DPP-4 inhibitors are new oral hypoglycemic drugs and hot spots developed and launched in recent years, and they pro-vide new choices for the clinical treatment of type 2 diabetes. In China, DPP-4 inhibitors that are approved to use in the treatment of type 2 diabetes are all imported products currently. In the paper, the current intellectual property situation of DPP-4 inhibitors that are developed and approved at home and abroad is researched and analyzed. Reasonable use of the patent information of DPP-4 inhibitors that is about to expire or have failed can provide good guidance for the subsequent development of DPP-4 inhibitors in domestic with promising curative effect and good market prospects, and can generate new patents in order to enhance the market competitiveness.

Objective:To study the in vitro and in vivo transdermal enhancement of one kind of arginine oligomer-chitosan ( CS-R9). Methods: In vitro mouse skin as the barrier, Franz diffusion cells were used to study the transdermal property of tinidazole ( TNZ) solution in vitro enhanced by CS-R9 using TNZ solution as the negative control and TNZ solution with Azone as the positive control. The rats were randomly divided into three groups, TNZ solution group ( the negative group) , TNZ solution with Azone group (the positive group) and TNZ solution with CS-R9 group. At the predetermined time intervals, 0. 5 ml blood was withdrawn from the rats and TNZ concentration was detected by HPLC to evaluate the enhancement of CS-R9 on TNZ in vivo. Results:Compared with the negative group, CS-R9 had significant enhancement on TNZ trandermal penetration in vitro(P <0.05), and showed no significant difference with Azone (P>0. 05). The in vivo results showed CS-R9 exhibited similar transdermal enhancement on TNZ as Azone at the same concentration (P>0. 05), and CS-R9 had sustalned-release property. Conclusion: CS-R9 has promising transdermal en-hancement on TNZ, which is valuable to be studied further.

OBJECTIVE:To reduce the disputes between pharmacists and patients and to provide references for the improvement of relationships between pharmacists and patients. METHODS: The characteristics of emergency dispensary work and the reasons that accountable for the disputes between pharmacists and patients in the emergency dispensary were analyzed, and aimed at which, some countermeasures were put forward. RESULTS & CONCLUSION: Pharmacists should change their thoughts and attach importance to the cultivation of their language arts so as to improve their capability of dealing with the disputes between pharmacists and patients.

Cyclic diguanylate (c-di-GMP) is a bacterial second messenger of growing recognition involved in the regulation of a number of complex physiological processes. In combinations to the related progress of Xanthomonas oryzae pv. oryzae, the causing agent of bacterial blight of rice in our lab, this review describes (1) the biosynthesis and hydrolysis of c-di-GMP and several mechanisms of regulation of c-di-GMP metabo-lism, (2) the contribution of c-di-GMP to regulating virulence, motility and biofilm formation, processes that affect pathogenesis of many bacteria, and (3) ways in which c-di-GMP may mediate these regulatory effects.

Objective To study the epidemiological characters and risk factors of nephrolithiasis in an island area,Putuo district, Zhoushan city.Methods With stratified cluster random sampling method,5 915 residents aged above 15 yrs and resided 5 yrs and above in Putuo district,Zhoushan city were selected,and surveyed with Ultrasound examination and questionnaire.X~2 tendency test and non-condition Logistic regression were conducted by means of SPSS software.Results After single factor analysis and Multi- factor analysis,the factors entered the model finally were sex(OR=0.543,95%CI:0.454~0.649),education status(OR=1.253,95%CI: 1.151～1.364),dietary habit(OR=0.882,95%CI:0.823～0.944),BMI(OR=1.274,95%CI:1.142～0.1.421),urinary tract infection(OR= 2.126,95%CI:1.663～2.718).Conclusion Risk factors for nephrolithiasis include dietary habit,education status,and urinary tract infection.The vegetables are the protection factor.

Objective To observe the effect of leukocytapheresis(LCAP)on the coagulation,fibrinolysis system and lung injury in the endotoxemia dog and explore the mechanism in the endotoxin-induced lung injury dog. Methods Endotoxemia-induced model in dogs was established by administration of lipopolysaccharide(LPS,2 mg/kg).Separation of the leucocytes wag performed with the automated continuous flow blood cell separators.A total of 30 male mongrel dogs were randomly divided into LPS group(group L,only injected with LPS,with no LCAP),sham LCAP group(group S,received sham LCAP at 12-14 hours after administration of LPS)and LCAP treatment group(group T,received LCAP at 12-14 hours after administration of LPS),10 dogs per group.The dynamic changes of the activated protein C(APC),soluble thrombomodulin and plagminogen activator inhibitor-1 in the serum were measured at 0 hour before LPS administration,at 2,6,12,14,16,24 and 36 hours after administration of LPS.Results Through LCAP,there found the following four results:(1) the APC level in the serum of the group T wag(50.805±4.422)μg/ml and(40.480±2.993)μg/ml at 14 hours and 16 hours respectively,which were significantly higher than(45.881±4.024)μml and(35.935±4.057)μg/ml in the group L(P<0.05).(2)The expressions of soluble thrombomadulin in the group T was (9.688±O.914)μml and(10.492±O.865)μg/ml at 14 hours and 16 hours respectively,which was statistically lower than(11.005±0.854)μg/ml and(12.04±0.954)ug/ml in the group L(P<0.05).(3)Thelevel of plagminogen activatorinhibitor-1 in the group T was lower than that in the group the group T Wag statistically lower than that in the group L(ALI/ARDS occurred in 2 and 7 dogs of the groups T and L respectively within 36 hours after infusion of LPS.P<0.05). Conclusions At the decrease the incidence of acute lung injury partly due to its role in improving the function of coagulation and fibrinolysis.

