Non-linear relationship between sleep duration and blood pressure in children with short stature.

Background: Evidence regarding the relationship between sleep duration and blood pressure is controversial. Therefore, the aim of this study was to investigate the relationship between sleep duration and blood pressure in children with short stature. Methods: A total of 1,085 participants with short stature were enrolled from the Affiliated Hospital of Jining Medical University in China. The variables involved in this study included sleep duration, anthropometric indicators and biochemical parameters. Sleep duration was evaluated in a face-to-face interview. Results: The average age of the 1,085 selected participants was 10.2 ± 3.5 years old, and approximately 763 (70.32%) of them were male. The results of adjusted linear regression showed that sleep duration was negatively associated with systolic blood pressure z scores (SBP-Z) and diastolic blood pressure z scores (DBP-Z) after adjusting for confounders (ß -0.07, 95% CI -0.13, -0.01 P = 0.038; ß -0.05, 95% CI -0.10, -0.01 P = 0.035, respectively). A nonlinear relationship was detected between sleep duration and blood pressure, including SBP-Z, DBP-Z and mean arterial pressure z scores (MAP-Z). The inflection point of the nonlinear relationship between sleep duration and SBP-Z is 10 h, and the inflection point of DBP-Z and MAP-Z is 8 h. Conclusion: This study revealed a nonlinear relationship between sleep duration and blood pressure in children with short stature. The findings suggest that the optimal sleep duration in children with short stature was 8-10 h, and sleep durations either too short or too long were associated with increased blood pressure levels.

Association between serum uric acid and triglyceride-glucose index in children and adolescents with short stature.

The aim of this study was to explore the relationship between serum uric acid (SUA) and the triglyceride-glucose (TyG) index, which is a more effective indicator of insulin resistance. The study participants included 1700 children and adolescents with short stature who were recruited at the Affiliated Hospital of Jining Medical University in China between March 2013 and April 2021. A positive association between SUA levels and the TyG index was detected by univariate analysis (p < 0.001). Furthermore, a nonlinear relationship was detected between SUA and the TyG index, whose point was 6.55 mg/dL. There was a positive association between SUA and the TyG index when the SUA level was greater than 6.55 mg/dL (ß 0.17, 95% CI: 0.07, 0.27; P < 0.001). However, we did not observe a significant relationship between SUA and the TyG index when the SUA level was less than 6.55 mg/dL (ß 0.02, 95% CI: - 0.01, 0.05; P = 0.091). In addition, a stratified analysis was performed to appraise changes in this relationship for different sexes. The relationship between SUA and the TyG index in males and females is consistent with that in the general population, showing a nonlinear relationship. However, the inflection points of SUA level were significantly higher in males than in females, and the inflection points were approximately 6.72 and 5.88 mg/dL, respectively. This study revealed a nonlinear relationship between SUA and the TyG index in children with short stature. The nonlinear relationship remained in gender stratification analysis, but the inflection point of SUA level was higher in men. Further studies are needed to establish a causal relationship between SUA levels and the TyG index in children with short stature.

Detecting Undifferentiation of Tertiary and County Hospitals in China in Adoption of DRG Instrument.

(1) Background: Undifferentiated function for medical institutes in different levels had been a barrier to China's healthcare reform. Thus, this study aimed to detect medical services that were capable offered both in tertiary and county hospitals in China and discuss the process of detection. (2) Method: Data of 2 tertiary hospitals that were city level and 12 county-level hospitals from one city in China were collected and grouped into diagnosis-related groups (DRGs). A strategy with four steps was devised by considering the aspects of service volume, in-hospital mortality rate, in-hospital adverse events rate, and inpatient cost. Additionally, a comparison of each indicator was made between city- versus county-level hospitals. (3) Results: There were no differences in service quality between the two levels of hospitals while county hospitals had lower average inpatient costs in 129 DRGs that covered 39.5% of all cases. About CNY 0.26 billion would be saved if certain cases were paid at county-level prices. (4) Conclusion: The study proposed a strategy with four steps that could help in locating the range of diseases in which patients' admission suffered from the problem of undifferentiation between hospitals' functions to reduce the irrational growth of healthcare expenditure.

