Search

Abstract This phase 3, observer-blinded, non-inferiority randomized trial (ClinicalTrials.gov: NCT05517642), conducted from September 2022 to May 2023 at three Malaysian sites, involved 540 adults previously vaccinated with three COVID-19 doses. Participants were randomized 1:1 to receive either one dose of inhaled Recombinant COVID-19 Vaccine (Ad5-nCoV-IH) or intramuscular tozinameran (BNT-IM). The study assessed safety, vaccine efficacy (VE) and immunogenicity against SARS-CoV-2 variants. The primary outcome was the non-inferiority of anti-spike protein receptor-binding domain (S-RBD IgG) antibodies, with a 97.5% confidence interval lower limit for the geometric mean concentration (GMC) ratio >0.67. Ad5-nCoV-IH showed lower immunogenicity than BNT-IM, with a GMC ratio of 0.22 and a seroconversion rate difference of -71.91%. Adverse drug reactions (ADRs) were less frequent with Ad5-nCoV-IH (39.26%) compared to BNT-IM (64.68%). No serious vaccine-related adverse events were reported. Both vaccines had comparable efficacy against COVID-19 variants. This study was funded by Tianjin Biomedical Science and Technology Major Project.

Abstract Background The purpose of this study was to investigate the typing of adenovirus (AdV) infection in children hospitalized with acute respiratory tract infection (ARTI) and its clinical characteristics. Methods Samples from 7832 hospitalized children with ARTIs from January 2021 to June 2022 were tested by multiplex PCR for AdV. AdV hex neighborhood genes were amplified and sequenced for typing by nested PCR. Results Three hundred twenty-eight cases were positive for AdV with rate of 4.48% (328/7832). No statistical difference in the rate of AdV detection was observed in different ages (P > 0.05). Among the 328 cases, 305 cases underwent amplification and sequence determination of AdV five-neighborhood, six-neighborhood and fibronectin genes. Only 237 cases were sequenced successfully for all 3 genetic fragments. The typing results of 231 cases with 3 genes were consistent, with 49.78% (115/231) of type 3, 41.56% (96/231) of type 7 and 8.66% (20/231) of other types identified. The main clinical symptoms in 231 children hospitalized with ARTI who were AdV positive were cough, sputum not easily coughable, Wheezing or shortness of breath and fever. Clinical diagnoses of 231 cases included: acute bronchitis 3.03% (7/231), capillary bronchitis 16.45% (38/231), pneumonia (mild/severe) 76.62% (177/231) (68.40% (158/231) in mild and 8.23% (19/231) in severe cases), bronchial asthma combined with pulmonary infection 3.46% (8/231). Higher percentage of shortness of breath, multilobar infiltration, and pleural effusion were found in type 7. Calcitoninogen in type 7 were significantly higher than those of type 3 and other types, and the white blood cell count was lower than those of type 3 and other types, and the difference was statistically significant (P

ObjectiveTo investigate how serum 25-hydroxyvitamin D (25[OH]D) affects height growth velocity and the risk of low bone mineral density (BMD) in children.DesignA population-based prospective cohort study.Patients and methodsA total of 10 450 participants with complete follow-up records from a cohort were included in the current study. Serum 25(OH)D concentrations were measured at baseline and 2-year follow-up, and the average of 2-time measurements was used for analysis. Low BMD was defined as calcaneus speed of sound Z-score ≤ −1. The associations of vitamin D with height growth velocity and the risks of incident low BMD were evaluated using adjusted β and risk ratio (RR).ResultsAfter multivariable adjustment, an inverse L-shaped association between serum 25(OH)D concentrations and height growth velocity was observed, leveling off up to 40–60 nmol/L. Overall, each 10 nmol/L higher serum 25(OH)D concentration was associated with a 0.15 cm/year higher height growth velocity (P < 0.001) and a 7% decreased risk of low BMD [RR (95%CI): 0.93 (0.87~0.98)]. Compared to those with vitamin D deficiency, participants who had sufficient vitamin D had a 22% lower risk for low BMD [RR(95%CI): 0.78 (0.62~0.98)]. However, no significant associations between vitamin D and the risk of low BMD were found in overweight and obese children.ConclusionThese findings highlight the importance of maintenance of sufficient 25(OH)D concentrations and healthy body weight during childhood in height growth and bone health promotion.

Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53 in vitro and in vivo, representing a viable therapeutic strategy for cancer treatment. Using phage display techniques, we previously identified a potent peptide activator of P53, termed PMI (TSFAEYWNLLSP), with binding affinities for both MDM2 and MDMX in the low nanomolar concentration range. Here we report an ultrahigh affinity, dual-specificity peptide antagonist of MDM2 and MDMX obtained through systematic mutational analysis and additivity-based molecular design. Functional assays of over 100 peptide analogs of PMI using surface plasmon resonance and fluorescence polarization techniques yielded a dodecameric peptide termed PMI-M3 (LTFLEYWAQLMQ) that bound to MDM2 and MDMX with Kd values in the low picomolar concentration range as verified by isothermal titration calorimetry. Co-crystal structures of MDM2 and of MDMX in complex with PMI-M3 were solved at 1.65 and 3.0 Å resolution, respectively. Similar to PMI, PMI-M3 occupied the P53-binding pocket of MDM2/MDMX, which was dominated energetically by intermolecular interactions involving Phe3, Tyr6, Trp7, and Leu10. Notable differences in binding between PMI-M3 and PMI were observed at other positions such as Leu4 and Met11 with MDM2, and Leu1 and Met11 with MDMX, collectively contributing to a significantly enhanced binding affinity of PMI-M3 for both proteins. By adding lysine residues to both ends of PMI and PMI-M3 to improve their cellular uptake, we obtained modified peptides termed PMI-2K (KTSFAEYWNLLSPK) and M3-2K (KLTFLEYWAQLMQK). Compared with PMI-2K, M3-2K exhibited significantly improved antitumor activities in vitro and in vivo in a P53-dependent manner. This super-strong peptide inhibitor of the P53-MDM2/MDMX interactions may become, in its own right, a powerful lead compound for anticancer drug development, and can aid molecular design of other classes of P53 activators as well for anticancer therapy.

ObjectiveLittle is known about pre-pandemic cardiovascular health (CVH) status and its temporal variation in Chinese children. Thus, we aimed to evaluate the secular trends and associated factors of CVH in Chinese urban children from 2004 to 2019.MethodsWe identified 32,586 individuals in Beijing, aged 6 to 18 years, from three independent cross-sectional studies conducted in 2004, 2014, and 2019, respectively. CVH was assessed by 7 metrics according to modified American Heart Association criteria, including smoking, physical activity, diet, body mass index, total cholesterol, blood pressure, and fasting glucose. Multivariable logistic regression was used to assess the associations between sociodemographic characteristics and the ideal CVH status.ResultsThe proportion of ideal CVH decreased from 27.7% (boys 26.6%, girls 28.9%) in 2004 to 4.2% (boys 3.8%, girls 4.8%) in 2014, and then increased to 16.2% (boys 13.5%, girls 18.9%) in 2019. Overall, ideal smoking was the most prevalent CVH component during 2004–2019 (2004, 97.5%; 2014, 92.9%; 2019, 98.0%), while ideal physical activity (2004, 27.6%; 2014, 14.4%; 2019, 28.0%) and dietary intake (2004, 26.0%; 2014, 10.7%; 2019, 23.5%) were the least prevalent components. Notably, the proportion of ideal body mass index (2004, 77.5%; 2019, 59.7%) and blood pressure (2004, 73.6%; 2019, 67.3%) continuously decreased from 2004 to 2019. Girls, parental normal weight status, free of family CVD history, and lower levels in fat mass were associated with higher odds of ideal CVH.ConclusionThe cardiovascular health in Chinese urban children deteriorated during 2004–2019. Distinct strategies are required to mitigate socioeconomic inequity in the intervention of CVH promotion.

