Gender Difference and Changes in the Prevalence of Obesity Over Time in Children Under 12 Years Old: A Meta-analysis.

Objective: Evaluating changes over time in the odds of obesity according to sex. Methods: PubMed, Embase, Cochrane Library, and China National Knowledge Database were searched for relevant studies. Full-text studies evaluating the influence of sex on obesity were analyzed. We used R 3.4.3 to assess the impact of results in the selected studies, calculated pooled prevalence and odds ratio (OR) with their respective 95% confidence intervals (CIs). P<0.10 and I2>50% indicated high heterogeneity, and the random-effects model was used, otherwise, the fixed-effects model was used. Results: The included studies reported the prevalence of obesity in children covering 1987-2017 intervals. The pooled prevalence of obesity in boy and girl groups were 0.13 (95% CI: 0.08, 0.20) and 0.10 (95% CI: 0.07, 0.13). In the analysis of the boy group, the pooled OR in earlier time (1987-2013) vs. recent time (2011-2017) was 0.98 (95% CI: 0.76, 1.26). The estimated OR for girls in earlier vs. recent time was 1.01 (95% CI: 0.80, 1.28). In the analysis of studies with follow-up period ≥ 10 years, the pooled OR for obesity in earlier vs. recent time period was 0.99 (95% CI: 0.76, 1.30). For those with follow-up period < 10 years, the pooled OR in earlier vs. recent time period was 0.94 (95% CI: 0.57, 1.54). Conclusions: Comprehensive measurements are required to control obesity among children albeit with nonsignificant gender difference and time trend for obesity rates in children.

Two novel heterozygous variants in RecA2 domain of the DHX37 cause 46,XY gonadal dysgenesis and testicular regression syndrome.

INTRODUCTION: The pathogenic variants in DEAH-box RNA helicase DHX37 are one of the major causes of 46,XY gonadal dysgenesis and TRS. To date, only 13 different missense variants have been reported. We report two additional cases with different clinical presentation carrying two novel variants in the DHX37 gene. CASE PRESENTATION AND RESULTS: Case 1 (4.4-year-old boy), presented with significant micropenis and cryptorchidism and was diagnosed as TRS. Case 2 (13.5-year-old girl), had a 46,XY karyotype with female external genitalia and was diagnosed as GD. Two novel DHX37 variants affecting the RecA2 domain, p.G478R and p.L627F, were identified in these cases. Both variants identified in the probands were also present in their unaffected mother. DISCUSSION/CONCLUSION: Our findings broaden the variant spectrum of DHX37 in 46,XY DSD individuals.

Corrigendum: Association of polymicrobial interactions with dental caries development and prevention.

[This corrects the article DOI: 10.3389/fmicb.2023.1162380.].

Association of polymicrobial interactions with dental caries development and prevention.

Dental caries is a common oral disease. In many cases, disruption of the ecological balance of the oral cavity can result in the occurrence of dental caries. There are many cariogenic microbiota and factors, and their identification allows us to take corresponding prevention and control measures. With the development of microbiology, the caries-causing bacteria have evolved from the traditional single Streptococcus mutans to the discovery of oral symbiotic bacteria. Thus it is necessary to systematically organized the association of polymicrobial interactions with dental caries development. In terms of ecology, caries occurs due to an ecological imbalance of the microbiota, caused by the growth and reproduction of cariogenic microbiota due to external factors or the disruption of homeostasis by one's own factors. To reduce the occurrence of dental caries effectively, and considering the latest scientific viewpoints, caries may be viewed from the perspective of ecology, and preventive measures can be taken; hence, this article systematically summarizes the prevention and treatment of dental caries from the aspects of ecological perspectives, in particular the ecological biofilm formation, bacterial quorum sensing, the main cariogenic microbiota, and preventive measures.

Mannose-Binding Lectin Reduces Oxidized Low-Density Lipoprotein Induced Vascular Endothelial Cells Injury by Inhibiting LOX1-ox-LDL Binding and Modulating Autophagy.

