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This study aimed to assess the associations of total body fat and fat distribution with bone mineral density (BMD) among children and adolescents in this cross-sectional study. A total of 1032 boys and 897 girls aged 6-17 years were enrolled between May 2019 and June 2019 in Guangzhou, China. BMD, total body fat (fat mass index [FMI] and body fat percentage [BF%]), and fat distribution (trunk-to-limb and android-to-gynoid ratios) were measured by dual-energy X-ray absorptiometry. Inverse probability of treatment weighting regression was used to explore the association between fat and BMD. Traditional regression of covariate adjustment was applied as sensitivity analysis. Regression with inverse probability weighting suggested BF% and android-to-gynoid ratio were negatively associated with BMD in boys (β = - 0.12 and - 0.16, respectively; P 0.05). Android-to-gynoid ratio was also inversely associated with BMD in girls (β = - 0.08, P 0.05). When stratified by age, the negative associations were retained in boys aged 12-17 years (β = - 0.23 and - 0.25, respectively; P 0.001). But for girls, it showed a positive association of FMI with BMD in the 6-9 years group (β = 0.33, P 0.001) and a negative association between the android-to-gynoid ratio and BMD in the 10-17 years group (β = - 0.10, P 0.05). Traditional regression supported the robustness of the results. Conclusion: Total body fat is positively associated with BMD in younger girls but inversely associated in older boys. As for abdominal adipose, it is associated with lower BMD in both older boys and girls. What is Known: • The lean mass has been consistently positively associated with bone mineral density (BMD) among children and adolescents. However, the impact of fat mass on BMD remained controversial. • Beyond total body fat, site-specific fat mass, especially abdominal adiposity, might impede bone formation. What is New: • The associations of total body fat and fat distribution with BMD in children and adolescents were gender- and age-specific. • More attention should be paid to the abdominal fat accumulation to promote bone health in older children.

Ginsenoside compound K (CK) has been shown to exhibit anti-inflammatory properties. In this study, to encourage biomedical applications of biosynthesized gold nanoparticles (AuNPs) with anti-inflammatory effects, AuNPs loaded with ginsenoside compound K were prepared using a self-assembly technique with chitosan as the carrier. Optimal conditions for chitosan-ginsenoside CK‑gold nanoparticles (CS-CK-AuNPs) formation were monitored using UV-Vis absorption spectroscopy. The physicochemical characterization of CS-CK-AuNPs was performed using FE-TEM, FE-SEM, XRD, DLS, FTIR and NMR techniques. In the stability test, CS-CK-AuNPs did not show any significant changes up to 4 weeks. Fluorescence imaging demonstrated that CS-CK-AuNPs promoted cellular uptake in vitro, but did not exhibit significant cytotoxicity at concentrations below 40 μg/mL. Additionally, the CS-CK-AuNPs inhibited NO production, and reduced the expression and secretion of inflammatory cytokines (IL-1β, IL-6, and TNF-α) via inhibition of the nuclear factor-kappaB (NF-κB) pathway in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Thus, CS-CK-AuNPs are novel candidates for developing anti-inflammatory agent. This study also confirms the superiority of chitosan AuNPs as oral delivery vehicles for inflammation-related diseases.

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.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-β, 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-β 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.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.

Tuberculosis (TB) is a severe infectious disease worldwide. The increasing emergence of drug-resistant Mycobacterium tuberculosis (Mtb) has markedly hampered TB control. Therefore, there is an urgent need to develop new anti-TB drugs to treat drug-resistant TB and shorten the standard therapy. The discovery of targets of drug action will lay a theoretical foundation for new drug development. With the development of molecular biology and the success of Mtb genome sequencing, great progress has been made in the discovery of new targets and their relevant inhibitors. In this review, we summarized 45 important drug targets and 15 new drugs that are currently being tested in clinical stages and several prospective molecules that are still at the level of preclinical studies. A comprehensive understanding of the drug targets of Mtb can provide extensive insights into the development of safer and more efficient drugs and may contribute new ideas for TB control and treatment.

