RESUMO
Alzheimer's disease (AD) is a common and serious form of elderly dementia, but early detection and treatment of mild cognitive impairment can help slow down the progression of dementia. Recent studies have shown that there is a relationship between overall cognitive function and motor function and gait abnormalities. We recruited 302 cases from the Rehabilitation Hospital Affiliated to National Rehabilitation Aids Research Center and included 193 of them according to the screening criteria, including 137 patients with MCI and 56 healthy controls (HC). The gait parameters of the participants were collected during performing single-task (free walking) and dual-task (counting backwards from 100) using a wearable device. By taking gait parameters such as gait cycle, kinematics parameters, time-space parameters as the focus of the study, using recursive feature elimination (RFE) to select important features, and taking the subject's MoCA score as the response variable, a machine learning model based on quantitative evaluation of cognitive level of gait features was established. The results showed that temporal and spatial parameters of toe-off and heel strike had important clinical significance as markers to evaluate cognitive level, indicating important clinical application value in preventing or delaying the occurrence of AD in the future.
Assuntos
Disfunção Cognitiva , Marcha , Aprendizado de Máquina , Humanos , Disfunção Cognitiva/diagnóstico , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/diagnóstico , Fenômenos Biomecânicos , Análise da Marcha/métodos , Masculino , Idoso , Feminino , Cognição , Caminhada , Dispositivos Eletrônicos VestíveisRESUMO
Polymyxin E sulfate, a hydrophilic drug with high tissue toxicity, was formulated into a stable liposome to reduce its in vivo toxicity. The liposome was prepared using both a reverse phase evaporation and freezing-thawing method. The encapsulation efficiency was determined by high-performance liquid chromatography. The influence of the freezing-thawing process on the liposome's stability was evaluated using a centrifugation test. The dialysis method was employed to investigate the in vitro release profile of the drug-loaded liposome. The toxicity of the polymyxin E sulfate-loaded liposome was compared with the polymyxin E sulfate solution in Kunming mice by intravenous administration. A freeze-drying (lyophilization) technique was utilized to prepare the proliposome. A cryoprotectant formulation was optimized by the evaluation of the particle diameter and encapsulation efficiency of the redispersed proliposomes, while the influence of the concentration and method of the addition of the cryoprotectant on the protective effect was investigated as well. It was found that the stability and encapsulation efficiency of the liposome could be improved by the freezing-thawing process. The delayed drug release profile of the drug-loaded liposome was observed in vitro, and a comparison with the polymyxin E sulfate solution revealed that the in vivo toxicity of the polymyxin E sulfate-loaded liposome was significantly reduced. Sucrose and mannitol at a weight ratio of 1:0.8:0.6 (phospholipids:mannitol:sucrose) added inside displayed the greatest protective effect on the polymyxin E sulfate liposome during freeze-drying. The rehydrated proliposomes with optimized cryoprotectants produced an acceptable particle diameter (204.1 nm) and a satisfactory encapsulation efficiency percentage (51.48%), thus demonstrating a practical method for preparation of polymyxin E sulfate-loaded proliposome. A combination of the reverse phase evaporation and freezing-thawing methods was found to be suitable for the preparation of hydrophilic drug-loaded liposome. The toxicity of polymyxin E sulfate was reduced by its encapsulation in a liposome, thus constituting a promising drug delivery system suitable for further development. The method of addition had an insignificant effect on the appearance of the product but obviously influenced the particle diameter and encapsulation efficiency. The inside addition method produced a greater protective effect in this study.