Dynamic influence of maternal education on height among Chinese children aged 0-18 years.

Background: Maternal education is one of key factors affecting nurturing environment which significantly impacts children's height levels throughout their developmental stages. However, the influence of maternal education on children's height is less studied. This study aims to investigate the dynamic influence of maternal education on children's height among Chinese children aged 0-18 years. Methods: Children undergoing health examinations from January 2021 to September 2023 were included in this study. Clinical information including height, weight, maternal pregnancy history, blood specimens for bone metabolism-related indicators and maternal education level was collected. Children's height was categorized into 14 groups based on age and gender percentiles, following WHO 2006 growth standards. One-way analysis of variance (ANOVA), linear regression, chi-square test and Fisher's exact test were applied for data analysis. Results: A total of 6269 samples were collected, including 3654 males and 2615 females, with an average age of 8.38 (3.97) for males and 7.89 (3.55) for females. Significant correlations between maternal education level, birth weight, birth order, weight percentile, vitamin D, serum phosphorus, alkaline phosphatase levels, and children's height were identified. Birth weight's influence on height varied across age groups. Compared with normal birth weight children, low birth weight children exhibited catch-up growth within the first 6 years and a subsequent gradual widening of the height gap from 6 to 18 years old. Remarkably, the impact of maternal education on height became more pronounced among children above 3-6 years old, which can mitigate the effect of low birth weight on height. Conclusion: We found that weight percentile, birth weight, birth order, bone marker levels, and maternal education level have significant effect on height. Maternal education attenuates the impact of low birth weight on height. The findings indicated that maternal education plays a consistent and critical role in promoting robust and healthy growth.

Serum Uric Acid Levels among Chinese Children: Reference Values and Association With Overweight/Obesity.

This study aimed to investigate the reference values for serum uric acid (SUA) levels and their association with overweight/obese in children. We conducted a retrospective analysis of 8522 participants, including 6227 normal weight children, aged 2 to 18 years in China. Among normal children, SUA levels increased with age, showing significant sex differences in children over 10 years. Age-specific and sex-specific 95% reference intervals for SUA levels were established. Furthermore, we observed that the percentage of overweight/obesity significantly increased as SUA quartiles rose. Elevated SUA levels were associated with a high odds ratio (OR) for overweight/obesity (OR = 4.45, 95% confidence interval = 3.33, 5.93). We propose that the 97.5th percentile is a suitable value for defining elevated SUA levels, and there is a positive correlation between SUA levels and the presence of overweight or obesity.

The oxytocin receptor rs2254298 polymorphism and alcohol withdrawal symptoms: a gene-environment interaction in mood disorders.

Objective: Alcohol use disorder (AUD) is a common mental disorder characterized by repeated withdrawal episodes. Negative emotions during withdrawal are the primary factors affecting successful abstinence. Oxytocin is a critical modulator of emotions. OXTR, the oxytocin receptor, may also be a promising candidate for treating alcohol withdrawal symptoms. Previous studies indicated that people with different genotypes of OXTR rs2254298 were reported to suffer from more significant depressive or heightened anxiety symptoms when experiencing early adversity. The present study aims to explore the modulatory role of the polymorphism OXTR rs2254298 on mood disorders during alcohol withdrawal and to help researchers better understand and develop effective relapse prevention and interventions for alcohol use disorders. Methods: We recruited 265 adult Chinese Han men with AUD. Anxiety and depressive symptoms were measured using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Alcohol dependence levels were measured using Michigan Alcoholism Screening Test. Genomic DNA extraction and genotyping from participants' peripheral blood samples. Result: First, a multiple linear regression was used to set the alcohol dependence level, OXTR.rs2254298, interaction terms as the primary predictor variable, and depression or anxiety as an outcome; age and educational years were covariates. There was a significant interaction between OXTR rs2254298 and alcohol dependence level on anxiety (B = 0.23, 95% confidence interval [CI]: 0.01-0.45) but not on depression (B = -0.06, 95% CI: -0.30 - 0.18). The significance region test showed that alcohol-dependent men who are GG homozygous were more likely to experience anxiety symptoms than subjects with the A allele (A allele: ß = 0.27, p < 0.001; GG homozygote: ß = 0.50, p < 0.001). Finally, re-parameterized regression analysis demonstrated that this gene-environment interaction of OXTR rs2254298 and alcohol dependence on anxiety fits the weak differential susceptibility model (R2 = 0.17, F (5,259) = 13.46, p < 0.001). Conclusion: This study reveals a gene-environment interactive effect between OXTR rs2254298 and alcohol withdrawal on anxiety but not depression. From the perspective of gene-environment interactions, this interaction fits the differential susceptibility model; OXTR rs2254298 GG homozygote carriers are susceptible to the environment and are likely to experience anxiety symptoms of alcohol withdrawal.

