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INTRODUCTION: Automated bone age assessment (BAA) is of growing interest because of its accuracy and time efficiency in daily practice. In this study, we validated the clinical applicability of a commercially available artificial intelligence (AI)-powered X-ray bone age analyzer equipped with a deep learning-based automated BAA system and compared its performance with that of the Tanner-Whitehouse 3 (TW-3) method. METHODS: Radiographs prospectively collected from 30 centers across various regions in China, including 900 Chinese children and adolescents, were assessed independently by six doctors (three experts and three residents) and an AI analyzer for TW3 radius, ulna, and short bones (RUS) and TW3 carpal bone age. The experts' mean estimates were accepted as the gold standard. The performance of the AI analyzer was compared with that of each resident. RESULTS: For the estimation of TW3-RUS, the AI analyzer had a mean absolute error (MAE) of 0.48 ± 0.42. The percentage of patients with an absolute error of < 1.0 years was 86.78%. The MAE was significantly lower than that of rater 1 (0.54 ± 0.49, P = 0.0068); however, it was not significant for rater 2 (0.48 ± 0.48) or rater 3 (0.49 ± 0.46). For TW3 carpal, the AI analyzer had an MAE of 0.48 ± 0.65. The percentage of patients with an absolute error of < 1.0 years was 88.78%. The MAE was significantly lower than that of rater 2 (0.58 ± 0.67, P = 0.0018) and numerically lower for rater 1 (0.54 ± 0.64) and rater 3 (0.50 ± 0.53). These results were consistent for the subgroups according to sex, and differences between the age groups were observed. CONCLUSION: In this comprehensive validation study conducted in China, an AI-powered X-ray bone age analyzer showed accuracies that matched or exceeded those of doctor raters. This method may improve the efficiency of clinical routines by reducing reading time without compromising accuracy.
Assessing bone age, or how developed a child's skeleton is, is important in medical care, but the standard method can be time-consuming. Using AI to automatically assess bone age from X-ray images may improve efficiency without reducing accuracy. In this study, we evaluated how well an AI-powered X-ray bone age analyzer performed compared to the established TannerWhitehouse 3 (TW-3) method. X-ray images from 900 Chinese children and adolescents were collected from 30 centers. Six doctors (three experts, three residents) and the AI system independently assessed the TW-3 radius, ulna, and short bones (RUS) and TW-3 carpal bone age. The experts' assessments were considered the gold standard. The AI analyzer had an average error of 0.48 years for TW3-RUS bone age, with 87% of assessments within 1 year of the experts. For TW3 carpal bone age, the AI had an average error of 0.48 years, with 89% within 1 year. These results were similar to or better than those of the resident raters. These findings show the AI-powered analyzer can assess bone age as accurately as human raters. This technology may improve clinical efficiency by reducing the time required for bone age assessments without compromising accuracy.
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OBJECTIVES: To determine the dose-dependent associations between antenatal corticosteroids (ANS) exposure and the rates of major morbidities, and the early weight loss percentage (EWLP) in hospital among extremely preterm infants (EPI) or extremely low birthweight infants (ELBWI). METHODS: A multicentre, retrospective cohort study of EPI or ELBWI born between 2017 and 2018 was conducted. Infants were classified into no ANS, partial ANS and complete ANS exposure group; three subgroups were generated by gestational age and birth weight. Multiple logistic regression and multiple linear regression were performed. RESULTS: There were 725 infants included from 32 centres. Among no ANS, partial ANS and complete ANS exposure, there were significant differences in the proportions of bronchopulmonary dysplasia (BPD) (24.5%, 25.4% and 16.1%), necrotising enterocolitis (NEC) (6.7%, 2.0% and 2.0%) and death (29.6%, 18.5% and 13.5%), and insignificant differences in the proportions of intraventricular haemorrhage (IVH) (12.5%, 13.2% and 12.2%), and extrauterine growth restriction (EUGR) (50.0%, 56.6% and 59.5%). In the logistic regression, compared with no ANS exposure, complete ANS reduced the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91), NEC (OR 0.21, 95% CI 0.08 to 0.57) and death (OR 0.36, 95% CI 0.23 to 0.56), and partial ANS reduced the risk of NEC (OR 0.23, 95% CI 0.07 to 0.72) and death (OR 0.54, 95% CI 0.34 to 0.87). Compared with partial ANS exposure, complete ANS decreased the risk of BPD (OR 0.58, 95% CI 0.37 to 0.91). There were insignificant associations between ANS exposure and IVH, EUGR. In the multiple linear regression, partial and complete ANS exposure increased EWLP only in the ≥28 weeks (w) and <1000 g subgroup (p<0.05). CONCLUSIONS: Different doses of ANS (dexamethasone) exposure were protectively associated with BPD, NEC, death in hospital, but not EUGR at discharge among EPI or ELBWI. Beneficial dose-dependent associations between ANS (dexamethasone) exposure and BPD existed. ANS exposure increased EWLP only in the ≥28 w and<1000 g subgroup. ANS administration, especially complete ANS, is encouraged before preterm birth. TRIAL REGISTRATION NUMBER: NCT06082414.
