AIM:To study the effects of N-palmitoylethanolamide ( PEA) on the anxiety-and depression-like behaviors of the mouse model induced by restraint stress , and to explore the possible mechanism of anxiolytic and antide-pressant effects of PEA .METHODS:The mice were intragastrically treated with 2.5, 5 and 10 mg/kg of PEA for 21 con-secutive days once daily .Thirty min after intragastric administration , the mice ( except the normal control group ) were placed in the glass tube to accept 4-h chronic restraint stress for 21 d.After the last administration , the mice were submit-ted to the forced stress test and the open field test (OFT) to observe the effects of PEA on the depression-like behaviors. The cumulative immobility time was recorded during the 4-min interval in the forced swimming test ( FST) or during the 5-min interval in the tail suspension test (TST).The elevated plus maze (EPM) test was used to investigate the effect of PEA on the mouse anxiety-like behaviors , and the water maze method was used to investigate the learning and memory abi-lities, spatial orientation and cognitive function of mice .After the behavior tests , the serum was collected and the hippo-campus was removed . The serum contents of adrenocorticotropic hormone ( ACTH ) , cortisol ( CORT ) and 5-hydroxytryptamine (5-HT) in the hippocampus were detected by ELISA .The changes of acetylcholinesterase ( AChE) ac-tivity in the hippocampal homogenate was measured by spectrophotometry .RESULTS:Compared with model group , in the FST or TST, the immobility time in the mice treated with PEA at 2.5~10 mg/kg and fluoxetine was significantly reduced . In the OFT, the total locomotion distance and total movement time were increased significantly in the mice , but only 10 mg/kg PEA and fluoxetine increased the numbers of rearing .In the EPM test , the percentage of the time spent in open arms, the entries into open arms and the total locomotion distance in 4 arms in the mice were significantly increased .In wa-ter maze test , PEA at 5 and 10 mg/kg and fluoxetine significantly shortened the latency to find the security zone in the mice, and PEA at 10 mg/kg and fluoxetine obviously shorten the swimming distance .Compared with model group , PEA at 10 mg/kg and fluoxetine reduced the mouse serum levels of ACTH and CORT , and the adrenal index , increased the 5-HT content and decreased the AChE activity in the hippocampus .CONCLUSION:PEA produces antagonistic effects on an-xiety-and depression-like behaviors in the mice induced by restraint stress .Its specific mechanism may be related to the re-gulation of the hypothalamic-pituitary-adrenal axis function by increasing the 5-HT level in hippocampus , thus participating in the regulation of central cholinergic system .

Objective: To observe the effect of edaravone combining ulinastatin on brain protection in patients of type A aortic dissection (AAD) after total arch replacement. Methods: A total of 60 AAD patients with total arch replacement in our hospital from 2014-09 to 2016-01 were prospectively studied. Based on peri-operative application of edaravone and ulinastatin, the patients were divided into 2 groups: EU group: 1) the patients received ulinastatin 300000 U/8h and edaravone 0.5mg/Kg/12h from administration to 3 days post-operation, 2) during cardiopulmonary bypass, the patients received ulinastatin 300000 U/2h and edaravone 0.5mg/Kg; Control group, the patients had no such treatment.n=30 in each group. The following items were observed:①operative condition;②blood levels of speciifc brain injury markers as S-100 and neuron speciifc enolase (NSE) at different time points: beginning of surgery (T0), opening aorta clamp (T1), right after cardiopulmonary bypass (T2), entering ICU (T3), 24h post-operation (T4) and 3 days post-operation (T5); ③post-operative condition. Results:①Durations of operation, cardiopulmonary bypass, cardiac arrest and bilateral antegrade selective cerebral perfusion (BACP), the frequency of BACP and UACP (unilateral antegrade selective cerebral perfusion), the lowest rectal temperature and blood levels of S-100, NSE at T0 were similar between 2 groups.②Compared with Control group, EU group had decreased S-100 and NSE from T1 to T5,P<0.05.③The in-hospital and ventilation time, frequency of PND and TND, the patients with CSS score≥16 before discharge and the in-hospital death rate were similar between 2 groups,P>0.05. Conclusion: Edaravone combining ulinastatin had brain protective effect in AAD patients after total arch replacement;it may reduce blood speciifc brain injury markers while the clinical signiifcance should be further investigated.

