Harnessing endogenous transcription factors directly by small molecules for chemically induced pluripotency inception.

Chemistry-alone approach has recently been applied for incepting pluripotency in somatic cells, representing a breakthrough in biology. However, chemical reprogramming is hampered by low efficiency, and the underlying molecular mechanisms remain unclear. Particularly, chemical compounds do not have specific DNA-recognition domains or transcription regulatory domains, and then how do small molecules work as a driving force for reinstating pluripotency in somatic cells? Furthermore, how to efficiently clear materials and structures of an old cell to prepare the rebuilding of a new one? Here, we show that small molecule CD3254 activates endogenous existing transcription factor RXRα to significantly promote mouse chemical reprogramming. Mechanistically, CD3254-RXRα axis can directly activate all the 11 RNA exosome component genes (Exosc1-10 and Dis3) at transcriptional level. Unexpectedly, rather than degrading mRNAs as its substrates, RNA exosome mainly modulates the degradation of transposable element (TE)-associated RNAs, particularly MMVL30, which is identified as a new barrier for cell-fate determination. In turn, MMVL30-mediated inflammation (IFN-γ and TNF-α pathways) is reduced, contributing to the promotion of successful reprogramming. Collectively, our study provides conceptual advances for translating environmental cues into pluripotency inception, particularly, identifies that CD3254-RXRα-RNA exosome axis can promote chemical reprogramming, and suggests modulation of TE-mediated inflammation via CD3254-inducible RNA exosome as important opportunities for controlling cell fates and regenerative medicine.

Family History of Type 2 Diabetes and Its Association with Beta Cell Function and Lipid Profile in Newly Diagnosed Pediatric Patients with Type 1 Diabetes.

OBJECTIVE: The objective of this study was to explore the associations between a family history of type 2 diabetes (T2D) and beta-cell function, as well as lipid profile, in pediatric patients newly diagnosed with type 1 diabetes (T1D). METHODS: A retrospective analysis was conducted on children under 14 years of age who were newly diagnosed with T1D at the Children's Hospital of Zhejiang University between August 2018 and August 2022. Clinical features, metabolic profiles, beta-cell function, and lipid profile were evaluated. RESULTS: A total of 316 children were diagnosed with new-onset T1D. Among them, 28.2% had a family history of T2D. Patients with T1D who had a family history of T2D experienced a later onset of the disease (p = 0.016), improved HOMA2-%B levels (p = 0.003), and increased concentrations of HDL-C (p = 0.005). In addition, no statistically significant differences in age at onset, HOMA2-%B levels, or HDL-C were found when assessing the interaction between family history of T2D and type of diabetes mellitus (autoimmune T1D/idiopathic T1D). CONCLUSION: A family history of T2D may contribute to the heterogeneity of T1D patients in terms of HOMA2-%B levels and lipid profile. This highlights the significance of taking into account T2D-related factors in the diagnosis and treatment of T1D.

Long-Term Efficacy and Safety of Recombinant Human Growth Hormone in Children Born Small for Gestational Age.

There is a lack of long-term data on the benefit of growth hormone (GH) treatment in Chinese children born small for gestational age (SGA). This study was conducted to assess the long-term efficacy and safety of GH treatment in children born SGA. One hundred and twenty prepubertal SGA children who did not achieve catch-up growth with height remained less than -2 standard deviations (SD) below gender-specific height were enrolled in this two-year, randomized, dose-comparative study followed by an extension study of up to 10 years. Daily subcutaneous injections of 0.23 mg/kg/week [low-dose (LD) group] or 0.46 mg/kg/week [high-dose (HD) group] somatropin were given for 104 weeks. Dosing in the extension study was≤0.46 mg/kg/week. The main outcome measures were change in height SD score (ΔHT-SDS), height velocity, insulin-like growth factor (IGF)-1, and IGF-1/IGF binding protein-3 (IGFBP-3) molar ratio. ΔHT-SDS at week 104 was 0.91±0.53 and 1.52±0.64 in the LD and HD groups (intergroup p<0.0001), respectively, and continued in an upward trend throughout the extension study, remaining above+2 for those who received treatment for a total of 7 years or more. At week 104, significant improvements were observed in height velocity, IGF-1 SDS, and IGF-1/IGFBP-3 molar ratio. Adult HT-SDS was -0.81±1.68 for boys and -0.82±1.05 for girls (p=0.9837). Glucose metabolism and thyroid function were within the normal reference range throughout treatment. Long-term recombinant human GH treatment was tolerable and effective at improving height in children born SGA.