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Recém-Nascido de Peso Extremamente Baixo ao Nascer , Lactente Extremamente Prematuro , Redução de Peso , Humanos , Recém-Nascido , Feminino , Estudos Retrospectivos , Masculino , Gravidez , Redução de Peso/efeitos dos fármacos , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/prevenção & controle , Displasia Broncopulmonar/epidemiologia , Displasia Broncopulmonar/prevenção & controle , Displasia Broncopulmonar/mortalidade , Relação Dose-Resposta a Droga , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Idade Gestacional , Doenças do Prematuro/epidemiologia , Doenças do Prematuro/prevenção & controle , Doenças do Prematuro/mortalidadeRESUMO
Treatment strategies for paediatric neuroblastoma as well as many other cancers are limited by the unfavourable tumour microenvironment (TME). In this study, the TMEs of neuroblastoma were grouped by their genetic signatures into four distinct subtypes: immune enriched, immune desert, non-proliferative and fibrotic. An Immune Score and a Proliferation Score were constructed based on the molecular features of the subtypes to quantify the immune microenvironment or malignancy degree of cancer cells in neuroblastoma, respectively. The Immune Score correlated with a patient's response to immunotherapy; the Proliferation Score was an independent prognostic biomarker for neuroblastoma and proved to be more accurate than the existing clinical predictors. This double scoring system was further validated and the conserved molecular pattern associated with immune landscape and malignancy degree was confirmed. Axitinib and BI-2536 were confirmed as candidate drugs for neuroblastoma by the double scoring system. Both in vivo and in vitro experiments demonstrated that axitinib-induced pyroptosis of neuroblastoma cells activated anti-tumour immunity and inhibited tumour growth; BI-2536 induced cell cycle arrest at the S phase in neuroblastoma cells. The comprehensive double scoring system of neuroblastoma may predict prognosis and screen for therapeutic strategies which could provide personalized treatments.
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Axitinibe , Imunoterapia , Neuroblastoma , Microambiente Tumoral , Neuroblastoma/imunologia , Neuroblastoma/terapia , Neuroblastoma/patologia , Neuroblastoma/tratamento farmacológico , Humanos , Microambiente Tumoral/imunologia , Prognóstico , Animais , Imunoterapia/métodos , Linhagem Celular Tumoral , Axitinibe/uso terapêutico , Criança , Masculino , Feminino , Pré-Escolar , Camundongos , Lactente , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células/efeitos dos fármacosRESUMO
OBJECTIVES: This study aimed to identify discrepancies in the retinal nerve fiber layer (RNFL) between type 1 diabetes mellitus (T1DM) children without retinopathy and healthy subjects in northern China. METHODS: This was a cross-sectional hospital-based study carried out from Jan 2019 until Jul 2021â¯at the department of pediatrics in Tianjin medical university general hospital. Children with T1DM but no retinal disease were screened. RNFL thickness was obtained via spectral domain optical coherence tomography. Disease duration, HbA1c, 25-hydroxyvitamin D level, insulin regimen, and diet control status were also collected. RESULTS: A total of 20 children with T1DM and 20 matched health participants were enrolled. The mean age in the T1DM group was 10.3 ± 2.8 years, and the median duration of diabetes was 1 (range 1-3) year. Children with T1DM had thinner average RNFL than control subjects (105 ± 6 vs. 110 ± 11⯵m, p=0.008), especially in temporal and nasal parts. There was a significant negative association between HbA1c levels and the RNFL thickness in the T1DM group (B (95â¯% confidence interval): -4.313 (-7.055 to -1.571); p=0.005). CONCLUSIONS: In our study, the decreased thickness of RNFL was negatively associated with elevated HbA1c in children with early stages of T1DM.