Our current research aims to evaluate the efficiency of a flavor enhancer, maltol (produced by heating ginseng) against cisplatin-evoked cardiotoxicity by establishing cisplatin-induced heart injury in vivo and H9C2 rat cardiomyocyte model. The cisplatin-treated mice at 3 mg/kg for four times on the 7th, 9th, 11th and 13th day, and in them appeared a serious cardiac damage accompanied with the increase in indicators of heart damage. Multiple exposure of 3 mg/kg for four times of cisplatin increased cardiac cells apoptosis with increased expression of Bax and cleaved-caspase 3, and decreased expression of Bcl-2. Interestingly, supplement of maltol at doses of 50 and 100 mg/kg for 15 days significantly suppressed the cardiac disturbance. In cultured H9C2 cells, maltol enhanced PI3K/Akt expression level during cisplatin treatment, and reduced cisplatin-induced apoptosis. Notably, inhibition of PI3K/Akt by LY294002 and HY-10249A lessened the efficacy of maltol. In mice, maltol apparently induced PI3K/Akt in heart tissues and protected against cisplatin-induced cardiotoxicity. In conclusion, maltol exerted the protective effects against cisplatin-induced cardiotoxicity, at least partially by inhibiting the activation of PI3K/Akt signaling pathways in cardiomyocytes, to ease oxidative stress, and alleviate reactive oxygen species-mediated apoptosis.

Introduction: Anti-phospholipase A2 receptor antibody (PLA2R-Ab) is highly specific for primary membranous nephropathy (PMN). Here, we compare the diagnostic value of different circulating PLA2R-Ab cutoff titers in multicenter cohorts, with particular focus on determining the optimal cutoff value for Chinese patients. Methods: In total, 288 patients with PMN and 301 with other nephropathies were recruited retrospectively from five hospitals in China between September 2011 and October 2018. PLA2R-Ab in serum obtained at renal biopsy was determined by enzyme-linked immunosorbent assay. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) curve of PLA2R-Ab in diagnosing PMN were assessed. Diagnostic efficiency was evaluated by internal validation. Results: The sensitivity, specificity, PPV, NPV, and Youden index for PMN diagnosis were 71%, 90%, 88%, 75%, and 0.61 at the cutoff of 3.8 RU/mL; 74%, 86%, 84%, 76%, and 0.60 at 2.7 RU/mL; 68%, 92%, 90%, 73%, and 0.60 at 5.2 RU/mL; 64%, 95%, 93%, 72%, and 0.59 at 9.0 RU/mL; 57%, 96%, 94%, 68%, and 0.54 at 14.0 RU/mL; 51%, 97%, 95%, 66%, and 0.49 at 20.0 RU/mL; 47%, 98%, 96%, 64%, and 0.45 at 40.0 RU/mL, respectively. The area under the ROC curve was 0.83. Conclusion: By comprehensively considering specificity and sensitivity, we show that 3.8 RU/mL is the optimal cutoff of PLA2R-Ab in Chinese PMN patients, with a sensitivity of 71% and a specificity of 90%. The cutoff values were 5.2 RU/mL and 9.0 RU/mL when the diagnostic specificity was increased to 92% and 95%, respectively.

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.

Objective: This study was aimed at screening differentially expressed genes (DEGs) and exploring the potential immune mechanism induced by the Bacillus Calmette-Guerin (BCG) vaccine in a humanized mouse model. Methods: Candidate DEGs between mice vaccinated with BCG or injected with PBS were identified through transcriptomics, and their biological functions, signaling pathways, and protein interaction networks were analyzed through bioinformatics. Results: A total of 1035 DEGs were identified by transcriptomics: 398 up-regulated and 637 down-regulated. GO analysis indicated that these DEGs were significantly enriched in cell adhesion, oxygen transport, receptor complex, carbohydrate binding, serine-type endopeptidase activity, and peroxidase activity terms. KEGG analysis indicated that these DEGs were involved in the Rap1 signaling pathway, axon guidance, PI3K-Akt signaling pathway, natural killer cell mediated cytotoxicity, and cytokine-cytokine receptor interaction. Protein interaction network analysis demonstrated that the Myc, Vegfa, and Itgb3 proteins had the highest aggregation degree, aggregation coefficient, and connectivity. Conclusion: The BCG vaccine induced 1035 DEGs in humanized mice. Among them, the differentially expressed down-regulated genes myc and itgb3 involved in the PI3K-Akt signaling pathway may play essential roles in the immune mechanism of the BCG vaccine.

