Objective To analyze the expression levels and clinical significance of N-myc down-stream-regulated gene 3(NDRG3)and semaphoring 3A(SEMA3A)in elderly patients with acute ischemic stroke(AIS).Methods A total of 100 elderly AIS patients admitted to Department of Geriatrics of Liaocheng People's Hospital from September 2020 to September 2022 were included as the study group.According to their NIHSS score at admission,they were divided into mild(34 cases),moderate(31 cases)and severe(35 cases)subgroups.All patients were followed up for 3 months after discharge.And they were assigned into good prognosis group(69 cases)and poor prognosis group(31 cases)based on the modified Rankin scale score.Another 100 healthy individ-uals who underwent physical examination in our hospital during the same period were recruited as the control group.Western blotting was used to detect the protein expression of NDRG3 and SEMA3A in peripheral blood mononuclear cells(PBMC).ELISA was applied to measure the con-tents of VEGF,TGF-1,TNF-α,and IL-17 in peripheral blood samples.Spearman rank correlation analysis was performed to analyze the correlation of NDRG3 and SEMA3A levels with NIHSS score,and ROC curve was plotted to analyze the values of NDRG3 and SEMA3A in predicting poor prognosis in elderly AIS patients.Results The expression levels of NDRG3 and SEMA3A in PBMC were obviously higher in the study group than the control group(1.11±0.16 vs 0.76± 0.13,0.78±0.13 vs 0.42±0.09,P＜0.01).The levels in the mild,moderate and severe subgroups were significantly higher than that of the control group(P＜0.01).The poor prognosis group had statistically higher expression levels of NDRG3 and SEMA3A than the good prognosis group(P＜0.01).Spearman rank correlation analysis showed that the NIHSS score was positively corre-lated with the expression levels of NDRG3 and SEMA3A in elderly AIS patients(r=0.597,P＜0.01;r=0.618,P＜0.01),while the NDRG3 level was positively correlated with that of SEMA3 A(r=0.477,P＜0.01).ROC curve analysis indicated that the AUC value of combined NDRG3 and SEMA3A levels was superior to that of NDRG3 and SEMA3A alone in predicting of poor progno-sis(0.962 vs 0.861,0.880,P＜0.01).Conclusion The levels of NDRG3 and SEMA3A proteins are up-regulated in elderly AIS patients,and are closely associated with the severity and prognosis of the disease.