A late eating midpoint is associated with increased risk of diabetic kidney disease: a cross-sectional study based on NHANES 2013-2020.

BACKGROUND: Modifying diet is crucial for diabetes and complication management. Numerous studies have shown that adjusting eating habits to align with the circadian rhythm may positively affect metabolic health. However, eating midpoint, eating duration, and their associations with diabetic kidney disease (DKD) are poorly understood. METHODS: The National Health and Nutrition Examination Survey (2013-2020) was examined for information on diabetes and dietary habits. From the beginning and ending times of each meal, we calculated the eating midpoint and eating duration. Urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g and/or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 were the specific diagnostic criteria for DKD. RESULTS: In total, details of 2194 subjects with diabetes were collected for analysis. The overall population were divided into four subgroups based on the eating midpoint quartiles. The prevalence of DKD varied noticeably (P = 0.037) across the four categories. When comparing subjects in the second and fourth quartiles of eating midpoint to those in the first one, the odds ratios (ORs) of DKD were 1.31 (95% CI, 1.03 to 1.67) and 1.33 (95% CI, 1.05 to 1.70), respectively. And after controlling for potential confounders, the corresponding ORs of DKD in the second and fourth quartiles were 1.42 (95% CI, 1.07 to 1.90) and 1.39 (95% CI, 1.04 to 1.85), respectively. CONCLUSIONS: A strong correlation was found between an earlier eating midpoint and a reduced incidence of DKD. Eating early in the day may potentially improve renal outcomes in patients with diabetes.

Association between the platelet/high-density lipoprotein cholesterol ratio and nonalcoholic fatty liver disease: results from NHANES 2017-2020.

The platelet/high-density lipoprotein cholesterol ratio (PHR) is a novel inflammatory and hypercoagulability marker that represents the severity of metabolic syndrome. Liver metabolic syndrome is manifested by nonalcoholic fatty liver disease (NAFLD), which is associated with inflammation and hypercoagulability. This cross-sectional investigation aimed to identify the relationship between PHR and NAFLD. Participants in the National Health and Nutrition Examination Survey (NHANES) 2017-2020 were evaluated for hepatic steatosis and fibrosis using vibration-controlled transient elastography. The PHR was calculated as the ratio of platelets to high-density lipoprotein cholesterol. Increased PHR was associated with an increased incidence of NAFLD and hepatic fibrosis. Compared with patients in the first PHR quartile, after adjustment for clinical variables, the corresponding odds ratio (OR) for NAFLD in the fourth quartile was 2.36 (95% CI, 1.76 to 3.18) (p < 0.05); however, the OR for hepatic fibrosis was not statistically significant (p > 0.05). Furthermore, restricted cubic spline analyses showed an S-shaped association between PHR and NAFLD and an L-shaped relationship between PHR and hepatic fibrosis. The results support the effectiveness of PHR as a marker for NAFLD and hepatic fibrosis. Therefore, interventions to improve the PHR may be of benefit in reducing the incidence of both hepatic steatosis and fibrosis.

Serum stromal cell-derived factor-1 levels are associated with diabetic kidney disease in type 2 diabetic patients.

The present study was designed to explore whether serum stromal cell-derived factor-1 (SDF-1) levels were associated with diabetic kidney disease (DKD). Serum SDF-1 levels were measured by sandwich ELISA. Patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g for 3 months were identified as having DKD. Among the recruited type 2 diabetic patients, 18.71% (n = 32) were found to have DKD, and the serum SDF-1 levels of these patients were higher than those of patients without DKD (p < 0.05). Serum SDF-1 levels were positively correlated with cystatin C levels, the UACR and DKD incidence (r = 0.330, 0.183 and 0.186, respectively, p < 0.05) and inversely related to eGFR (r = -0.368, p < 0.001). After adjusting for other clinical covariates by multivariate logistic regression analyses, serum SDF-1 levels were found to be an independent contributor to DKD, and the odds ratio (95% confidence interval) was 1.438 (1.041-1.986). Furthermore, receiver operating characteristic analysis revealed that the optimal SDF-1 cutoff value for indicating DKD was 5.609 ng/mL (its corresponding sensitivity was 82.00%, and specificity was 46.90%). Our results demonstrated that serum SDF-1 levels were closely associated with DKD and could be considered a potent indicator for DKD in patients with T2D.