With climate change and rising sea levels, the coastal zone’s flood risk is deteriorating. Previous researches have shown a gradually degrading capacity of traditional hard engineering structures (e.g., seawall, dikes, etc.) on flood mitigation due to problems such as land subsidence and insufficient maintenance. To remedy the defects, the “building with nature concept” for coastal protection with saltmarshes was examined by combining field measurements and numerical simulations. The advantages of saltmarsh over traditional seawall on flood protection was demonstrated from the perspective of both flood area mitigation and economic gain, based on scenario simulations. Results show that tidal wetlands are essential in mitigating significant wave heights (Hs) and current velocities even during storm conditions. The storm wave and current velocity reduction ratio ( \begin{document}$R{R}_{{\rm{w}}}$\end{document} and \begin{document}$R{R}_{{\rm{c}}}$\end{document} ) by saltmarshes on Chongming Dongtan Shoal (CMDS) during Typhoon 9711 is approximately 11% and 51%, respectively. The wave and current mitigation by Scirpus mariqueter are more efficient than Spartina alterniflora and Phragmites australis during measurements in 2010, which were approximately 0.3 m and 0.2 m/s, 0.125 m and 0.155 m/s, 0.086 m and 0.128 m/s per kilometer width, respectively. The summer saltmarsh area 54.2 km2 on CMDS protects approximately 32 km2 land area behind the seawall from being flooded, equivalent to the seawall heightening of approximately 0.42 m on equivalent flood mitigation. The performance of cost-and-benefit analysis shows a relatively higher (by 3%–7%) net present value (NPV) and a higher (by 1.5 times) benefit-cost ratio (BC) of nature-based solution (i.e., saltmarsh restoration) compared with traditional hard engineering solution (i.e., seawall construction). Thus, building seawall with nature, such as a hybrid flood protection measure, should be implemented in the future coastal redesign and maintenance.

AIMS AND OBJECTIVES This study aimed to determine the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation in China. BACKGROUND Aerosol therapy is a routine operation for intensive care unit (ICU) nurses; however, evidence of the knowledge and current practices of ICU nurses regarding aerosol therapy for patients with invasive mechanical ventilation is insufficient in China. DESIGN A total of 433 hospitals in 92 cities (including 31 capital cities) in 31 provinces in China participated in the study. METHODS A questionnaire was used to investigate the knowledge and current practices of ICU nurses regarding aerosol therapy for patients treated with invasive mechanical ventilation, including 42 questions covering five aspects: sociodemographic information, aerosolisation devices, atomised drugs, atomisation operation and atomisation-related knowledge. Descriptive analyses of the distribution of the sample are reported as percentages and medians. Univariate and multivariate analysis was used to detect the factors of the interviewee's atomisation knowledge and practices scores. A STROBE checklist was used to guide the reporting of the research. RESULTS Of the 1995 questionnaires that were returned, 1978 were analysed. Bronchodilators and glucocorticoids were the most frequently administered drugs. Seventy-four per cent of the total respondents reported placing a filter on the expiratory limb during aerosol therapy, and 47% of these reported that the filter was changed once a day. Only 13% of the respondents reported always turning the heating humidifier off during aerosol therapy, and 48% never did. Knowledge about the optimal droplet size or atomisation yield was poor. Work experience in the ICU and frequency of atomisation training were the independent influencing factors for atomisation knowledge and practice scores (F = 279.653, p

Desulfurization sorbent with a high active component utilization is of importance for the removal of H

Background More and more studies have shown that high salt intake changed intestinal microbiota and host metabolites. However, no studies have explored the association of a high-salt diet with intestinal microbiota and metabolites in children and adolescents. Therefore, we aimed to explore the relationship between salt intake and intestinal microbiota and host metabolites in Chinese boarding school children and adolescents based on 24-h urinary sodium excretion over three consecutive days. Methods This cross-sectional study was conducted in three boarding schools, from September to October 2021. In 153 children, we analyzed the diversity of intestinal microbiota as well as microbiota composition in normal salt (salt intake Prevotella and Lachnospira (P

Sorbent with a great quantity of highly dispersed active components is of importance to achieve excellent desulfurization performance. Thus, Zn@MnOx/porous carbon nanofibers (PCNFs) sorbents have been constructed via electrospinning, carbonization, activation and hydrothermal techniques in this study. The as-prepared sorbent realizes a sulfur capacity of 9.63 g S 100 g-1 sorbent and a utilization rate 117% of ZnO, which could be attributed to the synergetic effects of the enlarged surface area of PCNFs and uniformly distributed active components. The specific surface area of modified PCNFs is nearly five times higher than that of the pristine CNFs, providing larger loading area and more attachment sites for metal oxides. Activation with KMnO4 not only generates active MnOx components but also presets ‘seed’ for ZnO crystals growth, which is beneficial for the high dispersion of nano-sized active components. The presented method is beneficial to producing sorbents with better structure and promoted desulfurization performance.

