Uncovering the potential molecular mechanism of liraglutide to alleviate the effects of high glucose on myoblasts based on high-throughput transcriptome sequencing technique.

BACKGROUND: Myoblasts play an important role in muscle growth and repair, but the high glucose environment severely affects their function. The purpose of this study is to explore the potential molecular mechanism of liraglutide in alleviating the effects of high glucose environments on myoblasts. METHODS: MTT, western blot, and ELISA methods were used to investigate the role of liraglutide on C2C12 myoblasts induced by high glucose. The high-throughput transcriptome sequencing technique was used to sequence C2C12 myoblasts from different treated groups. The DESeq2 package was used to identify differentially expressed-mRNAs (DE-mRNAs). Then, functional annotations and alternative splicing (AS) were performed. The Cytoscape-CytoHubba plug-in was used to identify multicentric DE-mRNAs. RESULTS: The MTT assay results showed that liraglutide can alleviate the decrease of myoblasts viability caused by high glucose. Western blot and ELISA tests showed that liraglutide can promote the expression of AMPKα and inhibit the expression of MAFbx, MuRF1 and 3-MH in myoblasts. A total of 15 multicentric DE-mRNAs were identified based on the Cytoscape-CytoHubba plug-in. Among them, Top2a had A3SS type AS. Functional annotation identifies multiple signaling pathways such as metabolic pathways, cytokine-cytokine receptor interaction, cAMP signaling pathway and cell cycle. CONCLUSION: Liraglutide can alleviate the decrease of cell viability and degradation of muscle protein caused by high glucose, and improves cell metabolism and mitochondrial activity. The molecular mechanism of liraglutide to alleviate the effect of high glucose on myoblasts is complex. This study provides a theoretical basis for the clinical effectiveness of liraglutide in the treatment of skeletal muscle lesions in diabetes.

Relationship Between Hypertriglyceridemic Waist Phenotype and Disposition Index in Chinese Men With Normal Glucose Tolerance.

The relationship between hypertriglyceridemic waist (HTGW) phenotype, insulin sensitivity, and pancreatic ß-cell function remains still unclear in subjects with normal glucose tolerance (NGT). The objective is to detect whether the disposition index (DI) could be used as a predictive indicator of insulin sensitivity and pancreatic ß-cell function in men with HTGW phenotype and NGT. A total of 180 men without diabetes were recruited in this study and underwent an oral glucose tolerance test (OGTT) to calculate DI based on the OGTT. Subjects were put into Group A (normal waist circumference [WC] and triglyceride [TG] concentrations), B (enlarged WC or elevated TG concentrations), and C (HTGW phenotype, both enlarged WC and elevated TG concentrations) (n = 60 for each group) according to WC and TG concentrations. The OGTT plasma glucose concentrations at 0.5 and 1 hr for patients in Groups B and C were higher than those in Group A (both p < .05). Group C patients had significantly lower 1/[fasting insulin] values and DI than those in Group A (p < .05), and the 1/[fasting insulin] values in Group C were significantly lower than those in Group B (p < .05). DI correlated positively with high-density lipoprotein cholesterol (p < .05), which was independently associated with WC (p = .002) and TG (p = .009). The HTGW phenotype is associated with decreased DI among men with NGT, indicating decreased DI is a strong predictor of future impaired glucose tolerance, which can provide guidance and reference for screening patients with potential impaired glucose tolerance in Chinese community population.

Relationship Between Hyperuricemia-Waist Phenotype and Obstructive Sleep Apnea in Type 2 Diabetes Mellitus.

