Parecoxib mitigates lung ischemia-reperfusion injury in rats by reducing oxidative stress and inflammation and up-regulating HO-1 expression

ABSTRACT Purpose: To investigate the protective effect of parecoxib against lung ischemia-reperfusion injury (LIRI) in rats and the mechanism. Methods: Thirty rats were divided into sham-operated, LIRI and LIRI+parecoxib groups. LIRI model (ischemia for 60 min, followed by reperfusion for 120 min) was constructed in LIRI and LIRI+parecoxib groups. In LIRI+parecoxib group, 10 mg/kg parecoxib was given via femoral vein 15 min before ischemia beginning. At the end of the reperfusion, blood gas analysis, lung wet to dry mass ratio measurement, lung tissue biochemical determination and heme oxygenase-1 (HO-1) protein expression determination were performed. Results: Compared with LIRI group, in LIRI+parecoxib group the oxygenation index was significantly increased, the alveolar-arterial oxygen partial pressure difference was significantly decreased, the lung wet to dry mass ratio was significantly decreased, the lung tissue malondialdehyde content was significantly decreased, the lung tissue superoxide dismutase and myeloperoxidase activities were significantly increased, the lung tissue tumor necrosis factor α and interleukin 1β levels were significantly decreased, and the lung tissue HO-1 protein expression level was significantly increased (all P < 0.05). Conclusions: Parecoxib pretreatment can mitigate the LIRI in rats by reducing oxidative stress, inhibiting inflammatory response and up-regulating HO-1 expression in lung tissue.

Correlation between Ki-67 and PD-L1 expression in non-small cell lung cancer tissues and its effect on patients’prognosis / 中国肿瘤生物治疗杂志

@# Objective:To investigate the relationship between Ki-67 and PD-L1 in patients with non-small cell lung cancer (NSCLC) and their effects on prognosis. Methods: A total of 401patients, who were pathologically diagnosed as NSCLC in Changhai Hospital from January 2012 toAugust 2018, were enrolled as study subjects; and the patients were immunohistochemically tested for PD-L1 and Ki-67. The clinical and pathological data were collected, and the follow-up was performed regularly. The correlation between Ki-67 and PD-L1 and their effects on postoperative DFS and post-chemotherapy PFS were statistically analyzed. Results: Positive rates of PD-L1 and Ki-67 in NSCLC tissues were 37.9% (152/401) and 96.3% (386/401), respectively. Univariate analysis showed that Ki-67 was an influencing factor for PD-L1 expression (OR=0.33, 95%CI=0.28-0.39, P<0.0001); Curve Fitting analysis showed a positive correlation between Ki-67 and PD-L1; threshold effect analysis, segmentation multivariate logistic and ROC curve analysis showed 14% is a relatively suitable threshold for Ki-67 to be combined with PD-L1. Kaplan-Meier analysis showed that patients in Ki-67 high expression group had a significantly shorter post-operative DFS than those in Ki-67 low expression group ([21.88±11.25] vs [41.22±16.25]m, P< 0.0001), patients in PD-L1 positive group had a significantly shorter DFS than those in PD-L1 negative group ([24.75±14.59] vs [38.27± 16.75]m, P<0.0001)], and patients in Ki-67 high/PD-L1 positive group had the shortest DFS as compared to the other three groups ([20.57±11.33] vs [24.11±10.79], [36.00±16.79], [42.91±15.77]m, P<0.0001).As for post-chemotherapy PFS, patients in Ki-67 high expression group was significantly longer than those in Ki-67 low expression group [(7.70±3.01) vs (5.80±2.99)m, P=0.016), but there was no significant difference between PD-L1 positive group and PD-L1 negative group [(7.04±3.21) vs (6.33±3.06)m, P=0.22); for combined evaluation with Ki-67 and PD-L1, the PFS of two Ki-67 high expression groups was significantly longer than the other two Ki-67 low expression groups [(7.74±3.25) vs (7.43±2.38) vs (4.91±1.97) vs (6.02±3.19)m, P=0.041). Conclusion: Ki-67 is positively correlated with PD-L1 in NSCLC patients, and Ki-67 14% is a suitable threshold for combined use with PD-L1. Both Ki-67 and PD-L1 are predictors of poor prognosis. The combination of the two has an "additive effect" on the prediction of poor prognosis, and patients with high Ki-67 expression are more sensitive to chemotherapy.