Background The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. Methods BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. Results After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P P P Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. Conclusions NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

Latent tuberculosis infection (LTBI) is a challenging problem in preventing, diagnosing, and treating tuberculosis (TB). The innate and adaptive immune responses are essential for eliminating or killing the mycobacteria.

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.

Latent tuberculosis infection (LTBI) is the primary source of tuberculosis (TB) but there is no suitable detection method to distinguish LTBI from active tuberculosis (ATB). In this study, five antigens of Mycobacterium tuberculosis belonging to LTBI and regions of difference (RDs) were selected to predict Th1 and cytotoxic T lymphocyte (CTL) epitopes. The immunodominant Th1 and CTL peptides were identified in mouse models, and their performance in distinguishing LTBI from ATB was determined in mice and humans. Ten Th1 and ten CTL immunodominant peptides were predicted and synthesized

Plant extract-mediated synthesis of metal nanoparticles (NPs) is an eco-friendly and cost-effective biosynthesis method that is more suitable for biological applications than chemical ones. We prepared novel gold NPs (AuNPs)

Functional complete revascularization (FCR) after percutaneous coronary intervention (PCI) as determined by the residual functional SYNTAX score (rFSS) based on pressure wire fractional flow reserve assessment has been associated with an improved prognosis.This study sought to determine the rates and clinical implications of FCR as assessed by the quantitative flow ratio (QFR), and to determine the outcomes of pre-PCI QFR guidance compared with standard angiography guidance in patients achieving and not achieving FCR after PCI.In the randomized, sham-controlled, blinded, multicenter FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial, QFR-guided PCI reduced the 1-year rate of major adverse cardiac events (MACE) compared with angiography-guided PCI. In the present prespecified substudy, the incidence of MACE was compared according to the presence of post-PCI FCR (rFSS = 0 based on core laboratory-assessed QFR) in the QFR-guided and angiography-guided groups.Among 3,781 patients with available rFSS assessments, 3,221 (85.2%) achieved FCR, including 88.1% after QFR guidance and 82.2% after angiography guidance (P 0.001). Patients with FCR had a markedly lower rate of 1-year MACE compared with those with functional incomplete revascularization (FIR) (rFSS ≥1) (5.1% vs 19.7%; P 0.001). Prognostic models including the rFSS had higher discrimination and reclassification ability than those with the anatomic residual SYNTAX score. The relative risks for 1-year MACE with QFR-guided compared with the angiography-guided lesion selection were consistent in patients achieving FCR (4.1% vs 6.3%; HR: 0.65; 95% CI: 0.47-0.88) and in those with FIR (18.7% vs 20.4%; HR: 0.90; 95% CI: 0.61-1.32) (PIn this large-scale trial, achieving FCR after PCI was associated with markedly lower 1-year rates of MACE. Compared with standard angiography guidance, QFR-guided PCI lesion selection improved the likelihood of achieving FCR and improved 1-year clinical outcomes in patients with both FCR and FIR.

Silymarin exhibits an anti-inflammatory property in various cancers and inflammatory diseases. In our previous work, silymarin-mediated selenium nanoparticles (SeNPs) (Si-SeNPs) were developed using a green synthesis technique, and its potential as an anticancer agent was confirmed. In order to further examine the extended comprehensive potential of Si-SeNPs, this investigation focuses on studying the enhanced anti-inflammatory effect of Si-SeNPs in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction were used to evaluate the expression of pro-inflammatory mediators and cytokines. Western blotting and immunofluorescence assays were conducted to assess the protein expression of p-PI3K, p-Akt, p-NF-κB, and p-IκBα. Compared to silymarin, Si-SeNPs exhibited a significantly increased inhibitory effect on LPS-induced release of nitric oxide and the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) in RAW264.7 cells. A western blot assay indicated that Si-SeNPs downregulated the PI3K/Akt and NF-κB signaling pathways. The immunofluorescence assay suggested that Si-SeNPs inhibited the nuclear translocation and the activation of NF-κB. In addition, 740 Y-P (PI3K agonist) was used to demonstrate that activating the PI3K/Akt signal could partially reverse the inflammatory response, suggesting a causal role of the PI3K/Akt signaling pathway in the anti-inflammatory effect of Si-SeNPs. Consequently, these findings indicate that Si-SeNPs could be a functional agent of the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages through inhibiting the PI3K/Akt/NF-κB signaling pathway. In addition, biosynthesized Si-SeNPs could be more effective at reducing inflammation than only silymarin extracts. Thus, this study lays an experimental foundation for the clinical application of using biosynthesized SeNPs as a novel candidate in the field of inflammation-associated diseases.

