OBJECTIVE:To investigate the rule for circulation system structure of drug market,and to analyze drug circulation costs.METHODS:The rules for macrostructure and microstructure of drug circulation were analyzed.The quantitative conception of circulation links(y),circulation extents(n),last nodes(m) and transaction relations were introduced and their relationship were investigate using mathematic model.The proportions of transaction relation in various sections were adopted to analyze circulation cost.RESULTS:There were rules for macrostructure and microstructure of drug circulation.The microstructure showed as a dendrogram circulation structure.Last nodes(m) and circulation extents(n) determinated circulation links(y),relationship between them was y=lnm/lnn.The proprotion of transaction relations in the last link was much higher than in the middle links.CONCLUTIONS:According to the mathematic model,transaction relations mainly concentrate in the last link.As a result it is not possible for us to cut down the quantity of transaction relations and the circulation costs through compaction of the middle links.

OBJECTIVE:To reveal the relationship between mark-up rate and false high price of drug and to study the formation mechanism of drug brokerage.METHODS:Based on the concrete condition,the ratio of circulation costs to production costs was analyzed with mathematical technology to establish price curve equation.The price base line and the formation mechanism of drug brokerage at condition of mark-up rate were analyzed.RESULTS & CONCLUSIONS:If the circulation costs had no elasticity and mark-up rate(?) was less than the ratio of circulation cost to production cost,there were three kinds of results:if price was determined according to the rule,drug had withdrawn from the market in view of unbalance of the circulation costs;false production costs induced the false high price of drug;brokerage of drugs were conducted.Theoretically the less the value of ? makes,the more false high price and brokerage of drug are.

Objective To develop and verify a reporter gene assay(RGA) for the detection of biological activity of human growth hormone(hGH).Methods The biological activity of hGH was evaluated by the expression of luciferase(Luc)activated by hGH binding to hGH receptor(hGHR) on HEK293/GH-Luc cell membrane.The developed detection conditions were as follows:the initial concentration of sample was 1 μg/mL;the cell inoculation amount was(2.45～2.66) × 10~4 cells/well;the sample was of 3-fold serial dilution,with a total of 8 dilutions and the incubation time was 18～24 h.The relative biological activity of the sample was calculated by measuring Luc intensity and comparing it with the national standard by four-parameter fitting.The developed method was verified for specificity,repeatability,intermediate precision,relative accuracy,linear range and durability.Results The excipient components in product and the serum components in culture medium showed no effect on the activity detection results;The geometric coefficient of variation(GCV) of relative titer of one batch of samples in six repeated detections was 6.794%,much lower than 20%.The relative titer GCV detected by two experimenters in different batches of samples at different times were both lower than 20%;The relative deviations of the relative titer determination values of samples at different concentrations were within ±12%,the slope of linear regression equation was 0.982,the linear range was 0.6～1.6 μg/mL,and the coefficient of determination(R~2) was 0.997;The GCV of three batches of stock solutions and one batch of finished products were 4.758%,4.430%,7.294% and 2.771% respectively under the conditions of different cell generation,cell density and sampling location,all of which were less than 20%.Conclusion The developed RGA showed good specificity,repeatability,intermediate precision,relative accuracy,linear range and durability,which met the application requirements and was expected to replace the traditional in vivo biological activity detection methods for the activity evaluation and quality control of hGH.

