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Objective:To evaluate the relationship between long-term learning and memory impairment induced by sevoflurane anesthesia and postsynaptic density protein-95 (PSD-95)/Kalirin-7/Ras-related C3 botulinum toxin substrate 1 (Rac1) signaling pathway in neonatal rats.Methods:Sixty SPF male Wistar rats, aged 7 days, weighing 12-18 g, were divided into 5 groups ( n=12 each) using a random number table method: control group (group C), 1% sevoflurane anesthesia for 2 h group (group S 1), 1% sevoflurane anesthesia for 4 h group (group S 2), 2% sevoflurane anesthesia for 2 h group (group S 3) and 2% sevoflurane anesthesia for 4 h group (group S 4). Morris water maze test was performed at 4, 8 and 12 weeks after anesthesia.The rats were sacrificed after the last Morris water maze test, and the hippocampal tissues were obtained for microscopic examination of the pathological changes (using HE staining), neuron apoptosis (by TUNEL staining), and expression of PSD-95, Kalirin-7 and Rac1 protein and mRNA (by Western blot and quantitative real-time polymerase chain reaction). The apoptosis rate was calculated. Results:Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, the time of stay in the target quadrant was shortened, and the apoptosis rate of hippocampal neurons was increased at 4th, 8th and 12th weeks after anesthesia, phosphorylated Rac1/Rac1 ratio was decreased, and the expression of PSD-95 and Kalirin-7 protein and mRNA was down-regulated in S 1, S 2, S 3 and S 4 groups ( P<0.05). Compared with group S 4, the escape latency was significantly shortened, the number of crossing the original platform was increased, the time of stay in the target quadrant was prolonged, and the apoptosis rate of hippocampal neurons was decreased, phosphorylated Rac1/Rac1 ratio was increased, the expression of PSD-95 and Kalirin-7 protein and mRNA was up-regulated, and the histopathological changes of hippocampal tissues were attenuated in S 1, S 2 and S 3 groups ( P<0.05). Conclusions:The mechanism by which sevoflurane anesthesia induces long-term learning and memory impairment may be related to inhibition of activity of PSD-95/Kalirin-7/Rac1 signaling pathway in hippocampi of neonatal rats.
ABSTRACT
Among all gynecological tumors, ovarian cancer is the third most common cancer but the most lethal one. Currently, the standard first-line treatment for ovarian cancer is cytoreductive surgery combined with platinum and paclitaxel chemotherapy. Although the patients with ovarian cancer respond to the standard therapeutic approach and gain a high remission rate, the most patients relapse after about 2 years of complete remission, the recurrence rate is as high as 80%. The patients with recurrent epithelial ovarian cancer are resistant to almost all chemotherapy drugs due to the acquired resistance. Multidrug resistance to chemotherapy is a major cause of treatment failure. Therefore, it is an urgent problem to reveal the molecular mechanism of ovarian cancer resistance. In recent years, tumor microenvironment as an emerge concept has provided a new perspective for the study of tumorigenesis, progression and drug-resistance. Ovarian cancer is characterized by a unique tumor microenvironment that impairs immune surveillance and mediates therapy resistance. Explaining the mechanism of chemotherapy resistance from the perspective of ovarian cancer microenvironment is helpful to find effective targets reversing the drug resistance of ovarian cancer. This review first introduces the general situation of drug resistance and microenvironment of ovarian cancer, and then focuses on the research progress in the relationship of various components of ovarian cancer microenvironment with drug resistance, in order to explain the occurrence mechanisms of ovarian cancer resistance and find effective targets in the microenvironment to solve the problem of clinical drug resistance. In the end, the forward research directions in this field are prospected in this review.
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Objective To investigate the effect of general anesthesia with sevoflurane or intravenous propofol on anesthesia recovery period in obstructive jaundice patients. Methods Thirty ASA Ⅰ or Ⅱ and Child A obstructive jaundice patients were randomly divided into two equal groups (n=15 each). The patients in group S received inhalation anesthesia with sevoflurane and those in group P intravenous anesthesia with propofol during operation for obstructive jaundice. The patients were premedicated with intramuscular phenobarbital 100mg and atropine 0.5mg, anesthesia was induced with midazolam 0.05mg/kg, atracurium 0.5mg/kg, propofol 1.5-2.5mg/kg and fentanyl 4μg/kg. Maintained with TCI of propofol (target plasmaconcentration was set at 3.5mg/L) or sevoflurane inhalation (end-tidal sevoflurane concentration was 2%-3%) and intermittent i. v. boluses of fentanyl. EGG, HR, MAP, SpO<,2> and end-tidal sevoflurane concentration were continuously monitored during operation. Duration of anesthesia, the volume of infusion and fentanyl were recorded, awaking time, extubation and regained consciousness after operation were recorded. Results There were no significant differences between the two groups in average age, sex, body-weight, duration of anesthesia, the parameters of MAP and HR (P>0.05). The awaking time was (7.9±1.5) minutes in group S and (26.1±8.8) minutes in group P. The extubation time was (8.5±2.5) minutes in group S and (27.8±11.2) minutes in group P. The regained consciousness time was (13.1±4.4) minutes in group S and (33.7±12.5) minutes in group P. The incidence of lethargy, fidget were higher in group P than those in group S. Conclusion Both sevoflurane and propofol can provide satisfactory anesthesia for the operation of obstructive jaundice, but the recovery of influence caused by sevoflurane is faster and more steady than that caused by propofol.
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Objective The authors present a retrospective analysis of 22 patients with primary central nervous system lymphoma(PCNSL) in order to provide a reasonable basis for the diagnosis and treatment of the disease. Methods This report involves a clinicopathological study of 22 patients with histologically proven PCNSL,all diagnosed between January 1993 and May 2000. Univariate and multivariate regression analysis are used to determine prognostic factors significantly associated with an unfavorable or favorable impact on survival. Results The cohort included 11 men and 11 women whose median age at diagnosis was 49.5 years. At the end point of follow-up, 11 died. The median survival time for the patients in study was 14.5 months. With univariate and multivariate regression analysis, prognostic factors significantly associated with survival included intrathecal injection(P=0.005) and local/diffuse neurological deficit(P=0.031). Conclusion There continues to be a significantly increasing incidence of PCNSL. This survey throws light on the clinical and prognostic features of this uncommon disease. Through univariate and multivariate regression analysis the authors highly recommend a theraputic regime including surgery, intrathecal injection and chemotherapy, especially those drugs capable of passing blood-brain barrier, for example high dose MTX.
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The effect of Flavonoids of Gly-cyrrhiza (FG) on ethanol-induced liver injury was studied in mice. Administration of FG to mice prior to ethanol treatment ,either once daily for four days or a single dose, the increase of malondialdehyde and the decrease of reduced glutathione were inhibited dose- dependently.Electron microscopic examination showed that the ethanol-induced damage of hepatocytes could be ameliorated by FG pretreatment. However, no protective effect was observed when FG was administrated to mice after ethanol intoxication.