AlM: To explore the inhibiting effect of FTY720 on corneal neovascularization ( CNV) of rat.METHODS: MTT assay and cells scratch were adopted to observe hyperplasia of human umbilical vein endothelial cells ( HUVECs ) and cell migration induced by sphingosine-1-phosphate(S1P) after using FTY720 of different concentration. The effect of FTY720 on CNV induced by S1P in a rat corneal micropocket model was detected. 30SD rats were randomly divided into group A, group B and group C with 10 rats per group. S1P and 0μg, 5μg, and 20μg FTY720 controlled-released particles were implanted into the corneal stroma. The growth of CNV and having pathological examination on 12d after the operation was observed. Findings was analyzed by one-way ANOVA.RESULTS: 10, 102 , 103 , and 104 nmol/L FTY720 and HUVECs co-incubate 72h could inhibit cell proliferation (P < 0. 01 ), 24h after the function of 10, 100nmol/L FTY720, it could inhibit S1P-induced cell migration and the ability of restricting cell proliferation and cell migration was enhanced with increasing concentration of FTY720. On 12d, after rat corneal micropocket controlled-release particles was implanted into groups A, B, C, the CNV area were respectively 10. 05±1. 19, 6. 59±0. 95, 2. 70± 0.68mm2(F=145. 155, P<0. 01), group A and group B was statistically different and this was the same case between group B and group C (P<0. 01).CONCLUSlON:FTY720 can inhibit S1P-induced corneal neovascularization.

The effects of ultrafine grinding on the dissolution rates of the effective components in Sanjie Zhentong capsule (SZC) were studied in this experiment. Fine and ultrafine powder of SZC intermediates were made by ordinary grinding and ultrafine grinding technology, and then granulated by wet granulation. SZC were prepared by fine powder, ultrafine powder and ultrafine granules, respectively. With resveratrol and loureirin B as investigated indexes, dissolution rates of the four intermediates in SZC were determined by cup method and HPLC. The dissolution rates of resveratrol in SZC prepared by fine powder, ultrafine powder and ultrafine granules were 26.11%, 63.27%, 67.49%, respectively; and the dissolution rates of loureirin B were 7.160%, 20.29%, 23.05%, respectively. The dissolution rate of resveratrol and loureirin B in SZC prepared by ultrafine granules was the best. D90 size of ultrafine grinding was 13.221 μm and could improve the dissolution rates of resveratrol and loureirin B in SZC.
Capsules ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Particle Size ; Silicones ; chemistry ; Solubility ; Technology, Pharmaceutical ; methods

Adult ; Cardiovascular Diseases ; physiopathology ; Cardiovascular Physiological Phenomena ; Case-Control Studies ; Female ; Heart ; physiopathology ; Humans ; Pregnancy ; Sports ; Stress, Psychological ; physiopathology

This study is to establish physiologically based pharmacokinetic (PBPK) models of famitinib in rat and monkey, and then to predict the pharmacokinetics and tissue distribution of famitinib in human based on the PBPK models. According to published paper, previous studies and the chemical properties of famitinib predicted by ACD/ADME suite and SimCYP, the PBPK models of rat and monkey were established and optimized using GastroPlus. And then, the PBPK models were applied to predict the pharmacokinetic and tissue distribution of famitinib in human. The results showed that the PBPK models of rat and monkey can fit the observed data well, and the AUC0-∞, ratios of observed and calculated data in rat and monkey were 1.00 and 0.97, respectively. The AUC0-∞, ratios of observed and predicted data in human were 1.63 (rat to human) and 1.57 (monkey to human), respectively. The rat and monkey PBPK models of famitinib were well established, and the PBPK models were applied in predicting pharmacokinetic of famitinib in human successfully. Hence, the PBPK model of famitinib in human could be applied in future drug-drug interaction study.
Animals ; Antineoplastic Agents ; pharmacokinetics ; Haplorhini ; Humans ; Indoles ; pharmacokinetics ; Models, Biological ; Pyrroles ; pharmacokinetics ; Rats ; Receptor Protein-Tyrosine Kinases ; antagonists & inhibitors ; pharmacokinetics ; Tissue Distribution