Objective: This study aimed to propose the hyperuricemia-waist (HUAW) phenotype and investigate the relationship between the HUAW phenotype and obstructive sleep apnea (OSA) in type 2 diabetes mellitus (T2DM). Methods: We enrolled 255 patients with T2DM (165 male and 90 female) from the First Hospital of Qinhuangdao. The sleep test was performed, and serum uric acid (UA) levels and waist circumference (WC) were calculated. The HUAW phenotype was defined as serum UA concentrations ≥420 µmol/L and WC ≥90 cm (male) and ≥85 cm (female). The participants were categorized into four phenotype groups based on the mentioned cutoffs: normal WC and normal UA concentrations (group A); normal WC and elevated UA concentrations (group B); enlarged WC and normal UA concentrations (group C); and enlarged WC and elevated UA concentrations (group D). Among these participants, 17.6% were characterized by the HUAW phenotype, 80.0% had OSA, and 47.0% had moderate-to-severe OSA. The prevalence of OSA was 43.4%, 71.4%, 89.7%, and 97.8% in groups A, B, C, and D, respectively. The prevalence of moderate-to-severe OSA was 7.5%, 28.6%, 56.9%, and 72.7% in groups A, B, C, and D, respectively. After adjusting for age, sex, duration of diabetes, glycosylated hemoglobin A1c, smoking, and drinking, the HUAW phenotype was found to be significantly associated with OSA and moderate-to-severe OSA. Conclusion: The present study proposed the HUAW phenotype and demonstrated that in T2DM, the HUAW phenotype was associated with OSA, especially with moderate-to-severe OSA. Unlike T2DM without the HUAW phenotype, T2DM with the HUAW phenotype showed a significantly higher prevalence of OSA, especially moderate-to-severe OSA. Thus, early sleep studies should be routinely examined in individuals with T2DM who display the HUAW phenotype.

J-shaped association between uric acid and breast cancer risk: a prospective case-control study.

BACKGROUND/AIM: In terms of breast cancer risk, there is no consensus on the effect of uric acid (UA) levels. The aim of our study was to clarify the link between UA and breast cancer risk in a prospective case-control study and to find the UA threshold point. METHODS: We designed a case-control study with 1050 females (525 newly diagnosed breast cancer patients and 525 controls). We measured the UA levels at baseline and confirmed the incidence of breast cancer through postoperative pathology. We used binary logistic regression to study the association between breast cancer and UA. In addition, we performed restricted cubic splines to evaluate the potential nonlinear links between UA and breast cancer risk. We used threshold effect analysis to identify the UA cut-off point. RESULTS: After adjusting for multiple confounding factors, we found that compared with the referential level (3.5-4.4 mg/dl), the odds ratio (OR) of breast cancer was 1.946 (95% CI 1.140-3.321) (P < 0.05) in the lowest UA level and 2.245 (95% CI 0.946-5.326) (P > 0.05) in the highest level. Using the restricted cubic bar diagram, we disclosed a J-shaped association between UA and breast cancer risk (P-nonlinear < 0.05) after adjusting for all confounders. In our study, 3.6 mg/dl was found to be the UA threshold which acted as the optimal turning point of the curve. The OR for breast cancer was 0.170 (95% CI 0.056-0.512) to the left and 1.283 (95% CI 1.074-1.532) to the right of 3.6 mg/dl UA (P for log likelihood ratio test < 0.05). CONCLUSION: We found a J-shaped association between UA and breast cancer risk. Controlling the UA level around the threshold point of 3.6 mg/dl provides a novel insight into breast cancer prevention.

Height-Corrected Definition of Metabolic Syndrome Is a Simple and Effective Method for Identifying Insulin Resistance and Low-Grade Inflammation in Adolescents: Metabolic Syndrome in Adolescents.

The purpose of this study was to evaluate the feasibility of the height-corrected definition of metabolic syndrome(MetS) in adolescents. A retrospective study was conducted on US adolescents aged 12 to 17 years. Waist-to-height ratio and blood pressure-to-height ratio were substituted for waist circumference and blood pressure when defining MetS in adolescents. The proportions of insulin resistance of adolescents with 1 (30.1%), 2 (50.7%), and ≥3 components (77.8%) of MetS were 2.578 (P < .001), 6.882 (P < .001), and 23.992 (P < .001) times than the proportion of adolescents without the component of MetS (14.2%). The proportions of low-grade inflammation of adolescents with 1 (3.4%), 2 (5.3%), and ≥3 components (14.4%) of MetS were 2.050 (P = .106), 3.699 (P = .005), and 10.664 (P < .001) times than the proportion of adolescents without the component of MetS (1.7%). This study demonstrates that height-corrected definition of MetS is a simple and accurate method for identifying insulin resistance and low-grade inflammation in adolescents.