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Diabetes Mellitus Tipo 1 , Retinopatia Diabética , Humanos , Criança , Adolescente , Estudos Transversais , Células Ganglionares da Retina , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Fibras Nervosas , Tomografia de Coerência Óptica/métodos , China/epidemiologiaRESUMO
Background: In 2020, our center established a Tanner-Whitehouse 3 (TW3) artificial intelligence (AI) system using a convolutional neural network (CNN), which was built upon 9059 radiographs. However, the system, upon which our study is based, lacked a gold standard for comparison and had not undergone thorough evaluation in different working environments. Methods: To further verify the applicability of the AI system in clinical bone age assessment (BAA) and to enhance the accuracy and homogeneity of BAA, a prospective multi-center validation was conducted. This study utilized 744 left-hand radiographs of patients, ranging from 1 to 20 years of age, with 378 boys and 366 girls. These radiographs were obtained from nine different children's hospitals between August and December 2020. The BAAs were performed using the TW3 AI system and were also reviewed by experienced reviewers. Bone age accuracy within 1 year, root mean square error (RMSE), and mean absolute error (MAE) were statistically calculated to evaluate the accuracy. Kappa test and Bland-Altman (B-A) plot were conducted to measure the diagnostic consistency. Results: The system exhibited a high level of performance, producing results that closely aligned with those of the reviewers. It achieved a RMSE of 0.52 years and an accuracy of 94.55% for the radius, ulna, and short bones series. When assessing the carpal series of bones, the system achieved a RMSE of 0.85 years and an accuracy of 80.38%. Overall, the system displayed satisfactory accuracy and RMSE, particularly in patients over 7 years old. The system excelled in evaluating the carpal bone age of patients aged 1-6. Both the Kappa test and B-A plot demonstrated substantial consistency between the system and the reviewers, although the model encountered challenges in consistently distinguishing specific bones, such as the capitate. Furthermore, the system's performance proved acceptable across different genders and age groups, as well as radiography instruments. Conclusions: In this multi-center validation, the system showcased its potential to enhance the efficiency and consistency of healthy delivery, ultimately resulting in improved patient outcomes and reduced healthcare costs.
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Serum 25-hydroxyvitamin D (25(OH)D) is an indicator of nutritional status in the body. Vitamin D (VD) is important for promoting calcium and phosphorus absorption and bone health. This work investigated the correlation between 25(OH)D level and bone density and bone development in infants. the bone density in 150 infants aged 0 to 3 years was measured by ultrasound. Based on the values of bone density, the infants were grouped into a normal (N) group (n = 95) and an abnormal (ABN) group (n = 55). At the same time, serum 25(OH)D, calcium, phosphorus, alkaline phosphatase (ALP), and parathyroid hormone (PTH) levels were detected to analyze their correlations. 25(OH)D, calcium, and phosphorus levels in the ABN group were greatly decreased, while ALP and PTH levels were increased obviously, all presenting remarkable differences with those in the N group (P<0.05). 25(OH)D was positively linked with bone density (r=0.918, P<0.01), calcium level (r=0.316, P<0.05) and phosphorus level (r=0.209, P<0.05) but showed negative associations with ALP level (r=-0.428, P<0.01) and PTH level (r=-0.327, P<0.05). elevating 25(OH)D was crucial in reducing the incidence of abnormal bone density, bettering bone metabolism, and improving the bone health of infants.
