Differences of anticholinergic drug burden between older hospitalized patients with and without delirium: a systematic review and meta-analysis based on prospective cohort studies.

OBJECTIVES: This review aims to comprehensively summarize the differences in anticholinergic drug burden (ADB) scores between older hospitalized patients with and without delirium. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library and CINAHL EBSCOhost databases to identify prospective cohort studies exploring the relationship between ADB and the occurrence of delirium in older hospitalized patients. The primary outcome of the review was the mean ADB scores for the delirium and non-delirium groups, and the secondary outcome was the scores for the subsyndromal and non-delirium groups. The standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) were incorporated using a fixed-effect method. Moreover, we performed subgroup analysis according to the admission type, age, the ADB scale type and the ADB classification. RESULTS: Nine prospective cohort studies involving 3791 older patients with a median age of 75.1 (71.6-83.9) were included. The ADB score was significantly higher in the delirium group than in the non-delirium group (SMD = 0.21, 95%CI 0.13-0.28). In subgroup analysis, the age subgroup was split into < 75 and ≥ 75 according to the median age of the older people. There were significant differences in ADB scores between older people with delirium and those without delirium in various subgroups: surgical (SMD = 0.20, 95%CI 0.12-0.28), internal medicine (SMD = 0.64, 95%CI 0.25-1.02), age < 75 (SMD = 0.17, 95%CI 0.08-0.26), age ≥ 75 (SMD = 0.27, 95%CI 0.15-0.39), ADS scale (SMD = 0.13, 95%CI 0.13-0.40), ARS scale (SMD = 0.15, 95%CI 0.03-0.26), ACB scale (SMD = 0.13, 95%CI 0.01-0.25), pre-admission ADB (SMD = 0.24, 95%CI 0.05-0.43) and ADB during hospitalization (SMD = 0.20, 95%CI 0.12-0.27). CONCLUSIONS: We found a quantitative relationship between ADB and delirium in older patients admitted for internal medicine and surgery. And this relationship remained significant in different age, ADB scale type and ADB classification subgroups. However, the actual difference in ADB scores between patients with delirium and without delirium was small. More high-quality observational studies should be conducted to explore the impact of ADB on delirium and subsyndromal delirium. CLINICAL TRIAL REGISTRATION: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42022353649].

Higher dietary live microbe intake is associated with a lower risk of sarcopenia.

OBJECTIVE: This study aimed to investigate the potential association between dietary live microbe intake and sarcopenia. METHODS: Data from 5368 participants were gathered from the National Health and Nutrition Examination Survey (NHANES). Dietary information was assessed using a self-report questionnaire. The participants were categorized into low, medium, and high dietary live microbe groups. Sarcopenia was defined according to the National Institutes of Health (NIH) definition (appendicular skeletal muscle mass/body mass index <0.789 for men and <0.512 for women). Multivariate regression analysis and stratified analyses were performed. RESULTS: After adjusting for potential confounding factors, individuals in the high dietary live microbe group exhibited a lower prevalence of sarcopenia compared to those in the low dietary live microbe group. The adjusted odds ratio (with 95% confidence intervals) was 0.63 (0.44-0.89) (p for trend <0.05). Subgroup analyses indicated a potential difference in the impact of dietary live microbe intake on sarcopenia between individuals with and without diabetes (p for interaction = 0.094). CONCLUSION: Higher dietary live microbe intake was associated with a lower risk of sarcopenia.

Decreased TLR7 expression was associated with airway eosinophilic inflammation and lung function in asthma: evidence from machine learning approaches and experimental validation.

BACKGROUND: Asthma is a global public health concern. The underlying pathogenetic mechanisms of asthma were poorly understood. This study aims to explore potential biomarkers associated with asthma and analyze the pathological role of immune cell infiltration in the disease. METHODS: The gene expression profiles of induced sputum were obtained from Gene Expression Omnibus datasets (GSE76262 and GSE137268) and were combined for analysis. Toll-like receptor 7 (TLR7) was identified as the core gene by the intersection of two different machine learning algorithms, namely, least absolute shrinkage and selector operation (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), and the top 10 core networks based on Cytohubba. CIBERSORT algorithm was used to analyze the difference of immune cell infiltration between asthma and healthy control groups. Finally, the expression level of TLR7 was validated in induced sputum samples of patients with asthma. RESULTS: A total of 320 differential expression genes between the asthma and healthy control groups were screened, including 184 upregulated genes and 136 downregulated genes. TLR7 was identified as the core gene after combining the results of LASSO regression, SVM-RFE algorithm, and top 10 hub genes. Significant differences were observed in the distribution of 13 out of 22 infiltrating immune cells in asthma. TLR7 was found to be closely related to the level of several infiltrating immune cells. TLR7 mRNA levels were downregulated in asthmatic patients compared with healthy controls (p = 0.0049). The area under the curve of TLR7 for the diagnosis of asthma was 0.7674 (95% CI 0.631-0.904, p = 0.006). Moreover, TLR7 mRNA levels were negatively correlated with exhaled nitric oxide fraction (r = - 0.3268, p = 0.0347) and the percentage of peripheral blood eosinophils (%) (r = - 0.3472, p = 0.041), and positively correlated with forced expiratory volume in the first second (FEV1) (% predicted) (r = 0.3960, p = 0.0071) and FEV1/forced vital capacity (r = 0.3213, p = 0.0314) in asthmatic patients. CONCLUSIONS: Decreased TLR7 in the induced sputum of eosinophilic asthmatic patients was involved in immune cell infiltration and airway inflammation, which may serve as a new biomarker for the diagnosis of eosinophilic asthma.

