Transforming growth factor-ß1 attenuates inflammation and lung injury with regulating immune function in ventilator-induced lung injury mice.

Ventilator-induced lung injury (VILI) is a lung injury induced or aggravated by mechanical ventilation. Transforming growth factor (TGF)-ß1 is a cytokine that mediates immune function, enabling inflammatory attenuation and tissue repair. Here, we hypothesized that it plays an important role in the attenuation of VILI and inflammation. Ventilation with high tidal volume was performed on C57BL/6 mice to establish a VILI model. After 4 h of ventilation, mice were sacrificed (end of ventilation [EOV]) or extubated for resuscitation at 4 h (post-ventilation 4 h [PV4h]), 8 h (PV8h) and 24 h post-ventilation (PV1d). Recombinant mouse TGF-ß1 (rTGF-ß1) and the neutralization antibody of TGF-ß1 (nTAb) were used in vivo to examine the effect of TGF-ß1 on immune function and inflammatory attenuation in VILI mice. Lung injury was exacerbated at the same trend as the interleukin (IL)-1ß level, peaking at PV1d, whereas IL-6 and tumor necrosis factor (TNF)-α levels gradually reduced. Most active phagosomes, swollen round mitochondria, and cavitating lamellar bodies were observed at PV4h. The CD4+ T cells were significantly increased from PV4h to PV1d, and the CD8a + T cells were higher in the PV4h and PV1d groups; furthermore, the mice in the PV8h group showed highest proportion of CD4+CD8a+ T cells and CD4+/CD8a+ ratio. CD19 + and CD5 + CD19 + B cells in VILI mice began to increase at PV1d. The pulmonary expression of latent and monomer TGF-ß1 increased at PV4h and PV8h. Treatment of rTGF-ß1 only induced high expression of latent and monomer TGF-ß1 at EOV to decrease pulmonary levels of IL-1ß, IL-6, and TNF-α; however, lung injury attenuated from EOV to PV1d. TGF-ß1 induced the delayed elevation of CD4+/CD8a+ T cells ratio and activation of pulmonary CD4+CD8a+ double-positive T cells under certain conditions. Elastic fibers and celluloses, although relatively less proteoglycan, were observed with the overexpression of TGF-ß1 at PV4h and PV8h. In conclusion, TGF-ß1 attenuates the inflammatory response and lung injury of VILI via immune function regulation.

Effects of dexmedetomidine versus midazolam for premedication in paediatric anaesthesia with sevoflurane: A meta-analysis.

Background Dexmedetomidine (DEX), an α2-adrenergic receptor agonist, produces ideal sedation and early postoperative recovery for premedication in paediatric surgery, reducing preoperative anxiety and facilitating smooth induction of anaesthesia. We performed a meta-analysis to compare the effects of DEX and midazolam (MDZ) in paediatric anaesthesia with sevoflurane. Methods PubMed, Ovid, Web of Science, and Public Health Management Corporation were searched through December 2016 for randomized controlled trials (RCTs) that compared DEX and MDZ in children undergoing sevoflurane anaesthesia. The risk ratio (RR) with 95% incidence interval (95%CI) was used for dichotomous variables. Results Twelve RCTs involving 422 patients in the DEX group and 448 patients in the MDZ group were included. Patients in the DEX group had a significantly lower incidence of unsatisfactory sedation (RR [95%CI] = 0.71 [0.57-0.89]), unsatisfactory parental separation (RR [95%CI] = 0.56 [0.35-0.87]), and rescue analgesia (RR [95%CI] = 0.52 [0.35-0.77]) than patients in the MDZ group. However, both groups had a similar incidence of unsatisfactory mask acceptance, emergence agitation, and postoperative nausea and vomiting. Conclusion Compared with MDZ, DEX is beneficial in paediatric anaesthesia with sevoflurane because of its lower incidence of unsatisfactory sedation, parental separation, and rescue analgesia.