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Densidade Óssea , Cálcio , Humanos , Lactente , Vitaminas , Fosfatase Alcalina , Corantes , DEET , FósforoRESUMO
Background: In China, the number of preterm infants is the second largest globally. Compared with those in developed countries, the mortality rate and proportion of treatment abandonment for extremely preterm infants (EPIs) are higher in China. It would be valuable to conduct a multicenter study and develop predictive models for the mortality risk. This study aimed to identify a predictive model among EPIs who received complete care in northern China in recent years. Methods: This study included EPIs admitted to eighteen neonatal intensive care units (NICUs) within 72 hours of birth for receiving complete care in northern China between January 1, 2015, and December 31, 2018. Infants were randomly assigned into a training dataset and validation dataset with a ratio of 7:3. Univariate Cox regression analysis and multiple regression analysis were used to select the predictive factors and to construct the best-fitting model for predicting in-hospital mortality. A nomogram was plotted and the discrimination ability was tested by an area under the receiver operating characteristic curve (AUROC). The calibration ability was tested by a calibration curve along with the Hosmer-Lemeshow (HL) test. In addition, the clinical effectiveness was examined by decision curve analysis (DCA). Results: A total of 568 EPIs were included and divided into the training dataset and validation dataset. Seven variables [birth weight (BW), being inborn, chest compression in the delivery room (DR), severe respiratory distress syndrome, pulmonary hemorrhage, invasive mechanical ventilation, and shock] were selected to establish a predictive nomogram. The AUROC values for the training and validation datasets were 0.863 [95% confidence interval (CI): 0.813-0.914] and 0.886 (95% CI: 0.827-0.945), respectively. The calibration plots and HL test indicated satisfactory accuracy. The DCA demonstrated that positive net benefits were shown when the threshold was >0.6. Conclusions: A nomogram based on seven risk factors is developed in this study and might help clinicians identify EPIs with risk of poor prognoses early.
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The FK506-binding protein 51 (FKBP51, encoded by FKBP5 gene) has emerged as a critical regulator of mammalian endocrine stress responses and as a potential pharmacological target for metabolic disorders, including type 2 diabetes (T2D). However, in ß cells, which secrete the only glucose-lowering hormone-insulin, the expression and function of FKBP5 has not been documented. Here, using human pancreatic tissue and primary human islets, we demonstrated the abundant expression of FKBP5 in ß cells, which displayed an responsive induction upon acute inflammatory stress mimicked by in vitro treatment with a cocktail of inflammatory cytokines (IL-1ß, IFN-γ, and TNF-α). To explore its function, siRNAs targeting FKBP5 and pharmacological inhibitor SAFit2 were applied both in clonal NIT-1 cells and primary human/mice islets. We found that FKBP5 inhibition promoted ß-cell survival, improved insulin secretion, and upregulated ß-cell functional gene expressions (MAFA and NKX6.1) in acute-inflammation stressed ß cells. In primary human and mice islets, which constitutively suffer from inflammation stress during isolation and culture, FKBP5 inhibition also presented decent performance in improving islet function, in accordance with its protective effect against inflammation. Molecular studies found that FKBP5 is an important regulator for FOXO1 phosphorylation at Serine 256, and silencing of FOXO1 abrogated the protective effect of FKBP5 inhibition, suggesting that it is the key downstream effector of FKBP5 in ß cells. At last, in situ detection of FKBP5 protein expression on human and mice pancreases revealed a reduction of FKBP5 expression in ß cells in human T2D patients, as well as T2D mice model (db/db), which may indicate a FKBP5-inhibition-mediated pro-survival mechanism against the complex stresses in T2D milieus.