Use of speckle tracking echocardiography in evaluating cardiac dysfunction in patients with acromegaly: an update.

In recent years, cardiovascular disease has garnered increasing attention as the second leading cause of death in individuals with acromegaly, following malignancy. Identifying cardiac dysfunction early in acromegaly patients for timely intervention has become a focal point of clinical research. Speckle tracking echocardiography, a well-established ultrasound technique, surpasses conventional Doppler ultrasound in its sensitivity to assess both local and global cardiac mechanics. It can accurately detect subclinical and clinical myocardial dysfunction, including myocardial ischemia, ventricular hypertrophy, and valvular changes. Over the past five years, the use of speckle tracking echocardiography in acromegaly patients has emerged as a novel approach. Throughout the cardiac cycle, speckle tracking echocardiography offers a sensitive evaluation of the global and regional myocardial condition by quantifying the motion of myocardial fibres in distinct segments. It achieves this independently of variations in ultrasound angle and distance, effectively simulating the deformation of individual ventricles across different spatial planes. This approach provides a more accurate description of changes in cardiac strain parameters. Importantly, even in the subclinical stage when ejection fraction remains normal, the strain parameters assessed by speckle tracking echocardiography hold a good predictive value for the risk of cardiovascular death and hospitalization in acromegaly patients with concomitant cardiovascular disease. This information aids in determining the optimal timing for interventional therapy, offering important insights for cardiac risk stratification and prognosis. In the present study, we comprehensively reviewed the research progress of speckle tracking echocardiography in evaluating of cardiac dysfunction in acromegaly patients, to pave the way for early diagnosis of acromegaly cardiomyopathy.

Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet-induced obesity mice through a dual inhibition of the GIP-GIPR signaling axis.

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone secreted by K cells in the small intestine and is considered an obesity-promoting factor. In this study, we systematically investigated the anti-obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) and the underlying mechanism for the first time. Our results showed that intragastric SY/HSYA, rather than an intraperitoneal injection, notably decreased serum GIP levels and GIP staining in the small intestine in diet-induced obese (DIO) mice. Moreover, intragastric SY/HSYA was also first found to significantly suppress GIP receptor (GIPR) signaling in both the hypothalamus and subcutaneous White adipose tissue. Our study is the first to show that intragastric SY/HSYA obviously reduced food intake and body weight gain in leptin sensitivity experiments and decreased serum leptin levels in DIO mice. Further experiments demonstrated that SY treatment also significantly reduced leptin levels, whereas the inhibitory effect of SY on leptin levels was reversed by activating GIPR in 3 T3-L1 adipocytes. In addition, intragastric SY/HSYA had already significantly reduced serum GIP levels and GIPR expression before the serum leptin levels were notably changed in high-fat-diet-fed mice. These findings suggested that intragastric SY/HSYA may alleviate diet-induced obesity in mice by ameliorating hyperleptinemia via dual inhibition of the GIP-GIPR axis.

A novel anti-obesity mechanism for liraglutide by improving adipose tissue leptin resistance in high-fat diet-fed obese mice.

