ObjectiveTo evaluate the effect of time-related administration of methotrexate (MTX) on neural cell apoptosis in rats after spinal cord injury (SCI) so as to investigate its potential neuroprotective mechanism and appropriate administration time. MethodA total of 120 male Sprague Dawley rats, 247-286 g in weight, were randomly divided into 4 groups (n=30) :sham group (group A), control group (group B), MTX treating group (group C), and MTX prophylaxis group (group D). The SCI model was established in the rats of groups B, C, and D by improved Allen method, and just laminectomy was performed in group A. MTX (0.5 mg/kg) was administered with tail vein injection at 1, 6, 12, 18, and 24 hours after injury in group C, and at 30 minutes before injury and at 6, 12, 18, and 24 hours after injury in group D; the equivalence saline was injected at 1, 6, 12, 18, and 24 hours after injury in groups A and B. Basso-Beattie-Bresnahan (BBB) score was used to evaluate the neural function at 1, 3, 7, 14, and 21 days after injury, HE staining to observe histological changes, immunohistochemical staining and TUNEL method to measure the expression of Caspase-3 and neural cells apoptosis, respectively. ResultsTen rats died during the experiment in groups B, C, and D; 25 rats in each group were included into the experiments at last. BBB score of group A was significantly higher than that of groups B, C, and D at all time points after injury (P<0.05) . BBB score of groups C and D were significantly higher than that of group B at 3, 7, 14, and 21 days (P<0.05) , and BBB score of group D was significantly higher than that of group C at 3, 7, and 14 days (P<0.05) . The histological observation showed normal structure of spinal cord at all time points after injury in group A. While the degree of SCI in group D was lighter than that in groups B and C, and group C was lighter than group B. At 14 days after injury, the degree of SCI in groups B, C, and D tend to keep the same. The number of Caspase-3 and TUNEL positive cells of groups B, C, and D was significantly more than that of group A at all time points after injury (P<0.05) , group B was significantly more than groups C and D (P<0.05) . The number of Caspase-3 positive cells of group C was significantly more than that of group D at 3, 7, and 14 days (P<0.05) . While the number of TUNEL positive cells of group C was significantly more than that of group D at 3 and 7 days (P<0.05) . And the number of Caspase-3 positive cells and TUNEL positive cells was positively correlated in groups B, C, and D (P<0.05) at 1, 3, 7, 14, and 21 days after injury. ConclusionsLow-dose MTX may effectively reduce the degree of the secondary injury of spinal cord by reducing the nerve cell apoptosis. Better effect can be obtained when MTX is used as prevent method than as a way of treatment.
ObjectiveTo explore effect of lymph node ratio (LNR) on prognosis for patients with stage Ⅲ colorectal cancer. MethodsThe clinicopathologic data of 1 424 stage Ⅲ patients who underwent curative resection in this hospital from January 2009 to December 2013 were analyzed retrospectively. These patients were divided into low LNR group (LNR<optimal cut-off value) and high LNR group (LNR≥optimal cut-off value) according to the optimal cut-off value by receiver operating characteristic curve. The correlation between prognosis and clinicopathologic features was analyzed by using univariate analysis and Cox's proportional hazards regression model. The 5-year cumulative disease-free survival (DFS) and overall survival (OS) were calculated by using Kaplan-Meier method. ResultsThe area under the receiver operating characteristic curve was 0.639, the optimal cut-off value of LNR was 0.267. The 5-year cumulative DFS and OS of the low LNR group were significantly higher than those of the high LNR group (DFS:53.8% versus 34.4%, P<0.001; OS:60.5% versus 44.5%, P<0.001). The results of univariate analysis showed that the preoperative carcinoembryonic antigen (CEA) level, degree of differentiation, TNM stage, pT stage, pN stage, vascular invasion, tumor diameter, and LNR were associated with the DFS and OS (P<0.05), but the number of lymph nodes retrieved was only associated with the DFS (P<0.05). The results of Cox analysis showed that the preoperative CEA level, degree of differentiation, TNM stage, and LNR were the independent prognostic factors for the DFS and OS (P<0.05), but the number of lymph nodes retrieved and the vascular invasion were only the independent prognostic factors for the DFS (P<0.05). ConclusionLNR is a prognostic factor in stage Ⅲ colorectal cancer, and it might be as a supplement for TNM staging system.