Alternative skeletal muscle index for sarcopenia diagnosis in elderly patients with type 2 diabetes mellitus: A pilot study.

Purpose: To determine an alternative skeletal muscle index (a-SMI), easy diagnosis of sarcopenia in elderly patients with type 2 diabetes mellitus (T2DM). Patients and methods: This cross-sectional study included 223 inpatients with T2DM (100 males, age range 60-89; 123 females, age range 60-87). Screening for grip strength and gait speed, measuring SMI by dual-energy X-ray absorptiometry (d-SMI) for sarcopenia diagnosis, according to the Asian Working Group for Sarcopenia (AWGS) 2019 consensus. The a-SMI was established by binary logistic regression analysis with positive screening population. To assess the conformance of the new diagnostic approach with the AWGS 2019. Results: Sarcopenia was present in 36.3% of the study population. 59 had normal d-SMI and 81 had low d-SMI in screening patients with probable sarcopenia. In univariate analyses for all positive screening population, body mass index (BMI), 25-hydroxyvitamin D (25 - (OH) VitD), high density lipoprotein cholesterol (HDL-C), hypertension (HTN), and gender were correlates of d-SMI. Binary logistic regression analysis revealed that male (B = 2.463, 95%CI: 3.640 ~ 37.883, p = 0.000), HTN (B = 1.404, 95%CI: 1.599 ~ 10.371, p = 0.003), BMI (B = -0.344, 95%CI: 0.598 ~ 0.839, p = 0.000), 25-(OH) VitD (B = -0.058, 95%CI: 0.907 ~ 0.982, p = 0.004) were independent factors for d-SMI detection. Based on the extracted four correlates, the a-SMI was determined. The area under receiver operating characteristic (ROC) curve was 0.842, sensitivity and specificity for the new diagnostic approach were 84.0% and 84.5%. In a statistical measure of agreement between the AWGS 2019 and the new diagnostic approach, the kappa coefficient was 0.669 (p < 0.001). Conclusion: The a-SMI - based on gender, obesity status, 25-(OH) VitD, and HTN history - can be used in the absence of the d-SMI to supplement the algorithm for sarcopenia diagnosis in elderly patients with T2DM.

The relationship between obesity and bone mineral density in children and adolescents: analysis of the National Health and Nutrition Examination Survey.

Childhood and puberty are important period for the skeleton grows. Fat mass, especially visceral adipose tissue, was negatively correlated with areal bone mineral density in children and adolescents. The present study suggests that fat mass, especially visceral adipose tissue, has a slightly negative association with bone development in children and adolescents. PURPOSE: This study observed the relationship between fat mass and distribution, and areal bone mineral density (aBMD) in children and adolescents. METHODS: A retrospective study was conducted on US children and adolescents aged 8-19 years. Whole body (less head) aBMD was evaluated. Height (Ht) adjusted Z-scores for aBMD were calculated. RESULTS: After controlling for age, gender, race, and lean body mass index (LBMI) Z-score, there were significant negative associations between fat mass index (FMI) Z-score and aBMD Ht-Z-adjusted Z-score (ß = - 0.272, P < 0.001, R2 = 0.033). In the linear regression models with aBMD Ht-Z-adjusted Z-score as the dependent variable, the regression coefficients of android fat mass were - 0.241 (P < 0.05, R2 = 0.002), - 0.473 (P < 0.001, R2 = 0.036), and - 0.474 (P < 0.001, R2 = 0.038) for healthy weight, overweight, and obesity group, respectively. The regression coefficients of visceral adipose tissue (VAT) mass were - 0.218 (P > 0.05, R2 = 0.001), - 2.025 (P < 0.001, R2 = 0.044), and - 1.826 (P < 0.001, R2 = 0.039), and the regression coefficients of subcutaneous adipose tissue (SAT) mass were - 0.467 (P < 0.001, R2 = 0.004), - 0.339 (P < 0.01, R2 = 0.024), and - 0.347 (P < 0.001, R2 = 0.018) for healthy weight, overweight, and obesity group, respectively. CONCLUSIONS: The present study suggests that fat mass has a slightly negative association with bone development in children and adolescents. Trunk fat accumulation, especially visceral adipose tissue, was correlated with the lower level of aBMD. This association was obvious in overweight and obese children.