ABSTRACT Importance Several methods have been established in recent decades that allow use of spot urine to estimate dietary sodium intake. However, their accuracies have been controversial in children. Objective To validate the performance of three commonly used methods—the Kawasaki, Tanaka, and International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) methods. Additionally, this study explored the accuracies of the Tanaka and INTERSALT methods by using spot urine samples taken at four separate times. Method Forty‐one adolescents aged 14 to 16 years completed two non‐consecutive 24‐hour urine collections and their mean values were used as reference data. The second‐morning urine was used for assessment with the Kawasaki method; a casual spot urine and spot urine samples taken at four separate times (morning, afternoon, evening, and overnight) were used for assessment with the Tanaka and INTERSALT methods. Results The mean differences were 1801 mg, 542 mg, 47 mg, and −31 mg for the Kawasaki, Tanaka, INTERSALT1 (with potassium), and INTERSALT2 (without potassium) methods with their required spot urine, respectively. The proportions of relative difference levels within ± 10% were 4.9% for the Kawasaki method, 19.5% for the Tanaka method, 36.6% for the INTERSALT1 method, and 36.6% for the INTERSALT2 method. Interpretation The INTERSALT method seemed to provide minimally biased estimations of mean population sodium intake with casual spot urine. However, there is a need to be cautious regarding inconsistencies in estimation among different levels of sodium intake. The methods assessed in this study were unable to accurately estimate sodium intake at the individual level.

ABSTRACT Importance Childhood and adolescence are critical periods for lifelong bone mineral accrual, but few studies have determined the impact of childhood adiposity on adult bone density. Objective To determine the long‐term impact of childhood adiposity on adult areal bone mineral density (aBMD) and the effect of adult adiposity on this relationship. Methods We conducted a longitudinal study of 1156 adults (56.3% men), for whom skinfold thickness (SFT) had been measured during childhood (6–18 years) and fat mass percentage (FMP) and aBMD were measured during adulthood (29–43 years). Adult aBMD in the lumbar spine (LS), femoral neck (FN), arms, and legs was measured using dual‐energy X‐ray absorptiometry. The direct effect of childhood SFT and its indirect effect through adult FMP on adult aBMD were estimated using general linear regression and a causal steps approach. Results Significant positive associations between childhood SFT and adult aBMD were found in the LS in men (β = 0.089, P = 0.044) and in all the skeletal sites in women. With respect to the adult fat–bone relationship, high adult FMP was associated with low aBMD in most of the sites in men, but with high FN aBMD in women (β = 0.144, P = 0.002). Moreover, suppressive effects of adult FMP on the associations between childhood SFT and adult aBMD in the LS (−34.8%) and legs (−67.1%) of men, and a positive effect on the FN aBMD in women (17.0%) were identified. Interpretation Childhood adiposity appears to have a positive long‐term effect on adult aBMD, which may be reduced by adiposity in adult men but reinforced by adiposity in adult women.

Abstract Background Increasing evidences have showed that neuroimaging markers of SVD can predict the short-term outcome of acute ischemic stroke (AIS). It is unclear that whether neuroimaging markers of SVD are also associated with short-term outcomes of minor cerebrovascular events. In the present study, we investigate neuroimaging markers of SVD in order to explore their roles in prediction of short-term outcome in patients with minor cerebrovascular events. Methods Consecutive first-ever stroke patients (n = 546) from the Affiliated Jiangning Hospital of Nanjing Medical University were enrolled. A total of 388 patients were enrolled according to minor cerebrovascular events definition (National Institutes of Health Stroke Scale Score ≤ 3) and exclusion criteria. MRI scans were performed within 7 days of stroke onset, and then neuroimaging markers of SVD including WMH, lacunes, cerebral microbleeds (CMB), and perivascular spaces (PVS), SVD burden scores were assessed. We completed baseline characteristics and evaluated the relationships of short-term outcomes to SVD neuroimaging markers and SVD scores. The 90-day modified Rankin Scale (mRS) was thought as primary outcome and was dichotomized as good functional outcome (mRS 0–1) and poor outcome (mRS 2–6). Secondary outcomes were stroke progression and stroke recurrence. Results Higher age, National Institutes of Health Stroke Scale (NIHSS) upon admission, lipoprotein-associated phospholipase A2 (LP-PLA2) and lacunes, Fazekas score were correlated with poor functional outcome (P

In this paper, a broadband double-ridge horn antenna (DRHA) covering 5G millimeter-wave (mm-wave) band is proposed, which maintains stable radiation pattern and gain in the entire band. By redesigning the transition between coaxial and waveguide, there is no splitting or deterioration in the axis pattern throughout the entire 18–54 GHz frequency band, and the VSWRs are all below 2. Meanwhile, by replacing the H-Side wall of the antenna with metal grid, the variation on 3 dB beamwidth of the radiation pattern also become more stable against frequencies. In order to fabricate the prototype successfully, the method of block processing and assembly is adopted, which can ensure high precision machining and make the assembly simple and easy to operate. Prototype measurement results show that the VSWR of the antenna is in well agreement with the simulation ones, while the gain is stable as well as no pattern splitting in the entire frequency band can be observed. It will find potential applications in 5G mm-wave frequency band, especially in the field of antenna measurement system as a standard calibration antenna or a probe antenna.

