BackgroundWe aimed to explore whether monocyte to lymphocyte ratio (MLR) provides predictive value of the lesion severity in patients with coronary artery disease (CAD).MethodsFive hundred forty-three patients undergoing coronary angiography were analyzed in this retrospective study. Patients with coronary stenosis were divided into three groups on the basis of Syntax score. The control group consisted of patients with normal coronary arteries. MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. Multivariate logistic analysis was used to assess risk factors of CAD. Ordinal logistic regression analysis was used to assess the relationship between MLR and the lesion severity of coronary arteries.ResultsMLR was found to be an independent risk factor of the presence of CAD (OR: 3.94, 95% CI: 1.20–12.95) and a predictor of the lesion severity (OR: 2.05, 95% CI: 1.15–3.66). Besides, MLR was positively correlated with Syntax score(r = 0.437, p < 0.001). In the receiver-operating characteristic (ROC) curve analysis, MLR, with an optimal cut-off value of 0.25, predicted the severe coronary lesion with a sensitivity of 60.26% and specificity of 78.49%.ConclusionsMLR was an independent risk factor of the presence of CAD, and a predictor of the lesion severity. Compared to neutrophil to lymphocyte ratio (NLR), MLR has better performance to reflect the severity of coronary lesion.

BackgroundThe protective effect of Neuregulin-1 (NRG-1) on heart failure is well established. In this study, we assessed whether NRG-1 could protect the heart by mimicking the cardioprotective effects of ischaemic postconditioning (IP).MethodsWe used a myocardial reperfusion injury rat model in vivo to compare the cardioprotective effects of NRG-1(3 μg/kg, iv. at the onset of reperfusion) and IP. In Langendorff isolated heart perfusion experiments, we used the erythroblastic leukaemia viral oncogene homolog 4 (ErbB4) inhibitor AG1478, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and a mitogen-activated protein/extracellular signal regulated kinase (MEK) inhibitor PD98059 to clarify whether the protective effects of NRG-1and IP depend on the NRG-1/ErbB4 signals and the reperfusion injury salvage kinase (RISK) pathway. Infarct size was detected by Evans blue and TTC. Apoptosis was detected by TUNEL assays. The expression of NRG-1/ErbB4 and downstream ERK1/2, AKT, AMPK and p70s6K were detected by western blotting. Hematoxylin/eosin (H&E) staining was used for histological analysis.ResultsWe found that NRG-1 and IP had similar effects on reducing myocardial infarct size and apoptosis in vivo. NRG-1 heart protein levels were upregulated in the IP group. Phosphorylation of AKT, ERK1/2 and ErbB4 were also increased in both the IP and NRG-1 groups. Furthermore, in Langendorff analyses, the ErbB4 inhibitor AG1478 suppressed the phosphorylation of ErbB4 and the RISK pathway and aggravated myocardial edema and fiber fracture, thereby inhibited the cardioprotective effects in both the IP and NRG-1 groups. For assessment of downstream signals, the PI3K inhibitor LY294002 and the MEK inhibitor PD98059 suppressed the phosphorylation of AKT and ERK1/2 respectively and abolished the cardioprotective effects induced by IP and NRG-1.ConclusionIn conclusion, both IP and NRG-1 could reduce infarct size and apoptosis through ErbB4-dependent activation of the RISK pathway in the same model; these results indicated the therapeutic potential of NRG-1 as a pharmacological postconditioning agent against myocardial reperfusion injury.

Background Carotid artery stenosis, mainly caused by carotid atherosclerosis, is related to ischemic stroke. This study was to investigate whether monocyte/lymphocyte ratio (MLR) was associated with increased severity of carotid stenosis in patients with ischemic stroke. Methods A total of 395 participants with ischemic stroke were retrospectively analyzed. The severity of carotid stenosis was evaluated by ultrasound examination. Patients were divided into two groups: nonsevere stenosis group and severe stenosis group. Multivariate logistic analysis was used to evaluate risk factors. Results A significant correlation was found between MLR and the severity of carotid stenosis in patients with ischemic stroke. MLR was the independent risk factor of carotid stenosis (OR: 9.74, 95% CI: 1.16–81.54). In the ROC curves analysis, a cutoff value of 0.20 for MLR predicted the severity of carotid stenosis with a sensitivity of 80.40% and specificity of 26.40% (ROC area under the curve: 0.598, 95% CI: 0.53–0.67, p = .004). Conclusion Monocyte/lymphocyte ratio plays important roles in carotid stenosis in patients with ischemic stroke and is an independent risk factor of the severity of carotid stenosis. Therefore, MLR might be considered a potential index in the diagnosis of carotid stenosis in patients with ischemic stroke.

Tyrosine 177 and the Src homology 2 (SH2) domain play important roles in linking p185Bcr-Abl to downstream pathways critical for cell growth and survival. However, a mutant p185(Y177FR552L) (p185(YR)), in which tyrosine 177 and arginine 552 in the SH2 domain are mutated, is still capable of transforming hematopoietic cells in vitro. Transplant of these cells into syngeneic mice also leads to leukemogenesis, albeit with a phenotype distinct from that produced by wild-type p185Bcr-Abl (p185(wt))-transformed cells. Here we show that G-protein coupled receptor 34 (Gpr34) expression is markedly up-regulated in p185(YR)-transformed cells compared to those transformed by p185(wt). Knockdown of Gpr34 in p185(YR) cells is sufficient to suppress growth factor-independent proliferation and survival in vitro and attenuate leukemogenesis in vivo. The Erk and phosphatidylinositol 3-kinase/Akt pathways are activated in p185(YR) cells and the activation is dependent on Gpr34 expression. These studies identify Gpr34 as an alternative pathway that may mediate p185Bcr-Abl-induced transformation and leukemogenesis.