Alzheimer′s disease(AD)is one of the most common causes of cognitive impairment.“Aβhypothesis”and“tau protein aggregation hypothesis”are two representative hypotheses in relation to AD pathology. But recently,therapeutic strategy target?ing on reducing Aβdeposition failed in clinical trials. On the other hand,as the phosphorylation of tau protein is regulated by multiple upstream kinases,inhibition of a single kinase usually cannot effectively suppress the aggregation of the tau. While blocking multiple kinases at the same time will produce serious side effects. Currently,targeting on Aβand tau protein get into awkward situations. In view of this,researchers are looking for new drug targets for improving cognitive function. Phosphodiesterase 4(PDE4 4)is an enzyme responsible for the hydrolysis of cAMP in the body. There are four subtypes for PDE4,and PDE4A,B and D are highly expressed in the central nervous system. Inhibition of PDE4 causes activation of cAMP/PKA/CREB/BDNF signal pathway,which is beneficial for the strengthening and consolidation of learning and memory. This review will focus on the most recent evidence regarding the role of PDE4 in learning and memory.

Cell adhesion molecules (CAMs) are involved in glycoproteins expressed on cell surfaces which play an essential role in clinical disorders. At present, there are several groups of anti inflammatory drugs interfere with the expression of CAMs either directly or indirectly. This paper reviews the study of recent finding pharmacological agents associated with CAMs.

BACKGROUND: The upward attack of drug-heat is a special type of syndromes of coexistence of cold and heat, it influence the treatment and conversion of the primary disease.OBJECTIVE: To investigate the pathophysiological basis of upward attack of drug-heat.DESIGN: A randomized and controlled observation. SETTING: Department of Traditional Chinese Medicine (TCM) of the People' s Central Hospital of Huizhou City.PARTICIPANTS: Totally 427 patients with cold syndrome, visiting on Department of TCM of the People's Central Hospital of Huizhou City from January 1996 to December 2001, were given warm-heat remedy. Among them 66 cases, 30 males and 36 females, got upward attack of drug-heat during the process of treatment were enrolled. All these subjects, according to their visiting order, at a ratio of 2:1, were chosen as treatment group (44 cases) and control group (22 cases).METHODS: For the patients in treatment group: Rhubarb 6 g was added boiling water 100 mL and soaked for 8 minutes, then the soaking solution was given to the patients, once a day, for 3 days successively. For patients in control group: Table salt 6 g was added boiling water 100 mL for soaking for 8 minutes, after the salt was completely dissolved, the solution was given to the patients, once a day for 3 days successively. The patients of the two groups were at the same time given remedy to treat cold syndrome. The changes of free triiodothyronine (FT3), free thyronine (FT4), high sensitizing thyroid-stimulating hormone (HS-TSH) and cortisol of the patients were detected before and after administration of warm-heat remedy, before and after medication with rhubarb. MAIN OUTCOME MEASURES: ① The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of warm-heat remedy. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of rhubarb. ③ Comparison of the therapeutic effects in the two groups.RESULTS: All 66 patients involved entered the final result analysis. ①The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of warm-heat remedy: FT3 and FT4 were decreased as compared with those before treatment [(2.51±1.20),(6.50±2.30); (10.01±3.21), (15.50±6.31) pmol/L], but HS-TSH and cortisol were increased as compared with those before treatment [(8.25 ±3.75),(4.11±1.75) mU/L; (0.56±0.17), (0.43±0.10) μmol/L]. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of rhubarb: FT3 and FT4 ywere increased as compared with those before treatment[(4.71 ±1.56), (2.45±1.25); (14.21 ±4.61),(10.21±3.52) pmol/L], but HS-TSH and cortisol were decreased as compared with those before treatment [(6.24±2.25), (8.35±3.51) mU/L; (0.48±0.10),(0.60±0.17) μmol/L]. ③ Comparison of the therapeutic effects in the two groups: The rate of excellenly effect in treatment group was obviously higher than that in control group (33%, 5%).CONCLUSION: The pathophysiological basis of upward attack of drug heat is stress state of the body, the secretions of the pituitary-thyroid axis play a role of physiological protection, the adrenocortical function is hyperactive, and rhubarb can control this stress state through inhibiting the metabolism of the body.

Traditionally,the nellrorl of central nervous system has been regarded as lack of regeneration capability.Recent studies have found that cerebral ischemia may activate neurogenesis in brains of adult mammals,and bring new hope for neural repair after ischemic brain injury.It is very necessary to fully understand the site of neurogenesis,process and neurogenesis after cerebral ischemia and its regulation mechanisms in adult mammals.

Objective To investigate the clonal origin of malignant cells in multifocal urothelial carcinoma. Methods p53 protein expressions were detected by immunohistochemistry in 22 pieces of tumor tissues from 10 patients with urothelial neoplasms.Mutation in p53 was inferred on the basis of immuno staining . Results The p53 protein expression of various tumors in the same patient completely matched, reflecting that the gene status of the multifocal tumor being the same. Conclusions The results strongly support the view that multifocal urothelial tumors are derived from the monoclonal cell.