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Objective: This study aims to summarize the clinical characteristics of one teenager with autoimmune polyglandular syndrome (APS) type III C + D to improve the understanding of APS III C + D and its effect of thyroid function. Methods: This article reported the clinical manifestations, laboratory examinations, treatment methods, and outcomes of an adolescent with anemia admitted to the Pediatrics Department of Tianjin Medical University General Hospital in July 2020 and reviewed the literature. Results: A girl, aged 13 years and 1 month, was admitted to the hospital due to anemia for more than 4 years and episodic abdominal pain for 1 week. Four years ago, the girl went to a local hospital for "vitiligo", and a routine blood test revealed anemia. The lowest hemoglobin (HGB) was 61 g/L, and the blood test revealed iron deficiency anemia. She had no menstrual cramps for 2 months. Urine routine showed protein 3+â¼4+ and 258 red blood cells (RBCs)/high-power field. Urine protein was 3,380 mg/24 h. Free thyroxine was low, thyroid-stimulating hormone was >100â uIU/ml, thyroid peroxidase antibody was >1,000â IU/ml, and thyroglobulin antibody and thyrotropin receptor antibody were negative. Pituitary magnetic resonance imaging showed a mass in the sellar region with a uniform signal and a maximum height of about 15.8 mm. The result of the antinuclear antibody was 1:80 homogeneous type, and anti-dsDNA and anticardiolipin antibodies IgA and IgM were slightly higher. Thyroxine and iron were given for 1 month, menstruation resumed, and urine protein and RBC count decreased. After 5 months of treatment, free thyroid function, HGB, RBCs in urine, and pituitary returned to normal. Later, a renal biopsy showed changes in focal proliferative glomerulonephritis, and the girl was diagnosed with lupus glomerulonephritis type III. After 3 days of shock therapy with methylprednisolone, prednisone, mycophenolate mofetil, and other treatments were administrated for 1 year. At the time of writing, urine protein was 280 mg/24 h. Conclusion: Co-occurrence of Hashimoto's thyroiditis, vitiligo, anemia, pituitary hyperplasia, and lupus nephritis is rare. It is very important to pay attention to the screening of thyroid function.
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CONTEXT: Age of pubertal onset has been decreasing in many countries but there have been no data on pubertal development in Chinese children over the last decade. OBJECTIVE: The primary objective of the study was to evaluate the current status of sexual maturation in Chinese children and adolescents. Secondary objectives were to examine socioeconomic, lifestyle, and auxological associations with pubertal onset. METHODS: In this national, cross-sectional, community-based health survey, a multistage, stratified cluster random sampling method was used to select a nationally representative sample, consisting of 231 575 children and adolescents (123 232 boys and 108 343 girls) between 2017 and 2019. Growth parameters and pubertal staging were assessed by physical examination. RESULTS: Compared to 10 years previously, the median age of Tanner 2 breast development and menarche were similar at 9.65 years and 12.39 years respectively. However, male puberty occurred earlier with a median age of testicular volume ≥4 mL of 10.65 years. Pubertal onset did occur earlier at the extremes, with 3.3% of the girls with breast development at 6.5-6.99 years old, increasing to 5.8% by 7.5-7.99 years old. Early pubertal onset was also noted in boys, with a testicular volume ≥ 4 mL noted in 1.5% at 7.5-7.99 years, increasing to 3.5% at 8.5-8.99 years old. Obesity and overweight increased risk of developing earlier puberty relative to normal weight in both boys and girls. CONCLUSION: Over the past decade, pubertal development is occurring earlier in Chinese children. While the cause is multifactorial, overweight and obesity are associated with earlier puberty onset. The currently used normative pubertal data of precocious puberty may not be applicable to diagnose precocious puberty.
