Enhancing insulin sensitivity in type 2 diabetes mellitus using apelin-loaded small extracellular vesicles from Wharton's jelly-derived mesenchymal stem cells: a novel therapeutic approach.

BACKGROUND: Type 2 diabetes mellitus (T2DM), characterized by ß-cell dysfunction and insulin resistance (IR), presents considerable treatment challenges. Apelin is an adipocyte-derived factor that shows promise in improving IR; however, it is limited by poor targeting and a short half-life. In the present study, engineered small extracellular vesicles (sEVs) derived from Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) loaded with apelin were used to address the limitations of the therapeutic application of apelin. METHODS: WJ-MSCs were transduced to obtain engineered sEVs loaded with overexpressed apelin (apelin-MSC-sEVs) and the control sEVs (MSC-sEVs). T2DM mice were injected with apelin-MSC-sEVs and MSC-sEVs, and blood glucose monitoring, glucose and insulin tolerance tests, confocal microscopy, and immunocytochemical analysis were performed. IR models of 3T3-L1 adipocytes were employed to detect GLUT4 expression in each group using western blotting; the affected pathways were determined by measuring the changes in Akt and AMPK signaling and phosphorylation. RESULTS: Upon successful engineering, WJ-MSCs demonstrated significant overexpression of apelin. The genetic modification did not adversely impact the characteristics of sEVs, ranging from surface protein markers, morphology, to particle size, but generated apelin-overexpressed sEVs. Apelin-MSC-sEVs treatment resulted in notable enhancement of Akt and AMPK pathway activities within 3T3-L1 adipocytes and adipose tissues of T2DM mice. Furthermore, the apelin-loaded sEVs significantly reduced plasma glucose levels, increased pancreatic ß-cell proliferation, improved insulin and glucose tolerance, and modulated pro-inflammatory cytokine profiles, compared to mice treated with the control sEVs. CONCLUSION: Our study developed novel genetically engineered apelin-loaded sEVs derived from WJ-MSCs, and demonstrated their potent role in augmenting insulin sensitivity and regulating inflammatory responses, highlighting their therapeutic promise in T2DM management. The findings open new avenues for the development of clinically viable treatments for T2DM in humans using the apelin-loaded sEVs.

miR-128-3p inhibits high-glucose-induced peritoneal mesothelial cells fibrosis via PAK2/SyK/TGF-ß1 axis.

AIM: To elucidate the mechanism of miR-128-3p in peritoneal fibrosis (PF). METHODS: Peritoneal mesothelial cells (PMCs) were dealt with high glucose (HG) for 3 days. The expressions of miR-128-3p, p21-activated kinase 2 (PAK2), spleen tyrosine kinase (SyK), and transforming growth factor-ß1 (TGF-ß1) were detected with quantitative real-time reverse transcription polymerase chain reaction. The levels of IL-1ß, TNF-α, IL-6, and monocyte chemotactic protein-1 in supernatant were measured by ELISA. Proteins of TGF-ß1, SyK, PAK2, α-SMA, collagen I, vimentin, ERK/AP-1, and IκBα/NF-κB pathway related proteins were measured by Western blot. The correlation between miR-128-3p and PAK2 was found by bioinformatics analysis and luciferase reporter gene analysis. RESULTS: miR-128-3p was decreased while PAK2, SyK, and TGF-ß1 were increased in HG-induced PMCs. Moreover, miR-128-3p inhibited HG-induced fibrosis and inflammation in PMCs by targeting PAK2. PAK2 activated SyK, which induced TGF-ß1 expression through ERK/AP-1 and IκBα/NF-κB pathways to promote HG-induced fibrosis of PMCs. CONCLUSION: miR-128-3p inhibited HG-induced PMCs fibrosis via PAK2/SyK/TGF-ß1 axis.

CHA2DS2-VASc score as a prognostic indicator in patients with atrial fibrillation undergoing coronary stenting.

