Objective:To explore the role and mechanism of nuclear factor erythroid 2-related factor 2 (NRF2) in lung injury in mice with Staphylococcus aureus-induced sepsis. Methods:A sepsis mouse model with Staphylococcus aureus infection was created using wild-type C57BL/6 male mice and NRF2 -/- male mice aged six to eight weeks. The mice were divided into four groups with five in each group. In WT control group and NRF2 -/- control group, the wild type mice and NRF2 -/- mice were intraperitoneally injected with 100 μL phosphate buffered saline (PBS) respectively. In WT model group and NRF2 -/- model group, the wild type mice and NRF2 -/- mice were intraperitoneally injected with 100 μL PBS containing Staphylococcus aureus (3×10 8 colony forming unit (CFU)/mL) respectively. The lung samples were taken under anesthesia six hours after injection, and hematoxylin and eosin staining was performed to observe tissuse lesions. The survival of the mice was evaluated. The protein concentrations and cell counts in the bronchoalveolar lavage fluid (BALF), the mRNA relative expressions of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in lung tissues, and the serum levels of myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) were compared among the four groups. Independent samples t test was used for statistical comparison. Results:After six days of observation, no mice died in WT control group and NRF2 -/- control group, three mice died in WT model group on day 3, and four mice died in NRF2 -/- model group on day 4. The pathological staining showed that macrophage infiltration and alveolar structure damage occurred in the lung tissuse of WT model group, and the damage were more significant in NRF2 -/- model group. The protein concentrations and cell counts in BALF of mice in WT control group were (342±23) μg/mL and (5.78±2.67)×10 5/mL, respectively, those in WT model group were (657±39) μg/mL and (10.78±5.57)×10 5/mL, respectively, those in NRF2 -/- control group were (312±45) μg/mL and (5.67±1.46)×10 5/mL, respectively, and those in NRF2 -/- model group were (957±85) μg/mL and (13.85±3.72)×10 5/mL, respectively. The protein concentrations and cell counts in WT model group were higher than those in WT control group ( t=6.56, P<0.001 and t=8.21, P<0.001, respectively), while lower than NRF2 -/- model group ( t=2.32, P=0.001 and t=3.11, P=0.002, respectively). The differences were all statistically significant. Compared with the WT model group, the mRNA relative expressions of TNF-α (4.345±1.131 vs 12.375±4.534), IL-1β (5.395±2.112 vs 6.865±2.185), IL-6 (2.964±0.945 vs 5.467±1.855) in the lung tissues of NRF2 -/- model group increased, and the serum levels of MPO (2.956±1.211 vs 4.745±1.945) and MDA (4.333±1.652 vs 8.234±3.734) increased, while the level of SOD (17.121±8.183 vs 11.967±8.122) decreased, with statistically differences ( t=1.77, 4.67, 2.99, 7.99, 10.45 and 8.45, respectively, all P<0.05). Conclusions:The absence of NRF2 gene can exacerbate the inflammatory response and oxidative stress in mice with Staphylococcus aureus-induced sepsis, leading to more severe lung tissue damage.

Objective:To explore the role and mechanism of nuclear factor erythroid 2-related factor 2 (NRF2) in lung injury in mice with Staphylococcus aureus-induced sepsis. Methods:A sepsis mouse model with Staphylococcus aureus infection was created using wild-type C57BL/6 male mice and NRF2 -/- male mice aged six to eight weeks. The mice were divided into four groups with five in each group. In WT control group and NRF2 -/- control group, the wild type mice and NRF2 -/- mice were intraperitoneally injected with 100 μL phosphate buffered saline (PBS) respectively. In WT model group and NRF2 -/- model group, the wild type mice and NRF2 -/- mice were intraperitoneally injected with 100 μL PBS containing Staphylococcus aureus (3×10 8 colony forming unit (CFU)/mL) respectively. The lung samples were taken under anesthesia six hours after injection, and hematoxylin and eosin staining was performed to observe tissuse lesions. The survival of the mice was evaluated. The protein concentrations and cell counts in the bronchoalveolar lavage fluid (BALF), the mRNA relative expressions of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) in lung tissues, and the serum levels of myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) were compared among the four groups. Independent samples t test was used for statistical comparison. Results:After six days of observation, no mice died