Hyperin Enhances the Sensitivity of HCT8/VCR Colon Cancer Cell Line to Vincristine by Down-Regulating P-Glycoprotein.

BACKGROUND: Long-term chemotherapy reduces the sensitivity of colon cancer cells to chemotherapeutics like vincristine (VCR) and lead to drug resistance, which has become a major barrier for colon cancer treatment. Calcium antagonists are used as clinical tumor multidrug resistance reversal agents to regulate the P-glycoprotein (P-gp) level and block efflux pump function now, but they have significant side effects. Hyperin as active component with low toxicity in traditional Chinese medicine has calcium antagonistic effect. Thus, the purpose of this study was to evaluate the inhibitory effect of hyperin on the growth of HCT8/VCR colon cancer cell line (vincristine-resistant) and analyze the enhancing effect of hyperin on the sensitivity of cancer cells to VCR and its relationship to the expression and function of P-gp. METHODS: Using the MTT method, we investigated the influence of hyperin, VCR alone, and hyperin plus VCR on the growth of HCT8/VCR cells. Western blot analysis was employed to detect the expression of P-gp, and flow cytometry was used to evaluate P-gp function by detecting the fluorescence intensity of intracellular Rho123. RESULTS: The inhibitory effect of hyperin at the dose of 12.5 µM on HCT8/VCR cell growth was not enhanced as time progressed and no significant inhibitory effect was found for VCR-treated cells at the dose of 2 µM. But the inhibition of cell growth was observed after the combined treatment of hyperin (12.5 µM) and VCR (2 µM). P-gp expression levels in HCT8/VCR cells treated with hyperin plus VCR were markedly lower than the levels in control cells and those treated with VCR. In addition, the intensity of Rho123 fluorescence of HCT8/VCR cells treated with hyperin plus VCR or hyperin alone was significantly higher than intensity observed in control cells and those treated with VCR alone. CONCLUSIONS: Hyperin synergistically augments the growth inhibitory effect of vincristine. The underlying mechanism most probably involves down-regulation of P-gp expression and inhibiting the function of the P-gp pump in HCT8/VCR cells.

Combined exposure to nano-silica and lead induced potentiation of oxidative stress and DNA damage in human lung epithelial cells.

Growing evidence has confirmed that exposure to ambient particulate matters (PM) is associated with increased morbidity and mortality of cardiovascular and pulmonary diseases. Ambient PM is a complex mixture of particles and air pollutants. Harmful effects of PM are specifically associated with ultrafine particles (UFPs) that can adsorb high concentrations of toxic air pollutants and are easily inhaled into the lungs. However, combined effects of UFPs and air pollutants on human health remain unclear. In the present study, we elucidated the combined toxicity of silica nanoparticles (nano-SiO2), a typical UFP, and lead acetate (Pb), a typical air pollutant. Lung adenocarcinoma A549 cells were exposed to nano-SiO2 and Pb alone or their combination, and their combined toxicity was investigated by focusing on cellular oxidative stress and DNA damage. Factorial analyses were performed to determine the potential interactions between nano-SiO2 and Pb. Our results showed that exposure of A549 cells to a modest cytotoxic concentration of Pb alone induced oxidative stress, as evidenced by elevated reactive oxygen species generation and lipid peroxidation, and reduced glutathione content and superoxide dismutase and glutathione peroxidase activities. In addition, exposure of A549 cells to Pb alone induced DNA damage, as evaluated by alkaline comet assay. Exposure of A549 cells to non-cytotoxic concentration of nano-SiO2 did not induce cellular oxidative stress and DNA damage. However, exposure to the combination of nano-SiO2 and Pb potentiated oxidative stress and DNA damage in A549 cells. Factorial analyses indicated that the potentiation of combined toxicity of nano-SiO2 and Pb was induced by additive or synergistic interactions.

