Acute lung injury (ALI) is the leading cause of morbidity and mortality in critically ill patients. Neutrophil extracellular traps (NETs) have been well documented in the ALI model of bacterial infection. In the present study, we demonstrated that poly I:C could induce pulmonary NETs. Upon poly I:C intratracheal inoculation, neutrophil infiltration in the bronchoalveolar lavage fluid (BALF) was significantly increased. Furthermore, the inflammatory cytokines IL-1β, IL-6, and TNF-α in the lung were also significantly elevated. Neutrophil depletion abolished NETs and decreased both neutrophil infiltration and IL-1β in the lung. As expected, DNase I, an inhibitor of MPO and NADPH, decreased pulmonary inflammation and NETs. Blocking of the poly I:C receptor TLR3 reduced lung inflammation and NETs. The MAPK kinase inhibitor p38 diminished the formation of NETs and restored the expression of the tight junction protein claudin-5 in the mouse lung when challenged with poly I:C. In summary, poly I:C induced the formation of pulmonary NETs and ALI, which may be associated with the activation of p38 MAPK and the decreased expression of claudin-5.

To investigate the correlation between carbapenem consumption and rates of antimicrobial resistance in Acinetobacter baumannii, carbapenem consumption was expressed as defined daily dose based on the World Health Organization (WHO) anatomical therapeutic chemical classification index. Clinical isolates from 2001-2009 were collected and analyzed using WHONET 5.4 software. Results show that the consumption of imipenem/cilastatin, meropenem, and total carbapenem is significantly correlated with imipenem resistance in A baumannii (r = 0.818, P = .007; r = 0.817, P = .007; r = 0.827, P = .006). Furthermore, total carbapenem consumption is significantly correlated with meropenem resistance in A baumannii (r = 0.900, P = .037). In addition, consumption of imipenem/cilastatin, meropenem, and total carbapenem is associated with A baumannii resistance to piperacillin-tazobactam, ceftazidime, cefepime, amikacin, and levofloxacin. These drugs are mainly β-lactams, aminoglycosides, and fluoroquinolones. The imipenem and meropenem resistance rates are significantly correlated with resistance rates to numerous antimicrobial drugs (eg, β-lactams, aminoglycosides, and fluoroquinolones) in A baumannii. Therefore, increased consumption of carbapenem may contribute to the development of resistance in A baumannii to imipenem, meropenem, and other antimicrobial drugs. Cross-resistance possibly occurs among imipenem/cilastatin and meropenem, as well as with β-lactams, aminoglycosides, and fluoroquinolones.

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Midkine (MK) is a heparin-binding growth factor overexpressed in various human cancers. In the current study, a positive correlation was observed between MK expression and MICA/B serum levels of gastric cancer patients. In addition, MK transfection significantly increased MICA/B expression in gastric cancer cells. The soluble MICA/B expression was also elevated. Furthermore, MK transfection inhibited CD107a and Granzyme B expression, thereby suppressing the natural killer (NK) cell cytotoxicity in vitro. The phosphorylation of p38 MAPK and its promotion of CHOP expression were also observed after MK treatment and transfection. CHOP was indirectly bound to the MICA/B promoter region by interacting with AP-1, leading to MICA/B transcription. Overall, the current study shows that MK expression in tumor cells indirectly suppresses NK cytotoxicity by inducing MICA/B expression and suppressing NKG2D expression.