[ABSTRACT]OBJECTIVETo investigate the therapeutic effect of early combination treatment with intratympanic glucocorticoid injection for sudden sensorineural hearing loss(SSNHL).METHODSTotal of 178 patients with diagnosis of SSNHL, including 44 with hearing loss at middle-low frequencies,50 at high frequencies,44 at all frequencies and 40 at total deafness, were randomly divided into combination treatment group (CT group) and systemic oral prednisone group (OP group).CT group (82 patients) received intratympanic administration of methylprednisolone and oral prednisone in tapering doses. Pure-tone threshold audiometry (PTA) was performed at week 8 after beginning of therapy. RESULTSIn middle-low frequencies, the final PTA and PTA improvement were 26.14±24.82 dB and 42.23±1.61 dB in CT group respectively, and were 37.91±13.98 dB and 30.00±13.30 dB in OP group respectively (both P<0.05). In high frequencies, all frequencies and total deafness SSNHL group, the differences of the final PTA and PTA improvement were not statistically significant in both groups. The PTA improvement in CT group for total deafness (26.52±14.03) dB was more than that of OP group (22.06±11.17)dB (t=2.361,P<0.05). In middle-low frequencies, the recovery rate was 72.73%(16 cases) in CT group, and 40.91% (9 cases) in OP group, the difference was significant (χ2=4.539,P<0.05), but not in apparent effective rate, effective rate and total effective rate. In high frequencies, all frequencies and total deafness, there were no significant differences in therapeutic effect. The recovery rate of total CT group (40.24%) was significantly increased compared with that of OP group (26.04%)(χ2=4.061,P<0.05), the differences of apparent effective rate, effective rate and total effective rate were not statistically significant in both groups.CONCLUSIONFor low-middle frequencies SSNHL, the early combination treatment with intratympanic glucocorticoid injection leads to higher hearing recovery and therapeutic effect compared with traditional oral prednisone. Systemic application should be applied for high frequencies, all frequencies and total deafness of SSNHL.

Objective To evaluate the efficacy of integrated traditional Chinese medicine(TCM)and western medicine in treatment of acute exacerbations of chronic obstructive pulmonary disease(AECOPD)combined with respiratory failure,TCM syndromes of spleen-kidney-yang deficiency and phlegm-dampness by comparison between the integrated therapy and simple western therapy in treatment of the disease. Methods 160 patients with AECOPD combined with respiratory failure,spleen-kidney-yang deficiency and phlegm-dampness syndrome in the intensive care units(ICU)of Affiliated Hospital of Chengdu University of TCM and other four hospitals were randomly allocated into two groups in this double-blinded,multicenter,prospective,randomized,controlled trial. In the control group (78 cases),western medicine and placebo were given to the patients,and in the treatment group(82 cases), conventional western medicine plus fei-shuai mistura 25 mL were administered,four times per day,the therapeutic course lasting for 2 weeks in both groups. The all-cause mortality,respiratory failure-cause mortality,improvement of modified Medical Research Council(mMRC)Dyspnea Scale grades,6 minutes walk distance(6MWD),the forced expiratory volume in 1 second/forced vital capacity(FEV1/FVC)were observed in the 28 days after the end of treatment. Results In the comparisons between the control and treatment groups,there were no statistical significant differences in the all-cause mortality〔54.87%(45/82)vs. 64.10%(50/78)〕and the cases of FEV1/FVC(both P>0.05)in the 28 days after the end of treatment;the 28 day respiratory failure-cause mortality was significantly decreased〔19.51%(16/82)vs. 33.33%(26/78),P<0.05〕,the number of patients with mMRC Dyspnea Scale grades (1-2)was obviously increased(22 cases vs. 7 cases,P<0.05),and the number of patients with 6 MWD grades (4-6)was markedly enhanced in the treatment group(21 cases vs. 8 cases,P<0.05). Conclusions The integrated TCM and western medicine has better therapeutic results in improvement of the patients' degree of dyspnea, 6 MWD and respiratory failure mortality than simple treatment with western therapy for treatment of patients with AECOPD combined with respiratory failure, spleen-kidney-yang deficiency and phlegm-dampness syndrome. However,in regard to the effect on pulmonary function and all cause mortality,the integrated therapy for treatment of such patients in short term has no significant effect.

The study compared the traditional medical microbiology experimental teaching with a new experimental teaching pattern,with the students majoring in anaesthesia as the research object. The new pattern mainly deals with the cultivation of the students' creativity by reforming and exploring the plan,the content,the method of experimental teaching and the ways of checking the students' work, adding general and designing experiment,and working out the PPT of the experiments.The result shows the new experimental teaching pattern contributes to the cultivation of the students'abilities of performing experiment, the ways of thinking, creativity and comprehensive analysis. It's better than the traditional experimental teaching pattern.A new medical microbiology experimental teaching systerm which is suit to the students majoring in anaesthesia has been established.