Background and ObjectivesVitamin D has been indicated to play an important role in the optimal function of the cardiovascular system. However, with limited evidence, it remains unclear whether vitamin D status transition during childhood would affect cardiometabolic risk factors. Thus, we aimed to identify the associations of the longitudinal trajectory of vitamin D status with cardiometabolic risk factors in children.MethodsA total of 10,482 participants with complete follow-up records from a large population-based prospective cohort study were included in this analysis. The 25-hydroxyvitamin D [25(OH)D] concentrations, blood pressure, blood lipids, and fasting blood glucose were determined. Vitamin D deficiency was defined as serum 25(OH)D concentrations below 30 nmol/L according to the Institute of Medicine recommendations. Based on the vitamin D status at baseline and follow-up, we identified four possible trajectories: (1) persistent non-deficiency (reference); (2) baseline non-deficiency to follow-up deficiency; (3) baseline deficiency to follow-up non-deficiency; (4) persistent deficiency. The relationships between cardiometabolic risk factors and vitamin D trajectories were evaluated using adjusted risk ratios (RRs).ResultsOverall, 35.1 and 24.2% of participants had vitamin D deficiency at the baseline and follow-up, respectively, and 15.1% were under the condition of persistent vitamin D deficiency. Compared to children with persistent non-deficiency, those who shifted from non-deficiency at baseline to deficiency at follow-up had a 2.09-fold (95% CI: 1.36, 3.23) increased risk of high triglyceride (TG). Besides, children with altered vitamin D status from deficiency to non-deficiency during follow-up were still at a significantly higher risk of high total cholesterol (TC) than the reference group [RR (95% CI): 1.39 (1.04, 1.86)]. Finally, children with persistent vitamin D deficiency were at the highest risks of high TC [RR (95% CI): 1.61 (1.18, 2.19), Ptrend < 0.001], high low-density lipoprotein cholesterol (LDL-C) [RR (95% CI): 1.53 (1.04, 2.27), Ptrend = 0.046], and high TG [RR (95% CI): 1.96 (1.34, 2.87), Ptrend = 0.003].ConclusionOur results suggest that persistent vitamin D deficiency might increase the risk of dyslipidemia in children, and vitamin D deficiency could have has short- and long-term effects on TG and TC, respectively.

Limonin is one of the research hotspots in natural drug development. However, its low solubility in water leads to poor oral bioavailability, discouraging the further study of its potential as a candidate compound. In order to overcome this limitation, and to enhance its biological activities, a novel limonin derivative—HY-071085—was synthesized by structural modification, and has exhibited strong anti-inflammatory and analgesic activity. In order to achieve a thorough understanding of the biological actions of HY-071085 in vivo, this study evaluated the pharmacokinetics and bioavailability of HY-071085 in rats and beagle dogs, and the distribution and excretion in rats. Using ultra-high-performance liquid chromatography-tandem mass spectrometry, the kinetic profiles of HY-071085 in the plasma of healthy rats and beagle dogs after a single gavage, repeated gavages and the intravenous injection of HY-071085 were studied. The tissue distribution (heart, liver, spleen, lung, kidney, gastric tissue, intestine, brain, skin, testis, ovary and womb) and excretion of HY-071085 were also studied. These results showed that HY-071085 has nonlinear dynamic characteristics in rat and beagle dog plasma. It was found that the plasma concentrations of HY-071085 in female rats were significantly higher than those in male rats after a single oral administration. There were gender differences in the kinetic behavior of HY-071085 in rats; however, there was no difference identified in dogs. HY-071085 was mainly eliminated as metabolites in rats, and was distributed in most of the tissues except the brain, with the highest content being in the gastric tissue and intestinal arease, followed by the liver, spleen, fat, lung, kidney, ovary and heart. The bioavailability of HY-071085 in male and female rats was 2.8% and 10.8%, respectively, and was about 13.1% in beagle dogs. The plasma protein binding rate of HY-071085 in rats, beagle dogs and humans ranged from 32.9% to 100%, with obvious species differences. In conclusion, our study provides useful information regarding the absorption, distribution and excretion of HY-071085, which will provide a good base for the study of the mechanism of its biological effects.

