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Background Childhood allergic diseases are increasing worldwide with unprecedented complexity and severity, and they cause a major burden on health and healthcare costs. We aimed to identify potential factors, both in isolation and in combination, associated with allergic diseases among preschool-aged children, and to construct a nomogram prediction model based on significant factors. Methods We cross-sectionally recruited 9,501 preschool-aged children from 30 kindergartens in Beijing and Tangshan. Allergic diseases were ascertained according to the "International Study of Asthma and Allergies in Childhood" questionnaire. Risk for allergic diseases is quantified by odds ratio (OR) with 95% confidence interval (CI). Results Four factors were identified to be independently, consistently, and significantly associated with the risk for allergic diseases overall and by four clinical manifestations separately, including bedtime (per 1 hour late) (taking asthma/wheezing as an example, OR, 95% CI, P: 1.21, 1.08 to 1.35, 0.001), outdoor activities ≤1.5 h per day (1.45, 1.26 to 1.68, 3.77E-07), family history of allergic diseases (2.23, 1.92 to 2.60, 0.00E+00), and antibiotic use during childhood (3.64, 2.44 to 5.42, 1.66E-10). Further analyses revealed that family history of allergic diseases acted with antibiotic use during childhood in an additive manner. For practical reasons, risk prediction nomogram models were constructed for allergic diseases respectively in Beijing and Tangshan based on significant and conventional factors, and the prediction accuracy was good, with the C-index 69% in Tangshan and 68% in Beijing (both P=0.00E+00). Conclusions Our findings identified four factors in significant association with the risk for allergic diseases, and in particular family history of allergic diseases and antibiotic use during childhood acted additively.

BACKGROUND We aimed to identify potential risk factors for recurrent respiratory tract infection among Chinese preschool-aged children, and further to construct a nomogram prediction model. METHODS This is a cross-sectional survey conducted in Beijing. Utilizing a stratified cluster random sampling strategy, a total of 7222 children from 20 kindergartens were enrolled. Data are analyzed by STATA software and R language. RESULTS Five independent factors were identified to be significantly associated with recurrent respiratory tract infection risk overall and by pathogenic sites. The significant odds of recurrent respiratory tract infection was 8.31 (95% confidence interval [CI]: 5.69-12.12, P

We aimed to identify the contributing predictors for short stature and pre-shortness in Chinese preschool-aged children, and further to construct nomogram prediction models. A large cross-sectional, kindergarten-based study was conducted during September–November, 2019 in Beijing. Utilizing a stratified random sampling method, total 20 kindergartens with 7310 children with complete data were eligible for analysis. The prevalence of short stature and pre-shortness was 3.0% (n = 222) and 11.6% (n = 848), respectively. Six contributing predictors were significantly associated with short stature, including parental height (odds ratio, 95% confidence interval, P: 0.773, 0.69–0.86

Objectives: We aimed to identify potential risk factors, both individually and interactively, associated with overweight and obesity among preschool–aged children, and further to create a risk prediction nomogram model. Results: After graded multivariable adjustment, maternal body mass index (BMI) (odds ratio, 95% confidence interval, P under China criteria: 1.07, 1.05 to 1.10

We aimed to assess the effects of recombinant human growth hormone (rhGH) replacement therapy on metabolic changes by synthesizing data from clinical trials involving children with idiopathic growth hormone deficiency (IGHD). Two investigators independently completed literature search, quality assessment, and data extraction. Effect-size estimates are expressed as weighted mean difference (WMD) with 95% confidence interval (CI). A total of 16 clinical trials involving 1319 children were eligible for analysis. Overall analyses showed that total cholesterol was significantly decreased after rhGH replacement therapy (WMD: −0.20 mmol/l; 95% CI: −0.30 to −0.10; p