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Sobrepeso , Puberdade Precoce , Criança , Feminino , Humanos , Masculino , Estudos Transversais , População do Leste Asiático , Menarca , Obesidade , Sobrepeso/epidemiologia , Puberdade , Puberdade Precoce/epidemiologia , Puberdade Precoce/etiologia , Puberdade Precoce/diagnóstico , Maturidade SexualRESUMO
MSCs have been demonstrated to have a great benefit for type 1 diabetes mellitus (T1DM) due to their strong immunosuppressive and regenerative capacity. However, the comprehensive mechanism is still unclear. Our previous study indicated that transforming growth factor beta induced (TGFBI) is highly expressed in human umbilical cord-derived mesenchymal stem or stromal cells (hUC-MSCs), which are also implicated in T1DM. In this study, we found that infusion of TGFBI knockdown hUC-MSCs displayed impaired therapeutic effects in T1DM mice and decreased immunosuppressive capability. TGFBI knockdown hUC-MSCs could increase the proportion of T-cell infiltration while increasing the expression of IFN-gamma and interleukin-17A in the spleen. In addition, we also revealed that hUC-MSC-derived TGFBI could repress activated T-cell proliferation by interfering with G1/S checkpoint CyclinD2 expression. Our results demonstrate that TGFBI plays a critical role in MSC immunologic regulation. TGFBI could be a new immunoregulatory molecule controlling MSC function for new treatments of T1DM. Schematic Representation of the Immunosuppression capacity of hUC-MSC by TGFBI.
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Diabetes Mellitus Tipo 1 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Animais , Camundongos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Estreptozocina/metabolismo , Estreptozocina/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Células-Tronco Mesenquimais/metabolismo , Proliferação de Células/genética , Cordão UmbilicalRESUMO
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.
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Estatura , População do Leste Asiático , Adolescente , Masculino , Feminino , Criança , Humanos , Peso Corporal , Estudos Transversais , China/epidemiologia , Valores de ReferênciaRESUMO
OBJECTIVES: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS: There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.
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Anemia de Diamond-Blackfan , Obesidade Infantil , Criança , Masculino , Feminino , Humanos , Anemia de Diamond-Blackfan/epidemiologia , Anemia de Diamond-Blackfan/genética , Obesidade Infantil/complicações , Glucocorticoides/uso terapêutico , Prevalência , Fatores de Risco , Proteínas Ribossômicas/genética , MutaçãoRESUMO
Evidence exists reporting that miR-410 may rescue neurological deficits, neuronal injury, and neuronal apoptosis after experimental hypoxic ischemia. This study aimed to explore the mechanism by which miR-410 transferred by bone marrow-derived mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) may alleviate hypoxic-ischemic brain damage (HIBD) in newborn mice. BMSCs were isolated from total bone marrow cells of femur and tibia of newborn mice, and primary neurons were extracted from the cerebral cortex of newborn mice within 24 h of birth. EVs were extracted from BMSCs transfected with the mimic or inhibitor of miR-410. Primary neurons were subjected to hypoxia and treated with overexpression (oe)-HDAC4, small interfering RNA (siRNA)-ß-catenin, or Wnt pathway inhibitor and/or EV (miR-410 mimic) or EV (miR-410 inhibitor). A neonatal mouse HIBD model was established and treated with EVs. When BMSC-EVs were endocytosed by primary neurons, miR-410 was upregulated, neuronal viability was elevated, and apoptosis was inhibited. miR-410 in BMSC-EVs targeted HDAC4, thus increasing neuronal viability and reducing apoptosis. Conversely, overexpression of HDAC4 activated the Wnt pathway and enhanced the nuclear translocation of ß-catenin. Treatment with miR-410-containing BMSC-EVs improved learning and memory abilities of HIBD mice while attenuating apoptosis by inactivating the Wnt pathway via targeting HDAC4. Taken together, the findings suggest that miR-410 delivered by BMSC-EVs alleviates HIBD by inhibiting HDAC4-dependent Wnt pathway activation.
