OBJECTIVE:To provide a new idea for enhancement of core competitiveness of pharmaceutical enterprises in China and supply advice for building virtual marketing network.METHODS:The concept and theory of virtual management and virtual marketing network were interpreted and analyzed according to the status quo of pharmaceutical enterprises in China.RESULTS & CONCLUSION:Virtual marketing network is a new idea for the development of pharmaceutical enterprises.Enterprises should establish a standard cooperative relation with the dealers in order to prevent risks and promote core competitiveness of enterprises.

10.3969/j.issn.2095-4344.2013.26.016

Objective To explore the expression of KAI1/CD82,E-cadherin and β-catenin in endometrial carcinoma,and to investigate their correlations to clinicopathological parameters of endometrial carcinoma. Methods The expressions of KAI1/CD82,E-cadherin and β-catenin in 76 specimens of endometrial carcinoma,15 specimens of atypical endometrial hyperplasia and 20 specimens of proliferative endometrium were examined by immunohistochemical envision technique.Their correlations to clinicopathological parameters of endometrial carcinoma were statistically analyzed. Results Compare to normal proliferative phase endometrium and atypical endometrial hyperplasia,the expression of KAI1/CD82 in endometrial carcinoma was significantly decreased(P ＜0.01),the abnormal expression of E-cadherin and β-catenin in endometrial carcinoma were significantly higher(all P <0.01).In endometrial carcinoma,the expression of KAI1/CD82 was negative correlated with histological grade and depth of myometrial invasion(P <0.01,P <0.05); The abnormal expression of the E-cadherin is related to histological grade and type(P <0.01,P<0.05); The abnormal expression of β-catenin was positively correlated with histological grade and FIGO stage(P ＜0.01 ,P <0.05).The down-regulation expression of KAI1/CD82 was closely associated with the abnormal expression of E-cadherin and beta-catenin in endometrial carcinoma(P <0.01,P <0.05). Conclusion The down-regulation of KAI1/CD82 and the aberrant expression of E-cadherin and β-catenin could be involved in the development of endometrial carcinoma.The loss or reduced expression of KAI1/CD82 was closely associated with the abnormal expression of E-cadherin and β-catenin in endometrial carcinoma.

Objective To investigate the myelination of rat brain at different developmental stages.Methods Luxol fast blue staining,immunohistochemistry and Western blotting were applied to determine the distribution and alternation of myelin sheath in the brains of SD rats at different developmental stages.Results Negative LFB and MBP staining were shown at the stages of embryonicage 18 d(E18),postnatal age 0 d(P0) and P2.At P7,the corpus callosum was weakly stained by LFB.The positive stain of LFB and MBP occurred in P15 on the corpus callosum.With the development going on,the stain turned out stronger,especially in P30,which was similar with that in P90 and P720.The results of Western blot analysis showed the expression of MBP in rat brain was gradually increased with the development of rat brain.Conclusion The myelination starts before P15 in rat brain and becomes mature in P30.The optimal observation time of myelin is 30 d born after.

The morbidity of deep vein thrombosis (DVT) after total hip replacement,total knee replacement or hip fractures surgery is high,and there is no effect way to prevent.Rivaroxaban is an oral,direct factor Xa inhibitor.The prevention effect of rivaroxaban to DVT after orthopedic surgery is stronger than enoxaparin.The view summarizes the mechanism,pharmacokinetics,interaction of drugs and the antithrombotic effect after orthopedic surgery.

objective To introduce the design concept and structure of a new type of lumbar intervertebral fusion cage ,and to e-valuate its biomechanical properties .Method A partially bioasorbable interbody fusion cage(PBIFC) made of nano hydroxyapatite and poly amino acid /calcium sulfate copolymer materials was developed .Range of motion(ROM ) ,compressive load ,and pull-out test on flexion ,extension ,lateral bending ,and torsion moment on fresh calf L3/L4 specimens of functional spinal union were carried out of iliac bone group ,PBIFC group ,and nano hydroxyapatite/polyamide 66(nHA/PA66) group .Result Of each movement ,the ROM value of iliac bone group are higher than the other two groups ,the difference was statistically significant (P<0 .05) ,and the ROM value of nHA/PA66 group are higher than PBIFC group ,but no statistical difference(P>0 .05) .The pull-out strength of PB-IFC group are higher than iliac bone group ,and the difference was statistically significant (P<0 .05);The pull-out strength of PB-IFC group is lower than the traditional group ,but no statistical difference(P>0 .05) .The compressive load of iliac bone group was lower than that of two cage group ,the difference was statistically significant (P<0 .05) .The compressive load of PBIFC group is slightly lower than the traditional group ,but no statistical difference(P>0 .05) .Conclusion With good implant stability ,pull-out resistance ,and compression resistance performance ,PBIFC can meet the biomechanics requirements of clinical implant .

