AIM:To explore a more accurate and reliable pathological model of the chronic bronchitis , which has improved from the former single-factor modeling method of the disease .METHODS:The mice in complex group were treated with lipopolysaccharide ( LPS) by tracheal injection on the 1st day and nasal drops on the 14th day, and from the 2nd day to 30th day, the animals were given passive smoking and sulfur dioxide ( SO2 ) inhalation ( except on the 14th day).The mice in SO2 group were exposed to SO2 2 min per day, while in smoking group, the mice were exposed to smoke for about 1 h per day (4 cigarettes each time until one pack of cigarettes were burning up ).In LPS group, the mice had tracheal injection of LPS on the 1st day and nasal drops of LPS on the 14th day and 30th day.Every modeling process las-ted for 30 days.After modeling, the improvement of chronic bronchitis model was evaluated by testing the general condi-tions of the mice , analyzing leukocyte count in bronchoalveolar lavage fluid ( BALF ) , and observing the morphological changes of the bronchial and lung tissues .RESULTS:After modeling, the mice in every model group experienced symp-toms including wet nose, cough, dry and lusterless hair, arched back and curled-up body, showing inactive, and slow down in response .The mice in complex group gained the lowest weight compared to other groups .From each model group , the inflammatory cells infiltrated evidently around the bronchial walls , especially in the bronchial cavity , and the mucilage secretion in the airway increased .The total number of leukocytes in BALF increased significantly in complex group .The in-flammatory cell count in the lung tissue indicated that the mice in complex group had significantly higher levels of inflamma -tory cell infiltration.Besides, the comparison between smoke group and LPS group was statistically significant .CONCLU-SION:Smoking, SO2 inhalation and LPS injection induce bronchial lung disease in mice , and the complex chronic bron-chitis mouse model is a better model with the pathological changes of bronchus , lung tissue and BALF , and pathogenesis of chronic bronchitis .

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.