BACKGROUND:Type 2 diabetes mellitus (T2DM) and its complications, including diabetic lower extremity arterial disease (DLEAD) and diabetic foot (DF), impose significant health burdens worldwide. However, the differential expression of microRNAs (miRNAs) between T2DM and its complications and its causal effects remain poorly understood. METHODS:We conducted an exosome-wide association study (EWAS) comparing miRNA profiles between T2DM and its complications, including DLEAD and DF, without healthy controls. The significant miRNAs identified between DM and its complications were further validated by integrating cis-miRNA expression quantitative trait loci (cis-miR-eQTLs) and genome-wide association study (GWAS) summary data of T2DM and peripheral arterial disease (PAD) through two-sample Mendelian randomization (MR) analysis. RESULTS:We identified several differential expressions of miRNAs between T2DM, DLEAD, and DF, such as hsa-miR-409-3p between T2DM and DLEAD, hsa-miR-543 between T2DM and DF and hsa-miR-206 between DLEAD and DF. The two sample MR analysis revealed potential causal relationships between dysregulated miRNAs and T2DM and its complications, such as hsa-miR-30b-3p and hsa-miR-30b-5p showed causal associations with T2DM and PAD respectively. CONCLUSIONS:Our study elucidates the miRNA signatures associated with T2DM and its complications. These findings provide insights into the pathogenesis of T2DM and its complications and suggest potential therapeutic targets for intervention.

Chronic kidney disease (CKD) causes a significant health and economic burden across the world. This study aimed to evaluate the effects of zinc on CKD-mineral bone disorder (CKD-MBD) and autophagy in CKD rats by a diet containing 0.25% adenine and low vitamin K and to explore its mechanism of action on autophagy and calcification in a vascular smooth muscle cell (VSMC) calcification model using 10 mM β-glycerophosphate (β-GP). In vivo experiments showed that zinc supplementation improved blood and urinary biochemistry, corrected abnormalities related to bone metabolism in rats with CKD, promoted autophagy, and reduced aortic calcification. In vitro, zinc reduced the calcification of VSMCs induced by β-GP. During VSMC calcification, zinc further upregulated autophagy levels and the phosphorylated extracellular regulatory kinase1/2 (ERK1/2) levels in a high-phosphorus environment. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, or with U0126, an ERK1/2 pathway inhibitor, decreased autophagy and increased calcification. In conclusion, zinc improved CKD-MBD by inhibiting vascular calcification (VC) and ameliorating bone metabolism disorders. Furthermore, zinc alleviates VC in CKD by activating ERK1/2-mediated autophagy.

AimThe aim of this study is to explore the association between red blood cell distribution width–to–albumin ratio (RAR) and the risk of peripheral artery disease (PAD) in patients with diabetes.MethodsThis cross-sectional study extracted the data of 1,125 participants with diabetes from the National Health and Nutrition Examination Survey database. A weighted univariable logistic regression model was used to explore variables associated with PAD. With PAD as the outcome variable, a weighted logistic regression model was established. The odds ratio (OR) and 95% confidence interval (CI) were effect size.ResultsAfter adjusting for covariates, the risk of PAD in patients with diabetes was observed in those with higher RAR (OR = 1.83; 95% CI: 1.06–3.15). In addition, RAR ≥3.25 was related to increased risk of PAD in patients with diabetes (OR = 2.04; 95% CI: 1.05–3.95). In people with diabetes aged ≥65, RAR was a risk factor for PAD with an OR value of 2.67 (95% CI: 1.30–5.46). RAR ≥3.25 was associated with increased risk of PAD (OR = 3.06; 95% CI: 1.15–8.11) relative to RAR <2.80. In people with diabetes who smoked, the risk of PAD was elevated in those with RAR ≥3.25 (OR = 2.85; 95% CI: 1.28–6.32). As for patients with cardiovascular disease, the risk of PAD was elevated as the increase of RAR (OR = 2.31; 95% CI: 1.05–5.10). RAR ≥3.25 was correlated with increased risk of PAD (OR = 3.75; 95% CI: 1.42–9.87). The area under the curve of RAR for the risk of PAD in patients with diabetes was 0.631 (95% CI: 0.588–0.675).ConclusionA higher RAR was related to increased risk of PAD in patients with diabetes. The findings might offer a reference for the management of PAD in patients with diabetes.

Diabetic foot ulcer (DFU) complications involve autophagy dysregulation. This study aimed to identify autophagy-related bioindicators in DFU. Differentially expressed genes (DEGs) between DFU and healthy samples were analysed from the Gene Expression Omnibus (GEO) datasets, GSE7014 and GSE29221. The roles of autophagy-related DEGs were investigated using protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, Gene Ontology (GO) enrichment, and Gene Set Enrichment Analysis (GSEA). Immune cell infiltration's correlation with these DEGs was also assessed. From the Human Autophagy Database (HADB), 232 autophagy-related genes (ARGs) were identified, with an intersection of 17 key DEGs between GSE7014 and GSE29221. These genes are involved in pathways like autophagy-animal, NOD-like receptor signalling, and apoptosis. In the protein network, epidermal growth factor receptor (EGFR) and phosphatase and tensin homologue (PTEN) showed significant interactions with ARGs. Survival analysis indicated the prognostic importance of calpain 2 (CAPN2), integrin subunit beta 1 (ITGB1), and vesicle-associated membrane protein 3 (VAMP3). Lower immune scores were observed in the type 2 diabetes mellitus (DM2) group than in controls. Autophagy and ARGs significantly influence DFU pathophysiology.

