Phosphodiesterases(PDEs) is the only protein enzyme family,which catalyze the hydrolysis of cyclic nucleotide second messages(cAMP and cGMP).PDEs regulate many physiologic and pathologic processes.Recent advance showed that PDE7 hydrolyze cAMP exclusively and is divided into PDE7A and PDE7B. PDE7 mainly express in immune and inflammatory cells.The selective inhibition of this family generates profound,functional effects and PDE7 has been used as a therapeutic target for diseases related with inflammation,such as chronic obstructive pulmonary disease(COPD),rheumatoid arthritis and Alzheimers disease(AD).

AIM The aim of our study was to establish drug screening models which can evaluate samples' effects on cytokines related with inflammtion, capable of fast and efficient screening of anti-inflammatory lead compounds on the release of inflammtory cytokines. METHODS Heparinized human blood leukocytes was evaluated as a model to study the effects of various classes of anti-inflammatory lead compounds on cytokine release/biosynthesis from leukocytes. Human blood leukocytes was stimulated with LPS (final concentration 0.5～50 mg?L -1), with or without test drugs (diclofenac, a cytooxygenase inhibitor, nordihydroguaiaretic acid NDGA, a 5-lipoxygenase inhibitor) for 1～4 h to induce cytokine release. RESULTS Human blood leukocytes stimulated with LPS could product IL-1, IL-8 and TNF-? in a dose-dependent manner. Human blood leukocytes was stimulated with LPS(5 mg?L -1) for 4h to induce cytokine release. TNF-?, IL-1 and IL-8 time-course profiles were determined in culture media, using bioassays and ELISA. LPS-mediated release of IL-1 and TNF-? was significantly suppressed by NDGA and Diclofenac. In LPS stimulated blood, NDGA and Diclofenac inhibited the release of TNF-?(IC 50 of 149 ?mol?L -1 and 23.88 ?mol?L -1) or IL-1 (IC 50 of 222.57 ?mol?L -1 and 126 ?mol?L -1). CONCLUSION This human blood leukocytes screening system in vitro has the potential to screen new cytokine release inhibitors and sites of action of new anti-inflammatory lead compounds, and increases the screening efficiency.

The anti-inflammatory mechanism of non-steroidal anti-inflammatory drugs (NSAIDs) is mainly due to inhibition of COX-2 activity. NSAIDs can also inhibit COX-2 expression and produce anti-inflammatory effect independent of COX. These COX-independent mechanisms include inhibiting transcription factors such as NF-?B and AP-1, interfering with signal transduction pathways through actions on Erk、p38MAPK、IKK and RSK2, activating PPAR? and HSF-1, inhibiting iNOS and transport of prostanoids from their generating cells.

PKC plays a pivotal role in the mechanism of myocardial preconditioning. After preconditioning, PKC is activated and translocated to membranes and cytoskeleton structures by multiple endogenous substances such as adenosine, calcium, etc. Recent studies imply that MAPK carries the signal from PKC to the mitochondria K ATP channel and thus protect the heart.

The research and development (R & D) of novel Chinese materia medica (CMM) have made a great progress in recent years.But problems still exist in druggability evaluation of novel CMM,such as uncertain evaluation content and lack of key technology.Druggability evaluation is the key to the success or failure for R & D of novel CMM.Observation on the effect and safety of novel CMM is the core of druggability evaluation.The important pharmacological problems include the choice of evaluation indicator,clinical indication,analysis of material basis,investigation of mechanism,research on pharmacokinetics and safety evaluation.Modem technologies should be used in druggability evaluation.We should have a correct understanding of the concept of novel CMM.The grasp of the meaning of novel drugs and the essence of CMM theory will be helpful for R & D of novel CMM.

Danshen-Radix Salviae Miltiorrhizae，is one of the common traditional Chinese medicines，which has been used clinically in the treatment of cardiovascular diseases more than 20 centuries.The active ingredients of Danshen has been researched 5 decades by the modern methods.Many researchers investigated the pharmacological effects of water soluble ingredients of Danshen-salvianolic acids in vivo and in vitro.The results demonstrated that salvianolic acids have different pharmacological effects such as potent antioxidative effects，scavenging free radicals，protect neural cells against injuries caused by anoxia， etc.In present paper，the pharmacological effects of salvianolic acids and the mechanisms of their actions are reviewed based on the research results obtained in our laboratory and other authors.

