Objective:To investigate the role of heme oxygenase-1(HO-1)regulating autophagy and its impact on the intracel-lular growth of Mycobacterium abscessus(M.abs).Methods:The standard strain of M.abs ATCC19977 was used to stimulate mouse RAW264.7 macrophages with a specified multiple of infection(MOI)for a specified time.Western blot analysis was performed to detect the expression levels of HO-1 protein and autophagy related proteins Atg5,LC3Ⅱ and p62.Macrophages were pretreated with HO-1 specific inducer CoPP and enzyme activity inhibitor SnPP for 12 h,and incubated with M.abs for 2 h.Amikacin removed extra-cellular bacteria and continued to culture until the specified time,and cell activity was detected by CCK-8 method.Western blot and LysoTracker Red were used to detect the regulatory relationship between HO-1 protein and autophagy related proteins.Bacterial survival and TNF-α secretion levels were detected by colony count and ELISA.Results:Compared with the control group,M.abs could induce increased expression of HO-1,Atg5,LC3Ⅱ and p62 proteins.Over-expression and inhibition of HO-1 were found to effectively regu-late the expressions of Atg5,LC3Ⅱ and p62 induced by M.abs.LysoTracker Red,colony count,and ELISA results demonstrated that SnPP promoted the increasement of intracellular lysosomes,significantly inhibited M.abs intracellular proliferation,and reduced TNF-α secretion.Conclusion:Inhibition of HO-1 can enhance the autophagy flow induced by M.abs and reduce the intracellular growth of M.abs,which provides scientific basis for the development of targeted drugs targeting HO-1.

OBJECTIVE To investigate the pathogens of pulmonary infection and their influencing factors in patients with initially treated pulmonary tuberculosis(PTB),and to analyze the diagnostic efficacy of systemic inflamma-tory response index(SIRI)for pulmonary infection.METHODS The clinical data of 459 patients with initially trea-ted PTB admitted to Changsha Central Hospital from Jan.to Dec.2023 were retrospectively analyzed,and they were divided into the combined group(n=90)and the non-combined group(n=369)according to the combina-tion of other pulmonary infections at the time of consultation.The pathogens of pulmonary infection,as well as the levels of monocytes(MN),neutrophils(NE),and lymphocytes(LYM),were analyzed,and the SIRI was calculated.The risk factors of pulmonary infection in initially treated PTB patients were explored by multivariate logistic regression analysis,and the diagnostic value of SIRI for pulmonary infection in initially treated PTB pa-tients was evaluated by receiver operating characteristic(ROC)curve.RESULTS The rate of pulmonary infection in 459 initially treated PTB patients was 19.61％(90/459),and a total of 103 pathogens were detected,of which 64 strains of gram-negative bacteria accounted for 62.14％,followed by 28 strains of gram-positive bacteria ac-counting for 27.18％,and 11 strains of fungi accounting for 10.68％,with Pseudomonas aeruginosa,Klebsiella pneumoniae and Staphylococcus aureus being predominant.Age(OR=1.908,95％CI:1.375-2.647),comor-bid diabetes(OR=2.073,95％CI:1.462-2.938),pulmonary cavities(OR=2.323,95％CI:1.588-3.398),delayed medical treatment(OR=2.024,95％CI:1.467-2.791)and elevated SIRI(OR=2.855,95％CI:1.851-4.402)were risk factors for pulmonary infection in initially treated PTB patients(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of SIRI for diagnosing pulmonary infection in initially treated PTB cases was 0.876(0.824-0.928),with a cut-off value of 4.96×109/L,a specificity of 85.91％,and a sen-sitivity of 86.67％.CONCLUSIONS The main pathogens in patients with initially treated PTB complicated with pulmonary infection are Pseudomonas aeruginosa and Klebsiella pneumoniae.Age,comorbid diabetes mellitus,pulmonary cavity,delayed medical treatment and elevated SIRI are all influencing factors for pulmonary infection in patients with initially treated PTB,and monitoring of SIRI can to some extent assist in diagnosis of whether pa-tients with initial treatment PTB are complicated with other pulmonary infections.

