RESUMEN
Background: Carbapenems and ß-lactam and ß-lactamase inhibitors (BLBLIs) have been used empirically in nosocomial pneumonia, but their efficacy and safety are controversial. Objective: We carried out a systematic review with meta-analysis to evaluate the efficacy and safety of carbapenems versus BLBLIs against nosocomial pneumonia. Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI, Wangfang, VIP and Sinomed were searched systematically through April 29, 2023 for clinical trials comparing carbapenems with BLBLIs for treatment of nosocomial pneumonia. Random-effects models were used to evaluate the impact of treatment on the risk ratio (RR) of all-cause mortality, clinical response, microbiologic response, resistance by Pseudomonas aeruginosa, adverse effects (AEs), and serious adverse effects. The quality of the evidence was assessed with the Cochrane risk of bias tool. The review was registerted in the INPLASY (INPLASY202340113). Results: Seven randomized controlled trials containing 3306 patients met our inclusion criteria Our meta-analysis showed no significant difference in all-cause mortality (RR = 0.88, 95% confidence interval [CI] = 0.75-1.03, I2 = 0%) or clinical cure (1.02, 0.96-1.09, 30%) or clinical failure (1.19, 0.97-1.47, 0%) or microbiologic clinical cure (0.98, 0.89-1.06, 40%) or Pseudomonas aeruginosa resistance (RR 2.43, CI 0.86-6.81, 49%, P = 0.09) or adverse events (0.98, 0.93-1.02, 0%) between carbapenems groups versus BLBLIs groups, but a significant difference was found for severe adverse events (RR 0.83, CI 0.73-0.94, 0%). Conclusion: Differences in the prevalence of mortality, clinical cure, or clinical failure were not observed between carbapenems groups versus BLBLIs groups in terms of nosocomial pneumonia. The use of carbapenems was linked to a tendency towards the emergence of P. aeruginosa resistance, however, no statistically significant difference was observed.
RESUMEN
Urotensin II (UII), a somatostatin-like cyclic peptide, was originally isolated from the fish urophysis. Our previous study showed that UII stimulates the proliferation of A549 lung adenocarcinoma cells and promotes tumor growth in a nude mouse xenograft model, suggesting that UII may contribute to the pathogenesis of lung adenocarcinoma. In this study, the underlying mechanism for UII to promote lung adenocarcinoma growth was explored by observing the effect of UII on the tumor inflammatory microenvironment in tumor-bearing nude mice. Immunohistochemical analysis showed that UII promoted the infiltration of CD68(+) tumor-associated macrophages (TAMs) in the tumor micro-environment. Enzyme-linked immunosorbent assay (ELISA) demonstrated that UII promoted the release of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9). Western blot analysis showed that UII promoted the activation of nuclear factor-κB (NF-κB). These findings suggest that the enhanced levels of IL-6, TNF-α and MMP-9 in the tumor microenvironment, which likely resulted from increased activation of NF-κB induced by UII, may be one of the important mechanisms by which UII promotes lung adenocarcinoma growth. These findings imply that antagonists of UII or urotensin II-receptor (UT-R) have potential for the prevention and treatment of lung adenocarcinoma.