Negative Correlation of Serum Total Bile Acid With Albuminuria in Patients With Type 2 Diabetes Mellitus: A Cross-sectional Study.

Context: The treatment of diabetic nephropathy (DN) is still quite limited. DN remains poorly understood due to the complexity of and differences in its etiology. Therefore, potential biomarkers for diagnosis and targeted treatments are urgently needed. Objective: The study aimed to analyze the associations between circulating total bile acid (TBA) levels and the risk of DN in Chinese patients with type 2 diabetes mellitus (T2DM) and to determine the differences in the TBA levels of males and females, including pre- and postmenopausal women, to find clues for the screening of DN. Design: The research team performed a retrospective study. Setting: The study took place at the Second Affiliated Hospital at the School of Medicine of Zhejiang University in Zhejiang, China. Participants: Participants were 1785 T2DM patients admitted to the hospital between April 2008 and November 2013. Groups: The research team separated participants into three groups: (1) the normoalbuminuria or normal group, with a UACR <30 mg/g·Cr (2) the microalbuminuria (MAU) group, with a UACR of 30-299 mg/g·Cr; and (3) the macroalbuminuria (MAC) group, with a UACR of ≥300 mg/g·Cr. Outcome Measures: Between the three groups, the research team compared: (1) the demographic and clinic characteristics of the normal, MAU, and MAC groups; (2) TBA distribution by age; (3) TBA distribution by gender; and (4) TBA quartiles. The team also examined the associations between TBA and albuminuria, identifying the odds ratios (OR) and relevant 95% confidence intervals (CI) using multiple logistic regression. Results: The study found that: (1) the MAC group's TBA was significantly lower than those of the normal and MAU groups; (2) the TBA of postmenopausal women was significantly higher than that of premenopausal women; (3) the incidence of MAC was obviously increased with TBA levels; (4) the risks for MAU group didn't change significantly with increasing TBA levels; (5) the MAC group's odds ratios (ORs) were 0.61 between Q2 and Q1, 0.44 between Q3 and Q1, and 0.38 between Q4 and Q1; and (6) for men and postmenopausal women, the TBA levels of those in Q3 and Q4 might decrease the risk of MAC, whereas no such correlation existed for MAU. Conclusions: An independent negative association exists between TBA levels and MAC in T2DM. The decrease of circulating TBA might be a prospective clinical factor for determining established DN, especially for males and postmenopausal females.

Growth charts of brain morphometry for preschool children.

Brain development from 1 to 6 years of age anchors a wide range of functional capabilities and carries early signs of neurodevelopmental disorders. However, quantitative models for depicting brain morphology changes and making individualized inferences are lacking, preventing the identification of early brain atypicality during this period. With a sample size of 285, we characterized the age dependence of the cortical thickness and subcortical volume in neurologically normal children and constructed quantitative growth charts of all brain regions for preschool children. While the cortical thickness of most brain regions decreased with age, the entorhinal and parahippocampal regions displayed an inverted-U shape of age dependence. Compared to the cortical thickness, the normalized volume of subcortical regions exhibited more divergent trends, with some regions increasing, some decreasing, and some displaying inverted-U-shaped trends. The growth curve models for all brain regions demonstrated utilities in identifying brain atypicality. The percentile measures derived from the growth curves facilitate the identification of children with developmental speech and language disorders with an accuracy of 0.875 (area under the receiver operating characteristic curve: 0.943). Our results fill the knowledge gap in brain morphometrics in a critical development period and provide an avenue for individualized brain developmental status evaluation with demonstrated sensitivity. The brain growth charts are shared with the public (http://phi-group.top/resources.html).

Pediatric diabetes in China: Challenges and actions.

Pediatric diabetes is growing in China. The annual incidence of childhood type 1 diabetes is about 2.02-5.3 per 100,000 person-years. Type 2 diabetes in children and adolescents is increasing dramatically with the high-speed urbanization of China. The prevalence of type 2 diabetes varies from 1.64/100, 000 to 15.16/100,000 based on the geography and economy. Monogenic diabetes used to be underestimated in China and now more cases are emerging. In this review, we give an overview of pediatric diabetes in China, present the progresses and challenges in management of pediatric diabetes, and discuss the government policy and potential actions in China, for better life quality of diabetic families.

