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.

Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by cognition impairment and behavioral abnormalities.While the mechanisms involved in AD remain unclear,various hypotheses have been proposed regarding pathogenesis of AD,among which the oxidative stress hypothesis has attracted more and more attention.In the present article,the relationship between oxidative stress and AD is reviewed,including sources of neuronal oxygen radical generation,the link of oxidative stress to pathogenesis of AD,preclinical and clinical studies of AD,therapeutic effects of antioxidants and phosphodiesterase inhibitors on AD.

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.

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.

Imaging examination results of 50 breast cancer patients undergoing surgical treatment between January 2006 and December 2007 were retrospectively analyzed. Our data showed that 32 patients (64%) had positive results in contrast-enhanced CT, and metastases to lung, mediastinal lymph node, axillary lymph node, or chest wall were found in 22 (44.0%), 11 (22.0%), 10 (20.0%), and 3 patients (6.0% ), respectively. Only 10 patients (20%) had abnormal image manifestation in X-ray, 8 of which showed metastases to lung. In summary, contrast-enhanced CT examinations may be more useful in the detection of metastases in post-operative follow up of breast cancer.

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 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.

Objective To explore the value and efficacy of retroperitoneal laparoscopic adrenalectomy.Methods From August 2002 to December 2007,a total of 401 cases of retroperitoneal laparoscopic adrenalectomy were performed in our hospital.Among the cases,nonfunctioning adenoma was diagnosed in 151 patients;hyperaldosteronism was detected in 139,Cushing’s syndrome in 37,pheochromocytoma in 19,myelolipoma in 13,and other diseases were found in 42.Results Among the cases,5 were converted to open surgery because of difficulties in the operation due to a huge tumor(1),extensive adhesion between the tumor and the inferior vena cava(2),or massive bleeding(2).The other 396 cases of retroperitoneal laparoscopic adrenalectomy were completed successfully with a mean operation time of 105 minutes(30 to 270 minutes),and a median blood loss of 45 ml(20 to 1000 ml).Two of these patients had massive hemorrhage(1000 and 800 ml respectively),and received red blood cells transfusion(2 U) during the surgery.The rupture of the inferior vena cava or diaphragm occurred in two cases,and was repaired under a laparoscope.Follow-up was available for up to 1 to 64 months(mean 23.9) in 364 patients;none of them had long-term complications or recurrent benign tumors.Conclusions Retroperitoneal laparoscopic adrenalectomy should be used as the first choice for benign adrenal neoplasms,since the procedure is safe,effective,and minimally invasive,and the patients recovery quickly after the surgery.

OBJECTIVE: To observe the effects of ginkgolide (GL) on the cerebral blood flow in dogs. METHODS: Dogs anesthetized with sodium pentobarbital were randomly divided into 5 groups, with 4 dogs in each group. Ginkgolide of 4.86, 14.6 and 43.7 mg/kg and Xingling Granule of 0.22 g/kg were administered by gavage to the dogs in each of 4 groups. The dogs in the other group were administered with edible oil (1 ml/kg) as control group. The cerebral blood flow, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and electro-cardiogram of the dogs were measured at different times after the administration. RESULTS: Ginkgolide of 4.86, 14.6 and 43.7 mg/kg had no obvious effects on the blood pressure and the heart rate. Ginkgolide of 14.6 and 43.7 mg/kg increased the cerebral blood flow 90 minutes after administration, and ginkgolide of 43.7 mg/kg obviously decreased the cerebral vascular resistance 150 minutes after administration. CONCLUSION: Ginkgolide can increase the cerebral blood flow and decrease the cerebral vascular resistance, and it has no obvious effects on blood pressure and heart rate in dogs.