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AIM:To investigate the effect of Tongsai granules(TSG)on epithelial barrier dysfunction in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and the underlying mechanism.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into control group,model group,TSG group,and moxifloxacin(MXF)+salbutamol(STL)group.Rat COPD model was established over 8 weeks.On day 3 of week 9,the rats with COPD were intratracheally administered Klebsiella pneumoniae to establish the AECOPD model.On days 1 to 2 and 4 to 7 in week 9,saline was administered via oral gavage to the rats in control and model groups,and the rats in TSG and MXF+ STL groups were treated daily with TSG and MXF+STL by gavage,respectively.Peak expiratory flow(PEF),histopatho-logical changes,and the expression levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α),matrix me-talloproteinase 2(MMP2),MMP9,zonula occludens-1(ZO-1),E-cadherin(E-Cad)and occludin(OCC)were deter-mined.Moreover,human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract(CSE)and treated with different TSG fractions,and the protein levels of ZO-1,E-Cad,OCC,epidermal growth factor receptor(EGFR),phosphorylated EGFR(p-EGFR),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were determined.RESULTS:Treatment with TSG significantly reduced bronchial wall thickness,mean linear intercept,and the levels of IL-1β,IL-6,TNF-α,MMP2 and MMP9(P＜0.05 or P＜0.01),significantly increased mean alveolar number and PEF(P＜0.01),and up-regulated the ZO-1,E-Cad and OCC protein levels(P＜0.01)in the lungs of AECOPD rats.Treatment with TSG2,the second TSG fraction,increased the protein levels of ZO-1,E-Cad and OCC in a dose-dependent manner in CSE-exposed BEAS-2B cells(P＜0.05 or P＜0.01).Network pharmacology analysis of 328 targets of the com-pounds in TSG2 and 3 864 genes related to AECOPD suggested that TSG2 relieved AECOPD likely through the regulation of ERBB2,ERK,EGFR,IL and WNT signaling pathways.Treatment with TSG2 also inhibited CSE-induced increases in p-EGFR and p-ERK levels in BEAS-2B cells(P＜0.05 or P＜0.01).CONCLUSION:Treatment with TSG could maintain airway epithelial barrier function in AECOPD rats,likely through the inhibition of EGFR/ERK signaling pathway.
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Objective@#To explore the relationship between the level of mental stimulation and the suicide attempts of rural residents in Shandong Province.@*Methods@#A 1:1 matched case-control study was designed to collect 1 200 cases from a survey of three suicide attempts in rural areas of Shandong Province. Controls were selected according to the following matched factors: age difference within 3 years, same gender, same village or neighboring village, no blood relationship, no suicide history. The basic characteristics of all subjects were collected through the questionnaire, and the level of mental stimulation of life events was measured. Multivariate conditional logistic regression model was used to analyze the relationship between the level of mental stimulation of life events and suicide attempts.@*Results@#The mean age of the case group and the control group was both (36.6±0.3) years old, and 35.8% (430/1 200) were males in each group. The low-medium level of mental stimulation of negative life events in the case group was 16.7% (200/1 200) and 61.7% (740/1 200), respectively, which was higher than that in the control group, about 2.5% (30/1 200) and 29.3% (352/1 200) (all P values <0.05), respectively. A total of 11.1% (133/1 200) of the case group had positive life events, which was lower than that of the control group [16.8% (201/1 200)] (all P values<0.05). Multivariate logistic regression model analysis showed that after the adjustment of gender, age, place of residence, education level, marital status, occupation, family income, somatic disease, mental disorders, family history of suicide, and opposite life events, the low-medium and high level of mental stimulation of negative life events were risk factors for suicide attempts, with OR (95%CI) as 5.88 (4.53-7.64) and 13.94 (8.15-23.86), respectively. Mental stimulation of positive life events was protective factor of suicide attempts, with OR (95%CI) as 0.58 (0.41-0.82).@*Conclusion@#Mental stimulation of negative and positive life events were risk and protective factors for suicide attempts.