Although naturally occurring flavonoids have shown beneficial effects on the side effects caused by cisplatin, there are few reports on the protective effect of dihydrochalcone on the cisplatin-induced toxicity. Trilobatin (TLB), as the major sweetener and active ingredient in

ObjectiveTo evaluate the prevalence of hyperglycemia and dyslipidemia among different body composition and investigate the associations of body composition indicators, especially the muscle mass, with glucose and lipids metabolism in children and adolescents.MethodsThis nationwide cross-sectional study included 8,905 children and adolescents aged 6 to 18 years. All participants underwent dual-energy x-ray absorptiometry and their blood-concentrated glucose and lipids (including TC, TG, LDL-C and HDL-c) were measured. Mixed model, hierarchical analysis, and piecewise regression were used to study the effect of body composition indicators, especially the muscle mass, on glucose and lipids metabolism.ResultsThe greatest prevalence of high total cholesterol (TC, 6.9% and 6.9%) and high triglyceride (22.3% and 6.6%) was found in both boys and girls with high muscle mass and high fat mass, and girls with high muscle mass and high fat mass also had the highest prevalence of hyperglycemia (7.1%). After fat stratification, higher muscle mass was associated with lower odds of hyperglycemia (OR = 0.62; 95%CI: 0.46,0.84; P = 0.002) and muscle mass was inversely associated with TC (β = −0.07; 95%CI: -0.12,-0.03; P < 0.001) in boys with normal fat mass, but high muscle mass was not significantly associated with hyperglycemia and TC in high-fat-mass group (P = 0.368 and 0.372).ConclusionsThe body composition phenotype of high muscle and high fat mass have the highest prevalence of dysglycemia and dyslipidemia. Higher muscle mass was associated with a lower risk of hyperglycemia and TC levels in individuals only with normal fat mass.

Introduction We previously demonstrated that magnesium ions (Mg2+) was a novel therapeutic alternative for osteoarthritis (OA) through promoting the hypoxia inducible factor-1α (HIF-1α)-mediated cartilage matrix synthesis. However, oxidative stress can inhibit the expression of HIF-1α, amplify the inflammation that potentially impairs the therapeutic efficacy of Mg2+ in OA. Vitamin (VC), a potent antioxidant, may enhance the efficacy of Mg2+ in OA treatment. This study aims to investigate the efficacy of combination of Mg2+ and VC on alleviating joint destruction and pain in OA. Material and methods Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline, MgCl2 (0.5 mol/L), VC (3 mg/ml) or MgCl2 (0.5 mol/L) plus VC (3 mg/ml) at week 2 post-operation, twice weekly, for 2 weeks. Joint pain and pathological changes were assessed by gait analysis, histology, western blotting and micro-CT. Results Mg2+ and VC showed additive effects to significantly alleviate the joint destruction and pain. The efficacy of this combined therapy could sustain for 3 months after the last injection. We demonstrated that VC enhanced the promotive effect of Mg2+ on HIF-1α expression in cartilage. Additionally, combination of Mg2+ and VC markedly promoted the M2 polarization of macrophages in synovium. Furthermore, combination of Mg2+ and VC inhibited osteophyte formation and expressions of pain-related neuropeptides. Conclusions Intra-articular administration of Mg2+ and VC additively alleviates joint destruction and pain in OA. Our current formulation may be a cost-effective alternative treatment for OA., Graphical abstract Image 1, Highlights • Magnesium ions (Mg2+) and vitamin C (VC) efficaciously alleviates joint pathology and pain in OA. • Mg2+ + VC markedly increase expression of HIF-1a, a key anabolic factor in cartilage. • Mg2+ + VC significantly promote M2 polarization of synovial macrophage, may subsequently reduce inflammatory pain. • Mg2+ + VC also inhibit osteophyte formation and productions of pain-related neuropeptides.

