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 analyze that if the quality of ethics review is closely related to the protection of human subjects' right and interest. Methods:This article has analyzed all the issues raised by local Ethics Committee in the process of review in recent two years since guideline of ethical review of drug clinical trials was published, summed up the most common problems occurred in protocols and informed consents. Results:Total 94 new drug or medical device clinical trial projects were reviewed by the local ethics committee, among which 29 projects were ap-proved through regular full board meeting, the approval rate in the initial review was 31%. The most common prob-lems in protocols include: the research backgrounds, design, and risk-benefit ratio; Main issues raised on in-formed consent focused on the contents, language and signature terms. Conclusions:The protection of subjects needs more improvement of capability of investigator, sponsor, drug clinical trial institution and the ethics commit-tee.

Objective To study the role of prefrontal cortex in maintenance of working memory(WM)using event-related functional MRI(ER-fMRI).Methods Twenty healthy subjects completed a relative lower,high load version of the sternberg item recognition task during ER-fMRI.The brain areas showing activity on average across the two loads for maintenance phase were obtained with group analysis.Load dependent activity was identified with inter-group analysis.Results The maintenance phase were relevant to the activity in dorsolateral prefrontal cortex(DLPFC),ventrolateral prefrontal cortex(VLPFC),parietal lobe,supplementary motor area(SMA)and premotor cortex(PMA).Brain regions including VLPFC showed increased activation for high load level.Conclusion Functional difference but not anatomic difference between maintenance and manipulation in brain may be exist.

Objective To detect the expression level of Taurine up?regulated gene 1( TUG1) in the re?nal cell carcinoma and paired paracancerous normal tissues,then explore the relationships between the expression level of TUG1 and clinical characteristics.Methods RNA was Extacted from the resected renal cell carcinoma tissues and paired paracancerous normal tissues of 46 patients respectively,by reverse transcription to get cDNA, the expression level of the TUG1 was detected by RT?qPCR, the relationship between the expression level of TUG1 and the clinicopathological characteristics was analyzed by statistically software. Results The expression of TUG1 in renal cell carcinoma was obviously lower than that in paired paracancerous normal tissues(0.533±0. 027 vs. 1.000±0.298,t=-3.350,P<0.01).The△CT value of Tug1 in 46 cases of renal cell carcinoma after log?arithmic transformation,the minimum value was -5.535,maximum was 3.085,average value was -0.908,with the average of -0.908 as a dividing line,46 cases of renal cell carcinoma with 25 cases (54.34%) were down regulated the expression.The expression level of TUG1 of patients with renal carcinoma have no significant corre?lation with age,sex,type of renal cell carcinoma,TNM staging and UICC/AJCC staging(P>0.05).Conclusion The expression of TUG1 in renal cell carcinoma tissues are down?regulated,which also suggest that it may be re?lated to the tumorigenesis and development of renal cell carcinoma.

The recombinant adenovirus Toll like receptor 4 (TLR4) shRNA vector (pGSadeno-TLR4) was constructed and transfected into human aortic vascular smooth muscle cells (HA-VSMC).After HA-VSMC were treated with palmitate or different signaling pathway inhibitors,the mRNA and protein levels of interleukin-6 (IL-6)and NF-κB activity were tested with real-time PCR and ELISA,respectively.The results showed that palmitate increased mRNA and protein levels of IL-6 in HA-VSMC in a dose-dependent manner.The expression of IL-6 mRNA reached peak after treatment with 400 μmol/L of palmitate for 6 h,being 10.43 fold of control (P＜0.01).Treatment with 400 pmol/L of palmitate for 24 h maximally upregulated the protein level of IL-6,which was 2.18 fold of control (P＜0.01).NF-κB inhibitor parthenolide markedly inhibited palmitate-stimulated increased in IL-6 mRNA level by 65％ and protein level by 59％ (both P＜0.01).Protein kinase C (PKC) inhibitor chlerythrine suppressed palmitateinduced IL-6 mRNA expression by 24％ and IL-6 protein level by 28％.By contrast,extracellular signal-regulated protein kinase inhibitor PD98059 and phosphatidylinositol 3-kinase inhibitor wortmannin had no effect on the induction of IL-6 by palmitate.Blockade of TLR4 with pGSadeno-TLR4 significantly suppressed palmitate-induced IL-6 mRNA expression by 72％ and IL-6 protein expression by 75％ (both P＜0.01),along with decrease of NF-κB p65 activity decreased by 62％.These results suggest that TLR4/NF-κB and PKC pathways mediate palmitate-induced IL-6 expression in HA-VSMC.