Liraglutide has been approved for the treatment of obesity in the past few years. Both oxidative stress and leptin resistance are the critical drivers of obesity. The present study investigated the mechanism of liraglutide protection against obesity by ameliorating leptin resistance and oxidative stress. Male C57BL/6J mice were fed a high-fat diet (HFD) and subcutaneously injected with 200 µg/kg/d liraglutide for 20 weeks. Body weight, fat mass, serum levels of leptin, insulin, and superoxide dismutase (SOD) activities were measured. In addition, glucose and insulin tolerance tests were performed. The expressions of leptin, its signaling genes, and antioxidant enzymes were detected using RT-qPCR and western blot methods in liver and white adipose tissue (WAT) of mice. The results depicted that liraglutide treatment significantly slowed weight gain of body, reduced the fat mass, ameliorated glucose and lipid metabolism, and hepatic steatosis in HFD-fed obese mice. Further study demonstrated that liraglutide treatment resulted in decreased serum levels and the transcript levels of leptin as well as leptin signaling inhibitory regulators. However, it increased leptin receptor expression and the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in WAT (p < 0.05). In addition, the antioxidant enzyme expression was elevated in both liver and WAT of liraglutide-treated mice (p < 0.05). In conclusion, liraglutide conspicuously prevented obesity and ameliorated glucose and lipid metabolism in obese mice through a novel mechanism that improves peripheral leptin resistance in WAT and enhance the antioxidant enzyme expression in both liver and WAT.

Osteonecrosis of the jaw induced by bisphosphonates therapy in bone metastases patient: Case report and literature review.

Medication-related osteonecrosis of the jaw (MRONJ) is an increasingly common bone-related adverse event in recent years. We reported 3 bone metastases of patients who developed MRONJ after receiving bisphosphonates therapy. All patients underwent surgical necrotic bone resection combined with leukocyte and platelet-rich fibrin concentrate (L-PRF) therapy. After 6 months of follow-up, no recurrence and adverse event has been observed. This report shows that treatment with necrotic bone resection and L-PRF is an effective therapy and should be considered as an alternative treatment for the management of advanced cases of MRONJ.

Integrative analyses of hub genes and their association with immune infiltration in adipose tissue, liver tissue and skeletal muscle of obese patients after bariatric surgery.

Bariatric surgery (BS) is an effective treatment for obesity. Adipose tissue, liver tissue and skeletal muscle are important metabolic tissues. This study investigated hub genes and their association with immune infiltration in these metabolic tissues of obese patients after BS by bioinformatic analysis with Gene Expression Omnibus datasets. Differentially expressed genes (DEGs) were identified, and a protein-protein interaction network was constructed to identify hub genes. As a result, 121 common DEGs were identified and mainly enriched in cytokine-cytokine receptor interactions, chemokine signaling pathway, neutrophil activation and immune responses. Immune cell infiltration analysis showed that the abundance of M1 macrophages was significantly lower in adipose and liver tissue after BS (p<0.05). Ten hub genes (TYROBP, TLR8, FGR, NCF2, HCK, CCL2, LAPTM5, MNDA and S100A9) that were all downregulated after BS were also associated with immune cells. Consistently, results in the validated dataset showed that the expression levels of these hub genes were increased in obese patients and mice, and decreased after BS. In conclusion, this study analysed the potential immune and inflammatory mechanisms of BS in three key metabolic tissues of obese patients, and revealed hub genes associated with immune cell infiltration, thus providing potential targets for obesity treatment.

Intragastric safflower yellow and its main component HSYA improve leptin sensitivity before body weight change in diet-induced obese mice.

Our previous studies found that safflower yellow (SY) and its main component hydroxysafflor yellow A (HSYA) could alleviate obesity and improve leptin resistance in high-fat diet (HFD) induced obese mice. Therefore, our present study aimed to investigate whether the above effect of SY/HSYA was a direct effect or follow-up effect of weight loss and whether leptin was essential for the anti-obesity effect of SY/HSYA or not. HFD-induced obese mice were treated with SY or HSYA for 4 weeks, while ob/ob mice were treated with SY for 10 weeks. Body weight, food intake, fat mass, and serum leptin levels were measured. The leptin sensitivity experiment was conducted in HFD-induced obese mice. The expressions of leptin and its signaling-related genes were detected by RT-qPCR and Western blot methods. SY/HSYA treatment had no effect on food intake, energy expenditure, body weight, fat mass, and serum leptin levels in HFD-induced obese mice. However, the leptin sensitivity experiment showed that the food intake decreased by 18.4% in the HFD-SY group and the body weight gain decreased by 104.6% in the HFD-HSYA group, respectively (both P < 0.05). Furthermore, the expressions of leptin and leptin signaling inhibitory regulators were significantly decreased, while the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) were notably increased in WAT of HFD-induced obese mice, fully differentiated 3T3-L1 adipocytes after SY/HSYA intervention (all P < 0.05). Interestingly, SY treatment was ineffective on body weight, fat mass, and glucose metabolism in leptin-deficient ob/ob mice. SY/HSYA administration could firstly improve peripheral leptin resistance in adipose tissue of HFD-induced obese mice before their body weight was significantly changed, and leptin was essential for the anti-obesity effect of SY.

The characterization of metabolites alterations in white adipose tissue of diabetic GK Rats after ileal transposition surgery by an untargeted metabolomics approach.