ObjectiveTo explore the mechanism of Cangxi Tongbi capsules （CXTB） in regulating the p38 mitogen-activated protein kinase （p38 MAPK）/NOD-like receptor protein 3 （NLRP3）/cysteine protease-1 （Caspase-1） signaling pathway to inhibit pyroptosis of cartilage cells in knee osteoarthritis （KOA）. MethodSixty male SD rats were randomly divided into a sham operation group， a model group， low， medium， and high dose CXTB groups， and a positive control group， with 10 rats per group. The modified Hulth method was employed to establish a rat model of KOA. According to their respective assignments， rats were administered CXTB （0.25， 0.5， 1.0 g·kg^-1） and Celecoxib （24 mg·kg^-1） by gavage. The sham operation and model groups were given an equivalent volume of physiological saline. Treatment was performed once daily for 28 days. Micro-computed tomography （Micro-CT） was used to assess bone volume/total volume （BV/TV） and trabecular separation （Tb.Sp）. Joint degeneration was evaluated through hematoxylin-eosin （HE） staining， safranin-fast green （SO） staining， and Osteoarthritis Research Society International （OARSI） scoring. Western blot analysis was conducted to measure the expression levels of p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， NLRP3， Caspase-1， and gasdermin D （GSDMD） proteins. Real-time PCR was used to assess mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD genes. Enzyme-linked immunosorbent assay （ELISA） was used to measure serum concentrations of inflammatory cytokines including tumor necrosis factor-alpha （TNF-α）， interleukin-1 beta （IL-1β）， and interleukin-18 （IL-18）. After knee replacement surgery， cartilage tissue was analyzed using Western blot to assess the protein expression levels of p38 MAPK， p-p38 MAPK， NLRP3， Caspase-1， and GSDMD， and Real-time PCR was used to evaluate gene expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD. ResultMicro-CT analysis revealed significant narrowing of the joint space and increased bone spur formation in KOA rats compared with the sham operation group， with a decrease in BV/TV ratio and an increase in Tb.Sp value （P<0.01）. Serum levels of TNF-α， IL-1β， and IL-18 were elevated （P<0.01）. The protein expression levels of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD in cartilage were significantly increased （P<0.01）， and the mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD were also enhanced （P<0.01）. Significant differences in protein expression of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD were observed between normal and diseased cartilage tissues after knee replacement surgery （P<0.05）， and the gene expression of p38 MAPK， NLRP3， Caspase-1， and GSDMD were also significantly different （P<0.01）. HE and SO staining showed roughened joint surfaces， reduced cartilage thickness， and disordered cellular arrangement in KOA rats. OARSI scores were significantly higher （P<0.01）. Compared with the model group， treatment with low， medium， and high concentrations of CXTB resulted in increased BV/TV ratios and decreased Tb.Sp values in the knee joints of rats （P<0.01）. HE and SO staining indicated a trend towards smoother joint surfaces and reduced OARSI scores （P<0.01）. The protein expression levels of p-p38 MAPK， NLRP3， Caspase-1， and GSDMD were notably decreased （P<0.05）， as were the mRNA expression levels of p38 MAPK， NLRP3， Caspase-1， and GSDMD （P<0.01）. Additionally， serum concentrations of TNF-α， IL-1β， and IL-18 were significantly reduced （P<0.01）. ConclusionCXTB intervention may alleviate knee joint degeneration in KOA rats and inhibit the expression of inflammatory factors and pyroptosis of cartilage cells， thereby protecting cartilage. The underlying mechanism may involve modulation of the p38 MAPK/NLRP3/Caspase-1 signaling pathway.