Objective To compare the accuracy of 64-slice spiral coronary angiography (CTA) and myocardial perfusion imaging (MPI) in the detection of functionally relevant coronary artery disease (CAD). Methods Twenty patients diagnosed as CAD and 11 suspected CAD were studied. Both 64-slice spiral CTA and MPI images were analyzed. For the evaluation of CTA,luminal narrowing ≥50% and ＜50% were visually assessed. Perfusion defects on MPI were detected and allocated to their corresponding coronary vessels.Results Among total 124 coronary vessels, CTA detected stenoses ≥50% in 23 arteries, and 7 showed perfusion defects in the corresponding myocardial areas on MPI. Ten of 101 vessels had stenoses＜50%,and no perfusion defects in the corresponding myocardial areas was found on MPI. There was difference between the degree of coronary artery stenoses and the risk probabilities of myocardial ischemia (χ~2=6.667, P=0.01). No statistical difference was detected between the coronary artery stenoses site and the risk probabilities of myocardial ischemia (χ~2=6.839, P=0.065). The sensitivity, specificity, negative and positive predictive values of 64-slice spiral CTA in detecting perfusion defects on MPI was 41.18%, 85.05%, 90.01% and 30.43%, respectively.Conclusion 64-slice spiral CTA can display important morphologic information of coronary arteries, but with a low positive predictive value. MPI can be used as an important method to evaluate the change of heart function resulted from CAD.

Objective: To assess the health risk associated with drinking water in Hangzhou from 2016 to 2017,and to provide evidence for the safety of drinking water . Methods: The monitoring data of 5 genetic toxic substances（arsenic,hexavalent chromium,cadmium,chloroform,tetrachloromethane）and 13 body toxic substances（lead,mercury,selenium,cyanide,fluoride,nitrate,iron,ammonia nitrogen,manganese,copper,zinc,aluminum,volatile phenol）from 36 source water samples,36 finished water samples and 288 tap water samples in the main urban areas of Hangzhou were collected from 2016 to 2017. The health risk of drinking water containing the chemical pollutants mentioned above were assessed based on the evaluation models recommended by United States Environmental Protection Agency . Results: The concentrations of 5 genetic toxic substances and 13 body toxic substances in source water,finished water and tap water were all within the reference limits issued by Standards for Drinking Water Quality（GB 5749—2006）. The carcinogenic risk,non-carcinogenic risk and total health risk caused by the chemical pollutants in the source water were 2.18×10-5/a,7.75×10-9/a and 2.18×10-5/a. The carcinogenic risk,non-carcinogenic risk and the total health risk caused by the chemical pollutants in the finished water were 1.08×10-5/a,3.70×10-9/a and 1.08×10-5/a. The carcinogenic risk,non-carcinogenic risk and total health risk caused by the chemical pollutants in the tap water were 1.96×10-5/a,3.61×10-9/a and 1.96×10-5/a. The carcinogenic risk and total health risk caused by chemical pollutants ranged from high to low in the source water,tap water and finished water. The non-carcinogenic risks ranged from high to low in the source water,finished water and tap water . Conclusion The health risks of 18 chemical pollutants in drinking water in Hangzhou were at a low level,with the greater carcinogenic risk than the non-carcinogenic risk. Hexavalent chromium had the highest carcinogenic risk,while fluoride and aluminum had the highest non-carcinogenic risk.