A Retrospective Analysis of Patients with Short Stature in Eastern China between 2013 and 2019.

OBJECTIVE: To identify the aetiology of growth and development diseases and assess the long-term effectiveness of recombinant human growth hormone (rhGH) therapy in a real-life clinical setting and provide better guidance in clinical strategy and decision making. METHODS: This retrospective study included 1145 children and adolescents with short stature admitted to the Department of Endocrinology, Affiliated Hospital of Jining Medical University, from January 2013 to December 2019, of whom 484 received rhGH treatment. The related anthropometrics and laboratory examinations were assessed in all participants. RESULTS: A total of 1145 children and adolescents with short stature aged 10.5 ± 3.3 years, including 740 boys and 405 girls, were analysed in this study. The number of children and adolescents with short stature gradually increased per year from 2013 to 2019. The mean pretreatment height standard deviation score (SDS) and insulin-like growth factor-1 SDS were -2.93 ± 1.05 and -1.01 (-1.83--0.16), respectively. The majority of the children (658, 57.47%) were prepubescent. In total, 484 subjects aged 10.6 ± 3.2 years received rhGH and were followed up, and among them, 292 children were treated for more than one year. As the treatment time increased, the children's height SDS gradually increased, and most of them attained a height SDS within the normal range. The mean height SDS in children who were treated for more than one year was -3.0 ± 1.0 at baseline and gradually increased to -0.8 ± 0.3 by year 6. The results were consistent across subgroups of different aetiologies of short stature. CONCLUSIONS: Increasing attention has been given to the height of children during the period of 2013-2019 in eastern China. The present findings indicate that children with short stature need to be referred to a specialist centre to diagnose the cause of growth failure and that short children receiving rhGH therapy show a significant increase in height over time.

Association between insulin-like growth factor-1 and systolic blood pressure in children and adolescents with short stature.

The relationship between insulin-like growth factor-1 (IGF-1) and systolic blood pressure (SBP) is controversial in adults and children. The purpose of this study was to investigate the relationship between the IGF-1 standard deviation score (IGF-1 SDS) and SBP in children with short stature. A cross-sectional analysis including 1315 children with short stature was conducted from March 2013 to October 2020. We estimated IGF-1, blood pressure and other laboratory tests, and anthropometric indicators were also evaluated. Subgroup analyses of the pubertal stage, sex, growth hormone levels, thyroid hormone levels, fasting blood glucose levels, and triglyceride levels were performed. A positive association between the IGF-1 SDS and SBP was observed by univariate analysis (p < .001). We further found a nonlinear association between the IGF-1 SDS and SBP. The inflection point for the curve was found at an IGF-1 SDS level of -2.91. In multivariate piecewise linear regression, there was a positive association between the IGF-1 SDS and SBP when the IGF-1 SDS was greater than -2.91 (ß 1.56, 95% CI: 0.91, 2.22; p < .001). However, we did not observe a significant relationship between the IGF-1 SDS and SBP when the IGF-1 SDS level was less than -2.91 (ß -0.95, 95% CI -3.17, 1.28; p = .379). This association was consistent across subgroup analyses. The present study demonstrated that there is a nonlinear relationship between the IGF-1 SDS and SBP in children with short stature. Increased serum IGF-1 levels were associated with elevated SBP when the IGF-1 levels reached the inflection point.

Association between triglyceride glucose index and peak growth hormone in children with short stature.

Growth hormone (GH) secretion is related to many factors, such as weight and puberty, and the reproducibility of GH provocation tests is very poor. This study aimed to evaluate whether the triglyceride (TyG) index was associated with peak GH in children with short stature. This study included 1095 children with short stature divided into two groups based on peak GH level in GH provocation tests [GH deficiency (GHD) group = 733 children; non-GHD group = 362 children]. We found that the TyG index was significantly higher in the GHD group than in the non-GHD group (P < 0.001). A nonlinear relationship was detected between the TyG index and peak GH, whose point was 7.8. A significant negative association between the TyG index and peak GH was observed when the TyG index was greater than 7.8 (ß - 2.61, 95% CI - 3.98, - 1.24; P < 0.001), whereas, the relationship between the TyG index and peak GH was not significant when the TyG index was lower than 7.8 (ß 0.25, 95% CI - 1.68, 2.17; P = 0.799). There is a nonlinear relationship between the TyG index and peak GH, and a higher TyG index is associated with decreased peak GH in children with short stature.