Design of a Computer-Assisted System to Automatically Detect Cell Types Using ANA IIF Images for the Diagnosis of Autoimmune Diseases.

Indirect immunofluorescence technique applied on HEp-2 cell substrates provides the major screening method to detect ANA patterns in the diagnosis of autoimmune diseases. Currently, the ANA patterns are mostly inspected by experienced physicians to identify abnormal cell patterns. The objective of this study is to design a computer-assisted system to automatically detect cell patterns of IIF images for the diagnosis of autoimmune diseases in the clinical setting. The system simulates the functions of modern flow cytometer and provides the diagnostic reports generated by the system to the technicians and physicians through the radar graphs, box-plots, and tables. The experimental results show that, among the IIF images collected from 17 patients, 6 were classified as coarse-speckled, 3 as diffused, 2 as discrete-speckled, 1 as fine-speckled, 2 as nucleolar, and 3 as peripheral patterns, which were consistent with the patterns determined by the physicians. In addition to recognition of cell patterns, the system also provides the function to automatically generate the report for each patient. The time needed for the whole procedure is less than 30 min, which is more efficient than the manual operation of the physician after inspecting the ANA IIF images. Besides, the system can be easily deployed on many desktop and laptop computers. In conclusion, the designed system, containing functions for automatic detection of ANA cell pattern and generation of diagnostic report, is effective and efficient to assist physicians to diagnose patients with autoimmune diseases. The limitations of the current developed system include (1) only a unique cell pattern was considered for the IIF images collected from a patient, and (2) the cells during the process of mitosis were not adopted for cell classification.

The bidirectional associations between sarcopenia-related traits and cognitive performance.

While many studies have sought to explore the degree to which sarcopenia-related traits are associated with cognitive performance, these studies have yielded contradictory results without any clear indication of the causality of such relationships. In efforts to better understand associations between sarcopenia-related traits and cognitive ability, a series of multivariate linear regression assessments were carried out upon datasets derived through the National Health and Nutrition Examination Survey (NHANES). Of these, cognitive performance was assessed by the Digit Symbol Substitution Test (DDST), the Consortium to Establish a Registry for Alzheimer's Disease Immediate Recall Test (CERAD-IR), Delayed Recall Test (CERAD-DR) and Animal Fluency Test (AFT). Causal relationships between the two were further inferred via a two-sample Mendelian randomization (MR) analysis approach. Sarcopenia-related traits considered in these assessments included walking speed, appendicular skeletal muscle mass (ASM), and hand grip strength (HGS). Walking speed, ASM, and HGS were all significantly independently related to cognitive scores following adjustment for covariates. MR assessments also identified that each 1-SD higher walking speed and appendicular lean mass were causally and respectively associated with a 0.34 [standard error (SE) = 0.09; p < 0.001)] standardized score higher and a 0.07 (SE = 0.01; p < 0.001) standardized score higher cognitive score, whereas a higher hand grip strength was positively associated with a better cognitive performance. Reverse MR assessments also yielded similar findings. These data suggest that lower walking speed, muscle strength, and muscle mass were all closely related to lower cognitive performance irrespective of gender, and that there may be a mutually reinforcing relationship among these variables.

Association of serum stromal cell-derived factor 1 levels with EZSCAN score and its derived indicators in patients with type 2 diabetes.