Excessive glutamate leading to excitotoxicity worsens brain damage after SAH and contributes to long-term neurological deficits. The drug ifenprodil is a non-competitive antagonist of GluN1-GluN2B N-methyl-d-aspartate (NMDA) receptor, which mediates excitotoxic damage in vitro and in vivo. Here, we show that cerebrospinal fluid (CSF) glutamate level within 48 h was significantly elevated in aSAH patients who later developed poor outcome. In rat SAH model, ifenprodil can improve long-term sensorimotor and spatial learning deficits. Ifenprodil attenuates experimental SAH-induced neuronal death of basal cortex and hippocampal CA1 area, cellular and mitochondrial Ca2+ overload of basal cortex, blood-brain barrier (BBB) damage, and cerebral edema of early brain injury. Using in vitro models, ifenprodil declines the high-concentration glutamate-mediated intracellular Ca2+ increase and cell apoptosis in primary cortical neurons, reduces the high-concentration glutamate-elevated endothelial permeability in human brain microvascular endothelial cell (HBMEC). Altogether, our results suggest ifenprodil improves long-term neurologic deficits through antagonizing glutamate-induced excitotoxicity.

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., This longitudinal study presented sexual discrepancies in fat‐bone relationship from a life course perspective. 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.

Summary Background & Aims The rise in the prevalence of childhood obesity has increased the demand for accurately evaluating body fatness in pediatric population. The aim of this study was to provide a series of sex- and age-specific body fat reference centiles for evaluating total body fat development and fat distribution in Chinese children and adolescents using dual-energy x-ray absorptiometry (DXA). Methods A nationwide sample of Chinese children and adolescents aged 3-18 years (n=12,790) was drawn from a cross-sectional survey of the China Child and Adolescent Cardiovascular Health study (2013-2019). Fat measurements, including total fat mass index (FMI), total body fat percentage (BF%), regional FMI, trunk to leg (T/L) fat ratio and android to gynoid (A/G) fat ratio, were derived from whole body DXA scans. Sex- and age-specific centiles were estimated using the lambda-mu-sigma method and then compared with values derived from the US National Health and Nutrition Examination Survey (1999-2004) and Korean National Health and Nutrition Examination Survey (2008-2011). Results During early childhood, almost all body fat parameters decreased with age, except an increase in A/G ratio. After 7 years onward, drastic upward trends of total FMI and BF% were exhibited in boys till 10 years, followed by opposite downward trends during 11-14 years; while sustained increase of FMI was shown in girls across ages accompanied by relatively constant BF% levels. Meanwhile, steady increases were noticed for A/G ratio and T/L ratio, which were more pronounced in boys. In addition, the proposed body fat references were much lower than the US but similar to Koreans despite of subtle differences. Conclusions This is the first study to present a set of DXA-based body fat reference for Chinese children and adolescents aged 3-18 years. The new reference provides clinicians and researchers a useful tool for assessing body fat development and distribution patterns across the periods from early childhood to adolescence.

Importance The impact of long‐term burden of excessive body weight, beginning in childhood, on inflammatory status in adulthood has been poorly described. Objective To characterize the longitudinal body mass index (BMI) trajectory from childhood and examine its relationship with inflammatory status in adulthood. Methods We included 1285 adults who had 4–15 repeat measurements of BMI from childhood to adulthood. The area under the curve (AUC) of growth curves was calculated to characterize long‐term burden (total AUC) and trends (incremental AUC) of BMI. Results After adjusting for covariates, higher values of BMI in terms of childhood and adulthood, as well as total and incremental AUC, were strongly associated with elevated levels of adult C‐reactive protein (CRP) in the four race‐sex groups. There were significant differences in linear and nonlinear curve parameters between the normal and high CRP groups for all race‐sex groups (P < 0.01). Compared with participants who had consistently low BMI in both childhood and adulthood, participants with high BMI in adulthood had higher CRP levels (P < 0.001), irrespective of their childhood BMI status; participants with high BMI in childhood but low BMI in adulthood had similar adult CRP levels. Interpretation The impact of excessive body weight on inflammation is cumulative and exacerbated over time. The influence of childhood overweight/obesity on inflammatory status in adulthood can be alleviated by reducing adiposity in adulthood., Low‐grade inflammation is a mechanistic link between obesity and cardiometabolic disorders. We utilized longitudinal data from the Bogalusa Heart Study to examine the associations of cumulative burden and trajectory measures of body weight from childhood with chronic inflammation in adulthood.

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., The INTERSALT provided unbiased estimations of mean population sodium intake in adolescents aged 14 to 16 years.