Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children

AIM: To investigate the effect of lifestyle intervention on non-alcoholic fatty liver disease (NAFLD) in Chinese obese children. METHODS: Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided randomly into three groups. Group1, consisting of 38 obese children, was an untreated control group without any intervention. Group 2, consisting of 19 obese children in summer camp, was strictly controlled only by life style intervention. Group 3, consisting of 19 obese children, received oral vitamin E therapy at a dose of 100 mg/d. The height, weight, fasting blood glucose (FBG), fasting serum insulin (FINS), plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TCHO) and homeostasis model assent- insulin resistance (HOMA-IR) were measured at baseline and after one month. All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups. RESULTS: The monitor indices of BMI, ALT, AST, TG, TCHO and HOMA-IR were successfully improved except in group 1. BMI and ALT in group 2 were reduced more significantly than in group 3 (2.44 ± 0.82 vs 1.45 ± 0.80, P = 0.001; 88.58 ± 39.99 vs 63.69 ± 27.05, P = 0.040, respectively).CONCLUSION: Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children. Compared with vitamin E, lifestyle intervention is more effective. Therefore, lifestyle intervention should represent the first step in the management of children with NAFLD.

Non-alcoholic fatty liver disease:An early mediator predicting metabolic syndrome in obese children?

AIM:To investigate if non-alcoholic fatty liver disease (NAFLD) is an early mediator for prediction of metabolic syndrome,and if liver B-ultrasound can be used for its diagnosis.METHODS:We classified 861 obese children (6-16 years old) into three subgroups:group 0 (normal liver in ultrasound and normal transaminases);group 1 (fatty liver in ultrasound and normal transaminases);and group 2 (fatty liver in ultrasound and elevated transaminases).We measured the body mass index,waist and hip circumference,blood pressure,fasting blood glucose,insulin,homeostasis model assessment of insulin resistance (HOMA-IR),whole-body insulin sensitivity index (WBISI),lipid profile and transaminases in all the participants.The risk of developing metabolic syndrome (MS) was assessed according to the degree of liver fatty infiltration based on the B-ultrasound examination.RESULTS:Among the 861 obese children,587 (68.18%) were classified as having NAFLD,and 221 (25.67%) as having MS.The prevalence of MS in NAFLD children (groups 1 and 2) was 37.64% (221/587),which was much higher than that in non-NAFLD group (group 0,12.04%) (P < 0.01).There were significantly higher incidences concerning every component of MS in group 2 compared with group 0 (P < 0.05).The incidence of NAFLD in MS patients was 84.61% (187/221),which was significantly higher than that of hypertension (57.46%,127/221) and glucose metabolic anomalies (22.62%,50/221),and almost equal to the prevalence of dyslipidemia (89.14%,197/221).Based on the B-ultrasound scales,the presence of moderate and severe liver fatty infiltration carried a high risk of hypertension [odds ratio (OR):2.18,95% confidence interval (95% CI):1.27-3.75],dyslipidemia (OR:7.99,95% CI:4.34-14.73),impaired fasting glucose (OR:3.65,95% CI:1.04-12.85),and whole MS (OR:3.77;95% CI:1.90-7.47,P < 0.01).The state of insulin resistance (calculated by HOMA-IR and WBISI) deteriorated as the degree of fatty infiltration increased.CONCLUSION:NAFLD is not only a liver disease,but also an early mediator that reflects metabolic disorder,and liver B-ultrasound can be a useful tool for MS screening.

Association between UCP3 gene polymorphisms and nonalcoholic fatty liver disease in Chinese children

AIM:To confirm the hypothesis that polymorphisms of the uncoupling protein 3(UCP3)gene are associated with the occurrence of nonalcoholic fatty liver disease(NAFLD).METHODS:A total of 250 NAFLD patients(147 malesand 103 females)and 200 healthy individuals who served as controls(control,109 males and 91 females),aged between 6 and 16 years were enrolled in this study.The four non-synonymous single nucleotide polymorphisms(SNPs)in the UCP3 gene polymorphisms of rs1726745,rs3781907,rs11235972 and rs1800849,were genotyped using MassArray.Body mass index(BMI),waist and hip circumference,blood pressure(BP),fasting blood glucose(FBG),insulin and lipid profiles were measured and B-ultrasound examination was performed in all subjects.RESULTS:NAFLD patients showed risk factors for metabolic syndrome:elevated BMI,waist-to-hip ratio,BP,FBG,homeostasis model assessment-estimated insulin resistance,total triglyceride,total cholesterol and low-density lipoprotein-cholesterol,while decreased high-density lipoprotein-cholesterol level compared with the control group.The GG genotype distributions of rs11235972 in the NAFLD group differed significantly from that in the control group.We found that waist circumference between CC(58.76±6.45 cm)and CT+TT(57.00±5.59 cm),and hip circumference between CC(71.28±7.84 cm)and CT+TT genotypes(69.06±7.75 cm)were significantly different with and without rs1800849 variation(P<0.05).CONCLUSION:A higher prevalence of rs11235972 GG genotype was observed in the NAFLD group compared with the control group.No differences were observed for the other SNPs.However,there was a significant difference in body height in addition to waist and hip circumference between the CC(mutant type group)and CT+TT group with and without rs1800849 variation.

