To find novel antihepatitis drugs, a series of nitrate-oleanolic acid (OA) hybrids (10a, 10b, 11a-11e and 12a-12c) were designed and synthesized on the basis of previous studies using OA as lead compound, which is widely found in natural plants and liver-specific metabolism. In the present study, ten novel NO-releasing derivatives of OA were synthesized by connecting nitrate to the OA-3-OH through varying lengths of linkers containing antioxidants which were designed to increase the ability of these target compounds to scavenge free radicals. The structures of these objective compounds were determined by IR, MS, 1H NMR and elemental analysis. Their protective effects on anti-Fas mediated HepG2 cell apoptosis were in vitro evaluated by LDH assay. Compound 12a is the most potent inhibitor. Its effect on anti-Fas mediated HepG2 cell apoptosis and amount of NO-releasing in vitro are similar to those of positive control NCX-1000.

AIM To investigate whether the relaxation characteristics of phytoestrogens resveratrol and phloretin on contractile response of aortic strips are similar to that of estrogen and the mechanisms underground. METHODS Aortic strips from rabbits were suspended in organ baths containing Krebs solution, and then isometric tension was measured. RESULTS Resveratrol and phloretin inhibited the contractile responses to norepinephrine (NE), KCl and CaCl2, shifted their concentration-response curves rightward with pD2′ values of 2.89, 3.34, 3.37 for resveratrol and 3.23, 3.52, 3.77 for phloretin respectively. Also both of them concentration-dependently relaxed KCl-precontracted aortic strip. The relaxing response of resveratrol but not of phloretin in aortic strip was significantly reduced by removal of endothelium or incubation with Nω-L-nitro-arginine and methylthioninium chloride, however both their relaxant effects were not affected by indometacin and propranolol. In Ca2+-free Krebs solution containing 0.01 mmol·L-1 EGTA, resveratrol and phloretin inhibited NE-induced contraction which was caused by Ca2+ release from intracellular store, but did not affect the contraction which was induced by Ca2+ influx. CONCLUSION Resveratrol and phloretin can induce vasorelaxations which may relate to inhibition of Ca2+ influx through potential-dependent calcium channels and Ca2+ release from intracellular stores, and the relaxing response of resveratrol is endothelium-dependent in part, but of phloretin is not endothelium-dependent.

Objective To investigate the effects of endogenous estrogen on blood glucose level,serum insulin level,and plasma total antioxidant capacity in streptozotocin-induced diabetic female mice,and to explore possible protective effects of estrogen on pancreatic islet cells.Methods Female mice were randomly according to body weight divided into four groups:( 1 ) Sham( Sham operation and vehicle administration) ; ( 2 ) Ovx( ovariectomy and vebicle administration ) ; ( 3 ) Sham + STZ ( Sham operation and STZ administration ) ; and ( 4 ) Ovx + STZ ( ovariectomy and STZ administration).The diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ,50 mg/kg ).Blood glucose levels were measured once a week.Results The blood glucose level and malondialdehyde of Ovx group were higher than that in Sham group,while total anti-oxidant capacity ( T-AOC ) was lower than those in Sham group.the blood glucose level and MDA of Ovx+ STZ group were higher than those in Sham +STZ group,while T-AOC and serum insulin level were lower than those in Sham + STZ group.Conclusions Endogenous estrogen may have some protective effects on pancreatic islet function from streptozotocin-induced diabetes mellitus in female mice.

ObjectiveTo investigate the clinical value of endoscopic esophageal submucosal tunnel resection of gastric fundus-cardiac tumors originating from muscularis propria.Methods Clinical date of 18 patients with gastric fundus-cardiac submucosal tumors originating from muscularis propria who underwent endoscopic esophageal submucosal tunnel resection from January 2011 to December 2011 were retrospectively collected and analyzed.ResultsAll lesions were successfully and completely resected in 18 patients,with sizes ranging from 0.7 cm to 7.2 cm,mean (2.43 ± 1.91 ) cm.Pneumoretroperitoneum,pneumomediastinum and pneumohypoderma occured during the procedure in 2 cases,but spontaneously resolved in 3 days.Fever with increased WBC within 24 h after the procedure occurred in one patient,and was cured in two days with antibiotics.There were no severe complications including bleeding,perforation or death.All patients could have liquid diet 3 days later after the operation.Follow-up endoscopy at 1 week after the operation showed a healing of esophageal incision.ConclusionEndoscopic esophageal submucosal tunnel resection is a safe and effective method for gastric fundus-cardiac submucosal tumors originating from the muscularis propria,lessening the difficulty of traditional endoscopic resection.

