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Introduction Patients with type 2 diabetes mellitus (T2DM) are at a high risk of cognitive impairment, with insulin resistance playing a pivotal role. β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is considered a predictor of Alzheimer's disease. However, the potential roles of BACE1 in insulin resistance and the risk of cognitive impairment in T2DM remain unclear. Methods We measured plasma BACE1 levels, BACE1 cleavage activities for Swedish mutant amyloid precursor protein (APPsw) and insulin receptor β subunit (INSR-β), and soluble INSR (sINSR) levels in a clinical cohort study. Results T2DM patients with or without cognitive impairment exhibited elevated plasma BACE1 levels and BACE1 enzymatic activities for APPsw and INSR-β, and sINSR levels. Moreover, the glycemic status correlated with elevated BACE1 levels and BACE1-mediated INSR cleavage, which was associated with insulin resistance. Discussion The elevated BACE1 levels in T2DM may contribute to increasing the cognitive impairment risk through both amyloidogenesis and insulin resistance.

Background Recent studies showed that type 2 diabetes mellitus (T2DM) may increase the risk of cognitive impairment, but there are few biomarkers to diagnostically discriminate T2DM-associated cognitive impairment and cognitive impairment alone. In this study, we assessed certain cytokines involved in inflammation and vascular diseases and identified special panel of cytokines that could differentiate between T2DM and cognitive impairment. Objective To investigate associations and differences between T2DM and cognitive impairment by cytokines analysis. Methods A total of 264 participants were recruited, their blood samples were collected, and plasma and serum were separated and stored at - 80°C until the assessment of amyloid-β (Aβ)42, Aβ40 and 8 kinds of cytokines by Luminex multiplex assays. Results Plasma Aβ40 is higher whereas Aβ42/40 ratio is lower in cognitive impairment and T2DM-associated cognitive impairment compared to other groups. As compared to health control, YKL-40 level was upregulated in cognitive impairment, PRGN was downregulated in T2DM associated cognitive impairment, OPN was substantially decreased in T2DM, and IL-6 was elevated in cognitive impairment and T2DM-associated cognitive impairment. Interestingly, VEGF and S100B were induced in T2DM when compared with cognitive impairment, and NSE level in T2DM-associated cognitive impairment is significantly lower than in T2DM or cognitive impairment. Conclusion Aβ42, Aβ40, and Aβ42/40 ratio cannot distinguish T2DM-associated cognitive impairment from cognitive impairment. Certain cytokines (YKL-40, NSE, and VEGF) have good performance in distinguishing T2DM-associated cognitive impairment from simple cognitive impairment. Taken together, this may improve the accuracy of the diagnosis and establishment of individualized therapy.

Serum osteocalcin (OCN) is closely related to metabolic risk factors, and the relationship between OCN and atherosclerosis has been investigated. However, it is still controversial. Herein, we explored the potential correlation between serum total OCN and lower extremity atherosclerotic disease (LEAD) in 326 hospitalized Chinese patients with type 2 diabetes mellitus (T2DM). Femoral intima-media thickness (F-IMT) and lower limb atherosclerotic plaque were assessed through color Doppler ultrasound. Subjects with LEAD had significantly lower serum OCN levels compared with those without LEAD (14.54 [14.10-14.89] ng/mL versus 16.79 [15.86-18.04] ng/mL, p < 0.001). Spearman's correlation analysis revealed that serum OCN levels were positively associated with high density lipoprotein cholesterol (HDL-C) and negatively associated with fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPG), hemoglobin A1c (HbA1c), waist-to-hip ratio (WHR) and F-IMT. Multiple logistic analysis revealed that OCN (OR 0.938, 95% confidence interval (CI 0.933-0.950, p = 0.003) and glomerular filtration rate (GFR) (OR 0.990, 95% CI 0.985-0.996, p = 0.003) were independently and inversely associated with LEAD, while age (OR 1.140, 95% CI 1.127-1.148, p < 0.001), diabetes duration (OR 1.068, 95% CI 1.039-1.080, p < 0.005) and uric acid (UA) (OR 1.005, 95% CI 1.002-1.007, p = 0.032) were independently and positively associated with LEAD. Additionally, multiple linear regression analysis revealed that serum OCN levels were negatively associated with F-IMT (standardized β = -0.180, p = 0.002). In Chinese patients with T2DM, serum OCN levels were independently and inversely correlated with LEAD.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance and a systemic pro-inflammatory response. To date, no medications for NAFLD have been approved by relevant governmental agencies. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NAFLD. Hyperoside, a flavonoid compound mainly found in medicinal plants, has many biological effects, but the role of hyperoside in the physiological process of NAFLD is poorly defined. This study demonstrated that hyperoside exerts protective effects against high-fat diet (HFD)-induced NAFLD and regulates macrophage polarization in an Nr4A1-dependent manner. After 16 weeks on a HFD, hepatic steatosis, insulin resistance, and inflammatory responses were significantly ameliorated in hyperoside-treated HFD-fed wild-type mice, and hyperoside facilitated the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 subtype. Nr4A1 was found to be upregulated in hyperoside-treated HFD-fed mice, and hyperoside did not improve HFD-induced NAFLD or regulate macrophage polarization in Nr4A1-deficient mice. In conclusion, hyperoside may have therapeutic potential in preventing the pathological progression of NAFLD.