Optimized simplified pediatric diabetes severity warning system for the early identification of diabetic ketoacidosis in children.

OBJECTIVE: Diabetic ketoacidosis (DKA) is the leading cause of mortality in children with type 1 diabetes. Diagnosis of DKA is difficult in resource-limited areas owing to the unavailability of blood gas test, the gold standard for DKA diagnosis. The Simplified Pediatric Diabetes Severity Warning System (SPDSWS) has been developed to identify high-risk DKA patients with limited resources in China. Here we optimized and validated this system. METHODS: This study included 835 children admitted between January 2011 and June 2020 with the principal diagnosis of type 1 diabetes. Data were collected based on demographic and clinical characteristics. DKA and its severity were defined according to the criteria of ISPAD. SPDSWS was optimized based on logistic regression analyses and then was validated in a validation cohort. RESULTS: The 20-point optimized SPDSWS included strong positive urine ketone, young age, dehydration, fatigue, anorexia, vomiting, abdominal pain, abnormal pulse, and high blood glucose. The optimized SPDSWS predicted DKA with an AUC value of 0.882 in the derivation cohort. When the cut-point score ≥7 was used, the sensitivity and specificity were 75.5% and 86.0%, respectively, in the derivation cohort and were 90.0% and 85.8%, respectively, in the validation cohort. The optimized SPDSWS also predicted the moderate/severe DKA with an AUC value of 0.911 in the derivation cohort and 0.937 in the validation cohort. A score > 11 was associated with an extremely high incidence of DKA. CONCLUSIONS: The optimized SPDSWS could assist health care practitioners in underdeveloped remote areas to identify the children at high risk of DKA as early as on admission.

ISPAD Clinical Practice Consensus Guidelines 2022: Type 2 diabetes in children and adolescents.

Since the 2018 ISPAD guidelines on this topic, follow-up of large cohorts from around the globe have continued informing the current incidence and prevalence of co-morbidities and complications in young adults with youth-onset type 2 diabetes (T2D). This chapter focuses on the risk factors, diagnosis and presentation of youth-onset T2D, the initial and subsequent management of youth-onset T2D, and management of co-morbidities and complications. We include key updates from the observational phase of the multi-center Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial, the SEARCH for Diabetes in Youth (SEARCH) study and new data from the Restoring Insulin Secretion (RISE) study, a head-to-head comparison of youth onset vs adult-onset T2D. We also include an expanded section on risk factors associated with T2D, algorithms and tables for treatment, management, and assessment of co-morbidities and complications, and sections on recently approved pharmacologic therapies for the treatment of youth-onset T2D, social determinants of health, and settings of care given COVID-19 pandemic.

Construction of a new complete growth reference for urban Chinese children.

BACKGROUND: Growth chart is a valuable clinical tool to monitor the growth and nutritional status of children. A growth chart widely used in China is based on the merged data sets of national surveys in 2005. We aimed to establish an up-to-date, complete growth curve for urban Chinese children and adolescents with a full range of ages. METHODS: Using data collected in a large-scale, cross-sectional study (Prevalence and Risk factors for Obesity and Diabetes in Youth (PRODY), 2017-2019), we analyzed 201,098 urban children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations. Sex-specific percentiles of height-for-age and weight-for-age were constructed by Generalized Additive Models for Location Scale and Shape (GAMLSS) model. We also compared the median values of height-for-age or weight-for-age between our growth chart and the established growth reference using Welch-Satterthwaite T-Test. RESULTS: Consistent with the established growth reference, we observed that the P50 percentile of height-for-age reached plateaus at the age of 15 years (172 cm) and 14 years (160 cm) for boys and girls, respectively. In addition, boys aged 10 ~ 14 years and girls aged 10 ~ 12 years exhibited the most dramatic weight difference compared to those of other age groups (19.5 kg and 10.3 kg, respectively). However, our growth chart had higher median values of weight-for-age and height-for-age than the established growth reference with mean increases in weight-for-age of 1.36 kg and 1.17 kg for boys and girls, respectively, and in height-for-age of 2.9 cm and 2.6 cm for boys and girls, respectively. CONCLUSIONS: Our updated growth chart can serve as a reliable reference to assess the growth and nutritional status in urban Chinese children throughout the entire childhood.