Effects of Lactobacillus on hyperlipidemia in high-fat diet-induced mouse model.

Introduction: Hyperlipidemia refers to a group of lipid metabolism disorders characterized by increased levels of total cholesterol, triglyceride, and/or low-density lipoprotein cholesterol and/or decreased levels of high-density lipoprotein cholesterol. This study aims to investigate the effects of Lactobacillus on lipid metabolism and hepatic steatosis in male mice fed with a high-fat diet by measuring blood lipid, hepatic function and hepatocyte morphology. Material and methods: Eighty male Institute of Cancer Research (ICR) mice were fed with a high-fat diet for 6 weeks to establish hyperlipidemic models. Then, mice were treated with a high or low concentration of Lactobacillus of human source, mouse source, or plant source, respectively. Results: After 3 weeks of therapy, except for the human Lactobacillus treatment group, the blood cholesterol, triglyceride and low-density lipoprotein cholesterol in mice treated with Lactobacillus of mouse and plant source were lower than those in the hyperlipidemic model group. After 4 weeks of treatment, the levels of blood biochemical indexes in mice in all treatment groups were significantly different, when compared to those in the hyperlipidemic model group. Conclusions: Lactobacillus may regulate blood lipid in mice fed with a high-fat diet. Lactobacillus can improve the high cholesterol, high blood lipid, and injury of hepatic function, and prevent further development of atherosclerosis caused by a high-fat diet to some extent. Correct dietary structure is the basis for the treatment of dietary hyperlipidemia and its complications.

Frequency-dependent alterations in regional homogeneity associated with puberty hormones in girls with central precocious puberty: A resting-state fMRI study.

OBJECTIVE: Central precocious puberty (CPP) patients are at significantly higher risk of emotional, mental, and behavioral disorders than those normal pubertal population. However, to date, the definite mechanism of how puberty hormones affect patients with CPP remains unclear. This regional homogeneity (ReHo) study aimed to explore the impact of premature hypothalamus-pituitary-gonadal (HPG) axis activation on brain function alteration in girls with CPP, meanwhile, to explore the relationship between gonadotropin and gonadal hormones levels, abnormal brain activity and cognitive function. METHODS: In this prospective study, a total of 85 girls who were suspected of having CPP were enrolled from the Child Healthcare Department of the Second Affiliated Hospital of Wenzhou Medical University Hospital from June 2018 to May 2021, including 41 CPP girls and 44 non-CPP girls. All participants collected the 0, 30, 60 min blood luteinizing hormone (LH), follicle-stimulating hormone (FSH), 0, 30 min estradiol (E2) and baseline cortisol (COR) and prolactin (PRL) concentrations after gonadotrophin-releasing hormone (GnRH) stimulating test. Resting-state magnetic resonance imaging (rs-MRI) scans were performed for all participants at 2 weeks before the GnRH stimulating test, voxel-wise ReHo was calculated in the standard frequency band (0.01-0.10 Hz), and in slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz). Wechsler Intelligence Scale for Children Fourth Edition (WISC-IV) was also collected. Independent-sample t-test or Mann-Whitney U test was used to compare the differences between two groups. The correlation analysis among abnormal brain regions, serum hormone levels and WISC-IV scores were performed by Spearman or partial correlation analysis. RESULTS: Compared to the non-CPP group, the CPP group showed higher regional homogeneity (ReHo) values in the left inferior temporal gyrus (ITG.L), as well as lower ReHo values in left superior temporal gyrus (STG.L), left superior occipital gyrus (SOG.L) and the right middle gyrus (MTG.R) in slow4.in slow5 frequency band, CPP group demonstrated decreased ReHo values in bilateral orbital part of superior frontal gyrus and medial superior frontal gyrus. LIMITATION: Due to the cross-section design of this study, further research is needed to explore the relationships between age, premature activation HPG axis and brain function changes. CONCLUSION: Our findings demonstrate that premature HPG axis activation and alterations in puberty hormones, may lead to changes in brain activity and cognitive function. This rs-fMRI study may enhance our understanding of the neuroendocrine mechanisms of mood, behavior, and cognitive function alterations in patients with CPP.