Hepatic gluconeogenesis is the major contributor to hyperglycemia in diabetes. Long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been shown to promote hepatic insulin resistance; however, the underlying mechanism involving hepatic gluconeogenesis remains unclear. This study aims to investigate the potential role of MEG3 in hepatic gluconeogenesis. Mouse primary hepatocytes were used in this study. Cell transfection was performed for the overexpression or knockdown of specific genes. Expressions of MEG3, miR-302a-3p, CREB-regulated transcriptional coactivator 2 (CRTC2), protein kinase A (PKA), cAMP-response element binding protein (CREB), PPARγ coactivator-1α (PGC-1α), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6Pc) were determined by quantitative real-time polymerase chain reaction (qRT-qPCR) and Western blot analysis, respectively. The association among MEG3, miR-302a-3p, and CRTC2 was disclosed by dual-luciferase reporter assay. MEG3 was highly expressed in high glucagon-treated mouse primary hepatocytes. CREB-induced MEG3 upregulation increased gluconeogenic gene expression in high glucagon-treated primary hepatocytes, while MEG3 interference led to an opposite effect. MEG3 served as a competing endogenous RNA (ceRNA) to upregulate CRTC2 by targeting miR-302a-3p in primary hepatocytes, thereby increasing PGC-1α-PEPCK/G6Pc. CREB-upregulated MEG3-enhanced hepatic gluconeogenesis via mediating miR-302a-3p-CRTC2 axis, revealing that MEG3 might be a potential target and therapeutic strategy for diabetes.

Whether cisplatin plus vinorelbine (VC) or cisplatin plus docetaxel (DC) are equally effective in the treatment of advanced non-small-cell lung cancer (NSCLC) remains controversial. The aim of this study was to compare the VC and DC regimens in the first-line treatment of advanced NSCLC. A search was conducted through PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the Chinese Biomedical Literature database (CBM). The language of the publication was not considered to be a limitation. The recruited trials were evaluated for eligibility and quality and the data were extracted and analyzed. The endpoints were overall response, survival rate and toxicity. We analyzed 9 randomized controlled trials (RCTs), including a total of 1,886 patients. Patients receiving DC therapy exhibited a significantly higher response rate [relative risk (RR)=0.83, 95% CI: 0.73-0.95 and P=0.007] and 2-year survival rate (RR=0.65, 95% CI: 0.50-0.84 and P=0.001). However, the 1-year survival rate for the two cisplatin-based regimens were comparable (RR=0.90, 95% CI: 0.81-1.01 and P=0.07). Patients receiving the VC regimen more frequently developed grade 3/4 leucopenia, anemia and vomiting, whereas those receiving DC chemotherapy were more prone to grade 3/4 diarrhea. The incidence of grade 3/4 neutropenia, thrombocytopenia and nausea were similar between the two arms. In conclusion, our study indicated that DC is superior to the VC regimen in terms of tumor response rate, 2-year survival rate and safety for the first-line treatment of advanced NSCLC.

To improve the thawing technique and the thawing efficiency of high voltage electrostatic thawing, reducing the energy consumption, the effects of technical parameters on the thawing rate and energy consumption were investigated. Ice contained in the Petri dish was put in the high voltage electrostatic field which was made up of a multiple point pole and a plate pole. By changing the thawing voltage, the electrode spacing and the distance between the two neighboring needles, the factors related to the thawing rate and energy consumption were quantitatively studied. The results indicate that when the distance between the needle electrodes and the surface of the plate pole is constant, the thawing rate increases linearly while the thawing energy consumption increases nonlinearly with the supplied voltage. When the supplied voltage is not changed, the ice thawing rate and energy consumption are changed with the distance between the two neighboring needles. When the distance between the two neighboring needles is not changed, the ice thawing rate and energy consumption are changed with the electrode spacing. When the electrode spacing is 9 cm, the thawing rate is the highest while the energy consumption is relative least, 45 kV is the optimum value for thawing voltage.

To compare the effects of video or leaflet in conjunction with traditional patient education (TPE) with traditional patient education alone for the compliance and satisfaction of the patients with temporomandibular disorders (TMD).One hundred and thirty-three patients with TMD who needed intra-articular injection of hyaluronate were included and randomly divided into three groups: Group I accepted video education plus TPE, Group II accepted leaflet education plus TPE, Group III accepted TPE alone. All the participants were recorded by demographic characteristics (sex, age) before treatment, and their compliance, satisfaction and self-exercise were also recorded after one month followed-up.The baseline parameters (sex, age and diagnosis) of the groups were similar (P0.05). Seventeen participants lost in follow-up, including 4.5% in Group I, 11.1% in Group II and 22.7% in Group III. There were significant differences in lost rates among the three groups (P = 0.035). The rates of participants who exactly followed the appointed follow-up were higher in Group I and II than in group III (P = 0.04). And the satisfaction rates were 90.5% in Group I, 92.5% in Group II, 76.5% in Group III. The satisfaction rates of Group I and Group II were significantly higher than that of Group III (P = 0.05). The patients in Group I and Group II were more compliant with the self-exercise than that in Group III (P = 0.007).Adding video or leaflet education to the TPE could increase the patients' compliance, satisfaction and execution of the self-exercise.