Early recombinant human growth hormone treatment improves mental development and alleviates deterioration of motor function in infants and young children with Prader–Willi syndrome

Background Recombinant human growth hormone(rhGH)therapy has shown to improve height and body composition in children with Prader–Willi syndrome(PWS),the evidence of early rhGH treatment on motor and mental development is still accumulating.This study explored the time effect on psychomotor development,anthropometric indexes,and safety for infants and young children with PWS.Methods A phase 3,single-arm,multicenter,self-controlled study was conducted in six sites.Patients received rhGH at 0.5 mg/m2/day for first four weeks,and 1 mg/m2/day thereafter for up to 52 weeks.Motor development was measured using Peabody Developmental Motor Scales-second edition,mental development using Griffiths Development Scales-Chinese(GDS-C).Height standard deviation score(SDS),body weight SDS,and body mass index(BMI)SDS were also assessed.Results Thirty-five patients were enrolled totally.Significant improvements were observed in height,body weight,and BMI SDS at week 52;GDS-C score showed significant improvement in general quotient(GQ)and sub-quotients.In a linear regression analysis,total motor quotient(TMQ),gross motor quotient(GMQ),and fine motor quotient were negatively correlated with age;however,treatment may attenuate deterioration of TMQ and GMQ.Changes in GQ and locomotor sub-quotient in<9-month group were significantly higher than≥9-month group.Mild to moderate severity adverse drug reactions were reported in six patients.Conclusion Fifty-two-week treatment with rhGH improved growth,BMI,mental development,and lessened the deterioration of motor function in infants and young children with PWS.Improved mental development was more pronounced when instituted in patients<9 months old.

Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver disease.Using anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with obesity.Methods A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation cohort.The external validation cohort comprised 77 children.The assessment of liver fat content was performed using proton magnetic resonance spectroscopy.Anthropometry and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation cohort.The Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive model.Results The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner stage.The adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in children.Thus,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus

Since December 2019,an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China.As of 8 pm,31 January 2020,more than 20 pediatric cases have been reported in China.Of these cases,ten patients were identified in Zhejiang Province,with an age of onset ranging from 112 days to 17 years.Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCo V (the 4th edition) and current status of clinical practice in Zhejiang Province,recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health,the National Children's Regional Medical Center,Children's Hospital,Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

FTO gene polymorphisms and obesity risk in Chinese population: a meta-analysis

Background There is tremendous increase in obesity worldwide.Many factors including diet,life style,genetic,and epigenetic changes contribute to obesity.The fat mass and obesity-associated (FTO) gene polymorphisms are strongly associated with obesity.It has been reported that FTO single-nucleotide polymorphisms (SNPs) are associated with obesity in European populations;however,it was controversial in Chinese population.The present meta-analysis study was designed to investigate the association between FTO polymorphisms and obesity risk in Chinese population.Methods The investigators searched studies using the following databases:PubMed,web of science,and Cochrane Central Register of Controlled Trials.A random-effects model was used to calculate the pooled odds ratios (ORs).The heterogeneity among the studies was measured by I2 value.Subgroup analysis was used to find out the potential factors influencing the heterogeneity.Results A total of 18 articles including 26 studies were included in the present meta-analysis.Overall,the FTO SNPs were significantly associated with obesity in Chinese population (OR 1.30;95% CI 1.19-1.42;P < 0.001) under per-allele comparison.The subgroup analysis also showed strong association between four FTO SNPs (rs9939609,rs6499640,rs8050136,and rs 1558902) and obesity risk.Furthermore,subgroup analysis stratified by children/adolescent and adult groups showed same trend.Conclusion The present meta-analysis indicated that FTO SNPs are associated with obesity risk in both children/adolescents and adults in Chinese population.

