Background Explore markers to predict the clinical outcomes of checkpoint inhibitors have high unmet needs. The following study investigates whether hematologic parameter such as systemic immune‐inflammation index (SII), neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) is associated with nivolumab efficacy in advanced non‐small‐cell lung cancer (NSCLC). Methods Advanced/metastatic NSCLC patients treated with nivolumab monotherapy for second‐line or further‐line treatment at Jilin Cancer Hospital between March 2016 and July 2018 were enrolled in this retrospective study. The optimal cutoff values of SII, NLR, and PLR for predicting efficacy and prognosis were determined according to receiver operating characteristic (ROC) curve and the areas under the ROC curve. Progression‐free survival (PFS) and overall survival (OS) were calculated and compared using Kaplan‐Meier method and log‐rank test. Prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression (PHR) analyses. Results A total of 44 patients with advanced NSCLC were included; the median age was 60 (range: 43‐74). The optimal cutoff value of SII/NLR/PLR predicted PFS and OS was 603.5, 3.07, and 144. Low SII, NLR, and PLR were associated with longer PFS (HR for SII = 0.34, 95%CI 0.15‐0.76, P = 0.006; HR for NLR = 0.46, 95%CI 0.22‐0.99, P = 0.048; HR for PLR = 0.39, 95%CI 0.17‐0.94, P = 0.025) and OS (HR for SII = 0.16, 95%CI 0.05‐0.51, P = 0.005; HR for NLR = 0.20, 95%CI 0.06‐0.62, P = 0.002; HR for PLR = 0.20, 95%CI 0.06‐0.73, P = 0.008). NLR ≤ 3.07, PLR ≤ 144, SII ≤ 603.5 were independently associated with longer PFS and OS. Conclusion The SII, NLR, and PLR are promising prognostic predictor for patients with metastatic NSCLC patients.

The poor viability of transplanted stem cells hampers their therapeutic efficacy for treatment of myocardial infarction. The aim of this study was to investigate whether rosuvastatin improved survival of adipose-derived mesenchymal stem cells (AD-MSCs) after transplantation into infarcted hearts. AD-MSCs isolated from Tg(Fluc-egfp) mice which constitutively express both firefly luciferase (Fluc) and enhanced green fluorescent protein were transplanted into infarcted hearts with or without rosuvastatin administration. Longitudinal in vivo bioluminescence imaging and histological staining revealed that rosuvastatin enhanced the survival of engrafted AD-MSCs. Furthermore, combined therapy of AD-MSC and rosuvastatin reduced fibrosis, decreased cardiomyocyte apoptosis, and preserved heart function. AD-MSCs were then subjected to hypoxia and serum deprivation injury in vitro to mimic the ischemic environment. Rosuvastatin (10(-6) mmol/L) enhanced the viability and paracrine effect of AD-MSCs, and decreased their apoptotic rate. Western blotting revealed that rosuvastatin supplementation increased Akt and ERK phosphorylation, which resulted in FoxO3a phosphorylation and nuclear export. In addition, rosuvastatin administration decreased the pro-apoptotic proteins Bim and Bax, and increased the anti-apoptotic proteins Bcl-xL and Bcl-2. Furthermore, these effects were abolished by PI3K inhibitor LY294002 and MEK1/2 inhibitor U0126. This study demonstrates that rosuvastatin may improve the survival of engrafted AD-MSCs at least in part through the PI3K/Akt and MEK/ERK1/2 signaling pathways. Combination therapy with rosuvastatin and AD-MSCs has a synergetic effect on improving myocardial function after infarction.

No abstract