BACKGROUND: Patients with atrial fibrillation (AF) and coronary stenting had a poor prognosis. This study aimed to assess the accuracy of CHA2DS2-VASc score for predicting and grading adverse clinical outcomes in this population. METHODS: We reviewed the clinical data of all patients with previously documented nonvalvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. The study population was divided into three groups: 1) Low CHA2DS2-VASc score, ≦ 2 points, 2) Intermediate score, 3-4 points, and 3) High score, ≧ 5 points. Major adverse cardiac/cerebrovascular events (MACCE) were defined as a composite of all-cause death, nonfatal myocardial infarction, repeat revascularization and ischemic stroke/systemic thromboembolism (IS/SE). RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included, with the CHA2 DS2-VASc score of 3.6 ± 1.6. The median follow-up duration was 36.2 months. All-cause mortality increased 3 folds from the low score (4.8%) to the high score group (15.8%). The high score group had more IS/SE (7.4%) and MACCE (26.3%). The CHA2 DS2-VASc score ≧ 5 points was independently associated with all-cause death (hazard ratio [HR]: 2.303, 95% confidence interval [CI]: 1.492- 3.555), IS/SE (HR: 4.169, 95% CI: 2.216-7.845) and MACCE (HR: 1.468, 95% CI: 1.113-1.936) on multivariate Cox proportional hazards regression. The area under the receiver operating characteristic curve of the CHA2DS2-VASc score was 0.644 (95% CI: 0.624-0.663) for all-cause death, 0.647 (95% CI: 0.627-0.666) for IS/SE, and 0.592 (95% CI: 0.572-0.611) for MACCE. DISCUSSION: CHA2DS2-VASc score was a reliable prognostic indicator in patients with AF and coronary stenting.

Long-term outcomes of high-risk percutaneous coronary interventions under extracorporeal membrane oxygenation support: An observational study.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) offers hemodynamic support for patients undergoing high-risk percutaneous coronary interventions (PCIs). However, long-term outcomes associated with VA-ECMO have not previously been studied. AIM: To explore long-term outcomes in high-risk cases undergoing PCI supported by VA-ECMO. METHODS: In the present observational cohort study, 61 patients who received VA-ECMO-supported high-risk PCI between April 2012 and January 2020 at the Sixth Medical Center of Chinese People's Liberation Army General Hospital were enrolled. The endpoint characteristics such as all-cause mortality, repeated cardiovascular diseases, and cardiac death were examined. RESULTS: Among 61 patients, three failed stent implantation due to chronic total occlusions with severely calcified lesions. One patient showed VA-ECMO intolerance because of high left ventricular afterload. PCI was successfully performed in 57 patients (93.4%). The in-hospital mortality was 23.0%, and the overall survival was 45.9%, with a median follow-up period of 38.6 (8.6-62.1) mo. CONCLUSION: VA-ECMO can be used as a support in patients undergoing high-risk PCI as it is associated with favorable long-term patient survival.

AngioJet rheolytic thrombectomy in patients with thrombolysis in myocardial infarction thrombus grade 5: an observational study.

The aim of this study was to evaluate the effectiveness and safety of AngioJet rheolytic thrombectomy among patients with high thrombus burden. Routine manual thrombus aspiration in patients with ST-segment elevation myocardial infarction (STEMI) does not improve clinical outcomes and was associated with an increased rate of stroke. However, the safety of mechanical thrombus aspiration is still unknown. This was a retrospective, single-center study involving 621 patients with Thrombolysis In Myocardial Infarction thrombus grade 5. The primary outcome was the composite of major adverse cardiovascular events (MACE) within 12 months. The safety outcome was stroke within 1-year. Propensity matching score was calculated due to the significant baseline differences between the AngioJet rhelytic thrombectomy group and the routine treatment group. AngioJet rheolytic thrombectomy was performed in 117 patients. After propensity-score matching, there was no significant difference both in the incidence of MACE (11.1% vs 17.9%, hazard ratio, 1.641; 95% confidence interval [CI] 0.822 to 3.277, p = 0.161) and the incidences of stroke (1.7% vs 2.6%, hazard ratio 1.522; 95% confidence interval [CI] 0.254 to 9.107, p = 0.646) between two groups at 1-year follow-up. In patients with Thrombolysis In Myocardial Infarction thrombus grade 5, AngioJet rheolytic thrombectomy did not improve clinical outcomes at 1 year. However, AngioJet rheolytic thrombectomy did not increase the risk of stroke in patients with high thrombus burden.

Predictive models for adverse clinical outcomes in Chinese patients with atrial fibrillation undergoing percutaneous coronary intervention with stenting.