Association between serum uric acid and triglycerides in Chinese children and adolescents with short stature.

BACKGROUND: Elevated triglyceride (TG) levels are a biomarker for cardiovascular disease (CVD) risk. The correlation between serum uric acid (SUA) and TG concentrations in adults or obese children is well established. However, studies on SUA and TG in children with short stature are limited. AIM: To determine the relationship between SUA and TG levels in short children and adolescents. METHOD: This was a cross-sectional evaluation of a cohort of 1095 patients with short stature (720 males and 375 females). The related clinical characteristics, including anthropometric and biochemical parameters, were determined. RESULTS: Smooth curve fitting, adjusted for potential confounders was performed, which indicated the existence of a non-linear relationship between these measures. Piecewise multivariate linear analysis revealed a significant positive relationship between SUA and TG at SUA concentrations over 7 mg/dL (ß = 0.13, 95% CI: 0.05-0.22, P = 0.002) but no significant correlation at lower SUA levels (ß = 0.01, 95% CI: 0.01-0.04, P = 0.799). Furthermore, a stratified analysis was performed to appraise changes in this relationship for different sexes and standard deviation levels of body mass index (BMI). The non-linear relationship remained consistent in males and females with BMI standard deviation scores (BMI SDS) ≥ 0, with inflection points of 6.71 mg/dL and 3.93 mg/dL, respectively. Within these two groups, SUA and TG levels showed a positive association when SUA levels were higher than the inflection point (ß = 0.21, 95% CI: 0.11-0.31, P < 0.001 for males and ß = 0.1, 95% CI: 0.03-0.17, P = 0.005 for females). However, a specific relationship was not observed at lower SUA levels. No significant relationships were found between SUA and TG levels in males and females with BMI SDS < 0. CONCLUSION: The present study identified the non-linear association of SUA and TG levels with short children and adolescents. This relationship was based on BMI status. This finding suggests that health status should be considered for short stature children with high SUA levels, especially in children with a high BMI standard deviation score.

Association between Insulin-Like Growth Factor-1 and Relative Skeletal Maturation: A Retrospective Cohort Study of Short Children and Adolescents.

OBJECTIVE: Delays in skeletal maturity are related to bone mass and fracture risk in children, but the factors that determine it are unknown. We aimed to identify the association between insulin-like growth factor-1 (IGF-1) and skeletal maturation before and after growth hormone (GH) treatment. METHODS: In this retrospective cohort study, we observed 783 short children and adolescents, 229 of whom received GH therapy. Skeletal maturation was assessed based on the difference between bone age (BA) and chronological age (CA) (noted as BA-CA). Anthropometric data and laboratory values were measured, and BA was evaluated using the Greulich and Pyle method. RESULTS: The delayed BA group was defined as BA-CA < -2 SD (n = 457), and the occurrence rate of BA delay was 58.37%. A nonlinear relationship was observed between the IGF-1 standard deviation score (IGF-1 SDS) and BA-CA before and after GH therapy. Before GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than -2 SDS (ß 0.17, 95% CI 0.08, 027; P < 0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than -2 SDS (ß 0.07, 95% CI -0.12, 0.26; P = 0.454). After GH therapy, there was a significant positive association between the IGF-1 SDS and BA-CA when the IGF-1 level was lower than 2 SDS (ß 0.20, 95% CI 0.12, 028; P < 0.001). However, we did not observe a significant relationship between the IGF-1 SDS and BA-CA when the IGF-1 level was greater than 2 SDS (ß -0.03, 95% CI -0.33, 0.27; P = 0.866). CONCLUSION: BA is more delayed in short children and adolescents. There is a nonlinear relationship between IGF-1 and BA maturation in short children before and after GH treatment. These findings suggest that a low level of IGF-1 may contribute to BA delay in short children and adolescents.

Relationship between hemoglobin and insulin-like growth factor-1 in children and adolescents with idiopathic short stature.