Objective:To study the effect of leuprolide preoperative used in the patients with uterine fibroids .Methods:Totally 70 patients with uterine fibroids were divided into the observation group and the control group with 35 ones in each.The 35 patients in the control group were with laparoscopic myomectomy , and those in the observation group was given leuprolide , 3.75 mg per time, once in a month for 3 months, and then undergone laparoscopic myomectomy .The serum hormone levels , menstruation situation and fi-broids and uterus volume changes in the observation group were observed and compared before the treatment and after the 3-month leu-prolide treatment .The situation during the operation and after the operation , and the recurrence rate of uterine fibroids between the two groups were compared .Results:After the pretreatment of leuprolide , the levels of luteinizing hormone ( LH) , follicle-stimulating hor-mone (FSH) and serum estradiol (E2) in the observation group were significantly lower than those before the treatment (P<0.05), and the menstrual blood volume , uterine volume and fibroid volume were significantly lower than those before the treatment , and the differences were statistically significant (P<0.05).The blood loss during the operation and pelvic drainage of the observation group were significantly lower than those of the control group , and the ambulation time and length of hospital stay of the observation group were significantly shorter than those of the control group with statistically significant differences (P<0.05).Conclusion:Leuprolide preoperative used in the patients with uterine fibroids can significantly reduce serum hormone levels and fibroid volume , which are ben-eficial to myomectomy with smaller surgery invasion and better prognosis .

Objective: To improve the standardization method for ethanol potassium hydroxide volumetric solution. Methods: A new potentiometric titration method was established and compared with the indicator method described in Chinese Pharmacopeia (2010 edition) . Results:There was no significant difference between the results of the potentiometric method and the indicator method( P>0. 05). Furthermore, the potentiometric titration had significant jump range, good precision and high reliability. Conclusion:The po-tentiometric method can be used in the standardization of ethanol potassium hydroxide volumetric solution.

Objective To prepare optimization of notoginsenoside R1 chitosan nanoparticles,to provide a theoretical basis for clinical application of the drug.Methods Notoginsenoside R1 chitosan nanoparticles were prepared,HPLC method was used to detect the content of notoginsenoside R1 chitosan nanoparticles,preparation technology of nanoparticles were optimized by orthogonal experiment,and the optimized preparation technology of nanoparticles was verified.Results HPLC standard curve equation was A =911.49C -1803.4(r =0.999 9),linear range was from 25 to 900 g/mL.The intra day precision were 1.520%,0.884% and 0.969%(n =6),and the inter day precision were 1.591%,1.447% and 1.269%(n =6).The recovery rates of low,medium and high concentra-tions were (98.11 ±1.16)%,(101.27 ±0.59)% and (100.97 ±0.82)%.4 factors of orthogonal experiment:the concentration of chitosan,the mass ratio of drug and carrier,temperature and rotational speed,and 3 levels of each factor were selected.The average particle size,encapsulation efficiency and drug loading were selected as control indexes.The test results were determined by the method of comprehensive weighted scoring.The orthogonal design was designed according to L9(34)orthogonal design.The optimization process was 2% of chitosan concentration,20% of the weight ratio of drug and carrier,35 ℃ of temperature,600 r/min of rotational speed.According to the optimized process,the average particle size was (123.40 ±7.68)nm,the encapsulation efficiency was (58.41 ±1.59)%,and the drug loading amount was (10.46 ±0.53)%.Conclusion The optimized preparation process of notoginsenoside R1 chitosan nanoparticles is simple and easy to operate,the entrapment efficiency and drug loading amount were high. As a new dosage form,it has a good clinical application prospect.

Objective To investigate the 9 . 4 T of DTT in the diagnosis of SD rat C6 cerebral gliomas model about the change of CST on tumor progression and pathology confirmed. Methods ①10 μl C6 cell suspension of 106 cells number were implanted into the right caudate nucleus of brain hemisphere of 20 adult male SD rat with ster-eotactic technique. ②Application of 9. 4 T of DTT and DTI, meanwhile the routine T1-weighted imaging(T1WI), T2-weighted imaging(T2WI), contrast-enhanced T1WI,FLAIR imaging and diffusion tensor of the brain were ac-quired. Anatomic relationship between cerebral glioma and surrounding white matter fiber tracts was analyzed and measured the values of FA and MD in different areas on fractional anisotropic ( FA) map, color-coded directional map, three-dimensional (3D) white matter fiber tracts map, then stained with routine HE. Results All of SD rat C6 cerebral gliomas models 3 D white matter fiber tracts map by means of FA maps of DTI were successfully comple-ted. Apparently significant differences of FA values were found in solid tumor, surrounding edema, compared with normal white matter regions ( P<0.05 );but there was no significant difference among solid tumor and surrounding edema region (P>0.05);there were significant differences of MD values between solid tumor, surrounding edema and normal white matter region ( P<0.05 ) . Conclusion The 9 . 4 T of DTT offers the optimal visualization of An-atomic relationship between cerebral glioma and surrounding white matter fiber tracts in the different periods of the tumor moder.