Dysfunction of adipose tissue could lead to insulin resistance, obesity and type 2 diabetes. Thus, our present study aimed to investigate metabolites alterations in white adipose tissue (WAT) of diabetic GK rats after IT surgery. Ten-week-old male diabetic GK rats were randomly subjected to IT and Sham-IT surgery. Six weeks later, the untargeted metabolomics in WAT of diabetic GK rats was performed. Differential metabolites were selected according to the coefficient of variation (CV) of quality control (QC) sample <30%, variable importance in the projection (VIP) >1 and P < 0.05. Then, the hierarchical clustering of differential metabolites was conducted and the KEGG database was used for metabolic pathway analysis. A total of 50 (in positive ion mode) and 68 (in negative ion mode) metabolites were identified as differential metabolites in WAT of diabetic GK rats between IT group and Sham-IT group, respectively. These differential metabolites were well clustered, which in descending order of the number of involved differential metabolites is ubiquinone and other terpenoid-quinone biosynthesis, AMPK signalling pathway, pantothenate and CoA biosynthesis, ferroptosis, vitamin digestion and absorption, glycerophospholipid metabolism, phenylalanine metabolism, steroid hormone biosynthesis, neuroactive ligand-receptor interaction, porphyrin and chlorophyll metabolism and bile secretion, and correlated with the parameters of body weight, food intake, WAT mass and glucose metabolism, which were significantly improved after IT surgery. The differential metabolites in WAT of diabetic GK rats were mainly related to the pathway of energy metabolism, and correlated with the improved phenotypes of diabetic GK rats after IT surgery.

Nuciferine Inhibited the Differentiation and Lipid Accumulation of 3T3-L1 Preadipocytes by Regulating the Expression of Lipogenic Genes and Adipokines.

Purposes: Nuciferine, a main aporphine alkaloid component found in lotus leaf (Nelumbo nucifera), has been demonstrated to possess the property of reducing fat mass and alleviating dyslipidemia in vivo. The purpose of this study is to explore the effects of nuciferine on the proliferation and differentiation of 3T3-L1 cells and further investigate the possible underlying molecular mechanisms. Methods: 3T3-L1 preadipocytes were treated with 0∼20 µM nuciferine for 24∼120 h, the cell viability was assessed using CCK8. 3T3-L1 preadipocytes and human primary preadipocytes were then induced differentiation and the effects of nuciferine on the lipid metabolism in differentiating and fully differentiated adipocytes were observed by the methods of intracellular triglyceride (TG) assay, Oil Red O staining, RT-qPCR and western blot. Transient transfection and dual luciferase reporter gene methods were used to assess the effects of nuciferine on FAS promoter activities. Results: Nuciferine inhibited the proliferation of 3T3-L1 preadipocytes in a dose- and time-dependent manner. 20 µM nuciferine significantly attenuated lipid accumulation and reduced intracellular TG contents by 47.2, 59.9 and 55.4% on the third, sixth and ninth day of preadipocytes differentiation, respectively (all p < 0.05). Moreover, the mRNA levels of PPARγ, C/EBPα, C/EBPß, FAS, ACC, HSL and ATGL were notably decreased by 39.2∼92.5% in differentiating preadipocytes when treated with 5∼20 µM nuciferine (all p < 0.05). In fully differentiated adipocytes treated with 20 µM nuciferine for 48 h, the mRNA levels of FAS, ACC and SREBP1 were remarkably downregulated by 22.6∼45.2% compared with the controls (0 µM) (all p < 0.05), whereas the expression of adipokines FGF21 and ZAG were notably promoted by nuciferine. Similarly, in fully differentiated human primary adipocytes, the mRNA levels of FAS, ACC, SREBP1 were decreased and the expression of FGF21 and ZAG were elevated after treated with nuciferine (all p < 0.05). Further mechanism studies showed that 2.5∼20 µM nuciferine significantly decreased FAS promoter activities in 3T3-L1 preadipocytes. Conclusion: Nuciferine inhibited the proliferation and differentiation of 3T3-L1 preadipocytes. The inhibitory effects of nuciferine on adipogenesis might be due to the downregulation of PPARγ, C/EBPα and C/EBPß, which led to the reduction of intracellular lipid accumulation in 3T3-L1 cells and by downregulating the expression of critical lipogenic enzymes, especially of FAS, which was achieved by inhibiting the FAS promoter activities. Besides, nuciferine promoted the expression of adipokines in fully differentiated adipocytes.

Serum ZAG and Adiponectin Levels Were Closely Related to Obesity and the Metabolically Abnormal Phenotype in Chinese Population.

