Objective:To dynamically describe the drug concentration change in different time in vivo to understand the in vivo be-havior patterns and rules of drugs, provide reference for performing individual treatment and avoiding adverse drug reactions and lay foundation for dynamic description of physiological pharmacokinetic model. Methods:A two-compartment model was established using Simulink dynamic simulation and used in curve fitting and parameter estimation. The results from the model were compared with those from 3P97 software. Results:There was no significant difference between the results from the dynamic model and those from 3P97 soft-ware. Conclusion:The dynamic model can be used to dynamically simulate two-compartment model for oral administration. The re-sults from the dynamic simulation are more direct, and can correct the fitting error in 3P97 software.

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Animals ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; metabolism ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1 ; metabolism ; Lignans ; pharmacology ; Mice, Nude

Objective:To explore the regulation of Recipe Xiaoban No.1 on the expression of p53 in dystrophy of vulva.Methods:Expression of p53 was determined by immunohistochemical technique in skin lesion of prior treatment and posttreatment from 30 cases with chronic vulvar dystrophy,and normal skin from 23 health adults were served as controls.Results: Expression of p53 in various of chronic dystrophy of vulva before treatment was obviously higher than control group(P0.05).Conclusion:Recipe Xiaoban No.1 can obviously improve the clinical symptoms and decrease the expression rate of P53.

Objective To investigate the relationship of antithrombin‐Ⅲ activity and thrombosis risk in liver cirrhosis with Child‐Pugh classification .Methods In our hospital from June to December 2014 ,60 liver cirrhosis patients were selected randomly included into this experiment group ,The 60 cases of control group were from medical examination of health in our hospital .The plasma AT‐Ⅲ activity and D‐D concentration in all these cases were detected and analyzed .Results The AT‐Ⅲ in cirrhosis patients were significantly lower than which in healthy persons(P<0 .05) .The lower level of AT‐Ⅲ is in these patients which were in seri‐ous condition(P<0 .05) ,the abnormal rate of D‐D concentration is also higher at the same time(P<0 .05) .Conclusion The detec‐tion of AT‐Ⅲ level in patients with liver cirrhosis is directly related to the severity of clinical and thrombosis risk .The AT‐Ⅲ de‐tection level can be used to judge the patient′s condition and develop appropriate treatment strategies .

Background Our previous study demonstrated that epigallocateehin-gallate(EGCG),an active ingredient of green tea,has protective effect on optical nerve after optic nerve crush.Astrocyte was proved to play key role in the repair of nerve tissue,but the influence of EGCG on astrocyte is unclear.Glial flbrillary acidic protein (GFAP) is a special marker for astrocyte. Objective The aim of this study was to investigate the effect of EGCG on the expression of GFAP in optic nerve tissue after optic nerve crush. Methods Seventy-two clean Wistar rats were randomly divided into normal control group,sham+EGCG group,optic nerve crush+normal saline group(vehicle group),optic nerve crush+EGCG group.Optic nerve crush models were established by clamping optical nerve for 60 seconds by minitype optic nerve clipper with the force of 40 gram.Only ocular tissue was cut in the rats in sham group.Normal saline solution or EGCG(25 mg/kg)was intraperitoneally injected daily for 5 days consecutively and orally administered(2 mg/kg)daily afterwards.The expression of GFAP in optic nerve was detected by immunohistochemistry and quantified by Western blotting analysis on day 7,14 and 28 after modeling. Results lmmunochemistry showed that GFAP were weakly expressed in the rats of both normal group and sham+EGCG group with the sliSht brown staining in optic nerve tissue.The deeply brown staining for GFAP was seen in vehicle group,and the staining intensity weakened in optic nerve crush+EGCG group compared to vehicle group on days 7,14 and 28 after modeling.Western blotting analysis revealed that the expression level of GFAP in rat optic nerve tissue of vehicle group was significantly enhanced in comparison with normal control group(P＜0.01).On day 7 and 14 after optic nerve modeling,the expression levels of GFAP were evidently decreased in optic nerve crush+EGCG group in comparison with vehicle group(P＜0.05).However,on day 28 after modeling,no significant difference wag found in the expression levels of GFAP between vehicle group and optic nerve erush+EGCG group(P＞0.05). Conclusion EGCG down-regulates optic nerve crush-induced of GFAP in the optic nerve and therefore attenuates the activity of astrocytes,suggesting that EGCG might reduce the formation of glial scar.

Background Researches demonstrated that epigallocatechin-3-gallate(EGCG) can protect retinal ganglion cells(RGCs) against damage induced by retinal ischemia-reperfusion and optic nerve crush(ONC),but the effect of EGCG on lateral geniculate nucleus(LGN) was under study.Objective This study was designed to detect neuroprotective effect of EGCG on LGN in the rat model with ONC.Methods Forty-eight 7-week-old female clean Wistar rats were randomly divided into normal control group,sham operation+EGCG group,ONC+normal saline(NS) group and ONC+EGCG group.ONC models were created by clamping the optical nerve for 60 seconds with the clipper with the force of 40 grams in the right eyes of 24 rats.The EGCG solution(25mg/kg) was intraperitoneally injected from 2 days before operation daily for 5 consecutively days and orally administered(2mg/kg) after that,and NS was used in the same way for ONC+NS group.Four weeks after ONC,the brain tissue of the rats was obtained,and the neurons of dorsal LGN(dLGN) were counted by Nissl staining under the light microscopy.The expression of neurofilament triplet L(NF-L) was detected by immunohistochemistry and Western blot analysis.Meanwhile,the neuronal nitric oxide synthase(nNOS) positive cells were counted.Results Compared with normal control group,no significant differences were found in neuron number both between sham operation+EGCG group or ipsilateral LGN of operative eyes in ONC+normal saline group and ONC+EGCG group(P=0.906,0.561,0.794,0.646 respectively) in 4 weeks after ONC,but loss of neurons in contralateral LGN in both ONC+normal saline group and ONC+EGCG group were observed(P=0.000,0.015 respectively).However,compared with ONC+normal saline group,the density of neurons in ONC+EGCG group was higher(P=0.007).Moreover,a higher expression level of NF-L protein was seen in ONC+EGCG group compared with ONC+normal saline group at contralateral LGN of operative eyes(P=0.002).Concerning the number of nNOS positive cells in LGN,there was no significant difference among normal control group,sham operation+EGCG group and ONC+EGCG group(P＞0.05).The number of nNOS positive cells in the contralateral LGN of operative eyes of ONC+normal saline group was higher than that of ONC+EGCG group(P=0.000).Conclusion EGCG plays the protective effect on LGN after ONC in rats through mediating the expression of nNOS.