OBJECTIVE:To determine the content of the total flavonoid in Fructus Rosae Laevigatae.METHODS:Dual wavelength TLC scanner was selected with rutin as standard substance.The developing solvent was acetic ether-formic acid-water(8∶1∶1);?s=266 nm,and ?R=230 nm.RESULTS:The linear range of Fructus Rosae Laevigatae was 1～6 ?g,and the average recovery was 98.9% 2.397%(RSD=1.39%,n=6).CONCLUSION:The method is simple and accurate,and it is applicable for the quality control of Fructus Rosae Laevigatae.

Objective:To investigate the application of three-dimensional visualization technology in preoperative assessment of hilar cholangiocarcinoma. Methods:Thirty-eight patients with hilar cholangiocarcinoma who underwent surgery from March 2014 to April 2016 were enrolled in the retrospective study. Among the cases, an observational group of 18 patients had preoperative three-dimensional visualization surgical planning, while a control group of 20 patients did not have the visualization surgical plan. The preoperative diagnostic results were analyzed with the actual intraoperative findings. Related surgicall indicators between the two groups were compared. Results:No significant difference in the accuracy rates of longitudinal and vertical infiltration of cholangiocarcinoma between was observed the observational group and control group. While the vascular and ductal branching pattern of all patients are consistent with intraoperative findings, the coincidence rate was higher in the observational group than that in the control group (100%vs. 70%, P<0.05). The estimated liver volumes were also exactly consistent with the actual liver volume (r=0.986, P<0.001). In comparison with the control group, the average intraoperative blood loss and operative time of the observational group were significantly lower. However, the potential curative resection between the two groups exhibited no significant difference. Conclusion:Three-dimensional visualization technology can accurately complete the preoperative evaluation of hilarcholangiocarcinoma.

Osteoarthritis (OA) is a common chronic arthritis, mainly suffering the middle and elderly patients, and it is the main cause of arthralgia and articular functional disturbance. Studies have suggested that osteophyte formation was closely con?nected with the development of OA due to the stabilization of suffered joints and arthralgia induced by osteophytes. In tissue con?stitution and pathology, osteophyte is made up of bone, cartilage and connective tissue, stemming from MSCs. With the develop?ment of osteophytes, the proportion of bone increases while the proportion of cartilage and connective tissue decreases. What's more, in promotion factors of osteophytes, osteophyte formation was induced by the biomechanical and biochemical factors and their both effect. The biomechanical factors result from imbalance of articular biomechanics induced by cartilaginous degeneration and ligament trauma. And the biochemical factors result from alteration of articular microenvironment induced by metabolic disor?der of chondrocytes and synovitis. Furthermore, the both effects that the biomechanical factors induces biochemical alterations al?so co?promote osteophyte formation. And studies on the mechanism indicated that osteophyte formation was regulated by several signaling pathways and cytokines. TGF?β superfamily and Hedgehog signaling pathway were involved in modulating osteophyte formation. TGF?βand BMPs modulated the initiation and late stage of osteophyte formation respectively. And Hedgehog signaling pathway regulated the osteophyte formation with modulating the hypertrophy of chondral osteophytes. This paper emphatically re?views the development and mechanism of osteophytes in OA for deeply understanding the OA and bringing new ideas and methods for the precaution and treatment of OA.