Objective:To investigate the effects of various bio-adhesive polymers on bio-adhesive characteristics and release rate of 5-fluorouracil HP-β-CD inclusion complex thermo-sensitive gels. Methods: Bio-adhesive polymer, such as hydroxypropylmethylcellu-lose ( HPMC) , sodium alginate ( SA) , sodium hyaluronat ( HA) ,carbopol and polycarbophil was respectively used to prepare the ther-mo-sensitive gels, and the bio-adhesive force was studied. The phosphate buffer (pH 7. 2) was used and the drug release characteris-tics were studied using dialysis technique. Results: The bio-adhesive force of the gels with 0. 2% polycarbophil was 32. 3 g·ml-1 , and the drug release time was prolonged to 8 h. There was no obvious difference in the dissolution among the gels with the various bio-adhesive polymers. Conclusion:Using 0. 2% polycarbophil as the bio-adhesive polymer, 5-fluorouracil HP-β-CD inclusion complex thermo-sensitive gels show good bio-adhesive force and prolonged drug release characteristics.

Objective To observe the influences of stemona alkaloids on esterase isozymes activities and glycogen content of Oncomelania hupensis in order to explore the molluscicidal mechanism of stemona alkaloids.Methods O.hupensis snails were immersed in the liquid of stemona alkaloids at the concentration of 6.5 mg/L(72 h LC50),the surviving ones were picked out and sampled after being immersed for 12,24,48,72,96 h,then PAGE and anthrone colorimetry methods were used to observe the changes of liver esterase isozymes activities and tissue glycogen content of O.hupensis during the immersion period.A group of snails immersed in de-chlorinous water served as control.Results Esterase isozymes activities firstly increased,and then decreased until almost lost completely during the 96 h immersion period.Meanwhile,glycogen content gradually decreased as the immersion time extended.After being immersed for 96 h,glycogen content decreased by 72.00% compared with the control group.Conclusion Stemona alkaloids could inhibit the viability of O.hupensis by causing decrease of esterase isozymes activities and glycogen content.

Objective To investigate effects of Baishile Capsules on cAMP-CREB-BDNF signal pathway about hippocampal neurogenesis in model rats with chronic unpredicted stress depression. Methods SD rats were randomly divided into blank group, model group, fluoxetine hydrochloride group, and Baishile Capsules high, medium, and low dose groups. Chronic stress depression rat model was established by chronic and mild unpredictable stressors. All groups were given relevant medicine for 21 days. The open-field test, sugar consumption experiment, place navigation test, and space searching experiment were used to detect behavior changes of the rats. ELISA was used to detect content of corticosterone in plasma. The protein expressions of PKA, BDNF, and CREB were detected by immunohistochemical method. Results Compared with model group, Baishile Capsules high dose and medium dose groups could remarkably increase the number of vertical and horizontal activities and 1% sucrose partial eclipse. Platform latency and target quadrant searching time decreased significantly in Baishile Capsules high dose group (P<0.05), and content of corticosterone in plasma increased obviously (P<0.05) in Baishile Capsules all dose groups. Protein expressions of PKA, CREB, and BDNF in hippocampal DG and CA3 area increased significantly (P<0.05) in Baishile Capsules high dose group. Conclusion Baishile Capsules can promote hippocampal neurogenesis through the cAMP-CREB-BDNF signal pathway and realize anti-depression effect.

Objective To compare the anterograde amnesia produced by midazolam,propofol and dexmedetomidine when used to supplement sedation during neuraxial anesthesia.Methods Sixty patients of both sexes,aged 18-50 yr,with body mass index of 23-26 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective operation on lower limbs with neuraxial anesthesia,were divided into 3 groups (n =20 each) using a random number table:midazolam group (group M),propofol group (group P) and dexmedetomidine group (group D).When the height of anesthesia was kept below T10,midazolam in a loading dose of O.05 mg/kg was intravenously injected in group M,propofol in a loading dose of O.4 mng/kg was intravenously injected in group P,and dexmedetomidine in a loading dose of 0.6 μg/kg was intravenously injected in group D.The infusion rate of the 3 drugs was adjusted to maintain bispectral index value at 82-86.When Observer's Assessment of Alertness/Sedation Scale scores achieved 3 or 4 after administration,anterograde amnesia was measured by postoperative recall of cards.The development of intraoperative hypotension,bradycardia and respiratory depression was recorded.Results Compared with group M,the incidence of global amnesia was significantly decreased in P and D groups (P＜0.05).There was no significant difference in the incidence of global amnesia between group P and group D (P＞ 0.05).No patients developed hypotension,bradycardia or respiratory depression in three groups.Conclusion Midazolam produces better anterograde amnesia than propofol and dexmedetomidine when used to supplement sedation during neuraxial anesthesia.