Background: The aim of the study was to explore whether plasma stromal cell-derived factor 1 (SDF-1) levels are associated with the EZSCAN score and its derived indicators in patients with type 2 diabetes (T2D). Methods: From July 2020 to December 2020, a total of 253 patients with T2D were consecutively recruited. Serum SDF-1 levels were measured by sandwich ELISA. EZSCAN test was applied to evaluate the sudomotor function of each patient, and based on the results, EZSCAN score, cardiac autonomic neuropathy risk score (CANRS) and cardiovascular risk score (CVDRS) were calculated by particular algorithms. In addition, other relevant clinical data were also collected. Results: With increasing tertiles of serum SDF-1 levels, the CANRS and CVDRS significantly increased (both Pfor trend <0.001), while the EZSCAN score significantly decreased (Pfor trend <0.001). Moreover, serum SDF-1 levels were significantly and positively correlated with the CANRS and CVDRS (r = 0.496 and 0.510, respectively, both P < 0.001), and negatively correlated with the EZSCAN score (r = -0.391, P < 0.001). Furthermore, multivariate linear regression analyses were constructed, and after adjusting for other clinical covariates, serum SDF-1 levels were independently responsible for EZSCAN score (ß = -0.273, t = -3.679, P < 0.001), CANRS (ß = 0.334, t = 5.110, P < 0.001) and CVDRS (ß = 0.191, t = 4.983, P = 0.003). Conclusions: SDF-1 levels in serum were independently associated with the EZSCAN score and its derived indicators, such as CANRS and CVDRS in patients with T2D.

Comparisons of the Relationships Between Multiple Lipid Indices and Diabetic Kidney Disease in Patients With Type 2 Diabetes: A Cross-Sectional Study.

Background: Dyslipidemia is a well-recognized risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Growing evidences have shown that compared with the traditional lipid parameters, some lipid ratios may provide additional information of lipid metabolism. Thus, the present study aimed to investigate which lipid index was most related to DKD. Methods: This study was a cross-sectional study that enrolled patients with T2D from January 2021 to October 2021. Each participant was screened for DKD, and the diagnostic criterion for DKD is estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months. Fasting blood was collected to determine lipid profiles by an automatic biochemical analyzer, and lipid ratios were calculated based on corresponding lipid parameters. Spearman's correlation analyses were conducted to assess the correlations between lipid indices and kidney injury indices, and binary logistic regression analyses were conducted to explore the relationship between lipid indices and the risk of DKD. Results: A total of 936 patients with T2D were enrolled in the study, 144 (15.38%) of whom had DKD. The LDL-C/Apo B ratios were positively correlated with eGFR (r = 0.146, p < 0.05) and inversely correlated to cystatin C and UACR (r = -0.237 and -0.120, both p < 0.001). Multiple logistic regression demonstrated that even after adjusting for other clinical covariates, the LDL-C/Apo B ratios were negatively related to DKD, and the odds ratio (95% confidence interval) was 0.481 (0.275-0.843). Furthermore, subgroup analyses revealed that compared with patients with normal lipid profiles and a high LDL-C/Apo B ratio, the odds ratio of DKD in patients with normal lipid metabolism and a low LDL-C/Apo B ratio was 2.205 (1.136-4.280) after adjusting for other clinical covariates. Conclusion: In patients with T2D, the LDL-c/Apo B ratio was most closely associated with DKD among various lipid indices, and a lower LDL-C/Apo B ratio was associated with increased risks of DKD among patients with T2D.

The Positive Relationship Between the Low-Density Lipoprotein Cholesterol/Apoprotein B Ratio and Bone Turnover Markers in Patients With Type 2 Diabetes.