BACKGROUND: Growth-associated protein-43, a kind of protein relatedto axonal growth, plays a key role in promoting neural development, axonalregeneration, synaptic growth and structural and functional reconstructionand so on. In the study, we find that cyclovirobuxine D can protect braininjury in rats with experimental cerebral ischemia reperfusion.OBJECTIVE: To observe the effect of cyclovirobuxine D on the expression of growth-associated protein-43 mRNA in hypertensive rats with cerebral ischemia reperfusion.DESIGN: A randomized controlled animal experiment.SETTING: Foshan Hospital of Traditional Chinese Medicine of Guangdong Province; Central Laboratory of Guangdong Hospital of Traditional Chinese Medicine.MATERIALS: Cyclovirobuxine D is alkaloid monomer extracted from Chinese herb buxine. Cyclovirobuxine D powder with national protected traditional medicine number of ZYB20796057 was provided by Nanjing Xiaoyingyao Pharmaceutical Factory. Totally 120 two-to-three-month-old healthy male SD rats, of either gender, with body mass of 90 to 120 g, were used in this experiment.METHODS: This experiment was carried out in Foshan Hospital of Tra ditional Chinese Medicine of Guangdong Province and at the Central Laboratory of Guangdong Hospital of Traditional Chinese Medicine between June 2005 and March 2006. ①Stroke-prone-renovascular-hypertensive-rats models (RHRSP)were created by bilaterally narrowing the renal artery with silk loop clips. Totally 120 rats were randomly divided into blank group (n=20,renovascular hypertensive rats were given no treatments), sham operation group (n=20, rats were given only surgical trauma), model group (n=40, rats were given treatment of cerebral ischemia reperfusion) and cyclovirobuxine D-treated group (n=40, rats were given cyclovirobuxine D).② Unilateral occlusion of the middle cerebral artery ischemia reperfusion models were made with suture-occluded method. 6.48 mg/kg cyclovirobuxine D diluted by 1.5 mL normal saline was intraperitoneally injected into the rats of cyclovirobuxine D-treated group, twice per day; Normal saline was isochronously intraperitoneally injected into the rats of each subgroup of control group, 2 mL once, the method was the same as that of the cyclovirobuxine D-treated group; interval of injection time was 7 hours in each group. Rats in each group were executed on days 1, 7, 14 and 30after ischemia reperfusion. ③ Brain slice was prepared. The expression of growth-associated protein-43 mRNA of rats in each group was detected with in situ hybridization.MAIN OUTCOME MEASURES: ① The expression of growth-associated protein-43 mRNA around ischemia are following ischemia reperfusion for 2 hours. ②The expression of growth-associated protein-43 mRNA in hippocampus following ischemia reperfusion for 2 hours RESULTS: All the 120 rats entered the stage of result analysis. ① Immune in situ hybridization of growth-associated protein-43 mRNA: In situhybridization showed that expression of growth-associated protein-43 mRNA and expression of growth-associated protein-43 mRNA could be detected respectively in the hippocampus and marginal area of hematoma after ischemia and reperfusion.②The expression of growth-associated protein-43RNA around haematoma following cerebral ischemia reperfusion group as not found in blank group and sham-operation group; The expression of growth-associated protein-43 mRNA was found in the marginal zones around haematoma of rats in the model group on the 1st day following ischemia reperfusion and it was significantly increased on the 7th day, gradually reduced on the 14th day and still expressed on the 30th day but less,with significant difference at each time point (P ＜ 0.01); Expression of growth-associated protein-43 mRNA around haematoma at each time point was more in the cyclovirobuxine D-treated group than in the model group ,with significant difference (P ＜ 0.05). ③There was no significant difference of the expression of growth-associated protein-43 mRNA in hippocampus of rats following cerebral ischemia reperfusion between blank group and sham-operation group; Expression of growth-associated protein-43 mRNA was found in hippocampus of rats in the model group on the 1st day after modeling, and it reached the peak on the 7th day, gradually decreased on the 14th day and significantly decreased on the 30th day, but significantly more than that of sham-operation group; The expression of growth-associated protein-43 mRNA in hippocampus was significantly more at each time point in cyclovirobuxine D-treated group than in model group, with significant difference (P ＜ 0.01).CONCLUSION: Cyclovirobuxine D up-regulates the expression of growthassociated protein-43 mRNA after reperfusion and promotes axonal regeneration of rats with experimental cerebral ischemia.