The Diagnostic Utility of the Basal Luteinizing Hormone Level and Single 60-Minute Post GnRH Agonist Stimulation Test for Idiopathic Central Precocious Puberty in Girls.

Objective: The present study aimed to assess the diagnostic utility of the Luteinizing hormone (LH) levels and single 60-minute post gonadotropin-releasing hormone (GnRH) agonist stimulation test for idiopathic central precocious puberty (CPP) in girls. Methods: Data from 1,492 girls diagnosed with precocious puberty who underwent GnRH agonist stimulation testing between January 1, 2016, and October 8, 2020, were retrospectively reviewed. LH levels and LH/follicle-stimulating hormone (FSH) ratios were measured by immuno-chemiluminescence assay before and at several timepoints after GnRH analogue stimulation testing. Mann-Whitney U test, Spearman's correlation, χ2 test, and receiver operating characteristic (ROC) analyses were performed to determine the diagnostic utility of these hormone levels. Results: The 1,492 subjects were split into two groups: an idiopathic CPP group (n = 518) and a non-CPP group (n = 974). Basal LH levels and LH/FSH ratios were significantly different between the two groups at 30, 60, 90, and 120 minutes after GnRH analogue stimulation testing. Spearman's correlation analysis showed the strongest correlation between peak LH and LH levels at 60 minutes after GnRH agonist stimulation (r = 0.986, P < 0.001). ROC curve analysis revealed that the 60-minute LH/FSH ratio yielded the highest consistency, with an area under the ROC curve (AUC) of 0.988 (95% confidence interval [CI], 0.982-0.993) and a cut-off point of 0.603 mIU/L (sensitivity 97.3%, specificity 93.0%). The cut-off points of basal LH and LH/FSH were 0.255 mIU/L (sensitivity 68.9%, specificity 86.0%) and 0.07 (sensitivity 73.2%, specificity 89.5%), respectively, with AUCs of 0.823 (95% CI, 0.799-0.847) and 0.843 (95% CI, 0.819-0.867), respectively. Conclusions: A basal LH value greater than 0.535 mIU/L can be used to diagnose CPP without a GnRH agonist stimulation test. A single 60-minute post-stimulus gonadotropin result of LH and LH/FSH can be used instead of a GnRH agonist stimulation test, or samples can be taken only at 0, 30, and 60 minutes after a GnRH agonist stimulation test. This reduces the number of blood draws required compared with the traditional stimulation test, while still achieving a high level of diagnostic accuracy.

Glycoursodeoxycholic acid ameliorates diet-induced metabolic disorders with inhibiting endoplasmic reticulum stress.

Recent studies reveal that bile acid metabolite composition and its metabolism are changed in metabolic disorders, such as obesity, type 2 diabetes and metabolic associated fatty liver disease (MAFLD), yet its role and the mechanism remain largely unknown. In the present study, metabolomic analysis of 163 serum and stool samples of our metabolic disease cohort was performed, and we identified glycoursodeoxycholic acid (GUDCA), glycine-conjugated bile acid produced from intestinal bacteria, was decreased in both serum and stool samples from patients with hyperglycemia. RNA-sequencing and quantitative PCR results indicated that GUDCA alleviated endoplasmic reticulum (ER) stress in livers of high fat diet (HFD)-fed mice without alteration of liver metabolism. In vitro, GUDCA reduced palmitic acid induced-ER stress and -apoptosis, as well as stabilized calcium homeostasis. In vivo, GUDCA exerted effects on amelioration of HFD-induced insulin resistance and hepatic steatosis. In parallel, ER stress and apoptosis were decreased in GUDCA-treated mice as compared with vehicle-treated mice in liver. These findings demonstrate that reduced GUDCA is an indicator of hyperglycemia. Supplementation of GUDCA could be an option for the treatment of diet-induced metabolic disorders, including insulin resistance and hepatic steatosis, with inhibiting ER stress.

Long-chain noncoding RNA-GAS5/hsa-miR-138-5p attenuates high glucose-induced cardiomyocyte damage by targeting CYP11B2.