OBJECTIVE: This study aimed to evaluate predictors for adverse cardiovascular outcomes in patients with atrial fibrillation (AF) undergoing coronary stenting. METHODS: We retrospectively recruited consecutive patients with previously documented non-valvular AF who underwent coronary stenting between January 2010 and June 2015 in 12 hospitals of Beijing, China. Major adverse cardiac/cerebrovascular events (MACCE) were a composite of all-cause death, non-fatal myocardial infarction, repeat revascularization, and ischaemic stroke/systemic thromboembolism (IS/STE). Major bleeding referred to grade 2 or higher of Bleeding Academic Research Consortium criteria. RESULTS: A total of 2394 patients (men: 72.3% vs. women: 27.7%, median age: 67 years) were included. The CHA2DS2-VASc and HAS-BLED were 3.6 ± 1.6 and 1.9 ± 0.7, respectively. The median follow-up duration was 36.2 months. There were 230 (9.6%) deaths, 96 (4.0%) IS/STE, 426 (17.8%) MACCE, and 72 (3.0%) major bleeding. Multivariate Cox regression yielded predictive models for (1) all-cause death: diabetes, prior myocardial infarction, chronic kidney disease (CKD), ST-segment elevation myocardial infarction (STEMI) at presentation, heart failure, no use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and statins; (2) IS/STE: advanced age, prior history of ischaemic stroke and intracranial haemorrhage; (3) MACCE: prior history of myocardial infarction and ischaemic stroke, CKD, STEMI, heart failure, and no statin use; (4) major bleeding: prior major bleeding, prior myocardial infarction, CKD and use of oral anticoagulants. CONCLUSION: Chinese patients with AF and coronary stenting had high mortality and incidence of MACCE. We compiled separate predictive models for all-cause death, IS/STE, MACCE, and major bleeding.

Thrombus straddling a patent foramen ovale and pulmonary embolism: A case report.

BACKGROUND: Venous thromboembolism is a common vascular syndrome presenting as deep vein thrombosis and/or pulmonary embolism. Thrombus has the possibility of migrating into the left circulation via patent foramen ovale in certain extreme circumstances. Thrombus straddling a patent foramen ovale is a direct evidence of this scenario. However, the confirmed cases of thrombus in transit are still rare. CASE SUMMARY: A 32-year-old man suffered from recurrent syncope and intermittent dyspnea for 1 wk. Transthoracic echocardiography confirmed a thrombus straddling the patent foramen ovale, and thrombi were also found in the bilateral pulmonary artery by computed tomography. The man underwent inferior vena cava filter placement and thrombolysis with alteplase. Echocardiography showed the absence of thrombi in both the right atrium and left atrium 2 d after hospitalization. The man was discharged to home on warfarin without any complications 2 wk later. CONCLUSION: Scrutinizing intracardiac thrombi provides measurable value in pulmonary embolism as closure of patent foramen ovale may be considered in certain patients. Early intervention plays a critical role in thrombus straddling a patent foramen ovale. A sedentary lifestyle may predispose young adults to thromboembolism, even if there are no other risk factors.

[Construction and optimization of ecological network for nature reserves in Fujian Province, China]. / 福建省自然保护区生态网络的构建与优化.

The nature reserve is very important to biodiversity maintenance. However, due to the urbanization, the nature reserve has been fragmented with reduction in area, leading to the loss of species diversity. Establishing ecological network can effectively connect the fragmented habitats and plays an important role in species conversation. In this paper, based on deciding habitat patches and the landscape cost surface in ArcGIS, a minimum cumulative resistance model was used to simulate the potential ecological network of Fujian provincial nature reserves. The connectivity and importance of network were analyzed and evaluated based on comparison of connectivity indices (including the integral index of connectivity and probability of connectivity) and gravity model both before and after the potential ecological network construction. The optimum ecological network optimization measures were proposed. The result demonstrated that woodlands, grasslands and wetlands together made up the important part of the nature reserve ecological network. The habitats with large area had a higher degree of importance in the network. After constructing the network, the connectivity level was significantly improved. Although interaction strength between different patches va-ried greatly, the corridors between patches with large interaction were very important. The research could provide scientific reference and basis for nature protection and planning in Fujian Province.

[Simulation of vegetation landscape in Pingtan Island based on BP neural network model].

Taking GIS as technical platform and by using Matlab 7.0, the vegetation landscape in Pingtan Island was cut with 2 km x 2 km grid graph. The data of 50 quadrats were obtained. Forty-four of the 50 quadrates were used for model training, and the rest 6 were used for model checking. Fractal dimension, Shannon diversity index, and contagion index were selected as output data of the model, and the number of residential quarter, wind speed, and the distance from the coast were chosen as affecting factors. A BP neural network model of vegetation landscape in Pingtan Island was established, and was checked by error test. The results demonstrated that the major factors affecting the vegetation landscape spatial pattern and diversity in Pingtan Island were wind speed and the distance from the coast, and anthropogenic factors had greater effects on the spatial connection of vegetation landscape. The fitted results of the relationships between vegetation landscape and environmental and anthropogenic factors were basically accorded with the truth. The average error was 7.4%, and the minimum error was 0.2%, indicating that the model could be applied to quantitatively predict and simulate the vegetation landscape in Pingtan Island.