INTRODUCTION: To explore serum zinc-α2-glycoprotein (ZAG) and adiponectin in metabolically healthy non-obese (MHNO), metabolically healthy obesity (MHO), metabolically abnormal obesity (MAO) and metabolically abnormal diabetic obese (MADO) subjects and the relationship with metabolically phenotypes of obesity. METHODS: Two hundred twenty-five subjects including 32 with MHNO, 40 with MHO, 104 with MAO and 49 with MADO were enrolled. Baseline clinical data and biochemical variables were collected. Serum ZAG and adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Metabolically healthy (<3 metabolic abnormalities) or abnormal (≥3 metabolic abnormalities) subjects were classified based on the National Cholesterol Education Program-Adult Treatment Panel III (NCEP/ATP III) criteria. Obesity (body mass index ≥28 kg/m2) was recommended by China Obesity Task Force. RESULTS: Serum ZAG levels were higher in the MHO group, but were progressively lower in MAO and MADO groups (P all<0.05). In all subjects, total cholesterol, 2-hour postprandial blood glucose and homeostasis model assessment of adiponectin were independent variables to serum ZAG levels. Compared with subjects in the highest tertile of ZAG, the odds ratio (OR) of metabolically abnormal risks of subjects in the lowest and median tertiles of ZAG were higher both in a univariate and three adjustment models (P all<0.05). Serum ZAG could discriminate the metabolically abnormal phenotype with receiver operating characteristic (ROC) curve area of 0.622 (95% CI, 0.539-0.706, P<0.05). Combination of ZAG and adiponectin had improved diagnosis value accuracy, with ROC curve area of 0.703 (95% CI, 0.629-0.776, P<0.05), and 62.7% sensitivity and 73.6% specificity. CONCLUSION: Serum ZAG levels were higher in MHO subjects, but lower in MAO and MADO subjects. The decreased serum ZAG levels were closely related to the metabolically abnormal phenotype of obese patients. Serum ZAG, especially the combination with adiponectin might be the potential diagnostic biomarkers for metabolically abnormal obese patients.

Safflower yellow improves insulin sensitivity in high-fat diet-induced obese mice by promoting peroxisome proliferator-activated receptor-γ2 expression in subcutaneous adipose tissue.

AIMS/INTRODUCTION: Safflower yellow (SY) and its main component, hydroxysafflor yellow A, have been demonstrated to show anti-obesity effects. Peroxisome proliferator-activated receptor-γ2 (PPARγ2) is a critical transcription factor in adipose tissue metabolism. The aim of the present study was to explore the effects of SY in high-fat diet-induced obese mice, and further investigate the mechanism involving PPARγ2. METHODS: High-fat diet-induced obese mice were given 120 mg/kg/day SY for 8 weeks. Glucose and insulin tolerance tests were carried out. Fat mass and serum levels of glucose and insulin were measured. The expression of insulin signaling pathway-related genes and PPARγ2 in the adipose tissue was measured. In vitro, the effects of SY (0-500 mg/L) and hydroxysafflor yellow A (0-100 mg/L) on PPARγ2 promoter activities and PPARγ2 messenger ribonucleic acid (mRNA) levels in 3T3-L1 preadipocytes or adipocytes were also detected. RESULTS: Safflower yellow reduced fat mass, decreased glucose levels and improved insulin sensitivity in obese mice. SY also increased the mRNA levels of insulin signaling pathway-related genes, and increased PPARγ2 mRNA levels by 39.1% in subcutaneous adipose tissue (P < 0.05). In vitro, SY and hydroxysafflor yellow A significantly enhanced PPARγ2 promoter activities by 1.3-2.1-fold, and increased PPARγ2 mRNA levels by 1.2-1.6-fold in 3T3-L1 preadipocytes or adipocytes (P < 0.05). CONCLUSIONS: SY could reduce fat mass, decrease glucose levels and improve insulin sensitivity in high-fat diet-induced obese mice. The probable mechanism is to increase PPARγ2 expression by stimulating PPARγ2 promoter activities, further increasing the expression of insulin signaling pathway-related genes in subcutaneous adipose tissue.

Safflower Yellow and Its Main Component HSYA Alleviate Diet-Induced Obesity in Mice: Possible Involvement of the Increased Antioxidant Enzymes in Liver and Adipose Tissue.