Objective: To investigate the role of mannose-binding lectin (MBL) in modulating autophagy and protecting endothelial cells (ECs) from oxidized low-density lipoprotein (ox-LDL)-induced injury. Methods: Serum MBL concentration and carotid intima-media thickness (cIMT) were measured in 94 obese and 105 healthy children. ECs were transfected with MBL over-expression plasmid, LOX1 was knocked-down to explore the protective role of MBL in ox-LDL induced ECs injury. Dendritic cells (DCs) were co-cultured with ECs, and inflammatory factors, DC maturation, and autophagy was assessed. WT and ApoE-/- mice were fed with a high fat diet (HFD) with or without MBL-adenovirus injection for 16 weeks and aortic vascular endothelial tissue was isolated, then atherosclerotic plaque, cell injury and autophagy were analyzed. Results: Serum MBL concentration in obese children was lower than healthy controls and was negatively correlated with cIMT. The uptake of ox-LDL was decreased in LOX1 knock-down ECs. MBL over-expression in vitro inhibited LOX1-ox-LDL binding. Both LOX1 knock-down and MBL over-expression can ameliorate EC autophagy and cell injury. MBL over-expression in vivo alleviated atherosclerotic plaque formation, influenced DC maturation and down-regulated IL-6, IL-12, and TNF-a levels. Conclusions: MBL exerts a protective role in ox-LDL-induced EC injury by modulating DC maturation and EC autophagy via inhibiting LOX1-ox-LDL binding.

Mental health status of children with disorders of sexual development and their correlates.

Disorders of sexual development (DSD) refer to the congenital abnormalities of chromosomes, gonads, or gender anatomy. Children with DSD usually experience more stress. The present study aims to evaluate the mental health status of children with DSD, and to explore the potential relevant factors. We included 30 children with DSD and 30 age- and gender-matched children without DSD as the control group. All the children and their parents completed the scales of the Hamilton Anxiety Scale (HAMA). Children over 8 years old (n = 22) completed the Screen Scale for Child Anxiety Related Emotional Disorders (SCARED), the Depression Self-rating Scale for Children (DSRSC), and the Egna Minnen av Barndoms Uppfostran-own memories of parental rearing practices in childhood. DSD children had significantly higher somatic anxiety, mental anxiety, and total anxiety scores than the control group (p < 0.001). The scores of the SCARED, anxiety, and depression subscales of DSD children were higher than those of control children (p < 0.05 and p < 0.001, respectively). The correlation analysis showed that the score of generalized anxiety was positively related to age and entertainment. The regression analysis showed that age was a major factor that affected generalized anxiety in DSD children, and neuroticism was a major factor of anxiety disorder and separation anxiety in DSD children. Children with DSD have obvious anxiety problems, which are associated with family environmental factors (entertainment, success, and conflicts) and age. It is important to focus emphasis on emotional stability in children with DSD for detecting anxiety-related emotional disorders early.

High Prevalence of Cardiometabolic Comorbidities Among Children and Adolescents With Severe Obesity From a Large Metropolitan Centre (Hangzhou, China).