OBJECTIVE: Diabetic cardiomyopathy (DCM) is one of the complications experienced by patients with diabetes. In recent years, long noncoding RNAs (lncRNAs) have been investigated because of their role in the progression of various diseases, including DCM. The purpose of the present study was to explore the role of lncRNA GAS5 in high glucose (HG)-induced cardiomyocyte injury and apoptosis. MATERIALS AND METHODS: We constructed HG-induced AC16 cardiomyocytes and a streptozotocin (STZ)-induced rat diabetes model. GAS5 was overexpressed and knocked out at the cellular level, and GAS5 was knocked down by lentiviruses at the animal level to observe its effect on myocardial injury. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of GAS5. Cell proliferation and apoptosis after GAS5 knockout were detected by CCK-8, TUNEL, and flow cytometry assays. ELISA was used to detect the changes in myocardial enzyme content in cells and animal myocardial tissues during the action of GAS5 on myocardial injury. RESULTS: GAS5 expression was up-regulated in HG-treated AC16 cardiomyocytes and the rat diabetic myocardial injury model. The down-regulation of GAS5 could inhibit HG-induced myocardial damage. This work proved that the down-regulation of GAS5 could reverse cardiomyocyte injury and apoptosis by targeting miR-138 to down-regulate CYP11B2. CONCLUSION: We confirmed for the first time that the down-regulation of GAS5 could reverse CYP11B2 via the miR-138 axis to reverse HG-induced cardiomyocyte injury. This research might provide a new direction for explaining the developmental mechanism of DCM and potential targets for the treatment of myocardial injury.

The performance of noninvasive indexes of adults in identification of nonalcoholic fatty liver disease in children.

BACKGROUND: The aim of this study is to evaluate the performance of three existing prediction scores which are applicable to adults for identifying nonalcoholic fatty liver disease (NAFLD) in Chinese children. METHODS: We used data from routine check-up based medical records of 1845 children to validate the performance of three existing scoring systems including the hepatic steatosis index (HSI), Zhejiang University index (ZJU index), and triglyceride-glucose index (TyG index) in detection of NAFLD in children. Propensity score matching was applied to adjust for potential confounding effects in both training and validation cohorts. The area under the curve (AUC) of the receiver operating characteristic curve analysis was utilized to assess the performance of the three scoring systems. RESULTS: Children with NAFLD had higher scores of HSI, ZJU index, and TyG index when compared with the control group (children without NAFLD). Elevated HSI, ZJU index, and TyG index scores were significantly associated with the presence of pediatric NAFLD since adjusted odds ratio and 95% CI with per interquartile range elevation of the HSI, ZJU index, and TyG index were 32.81 (20.48, 52.55), 26.31 (16.97, 40.79), and 1.83 (1.57, 2.13), respectively. In terms of discrimination of NAFLD in children, the AUC of the HSI, ZJU index, and TyG index depending on the validation cohort were 0.964, 0.960, and 0.769, respectively. CONCLUSIONS: The HSI and ZJU index could be appropriate noninvasive biomarkers in distinguishing NAFLD in children from their controls with satisfied accuracy, which would emphasize the clinical and public health policy relevance of pediatric NAFLD. Our findings need to be confirmed by additional longitudinal studies.

Influence of the hypothalamus-pituitary-gonadal axis reactivation and pubertal hormones on gray matter volume in early pubertal girls.

OBJECTIVE: Puberty is a sensitive period of brain development accompany with pubertal hormones fluctuation. However, the underlying mechanisms of the impact of hypothalamus-pituitary-gonadal (HPG) axis reactivation and associated elevated pubertal hormones on brain structure are still unclear. Here, we investigated the brain structure differences between girls with and without HPG axis reactivation and the influence of pubertal hormones on these brain regions. METHODS: 126 girls aged 8-9.5 years underwent a gonadotropin-releasing hormone (GnRH) stimulation test to identify the HPG axis status and categorized into HPG+ group (n = 80) and HPG- group (n = 46). T1-weighted gradient echo three dimensional MRI was performed using a 3.0-Tesla scanner to assess the difference in GMV between the two groups. Correlation analyses were conducted to explore the relations between the brain regions showing significant GMV differences and serum hormone concentrations. RESULT: The HPG+ group showed significantly higher GMV in the bilateral lingual gyrus and lower GMV within the right orbital inferior frontal gyrus compare to the HPG - group. Furthermore, GMV in the right orbital inferior frontal gyrus was positively associated with plasma concentrations of follicle stimulating hormone (FSH) in HPG+ group. CONCLUSION: The present study suggests that the reactivated HPG axis could affects regional structural brain changes in early pubertal girls. FSH production play an important role in bilateral lingual gyrus, which are involved in vision processing, semantic processing and emotional expression.

