Objective To investigate the changes in the phosphorylation of N-methyl-D-aspartate (NMDA) receptors in spinal dorsal horns in a rat model of neuropathic pain induced by chronic compression of dorsal root ganglion (CCD).Methods Ninety-six male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 3 groups (n =32 each) using a random number table:control group (group C),sham operation group (group S) and group CCD.In CCD group,a small stainless steel needle (4 mm in length and 0.8 mm in diameter) was inserted into the L4,5 intervertebral foramen in pentobarbital sodium-anesthetized rats,developing intervertebral foramen stenosis and hence producing a chronic steady compression of the dorsal root ganglion.In group S,the intervertebral foramen was only exposed without inserting the needle.The paw withdrawal latency (PWL) was measured at 1 day before operation and 1,2 and 4 weeks after operation.The rats were then sacrificed after measurement of PWL and the lumbar enlargement segments of the spinal cord were removed for determination of the expression of interleukin-1β (IL-1β) and phosphorylation of NMDA receptor NR1 subunits at serine 896 (pNR1S896) on the injured side by immunohistochemistry and Western blot.Results Compared with group C,the PWL was significantly shortened at each time point after operation,and the expression of IL-1β and pNR1S896 was up-regulated in group CCD,and the PWL was shortened at 1 week after operation,the expression of IL-1β and pNR1S896 was up-regulated,and no significant change was found in PWL and expression of IL-1β and pNR1S896 at the other time points in group S.Compared with group S,the PWL was significantly shortened at each time point after operation,and the expression of IL-1β and pNR1S896 was up-regulated in group CCD,Compared with the baseline value at 1 day before operation,the PWL was slowly shortened starting from 1 week after operation,and decreased to the lowest level at 2 weeks after operation and maintained at this level for 2 weeks,the expression of IL-1β and pNR1S896 was slowly up-regulated starting from 1 week after operation,and increased to the highest level at 2 weeks after operation and maintained at this level for 2 weeks in group CCD,and the PWL was shortened at 1 week after operation,and the expression of IL-1β and pNR1 S896 was up-regulated in group S.Conclusion The development and maintenance of neuropathic pain induced by CCD are related to phosphorylation of NMDA receptors in spinal dorsal horns of rats.

Objective To study the effect of dexmetomidine on tracheal intubation under abdominal anesthesia.Methods From January 2015 to January 2018,100 patients were selected to perform tracheal intubation under abdominal anesthesia in Shanxi Provincial Hospital of Taiyuan.A total of 100 patients under abdominal surgery were randomly divided into two groups,with 50 patients in each group.The observation group was given dexmetomidine intravenous injection during the operation,while the control group was not given dexmetomidine during the operation.The blood pressure and heart rate of the two groups were compared before and after anesthesia.The recovery time of spontaneous respiration,eye opening time,extubation time,incidence of adverse events,cough score and restlessness score were compared between the two groups,and the cognitive function of the two groups was compared.Results After anesthesia,the systolic blood pressure [(103.75 ± 2.26) mmHg],diastolic blood pressure [(71.92 ± 1.95) mmHg],heart rate[(70.91 ± 1.89) rpm] in the observation group were significantly higher than those in the control group [(100.37 ±2.91)mmHg,(70.27 ± 1.84)mmHg,(69.08 ±1.63)] (t =6.487,4.532,5.185,all P ＜0.05).The recovery time of spontaneous respiration [(7.14 ± 1.37) min],eye opening time [(9.85 ± 2.31) min] and extubation time[(20.57 ±2.94)min]in the observation group were significantly shorter than those in the control group[(8.75 ± 1.89)min,(12.41 ±2.97)min,(24.06 ±3.42)min] (t =4.877,4.811,5.472,all P ＜0.05).The incidence rate of adverse events in the observation group (8％) was lower than 24％ in the control group (x2 =4.762,P ＜ 0.05).The score of cough and the score of restlessness in the observation group were (4.09 ± 1.63) and (4.27 ± 1.96),respectively,which were significantly lower than those in the control group [(6.24 ± 2.18) and (6.51 ± 2.32)] (t =5.186,5.215,all P ＜ 0.05).At 6 h after operation,the scores of MMSE,vocabulary memory,simple calculation and picture memory in the observation group were (23.95 ±2.13),(7.35 ± 1.08),(7.14 ± 1.12) and (7.26 ± 1.17),respectively,which were higher than those in the control group[(20.47 ± 1.91),(6.17 ± 0.94),(5.89 ± 1.04),(6.02 ± 0.89)] (t =8.601,5.828,5.783,5.965,all P ＜ 0.05).Conclusion The application of dexmetomidine in patients under general anesthesia under tracheal intubation can effectively reduce the fluctuation of hemodynamic indicators after anesthesia,help to maintain the hemodynamic stability of patients,and promote the recovery of consciousness after operation.It can prevent adverse events during recovery of anesthesia and reduce the effect of anesthesia on cognitive function of patients.