目的 探讨基于超声特征及基因检测技术构建甲状腺结节恶性风险预测模型的可行性.方法 回顾性分析 202 例行甲状腺手术患者的临床资料(模型建立组),所有患者均完善超声检查,而后采用甲状腺超声计算机辅助诊断(CAD)软件对其超声图像进行分析.以病理结果为金标准,对所有患者的临床信息、实验室信息及CAD软件图像分析信息进行logstic回归分析,并构建风险模型.另纳入同期完善穿刺前检查并行甲状腺细针穿刺(FNA)的 200 例患者作为模型验证组.采用受试者工作曲线(ROC)分析预测模型和不同年资医师对甲状腺结节良恶性的判断结果,比较诊断效能差异.结果 低回声强度、强回声点、边缘模糊程度、纵横比＞1 及血清促甲状腺激素(TSH)、甲状腺过氧化物酶抗体(TPOAb)、癌胚抗原(CEA)水平升高、基因突变阳性是甲状腺结节恶性的高危因素,结节最大径是保护因素(P<0.05 或0.01).甲状腺结节恶性风险预测模型的ROC线下面积 AUC为 0.891(95％CI 0.773～0.981),最佳预测临界值为 70.67％,敏感度为 85.63％,特异度为 82.13％,阳性预测值为 91.36％,阴性预测值为 76.81％.研究所构建的甲状腺结节恶性风险模型诊断效能高于中、低年资医师,低于高年资医师,特异度介于中、低年资医师之间(P<0.05).结论 根据超声特征、细针穿刺病理、TSH水平、TPOAb、基因检测联合logistic回归分析所构建的甲状腺结节恶性风险模型可有效辅助临床预测恶性甲状腺结节的发生.

目的:分析miR-106a、miR-124表达水平与分化型甲状腺癌发生发展及远期生存率的关系.方法:选取2016年1-6月广州市增城区中心医院收治的62例分化型甲状腺癌患者,行颈淋巴结穿刺和甲状腺癌根治手术,检测癌组织及癌旁组织的miR-106a、miR-124表达水平,分析miR-106a、miR-124表达水平与临床病理特征的相关性和临床预后的关系.结果:癌组织中miR-106a表达量高于癌旁正常组织,miR-124表达量显著低于癌旁正常组织(P<0.05);miR-106a在TNM分期Ⅲ期、淋巴转移、肿瘤直径>1 cm及被膜侵犯患者中呈较高表达,而miR-124在TNM分期Ⅲ期、淋巴转移、肿瘤直径>1 cm及被膜侵犯患者中呈较低表达(P<0.05);miR-106a高表达患者5年生存率显著低于低表达者,miR-124高表达患者5年生存率显著高于高表达者(P<0.05).结论:miR-106a、miR-124表达水平与分化型甲状腺癌患者临床分期和淋巴转移有关,其水平表达与患者5年内生存率密切相关.

目的:探讨利拉鲁肽联合前列地尔对糖尿病足患者的影响.方法:选取本院2018年2月-2020年2月收治的76例糖尿病足患者,随机数字表法将其分为观察组与对照组,各38例.对照组予以前列地尔进行治疗,观察组在对照组基础上予以利拉鲁肽进行治疗,比较两组患者临床疗效、不良反应和治疗前后空腹血糖(FBG)、餐后血糖(PBG)、糖化血红蛋白(HbA1c)、平均血糖波动幅度(MAGE)、日间血糖平均绝对差(MODD)及血糖在目标范围内时间(TIR)、血清胰岛素样生长因子结合蛋白-3(insulin-like growth factor binding protein-3,IGFBP-3)和Toll样受体9(toll-like receptor 9,TLR9)水平.结果:治疗后,观察组总有效率为94.74％,高于对照组的76.32％(P<0.05);两组患者治疗后FBG、PBG、HbA1c、MAGE、MODD水平均较治疗前降低,且观察组较对照组更低,TIR较治疗前显著升高,且观察组高于对照组(P<0.05);治疗后,两组患者血清IGFBP-3水平较治疗前升高,且观察组较对照组更高(P<0.05),治疗后,两组患者血清TLR9水平较治疗前降低,且观察组较对照组更低(P<0.05);治疗期间,观察组不良反应发生率为10.53％,与对照组的15.79％比较差异无统计学意义(P>0.05).结论:利拉鲁肽联合前列地尔可有效改善糖尿病足患者临床症状,控制血糖,改善血糖波动,升高血清IGFBP-3水平,降低血清TLR9水平,进而促进足部创面修复,疗效显著,值得临床推广.