Objective To evaluate the role of calpain in sevoflurane anesthesia-induced apoptosis in hippocampal neurons of aged rats.Methods Fifty-four healthy female Sprague-Dawley rats,aged 18 months,weighing 450-550 g,were randomly divided into 3 groups (n=12 each) using a random number table:control group (group C),sevoflurane group (Sev group) and calpain inhibitor M DL28170 group (group M).In group C,the rats inhaled 50％ O2-50％N2 for 3 h.In Sev group,the rats inhaled 3％ sevoflurane for 3 h.In group M,MDL28170 10 mg/kg was injected via the tail vein,30 min later 3％ sevoflurane was inhaled for 3 h,and MDL28170 was simultaneously infused at 3.33 mg · kg 1 · h-1 via the tail vein.Nine rats in each group were selected,and cognitive function was assessed by using Morris water maze test at 30 min before anesthesia and 1-5 days after anesthesia.The escape latency and frequency of crossing the original platform were recorded.After the end of Morris water maze test performed at 30 min before anesthesia and 1-5 days after anesthesia,3 rats in each group were sacrificed,and hippocampal tissues were obtained for detection of cell apoptosis (by flow cytometry) and intracellular [Ca2+] i.Apoptotic rate was calculated.Results Compared with group C,the escape latency was significantly prolonged,and the frequency of crossing the original platform was decreased,and the apoptotic rate and intracellular [Ca2+]i were increased at 1 day after anesthesia in Sev and M groups.Compared with group Sev,the escape latency was significantly shortened,the frequency of crossing the original platform was increased,and the apoptotic rate was decreased at 1 day after anesthesia,and no significant change was found in intracellular [Ca2+]i in group M.Conclusion Calpain activation is involved in sevoflurane anesthesia-induced apoptosis in hippocampal neurons of aged rats.

Objective:To establish a method for determining three residual organic solvents in nimodipine liposomes. Methods:The samples were injected into a DB-624 capillary column (30 m × 0. 32 nm,1. 8 μm) by a headspace sampler and analyzed with an FID detector, the carrier gas was nitrogen, the injector temperature was 250℃, and the detector temperature was 250℃. The column temperature was programmed raised. Results:Three residual solvents, namely ethanol, acetone and acetic ether were completely sepa-rated. There was a good linearity within the experimental concentration range. The average recovery was 98. 9%,98. 5% and 99. 4%(RSD=0. 32%,1. 12%,0. 76%,n=9), respectively. The detection limits was 0. 20, 0. 18 and 0. 22μg·ml-1, respectively . Con-clusion:The method is rapid, sensitive and accurate. It can be used in the determination of residual organic solvents in nimodipine li-posomes.

Objective To evaluate the role of mitochondria-mediated apoptosis in hippocampal neurons in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods Sixty healthy male Sprague-Dawley rats,aged 20 months,weighing 550-600 g,were randomly divided into 2 groups (n =30 each) using a random number table:control group (group C) and sevoflurane anesthesia group (group S).Animals inhaled pure oxygen and 3 ％ sevoflurane for 4 h in C and S groups,respectively.Ten rats were chosen at 1 and 6 days after anesthesia and hippocampal tissues were obtained for detection of cell apoptosis and mitochondrial membrane potential (MMP) (using flow cytometry) and expression of cytochrome c (Cyt c) in cytoplasm and activated caspase-3 in hippocampal neurons (by Western blot).The apoptotic rate was calculated.Results Compared with group C,the escape latency was significantly prolonged,the frequency of crossing the original platform,the percentage of time of staying at the original platform quadrant and MMP were decreased,the apoptotic rate was increased,and the expression of activated caspase-3 and Cyt c in cytoplasm was up-regulated in.group S.Conclusion The mechanism by which sevoflurane anesthesia induces cognitive dysfunction is related to the activation of mitochondria-mediated apoptosis in hippocampal neurons of aged rats.

