The article analyses the present dissension on non-clinical pharmacodynamics study of new drugs of Chinese materia medica,and reviews the questions of non-clinical effect evaluation,and gives the opinions and advices on non-clinical pharmacodynamics study.It may be a reference for the study of new drugs of Chinese materia medica.

Objective To study the anatomical variations adjacent to the umbilical portion of the left portal vein (U-point) radiologically and to determine their impact on treatment of hilar cholangiocarcinoma (HCCA).Methods From January 2014 to February 2016,47 consecutive patients who were diagnosed to suffer from Bismuth type Ⅰ,Ⅱ or Ⅲ a HCCA in our institution were retrospectively studied.All these patients underwent enhanced CT examination preoperatively and three-dimensional (3D) models were then reconstructed.Results Any variations of the left biliary system in relation to the U-point were analyzed.The findings showed that:B2 and B3 united above or lateral to the U-point in 31 patients (65.9％);B2 and B3 united medial to the U-point in 4 patients (8.5％);and B4 converged into B3 prior to B2 in 6 patients (12.8％).Rare variations were observed in 6 patients (12.8％).For the confluence patterns of B4:the central type was found in 10 patients (21.3％),the peripheral type in 35 patients (74.5％) and the combined type in 2 patients (4.2％).Analysis of the relationship between B1l and the confluence of B2 and B3 showed the distance to be (31.6 ± 6.2) mm in the above or the lateral patterns and (13.7 ± 4.7) mm in the medial pattern.The difference was significant (P ＜0.05).The distance from B1l to B4 was (7.1 ± 2.0) mm in the central and combined types but (16.4 ±4.0) mm in the peripheral type.The difference was significant (P ＜ 0.05).The left hepatic artery showed variations in the origin and course pattern in 4 (8.5％) and 6 patients (12.8％),respectively.The two-dimensional (2D) and 3D imagings showed excellent consistency in the evaluation of variations of the left biliary system in relation to the U-point and the left hepatic artery.Conclusions It is very important to know the variations of the left biliary and the vascular systems adjacent to the U-point in preoperative evaluating on resectability of HCCA.An accurate assessment could be accomplished using 2D imaging alone.However,3D reconstruction is a useful technique to use in complex case with locally advanced tumors.

Objective To evaluate the response of the lung tumor xenografts in nude mice to antiangiogenic treatment from perspectives of anatomic,vessel function,cellular and molecular level using the multimodality imaging techniques including optical imaging,dynamic contrast enhanced MRI(DCE-MRI)and diffusion weighted imaging(DWI).Methods The green fluorescent protein(GFP)was transplanted labeled using GFP-expressing NCI-H460 cells.After the transfection of GFP,NCI-H460 cells were implanted subcutaneously into nude mice.Ten days after implantion,12 nude mice whose tumor xenografts grew to 0.5-1.0 cm in the maximum diameter were randomly divided into 2 groups,and injected with phosphate-buffered saline and recombinant human endostatin respectively.Then the nude mice in the two groups underwent optical imaging,DCE-MRI and DWI.The volumes,photon counts,the quantitative MR vessel functional parameters including volume transfer constant(Ktrans),rate constant(Kep),volume of extravascular extracellular space(Ve)and maximum area under the enhancement curve(iAUC),and apparent diffusion coefficient(ADC)values of the tumors were recorded.Then tumors were collected and observed using the transmission electron microscopy and pathology examination,including HE staining,microvessel density(MVD)and the expressions of vascular endothelial cell growth factor(VEGF).The Kep and VEGF expressions in experimental group and control group were compared with x2 text,and other values were compared with t test.The Pearson and Spearman test were used for analyzing the correlation of values in the two groups.Results Seven days after inoculation,the fluorescence signals were detected and grew with the growth of the tumors.On the 7 day after starting therapy,the photon counts of experimental group and control group were(2.51 ± 2.43)× 1010(photon/sec)and(5.77 ± 3.25)× 1010(photon/sec),respectively with no significant differences(t =1.964,P ＞0.05).Two sample t test showed that the tumor volumes in experimental group were smaller than those in control group[(365 ± 56)vs(987 ± 265)mm3,t =0.001,P ＜ 0.01].There was a positive correlation(r =0.673,P ＜ 0.05)between the photon counts and the volumes of the tumors.The mean Ktrans,Kep,Ve and iAUC of experimental group were:(0.055 ±0.012)min-1,0.335(0.184—0.894)min-1,0.297 ± 0.041 and 7.334 ± 3.930,and those for control group were:(0.117 ± 0.027)rin-1,0.417(0.324-1.736)min-1,0.326:±:0.062 and 13.280 ± 4.245.There were significant differences of Krans and iAUC(t =5.155,2.518,P ＜ 0.05)between experimental group and control group.And there was a positive correlation(r =0.715,P ＜ 0.0 1)between the values of iAUC and MVD,but not the expressions of VEGF(r =0.484,P ＞ 0.05).The values of ADC in experimental group were higher than that in control group[(791 ± 38)× 10-6 vs(737 ± 43)×10-6 mm2/s],and there were significant differences(t =-2.299,P ＜ 0.05).Two sample t test showed that the MVD in experimental group were lower than that in control group[(11.9 ± 4.8)vs(19.2 ±4.3)item/hpf,t =2.774,P ＜ 0.05].The VEGF expressions in experimental group were lower than that in control group(x2 =4.000,P ＞ 0.05).It was observed that some cells in experimental group had degenerated and apoptotic signs by the electron microscopy.Conclusions Evaluating the response of lung tumor xenografts to antiangiogenic treatment at anatomical,vessel functional,cellular and molecular level using the multimedality imagings is applicable.And it will be in favour of evaluating the therapeutic effect promptly.