This study was prepared to identify and characterize potential factors associated with childhood asthma and wheeze in Chinese preschool-aged children. A comprehensive questionnaire was designed for children aged 3–6 years and their parents or guardians in Beijing and Tangshan from September to December 2020. The least absolute shrinkage and selection operator (LASSO) model was used to identify factors in a significant association with childhood asthma and wheeze, respectively. The LASSO model was internally validated using bootstrap resampling with 100 replications. A total of 9,529 questionnaires were certified as eligible for inclusion after stringent quality control. The prevalence of doctor-diagnosed childhood asthma and parent-reported wheeze was 2.8 and 6.2%, respectively. Factors simultaneously associated with childhood asthma and wheeze were children with a history of allergic rhinitis, hay fever, eczema, initial age of using antibiotics, body mass index category, and family history of asthma. Specifically, children's vitamin D supplement duration was significantly associated with childhood asthma, whereas the association with childhood wheeze was significant for intake frequency of night meals for children and their screen time. Modeling of significant factors in nomograms had decent prediction accuracies, with C-index reaching 0.728 and 0.707 for asthma and wheeze, respectively. In addition, internal validation was good, with bootstrap C-statistic of being 0.736 for asthma and 0.708 for wheeze. Taken together, our findings indicated that the development of asthma and wheeze among preschool-aged children was probably determined by the joint contribution of multiple factors including inherited, nutritional, unhealthy lifestyles, and history of allergic disease. Further validation in other groups is necessary.

Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder. Currently, increasing amounts of attention have been focused on the epidemiologic profiling of ADHD in children, viewed as a continuously distributed risk dimension throughout the whole lifespan. This study aimed to identify and characterize potential influential factors susceptible to ADHD-related symptoms among preschool-aged children. A comprehensive questionnaire was self-designed for both children and their parents or guardians and was distributed to 30 kindergartens from Beijing and Hebei, collecting potential influential factors in susceptibility to ADHD. ADHD was assessed by the Conner’s Abbreviated Symptom Questionnaire (C-ASQ), and 7,938 children were analyzed. Least absolute shrinkage and selection operator (LASSO) regression and hierarchical degree of adjustment were used to control possible covariates. Five factors, namely, children’s secondhand smoking exposure, breastfeeding duration, sleep mode, maternal pregnancy smoking exposure, and parental self-rating for patience, were identified to be independently and significantly associated with ADHD susceptibility. Meanwhile, dose–response relationships were observed between breastfeeding duration, parental self-rating for patience, and ADHD-related symptoms. Finally, a nomogram model was created for predicting ADHD susceptibility based on significant and conventional attributes under each criterion.

We aimed to identify the contributing predictors for short stature and pre-shortness in Chinese preschool-aged children, and further to construct nomogram prediction models.A large cross-sectional, kindergarten-based study was conducted during September-November, 2019 in Beijing. Utilizing a stratified random sampling method, total 20 kindergartens with 7310 children with complete data were eligible for analysis.The prevalence of short stature and pre-shortness was 3.0% (n = 222) and 11.6% (n = 848), respectively. Six contributing predictors were significantly associated with short stature, including parental height (odds ratio, 95% confidence interval, P: 0.773, 0.69-0.86,0.001), maternal height (0.723, 0.64-0.82,0.001), birthweight (0.826, 0.74-0.92, 0.001), birth height (0.831, 0.69-1.00, 0.046), children body mass index (1.204, 1.43-1.82,0.001), and maternal age at menarche (1.614, 1.43-1.82,0.001). Seven significant contributing predictors were found for pre-shortness, including parental height (0.805, 0.76-0.85,0.001), maternal height (0.821, 0.77-0.87,0.001), birthweight (0.881, 0.83-0.93,0.001), birth height (0.86, 0.78-0.95, 0.003), gestational weight gain (0.851, 0.77-0.94, 0.002), children body mass index (1.142, 1.05-1.24, 0.002), and chronic disease (4.016, 1.66-9.70, 0.002). The nomogram models for short stature and pre-shortness had descent prediction accuracies.Our findings indicate that short stature is predominantly determined by inherited and natal factors, and pre-shortness is additionally by modifiable factors.