Comparative dietary effectiveness of a modified government-recommended diet with avoidance of ultra-processed foods on weight and metabolic management in children and adolescents: An open-label, randomized study.

BACKGROUND AND OBJECTIVES: Childhood obesity is rapidly rising in China and effective diet interventions are needed. Here, we determine whether the Chinese government-recommended diet (GRD) or a modified diet of further restriction of sugar and ultra-processed food but without energy restriction, minimally processed diet (MPD) is effective on weight loss in children and adolescents with obesity/overweight. METHODS AND STUDY DESIGN: This open-label, randomized study included 60 children and adolescents between 5-18 years old with overweight/obesity. Participants were randomized 1:1 to the GRD or MPD and self-managed at home for 12 weeks. Both groups received general recommendations in physical activities. The changes were evaluated in body weight, fasting glucose and insulin, lipid metabolism and serum uric acid between baseline and week 12. RESULTS: The results indicated great reductions by time for BMI, BMI z-score, fat mass percentage and fat mass index in both groups. An obvious decrease by time for weight was found in the MPD group (p<0.001) as well as fasting glucose (p=0.005), fasting insulin (p=0.001), total cholesterol (p=0.007) and serum uric acid (p=0.006). As for the amount of visceral fat, greater reduction by time was observed in MPD group compared with GRD group. CONCLUSIONS: A 12-week self-intervention combining the Chinese government-recommended diet with physical activities was effective on weight loss in children and adolescents with overweight/obesity. The minimally processed diet was more effective on decreasing visceral fat mass and may be beneficial to improving insulin resistance. Further studies are required to assess long-term outcomes of the general public.

[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.

Progress on growth promoting therapies other than growth hormone.

Recombinant human growth hormone is a classical therapeutic drug for children with short stature. In recent years, as the mechanism of growth in children has been further explored, growth-promoting therapies other than growth hormone have made great progress. Recombinant human insulin-like growth factor (IGF)-1 is the main treatment for primary IGF-1 deficiency, and C-type natriuretic peptide (CNP) offers a therapeutic option for children with short stature due to chondrodysplasia. Growth hormone-releasing peptide analogues stimulate growth hormone release and may be used for growth-promoting therapy. In addition, gonadotropin-releasing hormone analogue (GnRHa) and aromatase inhibitors may delay the bone age in children and may be beneficial in improving final height. In this article, the research progress of growth-promoting therapies other than growth hormones is reviewed to provide more options for the clinical treatment of children with short stature.

M2IA: a web server for microbiome and metabolome integrative analysis.

MOTIVATION: Microbiome-metabolome association studies have experienced exponential growth for an in-depth understanding of the impact of microbiota on human health over the last decade. However, analyzing the resulting multi-omics data and their correlations remains a significant challenge due to the lack of a comprehensive computational tool that can facilitate data integration and interpretation. In this study, an automated microbiome and metabolome integrative analysis pipeline (M2IA) has been developed to meet the urgent needs for tools that can effectively integrate microbiome and metabolome data to derive biological insights. RESULTS: M2IA streamlines the integrative data analysis between metabolome and microbiome, from data preprocessing, univariate and multivariate statistical analyses, advanced functional analysis for biological interpretation, to a summary report. The functionality of M2IA was demonstrated using TwinsUK cohort datasets consisting of 1116 fecal metabolites and 16s rRNA microbiome from 786 individuals. Moreover, two important metabolic pathways, i.e. benzoate degradation and phosphotransferase system, were identified to be closely associated with obesity. AVAILABILITY AND IMPLEMENTATION: M2IA is public available at http://m2ia.met-bioinformatics.cn. CONTACT: yanni617@zju.edu.cn or fjf68@zju.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

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.

Ferritin as a key risk factor for nonalcoholic fatty liver disease in children with obesity.