Objective:To investigate the adhesion,proliferation and differentiation of the stem cells from human exfoliated deciduous teeth(SHEDs)on 3 different types of hydroxyapatite(HA)composite scaffold materials.Methods:Pulp cells from human exfoliated de-ciduous teeth were harvested from impacted deciduous teeth by enzyme digestion,expanded and cultured.Cells were verified by immuno-histochemical methods and in vitro differentiation test.Then the cells were cultured on HA/beta tricalcium phosphate (HA/TCP),HA/collagen (HA/COL)and HA/poly-ethylene propylene lactide (HA/PLGA)scaffold respectively.Adhesion rate was examined at hour 4,6,8 and 10 of culture,proliferation was observed by MTT assay on day 1,4,7 and 10 of culture,respectively.The osteogenic dif-ferentiation was studied by alkaline phosphatase(ALP)test,Von Kossa staining and calcium content measur.Results:The attachment of SHEDs was significantly lower on the HA/COL than on the other 2 scaffolds(P <0.05).The ALP activity,mineralization and calci-um content were the highest on HA/PLGA,and the last on HA/COL(P <0.05).Conclusion:HA/PLGA scaffold is more effective in the promotion of the proliferation,attachment and differentiation of SHEDs than HA/TCP and HA/COL scaffolds.

Objective: To study the relationship between the inhibitory effects of Tongxie Yaofang, a compound traditional Chinese herbal medicine, on the contraction of the colonic smooth muscle isolated from rats and calcium mobilization. Methods: By measuring the tension of the isolated colonic smooth muscle strips, the inhibitory effects of Tongxie Yaofang on the contraction induced by acetylcholine (ACh), KCl and exhausting Ca(2+) of internal calcium store were assessed respectively. Results: Tongxie Yaofang could concentration-dependently inhibit the contraction of isolated rat colonic smooth muscle strips induced by KCl and exhausting the Ca(2+) of internal calcium store. Tongxie Yaofang could also inhibit the tension of the second contractile phase induced by ACh (P<0.01, vs control), but had no influence on the first contractile phase. Conclusion: Tongxie Yaofang can inhibit the contraction of isolated rat colonic smooth muscle strips mainly by preventing the influx of extracellular Ca(2+), which may be associated with blocking voltage-dependent channel, store-operated channel and receptor-operated channel, but not by preventing the release of internal Ca(2+) from calcium store.

Objective To clarify the relationship between CT120,a novel human plasma membrane-associated gene,and the proliferation of lung adenocarcinoma cell line A549.Methods Expression vector(pcDNA3.1)containing antisense oligonucleotides of CT120 was constructed and transfected into the adenocarcinoma cell line A549.RT-PCR and Western blot detected the expression of CT120.Meantime,flow cytometry and soft agarose colony formation were applied for cell proliferation,and P53,CyclinD1 and CDK4 were detected by RT-PCR.ResultspcDNA3.1 containing antisense oligonucleotides of CT120 was successfully constructed and inhibited the expression of CT120 effectively by RT-PCR and Western blot.The expression of P53 was up-regulated and the expression of CyclinD1 and CDK4 were down-regulated.Conclusion The down-regulation of CT120 expression by antisense oligonucleotides technique may be a potential drug target for treatment of lung cancer.

Objective To investigate the feasibility of ~1H-MR spectroscopy(~1H-MRS)imaging to quantitatively detect fatty liver.Methods Twenty patients with fatty liver and 11 healthy volunteers underwent plain CT scan,conventional MR imaging and ~1H-MRS analysis.The blood lipid and liver function were tested on the same day as the MR examination.~1H-MRS sequence measured the peaks of H_2O and lipid,and the areas under the peaks.The relative contents of the lipid compound were calculated,and compared with the results of CT scan and liver function tests.Results The CT values of the normal group and the fatty liver group were(59?9)HU and(24?11)HU respectively.On ~1H-MRS a protruding high H_2O peak and a flat low lipid peak were observed in the normal group,while the protruding high H_2O peak and a high lipid peak appeared in the fatty liver group.The values of lipid peak in the normal group and the fatty liver group were(0.05?0.01)?10~5,(0.70?0.24)?10~5 respectively(t=4.32,P0.05),the areas under the lipid peak were(1.36?0.73)?10~9、(2.35?1.15)?10~9 respectively(t=5.21,P0.05).Conclusion ~1 H-MRS imaging is feasible to quantitatively detect liver fat and is a non-invasive method for detecting early fatty liver.