Background and Purpose: Serum level of lipoprotein-associated phospholipase A2 (Lp-PLA2) was associated with white matter hyperintensity (WMH). There were differences in the anatomical structure and pathophysiological mechanism between periventricular WMH (PVWMH) and deep subcortical WMH (DSWMH). In this study, we aimed to investigate the effects of serum Lp-PLA2 on the PVWMH and DSWMH.Methods: In total, 711 Chinese adults aged ≥45 years with cranial magnetic resonance imaging (MRI) were recruited in this cross-sectional study, who had received physical examinations in the Department of Neurology, the Affiliated Jiangning Hospital of Nanjing Medical University due to dizziness and headaches between January 2016 and July 2019. Enzyme linked immunosorbent assay (ELISA) was utilized to determine the serum Lp-PLA2. Fazekas scale was used to measure the severity of PVWMH (grade 0–3) and DSWMH (grade 0–3) on MRI scans. Ordinal regression analysis was carried out to investigate the relationship between serum Lp-PLA2 and PVWMH or DSWMH.Results: Finally, 567 cases were included in this study. The average level of serum Lp-PLA2 was 213.35±59.34 ng/ml. There were statistical differences in the age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Lp-PLA2 grade, creatinine, Hcy, and H-CRP (P < 0.05) in PVWMH groups. Ordinal regression analysis indicated that there was a lower risk of PVWMH in the patients with normal and moderately elevated serum Lp-PLA2 compared with those with significantly elevated serum Lp-PLA2 after adjusting age, hypertension, diabetes mellitus, atrial fibrillation, lacunar infarction, Cr, Hcy, and H-CRP. In addition, PVWMH was correlated to advanced age, hypertension, diabetes mellitus, and lacunar infarction. After adjusting for confounding factors, DSWMH was correlated to advanced age and lacunar infarction. There was no correlation between serum Lp-PLA2 and DSWMH.Conclusions: Serum Lp-PLA2 was closely associated with the pathogenesis of PVWMH rather than DSWMH. There might be different pathological mechanisms between PVWMH and DSWMH.

Objectives To demonstrate the accuracy and flexibility of using waist-to-height ratio (WHtR) as a screening tool for identifying children and adolescents with cardiometabolic risk (CMR) across a wide range of prevalence levels among general paediatric populations.Design A nationwide population-based cross-sectional study with all data collected at school settings in six cities of China.Participants A total of 8130 children and adolescents aged 7–18 years with complete anthropometric and CMR measurements based on blood tests were recruited.Outcome measures Elevated blood pressure, dyslipidaemia, elevated fasting blood glucose and central obesity were measured. The primary outcome, CMRs, was defined as meeting three or more of the above risk factors. The accuracy of WHtR for identifying CMRs was evaluated using areas under the curves (AUCs) with 95% CI of the receiver operating characteristic curve. The predictability of WHtR at given CMRs prevalence levels was estimated by positive predictive value (PPV) and negative predictive value.Results Overall, 6.1% of study participants were presented with CMRs. WHtR had high AUCs ranging from 0.84 (95% CI 0.81 to 0.88) to 0.88 (95% CI 0.86 to 0.90) in the total population and age-subgroup and gender-subgroup. The overall optimal WHtR cut-off value was 0.467, with boys having a higher cut-off than girls (0.481 vs 0.456). WHtR achieved an overall sensitivity of 0.89 and PPV of 18.8% at a specificity of 0.75. The screening performance of WHtR remained satisfactory across a wide range of given CMRs prevalence levels (5%, 10% and 20%).Conclusion WHtR as a screening tool could accurately and flexibly identify children affected with the clusters of three or more of CMR factors from the general paediatric population with various CMR prevalence levels. Our findings provide support for policy-making on early CMR identification and management in the high-risk group of children.

