Uric acid mediated the relationship between obesity and hypertension in children and adolescents: A population­based cohort study.

BACKGROUND AND AIM: Obesity and hyperuricemia (HUA) often coexist and have been widely accepted as risk factors for hypertension, but the role of uric acid (UA) in the relationship between obesity and hypertension remains unknown in children and adolescents. METHODS AND RESULTS: A total of 7525 subjects aged 6-16 years were from the School-based Cardiovascular and Bone Health Promotion Program (SCVBH) at baseline (2017) and followed up in 2019. Multivariable logistic regression with interaction terms, cross-lagged panel analysis, and causal mediation model were applied to delineate the joint impact of obesity and HUA on hypertension, including the interaction effect, the temporal association, and the mediating effect of UA in the relationship between obesity and hypertension. There were 10.8 % of the participants with normotension at baseline developed hypertension after two years of follow-up. Cross-lagged panel analysis showed that the two-time point association was significant only from baseline BMI to follow-up UA (ß1 = 0.302, P < 0.001), but not from baseline UA to follow-up BMI (ß2 = 0.002, P = 0.745). Multivariable logistic regression showed that both obesity and HUA increased the risk of hypertension, but no interaction effect between HUA and obesity. The causal mediation analysis found that UA partially mediated the association between BMI and SBP (mediate proportion: 20.3 %, 95 % CI: 17.4-22.9 %) or DBP (mediate proportion: 11.9 %, 95 % CI: 3.9-18.2 %). The results were consistent in the analysis of systolic hypertension rather than diastolic hypertension. CONCLUSIONS: It is mediating effect that UA played in the progress from obesity to hypertension, particularly systolic hypertension in children and adolescents.

Biochemical and molecular analysis of pediatric patients with metachromatic leukodystrophy in South China: functional characterization of five novel ARSA variants.

Metachromatic leukodystrophy (MLD) is a rare hereditary neurodegenerative disease caused by deficiency of the lysosomal enzyme arylsulfatase A (ARSA). This study described the clinical and molecular characteristics of 24 Chinese children with MLD and investigated functional characterization of five novel ARSA variants. A retrospective analysis was performed in 24 patients diagnosed with MLD at Guangzhou Women and Children's Medical Center in South China. Five novel mutations were further characterized by transient expression studies. We recruited 17 late-infantile, 3 early-juvenile, 4 late-juvenile MLD patients. In late-infantile patients, motor developmental delay and gait disturbance were the most frequent symptoms at onset. In juvenile patients, cognitive regression and gait disturbance were the most frequent chief complaints. Overall, 25 different ARSA mutations were identified with 5 novel mutations.The most frequent alleles were p.W320* and p.G449Rfs. The mutation p.W320*, p.Q155=, p.P91L, p.G156D, p.H208Mfs*46 and p.G449Rfs may link to late-infantile type. The novel missense mutations were predicted damaging in silico. The bioinformatic structural analysis of the novel missense mutations showed that these amino acid replacements would cause severe impairment of protein structure and function. In vitro functional analysis of the six mutants, showing a low ARSA enzyme activity, clearly demonstrated their pathogenic nature. The mutation p.D413N linked to R alleles. In western blotting analysis of the ARSA protein, the examined mutations retained reduced amounts of ARSA protein compared to the wild type. This study expands the spectrum of genotype of MLD. It helps to the future studies of genotype-phenotype correlations to estimate prognosis and develop new therapeutic approach.

DUCNP@Mn-MOF/FOE as a Highly Selective and Bioavailable Drug Delivery System for Synergistic Combination Cancer Therapy.