Hypoglycemic drug liraglutide alleviates low muscle mass by inhibiting the expression of MuRF1 and MAFbx in diabetic muscle atrophy.

BACKGROUND: Low muscle mass, that is, muscular atrophy, is an independent risk factor for type 2 diabetes mellitus (T2DM). Few studies investigated whether hypoglycemic drugs can alleviate low muscle mass and related mechanisms. METHODS: This study recruited 51 type 2 diabetes mellitus (T2DM) patients, who were divided into two groups based on skeletal muscle index (SMI) evaluated by Dual-energy X-ray absorptiometry (DXA): the experiment group (n = 25, SMI < 7 kg/m 2 ) and the control group (n = 26, SMI≥7 kg/m 2 ). GLP-1 levels were measured by ELISA. In vitro, 10 KK-A y mice (11- to 12-week-old) were assigned into two groups: liraglutide group (n = 5) and saline group (n = 5). Real-time PCR and Western blot were used to determine the expression levels of muscle specific ubiquitin protease E3, MuRF1, and MAFbx. RESULTS: T2DM patients with a higher SMI had significantly higher GLP-1 levels (t = 3.77, p < 0.001). SMI were positively associated with GLP-1 levels (ß = 0.435, p = 0.001) and inversely associated with age (ß = 0.299, p = 0.015). The incidence of low muscle mass at below the second quartiles was 10.55 times that of above the second quartiles (odds ratio = 10.556, p < 0.001). Liraglutide-treatment mice showed significant decrease in food intake, final body weight, fasting blood glucose, and significant increase in skeletal muscle mass, which coincided with the significant decrease in the expression levels of ubiquitin protease E3 MuRF1 and MAFbx. In vitro studies showed that liraglutide promoted myogenic differentiation and attenuated dexamethasone (DEX)-induced myotube atrophy. Ectopic expression of MuRF1 and MAFbx antagonized the beneficial effects of liraglutide on DEX-induced myotube atrophy. CONCLUSION: T2DM patients have muscular atrophy, and liraglutide alleviates muscular atrophy at least in part by inhibiting the expression of MuRF1 and MAFbx.

The dose-response relationship between sex hormones and hyperuricemia in different gender: NHANES 2013-2016.

Objectives: To access the dose-response relationship between sex hormones and hyperuricemia (HUA), and to find the cut-off value in different gender. Methods: 9,685 participants were derived from the database of National Health and Nutrition Examination Survey (NHANES). Restricted cubic spline (RCS) analysis were applied to explore the relationship between sex hormones and HUA after adjusting for confounding factors by propensity score match (PSM). Logistic regression was used to estimate the odds ratio (OR) and 95% CI. Results: The prevalence of HUA was 15.13% in female participants and 22.30% in male participants. Logistic regression analysis showed that estradiol (E2) was independently associated with HUA for a P value of 0.003 and 0.01in female and male participants, respectively. Testosterone (T) was only independently associated with HUA in male participants (P<0.001) but not in female participants (P = 0.59). RCS analysis showed a dose-response relationship between sex hormones and HUA. The risk of HUA increased as E2 lower than 29.6pg/mL in female participants and T lower than 389.1ng/dL in male participants. E2 higher than 23.6pg/ml was an independent risk factor for HUA in male participants. Conclusion: A dose-response relationship was found between sex hormones and HUA. The cut-off value of E2 in male and female participants was 29.6pg/mL and 23.6pg/mL, respectively, and the cut-off value of T in male participants was 389.1ng/dL. These results provide a reference for preventing HUA and hormone supplement therapy.

Irisin as a predictor of bone metabolism in Han Chinese Young Men with pre-diabetic individuals.