Abstract Background The genome-wide association study has founded hypertension-related single nucleotide polymorphism (SNP) rs11191548 near CYP17A1 encoding a key enzyme involved in steroid metabolism, but the molecular mechanisms are not understood and the associations of the SNP with hypertension-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNP and two hypertension-related traits, lipids and leptin. Methods We genotyped the SNP in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results The SNP rs11191548 was significantly associated with high-density lipoprotein cholesterol (HDL) (P = 0.014 and 0.028, respectively) and leptin (P = 0.011 and 0.026, respectively) under an additive model after adjustment for age, gender, and systolic blood pressure (SBP) or diastolic blood pressure (DBP). There was a statistically significant association of rs11191548 with high leptin after adjustment for age, gender, and SBP or DBP. The P-values remain significant after correction for multiple testing. Conclusions We demonstrate for the first time that the SNP rs11191548 near CYP17A1 is associated with HDL and leptin in Chinese children. These novel findings provide important evidence that HDL and leptin maybe possibly mediate the process of CYP17A1 involved in hypertension.

Background: The potential mechanism underlying the relationship between the risk of cardiovascular diseases and metabolically healthy obese (MHO) individuals remains unclear. The aim of the study was to prospectively investigate the potential role of the adipokines in the association between the MHO phenotype and hypertension in children and adolescents. Methods: A total of 1184 participants at baseline were recruited from a cohort of the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. The participants were classified according to their body mass index (BMI) and metabolic syndrome (MS) components. The levels of the adipokines, including leptin, adiponectin, and resistin, were measured. Results: MHO individuals had higher leptin levels (11.58 ug/L vs 1.20 ug/L), leptin/adiponectin ratio (1.18 vs 0.07), and lower adiponectin (11.65 ug/L vs 15.64 ug/L) levels compared to metabolically healthy normal-weight individuals (all P < 0.05). Compared to metabolically healthy normal-weight individuals, the prevalence of high leptin levels (26.5% vs 0.4%), low adiponectin levels (17.9% vs 6.3%) and a high leptin/adiponectin ratio (26.0% vs 2.1%) was higher in MHO individuals (all P < 0.01). The MHO individuals with abnormal adipokines were significantly more likely to developing hypertension (high leptin, relative risk 11.04; 95% confidence interval, 1.18–103.35; and high leptin/adiponectin ratio, relative risk 9.88; 95% confidence interval, 1.11–87.97) compared to metabolically healthy normal-weight individuals with normal adipokine levels. Conclusions: The abnormal adipokine levels contribute to the increased hypertension risk in MHO children and adolescents. The non-traditional risk factors should be highlighted in MHO children and adolescents in clinical practice and research.

Background. Genome-wide association studies have found an obesity-related single-nucleotide polymorphism rs10938397 near the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) encoding, an enzyme that catalyzes the deamination of the glucosamine-6-phosphate involved in the hexosamine signaling pathway, but the molecular mechanisms underlying the missing link between GNPDA2 and obesity remain elusive. Methods. As obesity is accompanied by an increase in the size and the number of adipocytes, the present study investigates the possible mechanism of the GNPDA2 in adipogenesis using GeneChip® Human Transcriptome Array 2.0 in human adipose-derived mesenchymal stem cells. Results. We found that overexpression of GNPDA2 enhanced accumulation of lipid droplets, and knocking down the gene decreased accumulation of lipid droplets. GO term enrichment analysis indicated that most differentially expressed genes (DEGs) affected by deficiency of GNPDA2 have functions to lipid and glucose metabolism. Further KEGG enrichment analysis showed that the greatest proportion of DEGs are involved in thermogenesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, carbon metabolism, and fatty acid metabolism including fatty acid degradation, elongation, and biosynthesis. Conclusion. These findings suggest that GNPDA2 may be a critical gene for lipid and glucose metabolism, and the expression level of GNPDA2 alters the transcriptome profile of human adipose-derived mesenchymal stem cells.

Abstract The fat mass- and obesity-associated gene (FTO) is significantly associated with obesity, but the associations of FTO with obesity-related traits are not fully described. We aimed to investigate the association of the FTO single nucleotide polymorphism (SNP) rs6499640 with lipid levels in Chinese children. A total of 3503 children aged 6-18 years were included in the present study. Lipid levels were analyzed and the SNP rs6499640 was genotyped using the TaqMan Allelic Discrimination Assay. Statistically significant associations were found between rs6499640 and low-density lipoprotein cholesterol (LDL-C) (p = 0.008), total cholesterol (TC) (p = 0.005), and triglycerides (TG) (p < 0.001) in girls under a dominant model adjusted for age and BMI. No statistical significance was found between the SNP and lipid levels in boys. We demonstrated for the first time that the SNP rs6499640 in FTO is associated with LDL-C, TC, and TG in Chinese girls. Our study identified a new risk locus for lipid levels in children.