Objective To investigate the effect of bevacizumab on apoptosis of drug resistant nasopharyngeal carcinoma(NPC) cells in vitro.Methods The human nasopharyngeal carcinoma(NPC) cell line CNE2 and its cisplatin-resistant CNE2/DDP cells were treated with bevacizumab and DDP in various concentrations.The lethal effects of the both drugs and the apoptosis rates on CNE2/DDP cells were then measured separately with MTT assay and flow cytometry,the mRNA expressions of Bcl-2 and Bax in CNE2,CNE2/DDP and CNE2/DDP/Bev cells were detected with semi-quantitative RT-PCR.Results The killing rate in 10?g/ml bevacizumab group was similar to that of blank group(0.0?4.1% vs.5.2?4.3%,P=0.180),while the rates of combination of 10?g/ml bevacizumab and DDP(0.1?g/ml and 0.2?g/ml,separately) were higher than that of using DDP only(42.3?6.5% vs.34.4?5.4%,P=0.041;62.6?5.5% vs.50.0?5.9%,P=0.009).The apoptotic rate of CNE2/DDP,which was caused by combining 0.1?g/ml DDP and 10?g/ml bevacizumab,was much higher than what was produced by DDP alone(87.29?3.38% vs.50.58?8.83%,P=0.049).By means of semi-quantitative RT-PCR assay,the expressions of Bcl-2 mRNA in CNE2,CNE2/DDP and CNE2/DDP/Bev cells were 0.613,0.952 and 0.135,respectively.Meanwhile,the expressions of Bax mRNA were 0.665,0.387 and 1.751,separately.Conclusion Bevacizumab can greatly increase the drug sensitivity of CNE2/DDP cells to DDP;apoptosis is inhibited in MDR cells,but it can be promoted by bevacizumab.

Aim Pharmacological intervention is one of important strategies to deal with spinal cord injury.The effect of Pharmacological intervention has highly differentiated features because of complex physiopathology mechanisms in SCI.Moreover contraindications,complications having different features,it is constantly the focal point in the selection of pharmacological intervention to protect spinal cord,attenuate secondary injury and promote injuried neuron regeneration.At present only several of those have been applied in clinic and the majority are still being carried out in clinic trial stage,even preclinical animal experiment stage.This paper made a particular review of the current situation in pharmacological intervention for spinal cord injury.

Objective To evaluate the feasibility and clinical efficacy of laparoscopic nephron-spring surgery for renal tumor.Methods From September 2004 to November 2006,29 patients with renal tumor underwent laparoscopic nephron-sparing surgery without hilar clamping or with temporary hilar control in our hospital.The retroperitoneal approach was used in 25 patients with 4 trocars.During the operation,the renal artery was exposed and then the vessel bundles were pulled out of the abdominal cavity through one of the trocars,passing by the renal artery without clamping it.Afterwards,fatty cysts surrounding or on the surface of the tumor were resected.Tumor excision was then performed using ultrasonic shears.An incision was made at the point 0.5 cm away from the margin of the tumor,and was extended deeply to completely cut the tumor.Meanwhile,bleeding was controlled with bipolar diathermy.The renal artery was occluded when necessary so that the tumor could be cut within a limited time duration.And the occlusion could be re-opened after controlling the bleeding.After the procedure,the renal incision was compressed with gauze,sutured with 2-0 absorbable sutures,and covered with fibrin sealant.In the other 4 patients,trans-peritoneal approach was used.The ureter was exposed near the lower pole of the kidney and separated towards the renal hilum to find out the renal artery.The following steps were similar to the above mentioned. Results In all the patients,the procedures were done without conversion to open surgeries.In this series,20 operations were completed without clamping the renal artery;and in the other 9,the mean time of renal artery occlusion was 14 min(5-20 min).In our patients,the mean operation time was 165 min(105-240 min),and the mean blood loss was 90 ml(20-800 ml).Two of the patients received blood transfusion during the surgery.The mean postoperative hospital stay was 9 d(7-17 d).No complications,such as urine leakage,occurred after the operation.Eighteen patients were followed up for a mean of 9 months(1-26 month),no recurrence of tumor was found.Conclusion Laparoscopic nephron-sparing surgery without hilar clamping or with contemporary hilar control is feasible and safe for patients with peripheral renal tumor not involving the renal collecting system.

AIM: To study the therapeutical effects of salvianolic acid B (Sal B) on myocardial infarction(MI) in dogs. METHODS : The models of myocardial infarction were produced by ligation of the left anterior descending (LAD) coronary artery in the anaesthetized dogs. The extent of myocardial ischemia was detected by epicardial-electrocardiogram and the extent of infarction was determhled by N-BT staining method. The parameter of lactate dehydrogenase was determined in the serums of dogs. RESULTS : It was indicated that the adminstration of Sal B(1、3 and 10mg/kg) by the way of intravenous injection reduced the extent of myocardial infarction (N-ST) ( P

Aim To investigate the effects of anti-morphine vaccines on pharmacological actions of morphine in mice.Methods Morphine-6-succinyl and morphine were conjugated respectively with Blue Carrier(BC) in the presence of carbodi-imide.After being immunized with both vaccines(M-BC,M-6-S-BC),the withdrawal syndrome and the abirritation were observed in mice.Results The withdrawal syndrome of the immune mice with M-6-S-BC and M-BC vaccines were reduced markedly compared with the model group,the skipping times were decreased and the latency was longer(P