Objective:To identify the potential pathogenic genes for perioperative neurocognitive disorder (PND) in the patients with digestive system tumors.Methods:The gene expression data of esophageal cancer, gastric cancer, colon cancer, rectal cancer and liver cancer in The Cancer Genome Atlas database were analyzed by bioinformatics analysis method, and the differentially expressed genes in tumor tissues in above-mentioned disease samples were identified compared with para-carcinoma tissues.Secretory proteome differential genes with the same expression trend in digestive system tumors were obtained by comparing with human secretory proteome genes.The correlation between secretomics and PND was determined by comparing with the GeneCards database.Hub genes were identified through PPI network construction and calculation, and the functions and signaling pathways of the above-mentioned differential genes were identified through GO and KEGG enrichment analysis.Results:Compared with para-carcinoma tissues, the expression of 2 640 genes was significantly up-regulated and the expression of 1 423 genes was down-regulated in esophageal cancer tissues; the expression of 3 748 genes was up-regulated and the expression of 908 genes was down-regulated in gastric cancer samples; the expression of 2 684 genes was up-regulated and the expression of 2 678 genes was down-regulated in colon cancer samples; the expression of 2 876 genes was up-regulated and the expression of 2 945 genes was down-regulated in rectal cancer samples; the expression of 1 484 genes was up-regulated and the expression of 723 genes was down-regulated in hepatocellular carcinoma samples.Among them, the expression of the encoding genes of 53 secreted proteins was uniformly up-regulated and the expression of the encoding genes of 20 secreted proteins was uniformly down-regulated in the above tumors.Twenty up-regulated genes and 3 down-regulated genes were associated with PND.PPI network analysis showed that MMP9 was the hub gene.The results of GO and KEGG analysis suggested that differentially expressed genes were mainly related to receptor-ligand activity, cytokine activity and chemokine activity, and were mainly enriched in signaling pathways related to cell cycle and cellular senescence.Conclusions:About 23 differentially expressed genes in digestive system tumors are potentially related to PND, of which MMP9 and other genes may be the hub genes, mainly acting on receptor-ligand binding, regulation of cytokine and chemokine activity, cell cycle, cellular senescence and other related signaling pathways.

Objective:To evaluate the role of acetaldehyde dehydrogenase 2 (ALDH2) in hippocampus in memory decline after myocardial ischemia-reperfusion (I/R) in rats.Methods:Twenty-four healthy male Sprague-Dawley rats, aged 2-3 months, weighing 220-280 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (group S), myocardial I/R group (group I/R) and ALDH2 agonist ALDA-1 group (group ALDA-1). Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion in anesthetized animals.ALDA-1 10 mg/kg was intraperitoneally injected at 5 min before ischemia in group ALDA-1.The positioning navigation training in Morris water maze test was started from 6 days before developing the model.The spatial exploration in Morris water maze test was performed at 24 h after developing the model.The rats were sacrificed after the end of behavioral experiment, and the hippocampus was extracted for microscopic examination of the pathological changes (by hematoxylin and eosin staining) and for determination of the apoptosis index (AI) (by TUNEL staining), activity of ALDH2 (by colorimetry), contents of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) (by enzyme-linked immunosorbent assay), and expression of ALDH2 and 4-HNE (by Western blot). Results:Compared with group S, the number of crossing the original platform was significantly decreased, the time spent in the target quadrant was shortened, the activity of ALDH2 in the hippocampus was decreased, the expression of 4-HNE was up-regulated, and the contents of 4-HNE and MDA and AI were increased in group I/R ( P<0.05). Compared with group I/R, the number of crossing the original platform was significantly increased, the time spent in the target quadrant was prolonged, the ALDH2 activity was increased, the expression of 4-HNE was down-regulated, and the contents of 4-HNE and MDA and AI were decreased in group ALDA-1 ( P<0.05). There was no significant difference in ALDH2 expression in hippocampus among the three groups ( P>0.05). Conclusions:The mechanism of memory decline developed after myocardial I/R may be related to the decrease in ALDH2 activity and promotion of accumulation of aldehydes in the hippocampus of rats.

Objective To investigate the relationship between glycoprotein synthase kinase-3 (GSK-3β) and mitochondrial cleavage protein (Drp-1) during diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.Methods Clean-grade healthy male Sprague-Dawley rats,weighing 250-300 g,were used in this study.Diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 30 g/kg.Forty rats with diabetes mellitus were divided into 5 groups (n =8 each) using a random number table method:ischemia-reperfusion (I/R) group,sevoflurane postconditioning group (SP group),sevoflurane postconditioning plus Drp1 inhibitor Mivi-1 group (SM group),sevoflurane postconditioning plus GSK-3β inhibitor SB216763 group (SB group) and sevoflurane postconditioning plus Mivi-1 plus SB216763 group (SMB group).Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.The rats inhaled 2.5％ sevoflurane for 10 min starting from 5 min before reperfusion in SP,SM,SB and SBM groups.Mivi-1 1.2 mg/kg was injected via the caudal vein at 15 min before reperfusion in group SM.SB216763 0.2 mg/kg was injected via the caudal vein at 5 min before reperfusion in group SB.Mivi-1 1.2 mg/kg and SB216763 0.2 mg/kg were injected via the caudal vein at 15 and 5 min before reperfusion,respectively,in group SMB.Blood samples were collected from the abdominal aorta at 120 min of reperfusion for determination of serum cardiac troponin Ⅰ (cTnⅠ) concentrations.The rats were sacrificed and myocardial specimens were obtained from the apex for determination of the cell apoptosis (by TUNEL) and expression of caspase-3 (by Western blot),and apoptotic index (AI) was calculated.Results Compared with group I/R,no significant change was found in caspase-3 expression,AI or serum cTnⅠ concentrations (P＞0.05),and the pathological changes of myocardium were comparable in group SP,and the expression of caspase-3 was significantly down-regulated,and AI and serum cTnⅠ concentration were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SP,the expression of caspase-3 was significantly down-regulated,AI and serum cTnⅠ concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SMB or group SB,the expression of caspase-3 was significantly down-regulated,AI and serum cTnI concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in group SMB.Conclusion It is not a single regulatory relationship between GSK-3β and Drp-1 in the pathophysiological process of diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.