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.

Of the 411 hepatitis with severe jaundice admitted, 124 ( 30. 17%) had head perspiration. Based on Zhang Zhongjing's etiologic - pathogenic conception, 102 cases of such patients were treated by the principle of cooling and activating blood, benefitting Qi and Yin. 89 cases had jaundice eliminated, 13 cases had residual jaundice. All 22 cases of chronic severe hepatitis survived. Of them, 9 early stage cases were all survived, 7 of the 8 cases of intermediate stage survived, only 1 out of 5 cases of late stage survived.

Objective To investigate the water equivalent of two solid water phantoms.Methods The X-ray and electron beam depth-ion curves were measured in water and two solid water phantoms,RW3 and Virtual Water.The water-equivalency correction factors for the two solid water phantoms were compared.We measured and calculated the range sealing factors and the fluence correction factors for the two solid water phantoms in the case of electron beams. Results The average differenee between the measurled ionization in solid water phantoms and water was 0.42%and 0.16%on 6 MV X-ray(t=-6.15.P=0.001and t=-1.65,P=0.419)and 0.21%and 0.31%on 10 MV X-ray(t=1.728,P=0.135 and t=-2.296,P=0.061),with 17.4%and 14.5%on 6 MeV electron beams(t=-1.37.P=0.208 and t=-1.47,P=0.179)and 7.0%and 6.0%on 15 MeV electron beams(t=-0.58.P=0.581 and t=-0.90,P=0.395).The water-equivalency correction factors for the two solid water Dhantoms varied slightly largely,F=58.54,P=0.000 on 6 MV X-ray,F=0.211.P=0.662 on 10 MV X.ray,F=0.97.P=0.353 on 6 MeV electron beams,F=0.14,P=0.717 on 15 MeV electron beams.However,they were almost equal to 1 near the referenee depths.The two solid water phantoms showed a similar tread of Cpl increasing(F=26.40,P=0.014)and hpl decreasing(F=7.45,P=0.072)with increasing energy.Conclusion The solid water phantom should undergo a quality control test before being clinical use.

Objective To explore and analyze effect of heparin combined with urokinase therapy on lower limb venous thrombosis.Methods 90 cases with lower extremity venous thrombosis were chosed and divided into control group of 45 cases and experimental group of 45 cases according with random number table method.Control group was given pure low molecular heparin treatment, experimental group was treated with small dose of urokinase static drop on the basis of control group, 7 days for a course, a total of 2 course of treatment.Compared two groups before and after treatment of lower limb venous patency rate changes, blood coagulation function index, adverse reactions and the recurrence rate.Results Compared with control group post-treatment.patency rate of posterior divisions, popliteal vein and posterior tibial vein of experimental group were significantly better (P<0.05).Experimental group post-treatment compared with control group post-treatment, PT, APTT, TT time had significant difference ( P <0.05 ).Patients incidence of adverse reactions were significantly lower than control group ( P <0.05 ).Patients were followed up for 1 year recurrence rate was significantly lower than control group ( P <0.05 ).Conclusion Effect of low molecular heparin combined with urokinase in the treatment of venous thrombosis of lower limbs significant and its prognosis is well.

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 the general anesthesia combined with peridural anesthesia on hirschsprung's radical operation through children abdominoscope. Methods 40 children patients with hirschsperung were elective eradicative operated by using endotrachal intubation complex vein general anesthesia combined with continuons peridural anesthesia.ECG,HR,MAP,SPO 2,P ET CO 2 were monitored, and blood gas were recorded and analyzed before pneumoperitoneum,15 minutes and 40 minutes after pneumoperitoneum,1 minute after deflation,before decannulation at the operation termination.Results Compared with before pneumoperitoneum date,HR inereased obviously 40 minutes after pneumoperitoneum,and before decannulation at the operation termination,peak pressure in airway increased obviously after pneumoperitoneum,the difference was notable,SPO 2 decreased after pneumoperitoneum,the difference was also significant.pH decreased gradually with the time prolongation,there was obviously difference.The trend of P ET CO 2 and PaCO 2 changes were analogous,P ET CO 2 had much notable difference after pneumoperitoneum,PaCO 2 had notable difference at the operation termination,and before decannulation,it was decreased to the basic value.Conlusions Hirschsprung's Disease eradical operation using general anesthesia combined with peridural anesthesia under abdominoscope guide,can immobilize ill children completely,relieve pain perfectly,muscular relaxation satisfactory,the physical interference to body is little and less complication.