Gray Matter Differences Between Premature Pubertal Girls With and Without the Reactivation of the Hypothalamic-Pituitary-Gonadal Axis.

The onset of puberty and related hormones exerts significant effects on brain morphometric and psychosocial development. The biological mechanisms underlying how the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis and puberty-related hormonal maturation sculpts human brain architecture remain elusive. To address this question, 105 premature pubertal girls (age 8-11 years) without menstruation underwent brain structural scanning on a 3T MR system, and the luteinizing hormone releasing hormone (LHRH) stimulation test was used to identify the reactivation of the HPG axis. Among the 105 girls, 63 were positive for HPG axis reactivation (HPG+), while the others showed negative (HPG-). Cortical thickness was calculated and compared between the two groups after adjusting for age. The brain regions showing inter-group differences were then extracted and correlated with the peak value of serum hormone after the LHRH stimulation test in entire sample. Compared to HPG- girls, HPG+ girls showed reduced cortical thickness mainly in the the right precuneus, right inferior temporal gyrus, and right superior frontal gyrus, while increased cortical thickness primarily in the left superior parietal lobe and right inferior parietal lobe. Linear-regression analysis revealed negative correlations between the cortical thickness of the right inferior parietal lobe with the peak value of FSH and the right precuneus with LH and E. These findings provide evidence to support the notion that the reactivation of HPG axis and changes of hormones during the early phase of hormonal maturation exert influences on the development of gray matter.

Zinc supplementation protects against diabetic endothelial dysfunction via GTP cyclohydrolase 1 restoration.

This study explored whether zinc supplementation alleviates diabetic endothelial dysfunction and the possible mechanisms underlying. We found that high glucose exposure significantly increased reactive oxygen species (ROS) and decreased guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1) and tetrahydrobiopterin (BH4) levels in bovine aortic endothelial cells (BAECs) in a time-dependent manner. High glucose increased zinc release from GTPCH1 in a similar trend. Zinc supplementation restored GTPCH1 and BH4 levels and blocked ROS accumulation in both BACEs and wild type GTPCH1 transfected HEK293 cells, but not in the zinc-free C141R mutant of GTPCH1 transfected ones. In vivo experiments showed that exogenous supplementation of zinc to streptozotocin (STZ)-induced diabetic mice partially improved the impaired maximal endothelium-dependent vasorelaxation, reversed the aberrant reduction of GTPCH1 and BH4, and suppressed the elevation of ROS in the aortas. In conclusion, our study demonstrated a novel mechanism that via GTPCH1 restoration zinc supplementation exerts a protective benefit on diabetic endothelial dysfunction.

Influence of the hypothalamus-pituitary-gonadal axis reactivation and corresponding surging sex hormones on the amplitude of low-frequency oscillations in early pubertal girls: A resting state fMRI study.

BACKGROUND: There has been a myriad of neuroimaging studies that have suggested that pubertal stages and sex steroid fluctuations contribute to pubertal brain maturation. Investigations on the influence of hypothalamus-pituitary-gonadal (HPG) axis reactivation and the correlated elevated sex hormones on brain maturation have not unraveled these interactions to date. Here, we aimed to explore the impact of the reactivated HPG axis on spontaneous brain activity changes, by analyzing the amplitude of low-frequency fluctuation (ALFF) in developing girls aged 8-11 years old. METHODS: The gonadotropin-releasing hormone (GnRH) stimulation test was used to determine the HPG axis status and categorize subjects into two groups (HPG+ or HPG- group). Intelligence quotient (IQ) and the parent-rated Child Behavior Checklist (CBCL) were used to evaluate cognitive and behavioral performance. Two-sample t-tests were used to compare intergroup differences, the relations between brain areas' activities, age and hormonal levels were conducted by Pearson or Spearman correlation analyses. RESULTS: Compared with the HPG- group, the HPG+ group showed decreased ALFF values in the left superior temporal gyrus (STG) but increased ALFF values in the right superior frontal gyrus (SFG). In addition, in the HPG+ group, prolactin (PRL) levels were positively correlated with ALFF values in the right SFG, and there was significant negative correlation between ALFF values in the left STG and CBCL activities scores. LIMITATIONS: Due to the cross-sectional design of the present study, further study is needed to determine the relationships between age, reawakening of the HPG axis and related sex hormones and spontaneous brain activity change. CONCLUSIONS: These findings suggested that the reactivated HPG axis and elevated PRL level could affect changes in brain activity and this effect may be the neuroendocrine basis of mood, cognition, and social behavior changes in early pubertal girls.