The experiment was conducted in the Central Laboratory of Tianjin Stomatological Hospital from November 2004 to March 2005. Epithelial cells were isolated from normal parotid gland tissues obtained form resected benign tumor of an adult, so as to prepare rat tail collagen. Two adult rats were selected to obtain the tendon fascia from rat tail, which were then immersed in the 500 mL of 0.1% glacial acetic acid. The infiltration culture board of collagen glacial acetic acid, proximal wall of culture flask and beaker with ammonia water were placed in a sterile containers to reserve at 37 ℃ for 72 hours. The epithelial cells were isolated from parotid gland tissues by enzyme digestion and cultured in 1:1 DMEM/F12 culture medium supplemented with some growth stimulating factors such as insulin (INS), hydrocortisone (HC) and isoproterenol (ISO) by using self-made rat tail collagen gel substrate. The cytomorphological characteristics of primary and passage cells were observed with inverted microscope. The result showed that the primary culture of parotid gland epithelial cells: cells were in polarity arrangement on the 4th day and formed in different size of acinus and pip kind structure. The serial subcultivation of parotid gland epithelial cells. In the culture period of 50 days, parotid gland epithelial cells were passed to the F3 generation, and the cells of F3 generation frozen in liquid nitrogen recovered and survived. It could be seen by HE staining that the cell body was bigger, the kytoplasm was abundant and the nuclear membrane was clear with one or two entoblasts. The karyogenetic division could be found in partial entoblast, whereas no abnormal karyogenetic division was seen.

AIM To study the protective effect of total salvianolic acid against cerebral ischemia reperfusion injury. METHODS The cerebral ischemia reperfusion model in mice was made by means of ligating bilateral common carotid arteries in mice. After reperfusion, latency, error number of step down test and the gasping time after cutting head in ischemia reperfusion mice were recorded. Spectrophotometric assay were used to measure the activity of superoxide dismutase (SOD), the contents malondialdehyde (MDA) and glutathione peroxidase (GSH) in brain of experimental mice brain homogenate. RESULTS In step down test, the ischemia reperfusion impaired the function of learning and memory in mice. The total salvianolic acid markedly improved the function of learning and memory, reduced the error number and extended the latency in ischemia reperfusion mice. The total salvianolic acid also significantly inhibited the changes of SOD, MDA and GSH in the cerebrum induced by ischemia reperfusion. CONCLUSION The total salvianolic acid has protective effect against cerebral ischemia reperfusion injury via its antioxidant activity.

AIM To study the protective effect of total salvianolic acid against cerebral ischemia reperfusion injury. METHODS The cerebral ischemia reperfusion model in mice was made by means of ligating bilateral common carotid arteries in mice. After reperfusion, latency, error number of step down test and the gasping time after cutting head in ischemia reperfusion mice were recorded. Spectrophotometric assay were used to measure the activity of superoxide dismutase (SOD), the contents of malondialdehyde (MDA) and glutathione peroxidase (GSH) in brain of experimental mice brain homogenate. RESULTS In step down test, the ischemia reperfusion impaired the function of learning and memory in mice. The total salvianolic acid markedly improved the function of learning and memory, reduced the error number and extended the latency in ischemia reperfusion mice. The total salvianolic acid also significantly inhibited the changes of SOD, MDA and GSH in the cerebrum induced by ischemia reperfusion. CONCLUSION The total salvianolic acid has protective effects against cerebral ischemia reperfusion injury via its antioxidant activity.

Objective To review the experience of aortic root internal drainage in the operation of type A aortic dissection.Methods This was a prospective and observational study.Clinical data were available from 20 cases of type A aortic dissection patients (A group) from March 2003 to March 2008,and anothcr 36 cases of type A aortic dissection patients (B group) from March 2008 to May 2013.All of patients received the operation of replacement of ascending aortic aneurysm and aortic arch replacement and descending aortic stented elephant trunk implantation in our hospital.The additional inside drainage were made between the aortic root aneurysm sac and right atrial appendage in B group.Perioperative and postoperative data including the operation time,the amount of bleeding,cardiopulmonary bypass time,the amount of red cell transfusion,number of postoperative cases re-operated for hemostasis,total drainage volume in 24 hours,amount of postoperative red blood cell transfusion,number of cases of postoperative pulmonary complications,and postoperative mortality rate were analyzed retrospectively.The data was analyzed using SPSS version10.0 software.The chi-square test was used for constituent ratios,whilest was applied to analysis of differences in above variables betweens two groups.Results There were significant differences in the amount of bleeding during surgery,cardiopulmonary bypass time,the amount of red cell transfusion,rate of postoperative re-operation,total drainage volume in 24 hours,amount of postoperative red blood cell transfusion,number of cases of postoperative pulmonary complications and postoperative mortality between the two groups (x2/t =2.658,2.381,2.265,3.056,6.862,2.896,2.316,7.215,7.668,P =0.012,0.034,0.007,0.016,0.013,0.032,0.008,0.008,respectively).Conclusions The method of aortic root internal drainage in the operation of type A aortic dissection could reduce the amount of bleeding and improve the success rate of operation.