BACKGROUND: The growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis is critical for the regulation of children's growth and development. Serum IGF-1 concentrations are usually low in individuals with idiopathic short stature (ISS) despite normal endogenous GH levels, and the associated underlying factors are unknown. This study aimed to explore the relationship between IGF-1 and hemoglobin (Hb) in children with ISS. METHODS: A cross-sectional analysis was performed including 178 children and adolescents with ISS who were enrolled from March 2013 to February 2019. The related clinical and biochemical parameters were evaluated for each patient. Univariate analysis, smooth curve fitting and multivariate piecewise linear regression were performed. RESULT: The mean levels of IGF-1 standard deviation scores (SDS) and Hb were - 0.99 (- 1.60 - -0.09) and 131.81 ± 9.36 g/L, respectively. Univariate analysis displayed a significant positive association between Hb and IGF-1 SDS (P < 0.001). After adjusting for potential confounding factors, the positive relationship between Hb and IGF-1 SDS remained (P = 0.001). Furthermore, there was an inflection point for Hb in the curve. In a multivariate piecewise linear regression model, IGF-1 SDS was significantly positively associated with Hb when Hb concentrations were lower than 145 g/L (B 0.05; 95% CI 0.02, 0.07; P < 0.001). However, IGF-1 SDS decreased with increasing Hb levels when Hb concentrations were greater than 145 g/L (B -0.15; 95% CI -0.23, - 0.06; P = 0.001). CONCLUSION: This study demonstrated that Hb is associated with IGF-1 in Chinese children and adolescents with ISS. The levels of IGF-1 increased with the elevation of Hb, but when the concentration of Hb exceeded a certain range, with the increase of Hb, IGF-1 decreased instead.

Analysis of clinical features and early warning signs in patients with severe COVID-19: A retrospective cohort study.

Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019. Although previous studies have described the clinical aspects of COVID-19, few studies have focused on the early detection of severe COVID-19. Therefore, this study aimed to identify the predictors of severe COVID-19 and to compare clinical features between patients with severe COVID-19 and those with less severe COVID-19. Patients admitted to designated hospital in the Henan Province of China who were either discharged or died prior to February 15, 2020 were enrolled retrospectively. Additionally, patients who underwent at least one of the following treatments were assigned to the severe group: continuous renal replacement therapy, high-flow oxygen absorption, noninvasive and invasive mechanical ventilation, or extracorporeal membrane oxygenation. The remaining patients were assigned to the non-severe group. Demographic information, initial symptoms, and first visit examination results were collected from the electronic medical records and compared between the groups. Multivariate logistic regression analysis was performed to determine the predictors of severe COVID-19. A receiver operating characteristic curve was used to identify a threshold for each predictor. Altogether,104 patients were enrolled in our study with 30 and 74 patients in the severe and non-severe groups, respectively. Multivariate logistic analysis indicated that patients aged ≥63 years (odds ratio = 41.0; 95% CI: 2.8, 592.4), with an absolute lymphocyte value of ≤1.02×109/L (odds ratio = 6.1; 95% CI = 1.5, 25.2) and a C-reactive protein level of ≥65.08mg/L (odds ratio = 8.9; 95% CI = 1.0, 74.2) were at a higher risk of severe illness. Thus, our results could be helpful in the early detection of patients at risk for severe illness, enabling the implementation of effective interventions and likely lowering the morbidity of COVID-19 patients.

Association between Alanine Aminotransferase and Growth Hormone: A Retrospective Cohort Study of Short Children and Adolescents.

