Liraglutide (Lir) is a glucagon-like peptide-1 receptor agonist that lowers blood sugar and reduces myocardial infarct size by improving endothelial cell function. However, its mechanism has not yet been clarified. Unfolded protein response (UPR) plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury. It determines the survival of cells. Endoplasmic reticulum position protein homologue 2 (CNPY2) is a novel initiator of UPR that also participates in angiogenesis. To this extent, the current study further explored whether Lir regulates angiogenesis through CNPY2. In our article, a hypoxia/reoxygenation (H/R) injury model of human umbilical vein endothelial cells (HUVECs) was established and the effect of Lir on HUVECs was first evaluated by the Cell Counting Kit-8. Endothelial tube formation was used to analyze the ability of Lir to induce angiogenesis. Subsequently, the effect of Lir on the concentrations of hypoxia-inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF), and CNPY2 was detected by enzyme-linked immunosorbent assay. To assess whether Lir regulates angiogenesis through the CNPY2-initiated UPR pathway, the expression of UPR-related pathway proteins (CNPY2, GRP78, PERK, and ATF4) and angiogenic proteins (HIF1α and VEGF) was detected by reverse transcription-polymerase chain reaction and Western blot. The results confirmed that Lir significantly increased the expression of HIF1α and VEGF as well as the expression of CNPY2-PERK pathway proteins in HUVECs after H/R injury. To further validate the experimental results, we introduced the PERK inhibitor GSK2606414. GSK2606414 was able to significantly decrease both the mRNA and protein expression of ATF4, HIF1α, and VEGF in vascular endothelial cells after H/R injury. The effect of Lir was also inhibited using GSK2606414. Therefore, our study suggested that the CNPY2-PERK pathway was involved in the mechanism of VEGF expression after H/R injury in HUVECs. Lir increased the expression of VEGF through the CNPY2-PERK pathway, which may promote endothelial cell angiogenesis and protect HUVEC from H/R damage.

Accumulating studies have confirmed the crucial role of long non-coding RNAs (ncRNAs) as favorable biomarkers for cancer diagnosis, therapy, and prognosis prediction. In our recent study, we established a robust model which is based on multi-gene signature to predict the therapeutic efficacy and prognosis in glioblastoma (GBM), based on Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. lncRNA-seq data of GBM from TCGA and CGGA datasets were used to identify differentially expressed genes (DEGs) compared to normal brain tissues. The DEGs were then used for survival analysis by univariate and multivariate COX regression. Then we established a risk score model, depending on the gene signature of multiple survival-associated DEGs. Subsequently, Kaplan-Meier analysis was used for estimating the prognostic and predictive role of the model. Gene set enrichment analysis (GSEA) was applied to investigate the potential pathways associated to high-risk score by the R package “cluster profile” and Wiki-pathway. And five survival associated lncRNAs of GBM were identified: LNC01545, WDR11-AS1, NDUFA6-DT, FRY-AS1, TBX5-AS1. Then the risk score model was established and shows a desirable function for predicting overall survival (OS) in the GBM patients, which means the high-risk score significantly correlated with lower OS both in TCGA and CGGA cohort. GSEA showed that the high-risk score was enriched with PI3K-Akt, VEGFA-VEGFR2, TGF-beta, Notch, T-Cell pathways. Collectively, the five-lncRNAs signature-derived risk score presented satisfactory efficacies in predicting the therapeutic efficacy and prognosis in GBM and will be significant for guiding therapeutic strategies and research direction for GBM.

Background: We aimed to determine the role of non-mydriatic fundus examination and artificial intelligence (AI) in screening diabetic retinopathy (DR) in patients with diabetes in the Metabolic Disease Management Center (MMC) in Tianjin, China. Methods: Adult patients with type 2 diabetes mellitus who were first treated by MMC in Tianjin First Central Hospital and Tianjin 4th Center Hospital were divided into two groups according to the time that MMC was equipped with the non-mydriatic ophthalmoscope and AI system and could complete fundus examination independently (the former was the control group, the latter was the observation group). The observation indices were as follows: the incidence of DR, the fundus screening rate of the two groups, and fundus screening of diabetic patients with different course of disease. Results: A total of 5039 patients were enrolled in this study. The incidence rate of DR was 18.6%, 29.8%, and 49.6% in patients with diabetes duration of ⩽1 year, 1–5 years, and >5 years, respectively. The screening rate of fundus in the observation group was significantly higher compared with the control group (81.3% versus 28.4%, χ² = 1430.918, p < 0.001). The DR screening rate of the observation group was also significantly higher compared with the control group in patients with diabetes duration of ⩽1 year (77.3% versus 20.6%; χ² = 797.534, p < 0.001), 1–5 years (82.5% versus 31.0%; χ² = 197.124, p < 0.001) and ⩾5 years (86.9% versus 37.1%; χ² = 475.609, p < 0.001). Conclusions: In the case of limited medical resources, MMC can carry out one-stop examination, treatment, and management of DR through non-mydratic fundus examination and AI assistance, thus incorporating the DR screening process into the endocrine clinic, so as to facilitate early diagnosis.

Aim: Elevated serum ferritin has been found to be closely related to type 2 diabetes mellitus. This study aimed to explore the relationship of high serum ferritin to metabolism and chronic complications in type 2 diabetes. Methods: This was a cross-sectional study. A total of 330 type 2 diabetes patients who visited an endocrine clinic were included for the analysis. Serum ferritin and metabolic parameters were recorded. The prevalence of chronic diabetic complications was evaluated. Based on serum ferritin, participants were divided into hyperferritinemia and normal-ferritin groups. Metabolic parameters and prevalence of chronic diabetic complications were compared. The relationship between hyperferritinemia and chronic diabetic complications was explored with multivariate logistic regression models. Data were statistically analyzed by sex. Results: Compared with the normal-ferritin group, the hyperferritinemia group showed higher levels of the serum inflammatory marker CRP and higher prevalence of diabetic retinopathy (DR) and coronary heart disease (CHD), regardless of sex (p< 0.05). Moreover, male patients with hyperferritinemia had increased serum triglyceride, alanine transferase, γ-glutamyltranspeptidase, urea nitrogen, creatinine, and uric acid and higher prevalence of microalbuminuria (p< 0.01). After controlling for demographics and metabolic profiles, hyperferritinemia remained an independent risk factor of DR (male OR 3.957, 95% CI 1.559– 10.041, p=0.004; female OR 2.474, 95% CI 1.127– 5.430, p=0.024) and CHD (male OR 2.607, 95% CI 1.087– 6.257, p=0.032; female OR 2.293, 95% CI 1.031– 5.096, p=0.042). Conclusion: This study found that hyperferritinemia was associated with increased CRP and higher prevalence of DR and CHD in type 2 diabetes. In men, high serum ferritin was also associated with dyslipidemia, hepatic dysfunction, and microalbuminuria.