Platelet-activating factor (PAF), an endogenous bioactive lipid generated by phospholipase A2 and other pathways, displays a variety of biological activities in the nervous system. It has been suggested that PAF plays important roles in neuronal physiological functions including acting as a retrograde messenger to enhance synapse plasticity and memory formation, via activation of its specific membrane receptors.Therefore,the drugs that mimic the action of PAF or modulate the production and inactivation of PAF maybe promising in memory-enhancing. However, under certain pathological conditions, such as Alzheimer's disease, HIV-associated dementia or post-ischemic neuronal death, acting as a potent inflammatory mediator and neurotoxin, PAF has been implicated in the pathophysiology of brain injury. So, modulating the metabolism and effects of PAF (e.g., blocking the PAF receptor) may become important strategies of intervention of Alzheimer's disease, HIV-associated dementia or post-ischemic neuronal death.

G protein-coupled receptors(GPCRs)mediate cell signaling transduction of most hormones and neurological transmitters and behave as the key targets for drug research and development.Recently,the evidence of allosteric modulation of GPCRs has been revealed.Allosteric modulators have the ability to selectively tune responses only in tissues in which the endogenous agonist exerts its physiological effects,and have the potential for greater receptor subtype selectivity.The GPCRs allosteric modulators have been found and some of them have been in clinical use.Under the strategy of allosterism on structure activity relationship and target directed screening,more and more GPCRs allosteric modulators will be developed in the future.

Objective To observe the effect of multiple monitoring of total intravenous anes-thesia on postoperative cognitive function in elderly patients.Methods Elective 100 patients undergo-ing general anesthesia for abdominal operation,56 males,44 females,aged 65-80 years,ASA physi-cal status Ⅱ or Ⅲ.All patients were divided into multiple monitoring group (group M)and routine monitoring group (group R)by random digital table method,n =50 each.In group M,the anesthesi-ologists modulated anesthetic drugs to make NTI of 37-56 and rSO 2 higher than 50% or not lower than the baseline value by 20%,while in group R the infusion rate of propofol,remifentanil and cisa-tracurium was adjusted by anesthesiologists according to anesthesiologist’s experiences by the pa-tients’monitoring index.Cognitive function of patients in the two groups were evaluated using MMSE 1 d before surgery and 1 d,3 d,7 d,1 month and 3 months after surgery.The occurrence of cognitive dysfunction 7 d,1 month and 3 months after surgery,the postoperative recovery and the dosage of propofol,remifentanil and cisatracurium were recorded.Blood was randomly selected from each group to determine the serum content of S100βand Aβ1-42 by ELISA method at the time point of before surgery (T0 ),one hour after starting surgery (T1 ),the end of surgery (T2 )and postopera-tive 24 hours (T3 ).Results The incidence of postoperative cognitive decline in group M on 1 d (8%vs.22%),3 d (2% vs.1 6%)after surgery were significantly lower than that in group R (P <0.05). Postoperative cognitive dysfunction between the two groups 7 d and 1 month,3 months after surgery has no statistical significance.The dose of propofol [(3.3 ± 0.8)mg · kg-1 · h-1 vs.(3.7 ± 0.7 ) mg·kg-1 ·h-1 ,P < 0.05 ] and cisatracurium [(104 ± 47 )μg · kg-1 · h-1 vs.(124 ± 68 )μg·kg-1 ·h-1 ,P <0.05]in group M was less than that in group R.The time of eye-opening [(10 ±3)min vs.(1 6±6)min,P <0.01],extubation [(13±3)min vs.(22±7)min,P <0.01]and lo-cation [(1 7±4)min vs.(27 ±9)min,P <0.01 ]was shorter in group M.Compared with T0 ,the serum level of S100βprotein was significantly increased in group M at T1 ,T2 and group R at T1-T3 (P <0.05);The level of serum S100βprotein in group M was significantly lower than that in group R (P <0.05).Compared with T0 ,Aβ1-42 protein level was significantly reduced in two groups at T1 and T2 (P <0.05),but there was no significant difference between the two groups.Conclusion Total intravenous anesthesia with multiple monitoring can reduce neural injury and reduce the incidence of early postoperative cognitive decline in elderly patients with abdominal surgery,but has no significant effect on the incidence of POCD.

Missing data plagues almost all surveys and researches. The occurrence of missing data will cause losses of original sample information and undermine the validity of the research results to some extents, so researchers should attach great importance to this problem. In this article, we introduced 3 kinds of missingness mechanism, namely missing completely at random, missing at random, and not missing at random. We summarized some common approaches to deal with missing data, including deletion, weighting approach, imputation and parameter likelihood method. Since these methods had its pros and cons , we should carefully select the proper way to handle missing data according to the missingness mechanism.

