Dysfunction of macroautophagy/autophagy in macrophages contributes to atherosclerosis. Impaired autophagy-lysosomal degradation system leads to lipid accumulation, facilitating atherosclerotic plaque. ATG14 is an essential regulator for the fusion of autophagosomes with lysosomes. Whether ATG14 plays a role in macrophage autophagy dysfunction in atherosclerosis is unknown. To investigate the effects of ATG14 on macrophage autophagy, human atherosclerotic plaque, apoe^−/- mice and cultured mouse macrophages were evaluated. Overexpression of ATG14 by adenovirus was used to reveal its function in autophagy, inflammation and atherosclerotic plaque formation. Results showed that impaired autophagy function with reduction of ATG14 expression existed in macrophages of human and mouse atherosclerotic plaques. Ox-LDL impaired autophagosome-lysosome fusion with reduction of ATG14 expression in macrophages. Overexpression of ATG14 in macrophages enhanced fusion of autophagosomes with lysosomes and promoted lipid degradation, decreasing Ox-LDL-induced apoptosis and inflammatory response. Augmenting ATG14 expression reversed the autophagy dysfunction in macrophages of apoe^−/- mice plaque, blunted SQSTM1/p62 accumulation, inhibited inflammation, and upregulated the population of Treg cells, resulting in alleviating atherosclerotic lesions. Abbreviations: ABCC1: ATP-binding cassette, sub-family C (CFTR/MRP), member 1; ABCA1: ATP-binding cassette, sub-family A (ABC1), member 1; Ad-Atg14: adenovirus vector carrying the mouse Atg14 gene; Ad-LacZ: adenovirus vector carrying the gene for bacterial β-galactosidase; apoe^−/-: apolipoprotein E knockout; ATG14: autophagy-related 14; CD68: CD68 antigen; DAPI: 4ʹ,6-diamidino-2-phenylindole; Dil-ox-LDL: Dil-oxidized low density lipoprotein; ELISA: enzyme-linked immunosorbent assay; HFD: high-fat diet (an atherogenic diet); IL: interleukin; LAMP2: lysosomal-associated membrane protein 2; LDL-C: low density lipoprotrein cholesterol; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; ND: normal diet; Ox-LDL: oxidized low density lipoprotein; PBMC: peripheral blood mononuclear cells; SQSTM1/p62: sequestosome 1; SREBF1/SREBP1c: sterol regulatory element binding transcription factor 1; SREBF2/SREBP2: sterol regulatory element binding factor 2; STX17: syntaxin 17; TC: serum total cholesterol; TG: triglyceride; TNF: tumor necrosis factor; IFN: interferon; Treg cell: regulatory T cell

Recent data have suggested that serum uric acid (SUA) level is positively associated with the development of type 2 diabetes (T2DM). Whether SUA is also independently associated with the development of vascular complications and mortality in T2DM is controversial. A computerized literature search of MEDLINE, Embase and PubMed database was conducted and the odds ratio (OR) or hazard ratio (HR) for per 0.1mmol/l increase in SUA in each study was calculated. Cochrane’s Q and I² statistics were used to evaluate heterogeneity among studies and pooling OR and HR with 95% confidence intervals (CIs) were calculated using random-effects models and fixed-effects models. The pooled analysis was performed using Stata 10.0. Our search yielded 9 eligible articles (16 ORs and HRs) including 20,891 T2DM patients. Pooled estimates for the relationship suggested that each 0.1 mmol/l increase in SUA resulted in a 28% increase in the risk of diabetic vascular complications and a 9% increase in the risk of diabetic mortality. In stratification-analysis, the positive relationship between SUA and vascular complications remained significant irrespective of mean age, adjustment for metabolic variables and medications. However, it was inconsistent in different populations (significantly positive in the Asian but not in Australian and Italian population) and sample sizes (significantly positive in the relatively large sample size [≥1000] but non-significant in the small sample size [<1000]). Results of this meta-analysis supported elevated SUA as an independent predictor of vascular complications and mortality in T2DM patients. SUA-lowering therapies might be helpful for prevention and treatment of vascular complications in this population.