Objective To conduct a computer simulation to evaluate the discrepancy between the cumulative doses calculated by four-dimensional computed tomography (4DCT) images and 4DCT scans (for real-time respiratory motions) due to the patient's irregular breathing.Methods A series of digital phantoms were generated from a patient's 4DCT images to simulate 4DCT images and 4DCT scans (for real-time respiratory motions) resulting from various irregular breathing curves.A six-field intensity-modulated radiotherapy plan was generated.Two cumulative doses in the target were calculated.The first one, named Dall, was calculated by tracking the point displacements in the target manifested on the 4DCT images;the second one, named D4D, was calculated based on the point displacements along the whole breathing motion during 4DCT scanning.Dose discrepancy between D4D and Dall was calculated to evaluate the correlation between breathing pattern and dose discrepancy in the target.Results The dose discrepancy in the target was correlated with mean motion excursion and the standard deviation of motion excursion.ΔDmin(ΔD99) in the target increased from 2.39%(2.04%) to 11.91%(5.24%) as the mean motion excursion increased from 5 mm to 15 mm, and increased from 5.93%(2.15%) to 14.65%(5.01%) as the standard deviation of motion excursion increased from 15% to 45% of the mean motion excursion.When the mean period increased from 3 s to 5 s or the standard deviation of period increased from 10% to 40% of the mean period,ΔDmin(ΔD99) in the target was greater than 6.0%(2.0%), but less than 9.0%(3.0%).When the target diameter was 2 cm, 3 cm, and 4 cm,ΔDminΔD99) in the target was 11.88%(5.50%), 6.91%(2.42%), and 7.53%(3.62%), respectively.Conclusions There is a large discrepancy between the cumulative doses calculated using 4DCT images and 4DCT scans (for real-time respiratory motions) when the patient has irregular breathing.This dose discrepancy depends on mean motion excursion and the standard deviation of motion excursion, but has little relationship with mean period, the standard deviation of period, and tumor volume.

OBJECTIVETo study the effect and mechanism of ginsenoside Rg1 on the spatial learning-memory ability in rats with Alzheimer's disease after transplanted with bone marrow mesenchymal stem cells (BMSCs).

METHODSUsing digital randomization table method, seventy-five male SD rats were divided into the bilateral FF transection model group (as the model group: ambi-hippocampal fimbria-fomix transected), the sham-operative control group (the SOC group: receiving the same modeling process as the model group, but without ambi-hippocampal fimbria-fomix transected), the ginsenoside Rg1 treatment group (as the treatment group: Two weeks after modeling ginsenoside Rg1 was peritoneally injected at the dose of 5 mg/kg, once daily for four weeks in total), the BMSCs transplanted treatment group [as the control group: Two weeks after modeling every rat received transplantation of BMSCs (10 microL, 1 x 10(6) cells)], and the ginsenoside Rg1 + BMSCs treatment group (as the combination group: They received both transplantation of BMSCs and peritoneal injection of ginsenoside Rgl). The spatial learning-memory ability of rats was detected by Morris water maze and the escape latency (s) was recorded, mRNA expression of nerve growth factor (NGF) was detected using Real-time PCR.

RESULTSSix weeks after the hippocampal fimbria-fomix (FF) transection, the escape latency o feach medication group was obviously shorter than that of the model group, and the spatial learning-memory ability of dementia rats was somewhat improved. The spatial learning-memory ability of rats in the combination group was (29.95 +/- 2.03) and the mRNA expression level of NGF was (1.13 +/- 0.15), better than those in the BMSCs group (44.36 +/- 1.43, 0.78 +/- 0.09, P<0.05).

CONCLUSIONSGinsenoside Rg1 could strengthen the spatial learning-memory ability in dementia rats after transplanted with BMSCs. Its mechanism might be possibly correlated with up-regulating mRNA expression of NGF in basal forebrain after BMSCs transplantation.

Animals ; Dementia ; psychology ; therapy ; Ginsenosides ; pharmacology ; therapeutic use ; Learning ; drug effects ; Male ; Memory ; drug effects ; Mesenchymal Stem Cell Transplantation ; Rats ; Rats, Sprague-Dawley

Objective To provide the evidence for cooperation in research on Kashin-Beck disease in China by ana-lyzing the research competence of authors in papers on Kashin-Beck disease and their cooperation .Methods Papers on Kashin-Beck disease were retrieved from 4 commonly used Chinese perodical databases .Key words Information was collected and organized using BICOMS to produce a co-words matrix,atlas of co-words was plotted using NetDraw, the data were analyzed using SPSS 17.0.Results Of the 3454 authors engaged in research of Kashin-Beck disease from 1957 to 2012,81 published 15 or more than 15 papers.Cluster analysis showed that these 81 authors were from Institute of Endemic Diseases,Xi'an Jiaotong University Medical School; Institute of Kashin-Beck Disease,Chinese Center for Endemic Disease Prevention and Control;Jilin No.2 Center for Endemic Disease Prevention and Control;Centers for Disease Prevention and Control of China Academy of Sciences , Henan Province and Gansu Province .Conclusion A large number of researchers are engaged in research of Kashin-Beck disease .Their research interest and charac-teristics are clear.However, the cooperation between different institutions is weak and should be strengthened.