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.

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 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.

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.

Objective To investigate the clinical effect of Levosimendan and Qiliqiangxin Capsule in congestive heart failure and influence in serum levels of NT-proBNP and Hcy.Methods 92 cases of patients with congestive heart failure in our hospital from January 2014 to June 2016 were selected and divided into observation group and control group,46 cases in each group.Patients in the control group were treated with Levosimendan on the basis of conventional treatment,and the observation group were treated with Levosimendan and Qiliqiangxin Capsule.Compared the clinical effect,safety,and the change of serum levels of NT-proBNP and Hey before and after treatment.Results The total effective rate of observation group were higher than control group,but the difference was no significant.After treatment,the left ventricular ejection fraction (LVEF),stroke volume (SV) in two groups were significantly higher than that before treatment,the left ventricular end diastolic diameter (LVEDD) were significantly lower than before treatment (P ＜ 0.05);and the LVEF and SV of the observation group were significantly higher than the control group,LVEDD was significantly lower than the control group (P ＜ 0.05).After treatment,serum levels of NT-proBNP and Hey of two groups were significantly better than before (P ＜ 0.05),and the observation group were better than control group (P ＜ 0.05).The difference in the adverse reaction rate was no significant.Conclusion The clinical curative effect of Levosimendan and Qiliqiangxin Capsule in congestive heart failure is distinct,which can effectively improve the clinical symptoms of patients,the cardiac function,serum levels of NT-proBNP and Hcy.

Objective To observe the activities of serum peroxidase capacity,and lipid peroxidation of children from Kaschin-Beck disease (KBD) areas of Xinghai county in Qinhai province,and to explore the relationship between antioxidant capacity and KBD.Methods Sixty four KBD and forty six health subjects without KBD were chosen from KBD endemic areas,which included primary schools of Tangnaihai,Xialujuan and Qushian of Xinghai county in Qinghai province,and fifty nine age-matched healthy control subjects without KBD were from a non-KBD endemic area,Nanfan primary school of Chang'an county in Shaanxi province.Twenty patients with KBD and twenty control subjects from KBD areas and non-KBD area were extracted by simple random sampling method.2,3-DAN fluorescence technique was used to test the hair and blood selenium.The biochemical techniques were used to test the indicators of oxidative stress including malondialdehyde(MDA),antioxidant enzyme activities,total antioxidant capacity(T-AOC),serum superoxide dismutase(SOD),catalase(CAT) and glutathione peroxidase(GSHPx).ResultsAll patients with KBD had significantly lower serum GSH-Px activities[ (59.53 ± 25.23)kU/L] and selenium levels in hair[ (67.64 ± 17.28)μg/L] and blood[(36.27 ± 13.29)μg/L],respectively,than that of control subjects from KBD areas [ ( 91.88 ± 22.99 ) kU/L,( 153.32 ± 24.31 ) μg/L,( 63.06 ± 13.66) μg/L ] and nonKBD areas[ ( 122.68 ± 41.74)kU/L,(242.35 ± 38.56)μg/L,(98.93 ± 17.18)μg/L,all P ＜ 0.05].Serum MDA levels in KBD patients[ (4.64 ± 1.11 )μmol/L] were significantly higher than that in control subjects from KBD [(3.31 ± 1.22)μmol/L] and non-KBD areas[ (3.43 ± 1.29)μmol/L,all P ＜ 0.05].On the other hand,T-AOC,SOD and CAT activities were significantly higher in both KBD[(19.80 ± 6.64),(55.80 ± 8.14),(16.45 ± 5.61 ) kU/L] and control subjects[ (21.71 ± 8.82),(57.45 ± 6.96),(15.63 ± 9.18)kU/L] from KBD areas than that of control subjects from non-KBD area[ (13.56 ± 5.38),(42.79 ± 8.10),(6.05 ± 2.71 )kU/L,all P ＜ 0.05 ].Hair selenium levels,blood selenium levels and GSH-Px activity of control subjects from KBD areas were,respectively,significantly lower than that in control subjects from non-KBD area(all P ＜ 0.05).Conclusions These findings strongly confirm the evidence that KBD patients are susceptible to oxidative stress.The results also show the increase in antioxidant enzymes,which could probably be due to adaptive response to pro-oxidant in KBD state.Hence,there seems to be an imbalance between oxidant and antioxidant systems in KBD patients.