ObjectiveTo investigate the feasibility and accuracy of dual energy CT (DECT) in detecting acute myocardial ischemic reperfusion injury in a swine model.Methods Acute myocardial ischemic reperfusion injury model was made by ligaturing the left anterior descending coronary artery (LAD)or the first diagonal artery ( D1 ) of swine heart,the first-pass contrast enhanced DECT was performed.And then pigs were sacrificed,and the hearts were removed,triphenyhetrazolium chloride staining was performed.The CT numbers of non-ischemic and ischemic regions were measured.In the short axis of the left ventricle,the ventricular wall was divided into 17 segments for analysis,segments with myocardial perfusion defect in DECT myocardial iodine maps,DECT ( 140,100 kV,weighted average 120 kV) were determined and compared with histopathology.The sensitivity,specificity and inter-modality agreement of DECT in detecting myocardial injury were calculated.One-way ANOVA test was used to analyze the differences between the CT number and weight of infracted myocardium measured on DECT at 140,100 kV,weighted average 120 kV in ischemic and normal regions.ResultsPartial sparse or defective perfusion in the apical anterior and septal wall were demonstrated in DECT myocardial iodine maps.The CT number of injured myocardium was significantly lower than that of normal myocardium at 140,100 kV,weighted average 120 kV.The sensitivity,specificity of DECT myocardial iodine maps were 85.2％ (23/27),86.2％ (94/109),and Kappa value was 0.62,the sensitivity,specificity at 140 kV were 88.9％ (24/27),92.7％ (101/109),and Kappa value was 0.76,the sensitivity,specificity at 100 kV were 85.2％(23/27),89.0％ (97/109),and Kappa value was 0.67,the sensitivity,specificity at weighted average 120 kV were 88.9％ (24/27),91.7％ ( 100/109),and Kappa value was 0.74.There were no significant differences between the weight of infracted myocardium measured on DECT at 140,100 kV,weighted average 120 kV and histopathological results ( F =0.419,P =0.741 ).ConclusionDECT myocardial iodine maps can detect acute myocardial ischemic reperfusion injury in a swine model and have a good correlation with histopathology.

Objective To investigate the feasibility and accuracy of dual energy CT myocardial iodine maps in detecting acute myocardial infarction in canine model. Methods Myocardial ischemia model was made by ligaturing left anterior descending coronary arteries (LAD) after thoracotomy in six dogs, while another 3 dogs undergoing thoracotomy not ligaturing LAD as control group. Before and three hours after operation, dual-source CT (DSCT) was performed, followed by resting 99Tcm-MIBI single photon emission computed tomography myocardial perfusion imaging. Then, dogs were sacrificed, and the hearts were removed, triphenyltetrazolium chloride staining and conventional HE staining were performed. CT number of non-ischemic and ischemic regions were measured and analyzed. The wall of the left ventricle in the short axis was divided into 17 segments, the segments of myocardial perfusion defect in DSCT myocardial iodine maps, SPECT, and pathology were determined. Student t test was used to analyze the difference of CT number between infarcted and non-infarcted myocardium. Kappa test was used for the accuracy of DSCT myocardial iodine maps and SPECT in detecting myocardial ischemia according to the pathological results. Results No abnormal regions were detected using DSCT myocardial iodine maps in preoperative control and infarction group. After thoracotomy, partial sparse or defective perfusion was consistently noted in six dogs' apical anterior and partition wall in both DSCT myocardial iodine maps and SPECT. In the infarcted group, the attenuation of infarction region (34.75 ± 16.66) HU was significantly decreased compared with preoperative measurements ( 123. 18 ± 15.38 ) HU ( t = 10. 526, P ＜ 0. 01 ); decreased perfusion in the infarcted region was also noted in the DSCT myocardial iodine maps and SPECT. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DSCT myocardial iodine maps and SPECT were 85.0% (34/40) , 84. 1% (95/113) ,65.4% (34/52) ,94. 0%(95/101) ,and 82. 5% (33/40), 90. 3% ( 102/113 ) ,75.0% (33/44) ,93.6% ( 102/109 ), respectively.Kappa values were 0. 63 and 0. 71 for the agreement of DSCT myocardial iodine maps and SPECT.Conclusion DSCT myocardial iodine maps is comparable diagnostic accuracy with rest SPECT myocardial perfusion imaging in detection of acute myocardial infarction in a canine model.

Hepatobiliary surgery is considered to be technically challenging because of complex intrahepatic and perihilar anatomical structures and variations.Nowadays, three-dimensional imaging technique plays an important role in the time of precise liver surgery.Three-dimensional images depict the spatial location of tumor, and the course, confluence pattern and variation of portal vein, hepatic artery, biliary system and hepatic vein distinctly while showing involved hepatic segments and the relationship with adjacent vessels from omnidirectional view, measuring the length of margin and future remnant liver.With the help of surgical simulation, surgeons can determine the significant vessels preoperatively.The application of three-dimensional imaging technique may improve the resectability and safety of complex hepatobiliary surgery, such as hilar cholangiocarcinoma, centrally located liver tumor, hepatolithiasis and living donor liver transplantation.Meanwhile, three-dimensional visualization facilitates the understanding of two-dimensional images and complicated surgical anatomy for surgeons.