Objective To evaluate the effect of preconditioning with nimodipine on postoperative cognitive dys function of aged rats.Methods Ninety healthy male Sprague-Dawley rats,aged 18 months,weighing 400-500 g,were randomly divided into 3 groups (n =30 each) using a random number table:nimodipine control group (group N),surgery group (group S),and nimodipine + surgery group (N+ S group).In N and N + S groups,nimodipine 1 mg/kg was intraperitoneally injected,while the equal volume of normal saline was given instead in S group.30 min later,group N inhaled pure oxygen for 2 h,and S and N + S groups inhaled 1.8 ％ isoflourane for 2 h when splenectomy was performed.Morris water maze test was performed on 1 day before operation and 1st,3rd and 7th days after operation.After the end of Morris water maze test at 1 day before operation and 1st and 7th days after operation,10 rats were sacrificed and brains were removed and hippocampi were isolated for determination of apoptosis in hippocampal neurons,intracellular [Ca2+] i in cytoplasm,and hippocampal Bcl-2 and Bax mRNA expression and for examination of ultrastructure of hippocampal neurons.Results Compared with the value before administration,the escape latency was significantly prolonged,the frequency of crossing the original platform was decreased,apoptotic rate and [Ca2+]i were increased,Bcl-2 mRNA expression was down-regulated,and Bax mRNA expression and Bax/Bcl-2 mRNA ratio were up-regulated at each time point after operation in S and N + S groups,and no significant changes were found in the parameters mentioned above in N group.Compared with group S,the escape latency was significantly shortened,the frequency of crossing the original platform was inecreased,apoptotic rate and [Ca2+]i were decreased,Bcl-2 mRNA expression was up-regulated,and Bax mRNA expression was down-regulated at each time point after operation in group N + S.Pathological changes were found in S and N + S groups and the damage was severer in S group than in N + S group.Conclusion Nimodepine preconditioning can prevent postoperative cognitive dysfunction of aged rats,and inhibition of calcium overloadinduced apoptosis in hippocampal neurons may be involved in the mechanism.

Objective To observe the effects of Baishile Capsules on the hippocampal PI3K signaling pathway in chronic mild unpredictable stress (CUMS) rats; To discuss its mechanism of action for anti-depression. Methods SD rats were randomly divided into 6 groups, control group, model group, fluoxetine group, Baishile Capsules high-, medium- and low-dose groups, with 10 rats in each group. The cums depression model was established, and gavage for medication was conducted at the same time for 21 days in a row. The behavioral changes of rats in each group were detected by the novel feeding experiment and Open-field experiment; monoamine neurotransmitter in serum were detected by ELISA; the expressions of PI3K, AKT and SGK1 in rat hippocampus were detected by immunofluorescence and Western blot test. Results Compared with the control group, feeding latency of rats in model group was significantly prolonged (P<0.01), horizontal and vertical activities were significantly reduced (P<0.01); the content of serum monoamine neurotransmitter decreased (P<0.01); the expressions of PI3K and AKT in hippocampus decreased, while the expression of SGK1 increased (P<0.01, P<0.05). Compared with the model group, Baishile Capsule high- and medium-dose groups can significantly shorten the incubation period of feeding rats (P<0.05), and increase the number of horizontal and vertical activities (P<0.01); the 5-HT and NE levels in serum were significantly elevated (P<0.05, P<0.01); the expressions of PI3K, AKT in hippocampal increased; the expression of SGK1 decreased (P<0.05, P<0.01). Conclusion Baishile Capsules can alleviate the depression like behavior in rat models, and regulate key factors of hippocampal PI3K signaling pathway, so as to exert antidepressant effects.

Objective To study the changes of behavior and depression-like classic indicators after hippocampal microinjection of K252a,and to establish a new animal model of depression.Methods SD rats were randomly divided into five groups,namely the control group,sham group,chronic stress depression model group,hippocampal of K252a microinjection group,and hippocampal microinjection K252a plus chronic stress group.Open field experiments,sucrose consumption test,and Morris water maze behavioral assay were used to assess the behavioral changes in the rats.ELISA was used to detect the plasma monoamine neurotransmitter,radioimmunoassay was used to determine the plasma CRH,ACTH,CORT contents,and western-blotting was performed to observe the protein expression of BDNF,CREB,ERK1/2,and BCL-2 in the hippocampus.Results Compared with the control group,the amount of activity,sugar consumption,learning and memory abilities were decreased(P<0.05 or P<0.01),also the serum monoamine neurotransmitters were decreased (P<0.01),HPA axis function was improved (P<0.01),and the expression of BDNF,CREB,ERK1/2,BCL-2 decreased in the CUMS group(P<0.05 or P<0.01),but there was no significant difference in the DMSO group.Compared with the DMSO group,the activity,consumption of sucrose,learning and memory ability were significantly decreased(P<0.05 or P<0.01),while the HPA axis function was increased (P<0.05 or P<0.01),the serum monoamine neurotransmitters decreased(P<0.05 or P<0.01),and the BDNF,CREB,ERK1/2,BCL-2 expressions in the hypocampus were significantly decreased(P<0.05 or P<0.01) in the K252a group and K252a + CUMS group.Compared with the CUMS group,the K252a group and K252a + CUMS group did not show significant changes in these parameters.Compared with the K252a group,these indicators were not significantly changed in the K252a + CUMS group.Conclusions The results of behavior,hematology,and molecular biology analysis show that this model has a great similarity to the classical model of CUMS in surface validity,construct validity,and functional validity.It may provide an alternative investigative technology platform for basic research and antidepressant drug screening.