Heterostructures comprising lanthanide-doped upconversion nanoparticles (DUCNPs) and metal-organic frameworks (MOFs) are emerging as promising nanosystems for integrating medical diagnosis and treatment. Here, the DUCNP@Mn-MOF nanocarrier was developed, which showed good efficiency for loading and delivering a cytotoxic antitumor agent (3-F-10-OH-evodiamine, FOE). The combined advantages of the pH-responsive and peroxidase-like properties of Mn-MOF and the unique optical features of DUCNPs granted the DUCNP@Mn-MOF/FOE system synergistic chemodynamic and chemotherapeutic effects. The DUCNP@Mn-MOF nanocarrier effectively overcame the intrinsic limitations of FOE, such as its unfavorable physicochemical properties and limited in vivo potency. This complexed nanosystem was responsive to the tumor microenvironment and showed excellent tumor targeting capability. Thus, DUCNP@Mn-MOF/FOE exhibited highly selective and bioavailable drug delivery properties and is promising for cancer therapy. In a mouse breast cancer model, DUCNP@Mn-MOF/FOE inhibited tumor growth without significant toxicity. Therefore, the proposed nanosystem represents a promising theragnostic platform for multimodal combination diagnosis and therapy of tumors.

Selenium spatial distribution and bioavailability of soil-plant systems in China: a comprehensive review.

Selenium (Se) has a dual nature, with beneficial and harmful effects on plants, essential for both humans and animals, playing a crucial role in ecosystem regulation. Insufficient Se in specific terrestrial environments raises concerns due to its potential to cause diseases, while excess Se can lead to severe toxicity. Thus, maintaining an optimal Se level is essential for living organisms. This review focuses first on Se transformation, speciation, and geochemical properties in soil, and then provides a concise overview of Se distribution in Chinese soil and crops, with a focus on the relationship between soil Se levels and parent materials. Additionally, this paper explores Se bioavailability, considering parent materials and soil physicochemical properties, using partial least squares path modeling for analysis. This paper aimed to be a valuable resource for effectively managing Se-enriched soil resources, contributing to a better understanding of Se role in ecosystems.

Structure and Electron Configuration of Imidazole-2-carboxaldehyde and Its Excited Triplet: Resonance Raman and Transient Absorption Spectroscopy and DFT Calculation Investigations.

Imidazole-2-carboxaldehyde (IC) can be generated in atmospheric waters and absorbs solar radiation in the near UV region to produce its excited triplet state (3IC), which contributes to the formation of a secondary organic aerosol (SOA). The photoreactivity of IC is significantly influenced by its surroundings, such as water and acidic environment, because IC is capable of transforming into gem-diol under above conditions. Meanwhile, the electron configuration of 3IC is critical in elucidating the reaction mechanism of 3IC with other anthropogenic and biogenic volatile organic compounds (VOCs). In this study, steady-state and time-resolved resonance Raman as well as transient absorption spectroscopic experiments were conducted to provide vibrational and kinetic information on IC and 3IC in the presence of water and acid conditions. Using density functional theory (DFT) calculations, the H-bonding at the carbonyl O was confirmed and the hydrated structure of IC and 3IC was determined. 1,4-Cyclohexadiene is a good hydrogen donor, and it has a second-order rate constant of ∼107 M-1 s-1 toward 3IC. The results of CASSCF calculations suggest that the hydrogen abstraction may involve the transition from the ππ* to nπ* triplet state via the surface-crossing point.

Analysis of the typing of adenovirus and its clinical characteristics in children with acute respiratory tract infection.

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 < 0.05). CONCLUSION: AdV type 3 and 7 were frequently found in hospitalized children with acute lower respiratory tract involvement. AdV type 7 seems to be associated with more severe outcome.

Differences in air displacement plethysmography, bioelectrical impedance analysis and dual-energy X-ray absorptiometry for estimating body composition in Chinese children and adolescents.