Objective: This study aimed to describe the clinical characteristics of children and adolescents with obesity, and the prevalence of cardiometabolic comorbidities over 10 years in this population from a large metropolitan centre in China. Methods: This was a cross-sectional study (2008-2017) of patients aged <18 years with obesity [body mass index (BMI) ≥ 95th percentile for age and sex] enrolled at the Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine (Hangzhou, Zhejiang Province). Clinical assessments included anthropometry, blood pressure, liver ultrasound, lipid profile, oral glucose tolerance test, and uric acid. For examination of outcomes, our study cohort was stratified by sex and age bands (<10 vs. ≥10 years), with the study period also split into two strata (2008-2012 and 2013-2017). Results: A total of 2,916 patients (1,954 boys and 962 girls) were assessed at a mean age of 10.5 years. Patients almost invariably presented severe obesity (median BMI SDS = 2.98; Q1 = 2.60, Q3 = 3.39). Obesity-related comorbidities were common among boys and girls, including type 2 diabetes mellitus (2.6% and 3.6%, respectively), abnormal glycaemia (33.6% and 35.5%, respectively), hypertension (33.9% and 32.0%, respectively), dyslipidaemia (35.2% and 39.6%, respectively), hyperuricaemia (16.2% and 8.3%, respectively), acanthosis nigricans (71.9% and 64.0%, respectively), abnormal liver function (66.9% and 47.0%, respectively), and non-alcoholic fatty liver disease (NAFLD) (63.8% and 45.1%, respectively); 38.7% of boys and 44.4% of girls aged ≥10 years had metabolic syndrome. Notably, the incidence of many cardiometabolic comorbidities was in 2013-2017 compared to 2008-2012. For example, rates of hypertension among boys aged <10 years and aged ≥10 years rose from 28.4% and 26.5% to 48.0% and 35.8%, respectively, and in girls from 20.3% and 20.8% to 41.7% and 39.6%, respectively. In 2013-2017, 9.5% of girls in the older group had metabolic syndrome compared to 2.2% in 2008-2013. Conclusions: We observed a high incidence of obesity-related cardiometabolic comorbidities among Chinese children and adolescents with severe obesity over 10 years. It was particularly concerning that rates of several comorbidities rose markedly over the study period, highlighting the need to address the obesity epidemic early in life (in China and elsewhere) to prevent the development of obesity-related comorbidities and, subsequently, of overt disease.

A Randomized Controlled Phase 3 Study on the Efficacy and Safety of Recombinant Human Growth Hormone in Children With Idiopathic Short Stature.

Background: To evaluate the safety and efficacy of daily somatropin (Jintropin®), a recombinant human growth hormone, in prepubertal children with ISS in China. Methods: This study was a multicenter, randomized, controlled, open-label, phase 3 study. All subjects were randomized 3:1 to daily somatropin 0.05 mg/kg/day or no treatment for 52 weeks. A total of 481 subjects with a mean baseline age of 5.8 years were enrolled in the study. The primary endpoint was change in (△) height standard deviation score (HT-SDS) for chronological age (CA). Secondary endpoints included △height from baseline; △bone age (BA)/CA; △height velocity (HV) and △insulin-like growth factor 1 (IGF-1 SDS). Results: △HT-SDS at week 52 was 1.04 ± 0.31 in the treatment group and 0.20 ± 0.33 in the control group (P < 0.001). At week 52, statistical significance was observed in the treatment group compared with control for △height (10.19 ± 1.47 cm vs. 5.85 ± 1.80 cm; P < 0.001), △BA/CA (0.04 ± 0.09 vs. 0.004 ± 0.01; P < 0.001), △HV (5.17 ± 3.70 cm/year vs. 0.75 ± 4.34 cm/year; P < 0.001), and △IGF-1 SDS (2.31 ± 1.20 vs. 0.22 ± 0.98; P < 0.001). The frequencies of treatment-emergent adverse events (TEAEs) were similar for the treatment and the control groups (89.8% vs. 82.4%); most TEAEs were mild to moderate in severity and 23 AEs were considered study-drug related. Conclusions: Daily subcutaneous administration of somatropin at 0.05 mg/kg/day for 52 weeks demonstrated improvement in growth outcomes and was well tolerated with a favorable safety profile. Trial Registration: ClinicalTrials.gov (identifier: NCT03635580). URL: https://clinicaltrials.gov/ct2/show/NCT03635580.

[Analysis of RECQL4 gene variant in a child with Rothmund-Thomson syndrome].

