In paraquat (PQ)‑induced acute lung injury (ALI)/ acute respiratory distress syndrome, PQ disrupts endothelial cell function and vascular integrity, which leads to increased pulmonary leakage. Anthrahydroquinone‑2,6‑disulfonate (AH2QDS) is a reducing agent that attenuates the extent of renal injury and improves survival in PQ‑intoxicated Sprague‑Dawley (SD) rats. The present study aimed to explore the beneficial role of AH2QDS in PQ‑induced ALI and its related mechanisms. A PQ‑intoxicated ALI model was established using PQ gavage in SD rats. Human pulmonary microvascular endothelial cells (HPMECs) were challenged with PQ. Superoxide dismutase, malondialdehyde, reactive oxygen species and nitric oxide (NO) fluorescence were examined to detect the level of oxidative stress in HPMECs. The levels of TNF‑α, IL‑1β and IL‑6 were assessed using an ELISA. Transwell and Cell Counting Kit‑8 assays were performed to detect the migration and proliferation of the cells. The pathological changes in lung tissues and blood vessels were examined by haematoxylin and eosin staining. Evans blue staining was used to detect pulmonary microvascular permeability. Western blotting was performed to detect target protein levels. Immunofluorescence and immunohistochemical staining were used to detect the expression levels of target proteins in HPMECs and lung tissues. AH2QDS inhibited inflammatory responses in lung tissues and HPMECs, and promoted the proliferation and migration of HPMECs. In addition, AH2QDS reduced pulmonary microvascular permeability by upregulating the levels of vascular endothelial‑cadherin, zonula occludens‑1 and CD31, thereby attenuating pathological changes in the lungs in rats. Finally, these effects may be related to the suppression of the phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (AKT)/endothelial‑type NO synthase (eNOS) signalling pathway in endothelial cells. In conclusion, AH2QDS ameliorated PQ‑induced ALI by improving alveolar endothelial barrier disruption via modulation of the PI3K/AKT/eNOS signalling pathway, which may be an effective candidate for the treatment of PQ‑induced ALI.
Objective To evaluate the policy effect of replacing hospitalization service with outpatient service and reducing diabetes-related avoidable hospitalizations by improving outpatient benefits package. Methods A database of hospital discharge from 2015 to 2017 in City Z was used. All diabetic inpatient cases enrolled in Urban Employee Basic Medical Insurance were selected as the intervention group, and diabetic inpatient cases enrolled in Urban and Rural Resident Basic Medical Insurance were selected as the control group. The Difference-in-Difference model was used to analyze the effect of improving outpatient benefits package level of diabetes from 1800 yuan (about $252.82) to 2400 yuan (about $337.09) per capita per year on avoidable hospitalization rate, average hospitalization cost and average length of stay. Results The avoidable hospitalization rate of diabetes mellitus decreased by 0.21 percentage points ( P < 0.01), the average total cost of hospitalization increased by 7.89% ( P < 0.01), and the average length of stay per hospitalization increased by 5.63% ( P < 0.01). Conclusions Improving the outpatient benefits package of diabetes can play a role in replacing hospitalization service with outpatient service, reducing diabetes-related avoidable hospitalizations, and reducing the disease burden and financial burden.
To investigate the predictive value of the arterial blood lactate to serum albumin ratio (LAR) on in-hospital mortality of patients with community-acquired pneumonia (CAP) admitted to the Intensive Care Unit (ICU).Clinical datasets of 1720 CAP patients admitted to ICU from MIMIC-IV database were retrospectively analyzed. Patients were randomly assigned to the training cohort (n=1204) and the validation cohort (n=516) in a ratio of 7:3. X-tile software was used to find the optimal cut-off value for LAR. The receiver operating curve (ROC) analysis was conducted to compare the performance between LAR and other indicators. Univariate and multivariate Cox regression analyses were applied to select prognostic factors associated with in-hospital mortality. Based on the observed prognostic factors, a nomogram model was created in training cohort, and the validation cohort was utilized to further validate the nomogram.The optimal cut-off value for LAR in CAP patients admitted to ICU was 1.6 (the units of lactate and albumin were, respectively, 'mmol/L' and 'g/dL'). The ROC analysis showed that the discrimination abilities of LAR were superior to other indicators except Sequential Organ Failure Assessment score and Simplified acute physiology score (SAPSII), which had the same abilities. Age, mean arterial pressure, SpO2, heart rate, SAPSII score, neutrophil-to-lymphocyte ratio, and LAR were found to be independent predictors of poor overall survival in the training cohort by multivariate Cox regression analysis and were incorporated into the nomogram for in-hospital mortality as independent factors. The nomogram model, exhibiting medium discrimination, had a C-index of 0.746 (95% CI = 0.715-0.777) in the training cohort and 0.716 (95% CI = 0.667-0.765) in the validation cohort.LAR could predict in-hospital mortality of patients with CAP admitted to ICU independently as a readily accessible biomarker. The nomogram that included LAR with other independent factors performed well in predicting in-hospital mortality.