Backgrounds: Some studies have reported association of circulating fibrinogen with the risk of chronic obstructive pulmonary disease (COPD), and the results are conflicting. To yield more information, we aimed to test the hypothesis that circulating fibrinogen is a promising biomarker for COPD by a meta-analysis. Methods: Data extraction and quality assessment were independently completed by two authors. Effect-size estimates are expressed as weighted mean difference (WMD) with 95% confidence interval (95% CI). Results: Forty-five articles involving 5586/18604 COPD patients/controls were incorporated. Overall analyses revealed significantly higher concentrations of circulating fibrinogen in COPD patients than in controls (WMD: 84.67 mg/dl; 95% CI: 64.24–105.10). Subgroup analyses by COPD course showed that the degree of increased circulating fibrinogen in patients with acute exacerbations of COPD (AECOPD) relative to controls (WMD: 182.59 mg/dl; 95% CI: 115.93–249.25) tripled when compared in patients with stable COPD (WMD: 56.12 mg/dl; 95% CI: 34.56–77.67). By COPD severity, there was a graded increase in fibrinogen with the increased severity of COPD relative to controls (Global Initiative for Obstructive Lung Disease (GOLD) I, II, III, and IV: WMD: 13.91, 29.19, 56.81, and 197.42 mg/dl; 95% CI: 7.70–20.11, 17.43–40.94, 39.20–74.41, and −7.88 to 402.73, respectively). There was a low probability of publication bias. Conclusion: Our findings indicate a graded, concentration-dependent, significant relation between higher circulating fibrinogen and more severity of COPD.

We aimed to assess the effects of recombinant human growth hormone (rhGH) replacement therapy on metabolic changes by synthesizing data from clinical trials involving children with idiopathic growth hormone deficiency (IGHD).Two investigators independently completed literature search, quality assessment, and data extraction. Effect-size estimates are expressed as weighted mean difference (WMD) with 95% confidence interval (CI).A total of 16 clinical trials involving 1319 children were eligible for analysis. Overall analyses showed that total cholesterol was significantly decreased after rhGH replacement therapy (WMD: -0.20 mmol/l; 95% CI: -0.30 to -0.10; p 0.001), and high-density lipoprotein was significantly increased (WMD: 0.29 mmol/l; 95% CI: 0.24 to 0.33; p 0.001). Marginal increase was noted for low-density lipoprotein (WMD: -0.22 mmol/l; 95% CI: -0.47 to 0.22; p = 0.092). Subsidiary and meta-regression analyses revealed that length of intervention and sample size were possible causes of heterogeneity. There was a low probability of publication bias.Our findings indicate an obviously favorable role of rhGH replacement therapy in lipid metabolism in children with IGHD, and this role might be dependent on length of intervention.

IntroductionMicroRNA-133a-3p (miR-133a-3p) is a potential gene regulator having an important role in the process of inflammation and lung injury. The present work studied the role of miR-133a-3p in sepsis-mediated acute respiratory distress syndrome (ARDS) and the mechanism involved.Material and methodsC57BL/6 mice were selected for the study. Protein expression of Bcl-2, cleaved caspase-3 and Bax was assessed by western blot analysis. Expression of mRNA was assessed by RT-PCR. Effects of inflammation were studied by myeloperoxidase (MPO) activity. Quantification of albumin was done by measuring the albumin conjugated with Evan’s blue. The alveolar macrophages were separated from the lungs of mice by the bronchoalveolar lavage procedure and were submitted to sepsis challenge in vitro; the macrophages were treated with lipopolysaccharide (LPS).ResultsTreatment of LPS resulted in upregulation of miR-133a-3p in alveolar macrophages. Suppression of miR-133a-3p halted the over-expression of inflammatory cytokines in macrophages and caused remission of histopathologic changes. The ARDS lungs showed a decrease in levels of proinflammatory cytokines and an increase in levels of apoptotic protein, establishing the protective role for miR-133a-3p. The results suggested sirtuin 1 (SIRT1) as a potential target of miR-133a-3p in the macrophages, also showing that expression of SIRT1 was inversely associated with expression of miR-133a-3p. The protective effect of miR-133a-3p down-regulation in LPS-mediated alveolar macrophages and sepsis-induced ARDS could be corrected by a SIRT1 inhibitor.ConclusionsDown-regulation of miR-133a-3p may exert a protective effect on lung tissue against sepsis-mediated ARDS by up-regulating the levels of SIRT1 via suppressing the inflammatory response and inhibiting the cellular apoptosis in lung tissues.