BACKGROUND: Irisin is a novel myokine both in mice and humans, and it can also be secreted by adipose tissue and the liver in a small amounts. There are few studies on irisin and bone metabolism. The aim of this study was to assess the relationship between serum irisin levels and bone metabolism and analyze its related factors in Han young male with pre-diabetic individuals. METHODS: This cross-sectional study included 41 pre-diabetes and 45 normal glucose tolerance (NGT). Anthropometric measurements, including height, weight, waist circumference (WC), and bone mineral content (BMC), were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 h of fasting, and the levels of glucose, insulin, lipids, serum irisin and bone turnover markers were measured. RESULTS: The levels of serum irisin (4.4 ± 1.4 vs. 6.3 ± 1.5 µg/mL), P1NP and OC were significantly lower and CTX was significantly higher in the pre-diabetes group (P < 0.05). BMC did not differ in the two groups (P > 0.05). Serum irisin levels negatively correlated with BMI (r =-0.325), FPG (r =-0.329), TG (r =-0.339) (P < 0.05) in NGT individuals. Serum irisin levels positively correlated with P1NP (r = 0.398), OC (r = 0.351), HDL-C (r = 0.432) and negatively correlated with FPG (r = -0.725), 2 h-PG (r = -0.360) (P < 0.05) in pre-diabetic individuals. Multiple regression analysis revealed that Serum irisin (ß = 9.768, P = 0.025) and WC (ß = -2.355, P = 0.002) were significant independent predictors for P1NP. CONCLUSION: Bone turnover markers were changed rather than bone mineral content in young men with pre-diabetes. In pre-diabetes individuals, serum irisin levels were reduced and close relationship with P1NP. Falling irisin levels may be a predictor of decreased bone formation in Han young men with pre-diabetes individuals.

The relationship between metabolic syndrome and bone mineral density in adolescents: analysis of the National Health and Nutrition Examination Survey.

OBJECTIVES: The purpose of this study was to observe the relationship between metabolic syndrome (MetS) and height (Ht) adjusted Z-scores for areal bone mineral density (aBMD) in adolescents. METHODS: A retrospective study was conducted on the United States adolescents aged 12-17 years. Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2011-2012, 2013-2014 and 2015-2016 cycles. Ht adjusted Z-scores for aBMD were calculated. RESULTS: A total of 969 adolescents (493 boys and 476 girls), aged 14.5 ± 1.7 years were enrolled in this study. After control for age, gender, race, 25-hydroxyvitamin D [25(OH)D], and lean body mass index (LBMI) Z-score, adolescents with MetS had significantly lower levels of total body (less head) aBMD Ht-Z-adjusted Z-score than adolescents with one, two components of MetS and without component of MetS (p<0.05) and significantly lower levels of lumbar spine aBMD Ht-Z-adjusted Z-score than adolescents with one component of MetS and without component of MetS (p<0.05). There were significantly negative associations between total body (less head) aBMD Ht-Z-adjusted Z-score and waist circumference (WC) (ß=-0.027, p<0.001, R2=0.057) and homeostasis model assessment insulin resistance (HOMA-IR) (ß=-0.225, p<0.001, R2=0.016). There were significantly negative associations between lumbar spine aBMD Ht-Z-adjusted Z-score and WC (ß=-0.039, p<0.001, R2=0.058) and HOMA-IR (ß=-0.251, p<0.001, R2=0.008). CONCLUSIONS: The present study demonstrates that MetS may have a negative effect on bone mineral density in adolescents. Abdominal obesity and insulin resistance play a major role on the decline of aBMD in adolescents.

Age, Pulse, Urea, and Albumin Score: A Tool for Predicting the Short-Term and Long-Term Outcomes of Community-Acquired Pneumonia Patients With Diabetes.

Objective: The predictive performances of CURB-65 and pneumonia severity index (PSI) were poor in patients with diabetes. This study aimed to develop a tool for predicting the short-term and long-term outcomes of CAP in patients with diabetes. Methods: A retrospective study was conducted on 531 CAP patients with type 2 diabetes. The short-term outcome was in-hospital mortality. The long-term outcome was 24-month all-cause death. The APUA score was calculated according to the levels of Age (0-2 points), Pulse (0-2 points), Urea (0-2 points), and Albumin (0-4 points). The area under curves (AUCs) were used to evaluate the abilities of the APUA score for predicting short-term outcomes. Cox regression models were used for modeling relationships between the APUA score and 24-month mortality. Results: The AUC of the APUA score for predicting in-hospital mortality was 0.807 in patients with type 2 diabetes (P<0.001). The AUC of the APUA score was higher than the AUCs of CURB-65 and PSI class (P<0.05). The long-term mortality increased with the risk stratification of the APUA score (low-risk group (0-1 points) 11.5%, intermediate risk group (2-4 points) 16.9%, high risk group (≥5 points) 28.8%, P<0.05). Compared with patients in the low-risk group, patients in the high-risk group had significantly increased risk of long-term death, HR (95%CI) was 2.093 (1.041~4.208, P=0.038). Conclusion: The APUA score is a simple and accurate tool for predicting short-term and long-term outcomes of CAP patients with diabetes.