OBJECTIVE To investigate the pathogens of pulmonary infection and their influencing factors in patients with initially treated pulmonary tuberculosis(PTB),and to analyze the diagnostic efficacy of systemic inflamma-tory response index(SIRI)for pulmonary infection.METHODS The clinical data of 459 patients with initially trea-ted PTB admitted to Changsha Central Hospital from Jan.to Dec.2023 were retrospectively analyzed,and they were divided into the combined group(n=90)and the non-combined group(n=369)according to the combina-tion of other pulmonary infections at the time of consultation.The pathogens of pulmonary infection,as well as the levels of monocytes(MN),neutrophils(NE),and lymphocytes(LYM),were analyzed,and the SIRI was calculated.The risk factors of pulmonary infection in initially treated PTB patients were explored by multivariate logistic regression analysis,and the diagnostic value of SIRI for pulmonary infection in initially treated PTB pa-tients was evaluated by receiver operating characteristic(ROC)curve.RESULTS The rate of pulmonary infection in 459 initially treated PTB patients was 19.61％(90/459),and a total of 103 pathogens were detected,of which 64 strains of gram-negative bacteria accounted for 62.14％,followed by 28 strains of gram-positive bacteria ac-counting for 27.18％,and 11 strains of fungi accounting for 10.68％,with Pseudomonas aeruginosa,Klebsiella pneumoniae and Staphylococcus aureus being predominant.Age(OR=1.908,95％CI:1.375-2.647),comor-bid diabetes(OR=2.073,95％CI:1.462-2.938),pulmonary cavities(OR=2.323,95％CI:1.588-3.398),delayed medical treatment(OR=2.024,95％CI:1.467-2.791)and elevated SIRI(OR=2.855,95％CI:1.851-4.402)were risk factors for pulmonary infection in initially treated PTB patients(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of SIRI for diagnosing pulmonary infection in initially treated PTB cases was 0.876(0.824-0.928),with a cut-off value of 4.96×109/L,a specificity of 85.91％,and a sen-sitivity of 86.67％.CONCLUSIONS The main pathogens in patients with initially treated PTB complicated with pulmonary infection are Pseudomonas aeruginosa and Klebsiella pneumoniae.Age,comorbid diabetes mellitus,pulmonary cavity,delayed medical treatment and elevated SIRI are all influencing factors for pulmonary infection in patients with initially treated PTB,and monitoring of SIRI can to some extent assist in diagnosis of whether pa-tients with initial treatment PTB are complicated with other pulmonary infections.

Objective:To investigate the role of heme oxygenase-1(HO-1)regulating autophagy and its impact on the intracel-lular growth of Mycobacterium abscessus(M.abs).Methods:The standard strain of M.abs ATCC19977 was used to stimulate mouse RAW264.7 macrophages with a specified multiple of infection(MOI)for a specified time.Western blot analysis was performed to detect the expression levels of HO-1 protein and autophagy related proteins Atg5,LC3Ⅱ and p62.Macrophages were pretreated with HO-1 specific inducer CoPP and enzyme activity inhibitor SnPP for 12 h,and incubated with M.abs for 2 h.Amikacin removed extra-cellular bacteria and continued to culture until the specified time,and cell activity was detected by CCK-8 method.Western blot and LysoTracker Red were used to detect the regulatory relationship between HO-1 protein and autophagy related proteins.Bacterial survival and TNF-α secretion levels were detected by colony count and ELISA.Results:Compared with the control group,M.abs could induce increased expression of HO-1,Atg5,LC3Ⅱ and p62 proteins.Over-expression and inhibition of HO-1 were found to effectively regu-late the expressions of Atg5,LC3Ⅱ and p62 induced by M.abs.LysoTracker Red,colony count,and ELISA results demonstrated that SnPP promoted the increasement of intracellular lysosomes,significantly inhibited M.abs intracellular proliferation,and reduced TNF-α secretion.Conclusion:Inhibition of HO-1 can enhance the autophagy flow induced by M.abs and reduce the intracellular growth of M.abs,which provides scientific basis for the development of targeted drugs targeting HO-1.