Objective To investigate the effect of inhibition of glycogen synthase kinase?3 beta ( GSK?3β) activity on sevoflurane postconditioning?induced cardioprotection in diabetic rats. Methods Healthy adult male Sprague?Dawley rats, weighing 250-300 g, in which diabetes mellitus was induced by intraperitoneal 1% streptozotocin 60 mg∕kg combined with high?fat and high?sucrose diet and confirmed by blood glucose level >16. 7 mmol∕L. Forty rats with diabetes mellitus were divided into 5 groups ( n=8 each) using a random number table: sham operation group ( S group ) , ischemia?reperfusion ( I∕R ) group, sevoflurane postconditioning group ( SP group) , GSK?3β inhibitor SB216763 group ( SB group) , and sevoflurane postconditioning plus SB216763 group ( SS group ) . Myocardial ischemia was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfu?
sion. The rats inhaled sevoflurane with the end?tidal concentration of 2.5% for 5 min starting from 1 min be?fore reperfusion in group SP. SB216763 0.2 mg∕kg was injected via the caudal vein at 1 min before reperfu?sion in group SB. In group SS, the rats inhaled sevoflurane with the end?tidal concentration of 2.5% for 5 min starting from 1 min before reperfusion, and SB216763 0.2 mg∕kg was injected via the caudal vein at 1 min before reperfusion. At 120 min of reperfusion, blood samples were collected from the carotid artery for determination of serum creatine kinase?MB (CK?MB) activity and cardiac troponin I (cTnI) concentra?tions. Myocardial specimens were collected at 120 min of reperfusion for microscopic examination of the pathological changes and for determination of myocardial infarct size ( by 2,3,5?triphenyltetrazolium chlo?ride staining) and phosphorylated GSK?3β (p?GSK?3β) expression (by Western blot). Results Com?pared with group S, the myocardial infarct size and serum CK?MB activity and cTnI concentration were sig?nificantly increased, and the expression of p?GSK?3βwas significantly down?regulated in I∕R, SP, SB and SS groups (P<0.05). Compared with group I∕R, the myocardial infarct size and serum CK?MB activity and cTnI concentration were significantly decreased, and the expression of p?GSK?3β was significantly up?regulated in SB and SS groups (P<0.05), and no significant change was found in the parameters men?tioned above in group SP ( P>0.05) . Compared with group SB, the myocardial infarct size and serum CK?MB activity and cTnI concentration were significantly decreased, and the expression of p?GSK?3β was sig?nificantly up?regulated in group SS (P<0.05). The pathological changes of myocardium were significantly attenuated in SB and SS groups as compared with group I∕R and group SP . Conclusion Inhibition of GSK?3β activity can improve sevoflurane postconditioning?induced cardioprotection in diabetic rats.