Objective To analyze the characteristics and significance of matrix metalloproteinase-9 (MMP-9) expression in the pathophysiological processes of tuberculous meningitis in mice.Methods Sixteen mice were intracerebroventricularly injected with H37RV suspension as the model group.Meanwhile,the other 16 mice were injected with 0.9％ sodium chloride solution as the control group.Thirty days later,all mice were decapitated and the brain tissue were respectively used to for Mycobacterium tuberculosis (M.tuberculosis) incubation,pathological changes observation,MMP-9 activity detection by zymography,blood-brain-barrier permeability and moisture content detection,and immunofluorescence stain of MMP-9,glial fibrillary acidic protein (GFAP) and integrin αM (OX-42).The t test was used to compare the differences between the two groups.Results Every experimental mouse was injected with (1.271±0.111) × 106 colony-forming units (cfu) M.tuberculosis.Thirty days later,the amount of M.tuberculosis in brain tissue homogenates was (4.900± 1.407) × 104 cfu/mL,and the hematoxylin and eosin staining showed dilatation of subarachnoid and ventricular and infiltration of a large number of inflammatory cells.The cumulative absorbance (A) of MMP-9 bands of brain tissue was 47 821 ± 19 932 in the model group and 10 082 ± 3 544 in the control group.The difference was statistically significant (t =3.728,P=0.010).The evans blue (EB) content of brain tissue was (11.8 ± 3.6) μg/g in model group and (4.7 ±3.4) μg/g in control group.The difference was statistically significant (t=2.887,P=0.028).The moisture of brain tissue was 0.849±0.035 in model group and 0.775±0.037 in control group.The difference was statistically significant (t=2.925,P=0.026).The immunofluorescence staining showed that the infected brain tissue expressed high degrees of MMP-9,GFAP and OX-42.And MMP-9 was overlapped with both GFAP and OX-42 obviously.Conclusions The activity of MMP-9 is significantly enhanced in brain tissue of mice suffering from tuberculous meningitis and participates in blood-brain barrier damage,tissue edema and inflammatory cells exudation.Microglia cells-astrocytes network is involved in the secretion of MMP-9.

Objective To evaluate the in vitro antifungal activity of Cinnamaldehyde in combination with Voriconazole (VRC) against clinically isolated Aspergillus fumigatus strains. Methods According to the Clinical and Laboratory Stan?dards Institute (CLSI) M38-A2 document,the minimal inhibitory concentrations (MIC) of Cinnamaldehyde and VRC alone or in combination against 42 clinical Aspergillus fumigatus isolates were determined by both microdillution method and check?board method respectively. The MIC50, MIC90, MICG and MICs distribution were compared between single drug and both in combination. The concentration-accumulative curve was drawn and fractional inhibitory concentration index (FICI) was cal?culated to evaluate the interaction between two test agents. Results The values of MIC50, MIC90 and MICG were significant?ly decreased (P<0.001) when combination of the two drugs than those of their single use, with their MIC distribution concen?tration-accumulative curves shifted to the left. The value of FICI of Cinnamaldehye-VRC combination ranged from 0.187 5 to 1.5. Sixteen strains (38.10%) of them showed the synergistic effect, 19 strains (45.23%) showed additive effect, and 7 strains (16.67%) showed an unrelated effect, and no antagonist effect on tested Aspergillus fumigatus strains in vitro. Conclu?sion Cinnamaldehye in combination with VRC mainly shows a combined synergic and additive inhibitory effect on Asper?gillus fumigatus isolates, and this combination appears to be more active against the test strains, which are less susceptible to voriconazole.

Objective To investigate the in vitro destructive effect of chlorogenic acid (CRA)/isochlorogenic acid (IRC)on Aspergillus fumigatus biofilm in a model of biofilm formation.Methods The in vitro biofilm model was established using clinical isolates of A.fumigatus.The minimum inhibitory concentrations (MIC)of antimicrobial agents against A.fumigatus were determined by microdilution method.Scanning electron microscope (SEM)and laser confocal scanning microscope (CLSM)were used to characterize the biofilm.Crystal violet staining method was used for biofilm quantitation.Results After reaction with CRA/IRC for 24 h or 48 h,observation of biofilm showed that A.fumigatus extracellular matrix was thinner than the control group.Biofilm quantitation showed that the optical densities were 1.05±0.19,1.14±0.26,0.99±0.14 for CRA group (1 024 mg/L,512 mg/L,256 mg/L);1.39±0.06,1.41±0.06,1.60±0.04 for IRC group (1 000 mg/L,500 mg/L,250 mg/L)at 24 h,and 1.91±0.17 for control group (P<0.05).The quantitation of biofilm showed that the optical densities were 2.25±0.05,2.27±0.05,2.31±0.03 for CRA group,2.26 ± 0.02,2.27±0.02,2.29±0.04 for IRC group at 48 h,and 2.36±0.01 for control group (P<0.05).Conclusions CRA/IRC has some inhibitory effect on the formation of A.fumigatus biofilm.