OBJECTIVE: This study aimed to examine the relationship between serum alanine aminotransferase (ALT) and growth hormone (GH) in children and adolescents with short stature. METHODS: In this retrospective cohort study, 670 Chinese children and adolescents with short stature were included, and 253 of them received recombinant human GH (rhGH) therapy. Anthropometric and biochemical indicators were measured. GH peak levels were assessed after provocation tests with L-dopa and insulin. The subjects were divided into 3 groups according to the GH peak level. The association between the GH peak and ALT was analyzed. The change of ALT during rhGH therapy was assessed by a generalized additive mixed model. RESULTS: Serum ALT and incidence of ALT elevation were both decreased across the GH tertiles (P = 0.002, 0.012, respectively). A univariate analysis showed that the GH peak was negatively associated with ALT (ß: -0.12; 95%CI: -0.22, -0.02; P = 0.023). Furthermore, multiple linear stepwise regression analysis demonstrated that the GH peak was independently related to ALT after adjusting for other confounding variables (ß: -0.12; 95%CI: -0.24, -0.00; P = 0.042). Besides, mean values of the change in ALT from baseline displayed that, during the early stages of rhGH treatment, serum ALT level indicated a temporary upward trend, but it subsequently gradually decreased (ß: -0.16; 95%CI: -0.23, -0.09; P < 0.001). CONCLUSIONS: GH secretion level was strongly negatively correlated with ALT in short children and adolescents. And rhGH therapy could reduce ALT level over time.

Low-density lipoprotein cholesterol levels are associated with insulin-like growth factor-1 in short-stature children and adolescents: a cross-sectional study.

BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) levels in childhood have recently been found to be the strongest predictive risk factor for coronary artery disease in adulthood. There is an increased level of LDL-C in children and adolescents with short stature. However, the underlying factors associated with increased LDL-C levels in children and adolescents with short stature are unknown. In addition, the insulin-like growth factor 1 (IGF-1) level in the short-stature population is usually below the normal reference range. The aim of this study was to investigate the relationship between IGF-1 standard deviation score (IGF-1 SDS) and LDL-C level in children and adolescents with short stature. METHODS: A cross-sectional study was conducted in a single centre of China, 557 short-stature children and adolescents whose height SDS was lower than - 2 SD after adjustment for age and gender were included. The related clinical and laboratory examinations, including anthropometric parameters, lipid profiles, IGF-1 levels and the levels of other cofactors, were assessed in all participants. RESULTS: The univariate analysis results showed a significant negative correlation between IGF-1 SDS and LDL-C levels (P = 0.006). Furthermore, a nonlinear relationship was observed between IGF-1 SDS and LDL-C by smooth curve fitting after adjusting for possible confounders. A multivariate piecewise linear regression model revealed a significant negative correlation between IGF-1 SDS and LDL-C when the IGF-1 level was greater than - 2 SDS (ß - 0.07, 95% CI -0.12, - 0.02; P = 0.006). However, we did not observe a significant relationship between IGF-1 SDS and LDL-C when the IGF-1 level was lower than - 2 SDS (ß 0.08, 95% CI -0.02, 0.17; P = 0.119). CONCLUSION: This study demonstrated a nonlinear relationship between IGF-1 and LDL-C independent of other potential confounding factors, suggesting that circulating IGF-1 may contribute to the regulation of LDL-C levels, thus meriting further investigation.

Association between Growth Hormone-Insulin-Like Growth Factor-1 Axis Gene Polymorphisms and Short Stature in Chinese Children.

OBJECTIVE: This study was designed to analyze the association between the growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis gene polymorphisms and short stature in Chinese children. METHODS: 181 growth hormone deficiency (GHD) patients and 206 normal stature controls were enrolled to attend this study. Five single-nucleotide polymorphisms in the GH receptor (GHR) and 5 SNPs within the GH-signaling pathway were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry. We conducted an association study between these SNPs and the risk of developing short stature. Linkage disequilibrium analysis was performed using Haploview software and the associations of the SNPs frequencies with short stature were analyzed using X2 tests. RESULTS: No significant difference was found in gender, weight, height, and BMI between the GHD and control groups, except that the age of GHD group was older than the control one. Allele and genotype frequencies were consistent with those expected from Hardy-Weinberg equilibrium. Compared with the controls, heterozygous genotype frequencies (CT) of rs12515480 and rs6873545 of GHR gene were significantly lower. Genotype frequencies of the other 8 SNPs did not show significant difference between these two groups. Considering a dominant model, an OR < 1 was observed for genotypes rs12515480 (OR = 0.532, P = 0.019) and rs6873545 (OR = 0.587, P = 0.017). CONCLUSIONS: The heterozygous genotypes of rs12515480 and rs6873545 of GHR gene were associated with decreased risk of GHD in Chinese children.