Alzheimers disease is a progressive neurodegeneration disorder that is characterised by the accumulation of ? amyloid deposits and neurofibrillary tangles. It has been long assumed that the disrupted interneuronal communication that occurs in AD brain does not involve widespread changes in postsynaptic receptor function. However, recent evidence suggests that both the neurotransmitter receptor/G protein modulated adenyl cyclase and the phosphatidylinositol hydrolysis signal transduction cascades are disrupted in AD. Such disruption in AD may provide a reason for the relative lack of success of neurotransmitter replacement therapies for the disorder. Moreover it can direct drug research and development for AD treatment.

AIM: To investigate the enhancement of ethanol on percutaneous permeation and topical anaesthesia of tetracaine gel. METHODS: Tetracaine (4%, w/w) gels were prepared by using 20% and 70% ethanol as penetration enhancers. Franz diffusion chamber and UV spectrophotometry were adopted in the transdermal osmotic test of isolated mouse skin. Von Frey test was used to evaluate the topical anesthetic effect of tetracaine gels. RESULTS: 20% and 70% ethanol greatly improved the percutaneous permeation of tetracaine gel (P

Nerve growth factor (NGF), one of the most potent growth factors for cholinergic neurons, has generated great interest as a potential target for the treatment of Alzheimers disease (AD). The degeneration of basal forebrain cholinergic neurons, which provides the major source of cholinergic innervation to the cerebral cortex and hippocampus, occurs early and contributes significantly to cognitive decline in AD. Those regions show high level expression of NGF and NGF receptors and depend on NGF for their survival and proper function. NGF executes its effects mainly by binding high affinity receptor TrkA in the remaining neurons of AD. Meanwhile, stimulation of neurons may protect those cells from the deleterious effects of AD, a phenomenon called “use it or lose it.”However, the use of NGF as therapeutic agent is limited by their hindered mobility through the blood brain barrier. Many theoretical and technical issues for NGF delivery to the target region in the brain remain to be solved, before NGF can live up to its potential for the treatment of AD.

The mechanisms of antidepressants are still unclear. There a re two classical theories on monoamine neurotransmitter or on neurotransmitter rec eptors, but both of them can not fully explain the delayed therapeutic action of antidepressants. Recently, many researches have focused on the postreceptor int racellular signal transduction as the mechanism of antidepressant action. G protein is the molecular basis of antidepressants. Neurotransmitter receptors and G protein are the two sectors of their therapeut ic action. They will ultimately influence intracellular signal transduction and result in relative effects such as phosphoration, the induction of neurotrophic factors and neurogenesis. This mechanism suggests a reasonable explanation for t he clinical delaying of antidepressants and it will do great help for the develo pment of antidepressants. It makes the design of novel, safe and more efficaciou s antidepressants possible and provides significant information for the elucidat ion of biology of depression.

Objective To investigate the protective effects of etomidate on the cortex and hippocampus against anoxia-reoxygenation (A/R) injury.Methods Male adult SD rats weighing 90-100 g were anesthetized with ether and decapitated. Their brains were immediately removed. Cortical and hippocampal slices were prepared and were randomly divided into 6 groups: group Ⅰ control; groupⅡ A/R; in group Ⅲ - Ⅵ the brain slices were first incubated in the presence of etomidate 3, 6, 15 ?mol?L-1 or etomidate 6 ?mol?L-1 + picrotoxin 50 ?mol?L-1 (GABA receptor antogonist) for 30 min. Then the slices were subjected to 10 min anoxia (95% N2 +5% CO2) followed by 120 min reoxygenation. The absorbance value (A490) of TTC staining (2. 3. 5-triphenyl tetrazolum chloride) and intracellular free Ca2+ ([Ca2+]i) accumulation were determined. Results The A490 in cortical and hippocampal slices were significantly decreased while [Ca2+] i significantly increased in A/R group as compared with control group. Different concentrations of etonlidate attenuated the changes induced by A/R especially 6 ?mol?L-1. The protective effects of etomidate could be antagonized by GABAA antagonist. Conclusion Etomidate can protect the cortex and hippocampus against A/R injury to some extent by acting on GABAA recoptor and decreasing intracellular Ca2+ overloading.

Lipoxygenase(LO) pathway had been implicated in the pathogenesis of such cardiovascular diseases as hypertension, atherosclerosis, restenosis, and palys and important role in the development of these disease. LO inhibitiors could suppress vascular contractile responses significantly, reduce blood pressure, inhibit migration of vascular smooth muscle cells(VSMC), attenuate neointimal thickening in the injuried arteries and generation reactive oxygen species(ROS), block monocyte binding to VSMC, etc. The effects of LO inhibitors were associated with marked inhibition of MAPK pathway. Therefore, inhibition of LO pathway may provide a new strategy for preventing and treating above diseases, suggesting that LO mat be a novel taget for such purposes.