Objective To investigate whether discontinuous sleep supplementation can reduce myocardial ischemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.Methods The rats were injected intra-peritoneal with 1％streptozotocin(STZ)30 mg/kg combined with high-fat and high-glucose diet to replicate diabetic model.Forty diabetic rats were randomly divided into four groups with 10 in each:sham surgery group(Sham group),ischemia-reperfusion group(I/R group),in which the left anterior descending coronary artery(LDA)was ligated for thirty minutes and reperfusion for 2 h,circadian rhythm disorder group(Crd group,24 h daily light and food),discontinuous sleep supplementation group(Dss group,every 3 hours of illumination and 1.5 hours break at night).We analyzed the myocardial infarct size(by 2,3,5-triphenyltetrazolium chloride stai-ning),determined serum creatine kinase-myoglobin(CK-MB)activity and cardiac troponinⅠ(cTnⅠ)concentrations;the expression level of BMAL1 and REV-ERBα was determined by Western blot.Results Compared to the sham group,the I/R group showed a significantly increased in myocardial infarct size,serum CK-MB activity and cTnⅠ concentration.The expression of the myocardial biological clock gene BMAL1 was down-regulated,while the ex-pression of REV-ERBα was up-regulated(P<0.05).Compared to the I/R group,the Crd group showed a signifi-cantly increase in myocardial infarct size,serum CK-MB activity and cTnⅠ concentration.The expression of the myocardial biological clock gene BMAL1 was down-regulated,while the expression of REV-ERBα was up-regulated(P<0.05).Compared to the Crd group,Dss group showed a significantly decrease in the myocardial infarct size,serum cTn concentration and CK-MB activity.Furthermore,there was an increased protein expression of BMAL1 and a decrease of REV-ERBα(P<0.05).Conclusions Discontinuous sleep supplementation can reduce myocardial is-chemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.

Objective To evaluate the effect of ulinastatin on postoperative cognitive dysfunction in preoperative sleep deprived aged rats.Methods Sixty clean healthy male Sprague-Dawley rats,aged 18 months,weighing 350-500 g,were divided into 3 groups (n=20 each) using a random number table:control group (group C),sleep deprivation group (group D) and ulinastatin group (group U).Sleep deprivation was induced by using modified multiple platform method in D and U groups,and then splenectomy was performed in three groups.Ulinastatin 100 U/g was intraperitoneally injected before sleep deprivation and immediately after operation in group U.Ten rats were randomly selected at 3 days after operation and sacrificed,and hippocampi were removed for determination of the contents of interleukin-1β (IL-1β),IL-6 and tumor necrosis factor-α (TNF-α) by enzyme-linked immunosorbent assay.Morris water maze test was performed at 3-7 days after operation in the rest ten rats in each group,and the escape latency and time of staying at the original platform were recorded.Results Compared with group C,the escape latency was significantly prolonged at 4-6 days after operation,the time of staying at the original platform was shortened,and the contents of IL-1β,IL-6 and TNF-α were increased at 3 days after operation in D and U groups (P＜0.05).Compared with group D,the escape latency was significantly shortened at 4-6 days after operation,the time spent in the original platform was prolonged,and the contents of IL-1β,IL-6 and TNF-α were decreased at 3 days after operation in group U (P＜0.05).Conclusion Ulinastatin can mitigate postoperative cognitive dysfunction in preoperative sleep deprived aged rats,which is related to inhibiting inflammatory responses.

Objective:To evaluate the effect of electroacupuncture on P2X4R-p38 mitogen-activated protein kinase (p38 MAPK)-brain-derived neurotrophic factor (BDNF) signaling pathway in trigeminal ganglion of rats with trigeminal neuralgia.Methods:Thirty-six clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), and electroacupuncture group (E group). The model was developed by chronic constriction of the infraorbital nerve in anesthetized animals. The infraorbital nerve was only exposed without ligation in group S. Rats received electroacupuncture stimulation at the Baihui and Xiaguan acupoints on the affected side for 20 min after developing the model, with a frequency of 80 Hz, twice a day, for 14 consecutive days in E group. Facial mechanical pain threshold (FMT) was measured at 1 day before developing the model and 3, 7, 14, 21 and 28 days after developing the model. The rats were sacrificed after the last behavioral testing, and the trigeminal ganglia were taken for examination of histopathological changes of trigeminal ganglion (by HE staining) and for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the FMT was significantly decreased at each time point after developing the model, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased ( P<0.05), the pathological changes of the trigeminal ganglion were obvious in group TN. Compared with group TN, the FMT was significantly increased at each time point after developing the model, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased ( P<0.05), and the pathological changes of the trigeminal ganglion were significantly attenuated in group E. Conclusions:The mechanism by which electroacupuncture alleviates trigeminal neuralgia may be related to inhibiting the activity of P2X4R-p38MAPK-BDNF signaling pathway and reducing neuroinflammation in rats.

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 evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.

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.