AIM: This study aimed to compare body composition (BC) measurements obtained by three widely used BC measuring methods, air displacement plethysmography (ADP), bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA), in Chinese children and adolescents by sex and different BMI categories. METHODS: We used three BC measuring methods to evaluate healthy Chinese children and adolescents aged 5-17 years with BMI categories ranging from underweight to obese. Fat mass (FM, kg), fat mass percentage (FMP, %), fat-free mass (FFM, kg) and appendicular skeletal muscle mass (ASM, kg) were measured by DXA, BIA and ADP on the same day within 1 h. RESULTS: A total of 172 Chinese children and adolescents were included in this study. The agreements for FM, FFM and ASM estimated by the three methods were excellent or good at the population level (intraclass correlation coefficient > 0.850, P < 0.05). However, ADP or BIA estimated lower body fat content and higher FFM than DXA (P < 0.001 for all). Moreover, the precise estimates significantly varied across BMI categories. In addition, the limit of agreements was wide, and the differences might not be clinically acceptable at the individual level. CONCLUSIONS: Body fat and FFM obtained by the three commonly used methods were highly correlated, but systematically different and influenced by BMI. This study provided a basis for mutual reference of measurements between three widely used methods.

Distinct causal effects of body fat distribution on cardiometabolic traits among children: Findings from the BCAMS study.

BACKGROUND AND AIMS: Observational studies reveal that different body fat measures are associated with cardiometabolic disease with different effects. However, causality is not reflected by such observations. To explore and compare the causal relationships of general obesity (measured by body mass index (BMI)), adipose obesity (measured by fat mass percentage (FMP)) and central obesity (measured by waist-to-height ratio (WHtR)) with cardiometabolic traits among children. METHODS AND RESULTS: We conducted one sample Mendelian randomization (MR) analysis in 3266 children from Beijing Children and Adolescents Metabolic Syndrome Study. Genetic instruments based on 28 SNPs were performed to explore and compare the causal associations of genetically BMI, FMP and WHtR with cardiometabolic traits. The genetic instruments were robustly correlated with observed BMI, FMP and WHtR. Each genetically 1-SD increment in BMI, FMP and WHtR were causally associated with increment in systolic blood pressure (SBP), diastolic blood pressure (DBP), log-transformed fasting plasma glucose (FPG), log-transformed HOMA-ß, and decrease in log-transformed high-density lipoprotein cholesterol (HDL), respectively (all P < 0.05 after Bonferroni correction). The receiver operating characteristic curve indicated that BMI and FMP showed stronger effects on SBP, DBP, HOMA-ß and HDL than WHtR (all P < 0.05). We also observed causal associations of BMI and FMP with log-transformed fasting insulin and HOMA-IR. CONCLUSIONS: The MR analysis based on population-based cohort indicated a causal relationship of adiposity and body fat distribution with cardiometabolic traits. When compared with central obesity, general obesity and adipose obesity might own stronger effects on blood pressure and blood lipids among children.

Ecological floating bed for decontamination of eutrophic water bodies: Using alum sludge ceramsite.

In this study, a combined ecological floating bed (C-EFB) with alum sludge ceramsite (ASC) was designed to improve the water purification effect of traditional ecological floating beds (T-EFBs). During the ASC preparation stage, alum sludge was shaped into a ball, air-dried, and fired under 600 °C. The physical and chemical properties of the ASC meet the requirements of Artificial Ceramsite Filter Materials for Water Treatment (CJ/T229-2008). This study investigated the increased capability of this new-type artificial substrate (ASC) on the removal of chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), total phosphorus (TP), and total nitrogen (TN) from eutrophic landscape water. Compared with the T-EFB, the C-EFB owns a higher purification efficiency. The highest average efficiency of COD, NH4+-N, TN and TP removals during the four operating stages was 78.2%, 58.1%, 46.7% and 53.2%, respectively, in the C-EFB, which were all higher than those of 53.5%, 32.4%, 27.2% and 25.8%, respectively, for the T-EFB. Among them, the C-EFB showed a higher advantage in the removal of TP. The results showed that the potential benefits of utilizing ASC in seriously eutrophic bodies of water.

High BMI with Adequate Lean Mass Is Not Associated with Cardiometabolic Risk Factors in Children and Adolescents.