OBJECTIVE: To explore the genetic basis for a child with Rothmund-Thomson syndrome (RTS). METHODS: The child has featured poikeloderma, short stature, cataract, sparse hair and skeletal malformation. Peripheral blood samples of the child and her family members were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. RESULTS: The child was found to harbor compound heterozygous variants of the RECQL4 gene, namely c.1048_1049delAG and c.2886-1G>A, among which c.2886-1G>A was unreported previously. According to the ACMG guidelines, the c.1048_1049delAG was predicted to be pathogenic (PVS1+PM3_Strong+PM2), while the c.2886-1G>A was predicted to be likely pathogenic (PVS1+PM2). CONCLUSION: The compound heterozygous variants of the RECQL4 gene probably underlay the pathogenesis of RTS in this patient. Above finding has enriched the mutational spectrum of the RECQL4 gene.

Surgical management and molecular diagnosis of persistent Müllerian duct syndrome in Chinese patients.

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.

Diabetes Education in Children and Adolescents with Type 1 Diabetes in China.

Background: The prevalence of Type 1 Diabetes is increasing in pediatrics and diabetes education plays one of the most important role in the management of diabetes, especially in children. However, the related evidence concerned diabetes education is rare in children and adolescents. Therefore, we aimed to investigate the status of diabetes education in hospital, which could help us know the reality of diabetes education. Methods: We choose a nurse who is mainly responsible for diabetes education and management in each hospital to fill out the questionnaire. Overall, 98 nurses were enrolled from tertiary children's specialized hospitals and pediatric wards of general tertiary hospitals from Jan 2018 to Dec 2019. Results: Of 98 nurses enrolled, 61 (63.3%) nurses from 98 hospitals responded, 39 (63.9%) of them received specialized training in diabetes. There were no differences in education characteristics among regions of China. There were 26(42.6%) hospitals have a full-time nurse for diabetes education or nurses with endocrinology training increased with the number of cases/year (P=0.02 and P=0.009). The use of game-based education, knowledge assessment at discharge did not vary among hospital volumes, and the presence of a psychiatrist (P=0.41, P=0.65, and P=0.85, respectively). Diet management education is the most common (23.0%) difficulty in children diabetes education. Conclusion: The level of diabetes education in children and adolescents varied among hospitals, but not among regions in China. There was a lack of resources provided for children and adolescents diabetes education in terms of training and specialized services.

10-Year Incidence of Diabetic Ketoacidosis at Type 1 Diabetes Diagnosis in Children Aged Less Than 16 Years From a Large Regional Center (Hangzhou, China).

Background: Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of type 1 diabetes (T1D), and a leading cause of death in children aged <15 years with new-onset T1D. Aims: i) to assess the incidence of DKA in children and adolescents newly diagnosed with T1D over a 10-year period at a large regional center in China; and ii) to examine the clinical symptoms and demographic factors associated with DKA and its severity at diagnosis. Methods: We carried out a retrospective audit of a regional center, encompassing all youth aged <16 years diagnosed with T1D in 2009-2018 at the Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China). DKA and its severity were classified according to ISPAD 2018 guidelines. Results: 681 children were diagnosed with T1D, 50.1% having DKA at presentation (36.0% mild, 30.0% moderate, and 33.9% severe DKA). The number of patients diagnosed with T1D progressively rose from approximately 39 cases/year in 2009-2010 to 95 cases/year in 2017-2018 (≈2.5-fold increase), rising primarily among children aged 5-9 years. DKA incidence was unchanged but variable (44.8% to 56.8%). At T1D diagnosis, 89% of patients reported polyuria and 91% polydipsia. Children presenting with DKA were more likely to report vomiting, abdominal pain, and particularly fatigue. DKA was most common among the youngest children, affecting 4 in 5 children aged <2 years (81.4%), in comparison to 53.3%, 42.7%, and 49.3% of patients aged 2-4, 5-9, and ≥10 years, respectively. Children with severe DKA were more likely to report vomiting, fatigue, and abdominal pain, but less likely to report polyuria, polydipsia, and polyphagia than those with mild/moderate DKA. Rates of severe DKA were highest in children aged <2 years (51.1%). Conclusions: The number of children diagnosed with T1D at our regional center increased over the study period, but DKA rates were unchanged. With 9 of 10 children reporting polyuria and polydipsia prior to T1D diagnosis, increasing awareness of this condition in the community and among primary care physicians could lead to earlier diagnosis, and thus potentially reduce rates of DKA at presentation.

