Objective:To investigate the effects of 25-hydroxyvitamin D 3-loaded polylactic acid microspheres on myocardial injury in rats with gestational diabetes mellitus as well as its regulatory effects on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3)-cysteinyl aspartate specific proteinase-1 (Caspase-1)-gasdermin D (GSDMD) signaling axis. Methods:25-Hydroxyvitamin D 3-loaded polylactic acid microspheres were prepared by W/O emulsification and solvent volatilization method. The morphology of the microspheres was observed by scanning electron microscope, the diameters of the microspheres were detected by laser particle size analyzer, and the cumulative release rate was calculated. Pregnant rats were injected intraperitoneally with streptozotocin to establish a rat model of gestational diabetes mellitus and were randomly divided into the model group, the control group, and the microsphere group, with 10 rats in each group. Another 10 pregnant rats were taken as the sham operation group. In the microsphere group, a total of 100 μl of microsphere suspension was injected at 4 points along the edge of the left ventricle, while the control group was injected with an equal amount of blank microspheres in the same way, and the sham operation group and the model group were injected with an equal amount of physiological saline in the same way. Samples were taken at 21 d of gestation for subsequent experiments. Fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) of the rat model were detected. Cardiac troponin I (cTnI) and serum creatine kinase isoenzyme (CK-MB) levels were detected by a fully automated biochemical analyzer. Interleukin (IL)-1β and tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activity, and malondialdehyde levels in myocardial tissues were detected by enzyme-linked immunosorbent assay (ELISA). Protein expression of NLRP3, Caspase-1 and GSDMD was detected by Western Blot. Results:The scanning electron microscope observation showed that the microspheres were regular spherical with uniform size, compact surface and no cracks. The diameter of the microspheres was (13.48 ± 2.04) μm, and the particle size distribution was concentrated and homogeneous. The release of 25-hydroxyvitamin D 3-loaded polylactic acid microspheres was slow in the first 5 days, and then the cumulative release rate increased significantly, and the cumulative release rate reached more than 80% on the 28th day, and then stabilized. Compared with the sham operation group, the levels of FBG, HOMA-IR, cTnI, CK-MB, IL-1β, TNF-α, malondialdehyde as well as the protein expression of NLRP3, Caspase-1 and GSDMD were increased in the model group, and the activities of FINS, SOD and GSH-Px were decreased (all P < 0.05). Compared with the model and control groups, the levels of FBG, HOMA-IR, cTnI, CK-MB, IL-1β, TNF-α, malondialdehyde, and protein expression of NLRP3, Caspase-1, and GSDMD were decreased in the microsphere group, and the activities of FINS, SOD, and GSH-Px were increased (all P < 0.05). Conclusions:The 25-hydroxyvitamin D 3-loaded polylactic acid microspheres can reduce blood glucose level and insulin resistance, reduce myocardial inflammation and oxidative stress injury, and alleviate myocardial injury in rats with gestational diabetes mellitus, possibly by inhibiting the NLRP3/Caspase-1/GSDMD signaling axis.

Objective Based on Chinese guidelines for the management of ischemic stroke, a standardized stroke management program was performed to provide intensive education and training for medical physicians, aiming to enhance their knowledge and ability for ischemic stroke prevention and treatment, thereby reducing patients′ in-hospital cost and length of stay, and improving patients′ clinical prognosis. Methods This study was conducted in 20 general hospitals throughout Hainan province. A total of 163 physicians from 20 hospitals involved in the management of stroke patients were trained by highly experienced physicians based on the Chinese guidelines for diagnosis and treatment of acute ischemic stroke 2014 and the Chinese guidelines for secondary prevention of ischemic stroke and transient ischemic attack 2014. Prior to and post the standardized stroke management training, the data of 3218 and 3367 patients with ischemic stroke were respectively collected. Quality of life assessments including the Barthel index (BI) and the modified Rankin Scale (mRS) score of all patients were recorded at baseline and after discharge. The length of stay and in-hospital cost were directly collected from the hospital information system. Results Physicians′ knowledge and ability manifested as testing scores were significantly improved after training (78.2 ± 15.5 vs 55.6 ± 10.7, t=69.1, P<0.01). The average length of stay of post-training patients was significantly shorter than that of pre-training patients ((8.7 ± 0.9) vs (11.7 ± 1.5) days, t=97.9, P<0.01). The average in-hospital cost of post-training patients was significantly less than that of pre-training patients ((7681.7 ± 1397.7) vs (11846.2 ± 2514.6) Yuan, t=82.5, P<0.01). Both BI (68.2 ± 3.2 vs 43.5 ± 5.3, t=227.7, P<0.01) and mRS score (2.74±0.51 vs 3.65±0.71, t=59.5, P<0.01) were significantly improved for post-training patients. Multivariate linear regression analysis illustrated that standardized stroke management was negatively associated with in-hospital cost (r=-0.461, P<0.01), length of stay (r=-0.357, P<0.01) and mRS score (r=-0.298, P<0.01), and was positively associated with levels of BI (r=0.376, P<0.01). Conclusion Standardized stroke management program might be a cost-effective choice for the management of ischemic stroke as it reduces the in-hospital cost and improves patients′BI and mRS levels.