Low Skeletal Muscle Area at the T12 Paravertebral Level as a Prognostic Marker for Community-Acquired Pneumonia.

RATIONALE AND OBJECTIVES: This study aimed to investigate whether the dorsal skeletal muscle area at 12th thoracic level (T12SMA) could be used as a predictor of in-hospital mortality and long-term survival among patients with community-acquired pneumonia (CAP). MATERIALS AND METHODS: A retrospective study was conducted on 1701 CAP patients who underwent chest computed tomography (CT) examinations at the First Hospital of Qinhuangdao. The primary outcome was in-hospital mortality. The T12SMA was analyzed. Multivariate regression logistic models were constructed to identify the prognostic markers of hospital mortality. Cox regression logistic models were constructed to identify the risk factors of long-term survival. RESULTS: The multiple logistic regression analysis showed that T12SMA [odds ratio (OR) = 0.946; p = 0.007], CURB-65 (OR = 1.521; p = 0.008), creatinine (OR = 1.003; p = 0.001), albumin (OR = 0.908; p = 0.001) and intensive care unit (ICU) (OR = 2.715; p = 0.007) were independent risk factors for predicting the in-hospital mortality. The cox regression logistic analysis showed that T12SMA (OR = 0.968; p = 0.000), age (OR= 1.036; p = 0.000), sex (OR= 1.435; p = 0.002), CURB-65 (OR = 1.311; p = 0.000), albumin (OR = 0.952; p = 0.000), creatinine (OR = 1.002; p = 0.000) and ICU (OR = 1.606; p = 0.001) were prognostic markers of long-term survival. CONCLUSION: T12SMA, CURB-65, creatinine, albumin and ICU were independent risk factors for in-hospital mortality among patients with CAP. And low T12SMA affected the in-hospital mortality and long-term survival of patients with CAP.

Influence of overweight and obesity on the mortality of hospitalized patients with community-acquired pneumonia.

BACKGROUND: Obesity is associated with a better prognosis in patients with community-acquired pneumonia (the so-called obesity survival paradox), but conflicting results have been found. AIM: To investigate the relationship between all-cause mortality and body mass index in patients with community-acquired pneumonia. METHODS: This retrospective study included patients with community-acquired pneumonia hospitalized in the First Hospital of Qinhuangdao from June 2013 to November 2018. The patients were grouped as underweight (< 18.5 kg/m2), normal weight (18.5-23.9 kg/m2), and overweight/obesity (≥ 24 kg/m2). The primary outcome was all-cause hospital mortality. RESULTS: Among 2327 patients, 297 (12.8%) were underweight, 1013 (43.5%) normal weight, and 1017 (43.7%) overweight/obesity. The all-cause hospital mortality was 4.6% (106/2327). Mortality was lowest in the overweight/obesity group and highest in the underweight group (2.8%, vs 5.0%, vs 9.1%, P < 0.001). All-cause mortality of overweight/obesity patients was lower than normal-weight patients [odds ratio (OR) = 0.535, 95% confidence interval (CI) = 0.334-0.855, P = 0.009], while the all-cause mortality of underweight patients was higher than that of normal-weight patients (OR = 1.886, 95%CI: 1.161-3.066, P = 0.010). Multivariable analysis showed that abnormal neutrophil counts (OR = 2.38, 95%CI: 1.55-3.65, P < 0.001), abnormal albumin levels (OR = 0.20, 95%CI: 0.06-0.72, P = 0.014), high-risk Confusion-Urea-Respiration-Blood pressure-65 score (OR = 2.89, 95%CI: 1.48-5.64, P = 0.002), and intensive care unit admission (OR = 3.11, 95%CI: 1.77-5.49, P < 0.001) were independently associated with mortality. CONCLUSION: All-cause mortality of normal-weight patients was higher than overweight/ obesity patients, lower than that of underweight patients. Neutrophil counts, albumin levels, Confusion-Urea-Respiration-Blood pressure-65 score, and intensive care unit admission were independently associated with mortality in patients with community-acquired pneumonia.