Objective:To investigate the effect of decoction of Fructus Mume (DFM) on the myoelectric activity of uterine smooth muscle of unpregnancy and early pregnancy rats and study its action mechanism.Methods: A pair of bipolar electrode was implanted on the serous surface of rat uterus. The DFM was injected into abdominal and the changes of uterine myoelectrical activity were observed.Results: The higher dose of DFM could enlarge the average amplitude of slow wave of uterine smooth muscle myoelectricity as well as increase the incidence and the maximal amplitude of the outbreak plexiform myoelectric wave. On the other hand, rats during early pregnancy were more sensitive to the DFM. Conclusions: The DFM enhances the myoelectricity activity of uterine smooth muscle of unpregnancy and early pregnancy rats which may result from enhacing the start cells electric activity and speeding up the action potential depolarization. Thus the DFM can serve as an effective clinical drug for anti early pregnancy.

Objective To preliminarily discuss the effect of thrombectomy with the TREVO device in patients with acute ischemic stroke.Methods Six patients with acute ischemic stroke treated with TREVO device at the Department of Neurointervention,Beijing Fengtai You′anmen Hospital from April to June 2016 were analyzed retrospectively,including 2 patients with middle cerebral artery (MCA)occlusion (time window from 2. 7 to 5. 5 h),4 with basilar artery occlusion (time window from 4. 0 to 7. 0 h). The effect of thrombectomy was evaluated by the modified thrombolysis in cerebral infarction (mTICI ) scores. The National Institutes of Health Stroke Scale (NIHSS)scores were used to evaluate the neurological status of patients before and after treatment. The prognosis was evaluated by the modified Rankin scale. Results (1 )After 1 to 2 embolectomies,the occlusive arteries of 5 patients achieved recanalization (mTICI gradeⅡb-Ⅲ;posterior circulation in 4 cases,MCA in 1 case). (2)Compared with at admission,the NIHSS score in 1 of 2 patients with MCA occlusion was reduced by 8 points at discharge,and 1 was not any improvement;compared with at admission,the NIHSS scores in 3 of 4 patients with basilar artery occlusion were decreased by 8-26 points at discharge,and 1 was not any improvement;in 2 patients with MCA occlusion,the modified Rankin scale scores were 0 to 1 at 3 months after discharge (0 in 1 case,4 in 1 case);the Rankin scale scores in 4 patients with basilar artery occlusion at 3 months after discharge were 0 in 1 case,1 in 2 cases,and 5 in 1 case.Conclusion The preliminary experience of using TREVO device embolectomy for patients with acute ischemic stroke shows that it is more safe and effective.

Objective To explore the effects of targeted silencing of the chemokine receptor 7 (CXCR7)gene on the invasion and migration of the melanoma cell line M14. Methods Western-blot analysis was performed to determine the protein expression of CXCR7 in melanoma cell lines M14 and A375, and CXCR7-overexpressing M14 cells were used in this study. Cultured M14 cells were divided into three groups: experimental group transfected with a small interfering RNA(siRNA)targeting CXCR7(CXCR7-siRNA), negative control group transfected with a negative control siRNA, blank control group receiving no treatment. Real-time quantitative PCR and Western-blot analysis were conducted to determine the mRNA and protein expressions of CXCR7 respectively in M14 cells, Transwell chambers were used to evaluate the invasive activity of M14 cells, and wound healing assay to estimate the migratory activity of M14 cells. Results The experimental group showed significantly decreased mRNA and protein expressions of CXCR7 compared with the negative control group and blank control group (CXCR7 mRNA: 0.412 ± 0.023 vs. 1.211 ± 0.117 and 1.000 ± 0.102, F = 30.068, P = 0.001; CXCR7 protein: 0.144 ± 0.005 vs. 1 and 1.016 ± 0.004, F =11 485.5, P = 0.000). The number of M14 cells crossing the polycarbonate membrane per high-power field (× 200)was significantly smaller in the experimental group than in the negative control group and blank control group (20.617 ± 1.503 vs. 42.000 ± 6.018 and 43.627 ± 2.152, F = 32.416, P = 0.001). Similarly, the number of migrating M14 cells in wound healing assay was significantly decreased in the experimental group compared with the negative control group and blank control group (15.00 ± 1.10 vs. 44.90 ± 2.20 and 45.30 ± 2.30, F = 2 411.945, P = 0.000). Conclusion Targeted silencing of the CXCR7 gene can significantly inhibit the invasion and migration of M14 cells in vitro, which may provide a potential target for the treatment of cutaneous melanoma.