Background: Dyslipidemia may contribute to low bone turnover in patients with type 2 diabetes (T2D) through mediating oxidative stress and atherosclerosis. The low-density lipoprotein cholesterol/apoprotein B (LDL-C/Apo B) ratio is a surrogate marker of small and density low-density lipoprotein cholesterol (sd-LDL-C), a most harmful group of LDL-Cs. The present study aimed to investigate the association between the LDL-C/Apo B ratio and bone turnover in patients with T2D. Methods: This study was a cross-sectional study enrolled patients with T2D from January 2021 to December 2021. Each participant was assessed for lipid profiles, bone turnover markers (BTMs), lumbar spine (L1-L4) and hip dual-energy X-ray absorptiometry (DXA) scans. Osteoporosis was diagnosed as a T-score lower than or equal to -2.5 at the spine or hip. Results: A total of 335 patients with T2D were enrolled in the study, and the LDL-C/Apo B ratio ranged from 0.78 to 4.00. Along with the LDL-C/Apo B ratio tertile ascending, osteocalcin (OC), C-terminal telopeptide (CTx) and N-terminal propeptide of type-I procollagen (PINP) levels gradually increased (all p < 0.05). There were no differences in lumbar spine and hip T-score, proportion of osteoporosis (all p > 0.05) among the three subgroups. The LDL-C/Apo B ratio was positively correlated with lnOC (r = 0.244, p < 0.001), lnCTx (r = 0.226, p < 0.01) and lnPINP (r = 0.211, p < 0.001). These significant positive correlations persisted even when divided into male and female subgroups. Furthermore, three multiple linear regression analyses were constructed to investigate the independent association of the LDL-C/Apo B ratio with the BTMs levels. After adjusting for other clinical parameters, the LDL-C/Apo B ratio was still significantly associated with OC level (ß = 0.199, t = 3.348, p < 0.01), CTx level (ß = 0.238, t = 4.084, p < 0.001) and PINP level (ß = 0.162, t = 2.741, p < 0.01). Conclusion: The LDL-C/Apo B ratio was significantly and positively associated with BTMs in patients with T2D. In clinical practice, more attention should be paid to the patients with T2D whose LDL-C/Apo B ratio is relatively low for the purpose of maintaining bone health.

Association between fibrinogen/albumin ratio and arterial stiffness in patients with type 2 diabetes: A cross-sectional study.

Background: Fibrinogen albumin ratio (FAR) is significantly correlated with the severity and prognosis of cardiovascular disease (CVD). Arterial stiffness is an early lesion of CVD, but no studies have examined the correlation between arterial stiffness and FAR. This study aimed to examine the relationship between FAR and arterial stiffness in patients with type 2 diabetes (T2D), as measured by brachial-ankle pulse wave velocity (baPWV). Methods: In this cross-sectional investigation, patients with T2D were enrolled between January 2021 and April 2022. In each patient, the levels of fibrinogen and albumin in the serum, and baPWV in the serum were measured. A baPWV greater than 1800 cm/s was utilized to diagnose arterial stiffness. Results: The study included 413 T2D patients. The mean age of these participants was 52.56 ± 11.53 years, 60.8% of them were male, and 18.6% of them had arterial stiffness. There were significant differences in baPWV level and proportion of arterial stiffness (p < .001) between the four subgroups categorized by the FAR quartile. The relationships between the FAR and baPWV and arterial stiffness were significantly favorable in the overall population and subgroups of elderly men and non-elderly men (p < .01), while they were insignificant in subgroups of elderly and non-elderly women (p > .05). To investigate the correlation between the FAR and baPWV, the arterial stiffness and the FAR in male T2D patients, respectively, multivariable logistic regression analysis and multiple linear regression analysis were developed. The lnFAR and lnbaPWV had a significant relationship in the multiple linear regression analysis fully adjusted model. After adjusting for potential covariables, multivariable logistic regression analysis revealed that the FAR was independently associated with arterial stiffness [OR (95% CI), 1.075 (1.031-1.120)]. In addition, receiver operating characteristic analysis indicated that the best FAR cutoff value for detecting arterial stiffness in male T2D patients was 76.67 mg/g. Conclusion: The level of FAR had an independent and positive correlation with baPWV and arterial stiffness in male patients with T2D, but not in female patients.

Effects and Mechanism of Ganoderma lucidum Polysaccharides in the Treatment of Diabetic Nephropathy in Streptozotocin-Induced Diabetic Rats.