BACKGROUND: Despite an increasing number of studies investigating the links between increased BMI and a better prognosis of cardiovascular disease, which has been termed the "obesity paradox," few of them take the lean mass into consideration. OBJECTIVES: This study aimed to explore the associations of body composition compartments, especially the lean mass, with cardiometabolic abnormalities in children and adolescents. METHODS: In a nationwide cross-sectional study of 6- to 18-y-old children (n = 8967, 50.1% boys), we measured body composition using DXA scan, and calculated BMI, fat mass index (FMI), and lean mass index (LMI). The exploratory outcomes were cardiometabolic abnormalities, including hypertension, dyslipidemia, hyperglycemia, and insulin resistance. Adjusted linear regression coefficients and ORs were calculated to assess the associations between body composition indicators and cardiometabolic abnormalities. RESULTS: Unlike BMI and FMI, LMI was inversely associated with homeostasis model assessment of insulin resistance (ß: -0.06; 95% CI: -0.09, -0.03; P < 0.001), fasting plasma glucose (ß: -0.08; 95% CI: -0.11, -0.05; P < 0.001), non-HDL cholesterol (ß: -0.10; 95% CI: -0.13, -0.08; P < 0.001), LDL cholesterol (ß: -0.12; 95% CI: -0.14, -0.09; P < 0.001), and total cholesterol (TC) (ß: -0.16; 95% CI: -0.19, -0.14; P < 0.001). After multivariable adjustment, all the odds of cardiometabolic abnormalities were increased from the lowest quartile to the highest quartile of BMI and FMI (P-trend < 0.05); however, the odds of high TC, high LDL cholesterol, hyperglycemia, and insulin resistance were decreased with LMI (P-trend < 0.05). Obese children with high LMI did not have significantly increased odds of high TC, high LDL cholesterol, and high non-HDL cholesterol compared with normal-weight children without high LMI. CONCLUSIONS: Greater lean mass may have a protective impact on high TC, high LDL cholesterol, hyperglycemia, and insulin resistance in children and adolescents. This finding suggests that the "obesity paradox" may be partly explained by high lean mass.

Association of neuroimaging markers of cerebral small vessel disease with short-term outcomes in patients with minor cerebrovascular events.

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 < 0.05), But after adjusting for confounding variables, among the neuroimaging markers of cerebral small vessel disease, only Fazekas score (OR, 1.343; 95% confidence interval, 1.020-1.770; P = 0.036) was found to be associated with poor outcome at 90 days. Higher Fazekas and SVD scores were not associated with stroke progression or stroke recurrence. CONCLUSION: WMH can predict the poor functional outcome of minor cerebrovascular events. Adding other neuroimaging markers of SVD and total SVD burden score, however, does not improve the prediction, which indicated WMH can as neuroimaging markers for guiding the treatment of minor cerebrovascular events.

[Value of body fat mass measured by bioelectrical impedance analysis in predicting abnormal blood pressure and abnormal glucose metabolism in children].

OBJECTIVE: To study the value of body fat mass measured by bioelectrical impedance analysis (BIA) in predicting abnormal blood pressure and abnormal glucose metabolism in children. METHODS: Stratified cluster sampling was used to select the students aged 6-16 years, and a questionnaire survey and physical examination were performed. The BIA apparatus was used to measure body fat mass. Body mass index (BMI), body fat mass index (FMI), and fat mass percentage (FMP) were calculated. Fasting blood glucose level were measured. RESULTS: A total of 14 293 children were enrolled, among whom boys accounted for 49.89%. In boys and girls, the percentile values (P60, P65, P70, P75, P80, P85, P90, P95) of FMI and FMP fitted by the LMS method were taken as the cut-off values. Based on the receiver operating characteristic curve analysis, the P70 values with a better value in predicting abnormal blood pressure and blood glucose metabolism were selected as the cut-off values for excessive body fat. When FMI or FMP was controlled below P70, the incidence of abnormal blood pressure or abnormal glucose metabolism may be decreased in 8.25%-43.24% of the children. CONCLUSIONS: The evaluation of obesity based on FMI and FMP has a certain value in screening for hypertension and hyperglycemia in children, which can be further verified in the future prevention and treatment of obesity and related chronic diseases in children.

