| Objective1.To analyze the risk factors of multi-drug resistant bacteria infection in the elderly with pulmonary infection,explore the predictive variables and establish a risk early-warning model of multidrug-resistant bacteria infection.2.To explore the risk factors related to the prognosis of multidrug-resistant bacteria in the elderly with pulmonary infection and to establish the prognostic prediction model of multidrug-resistant bacteria in the elderly with pulmonary infection.3.To study how to inhibit macrophage pyrotopia induced by Acinetobacter baumannii and explore a new treatment method for multidrug-resistant Acinetobacter baumannii.MethodsA total of 994 patients with pulmonary infection meeting the criteria were included in this retrospective cohort study.Data from Binhu Hospital of Hefei City and the First Affiliated Hospital of University of Science and Technology of China were selected as the multi-center external validation set.The remaining data(the Third Affiliated Hospital of Anhui Medical University,Anqing Municipal Hospital and Fuyang Hospital Affiliated to Anhui Medical University)were used as the training set((the ratio was about 3:7).In the first part,patients in the training set were divided into MDRB infection group and non-MDRB infection group according to the sputum culture isolation results.Lasso regression and Logistic multivariate analysis were used to study the risk factors of multi-drug resistant bacterial infection.The model was established by R4.2.1software and represented by Nomogram.ROC and calibration curves were used to evaluate the performance of the model internally(training set)and externally(validation set),and decision curve analysis(DCA)was used to evaluate the clinical application value of the model.In the second part,patients with multidrug-resistant bacteria infection in the infection training set(255 cases)were taken as individuals in the prognosis training set,and patients with multidrug-resistant bacteria infection in the infection verification set(100 cases)were taken as the prognosis verification set.According to the hospitalization time and outcome of patients with multidrug-resistant bacteria infection in the prognosis training set,Lasso univariate and COX regression analyses were performed to determine prognostic risk factors.The associated risk of each patient in the prognostic training set was scored according to prognostic independent risk factors,and patients were divided into low-risk group(<median)and high-risk group(>=median)according to the median risk score.Kaplan-Meier(K-M)survival curve was used to compare the survival of high-risk and low-risk groups.If the difference between the high-risk and low-risk groups was statistically significant,a prognostic prediction model was constructed based on independent prognostic factors and risk groups and verified.In the third part,macrophage RAW 264.7 was infected with multidrug-resistant Acinetobacter baumannii.Flow cytometry and western blotting were used to analyze the degree of apoptosis of RAW 264.7 cells after infection and the expression of key molecules GSDMD,Caspase-1,IL-18 and IL-1β.The effect of glycyrlic acid(GA)on the coke death degree of RAW 264.7 after infection was analyzed,and the expression degree of i NOS,a polarization marker,and JAK1/STAT1 pathway of RAW 264.7 after infection was analyzed by western blot.Results1.A total of 994 patients with pulmonary infection meeting the criteria were included,including 355 cases of multidrug-resistant bacteria infection and 589 cases of non-multidrug-resistant bacteria infection.A total of 355 patients were included in the prognosis study,and 66 died,with a mortality rate of 18.60%.By comparing the baseline demographics and characteristics of all patients in the training set and the verification set of infection and prognosis,there was no significant difference in general data between the two groups.2.Endotracheal intubation,antibiotic duration ≥2 weeks,combined with respiratory failure and cerebrovascular disease are independent risk factors for multidrug-resistant bacterial infection.Nomogram of an infection risk prediction model based on independent risk factors,The AUC values of the training set(internal verification)and the verification set(multi-center external verification)were 0.738 and 0.731,respectively,indicating that the model has good diagnostic ability.Hosmer-Lemeshow test(training set P=0.919,verification set P=0.152)indicates that the model has a good goodness of fit.The analysis of decision curve shows that the benefit of the model is reasonable.3.Respiratory failure,malnutrition,APACHEⅡscore >=20,Cr were independent prognostic factors of elderly patients with multidrug-resistant bacteria in the training concentration.Kaplan-Meier analysis showed that there was a statistically significant difference in survival time between high-risk group and low-risk group(P<0.001).The risk score of patients was inversely proportional to their survival,and a prognostic prediction model was constructed based on independent prognostic factors and risk groups.During internal and external verification,we found that the AUC value of the training set was 0.826,and that of the validation set was 0.805,suggesting that the diagnostic ability of the model was good.DCA curves suggest that Nomogram provides moderate net benefit in predicting the prognostic risk of MDRB infection,and calibration curves show good agreement between observed and predicted prognostic risks after multidrug-resistant infection.4.A.baumannii induced apoptosis and scorch death of macrophage RAW264.7 by activating caspase-1 and IL-1 β synthesis in vitro.Glycyrrhizic acid(GA)treatment significantly increased the survival rate of RAW264.7 treated by A.baumannii.At the same time,GA treatment can down-regulate the activation of pyroptosis related proteins GSDM,IL-1β,IL-18,NLRP3 and caspase-1 and 3 in A.baumannii-treated RAW264.7.In addition,GA can protect RAW264.7 from A.baumannii-induced pyroptosis and down-regulate the expression of i NOS,the M1 polarizing molecule in RAW264.7.Conclusion1.The infection rate of multidrug-resistant bacteria is high in the elderly with pulmonary infection.It is of great significance to actively correct respiratory failure,early off-line extubation,treat cerebrovascular diseases,strengthen rational use of antibiotics,and reduce the use time of antibiotics2.For elderly patients with multidrug-resistant bacteria in the lung infection,it is necessary to actively use the column chart for individual evaluation in the clinic,especially for patients with respiratory failure,malnutrition,APACHEⅡ score >=20 and high blood creatinine value,we should be alert to the possibility of poor prognosis,comprehensive consideration of various indicators,and develop the corresponding intervention measures.3.As a common anti-inflammatory drug in the clinic,glycyrrhizic acid(GA)can inhibite the inflammatory cascade reaction in macrophage infected with A.baumannii by suppressing pyroptosis and M1 polarization.This study showed that GA could be a good option for treatment of patients with pneumonia caused by A.baumannii in the future. |
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