OBJECTIVETo measure the volumetric changes of gray and white matters in patients with temporal lobe epilepsy(TLE)using voxel-based morphometric study(VBM)and correlate the changes with clinical parameters.

METHODSA total of 71 TLE patients were enrolled in the study,and 22 healthy subjects served as normal controls. Routine brain MRI and 3D fast spoiled gradient echo(FSPGR)T1-weighted images of all the subjects were acquired. The 3D structural images were co-registered,segmented and smoothed,and then the images were analyzed using the optimized VBM with preprocessed using Diffeomorphic Anatomical Registration using Exponentiated Lie algebra(DARTEL)algorithm. The global and local gray matter and white matter volume of each subject were calculated and compared between the TLE patients and normal controls. The potential correlations between the changes of the global and local gray and white matters in the TLE patients and the clinical parameters including the age at onset and the duration of epilepsy were explored.

RESULTSCompared to the normal controls,the TLE patients had diffuse volumetric reduction of gray and white matters in cerebrum both ipsilateral and contralateral to the seizure focus(P<0.05). Local gray matter reduction was found extensively in bilateral cerebral lobes,especially in the temporal and frontal lobes. Local white matter reduction was found in bilateral temporal,parietal and frontal lobes,in addition to the cingulate gyrus. The global gray matter volume(Global GMV)and the global white matter volume(Global WMV)were negatively correlated to the duration of epilepsy with the most significant change occurring in the first year of epilepsy. Global WMV dropped more quickly than Global GMV during the prolonged disease course.

CONCLUSIONSTLE patients have diffuse gray matter and white matter reduction,particularly in the early stage of epilepsy. The reduction of the white matter is more obvious than the gray matter.

Adolescent ; Adult ; Brain ; pathology ; Case-Control Studies ; Epilepsy, Temporal Lobe ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Male ; Middle Aged ; Temporal Lobe ; pathology ; Young Adult

Background Primary open angle glaucoma(POAG) is a common type of glaucoma.It has been well known that a lot of factors are associated with the pathogenesis of POAG,but genetic factor plays a critical role.Optineurin (OPTN)gene is the second confirmed POAG-relevant gene,and screening its mutation in the population contribute to the deeply understanding of the pathogenesis of POAG.Objective The present study was to investigate the association between sequence variants of OPTN gene and POAG in Chinese patients.Methods DNA was isolated from peripheral blood of 100 POAG patients and 60 cataract individuals.The coding exons of OPTN gene were amplified by PCR.PCR products were then sequenced directly to assay the variants and contrasted to original sequence in GenBank.This study was approved by the Ethical Committee of Shenzhen Eye Hospital.All the subjects signed the written inform consent.Results A case-controlled study was designed.The mean intraocular pressure (IOP)of the POAG patients was (29.0±6.5)mmHg,and that of the cataract patients was (13.7 ±2.4)mmHg.Variant of synonymous coding T34T was found in 60 POAG patients.Genetic type frequencies of AA,GA and GG were 10％,50％ and 40％ in the POAG patients,and those of cataract patients were 0,25％ and 75％ respectively,showing significant difference between them (x2 =20.416,P =0.000).The allele frequencies of A and G were 35％ and 65％ in the POAG patients,and those of cataract patients were 12.5％ and 87.5％,with a statistically significant difference (x2 ＝ 19.464,P =0.000).The sequence changes of non-synonymous coding variants (M98K,691-692insA G,R545Q,H486R) were also found in both POAG and cataract patients,but no significant difference was seen in the genetype and allele frequencies between two groups (P＞0.05).Conclusions No obvious association of OPTN gene variant with POAG is verified.The variant of T34T maybe increase the risk of POAG.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Basigin ; analysis ; Biomarkers, Tumor ; analysis ; genetics ; Carcinoma, Transitional Cell ; drug therapy ; genetics ; metabolism ; Gene Expression Profiling ; Humans ; In Situ Hybridization, Fluorescence ; Inhibitor of Apoptosis Proteins ; analysis ; Mutation ; Neoplasm Recurrence, Local ; metabolism ; Nuclear Proteins ; analysis ; Receptor, Fibroblast Growth Factor, Type 3 ; analysis ; genetics ; Tumor Suppressor Protein p53 ; analysis ; genetics ; Urinary Bladder Neoplasms ; drug therapy ; genetics ; metabolism

Aims To compare hippocampus between CUMS rats and normal rats, to find differentially ex-pressed proteins and to explore the pathogenesis of de-pression in the protein levels and biological marker. Methods Chronic unpredicted mild stress was taken to establish rat depression model. The ITRAQ-labeled proteins and peptides were separated by the cation col-umn, and differentially expressed proteins were detec-ted and identified by 2D LC-MS/MS. The functions of proteins were analyzed by bioinformatics. Results To-tally 5 109 proteins were identified, 33 differentially expressed proteins were identified, the expressions of 8 proteins were increased and 25 proteins downregulated. Conclusion ITRAQ based sereening is effective in discovering the nosogenesis of depression and new bio-logical marker.