Total sugar intake is associated with higher prevalence of depressive symptoms in obese adults.

Background: The existing literature has repeatedly assessed the association between sugar-sweetened beverages and depressive symptoms, but studies of the association of total dietary sugar with depressive symptoms and of this association in obese adults are scarce. Thus, the purpose of this cross-sectional study was to assess the association between total sugar consumption and depressive symptoms in the study population and then in the population stratified by body mass index. Methods: This study was conducted in a nationally representative sample of 16,009 adults from the 2011-2018 National Health and Nutrition Examination Survey in the US. Total sugar intake was assessed by 24 h dietary recalls, and depressive symptoms were assessed by the nine-item Patient Health Questionnaire. Logistic regression models were used to evaluate the association between total sugar consumption and depressive symptoms. Results: Total sugar intake was positively associated with higher prevalence of depressive symptoms, and the adjusted odds ratio (95% confidence interval) of depressive symptoms for the highest vs. lowest quintile of total sugar intake was 1.56 (1.18, 2.05). In stratified analysis, we found a positive association between total sugar intake and depressive symptoms in adults with body mass index ≥30 kg/m2 (P for trend = 0.013), whereas no association was found in normal weight or overweight adults. Conclusions: A higher intake of total sugar was associated with increased odds of clinically relevant depressive symptoms among obese adults. Further studies are necessary to confirm the role of total sugar in depressive symptoms among obese adults.

The Relationship Between Prediabetes and Bone Mass in Adolescents: Analysis of the National Health and Nutrition Examination Survey From 2005 to 2010.

Objective: The purpose of this study was to observe the relationship between impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and bone mineral density (BMD) in different sites in adolescents. Methods: A retrospective study was conducted on adolescents age 12-19 years of the United States. Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2005-2006, 2007-2008, and 2009-2010 cycles. IFG was defined as fasting plasma glucose (FPG) levels that were ≥5.6 and <7.0 mmol/L. IGT was defined as 2-h plasma glucose levels that were ≥7.8 and <11.1 mmol/L after the oral glucose tolerance test (OGTT). Results: After controlling for age, gender, race, and body mass index (BMI) Z-score, adolescents in different categories of IGT had significantly different levels of areal BMD (aBMD) and bone mineral apparent density (BMAD) (IGT main effect: P < 0.05 for all, two-way ANOVA). There was no main effect between different categories of IFG with regard to aBMD and BMAD (P > 0.05). There was no interaction between IFG and IGT with regard to aBMD and BMAD (P > 0.05). In multiple regression analysis, the 2-h plasma glucose maintained an independent association with femoral neck aBMD (ß = -0.011, 95% CI: -0.017~-0.006, P < 0.001, R2 = 0.012), total femur aBMD (ß = -0.015, 95% CI: -0.021~-0.009, P < 0.001, R2 = 0.018), total spine aBMD (ß = -0.015, 95% CI: -0.020~-0.010, P < 0.001, R2 = 0.018), and total spine BMAD (ß = -0.002, 95% CI: -0.003~0.000, P = 0.006, R2 = 0.003). Conclusion: The present study demonstrates that BMD was decreased in adolescents with IGT. Two-hour plasma glucose, not FPG, negatively correlated with BMD. The effect of 2-h plasma glucose was consistent across the sites of bone.

MiR-192-5p suppresses M1 macrophage polarization via epiregulin (EREG) downregulation in gouty arthritis.