BackgroundSince the inception of newborn screening programs in China in the 1990s, pregnancy among patients with inherited, metabolic disorders has become more common. This study explores the management and outcomes of planned, full-term pregnancies in patients with phenylketonuria (PKU).MethodMarried patients with PKU from 2012 to 2017 were enrolled to receive prenatal counseling and regular health assessments. Study-related assessments included the timing of Phe-restricted diets, maternal weight gain, gestational age, pregnancy complications, and blood Phe concentrations (both pre-conception and during pregnancy), obstetrical data, and offspring outcomes(e.g. anthropomorphic measurements and developmental quotients [DQs]).ResultsA total of six offspring were successfully delivered. The mean ± SD (range) age of the mother at delivery was 26.3 ± 4.7 (range: 21.1–32.5) years. The mean duration of Phe control before pregnancy was 5.5 ± 1.3(range: 3.1–6.5) months. During pregnancy, the proportion of blood Phe concentrations within the clinically-recommended target range (120–360 μmol/L) ranged from 63.2–83.5%. Low birth weight (r = 0.886,p = 0.016).ConclusionThis is the first report of women in China with PKU who successfully gave birth to clinically healthy babies. Infant outcomes were related to maternal blood Phe management prior to and during pregnancy. In maternal PKU patients with poor compliance to dietary treatment, sapropterin dihydrochloride (6R-BH4) may be an option to improve the management of blood Phe levels.

Summary Background Phenylketonuria (PKU) is a rare inborn disease, which, untreated, leading to severe neurobehavioral dysfunction. Considering its complexity, the management of PKU may bring a formidable economic burden to parents and caregivers. It is still unknown what the out-of-pocket expenses are for a patient with PKU in China. This paper explores the household financial burden of classical PKU and its impact on Chinese families in a quantitative manner for the first time. Methods A non-interventional and observational study was conducted at the China-Japan Friendship Hospital, one of the national centers for inherited metabolic disorders in China. The medical and non-medical household financial burdens were consolidated into a questionnaire to evaluate the out-of-pocket costs (OOPCs) of PKU treatment and follow-up. Findings The total OOPCs were USD$3766.1 (0y), USD$3795.2 (1–2 ys), USD$4657.7 (3–4 ys), USD$5979.9 (5–8 ys), and USD$5588.7 (9 ys and older) for PKU patients of different age groups. The median economic burden of classical PKU was 75.0 % of total annual family income (range 1.0–779.1 %), and 94.4 % of the families exceeding the threshold considered as catastrophic expenditure. There was a negative correlation between the financial burden and the proportion of time when Phe concentrations were in the desired target range (120–250 μmol/L) in 0–4-ys group (r = -0.474, p = 0.026). Conclusions The management of PKU is associated with a severe financial burden on patients’ families, which may lead to insufficient treatment or variation of blood Phe concentration. The current reimbursement policies are as yet inadequate. A national reimbursement system targeting treatment practices for PKU patients and other rare diseases across China is imperative. Electronic supplementary material The online version of this article (doi:10.1007/s10545-016-9995-0) contains supplementary material, which is available to authorized users.

Background:Phenylketonuria (PKU) is an autosomal recessive metabolic disorder. Dietary control of classic PKU needs restriction of natural proteins. The diet results in unbalanced nutrition, which might affect the physical development of the patients. Our aim was to evaluate bone mineral density (BMD) in children with PKU.Methods:To investigate the BMD of children with PKU, 41 children with PKU and 64 healthy controls were recruited (all 3–4 years of age). Body weight and height, BMD, Phe blood levels, thyroid function, calcium, phosphorus, iron metabolism markers, and vitamin D3 were measured.Results:Body height and BMD of patients were lower than in controls. The BMD of controls was positively associated with age, body weight and height. In patients, BMD was positively associated with body weight. There was no correlation between Phe blood levels and BMD in patients. Blood levels of alkaline phosphatase were higher in patients compared to controls. Blood calcium levels were higher in 4-year-old patients, while the body weight was lower compared to controls. Thyroid function, iron metabolism markers, vitamin D3 levels and IGF-1 levels were normal.Conclusions:Reduced BMD was observed in children with phenylketonuria, but the exact reasons for this remain to be elucidated.