>A (p.R218Q) was the pathogenic mutation in this pedigree.

Genotype-Phenotype Analysis, Neuropsychological Assessment, and Growth Hormone Response in a Patient with 18p Deletion Syndrome.

18p deletion syndrome is a rare chromosomal disease caused by deletion of the short arm of chromosome 18. By using cytogenetic and SNP array analysis, we identified a girl with 18p deletion syndrome exhibiting craniofacial anomalies, intellectual disability, and short stature. G-banding analysis of metaphase cells revealed an abnormal karyotype 46,XX,del(18)(p10). Further, SNP array detected a 15.3-Mb deletion at 18p11.21p11.32 (chr18:12842-15375878) including 61 OMIM genes. Genotype-phenotype correlation analysis showed that clinical manifestations of the patient were correlated with LAMA1, TWSG1, and GNAL deletions. Her neuropsychological assessment test demonstrated delay in most cognitive functions including impaired mathematics, linguistic skills, visual motor perception, respond speed, and executive function. Meanwhile, her integrated visual and auditory continuous performance test (IVA-CPT) indicated a severe comprehensive attention deficit. At age 7 and 1/12 years, her height was 110.8 cm (-2.5 SD height for age). Growth hormone (GH) treatment was initiated. After 27 months treatment, her height was increased to 129.6 cm (-1.0 SD height for age) at 9 and 4/12 years, indicating an effective response to GH treatment.

[Analysis of clinical phenotypes and genetic variations in a Chinese family affected with craniofacial and skeletal deformities].

OBJECTIVE: To identify pathogenic mutation in a pedigree affected with craniofacial and skeletal abnormalities featuring an autosomal dominant inheritance. METHODS: Clinical data and peripheral venous blood samples of the pedigree were collected. A total of 326 exons of skeletal disease-related genes were screened using Roche NimbleGen probes, and the results were confirmed by Sanger sequencing. Suspected variants were analyzed by bioinformatic software. RESULTS: A novel heterozygous mutation c.480C>A (p.160K>N) of HDAC4, the pathogenic gene for brachydactyly mental retardation syndrome, was found in the affected proband, his father and uncle. The proband and his father also carried a novel heterozygous c.880-882delAAG (p.294delK) mutation of TRPS1, the pathogenic gene for tricho-rhino-phalangeal syndrome. Bioinformatic analysis suggested that both mutations are pathogenic. In addition, three novel genetic variants, namely c.4817G>A (p.1606S>L) of MLL2, c.83A>G (p.28H>R) of TP63, and c.1712G>C (p.571T>S) of ERCC2, were also identified in this family. CONCLUSION: The HDAC4 c.480C>A (p.160K>N) mutation probably underlies the disease in this pedigree, while the TRPS1 c.880-882delAAG (p.294delK) mutation may be related with certain features of the affected family members. Genetic analysis has facilitated the diagnosis of this complex disease.

[Metabolic syndrome in overweight and obese schoolchildren in Beijing].

OBJECTIVE: To determine the prevalence and clinical phenotype of metabolic syndrome among overweight and obese schoolchildren in Beijing, and to compare the rates of diagnosis made according to the criteria of the National Cholesterol Education Program (NCEP) of the United States and International Diabetes Federation (IDF). METHODS: Based on Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study with body mass index (BMI), waist circumference (WC) and blood pressure measured, the overweight and obese children were screened among nearly 20 000 children 6-18 years of age in Beijing by Chinese BMI cutoffs for schoolchildren (7-18 years) and the US 2000 CDC Growth Charts--the 85th and 95th percentile (6 years) and were enrolled as the study population. Simultaneously a group of children with normal BMI were selected as the control group and based on the international method of age grouping, each of the above groups was divided further into 4 sub-groups in terms of age: 6-9, 10-12, 13-15 and 16-18 years old, respectively. Fasting plasma glucose (FPG) and insulin (FINS), serum high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) were examined. HOMA-IR index was calculated for estimating individual insulin resistance. A child who met any three or more of the following five criteria, according to NCEP definition, was diagnosed as MS. A diagnosis of MS using IDF definition required abdominal obesity plus any two or more of the other four criteria: (1) abnormal obesity: WC > or = P(90); (2) elevated BPs: SBP/DBP > or = P(90); (3) low HDL-C: HDL-C < 1.03 mmol/L (40 mg/dl); (4) high TG: TG > or = 1.24 mmol/L (110 mg/dl); (5) impaired fasting glucose (IFG): FPG > or = 5.6 mmol/L (100 mg/dl). RESULTS: The prevalence rates of MS by NCEP definition were: 0.9%, 7.6% and 29.8% in the normal weight (control group), overweight and obese children, respectively, which were higher than the rates diagnosed by IDF definition with 0.1%, 5.2% and 28.6% in the three groups. The prevalence rates of individual MS component among obese children were: 81.6% for abnormal obesity, 47.7% for elevated BPs, 35.6% for high TG, 16.9% for low HDL-C, and 13.4% for IFG. Elevated BPs (29.8%), abnormal obesity (27.4%) and high TG (26.0%) were the leading three abnormalities among overweight children. With the increase of BMI, the clustering of MS components and insulin resistance (HOMA-IR) were remarkably increased. HOMA-IR significantly increased as the number of MS component increased. CONCLUSIONS: MS has been in an epidemic status among the obese schoolchildren in Beijing. Abnormal obesity, elevated BPs and high TG were the three most common metabolic abnormalities for overweight and obese children. The prevalence rates of MS by NCEP definition in the present study was higher than those diagnosed by using IDF definition.