Ganoderma lucidum polysaccharides (GLP) have renal protection effect but there was no study on the diabetic nephropathy. This study was designed to investigate its effect and mechanism using a diabetic rat model induced by streptozotocin (50 mg/kg, i.p.). The diabetic rats were treated with GLP (300 mg/kg/day) for 10 weeks. The blood glucose, glycated hemoglobin, body weight, and the levels of blood creatinine, urea nitrogen, and urine protein were assessed. And renal pathologies were assessed by the tissue sections stained with hematoxylin-eosin, Masson's trichome, and periodic acid-Schiff. The expression of phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR), the autophagy proteins beclin-1, LC3-II, LC3-I, and P62; the apoptosis-related proteins caspase-3 and caspase-9; and the inflammation markers IL-6, IL-1ß, and TNF-ɑ were assessed. Results showed that GLP alleviated the impairment of renal function by reducing urinary protein excretion and the blood creatinine level and ameliorated diabetic nephropathy. The expression of p-PI3K, p-Akt, and p-mTOR in the diabetic kidney were significantly reduced in the GLP treatment group compared to the without treatment group. GLP treatment activated the autophagy indicators of beclin-1 and the ratio of LC3-II/LC3-I but reduced p62 and also inhibited the expression of caspase-3, caspase-9 and IL-6, IL-1ß, and TNF-ɑ. In conclusion, the effect of GLP amelioration diabetic nephropathy may be via the PI3k/Akt/mTOR signaling pathway by inhibition of the apoptosis and inflammation and activation of the autophagy process.

The association between normal serum sodium levels and bone turnover in patients with type 2 diabetes.

Background: Sodium is a critically important component of bones, and hyponatremia has firmly been established as a risk factor associated with the incidence of fragility fractures. However, researches have also revealed that lower serum sodium are linked to reductions in muscle mass and a higher risk of cardiovascular disease even when these levels are within the normal range. Accordingly, this study was developed to examine the relationships between normal serum sodium concentrations and bone turnover in patients with type 2 diabetes (T2D). Methods: Patients with T2D were enrolled in the present study from January 2021 to April 2022. All patients underwent analyses of serum sodium levels, oral glucose tolerance testing (OGTT), bone turnover markers (BTMs), and dual-energy X-ray absorptiometry (DXA) scanning. BTMs included bone formation markers osteocalcin (OC) and N-terminal propeptide of type-I procollagen (PINP), and bone resorption marker C-terminal telopeptide (CTx). Patients were stratified into three subgroups based on the tertiles of their serum sodium concentrations. Results: In total, 372 patients with T2D and sodium levels in the normal range were enrolled in this study. Serum OC and PINP levels were increased from subgroup with the low sodium tertile to that with the high sodium tertile (p for trend < 0.05), whereas CTx level was comparable among the subgroups. A positive correlation was detected between serum sodium levels and both lnOC (r = 0.210, p < 0.001) and lnPINP (r = 0.196, p < 0.001), with these relationships remaining significant even following adjustment for age, sex, body mass index (BMI), and HbA1c. Only after adjusting for these four factors a positive correlation was detected between serum sodium levels and CTx levels (r = 0.108, p < 0.05). Linear regression analyses revealed that following adjustment for potential covariates, serum sodium level was and positively significantly associated with lnOC level (ß = 0.134, t = 2.281, p < 0.05) and PINP level (ß = 0.179, t = 3.023, p < 0.01). Conclusion: These results highlight a significant association between low-normal serum sodium levels and low bone turnover.

Corrigendum: The association between normal serum sodium levels and bone turnover in patients with type 2 diabetes.

[This corrects the article DOI: 10.3389/fendo.2022.927223.].

Serum adenosine deaminase levels are associated with diabetic kidney disease in type 2 diabetic patients.