Initiation of the Hypothalamic-Pituitary-Gonadal Axis in Young Girls Undergoing Central Precocious Puberty Exerts Remodeling Effects on the Prefrontal Cortex.

Central precocious puberty (CPP) has been shown to exert significant effects on psychosocial development. These early puberty-related hormones and psychosocial functional changes are considered to be associated with specific brain development. However, the biological mechanisms underlying the sculpting of human brain architecture and modulation of psychosocial transformation by puberty-related hormonal maturation remain elusive, especially during the early phase of CPP. The current investigation aims to specify the brain regions in which early hormone-related maturation effects occur during CPP and their relationships with psychological functions. 65 young girls (aged 4.3-8.0 years) underwent structural imaging on a 3T MR system, completed psychological tests and performed the gonadotropin-releasing hormone (GnRH) stimulation test to identify hormonal manifestations of hypothalamic-pituitary-gonadal axis (HPG axis) activation. Based on the GnRH test, 28 young girls were identified with CPP, whereas the other 37 girls were identified with non-central precocious puberty (NCPP). Cortical parameters were calculated and compared between the two groups after adjusting for age, weight, and height. Brain regions showing group differences were extracted and correlated with serum hormone levels and psychological parameters. The CPP girls showed thinner cortices primarily in the right rostral middle frontal cortex. This morphological difference was positively correlated with stimulated estradiol (E2) levels. Further, higher E2 levels were significantly associated with higher hyperactivity scores. Premature HPG axis activation in CPP girls at an early stage appears to exert remodeling effects on brain anatomy, primarily in the prefrontal cortex, which may affect psychological development following the emergence of robust changes in sex hormones.

Altered Brain Structure and Functional Connectivity Associated with Pubertal Hormones in Girls with Precocious Puberty.

Pubertal hormones play an important role in brain and psychosocial development. However, the role of abnormal HPG axis states in altering brain function and structure remains unclear. The present study is aimed at determining whether there were significant differences in gray matter volume (GMV) and resting state (RS) functional connectivity (FC) patterns in girls with idiopathic central precocious puberty (CPP) and peripheral precocious puberty (PPP). We further explored the correlation between these differences and serum pubertal hormone levels. To assess this, we recruited 29 idiopathic CPP girls and 38 age-matched PPP girls. A gonadotropin-releasing hormone (GnRH) stimulation test was performed, and pubertal hormone levels (including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), prolactin, and cortisol) were assessed. All subjects underwent multimodal magnetic resonance imaging of brain structure and function. Voxel-based morphometry (VBM) analysis was paired with seed-to-voxel whole-brain RS-FC analysis to calculate the GMV and RS-FC in idiopathic CPP and PPP girls. Correlation analyses were used to assess the effects of pubertal hormones on brain regions with structural and functional differences between the groups. We found that girls with CPP exhibited decreased GMV in the left insula and left fusiform gyrus, while connectivity between the left and right insula and the right middle frontal gyrus (MFG), as well as the left fusiform gyrus and right amygdala, was reduced in girls with CPP. Furthermore, the GMV of the left insula and peak FSH levels were negatively correlated while higher basal and peak E2 levels were associated with increased bilateral insula RS-FC. These findings suggest that premature activation of the HPG axis and pubertal hormone fluctuations alter brain structure and function involved in the cognitive and emotional process in early childhood. These findings provide vital insights into the early pathophysiology of idiopathic CPP.

IL-17A contributes to myocardial ischemic injury by activating NLRP3 inflammasome in macrophages through AMPKα/p38MAPK/ERK1/2 signal pathway in mice.