Objective To evaluate the modified Physical and Operative Severity Score for the Enumera-tion of Mortality and Morbidity (POSSUM) in predicting the postoperative morbidity in patients with fractures of the pelvis and acetabulum. Methods The clinical data of 94 patients with pelvic and acetabular fractures were retrospectively analyzed. Their postoperative prognosis during hospital stay was evaluated with the POSSUM scoring system modified according to the features of orthopedics and pelvic and acetabular fractures. The peritoneum in-fection in the severity index of operation was replaced by operative approach, the several operations at one time by operative duration, and the cancer by the associated injury. The size and type of operation were made into 4 grades with corresponding orthopedic scores. The scores were compared between the complication group and the non-complication group. The receiver operator characteristic (ROC) curve was drawn to describe the coincidence degree, define the cut points, and evaluate its predicting capability. Results The mean preoperative physi-ological score (PS) and operative severity score (OS) in the complication group (38 cases) were significantly higher than those in the noncomptication (56 cases) (17.26 ± 2.84 vs 16.04 ± 2.77; 19.50 ± 5. 14 vs 13.00 ±3.81 ) ( P ＜ 0.05) . In the modified POSSUM, the area under ROC curve was 0. 856, the cut point 43%, sen-sitivity 73.68%, specificity 80. 36%, and coincidence degree 77.66%. Conclusions Since the modified POSSUM scoring system has a high capability of predicting postoperative morbidity for fractures of the pelvis and acetabulum, it can be helpful for surgeons to lower operative risks and ensure safety in operation. When the score is higher than the cut point, the risk is too great for an operation. Therefore, the fracture should be treated non-operatively or mini-invasively until the score is lower than the cut point.

Objective To investigate the feasibility, short-term efficacy and adverse effects of 125 I seed implantation guided by ultrasonography or CT in the treatment of recurrent rectal cancers. Methods A total of 15 patients (4 women and 11 men) with recurrent rectal cancer entered the study. Uneer epidural anesthesia, the patients were treated with 125 I seed implantation under the guidance of either transvaginal ultrasonography or CT scans. The prescribed matched peripheral dose (MPD) was 90~110 Gy, with an activity per seed of 0.50~0.70 mCi and the total number of sources implanted of 33~70. Chest and pelvic X-ray examinations were performed within 24~48 hours after implantation to determine whether or not seed misplacement or migration existed. An additional three-dimensional conformal radiation therapy with a 4~6 fields technique was required in 6 patients 4 weeks postoperatively, with 200~300 cGy/fx, 5 fx/week, up to a total dose of 4500~5 000 cGy. Additional chemotherapy with oxaliplatin, 5-fluorouracil and tetrahydrofolic acid for one treatment course was given in 2 patients. The patients were followed for 3~15 months and the tumors were evaluated by CT findings. Results Relief from pain was achieved at a mean of 7 days after procedure, offering a complete relief in 12 patients, a partial relief in 2, and no change in 1, the effective rate being 93%(14/15). Nine patients showed a complete remission, 2 showed a partial remission, 4 showed a progressive disease, the local control rate being 73%(11/15). Two patients died of the dissemination to lungs. In 1 patient 1 seed had migrated to the pelvic side-wall and did not cause any clinical morbidity in a follow-up of 12 months. Conclusion 125 I implantation in recurrence of rectum cancer guided by ultrasonography or CT was safety, minimally invasion, low morbidity and high efficacy, it was worth of development and promotion.

Objective To evaluate the direct deleterious effect of immunosuppressive agent to human islets, and to explore the suitable immunosuppressive protocol for human islet transplantation. Methods Human islet cells cultured in vitro were exposed to various therapeutic concentrations of four immunosuppressive agents for 72h respectively. Glucose-stimulating insulin secretion during incubation was measured using the ultrasensitive human insulin ELISA kit. The assessment of islet cell viability was studied with acridine orange (AO)-propidium iodide (PI). Results In vitro, low therapeutic concentrations had no deleterious effect on insulin secretion or viability of islet, but high concentration of the drugs was deleterious to ?-cell survival as well as insulin secretion. The effect of medium concentration varied significantly, and sirolimus tacrolimus demonstrated stronger deleterious effect on human islets than mycophenolic acid. Conclusion The direct deleterious effect of immunosuppressive agents to islet cells is dose-dependent, therefore immunosuppressive agent must be optimized after islet transplantation.

Objective To explore the clinical significance of experimental index in incomplete Kawasaki disease (iKD).Methods Eighty-eight cases of KD were reviewed,including iKD 36 cases (iKD group),complete KD(cKD) 52 cases (cKD group).The 88 cases were divided into traditional criterion group (43 cases) and supplement criterion group (45 cases).The experimental indexes of supplement criterion were compared between iKD group and cKD group.Results The rate of coronary artery lesion (CAL) in iKD group was significantly higher than that in cKD group [50.00％(18/36) vs.26.92％(14/52),P ＜ 0.05].Plasma NT-proBNP and cardiac troponin Ⅰ (cTnI) in CAL children (32 cases) in early were significantly higher than those in non CAL children (56 cases) [(468 ± 141) ng/L vs.(379 ± 120) ng/L and (0.95 ±0.22) μg/L vs.(0.49 ±0.15) μg/L,P ＜0.01].The diagnosis rates of KD in the 5th,7th,9th day in supplement criterion group were significantly higher than those in traditional criterion group [64.44％(29/45)vs.25.58％(11/43),84.44％ (38/45) vs.46.51％ (20/43),93.33％(42/45) vs.58.14％ (25/43),P ＜ 0.01].There was no statistical significance between iKD group and cKD group in C reactive protein,erythrocyte sedimentation rate,albumin,alanine aminotransferase,platelet,white blood cell,NT-proBNP and cTnI etc (P ＞ 0.05).There was no statistical significance between iKD group and cKD group in the positive rate of each experimental index (P ＞ 0.05).Conclusions There are some changes of supplement experimental index in acute phase of KD,but there is no statistical significance between iKD and cKD.Plasma NT-proBNP and cTnI are significantly higher in early KD.