Background: Visceral obesity is associated with high cardiovascular events risk in type 2 diabetes mellitus (T2DM). Whether normal-weight visceral obesity will pose a higher atherosclerotic cardiovascular disease (ASCVD) risk than body mass index (BMI)-defined overweight or obese counterparts with or without visceral obesity remains unclear. We aimed to explore the relationship between general obesity and visceral obesity and 10-year ASCVD risk in patients with T2DM. Methods: Patients with T2DM (6997) who satisfied the requirements for inclusion were enrolled. Patients were considered to have normal weight when 18.5 kg/m² ≤ BMI < 24 kg/m²; overweight when 24 kg/m² ≤ BMI < 28 kg/m²; and obesity when BMI ≥ 28 kg/m². Visceral obesity was defined as a visceral fat area (VFA) ≥ 100 cm². Patients were separated into six groups based on BMI and VFA. The odd ratios (OR) for a high 10-year ASCVD risk for different combinations of BMI and VFA were analysed using stepwise logistic regression. Receiver operating characteristic (ROC) curves for diagnosing the high 10-year ASCVD risk were constructed, and areas under the ROC curves were estimated. Potential non-linear relationships between VFA levels and high 10-year ASCVD risk were examined using restricted cubic splines (knot = 4). Multilinear regression was used to identify factors affecting VFA in patients with T2DM. Results: In patients with T2DM, subjects with normal-weight visceral obesity had the highest 10-year ASCVD risk among the six groups, which had more than a 2-fold or 3-fold higher OR than those who were overweight or obese according to BMI but did not have visceral obesity (all P < 0.05). The VFA threshold for high 10-year ASCVD risk was 90 cm². Multilinear regression showed significant differences in the effect of age, hypertension, drinking, fasting serum insulin, fasting plasma glucose, 2 h postprandial C-peptide, triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol on VFA in patients with T2DM (all P < 0.05). Conclusions: T2DM patients with normal-weight visceral obesity had a higher 10-year ASCVD risk than BMI-defined overweight or obese counterparts with or without visceral obesity, which should initiate standardised management for ASCVD primary prevention.

To evaluate the impact of thyroid nodule sizes on the diagnostic performance of thyroid imaging reporting and data system (TIRADS) and ultrasound patterns of 2015 American Thyroid Association (ATA) guidelines. Total 734 patients with 962 thyroid nodules were recruited in this retrospective study. All nodules were divided into three groups according to the maximal diameter (d < 10 mm, d = 10–20 mm and d > 20 mm). The ultrasound images were categorized based on TIRADS and ATA ultrasound patterns, respectively. A total of 931 (96.8%) and 906 (94.2%) patterns met the criteria for TIRADS and ATA ultrasound patterns. The AUC (0.849) and sensitivity (85.3%) of TIRADS were highest in d = 10–20 mm group. However, ATA had highest AUC (0.839) and specificity (89.8%) in d > 20 mm group. ATA ultrasound patterns had higher specificity (P = 0.04), while TI-RADS had higher sensitivity (P = 0.02). In nodules d > 20 mm, the specificity of ATA patterns was higher than TIRADS (P = 0.003). Our results indicated that nodule sizes may influence the diagnostic performance of TIRADS and ATA ultrasound patterns. The ATA patterns may yield higher specificity than TIRADS, especially in nodules larger than 20 mm.

High-resolution ultrasound (HRUS) is a sensitive tool for identifying thyroid nodules. Real-time elastography (RTE) and contrast-enhanced ultrasound (CEUS) are newly developed methods which could measure tissue elasticity and perfusion features. The aim of the present study was to evaluate and compare the diagnostic efficiency of HRUS, RTE, CEUS and their combined use in the differentiation of benign and malignant solid thyroid nodules.In total, 111 consecutive patients with 145 thyroid nodules who were scheduled for surgery were included in the study. All of them underwent HRUS, RTE, and CEUS examination. The independent ultrasound (US) predictors for malignancy were determined and quantified using logistic regression analysis, based on which a risk-scoring model was established for each method. The diagnostic efficiency of each method was assessed by receiver operating characteristic (ROC) curve analysis.HRUS showed the best diagnostic efficiency among the 3 US methods, with 74.6% sensitivity and 87.8% specificity. CEUS had higher sensitivity (85.7%), whereas RTE alone did not show much advantage. Combined use of RTE and HRUS increased the sensitivity (92.1%). The HRUS-RTE-CEUS combination could increase both the sensitivity and specificity (87.3%, 91.5%), with the best AUC (0.935) among all the methods.The overall diagnostic value of HRUS in predicting malignancy is the best among the 3 US methods. Combined use of RTE and CEUS and HRUS could improve the diagnostic efficiency for solid thyroid nodules.