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Hydrogen sulfide modulates acute lung injury in sepsis by inhibiting NLRP3 inflammasome activation in mice

Objective: To investigate the effects and mechanisms of the hydrogen sulfide donor GYY4137 on acute lung injury in sepsis. Methods: An acute lung injury model was established using the method of cecal ligation and puncture(CLP). Mice received an intraperitoneal injection of GYY4137 (50 mg/kg) or saline 30 minutes after surgery. C57BL/6J mice were divided into four groups: the sham operation group (Sham), the sham operation with GYY4137 group (GYY4137), the sepsis group (CLP), and the sepsis with GYY4137 group (CLP+GYY4137). Respiratory parameters (minute ventilation volume and expiratory flow 50) were measured using a whole-body plethysmography system. Lung tissue was evaluated by hematoxylin and eosin (H&E) staining, and inflammatory cells were identified by immunofluorescence. mRNA expression of inflammatory factors (interleukin-1β, interleukin-6) and adhesion molecules (vascular endothelial cadherin, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1) were quantified by real-time quantitative polymerase chain reaction (RT-PCR). Levels of NLRP3, Pro-IL-1β, IL-1β, and the cyclic guanosine monophosphate synthase (cGAS)/stimulator of interferon genes (Sting)/NF-κB signaling proteins were analyzed by Western blotting. In vitro, murine pulmonary microvascular endothelial cells were cultured and exposed to lipopolysaccharide (LPS, 1 μg/ml) and GYY4137 (25 μmol/L) to simulate sepsis-induced damage and to study the mechanism of hydrogen sulfide action. Levels of inflammatory factors and adhesion molecules in cells were quantified by RT-PCR. Data were analyzed for normal distribution using Shapiro-Wilk test, then variance homogeneity by Brown-Forsythe test. P-value<0.05 was set as statistical significance for all analyses. Results: (1) MV and EF50 values were significantly lower in the CLP group [(36.32±3.91)ml/min and (1.43±0.26)ml/s, respectively] compared to the Sham group [(50.14±6.07)ml/min and (2.70±0.46)ml/s, respectively]. These parameters were higher in the CLP+GYY4137 group [(45.83±2.33)ml/min and (2.02±0.16)ml/s, respectively] compared to the CLP group (P<0.05). (2) Severe lung tissue damage, alveolar collapse, increased septal thickening and exudation were observed in the CLP group and significantly reduced in the CLP+GYY4137 group (P<0.05). (3) Infiltration of inflammatory cells and mRNA levels of inflammatory factors and adhesion molecules were increased in the CLP group compared to the Sham group (P<0.05), and decreased in the CLP+GYY4137 group compared to the CLP group (P<0.05). (4) Protein levels of NLRP3, Pro-IL-1β, IL-1β, cGAS, Sting, and NF-κB were higher in the CLP group compared to the Sham group (P<0.05) and were reduced in the CLP+GYY4137 group compared to the CLP group (P<0.05). (5) LPS induced higher levels of inflammatory factors and adhesion molecules in pulmonary endothelial cells compared to the control, which were reduced in cells co-treated with GYY4137 and LPS (P<0.05). Conclusion: The hydrogen sulfide donor GYY4137 effectively modulates acute lung injury in septic mice by inhibiting NLRP3 inflammasome activation via the cGAS/Sting/NF-κB signaling pathway.

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Differential Diagnosis of Foot Drop: A Case Report

Differential diagnoses of ankle dorsiflexion weakness or foot drop are numerous and may include common fibular mononeuropathy, L5 and/or L4 nerve root lesion, partial sciatic neuropathy, acquired or hereditary peripheral polyneuropathy, central nervous system pathology, cervical or thoracic myelopathy and motor neuron disease. This case details the subjective and objective clinical exam, electrophysiological testing and interventions for a 54-year-old female with a referring diagnosis of a right foot drop deformity. The clinical exam identified distal, bilateral lower extremity (BLE) weakness and necessitated further evaluation of bilateral upper extremities (BUE) and cranial nerves. Electrophysiological testing, including nerve conduction studies (NCS) and needle electromyography (EMG), demonstrated findings consistent with motor neuron disease (MND) in all muscles tested in BUE, BLE, bilateral low lumbar paravertebral muscles and right tongue. A neurologist confirmed the presence of MND and determined this disease process was most likely amyotrophic lateral sclerosis. The patient was referred to the Neuromuscular Disease Clinic at a university hospital for further evaluation. Two months following the electrophysiological testing, the patient reported worsening weakness in BLE that had caused her to fall several times. She denied progression of BUE weakness or development of bulbar symptoms but relied on family members for assistance with some activities of daily living.

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A Comprehensive Proposal for Driver Licensing Reform in Ecuador

Ecuador faces a critical road safety challenge, characterised by high crash rates and concerning driver behaviours. The existing driver education and licensing processes have proven inadequate, underscoring an urgent need for comprehensive reform. This study proposes a Driver Learning System (DLS) for Ecuador, specifically designed to tackle these issues. Central to the DLS is the implementation of a three-stage Graduated Driver Licensing (GDL) system, which promotes progressive skill development and low-risk driving among novice drivers. The proposal also includes a thorough revision of driver education curricula, emphasising risk awareness, technological integration, and lifelong learning across all licence categories. The development of the GDL system was informed by an analysis of local crash statistics and driver behaviour studies, identifying critical areas for reform. Despite the potential of the DLS to significantly reduce traffic crashes in Ecuador, challenges such as stakeholder resistance and the need for funding for infrastructure improvements remain. Addressing these obstacles will be essential for the successful implementation of the DLS. The GDL, supplemented by a robust public awareness campaign, represents a promising path toward transforming the driving culture and enhancing road safety in Ecuador.

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