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Vesículas Extracelulares , Histona Desacetilases/metabolismo , Hipóxia-Isquemia Encefálica , Células-Tronco Mesenquimais , MicroRNAs , Animais , Medula Óssea/metabolismo , Encéfalo/metabolismo , Vesículas Extracelulares/metabolismo , Hipóxia/metabolismo , Hipóxia-Isquemia Encefálica/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neuroproteção , beta Catenina/metabolismoRESUMO
OBJECTIVE: This study aimed to analyze a comprehensive set of potential risk factors for obesity and overweight among Chinese children with a full range of ages and with wide geographical coverage. METHODS: In the Prevalence and Risk Factors for Obesity and Diabetes in Youth (PRODY) study (2017-2019), the authors analyzed 193,997 children aged 3 to 18 years from 11 provinces, autonomous regions, and municipalities that are geographically representative of China. All participants underwent physical examinations, and their caregivers completed questionnaires including dietary, lifestyle, familial, and perinatal information of participants. A multilevel multinomial logistic regression model was used to evaluate the potential risk factors. RESULTS: Among the actionable risk factors that were measured, higher consumption frequencies of animal offal (odds ratios [OR] for an additional time/day = 0.91, 95% CI: 0.88-0.95, same unit for OR below unless specified otherwise), dairy products (0.91, 95% CI: 0.88-0.94), freshwater products (0.94, 95% CI: 0.91-0.96), staple foods (0.94, 95% CI: 0.92-0.96), and coarse food grain (OR for every day vs. rarely = 0.92, 95% CI: 0.86-0.98) were associated with lower relative risk of obesity. However, higher restaurant-eating frequency (OR for >4 times/month vs. rarely = 1.21, 95% CI: 1.15-1.29) and longer screen-viewing duration (OR for >2 hours vs. <30 minutes = 1.16, 95% CI: 1.10-1.22) were associated with higher relative risk of obesity. Increased exercise frequency was associated with the lowest relative risk of obesity (OR for every day vs. rarely = 0.72, 95% CI: 0.68-0.77). CONCLUSIONS: Changes in lifestyle and diet of Chinese children may help relieve their obesity burden.
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Exercício Físico , Sobrepeso , China/epidemiologia , Feminino , Humanos , Obesidade/epidemiologia , Obesidade/etiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Gravidez , Prevalência , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c.609G>A homologous variant. METHODS: A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164 patients of cblC type with MMACHC c.609G>A homologous variant was conducted. The patients were diagnosed by biochemical and genetic analysis from January 1998 to December 2020. RESULTS: Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated from the age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance (P<0.05). CONCLUSION: Most of the patients with MMACHC c.609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.
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Erros Inatos do Metabolismo dos Aminoácidos , Hidrocefalia , Oxirredutases , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Feminino , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/enzimologia , Hidrocefalia/genética , Mutação , Oxirredutases/genética , Fenótipo , Gravidez , Estudos Retrospectivos , Convulsões/genéticaRESUMO
OBJECTIVE: The objective of this was to study the relationship between vitamin D receptor (VDR) and triggering receptor expressed on myeloid cells 1 (TREM-1) gene single-nucleotide polymorphisms (SNP) and neonatal sepsis susceptibility and prognosis. METHODS: The blood of 150 neonatal sepsis patients and 150 normal neonates was collected, and genomic DNA was extracted. Sanger sequencing was used to analyze the genotypes of VDR rs739837 and TREM-1 rs2234246. RESULTS: Vitamin D receptor rs739837 locus GT, TT genotype, dominant model, and recessive model were all protective factors for sepsis (0 < OR < 1, p < 0.05). The risk of sepsis in carriers of the rs739837 G allele was 0.65 times that of the rs739837 T allele (95% CI: 0.50-0.83, p < 0.001), CT, TT, dominant model, and recessive model at rs2234246 were risk factors for sepsis (OR > 1, p < 0.05). The risk of sepsis in carriers of the rs739837 T allele was 1.38 times that of carriers of the C allele (95% CI: 1.16-1.61, p < 0.001). The polymorphisms of VDR gene rs739837 and TREM-1 gene rs2234246 were not significantly correlated with the survival of patients with neonatal sepsis (p > 0.05). CONCLUSION: Vitamin D receptor gene rs739837 locus G>T is associated with a reduction in the risk of neonatal sepsis, TREM-1 rs2234246 C>T is associated with the increased risk of neonatal sepsis, but none of them was significantly associated with the prognosis of neonatal sepsis.
