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Immunotherapy with anti-programmed cell death protein 1 or programmed death ligand 1 (PD-L1) agents has demonstrated promising efficacy for the treatment of various types of malignancies. However, the role of PD-L1 as a tumor prognostic marker remains poorly understood. In the present study, the prognostic value of PD-L1 expression in esophageal carcinoma (EC) following definitive chemoradiotherapy (CRT) was investigated, and its associations with three systemic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were further explored. A total of 104 patients with non-metastatic EC, who underwent definitive CRT between January 2009 and December 2012, were retrospectively analyzed. The expression of PD-L1 was examined by immunohistochemistry and the impact of PD-L1 expression level on overall survival (OS) was assessed. Furthermore, pretreatment neutrophil, lymphocyte, platelet and monocyte counts were obtained from routine blood tests to calculate the NLR, PLR and LMR. PD-L1 was overexpressed in EC compared with normal esophageal epithelium, with a positive expression rate of 37.5%. Additionally, patients with positive PD-L1 expression had a lower NLR than those with negative PD-L1 expression (P=0.001). On multivariate analysis, the positive staining of PD-L1 was significantly associated with improved OS (HR, 0.6; 95% CI, 0.372-0.965; P=0.035). Kaplan-Meier survival analysis showed a similar result (P=0.009). Additionally, sex (HR, 0.449; 95% CI, 0.229-0.880; P=0.020), clinical stage III (HR, 2.471; 95% CI, 1.171-5.212; P=0.018), and receipt of concurrent chemoradiation (HR, 0.590; 95% CI, 0.368-0.945; P=0.028) were all independent prognostic factors in EC treated with definitive CRT. The correlation of NLR with PD-L1 expression validated the relevance of immunity and inflammation. In summary, the present study demonstrated that positive PD-L1 expression is associated with improved survival in patients with EC treated with radical CRT, indicating that PD-L1 is a promising prognostic marker. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the neuroprotective effects of naringin on the memory impairment of hydrocortisone mice, and to elucidate the potential underlying molecular mechanisms. In the present study, a hydrocortisone model was constructed. Novel object recognition, Morris water maze and step-down tests were performed in order to assess the learning and memory abilities of mice. Hematoxylin and eosin staining was used to observe pathological changes in the hippocampus and hypothalamus. Transmission electron microscopy was used to observe the ultrastructural changes in the hippocampus. Immunohistochemistry was used to detect the expression of ERα and ERβ. Western blotting was performed to detect the expression of each protein in the relevant system. It was found that naringin can significantly improve cognitive, learning and memory dysfunction in mice with hydrocortisone memory impairment. In addition, naringin can exert neuroprotective effects through a variety of mechanisms, including amyloid β metabolism, Tau protein hyperphosphorylation, acetylcholinergic system, glutamate receptor system, oxidative stress and cell apoptosis. Naringin can also affect the expression of phosphorylated-P38/P38, indicating that the neuroprotective effect of naringin may also involve the MAPK/P38 pathway. The results of the present study concluded that naringin can effectively improve the cognitive abilities of mice with memory impairment and exert neuroprotective effects. Thus, naringin may be a promising target drug candidate for the treatment of Alzheimer's disease. [ABSTRACT FROM AUTHOR]