Management strategies of neonatal jaundice during the coronavirus disease 2019 outbreak

The outbreak of coronavirus disease 2019 (COVID-19;formally known as 2019-nCoV) has become a most challenging health emergency.Owing to rigorous quarantine and control measures taken in China,routine neonatal health surveillance and follow-up have become challenging.Without follow-up surveillance,some rapid and progressive newborn diseases,such as bilirubin encephalopathy,may be ignored.The characteristics of onset age of kernicterus suggest that monitoring of bilirubin level at home provides a useful way to alert hospital visits and to prevent the development of extremely hyperbilirubinemia.Therefore,we developed an online follow-up program for convenient monitoring of bilirubin level of newborns that is based on our practical experiences.The aim is to make our management strategies of neonatal jaundice tailored to the infection prevention and control during the COVID-19 epidemic.

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.

Big challenges: obesity and type 2 diabetes in children and adolescents

Childhood obesity has emerged as an important public health problem not only in developed countries but in many developing countries [1,2].As we know, the increasing prevalenceof childhood obesity is associated with the grooving increaseof the incidence of adult diseases including type 2 diabetes mellitus, nonalcoholic fatty liver disease and other disease,which dramatically threaten public health.

New coronavirus: new challenges for pediatricians

The 2019-nCoV epidemic has become a major challenging public health problem in China.For standardizing the diagnosis and treatment strategies of 2019-nCoV pneumonia,National Health Commission of the People's Republic of China has released the Diagnosis and Treatment Standards of 2019-nCoVpneumonia,and updated the standards to the 4th edition based on the status of epidemic and accumulated experiences in clinical practice now [1].

A novel HNF4A mutation identified in a child with maturity onset diabetes of the young

Maturity-onset diabetes of the young(MODY)is a group of monogenic diabetes mellitus characterized by early-onset diabetes with dominant inheritance.To date,at least 14 different causative genes have been identified.HNF4A-MODY is relatively uncommon in China[I,2].We report a Chinese child with diabetes mellitus due to a heterozygous HNF4A mutation.

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 per-formed 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 posi-tives(100% specificity).While the 120-minute urine CP/creatinine had 100% sensitivity,it yielded markedly lower speci-ficity(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 diabe-tes.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.

Novel mitochondrial tRNAArg 10461A>G mutation in a pedigree with obesity

Obesity is one of the most prominent public health chailenges globally,with an over tenfold increase in the number of obese children over the last 40 years[1,2].The etiology of obesity,however,is incompletely understood owing to its complex and multifactorial nature[3].Most efforts to identify genetic determinants of childhood obesity have focused on nuclear genes.

Continuous age-and sex-specific reference ranges of liver enzymes in Chinese children and application in pediatric non-alcoholic fatty liver disease

Background Alanine aminotransferase(ALT)is widely used to screen patients with hepatic diseases.However,the current reference ranges(<50 U/L)were developed by laboratories and have not been validated in populations with a large number of healthy individuals.Methods This study collected venous blood and anthropometric data from a total of 13,287 healthy children aged 3 months to 18 years who underwent routine physical examinations in the Department of Pediatric Healthcare.We applied the least mean square algorithm to establish age-and sex-related reference percentiles of serum levels of transaminases.For validation,we recruited 4276 children and adolescents with obesity/overweight who underwent evaluation and metabolic tests in the hospital.Using receiver operating characteristic curves,we determined age-and sex-specific upper limit percentiles of liver enzymes for fatty liver diseases.Results This study revealed a significant correlation between serum transaminase levels and age and sex(P<0.01).These transaminase levels exhibited age-and sex-specific patterns.Among individuals in the non-alcoholic fatty liver disease(NAFLD)cohort,elevated ALT levels displayed a positive association with clinical markers of disease severity,including homeostatic model assessment of insulin resistance,waist-hip ratio,and serum uric acid levels(P<0.01).According to the receiver operating characteristic curves,ALT levels at the 92.58th percentile for boys and the 92.07th percentile for girls yielded the highest accuracy and specificity.Conclusions This study provides age-and sex-specific reference ranges for ALT,aspartate aminotransferase,andγ-glutamyltransferase in Chinese children and adolescents,making it the largest population study to date.Furthermore,the study establishes a precise upper limit for ALT levels,facilitating their use in NAFLD screening.