The incidence of brain lesions in central precocious puberty: The main cause for Chinese boys was idiopathic.

OBJECTIVE: Many studies show that brain lesions are the main cause of central precocious puberty (CPP) in males. However, the association rate has not been reported in China. This study aimed to assess the frequency of both abnormal and likely pathologic brain lesions by magnetic resonance imaging (MRI) in Chinese boys with CPP. DESIGN: This is a retrospective cross-sectional single-centre study. PATIENTS: 396 CPP boys were recruited from 2011 to 2019 in Children's Hospital, Zhejiang University School of Medicine, and 129 were eligible for our study. MEASUREMENTS: Diagnosis age, bone age, weight (kg), height (cm), puberty stage, MRI results and levels of sexual hormone were analysed. RESULTS: The number of CPP boys is increasing from 2011 to 2019 in China. Brain MRI findings were normal in 83.7% of CPP boys. Only 21 (16.3%) CPP boys were found with abnormal MRI findings including hamartoma, pineal cyst and other minor changes. CONCLUSION: In China, there is an increasing trend of male CPP over the last decade and the main cause is idiopathic, rather than pathogenic brain lesions. Further investigations about the aetiology for CPP with pathological brain lesions are needed.

Surrogate markers and predictors of endogenous insulin secretion in children and adolescents with type 1 diabetes.

BACKGROUND: No studies have examined endogenous insulin secretion in pediatric patients with type 1 diabetes in China using the gold-standard mixed-meal tolerance test. Because the latter is labor-intensive, we examined simpler surrogate markers of endogenous insulin secretion in Chinese youth, as previously reported for a European population. METHODS: Participants were 57 children and adolescents with type 1 diabetes aged 4.4-16.8 years (56% females). We performed 120-minute mixed-meal tolerance tests with serum C-peptide (CP) measurements every 30 minutes. Severe insulin deficiency (SID) was defined as CP peak < 0.2 nmol/L. Urine CP and creatinine levels were measured at 0 and 120 minutes. RESULTS: Twenty-five (44%) patients had SID. Fasting CP levels missed one case (96% sensitivity) with no false positives (100% specificity). While the 120-minute urine CP/creatinine had 100% sensitivity, it yielded markedly lower specificity (63%). Every 1-year increase in diabetes duration and 1-year decrease in age at diagnosis were associated with 37% (P < 0.001) and 20% (P = 0.005) reductions in serum CP area-under-the-curve, respectively. Thus, 86% of children aged < 5 years had SID compared to none among patients aged ≥ 11 years. CONCLUSIONS: Simple fasting CP measurements could be used to detect most SID cases in Chinese youth with type 1 diabetes. Fasting CP is a far more reliable measure of endogenous insulin secretion than the more commonly used insulin dose. Therefore, it could more precisely determine insulin secretory capacity to target those who could benefit, if treatments to preserve residual insulin secretion are developed.

Abdominal Adiposity and Total Body Fat as Predictors of Cardiometabolic Health in Children and Adolescents With Obesity.

