Efficacy of melanoma patients treated with PD-1 inhibitors: Protocol for an overview, and a network meta-analysis of randomized controlled trials.

BACKGROUND: Melanoma is a malignant tumor of melanocytes that produces pigments and can occur in the whole body. It is characterized by strong invasiveness, high metastasis rate and poor prognosis, and brings heavy burden to patients and society. In order to find the most effective and safe treatment measures, in this study, a network meta-analysis (NMA) for randomized controlled trials (RCTs) of advanced melanoma treated with PD-1 inhibitors will be conducted based on the existing systematic reviews (SRs) of PD-1 inhibitor in the treatment of advanced melanoma. METHODS: PubMed, EMBASE, Web of Science and the Cochrane Library were searched on December 18, 2018 to obtain systematic reviews of PD-1 inhibitor in the treatment of advanced melanoma. Assessing the Methodological Quality of Systematic Reviews (AMSTAR2) will be used to assess the methodological quality of systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach will be applied to evaluate the evidence quality of outcome measures, and the Cochrane's risk of bias tool will be utilized to appraise risks of bias of each embedded RCTs. And the outcomes are overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Hazard ratio (HR) or odds ratio (OR) with their 95% confidence interval (CI) were used to synthesize dichotomous outcomes, while the mean difference (MD) for the continuous variables. R3.5.1 will be used to create a network evidence map for direct and indirect comparative analysis. RESULTS: This study will provide a comprehensive summary of the current evidences related to the efficacy and safety of PD-1 inhibitor in advanced melanoma. CONCLUSION: Our findings will be useful to assist clinicians make reasonable decisions to the treatment of advanced melanoma. ETHICS AND COMMUNICATION: It is unnecessary for this NMA to acquire an ethical approval, because it is based on published researches. PROSPERO REGISTRATION NUMBER: CRD42019120017.

Breviscapine, a traditional Chinese medicine, alleviates myocardial ischaemia reperfusion injury in diabetic rats.

OBJECTIVE: The aim of this study was to explore the effects of breviscapine on the expressions of intercellular adhesion molecule-I (ICAM-I), ATPase activities and oxidative stress in ischaemia-reperfused (I/R) myocardium of diabetic rats. METHODS: Sprague Dawley rats were randomly divided into two groups (a diabetic group and a non-diabetic group), and each group divided into two subgroups including a control group and a breviscapine group. Reperfusion surgery was carried out in all rats.The contents of malonaldehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-P(x)) in serum and myocardial tissues were measured. The activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase in myocardial mitochondria were measured. The ICAM-I protein expressions in myocardium were determined with the immunohistochemical method. RESULTS: The activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase were significantly increased in diabetic rats in the breviscapine group compared with the control group. Compared with the non-diabetic control group, the contents of MDA in serum and myocardium were significantly increased in the diabetic control group. Breviscapine led to a reduction of the contents of MDA in the diabetic and non-diabetic group. Compared with the non-diabetic control group, the activities of SOD and GSH-P(x) in the myocardium were significantly decreased in the diabetic control group.The activities of SOD and GSH-P(x) in serum and myocardium were increased in the diabetic and non-diabetic group after breviscapine treatment. Compared with the non-diabetic control group, the ICAM- I protein expressions were increased significantly in the diabetic control group. Breviscapine decreased the ICAM-I protein expression in the diabetic and the non-diabetic group. CONCLUSION: Breviscapine may have protective effects on myocardial ischaemia reperfusion injury of diabetic rats by scavenging oxygen free radicals, decreasing the expressions of ICAM-I protein in myocardium and increasing the activities of Na(+)-K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase in myocardial mitochondria.