Gouty arthritis (GA) is a chronic inflammatory disease characterized by the deposition of monosodium urate (MSU) crystals within joints. MiR-192-5p is shown to be low-expressed in GA patients. However, the potential mechanism involving miR-192-5p in GA remains unclear. In the current study, a significant reduction in miR-192-5p and an increase in epiregulin (EREG) were observed in serum of GA patients, suggesting that miR-192-5p and EREG were involved in the pathogenic process of GA. A mouse GA model was established via 0.5 mg/20 µL MSU crystal administration. To investigate the effect of miR-192-5p on GA, mice were injected with miR-192-5p agomir or NC agomir before modeling. We found that miR-192-5p overexpression induced by miR-192-5p agomir reduced EREG expression, attenuated ankle joint swelling and synovial inflammatory cell infiltration and improved bone erosion in MSU-induced GA mice. MiR-192-5p decreased CD16/32+ (M1 marker) macrophages, but increased CD206 (M2 marker) expression in synovium of GA models. In vitro, RAW264.7 macrophages were stimulated with miR-192-5p mimic or NC mimic under IFNγ plus LPS-stimulated M1 polarization condition. MiR-192-5p reduced the release of inflammatory cytokines TNF-α and IL-1ß, decreased iNOS expression, and inhibited CD16/32 expression, indicating the blockade of M1 macrophage activation. Luciferase reporter system revealed the target interaction between miR-192-5p and EREG. Further rescue experiments demonstrated that EREG overexpression partly reversed the inhibitory role of miR-192-5p on M1 macrophage polarization manifested by elevated iNOS and CD16/32 levels. Collectively, miR-192-5p ameliorates inflammatory response in GA by inhibiting M1 macrophage activation via inhibiting EREG protein.

Measuring Synchronization between Spikes and Local Field Potential Based on the Kullback-Leibler Divergence.

Neurophysiological studies have shown that there is a close relationship between spikes and local field potential (LFP), which reflects crucial neural coding information. In this paper, we used a new method to evaluate the synchronization between spikes and LFP. All possible phases of LFP from -π to π were first binned into a freely chosen number of bins; then, the probability of spikes falling in each bin was calculated, and the deviation degree from the uniform distribution based on the Kullback-Leibler divergence was calculated to define the synchronization between spikes and LFP. The simulation results demonstrate that the method is rapid, basically unaffected by the total number of spikes, and can adequately resist the noise of spike trains. We applied this method to the experimental data of patients with intractable epilepsy, and we observed the synchronization between spikes and LFP in the formation of memory. These results show that our proposed method is a powerful tool that can quantitatively measure the synchronization between spikes and LFP.

Estimating Phase Amplitude Coupling between Neural Oscillations Based on Permutation and Entropy.

Cross-frequency phase-amplitude coupling (PAC) plays an important role in neuronal oscillations network, reflecting the interaction between the phase of low-frequency oscillation (LFO) and amplitude of the high-frequency oscillations (HFO). Thus, we applied four methods based on permutation analysis to measure PAC, including multiscale permutation mutual information (MPMI), permutation conditional mutual information (PCMI), symbolic joint entropy (SJE), and weighted-permutation mutual information (WPMI). To verify the ability of these four algorithms, a performance test including the effects of coupling strength, signal-to-noise ratios (SNRs), and data length was evaluated by using simulation data. It was shown that the performance of SJE was similar to that of other approaches when measuring PAC strength, but the computational efficiency of SJE was the highest among all these four methods. Moreover, SJE can also accurately identify the PAC frequency range under the interference of spike noise. All in all, the results demonstrate that SJE is better for evaluating PAC between neural oscillations.

Performance of Two Novel Obesity Indicators for the Management of Metabolic Syndrome in Young Adults.

Background: Metabolic syndrome (MetS) is a pathophysiological change based on the abnormal metabolism of many substances. The study aims to investigate the performance of visceral adiposity index (VAI) and lipid accumulation product (LAP) of MetS in young adults. Methods: 448 young adults aged between 19 and 24 years old in Qinhuangdao had been included in this cross-sectional study. Receiver operating characteristic (ROC) curve analyses were used to assess the accuracy of these two obesity indicators for MetS. Results: The prevalence of MetS was 2.0%. In male subjects, LAP had the highest area under the ROC curve (AUC) value (AUC = 0.963), followed by VAI (AUC = 0.937). In female subjects, LAP also had the highest AUC value (AUC = 0.931), followed by VAI (AUC = 0.861). No significant difference was found between the two obesity indicators (P > 0.05). Conclusion: The two obesity indicators were valuable for the screening of MetS in young adults, and LAP was the simpler of the two.