Objective To investigate the eftect of radiation dose of dual-source computed tomography (CT) dual energy single-phase enhanced scan in patients with esophageal cancer.Methods The prospective study was conducted.The clinicopathological data of 56 patients with esophageal cancer who were admitted to the Lishui Hospital of Zhejiang University between January 2015 and December 2016 were collected.All the patients were divided into the experimental group (undergoing dual-source CT dual energy single-phase enhanced scan) and control group (undergoing dual-phase CT enhanced scan) bv randomised block method.TNM classification of esophageal cancer (Seventh Edition) published by American Joint Committee on Cancer (AJCC) was used as a standard TNM staging.Two observers independently read films.All the patients underwent radical resection of esophageal cancer or palliative surgery,and then received adjuvant radiochemotherapy.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival of patients up to March 2017.Observation indicators:(1) consistencies of T staging,N staging and M staging;(2) accuracies of T staging,N staging and M staging (pathological results as a gold standard);(3) radiation dose of CT scan;(4) treatment and follow-up situations.The Kappa test was used for evaluating the consistency,κ≥0.75 as a good consistency,0.40≤κ＜0.75 as a normal consistency and κ＜0.40 as a poor consistency.Comparisons of count data and ratio were done by the chi-square test.Comparisons of measurement data were analyzed by the t test.Results A total of 50 patients were enrolled in the study,including 25 in the experimental group and 25 in the control group.(1) Consistencies of T staging,N staging and M staging:all the 50 patients finished successfully CT scans.Two observers considered that consistencies of T staging,N staging and M staging in the 2 groups were normal (κ =0.452,0.618,0.729,P＜0.05).Consistencies of N staging and M staging were superior to T staging.(2) The pathological results were used as a gold standard.Accuracies of T staging,N staging and M staging in the experimental and control groups were 72％,76％ and 88％,84％ and 92％,88％,respectively,with no statistically significant difference between the 2 groups (x2 =0.10,0.37,0.50,P＞0.05).(3) Radiation dose of CT scan:volume CT dose index (CTDIvol),dose length production (DLP) and effective radiation dose (E) were (10.35±2.01) mGy,(400.63± 34.13) mGy · cm,(5.61 ± 0.47) mSv in the experimental group and (3.55 ± 0.60)mGy,(140.66± 10.89) mGy · cm,(1.98±0.17) mSv in the control group,respectively.There were statistically significant differences in CTDIvol and E between the 2 groups (t =16.23,36.30,P＜0.05).(4) Treatment and follow-up situations:of 50 patients,43 patients received treatments,including 32 undergoing radical resection (11 receiving postoperative adjuvant chemotherapy),6 undergoing palliative surgery,3 receiving single radiotherapy and 2 receiving single chemotherapy.Thirty-six of 43 patients were followed up for 3-18 months,with a median time of 6 months.During follow-up,1-year survival rate was 61.1％.Conclusion Dual-source CT dual energy single-phase enhanced scan in patients with esophageal cancer cannot reduce accuracy of TNM staging,but decreased effectively radiation dose.

Aim To study the effect of genistein on contractility of isolated papillary muscles in guinea pig and its mechanisms.Methods Isolated guinea pig papillary muscles were suspended in organ baths containing KH solution,and the effect of genistein on contractility of myocardium was observed after an equilibration period.Results Genistein and isoprenaline hydrochloride showed positive inotropic effects on contractility of myocardium in a dose-dependent manner(1～100 ?mol?L~(-1)) Propranolol(1 ?mol?L~(-1)) and verapamil hydrochloride(0.5 ?mol?L~(-1)) attenuated the positive inotropic effect of isoprenaline hydrochloride(2 ?mol?L~(-1)),but did not change the effect of genistein(100 ?mol?L~(-1)).Furthermore,the enhancement of the contractility induced by elevation of extracellular Ca~(2+) concentration in papillary muscles did not show any change after pretreatment with genistein(1,10 ?mol?L~(-1)).Finally,the positive inotropic effect of genistein was attenuated partially by tamoxifen(1 ?mol?L~(-1)),however,was not influenced by sodium orthovanadate(1 ?mol?L~(-1)).Conclusions Genistein has the positive inotropic effect on guinea pig papillary muscles,which is not related to the activation of Ca~(2+) channel on cell membrane,? adrenoceptor and tyrosine kinase pathway,but this effect may involve in uptake and utilization of sarcoplasmic reticulum Ca~(2+).

Objective Indocyanine green (ICG) video angiography is widely used in aneurysm surgery.This study is to evaluate and analyze the effect of intraoperatively aneurysms clipping by quantitative analysis of ICG video angiography.Methods Twenty patients with cerebral aneurysms (six with anterior communicating artery aneurysms,five with communicating artery aneurysms and nine with middle cerebral artery aneurysms),admitted to our hospital from September 2012 to September 2013,were chosen in our study; they all underwent aneurysms clipping involving ICG.Same areas of interest (AOIs,aneurysm area,parent artery area and branch artery area) of images intercepted from angiogram videos before and after clipping of aneurysms were analyzed by Image-pro plus.Results Dramatic differences in time to peak of blood flow of aneurysm areas were observed before and after clipping of aneurysms ([10.975±1.208] s vs.[47.950±2.350] s,t=57.299,P=0.000).There were no dramatic differences in times to peak of blood flow of parent and branch vessels before aneurysms clipping and after aneurysms clipping ([10.600±1.619] svs.[10.350±1.452] s,t=0.641,P=0.529;[10.400±1.153] s vs.[10.425±1.311] s,t=-0.079,P=0.938).Conclusion Quantitative analysis is a good method to evaluate the effect of aneurysm clipping surgery according to the blood flow,which might improve the success rate.