The aim of the present study was to evaluate the association between adenosine deaminase (ADA) levels and diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). In this study, patients with T2D who had been screened for DKD were recruited. Patients with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or a urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g for 3 months were identified as having DKD. The prevalence of DKD was 13.3%, and the range of serum ADA levels was 4-37 U/L. Serum ADA levels were positively associated with cystatin C levels and UACR (r = 0.295 and r = 0.302, respectively, both P < 0.05) and negatively associated with eGFR (r = -0.342, P < 0.05). The proportion of participants with DKD increased significantly from 3.8% in the first tertile (T1) to 13.6% in the second tertile (T2) and 25.9% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for clinical risk factors for DKD via multiple logistic regression, the corresponding odds ratios (ORs) of DKD for the participants in T2 and T3 vs those in T1 of ADA were 5.123 (1.282-20.474) and 10.098 (1.660-61.431), respectively. Receiver operating characteristic (ROC) analysis revealed that the optimal cutoff value of ADA to indicate DKD was 10 U/L. Its corresponding sensitivity and specificity were 75.5 and 56.4%, respectively. Our results demonstrated that serum ADA levels were closely associated with DKD and partly reflect the risk of DKD in patients with T2D.

The association between serum adenosine deaminase levels and Graves' disease.

BACKGROUND: Adenosine deaminase (ADA) is essential for the differentiation and maturation of lymphocytes, while lymphocytes infiltration in thyroid tissue is a vital pathological feature of Graves' disease (GD). The aim of the present study was to compare the concentration of ADA between healthy controls (HC) and patients with GD, and evaluate the association between ADA and GD. METHODS: A total of 112 GD patients and 77 matched HC were enrolled in this study. Each participant was examined for thyroid hormones and autoantibodies, ADA concentration, and thyroid ultrasonography. RESULTS: Serum ADA levels in GD patients were significantly higher than that in HC subgroup (P < 0.001). In GD patients, serum ADA levels were positively associated with serum-free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb) levels, and total thyroid gland volume (thyroid VolT) and negatively associated with serum thyroid-stimulating hormone receptor (TSH) levels (all P < 0.05). There were no similar correlations in the HC subgroup. Multiple linear regression analysis suggested that serum TSH, FT3, and ADA levels played an important role in serum TRAb levels. CONCLUSIONS: Our results demonstrated that serum ADA levels were closely associated with GD.

The relationship between adenosine deaminase and heart rate-corrected QT interval in type 2 diabetic patients.

BACKGROUND: Prolonged heart rate-corrected QT (QTc) interval may reflect poor prognosis of patients with type 2 diabetes (T2D). Serum adenosine deaminase (ADA) levels are related to hyperglycemia, insulin resistance (IR) and inflammation, which may participate in diabetic complications. We investigated the association of serum ADA levels with prolonged QTc interval in a large-scale sample of patients with T2D. METHODS: In this cross-sectional study, a total of 492 patients with T2D were recruited. Serum ADA levels were determined by venous blood during fasting. QTc interval was estimated from resting 12-lead ECGs, and prolonged QTc interval was defined as QTc > 440 ms. RESULTS: In this study, the prevalence of prolonged QTc interval was 22.8%. Serum ADA levels were positively associated with QTc interval (r = 0.324, P < 0.0001). The proportion of participants with prolonged QTc interval increased significantly from 9.2% in the first tertile (T1) to 24.7% in the second tertile (T2) and 39.0% in the third tertile (T3) of ADA (P for trend < 0.001). After adjusting for other possible risk factors by multiple linear regression analysis, serum ADA level was still significantly associated with QTc interval (ß = 0.217, t = 3.400, P < 0.01). Multivariate logistic regression analysis showed that female (OR 5.084, CI 2.379-10.864, P < 0.001), insulin-sensitizers treatment (OR 4.229, CI 1.290-13.860, P = 0.017) and ADA (OR 1.212, CI 1.094-1.343, P < 0.001) were independent contributors to prolonged QTc interval. CONCLUSIONS: Serum ADA levels were independently associated with prolonged QTc interval in patients with T2D.

Association of sleep quality with glycemic variability assessed by flash glucose monitoring in patients with type 2 diabetes.