BACKGROUND: The association between serum ferritin and nonalcoholic fatty liver disease (NAFLD) in children with obesity is not clear. This study was designed to investigate whether serum ferritin can be an independent predictor for NAFLD. METHODS: According to the hepatic ultrasound results, a total of 347 children with obesity were enrolled in this study. Among them, 95 patients with NAFLD and 95 without NAFLD were matched for gender, age, blood pressure and body mass index, the odds ratios (OR) and 95% confidence intervals (CI) for the association of ferritin and the risk of NAFLD were analyzed. RESULTS: After propensity score matching, ferritin values of the patients with NAFLD were significantly higher than those without NAFLD group. Alanine aminotransferase and ferritin were strongly associated with NAFLD in multivariate stepwise logistic regression analysis. The medium and high levels of ferritin increased risk of NAFLD, and the adjusted ORs were 3.298 (95% CI:1.326-8.204), 7.322 (95% CI:2.725-19.574) across the ferritin concentration tertiles after adjustment for confounders. Ferritin was shown to be the best predictor for NAFLD with sensitivity and specificity of 60.0% and 77.9%, respectively, area under the curve was 0.733. CONCLUSION: The results show that serum ferritin can usefully be considered as a predictor of NAFLD in children with obesity.

Changes in Children's Healthcare Visits During Coronavirus Disease-2019 Pandemic in Hangzhou, China.

The lower than expected rates of children affected by coronavirus disease-2019 does not mean that there was no impact on children's health. Using data on pediatric healthcare visits before and after the breakout of coronavirus disease-2019 and historical data, we identified pediatric conditions that were most affected by the pandemic and epidemic control measures during the pandemic.

Epidemiological analysis of COVID-19 and practical experience from China.

The rapid spread of the epidemic has aroused widespread concern in the international community. Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) was first reported in China, with bats as the likely original hosts and pangolins as potential intermediate hosts. The current source of the disease is mainly patients infected with SARS-COV-2. Patients in the incubation period may also become sources of infection. The virus is mainly transmitted via respiratory droplets and contact, and the population is generally susceptible. The epidemic has progressed through the local outbreak stage and community transmission stage due to exposure at Wuhan's Huanan wholesale seafood market and is now in the stage of large-scale transmission due to the spread of the epidemic. The basic productive number (R0) at the beginning of the epidemic was 2.2, with an average incubation period of 5.2 days. The proportion of critically ill patients was 23.4%, the mortality rate was lower than those of SARS and Middle East respiratory syndrome, and 96.5% of deaths occurred in Hubei Province, where the outbreak occurred first. Among them, elderly men with underlying diseases had a higher mortality rate. Chinese medical staff have summarized a set of effective strategies and methods in the diagnosis and treatment of this disease that are worthy of reference for their international counterparts. With powerful government intervention and the efforts of Chinese medical staff, China's outbreak has gradually improved.

Epidemiological features and viral shedding in children with SARS-CoV-2 infection.

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.

Comparison of effect between dartos fascia and tunica vaginalis fascia in TIP urethroplasty: a meta-analysis of comparative studies.

BACKGROUND: Tubularized incised plate (TIP) urethroplasty is the most commonly performed procedure for hypospadias. Several flap procedures have been recommended to decrease the postoperative complication rate in TIP repair, but no single flap procedure is ideal. This study aimed to compare the outcomes of dartos fascia (DF) and tunica vaginalis fascia (TVF) as intermediate layers in TIP urethroplasty. METHODS: We searched PubMed, EMBASE, the Cochrane Library, Web of Science, clinicaltrials.gov, and other sources for comparative studies up to April 16, 2020. Studies were selected by the predesigned inclusion criteria. The primary outcomes were postoperative complications. The secondary outcomes were functional and cosmetic outcomes. RESULTS: The pooled RR with 95% CI were calculated. We extracted the relevant information from the included studies. Only 6 comparative studies were included. No secondary outcomes were reported. The RR of the total complications rate for DF was 2.41 (95% CI 1.42-4.07, P = 0.0001) compared with TVF in TIP repair. For each postoperative complication, the RRs were 6.48 (2.20-19.12, P = 0.0007), 5.95 (1.13-31.30, P = 0.04), 0.62 (0.25-1.52, P = 0.29), and 0.75 (0.23-2.46, P = 0.64) for urethrocutaneous fistula, prepuce-related complications, meatal/urethral stenosis, and wound-related complications, respectively. CONCLUSIONS: This meta-analysis reveals that compared to DF, TVF is a better option in TIP repair in terms of decreasing the incidence of the total postoperative complications, urethrocutaneous fistula, and prepuce-related complications. However there is limited evidence for functional and cosmetic outcomes. Overall, larger prospective studies and long-term follow-up data are required to further demonstrate the superiority of TVF over DF. TRIAL REGISTRATION: PROSPERO CRD42019148554.

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.