Purpose. Genome-wide association studies have found two obesity-related single-nucleotide polymorphisms (SNPs), rs17782313 near the melanocortin-4 receptor (MC4R) gene and rs6265 near the brain-derived neurotrophic factor (BDNF) gene, but the associations of both SNPs with other obesity-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNPs and adiponectin that has a regulatory role in glucose and lipid metabolism. Methods. We examined the associations of the SNPs with adiponectin in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study. Results. The SNP rs6265 was significantly associated with adiponectin under an additive model (P=0.02 and 0.024, resp.) after adjustment for age, gender, and BMI or obesity statuses. The SNP rs17782313 was significantly associated with low adiponectin under a recessive model. No statistical significance was found between the two SNPs and low adiponectin after correction for multiple testing. Conclusion. We demonstrate for the first time that the SNP rs17782313 near MC4R and the SNP rs6265 near BDNF are associated with adiponectin in Chinese children. These novel findings provide important evidence that adiponectin possibly mediates MC4R and BDNF involved in obesity.

The associations between common variants in the fat mass- and obesity-associated (FTO) gene and obesity-related traits may be age-dependent and may differ by sex. The present study aimed to assess the association of FTO rs9939609 with body mass index (BMI) and the risk of obesity from childhood to adolescence, and to determine the age at which the association becomes evident.Totally 757 obese and 2,746 non-obese Chinese children aged 6-18 years were genotyped for FTO rs9939609. Of these, a young sub-cohort (n = 777) aged 6-11 years was reexamined 6 years later. Obesity was defined using the sex- and age-specific BMI cut-offs recommended by the International Obesity Task Force.The associations of FTO rs9939609 with BMI and obesity did not appear until children reached 12-14 years. The variant was associated with an increased BMI in boys (β = 1.50, P = 0.004) and girls (β = 0.97, P = 0.018), respectively. Thereafter, the magnitude of association increased in girls at ages 15-18 years (β = 2.02, P0.05). Age was found to interact with the variant on BMI (P

BACKGROUND: Variants in gene encoding glucokinase regulator protein (GCKR) were found to have converse effects on triglycerides and glucose metabolic traits. We aimed to investigate the influence of GCKR variants for triglycerides and glucose metabolic traits in Chinese children and adults. METHODS AND RESULTS: We genotyped two GCKR variants rs1260326 and rs1260333 in children and adults, and analyzed the association between two variants and triglycerides, glucose, insulin and HOMA-IR using linear regression model, and estimated the effect on insulin resistance using logistic regression model. Rs1260326 and rs1260333 associated with increased triglycerides in children and adults (p

OBJECTIVE: Recent genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) associated with body mass index (BMI)/generalized obesity. In this study, we aimed to examine the associations of identified SNPs with risk of central obesity in a child population from China. METHODS: We genotyped 11 SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, BDNF rs6265, FAIM2 rs7138803, NPC1 rs1805081, SEC16B rs10913469, SH2B1 rs4788102, PCSK1rs6235, KCTD15 rs29941, BAT2 rs2844479) in the Chinese children (N = 3502, age range 6-18 years) from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS). Based on the age- and sex- specific waist circumference (WC) standards generated in the BCAMS study, 1196 central obese cases and 2306 controls were identified. RESULTS: Of 11 studied SNPs, four SNPs and genetic risk score (GRS) based on them were statistically significantly associated with central obesity by WC criteria (FTO rs9939609: OR = 1.29, 95%CI = 1.10-1.50, p = 0.001; MC4R rs17782313: OR = 1.27, 95%CI = 1.12-1.44, p = 1.32×10⁻⁴; GNPDA2 rs10938397: OR = 1.22, 95%CI = 1.09-1.37, p = 4.09×10⁻⁴; BDNF rs6265: OR = 1.20, 95%CI = 1.08-1.34, p = 8.86×10⁻⁴; GRS: OR = 1.25, 95%CI 1.16-1.34, p = 2.58×10⁻⁹) after adjustment for sex, age, pubertal stage, physical activity and family history of obesity. Similar observations were made using weight-to-height ratio (WHtR) criterion. However, other SNPs were not associated with central obesity by WC as well as WHtR criterion. CONCLUSIONS: Our study replicates the statistically significant association of four SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, BDNF rs6265) with risk of central obesity in the Chinese children.