BACKGROUND: Deterioration of sleep quality has been reported to contribute to the incidence of diabetes and may be responsible for glycemic status in diabetes. The present study explored the relationship between sleep quality and glycemic variability in patients with type 2 diabetes (T2D). METHODS: We recruited 111 patients with T2D for this cross-sectional study. Each patient underwent flash glucose monitoring for 14 days to obtain glycemic variability parameters, such as standard deviation of glucose (SD), coefficient of variation of glucose (CV), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), and time in glucose range of 3.9-10 mmol/L (TIR3.9-10). After 14 days of flash glucose monitoring, each patient received a questionnaire on the Pittsburgh Sleep Quality Index (PSQI) to evaluate subjective sleep quality. HbA1c was also collected to assess average glucose. RESULTS: HbA1c was comparable among the subgroups of PSQI score tertiles. Across ascending tertiles of PSQI scores, SD, CV and MAGE were increased, while TIR3.9-10 was decreased (p for trend < 0.05), but not MODD (p for trend = 0.090). Moreover, PSQI scores were positively correlated with SD, CV, MODD and MAGE (r = 0.322, 0.361, 0.308 and 0.354, respectively, p < 0.001) and were inversely correlated with TIR3.9-10 (r = - 0.386, p < 0.001). After adjusting for other relevant data by multivariate linear regression analyses, PSQI scores were independently responsible for SD (ß = 0.251, t = 2.112, p = 0.041), CV (ß = 0.286, t = 2.207, p = 0.033), MAGE (ß = 0.323, t = 2.489, p = 0.018), and TIR3.9-10 (ß = - 0.401, t = - 3.930, p < 0.001) but not for MODD (ß = 0.188, t = 1.374, p = 0.177). CONCLUSIONS: Increased glycemic variability assessed by flash glucose monitoring was closely associated with poor subjective sleep quality evaluated by the PSQI in patients with T2D.

Chlorpyrifos induces delayed cytotoxicity after withdrawal in primary hippocampal neurons through extracellular signal-regulated kinase inhibition.

In this study, the delayed effect and related mechanism after chlorpyrifos (CPF) withdrawal was studied in primary rat hippocampal neurons. The results showed that 10 muM CPF induced no detectable cytotoxicity during 96 h continuous exposure while its withdrawal after 48 h exposure induced evident cytotoxicity, as indexed by decreased methyl thiazolyl tetrazolium (MTT) metabolism, increased loss of neurons immunostained by neuron-specific enolase (NSE) antibody, and the increased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) positive cell rate in the following 24 h and 48 h incubation in the absence of CPF. Extracellular signal-related kinase (ERK)1/2 activation by phosphorylation was observed and persisted during CPF exposure. However, CPF withdrawal after 48 h exposure led to inhibition of ERK1/2 phosphorylation. Carbacol and nerve growth factor (NGF), which are ERK1/2 activators, protected the neurons after CPF withdrawal, while atropine and PD98059, which are ERK1/2 inhibitors, exacerbated the cytotoxicity, indicating the involvement of inhibition of ERK1/2 phosphorylation in CPF-induced delayed cytotoxicity. In conclusion, CPF withdrawal after exposure induced delayed cytotoxicity in cultured neurons. Inhibition of ERK1/2 phosphorylation was found to be related to the delayed cytotoxicity. This finding may provide a new insight into the toxicological mechanism of organophosphorus pesticides, especially chronic organophosphate-induced neuropsychiatric disorder characterized by delayed occurrence.

Chronic organophosphate (OP)-induced neuropsychiatric disorder is a withdrawal syndrome.

Chronic organophosphate-induced neuropsychiatric disorder is a less well-characterized syndrome, which is usually delay-occurred, persists long and is similar to the symptom of cholinergic deficit, its mechanism is unclear. The characteristics of chronic organophosphate-induced neuropsychiatric disorder are somewhat opposite to the direct action of OP pesticide, since withdrawal effect is usually opposite to the original effect of a drug, hypothesis that chronic organophosphate-induced neuropsychiatric disorder is a kind of withdrawal syndrome is suggested.