Body fat indicators perform better than body mass index in identifying abnormal lipid profiles in boys but not in girls.

BACKGROUND: BMI as a body weight indicator, may inadequately represent the biological effect of body fat on lipid profiles. This study aims to assess whether body fat indicators were superior to BMI for recognizing children with dyslipidemia. METHODS: A nationwide cross-sectional study involving 8944 pediatric participants aged 6-18 years. Measures of fat mass index (FMI), fat mass percentage (FMP), BMI, and four lipid profiles were obtained. RESULTS: Among boys, the standard multi-linear regression coefficients of FMI for TC, LDL-C, and TG were higher than those of BMI (P < 0.01), but not for HDL-C. Also, the prevalence ratios and area under curves (AUCs) of excess fat classified by FMI for specific abnormal lipid profiles (except for HDL-C) were greater than overweight classified by BMI. The AUCs for detecting children with abnormal TC, LDL-C, and TG of FMI-based excess fat were 3.9%, 5.6%, and 2.8% higher than those of BMI-based overweight, respectively, all P < 0.01. Among girls, the associations of BMI with lipid profiles were substantially similar to FMI. All these results were almost identical when FMP was used instead of FMI. CONCLUSIONS: DXA measured body fat performs better than BMI in identifying abnormal lipid profiles in boys but not in girls.

Clinical and molecular characteristics of patients with Gaucher disease in Southern China.

Gaucher disease (GD) is a common lysosomal storage disorder caused by the deficiency of acid ß-glucosidase, due to mutations in the GBA gene. To explore the clinical and molecular characteristics of GD patients from Southern China, GBA gene were analyzed by nest PCR and direct Sanger-sequencing. Novel missense mutations were transiently transfected in COS-7 cells by plasmid system for functional verification. Among the 22 GD patients, 19 patients were classified as type 1 and three as type 2. Over 60% of the type 1 patient had the onset before two years of age and about 42% of them died before three years of age. Six type 1 patients with L444P homozygous genotype, presented with early onset and severe hepatosplenomegaly. Four novel mutations Y22C, F109L, L149F and c.983_990delCCCACTGG were identified. The GBA activities in vitro of novel mutants Y22C, F109L and L149F were 20.2%, 6.9% and 6.5% of the wild-type, respectively. L444P mutation accounted for 47.7% of the mutant alleles. Our results revealed that type 1 GD tends to present with a severe phenotype among southern Chinese. L444P was the most prevalent mutation and L444P homozygous genotype was associated with severe type 1 GD. Three novel missense mutations identified were pathogenic.

Associations of the hypertension-related single nucleotide polymorphism rs11191548 with high-density lipoprotein cholesterol and leptin in Chinese children.

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.

Clinical features, BTD gene mutations, and their functional studies of eight symptomatic patients with biotinidase deficiency from Southern China.

Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disease, which develops neurological and cutaneous symptoms because of the impaired biotin recycling. Pathogenic mutations on BTD gene cause BTD deficiency. Clinical features and mutation analysis of Chinese children with BTD deficiency were rarely described. Herein, for the first time, we reported the clinical features, BTD gene mutations and their functional studies of eight symptomatic children with BTD deficiency from southern China. Fatigue, hypotonia, proximal muscular weakness, hearing deficits, rash and respiratory problems are common clinical phenotype of our patients. Seizures are observed only in patients with profound BTD deficiency. Five novel mutations were detected, among which c.637delC (H213TfsTer51) was found in 50% of our patients and might be considered as a common mutation. In vitro studies confirmed three mild mutations c.1368A>C (Q456H), c.1613G>A (R538H), and c.644T>A (L215H) which retained 10-30% of wild type enzyme activity, and six severe mutations c.235C>T (R79C), c.1271G>C (C424S), c.1412G>A (C471Y), c.637delC (H213TfsTer51), c.395T>G (M132W), c.464T>C (L155P), and c.1493dupT (L498FfsTer13) which retained <10% of wild type enzyme activity. c.1330G>C (D444H) decreased the protein expression but not activity of BTD enzyme, and H213TfsTer51 was structurally damaging while L498FfsTer13 was functionally damaging. These results will be helpful in establishing the definitive diagnosis of BTD deficiency at the gene level, offering appropriate genetic counseling, and providing clues to structure/function relationships of the enzyme.

Adipokines are Associated With Hypertension in Metabolically Healthy Obese (MHO) Children and Adolescents: A Prospective Population-Based Cohort Study.

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.

Early prenatal diagnosis of lysosomal storage disorders by enzymatic and molecular analysis.

OBJECTIVE: To report the 4-year experience of early prenatal diagnosis of lysosomal storage disorders (LSDs) at a center in mainland China. METHOD: Forty-seven pregnancies affected with LSDs were assed using enzymes and/or molecular studies. Prenatal studies were performed on 43 uncultured chorionic villi (CV) samples, two amniotic fluid samples, and two umbilical cord blood samples. RESULTS: Of the 47 fetuses, 23 (48.9%) were determined to normal, 13 (27.7%) to be carriers, and 11 (23.4%) diagnosed as affected. In this cohort, mucopolysaccharidoses (MPS) type II was the most common LSD, followed by Pompe disease and then metachromatic leucodystrophy. In the 17 MPS II cases, the four affected fetuses showed MPS II enzyme activity expression levels of 1.4% to 6.7%, while the enzyme activity levels of the 13 normal fetuses ranged from 72% to 240.4%. In the seven Pompe cases, three fetuses were normal with Pompe enzyme activity expression levels of 20%, 38.8%, and 77.3%, while four carrier pregnancies showed enzyme activity levels of 17.5%, 17.5%, 33.4%, and 13.8%, respectively. CONCLUSION: Based on different enzyme properties in uncultured CV, different prenatal diagnostic strategies should be adopted for MPS II and Pompe disease. Combining enzyme assay and molecular studies in uncultured CV improves the reliability of prenatal diagnosis of LSDs.

Clinical and molecular characteristics of 11 Chinese probands with GM1 gangliosidosis.

GM1 gangliosidosis is an autosomal recessive lysosomal storage disease caused by the deficiency of ß-galactosidase activity, precisely due to mutations in the GLB1 gene. To explore the clinical and molecular characteristics of GM1 gangliosidosis patients from China, GLB1 gene were analyzed in 11 probands with GM1 gangliosidosis by exploiting direct Sanger-sequencing. Among them, five patients were classified as the infantile type and the remaining six as the late-infantile or juvenile type. In these probands, eight novel mutations p.Y50N, p.Y237C, p.S267F, p.G453R, p.K578 N, c.618delC, c.475_478delGACA and c.1979_1980insG have been identified. Among them, three novel missense mutations p.Y50N, p.S267F and p.G453R were transiently transfected in COS-7 cells by plasmid system for functional verification. In vitro GLB1 activities carrying the aforesaid missense mutants p.Y50N, p.S267F and p.G453R were 0.11%, 0 and 0.55% of wild-type, respectively. Mutation c.495_497delTCT and p.S149F accounted for 22.7 and 13.6% of the mutant alleles, respectively. Our results expand the spectrum of GLB1 gene, provide new insights into the clinical and molecular characteristics of GM1 gangliosidosis in China.

Gender-specific association of the rs6499640 polymorphism in the FTO gene with plasma lipid levels in Chinese children.

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.