PURPOSE: Oxidative stress plays an important role in the pathogenesis of obesity and its associated disorders. Safflower yellow (SY) and hydroxysafflor yellow A (HSYA), the natural compounds isolated from Carthamus tinctorius L., has been found to possess antioxidative and anti-obesity properties. The purpose of the present study is to investigate whether SY and its main component HSYA alleviate obesity by the antioxidant effects. METHODS: Diet-induced obese (DIO) mice were treated with 200 mg/kg/d SY or HSYA for 10 weeks. Body weight, fat mass, serum biochemical parameters and superoxide dismutase (SOD) activities were measured. Glucose and insulin tolerance tests were performed. The expression of antioxidant enzymes in liver and adipose tissue were measured. In vitro, H2O2-induced oxidative stress HepG2 cells and 3T3-L1 adipocytes were treated with SY and HSYA to investigate the direct effects of SY and HSYA on the expression of antioxidant enzymes. RESULTS: SY and HSYA significantly decreased the body weight gain of DIO mice, and decreased fat mass to 57.8% and 61.6% of the control mice, respectively (P < 0.05). The parameters of glucose metabolism and liver function were improved after SY and HSYA treatment. The hepatic SOD activities and the mRNA levels of antioxidant enzymes in liver and adipose tissue of SY and HSYA treated mice were increased (P < 0.05). Meanwhile, the administration of SY and HSYA on the H2O2-induced oxidative stress HepG2 cells and adipocytes also increased the expression of the antioxidant factor and antioxidant enzymes to 1.2~3.3 folds of the control cells (P < 0.05). CONCLUSION: SY and its main component HSYA could significantly decrease the fat mass, and improve glucose metabolism and liver function in diet-induced obese mice. The beneficial effects of SY and HSYA on obesity and metabolism may be associated with the increased expression of antioxidant enzymes in liver and adipose tissue.

Low Serum ZAG Levels Correlate With Determinants of the Metabolic Syndrome in Chinese Subjects.

Introduction: Zinc-α2-glycoprotein (ZAG) is a novel adipokine, which is involved in metabolic syndrome (MetS). This study aimed to investigate the relationship between serum ZAG and MetS in Chinese adults, who diagnosed according to the 2005 International Diabetes Federation (IDF) criteria. Methods: A group of 151 MetS patients, 84 patients with central obesity and 70 healthy controls were enrolled. General clinical information, serum samples were obtained from all subjects and serum ZAG levels were determined via the commercial ELISA kits. Results: Serum ZAG levels were the highest in the control group, then gradually decreased with the severity of the metabolic abnormalities increased (8.78 ± 1.66 µg/mL for control vs. 8.37 ± 1.52 µg/mL for central obesity vs. 7.98 ± 0.94 µg/mL for MetS, P < 0.05). It was also decreased progressively with an increasing number of the MetS components (P for trend = 0.002). Additionally, serum ZAG/fat mass ratio was calculated and the similar changes were observed in the three groups (0.85 ± 0.53 µg/mL/kg for control vs. 0.39 ± 0.10 µg/mL/kg for central obesity vs. 0.36 ± 0.08 µg/mL/kg for MetS, P < 0.05). In the multiple regression analysis, group was a strong independent factor contributing to serum ZAG levels (P < 0.001). Furthermore, compared with subjects with the highest tertile of ZAG, subjects in the lowest tertile of ZAG had 1.946-fold higher risk of MetS (95% CI 1.419-6.117, P = 0.004). This phenomenon still existed after controlling for age, gender (Model 1), ALP, AST, Cr, UA, Urea based on Model 1 (Model 2), grip strength, smoking, drinking, birth place, current address, education level, manual labor, and exercise frequency based on Model 2 (Model 3). Receiver operation characteristic (ROC) curve analysis revealed that serum ZAG might serve as a candidate biomarker for MetS (sensitivity 57.6%, specificity 70.0% and area under the curve 0.655), and serum ZAG/fat mass ratio showed improved diagnosis value accuracy, with ROC curve area of 0.951 (95% CI, 0.920-0.983, P < 0.001), and 90.7% sensitivity and 88.6% specificity. Conclusions: Serum ZAG levels were lowered in patients with MetS and central obesity. The decreased serum ZAG levels were associated with the increased risks of MetS. Serum ZAG, especially serum ZAG/fat mass ratio might be the candidate diagnostic biomarkers for MetS.

Effects of 24 Weeks of Growth Hormone Treatment on Bone Microstructure and Volumetric Bone Density in Patients with Childhood-Onset Adult GH Deficiency.