Assuntos
Sepse Neonatal , Receptores de Calcitriol , Receptor Gatilho 1 Expresso em Células Mieloides , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Humanos , Recém-Nascido , Polimorfismo de Nucleotídeo Único , Prognóstico , Receptores de Calcitriol/genética , Receptor Gatilho 1 Expresso em Células Mieloides/genéticaRESUMO
BACKGROUND: Many researchers have reported predicting the outcome of oral food challenges (OFCs) on the basis of specific IgE (sIgE) levels. However, the clinical usefulness of the determination of IgE antibodies to egg allergen components in Chinese children with suspected boiled egg allergy is not well studied. OBJECTIVE: Our objective was to assess the diagnostic performance of sIgE to egg white and Gal d 1, 2, 3, and 5 based on the open challenge outcome for boiled egg. METHODS: A total of 48 child patients with a suspect of boiled egg allergy were included. Serum egg white and Gal d 1, 2, 3, and 5 sIgE were measured by ImmunoCAP. Diagnostic value was assessed by area under the receiver operating characteristic curves (AUC). RESULTS: Using the OFC results as the reference parameter, Gal d 1 sIgE had the highest AUC (0.84) compared with egg white (0.77) and other investigated components (ranging from 0.51 to 0.71). The clinical sensitivity and specificity for the sIgE to Gal d 1 at optimal cutoff (6.15 kUA/L) were 73.7% and 96.7%, respectively. Sensitization to Gal d 1 with a cutoff value of >7.48 kUA/L indicated a 90% probability of positive challenge. CONCLUSION: Quantitative measurements of Gal d 1 sIgE antibodies using ImmunoCAP are useful in the management of boiled egg allergy in Chinese children.
Assuntos
Alérgenos/imunologia , Hipersensibilidade a Ovo/epidemiologia , Hipersensibilidade a Ovo/imunologia , Clara de Ovo/efeitos adversos , Ovos/efeitos adversos , Imunoglobulina E/imunologia , Especificidade de Anticorpos/imunologia , Biomarcadores , Criança , Pré-Escolar , China/epidemiologia , Suscetibilidade a Doenças , Hipersensibilidade a Ovo/diagnóstico , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Masculino , Prognóstico , Curva ROC , Testes Cutâneos , Avaliação de SintomasAssuntos
Extubação , Doenças do Prematuro , Peso Corporal , Cafeína , Citratos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Mecânica RespiratóriaRESUMO
OBJECTIVE: To systematically describe the short stature of patients with Diamond-Blackfan anemia and to explore factors affecting the height development of patients with Diamond-Blackfan anemia. STUDY DESIGN: This cross-sectional study was conducted at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and the height, weight, and clinical data of 129 patients with Diamond-Blackfan anemia were collected from June 2020 to September 2020. RESULTS: The median height-age-z score (HAZ) of children affected by Diamond-Blackfan anemia was -1.54 (-6.36-1.96). Short stature was found in 37.98% of the patients. Specific Diamond-Blackfan anemia growth curves were developed for weight, height, and body mass index, separately for male and female patients. Multivariable logistic regression models showed that female sex (aOR 4.92; 95% CI 1.29-18.71; P = .0195), underweight (aOR 10.41, 95% CI 1.41-76.98, P = .0217), cardiovascular malformations (aOR 216.65; 95% CI 3.29-14279.79; P = .0118), and RPL11(aOR 29.14; 95% CI 1.18-719.10; P = .0392) or RPS26 (aOR 53.49; 95% CI 1.40-2044.30; P = .0323) mutations were independent risk factors for short stature. In the subgroup of patients who were steroid-dependent, patients with a duration of steroid therapy over 2 years (OR 2.95; 95% CI 1.00-8.66; P = .0494) or maintenance dose of prednisone >0.1 mg/kg per day (OR 3.30; 95% CI 1.02-10.72; P = .0470) had a higher incidence of short stature. CONCLUSIONS: Patients with Diamond-Blackfan anemia had a high prevalence of short stature. The risk of short stature increased with age and was associated with sex, underweight, congenital malformations, and RPL11 or RPS26 mutations. The duration of steroid therapy and maintenance dose of steroid was significantly associated with the incidence of short stature in steroid-dependent patients with Diamond-Blackfan anemia.