BACKGROUND: Acute myocardial infarction (AMI) is followed by an acute inflammation involving inflammasome activation, thereby inducing cardiac dysfunction. Interleukin-17A (IL-17A) involves in many inflammatory diseases, but its roles in inflammation following AMI are still obscure. The aim of this study is to investigate the roles of IL-17A in the inflammatory response following AMI and its underlying mechanisms. METHODS AND RESULTS: NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway were significantly activated under the induction of IL-17A in mouse peritoneal macrophages, which could be inhibited by AMPK inhibitor compound C (CC). Both p38MAPK and ERK1/2 inhibitors could partially inhibit the activation of NLRP3 inflammasome in macrophages treated by IL-17A. In vivo, IL-17A knockout not only decreased the infiltration of macrophages and the activation of NLRP3 inflammasome and AMPKα/p38MAPK/ERK1/2 signaling pathway in ischemic myocardium, but also improved cardiac function and reduced infarction size after the ligation of descending segment from left coronary artery for 3 days in mice, while IL-17A administration further aggravated the myocardial ischemic injury, which were prevented by CC administration. CONCLUSION: IL-17A aggravates inflammatory response during AMI by inducing macrophages infiltration and activating NLRP3 inflammasome through AMPKα/p38MAPK/ERK1/2 pathway.

Targeting amino acids metabolic profile to identify novel metabolic characteristics in atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia whose incidence is on the rise globally. However, the pathophysiologic mechanism of AF remains poorly understood and there has been a lack of circulatory markers to diagnose and predict prognosis of AF. In the present study, by measuring metabolic profile and analyzing plasma amino acid levels in AF patients, we sought to determine whether amino acid metabolism was correlated to the occurrence of AF. Methods: Consecutive patients admitted to hospital for AF were enrolled. Plasma samples were obtained after overnight fast and a profile of 61 amino acids was then measured using gas chromatography/mass spectrometry (GC/MS). Results: Twenty-three AF and thirty-seven control patients were enrolled in the study. A number of plasma amino acids were altered in AF, which showed significant prediction value for AF. Intriguingly, circulating 4-hydroxypyrrolidine-2-carboxylic was gradually lowered with the persistence of AF. Plasma amino acid levels were more strongly correlated with each other in AF as compared with control. Conclusion: By utilizing non-target metabolic profile surveys, we have found a number of altered amino acids, which exhibit diagnostic value for AF. Enhanced amino acids correlation network further identified AF as a metabolism disorder.

Association of SLC30A8 gene polymorphism with type 2 diabetes, evidence from 46 studies: a meta-analysis.

The solute carrier family 30 member 8 (SLC30A8) gene may be involved in the development of type 2 diabetes mellitus (T2DM) through disrupting ß-cell function. The aim of this study was to assess the association between SLC30A8 rs13266634 polymorphism and susceptibility to T2DM. We searched all reports regarding the association between SLC30A8 rs13266634 polymorphism and T2DM risk through Pubmed, Embase, and the Cochrane Library for English language reports and Chongqing VIP database, Wanfang data, CBMDisc, and CNKI for Chinese language studies. Allelic and genotype comparisons between cases and controls were evaluated, and odds ratios with 95 % confidence intervals were used to assess the strength of their association. A random effects model was selected. Publication bias was estimated using Begg's test. Forty-six studies were included in the analysis with a total of 71,890 cases and 96,753 controls. This meta-analysis suggests that SLC30A8 (rs13266634) polymorphism was associated with T2DM risk. Although previous meta-analyses have shown that this association was only found in Asian and European groups, and not in African populations, our analysis revealed the deleterious effect of SLC30A8 rs13266634 on T2DM in an African population when stratified by ethnicity under additive model even with a small number of studies.

The activation of p38 MAPK limits the abnormal proliferation of vascular smooth muscle cells induced by high sodium concentrations.

The aim of the present study was to ascertain whether high sodium levels can directly promote the proliferation of vascular smooth muscle cells (VSMCs) and to elucidate the underlying mechanisms. Additional sodium chloride (NaCl) was added to the routine culture medium. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. The mRNA expression level of proliferating cell nuclear antigen (PCNA) was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression levels of PCNA and phosphorylated c-Jun amino N-terminal kinase (p-JNK), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) were measured by western blot analysis. Cell proliferation assay revealed that Na+ rather than Cl- or osmotic pressure promoted the proliferation of the VSMCs. The high sodium level upregulated the expression of PCNA and the phosphorylation levels of JNK, ERK1/2 and p38 MAPK. The inhibition of JNK and ERK1/2 decreased PCNA expression. Of note, the inhibition of p38 MAPK using the inhibitor, SB203580, increased PCNA expression. However, when p38 MAPK was activated by anisomycin, PCNA expression was decreased. On the whole, our findings demonstrate that a relatively high sodium level per se directly promotes the proliferation of VSMCs through the JNK/ERK1/2/PCNA pathway. At the same time, this induction of the proliferation of VSMCs due to high sodium levels can be maintained at a low level via the activation of p38 MAPK.