OBJECTIVE: Adults with childhood-onset growth hormone deficiency (CO AGHD) have prominently impaired volumetric bone density (vBMD) and bone microarchitecture. Effects of recombinant human growth hormone (rhGH) on bone microarchitecture in CO AGHD were insufficiently evaluated. The objective of this study is to assess the effects of rhGH on bone microarchitecture and vBMD in CO AGHD patients. DESIGN: In this single-center prospective study, nine CO AGHD patients received rhGH treatment for 24 weeks. High-resolution peripheral quantitative computerized tomography (HR-pQCT) of distal tibia and radius was performed at baseline and at the end of treatment. Main outcomes were vBMD and morphometric parameters from HR-pQCT. RESULTS: After 24-week treatment, IGF-1 SDS gradually increased from -3.31 ± 1.56 to -1.92 ± 1.65 (p=0.113). Serum phosphate (1.17 ± 0.17 vs. 1.35 ± 0.18 mmol/L, p=0.030), alkaline phosphatase (83.6 ± 38.6 vs. 120.5 ± 63.7, p=0.045), and ß-CTX (0.67 ± 0.32 vs. 1.09 ± 0.58, p=0.022) were significantly elevated. In distal tibia, total vBMD (200.2 ± 41.7 vs 210.3 ± 40.9 mg HA/cm3, p=0.017), cortical area (89.9 ± 17.7 vs 95.5 ± 19.9 mm2, p=0.032), and cortical thickness (0.891 ± 0.197 vs 0.944 ± 0.239 mm, p=0.028) were significantly improved. Trabecular area decreased from 795.3 ± 280.9 to 789.6 ± 211.4 mm2 (p=0.029). Trabecular bone volume fraction increased from 0.193 ± 0.038 to 0.198 ± 0.036 (p=0.027). In radius, cortical perimeter (74.1 ± 10.0 vs 75.0 ± 10.9 mm, p=0.034), trabecular thickness (0.208 ± 0.013 vs 0.212 ± 0.013 mm, p=0.008), trabecular separation (0.743 ± 0.175 vs 0.796 ± 0.199 mm, p=0.019), and inhomogeneity of network (Tb.1/N.SD) (0.292 ± 0.087 vs 0.317 ± 0.096 mm, p=0.026) were significantly improved, while trabecular number (1.363 ± 0.294 vs 1.291 ± 0.325 1/mm, p=0.025) decreased significantly. CONCLUSIONS: Our results provide evidence for improvement of vBMD and bone microarchitecture in AGHD patients at a relatively early stage of rhGH treatment.

Serum Zinc-α2-Glycoprotein Levels in Patients with or without Coronary Artery Disease in Chinese North Population.

Coronary artery disease (CAD), the leading cause of morbidity and mortality, has imposed huge health and economic burdens globally. Zinc-α2-glycoprotein (ZAG) is a novel adipokine. Increasing evidence suggests the close relationship between serum ZAG levels and various cardiometabolic risk factors. However, the relationship between serum ZAG levels and CAD is still not fully clarified. We conducted this study to evaluate serum ZAG levels and its association with cardiovascular risk factors. A total of 129 patients with CAD, 99 patients with noncoronary artery disease (NCAD), and 121 controls were recruited in this retrospective study. CAD (coronary artery stenosis ≥50%) or NCAD (coronary artery stenosis <50%) patients who underwent coronary angiography were diagnosed according to the American Heart Association criteria. Serum ZAG levels were determined via commercial enzyme-linked immunosorbent assay (ELISA) kits. The results showed that serum ZAG levels in CAD and NCAD groups were significantly decreased when compared with those in the control group. Multiple stepwise regression analysis revealed that the grouping variable (control, NCAD, and CAD) was an independent determinant of serum ZAG levels (ß = -0.328, P < 0.001) after controlling other confounding factors. Further multivariate ordinary logistic regression analysis demonstrated that the risk of grouping at one level higher in subjects with the lowest tertile of ZAG levels was 2.28-fold higher than those with the highest tertile levels (OR = 3.281, 95% CI 1.782-6.038, P < 0.001). The receiver-operating characteristic (ROC) curve analysis showed that serum ZAG could distinguish CAD patients (AUC = 0.706, 95% CI, 0.643-0.770, P < 0.05), NCAD patients (AUC = 0.673, 95% CI, 0.602-0.743, P < 0.05), and NCAD and CAD patients (AUC = 0.692, 95% CI, 0.633-0.750, P < 0.05) from controls. In conclusion, serum ZAG levels were significantly decreased in NCAD/CAD patients. The decreased serum ZAG levels were independently associated with the presence of NCAD/CAD. ZAG might serve as a candidate diagnostic biomarker for NCAD/CAD.

Identification of U-shaped curve relation between proneurotensin and risk of coronary artery disease (CAD) in patients with premature CAD.