Objective To investigate the spatial distribution and clustering areas of Budd-Chiari syndrome in Heze City,Shandong Province,and to provide epidemiological information for further exploring the etiology and related risk factors of the disease.Methods Detailed residential addresses of 342 cases of patients (residents of Heze City) with diaphragm type Budd-Chiari syndrome diagnosed between 1995 and 2004 in Heze Municipal Hospital,Heze Shan County Central Hospital,Affiliated Hospital of Xuzhou Medical College,Shandong Provincial Hospital and Beijing Xuanwu Hospital were collected.Geographic information system (GIS) was used as a platform for data management and display.The nearest neighbor index,Ripley's K(d) function,Ripley's L(d) function and the nearest neighbor clustering method were applied to detect the spatial characters of Budd-Chiari syndrome in Heze City,Shandong Province.Crimestat 3.0 was used for spatial analysis.Results The nearest neighbor distance analysis showed that the nearest neighbor index was 0.6767 (Z =-11.4387,P ＜ 0.01).That was an aggregation at the first-order spatial scale.Within the study area,the first clustering radius of Budd-Chiari syndrome was 6.66 km,and the first clustering strength was 5.40; the average radius of the strongest clustering area was 126.61 km,and the clustering strength was 12.52,while the biggest clustering radius was larger than 222 km.After corrected by population,the gathering strength was slightly higher than that before the correction.Ten first-order hot spots were formed,and 95％ confidence interval aggregation number was 7,which meant the results were statistically significant(P ＜ 0.05),main clustering areas are in Mudan District,Shan County and Juancheng.One secondorder hot spot was gathered based on the first-order hot spot.Conclusions Spatial distribution of Budd-Chiari syndrome in Heze City,Shandong Province has showed spatial aggregation and heterogeneity.This study has a great epidemiological significance for further exploring the cause of Budd-Chiari syndrome.

Background The filtering surgery is the main method of treating glaucoma.Fibrosis of filtering bleb is a key cause of failure of operation.The study about application of anti-scaring drug in filtering surgery is a hotspot.Objective Present study was to investigate the anti-scaring effect of paclitaxel aher trabeculectomy.Methods Thirty-two adult clean domestic rabbits underwent standardized trabeculectomy and randomly divided into 4 groups.Normal saline solution was used beneath the scleral flap during trabeculectomy for 3 minutes in 16 eyes of 8 rabbits as controls.0.3 g/L mitomycin C,0.2 g/L paclitaxel or 0.3 g/L paclitaxel was administered at the same way respectively in other 3 groups.Intraocular pressure (IOP) was measured,and eye numbers with function blebs were compared among 4 groups at the 4th,7th,14th and 28th day after surgery.The opening of filtration tunnel and the number of inflammatory cells were observed by hematoxylin and eosin staining,and proliferation of new collagen fibers was evaluated by Masson trichrome method.This study complied with the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission(version 1988). Results No significant differences were found in the change of lOP among 4 groups before operation(F=0.54,P=0.83)and the 4th day aher operation(F=0.57,P=0.87).The IOP value was statistically lower in 0.3 g/L mitomycin C group,0.2 g/L paclitaxel group and 0.3 s/L paelitaxel group than the normal saline solution group(P＜0.05)with the lowest value in 0.3 s/L paclitaxel group in 7,14,28 days after operation(P＜0.05).Functional filtering bleb was seen in all the rabbit eyes in the 4th day after operation.In 7,14,28 days after operation,the number of eyes with functional bleb wag evidently more in 0.3 g/L mitomycin C group,0.2 g/L paclitaxel group and 0.3 g/L paclitaxel group compared with normal saline group(P＜0.05).The histological examination showed that the infiltration of inflammatory cells in filtering tunnel was much more obvious in normal saline solution group than the other groups with the most mild response in 0.3 g/L paclitaxel group.Masson trichrome revealed that proliferation of new collagen fibers in 0.3 g/L paclitaxel group was significantly decreased in comparison with those in other three groups at the 4th,7th,14th and 28th day after surgery(all P＜0.05). Conclusion Paclitaxel can inhibit the inflammatory response and collagen fibrosis and therefore open the filtering tunnel after it be used topically during the glaucoma trabeculectomy.

Objective To investigate the pathogenesis of peripheral blood mononuclear cells(PBMC) nuclear factor kappa-?B(NF-?B) in children with primary nephritic syndrome(PNS) and the effect of astragalus on the activity of NF-?B.Methods Twenty-five children with PNS and 20 normal children were studied.Isolated PBMC were separated from 5 mL venous blood in asepsis condition.NF-?B stimulator,NF-?B inhabitor and astragalus were added into the different tubes of PBMC,respectively.The nuclear protein was extracted from the pellets and the optical density(A) values of nuclear protein was measured by enzyme-linked immunosorbent assay(ELISA).Results The activity of PBMC NF-?B in PNS group was higher than that in normal group(P0.05).Astragalus could decrease the activity of PBMC NF-?B which had been stimulated by interleukin-1?(IL-1?)(P