in WT control group and NRF2 -/- control group, three mice died in WT model group on day 3, and four mice died in NRF2 -/- model group on day 4. The pathological staining showed that macrophage infiltration and alveolar structure damage occurred in the lung tissuse of WT model group, and the damage were more significant in NRF2 -/- model group. The protein concentrations and cell counts in BALF of mice in WT control group were (342±23) μg/mL and (5.78±2.67)×10 5/mL, respectively, those in WT model group were (657±39) μg/mL and (10.78±5.57)×10 5/mL, respectively, those in NRF2 -/- control group were (312±45) μg/mL and (5.67±1.46)×10 5/mL, respectively, and those in NRF2 -/- model group were (957±85) μg/mL and (13.85±3.72)×10 5/mL, respectively. The protein concentrations and cell counts in WT model group were higher than those in WT control group ( t=6.56, P<0.001 and t=8.21, P<0.001, respectively), while lower than NRF2 -/- model group ( t=2.32, P=0.001 and t=3.11, P=0.002, respectively). The differences were all statistically significant. Compared with the WT model group, the mRNA relative expressions of TNF-α (4.345±1.131 vs 12.375±4.534), IL-1β (5.395±2.112 vs 6.865±2.185), IL-6 (2.964±0.945 vs 5.467±1.855) in the lung tissues of NRF2 -/- model group increased, and the serum levels of MPO (2.956±1.211 vs 4.745±1.945) and MDA (4.333±1.652 vs 8.234±3.734) increased, while the level of SOD (17.121±8.183 vs 11.967±8.122) decreased, with statistically differences ( t=1.77, 4.67, 2.99, 7.99, 10.45 and 8.45, respectively, all P<0.05). Conclusions:The absence of NRF2 gene can exacerbate the inflammatory response and oxidative stress in mice with Staphylococcus aureus-induced sepsis, leading to more severe lung tissue damage.

Objective:To investigate the risk factors of acute lung injury (ALI) caused by Staphylococcus aureus infection, and to construct a risk warning model. Methods:Patients with Staphylococcus aureus infection confirmed by sputum or blood culture admitted to the Affiliated Hospital of Jiangnan University from January 1, 2020 to May 10, 2022 were enrolled and divided into ALI group and non-ALI group. The age, smoking status, C-reactive protein (CRP), procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), albumin, oxygenation index and other clinical data were compared between the two groups. Univariate analysis was performed by using independent sample t test and chi-square test. Binary logistic regression analysis was used to screen the independent risk factors of ALI caused by Staphylococcus aureus infection, and a risk warning model was constructed. The receiver operator characteristic (ROC) curve was used to evaluate the predictive ability of the model. Results:There were 96 cases of Staphylococcus aureus infection, including 68 cases (70.8%) in ALI group, of which 41 cases (60.3%) were positive in sputum culture and 27 cases (39.7%) were positive in blood culture. Compared with the non-ALI group, the proportion of patients aged ≥60 years in ALI group was lower (58.8%(40/68) vs 64.3%(18/28)), the proportion of smoking was higher (58.8%(40/68) vs 35.7%(10/28)), and the differences were both statistically significant ( χ2=0.76 and 0.03, respectively, both P<0.05). The levels of CRP, PCT and NLR in the ALI group were all higher than those in non-ALI group, while oxygenation index and albumin level were both lower, and the differences were all statistically significant ( t=-5.28, -3.46, -9.87, 12.83 and 3.08, respectively, all P<0.05). Binary logistic regression analysis showed that CRP (odds ratio ( OR)=1.973, 95% confidence interval (95% CI) 0.956 to 2.989), PCT ( OR=3.734, 95% CI 1.014 to 13.746), NLR ( OR=1.152, 95% CI 1.058 to 2.254) and albumin ( OR=1.527, 95% CI 1.110 to 2.102) were independent risk factors for ALI caused by Staphylococcus aureus infection. The areas under the ROC curve of CRP, PCT, NLR, albumin and the risk warning model constructed from the combination of four risk factors were 0.69, 0.81, 0.83, 0.78 and 0.93, respectively. The sensitivities were 65.14%, 89.91%, 84.40%, 56.88% and 98.17%, respectively. The specificities were 62.37%, 60.22%, 65.59%, 80.64% and 93.55%, respectively. The accuracy of the effectiveness test of the risk warning model was 84.97%. Conclusions:CRP, PCT, NLR and albumin are the independent risk factors for ALI caused by Staphylococcus aureus infection. The risk warning model based on the above factors has a good early warning effect on ALI caused by Staphylococcus aureus infection.