Objective: We aimed to assess the role of adipose tissue distribution in cardiometabolic risk (in particular insulin sensitivity) in a population of children and adolescents with obesity. Methods: In this cross-sectional study, participants were 479 children and adolescents with obesity (322 boys and 157 girls) aged 3 to 18 years attending the Children's Hospital at Zhejiang University School of Medicine (Hangzhou, China). Clinical assessments included anthropometry, body composition (DXA scans), carotid artery ultrasounds, and OGTT. Insulin sensitivity was assessed using the Matsuda index. Participants were stratified into groups by sex and pubertal stage. Key predictors were DXA-derived android-to-gynoid-fat ratio (A/G) and total body fat percentage (TBF%). Results: Irrespective of sex and pubertal stage, there was a strong association between increasing A/G (i.e., greater abdominal adiposity) and lower insulin sensitivity. In multivariable models, every 0.1 increase in A/G was associated with a reduction in insulin sensitivity in prepubertal boys [-29% (95% CI -36%, -20%); p < 0.0001], pubertal boys [-13% (95% CI -21%, -6%); p = 0.001], and pubertal girls [-16% (95% CI -24%, -6%); p = 0.002]. In contrast, TBF% was not associated with insulin sensitivity when A/G was adjusted for, irrespective of pubertal stage or sex. In addition, every 0.1 increase in A/G was associated with increased likelihood of dyslipidemia in prepubertal boys [adjusted odds ratio (aOR) 1.62 (95% CI 1.05, 2.49)], impaired glucose tolerance in pubertal boys [aOR 1.64 (95% CI 1.07, 2.51)] and pubertal girls [aOR 1.81 (95% CI 1.10, 2.98)], and odds of NAFLD in both prepubertal [aOR 2.57 (95% CI 1.56, 4.21)] and pubertal [aOR 1.69 (95% CI 1.18, 2.40)] boys. In contrast, higher TBF% was only associated with higher fasting insulin and ALT in pubertal boys, being also predictive of NAFLD in this group [aOR 1.15 per percentage point (95% CI 1.06, 1.26)], but was not associated with the likelihood of other cardiometabolic outcomes assessed in any group. Conclusions: A/G is a much stronger independent predictor of cardiometabolic risk factors in children and adolescents with obesity in China, particularly glucose metabolism.

Iron overload is related to elevated blood glucose levels in obese children and aggravates high glucose-induced endothelial cell dysfunction in vitro.

INTRODUCTION: This study was performed to investigate the role of iron overload in the early stage of hyperglycemia-induced vascular functional impairment. RESEARCH DESIGN AND METHODS: A total of 196 obese children were enrolled, and data regarding ferritin levels, blood glucose levels, intima-media thickness of carotid arteries, liver function and fibrosis index, hemoglobin, blood pressure, blood lipids, and inflammation indicators were collected. Ferritin levels were compared with a control group, which consisted of 148 healthy non-obese children who were age-matched and gender-matched. Endothelial cells were cultured in high glucose medium and supplemented with ferric citrate with or without iron remover (deferoxamine), a reducing agent (N-acetyl-cysteine), or a nuclear factor-κB (NF-κB) inhibitor (BAY 11-7082). Apoptosis, oxidative stress, nitric oxide levels, and endothelin content were evaluated. DNA microarray analysis was performed to analyze the expression of genes in the NF-κB signaling pathway. RESULTS: Obese children have significantly higher ferritin levels compared with the control group. Ferritin level was positively correlated with hemoglobin and was related to metabolic disorders, including impaired glucose tolerance, higher blood pressure, dyslipidemia, and impaired hepatic function. Endothelial cells treated with ferric citrate showed a significantly higher rate of apoptosis, higher levels of oxidative stress, and impaired vasomotor function under high glucose conditions. The above effects were rescued by treatment with an iron remover, reducing agent, or NF-κB inhibitor. Further, detection of phosphorylated-p65 distribution in cells confirmed activation of the NF-κB pathway. DNA microarrays and subsequent gene oncology enrichment analyses revealed the main processes activated in cells. CONCLUSION: Increased ferritin levels are related to impaired glucose tolerance and other metabolic disorders in obese children. At the cellular level, iron overload aggravated the endothelial cell dysfunction caused by high glucose.

Exosomal miRNAs Profile in Children's Nonalcoholic Fatty Liver Disease and the Correlation with Transaminase and Uric Acid.