BACKGROUND AND AIMS: Neurotensin (NT) is a gut hormone with broad effects on the cardiovascular system. Recent data suggested that circulating proneurotensin (pro-NT)-the stable precursor fragment of NT-could independently predict cardiovascular artery disease (CAD) development. However, serum pro-NT levels in patients with premature cardiovascular artery disease (PCAD) are still unknown. This study aims to determine serum pro-NT levels in patients with PCAD and investigate its relationship with PCAD risk. METHODS AND RESULTS: A total of 490 subjects, including 364 with PCAD and 126 without PCAD (NPCAD), and 182 controls were enrolled in the study. Data of baseline clinical parameters and biochemical variables were collected. Serum pro-NT levels were measured by ELISA. Serum pro-NT levels were higher in patients with PCAD than in controls (59.42 ± 66.66 vs. 38.07 ± 48.48 pg/mL, P < 0.05), especially in patients with BMI<25 kg/m2. Serum pro-NT levels were independently related to PCAD (ß = 0.349, P < 0.001), and the association revealed a U-shaped curve characteristic between pro-NT tertiles and CAD risk in patients with premature CAD and controls. Subjects with low and high tertiles of pro-NT levels had 1.79-fold and 2.23-fold higher risks of PCAD, respectively, than subjects with median pro-NT levels (P < 0.05). After adjusting for age, gender, and BMI in Model 1 and other confounders in Model 2 and Model 3, the U-shaped relationship remained significant. CONCLUSION: Serum pro-NT levels were significantly increased in patients with PCAD. The association between pro-NT levels and PCAD risk presents a U-shaped curve characteristic, which demonstrated that subjects with lower and higher pro-NT levels both were more likely to have PCAD.

OGDH promotes the progression of gastric cancer by regulating mitochondrial bioenergetics and Wnt/ß-catenin signal pathway.

BACKGROUND/AIMS: 2-oxoglutarate dehydrogenase (OGDH) is the first rate-limiting E1 subunit of OGDH complex (OGDHC), which plays as a regulatory point in the cross-road of TCA cycle and glutamine metabolism. Until now, the role of OGDH in carcinogenesis has been unclear. METHODS: In the present study, we determined the expression of OGDH in human gastric cancer (GC) tissues and cell lines by RT-qPCR, Western blotting and immunohistochemical staining respectively. The biological impacts of OGDH on cell growth and migration were explored through modulation OGDH expression in GC cells. Furthermore, mitochondrial functions and Wnt/ß-catenin signal were analyzed to elucidate the mechanism by which OGDH was involved in GC progression. RESULTS: The results showed that the levels of OGDH mRNA and protein were significantly higher in GC tissues, which was positively correlated with clinicalpathological parameters of GC patients. OGDH inhibitor SP significantly suppressed GC cell viability. Modulation of OGDH had distinct effects on cell proliferation, cell cycle and cell migration in the GC cell lines AGS and BGC823. Overexpression of OGDH resulted in the downregulation of the EMT molecular markers E-cadherin and ZO-1, the upregulation of N-cadherin and claudin-1. OGDH deficiency had the opposite outcomes in GC cells. Meantime, OGDH knockdown cells showed decreased mitochondrial membrane potential, oxygen consumption rate, intracellular ATP product, and increased ROS level and NADP+/NADPH ratio. Consistently, overexpression of OGDH enhanced the mitochondrial function in GC cells. Furthermore, OGDH knockdown reduced the expressions of ß-catenin, slug and TCF8/ZEB1, and the downstream targets cyclin D1 and MMP9 in GC cells. OGDH overexpression facilitated the activation of Wnt/ß-catenin signal pathway. Additionally, overexpression of OGDH promoted tumorigenesis of GC cells in nude mice. CONCLUSION: Taken together, these results indicate that OGDH serves as a positive regulator of GC progression through enhancement of mitochondrial function and activation of Wnt/ß-catenin signaling.

Autosomal dominant familial neurohypophyseal diabetes insipidus caused by a novel nonsense mutation in AVP-NPII gene.

Familial neurohypophyseal diabetes insipidus (FNDI) is a rare single-gene disorder caused by mutations of the arginine vasopressin-neurophysin II (AVP-NPII) gene. These changes impair the release of vasopressin from the posterior pituitary gland. In the present study, the AVP-NPII gene of a Chinese adult patient with central diabetes insipidus, the patient's symptomatic mother and an asymptomatic sister of the patient was sequenced. Examination of the family history revealed cases of FNDI across four generations. Gene sequencing analysis revealed a novel heterozygous mutation, c.268A>T (p.Lys90Ter), in exon 2 of the AVP-NPII gene, in the patient and the patient's mother, which led to the loss of 6 cysteine residues and aberrant disulfide bonds, which is predicted to alter the mature protein structure. The present study identified a novel heterozygous nonsense mutation of the AVP-NPII gene associated with FNDI, which broadens the spectrum of known mutations associated with this disorder and contributes to the understanding of its molecular basis.