A transient increase in insulin resistance (IR) is a component of puberty. We investigated the impact of body composition and adipokines on IR during puberty in Chinese children. This study included 3223 schoolchildren aged 6–18 years. IR was calculated using homeostasis model assessment (HOMA-IR). We revealed that body mass index (BMI) and waist circumference increased gradually during puberty in both genders, while fat-mass percentage (FAT%) increased steadily only in girls. Change of leptin showed striking sexual dimorphisms: in girls leptin increased steadily during puberty, whereas in boys, after a transient rise at the beginning of puberty, leptin declined by Tanner staging even in those overweight or obese. Inversely, adiponectin level decreased significantly during puberty. In both genders, HOMA-IR started to increase at the beginning of puberty, peaked in the middle, and revised at late puberty in overweight/obesity boys while it stayed high till the end of puberty in girls and normal weight boys. Multivariate regression analysis revealed that leptin presented a stronger indicator of HOMA-IR than anthropometric measures during puberty. Our results demonstrated that gender-specific FAT% and leptin changed with pubertal development. Leptin emerged as a stronger predictor of IR than traditional anthropometric indices, suggesting a prominent role in the development of pubertal IR.

BACKGROUND: The SNP (rs2230500) in PRKCH (the gene encoding protein kinase C η) is associated with ischemic stroke and cerebral hemorrhage in the Chinese population, but the molecular mechanisms are not clear. The aim of the present study is to investigate the association between the SNP and atherosclerosis that is common pathological basis of ischemic stroke and cerebral hemorrhage. METHODOLOGY/PRINCIPAL FINDINGS: We examined the associations of the SNP with carotid intima-media thickness (CIMT), atherosclerosis diagnosed by CIMT, and factors related with inflammation in the Beijing Child Blood Pressure Study. A total of 1190 subjects participated in the follow-up study. The SNP was genotyped by allele-specific real-time PCR assay. The SNP (rs2230500) in PRKCH was significantly associated with CIMT (in far wall of left common carotid arteries, P = 0.016; in far wall of right common carotid arteries, P = 0.012) under a recessive model after adjustment for age, gender, smoking, and hypertension. The SNP was also significantly associated with complement C3 (P = 0.012) under a dominant model after adjustment for age, gender, and high sensitivity C-reactive protein. CONCLUSIONS/SIGNIFICANCE: Our data provide evidence that the SNP (rs2230500) in PRKCH decreases the risk of CIMT that is a worthwhile predictor of stroke and complement system possibly mediates this process.

Data about metabolic syndrome (MetS) in children is limited in China. We aimed to assess the prevalence of MetS related components, and their association with obesity. Data were collected as part of a representative study on MetS among 19593 children, aged 6-18 years old in Beijing. General obesity was assessed by body mass index (BMI) and central obesity by waist circumference. Finger capillary blood tests were used to assess triglyceride (TG), total cholesterol (TC) and impaired fasting glucose (IFG). Vein blood samples were collected from a subsample of 3814 children aged 10-18 years to classify MetS. MetS was defined according to the International Diabetes Federation 2007 definition. The associations between MetS related components and the degree and type of obesity were tested using logistic regression models. The prevalence of overweight, obesity, high blood pressure, elevated TG, TC and IFG were 13.6%, 5.8%, 8.5%, 8.8%, 1.2% and 2.5%, respectively. Compared with normal weight children, overweight and obese children were more likely to have other MetS related components. In the subsample of 3814 children aged 10-18 years, the prevalence of MetS was much higher in obese subjects than in their normal weight counterparts (27.6% vs. 0.2%). Children with both general and central obesity had the highest prevalence of MetS. Compared with normal weight children, overweight and obese children were more likely to have MetS (overweight: OR=67.33, 95%CI=21.32-212.61; obesity: OR=249.99, 95% CI=79.51-785.98). Prevalence of MetS related components has reached high level among Beijing children who were overweight or obese. The association between metabolic disorders and obesity was strong.