OBJECTIVE: The incidence of non-alcoholic fatty liver disease (NAFLD) in children increased rapidly. However, the pathogenesis of NAFLD, especially how non-alcoholic fatty liver progress to non-alcoholic steatohepatitis, is still unclear. This study aims to explore the exosomal miRNAs profiles and the underline pathogenesis of child NAFLD. METHODS: Twenty NAFLD and 20 health control were enrolled in this study. Circulating exosomes were isolated, and RNA sequencing was performed in test set (3 NAFLD/3 Controls). The differentially expressed miRNAs (DEM) were further validated in validation set (17 NAFLD/17 Controls). Spearman correlation -analysis was used to investigate the association between DEM and clinical parameters. RESULTS: Eighty-two miRNAs were differentially expressed (absolute fold change >2 and p < 0.05) in the 2 groups, they were involved in fat acid metabolism, starch and sucrose metabolism, bile acid metabolism and inflammation. miRNA122-5p, miRNA34a-5p, -miRNA155-5p and miRNA146b-3p were up-regulated in NAFLD group (p < 0.05) and positively correlated with body mass index (r, 0.41-0.59), alanine aminotransferase (r, 0.36-0.52), aspartate transaminase (r, 0.31-0.48) and uric acid (UA, r, 0.51-0.69; p < 0.05). CONCLUSIONS: Circulating exosomal miRNAs may be involved in the pathogenesis of NAFLD and correlated with transaminase and UA.

A novel homozygous deletion in ATP6V0A4 causes distal renal tubular acidosis: A case report.

RATIONALE: Autosomal recessive distal renal tubular acidosis (dRTA) is a rare condition, most cases of which are caused by genetic mutations. Several loss-of-function mutations in the ATP6V0A4 gene have been recently reported. PATIENT CONCERNS: A 2-month, 24-day-old Chinese girl presenting with vomiting and diarrhea. DIAGNOSIS: dRTA was established by metabolic acidosis and hypokalemia. Mutational analysis of the ATP6V0A4 gene revealed a homozygous deletion of exons 13 and 14. The father was found to have a heterozygous loss of both exons, whereas the mother was normal. INTERVENTIONS: Patient was treated with potassium citrate. OUTCOMES: The patient has shown normal pH and potassium levels. LESSONS: This is the first case of a homozygous deletion in ATP6V0A4 reported in the literature. Although the initial auditory screening was normal in this case, this patient will nevertheless undergo long-term auditory testing.

[Impact of gonadotropin-releasing hormone analogs on body mass index in girls with idiopathic central precocious puberty: a long-term follow-up study].

OBJECTIVE: To study the impact of gonadotropin-releasing hormone analogs (GnRHa) on body mass index (BMI) in girls with idiopathic central precocious puberty (ICPP). METHODS: One hundred and thirty-four girls with ICPP were enrolled. Fifty-seven out of the 134 girls were treated with GnRHa for 1.69±0.43 years. The height, weight, bone age and BMI were measured before treatment, at the end of the treatment and after reaching near adult height and compared with those in the untreated 77 girls. RESULTS: The adult predicted height standard deviation score (SDS) at the end of treatment was significantly higher than that before treatment (P<0.01) and was similar to the target height SDS in the GnRHa treatment group (P>0.05). With GnRHa treatment, the near-adult height SDS was higher than the target height SDS (P<0.01). At the end of treatment, the BMI SDS slightly increased compared with pretreatment level (P>0.05). A significant reduction in the BMI was observed when reaching the near-adult height in the GnRHa treatment group compared to the level of pretreatment and the untreated group (P<0.01). However, the BMI in the GnRHa treatment group before treatment, at the end of the treatment and after reaching near adult height remained in the normal range (±1 SD). CONCLUSIONS: GnRHa may improve the final height in girls with ICPP. The alterations of BMI after GnRHa therapy fluctuate in a normal range.