Objective To investigate the effects of propofol on neuronal apoptosis in anterior horn of spinal cord in rabbits with spinal cord ischemia-reperfusion (IR) injury. Methods Sixty New Zealand white rabbits aged 4-6 months weighing 2.0-2.5 kg were randomized to receive normal saline (group C), 10% intralipid (group F) and propofol 30 mg/kg (group P1 ), 40 mg/kg (group P2), 50 mg/kg (group P3) and60 mg/kg (group P4 ). 10% intralipid was added to propofol solution to make the fluid infused equal in volume between the 6 groups ( n = 10 each). Spinal cord ischemia was induced by occlusion of abdominal aorta distal to the left renal arteries combined with simultaneous occlusion of bilateral common iliac arteries for 30 min. A catheter was inserted into abdominal aorta close to the site of occlusion via left femoral artery. Normal saline, 10% intralipid or different doses of propofol was infused through the catheter as soon as aorta was clamped at the rate of 12 ml·kg-1·h-1 for 30 min. The aorta and bilateral iliac arteries were then declamped. The L4-6 of spinal cord was removed at 48 h of reperfusion for microscopic examination and the total number of normal motor neurons in the anterior horn of spinal cord was counted. The total number of neurons and apoptosis neurons in the anterior horn of spinal cord was counted by TUNEL and the apoptosis index of neurons was calculated. The expression of caspase-3 in the anterior horn of spinal cord was determined by immunohistochemical technique. Results The number of normal motor neurons was significantly higher, and the apoptosis index and expression of caspase-3 were significantly lower in group P1-4 than in group C and F ( P < 0.05). Compared with group P1, the number of normal motor neurons was significantly increased and the apoptosis index was significantly decreased in group P2-4 and the expression of caspase-3 was down-regulated in group P3 and P4 ( P < 0.05). Compared with group P2, the number of normal motor neurons was significantly increased in group P3 while decreased in group P4, and the apoptosis index was significantly decreased and the expression of caspase-3 was down-regulated in group P3 and P4 ( P < 0.05). Compared with group P3, the number of normal motor neurons was significantly decreased and the apoptosis index was significantly increased and the expression of easpnse-3 was up-regulated in group P4 ( P < 0.05) . Conclusion Propofol 30-60 mg/kg infused through aorta during occlusion can inhibit the neuronal apoptosis and attenuate IR injury to spinal cord dose-dependently in rabbits. The underlying mechanism may be related to the down-regulation of caspase-3 expression.

[Abstract] Objective: To screen candidate epitopes of breast cancer HLA-A2 restrictive neoantigen and to identify high frequency mutation sites in breast cancer neoantigen by using bioinformatics method. Methods: NCBI and GDC databases were used to search missense mutation sites formed by single nucleotide mutation in breast cancer among reported literatures and sequencing data. The new antigen epitopes were predicted by HLA-A2 antigen epitope prediction website BIMAS, SYFPEITHI and artificial neural networkbased NetMHC4.0, and the epitopes with TAP binding power less than Intermediate were eliminated. The candidate epitopes were prioritized by mutation frequency and prediction results. Results: A total of 17 high-frequency mutation genes, including BTLA, ERBB2 and NBPF12 etc, were screened by the above-mentioned methods, and a total of 26 neoantigen epitopes were identified. The binding power of epitopes predicted using BIMAS and SYFPEITHI showed great difference (P<0.05), epitopes in high priority as GSTP1 (A114V , mutation frequency of 5.94%) and BRCA2 (N991H, mutation frequency of 5.40%) etc, were expected to be candidate neo-antigen epitopes; however, their mutation frequency was relatively too low to achieve“universal use” . The possibility of these epitopes used as general breast cancer neo-antigen epitopes is less likely. Conclusion: The common mutation frequency of breast cancer is lower than that of other tumors; it ’s difficult to find“universal”new antigen epitopes of breast cancer; the individualized neoantigen vaccine may be of more promise, which needs further research.