Objective To discuss operative treatment of old fractures of pelvis. Methods Since February 2000, 14 cases with old fracture of pelvis have been treated in our hospital with operative scar or callus settlement, traction and reduction, and internal fixation. Results All patients were followed up from 6 months to 3 years and 6 months. According to such indexes as pelvic shape, length difference between lower limbs, gait, and radiogram, the scores were excellent in 8 cases, fine in 4 and poor in 2, with the excellent and good rate being 85.7%. Conclusion With reasonable design and appropriate method, operative treatment is fit for old fractures of pelvis because it can avoid severe disability and improve the quality of life of the patients.

Objective:To simulate the occupancy rates of baicalein， quercetin and galangin on the target sites of xanthine oxidase in vivo. Method:In this experiment， the half inhibitory concentration （IC₅₀） of febuxostat， baicalein， quercetin and galangin against xanthine oxidase were determined by in vitro enzymatic reaction. Binding free energy was predicted by molecular docking technology and their association rate constant （k_on） and dissociation rate constant （k_off） were determined by surface plasmon resonance technology. Based on measured binding kinetic parameters （k_on and k_off） and extracted pharmacokinetic data， the target occupancy model in vivo was established. Result:The IC₅₀ values of febuxostat， baicalein， quercetin and galangin were 0.002 7， 1.63， 0.38， 1.59 µmol·L^-1， respectively. The IC₅₀ of febuxostat was very close to that reported in the literature. The predicted curve of target occupancy rate in vivo of febuxostat was consistent with its duration of clinical efficacy. When single intragastric administration of long-circulating liposomes of quercetin with dose of 100 mg·kg^-1 in rats， the time of target occupancy rate >70% in vivo lasted for about 3.9 h. When rats were orally administered baicalein and galangin with dose of 200 mg·kg^-1， the time of target occupancy rate >50% in vivo lasted for about 10 h and 1.7 h， respectively. Conclusion:The prediction model of xanthine oxidase target occupancy constructed by drug target binding kinetics and in vivo pharmacokinetic curves can effectively evaluate the in vivo inhibitory activity of compounds against the target.

Based on the target occupancy mathematical model, the binding kinetic process of potential active ingredients of lowering uric acid in Chrysanthemum morifolium with xanthine oxidase(XOD) was evaluated. The potential active ingredients of lowering uric acid in Ch. morifolium were screened by UPLC-Q-Exactivems MS technology, reference substance identification and in vitro enzymatic kinetics experiments. The binding kinetic parameters of xanthine oxidase and potential inhibitor in Ch. morifolium were determined by surface plasma resonance(SPR). The verified mathematical model of the XOD target occupancy evaluated the kinetic binding process of inhibitors and xanthine oxidase in vivo. According to UPLC-Q-Exactive MS and reference substance identification, 39 potential uric acid-lowering active ingredients in Ch. morifolium extracts were identified and the inhibitory activities of 23 compounds were determined. Three potential xanthine oxidase inhibitors were screened, namely genistein, luteolin, and apigenin. whose IC_(50 )were 1.23, 1.47 and 1.59 μmol·L~(-1), respectively. And the binding rate constants(K_(on)) were 1.26×10~6, 5.23×10~5 and 6.36×10~5 mol·L~(-1)·s~(-1), respectively. The dissociation rate constants(K_(off)) were 10.93×10~(-2), 1.59×10~(-2), and 5.3×10~(-2 )s~(-1), respectively. After evaluation by different administration methods, the three selected compounds can perform rapid and sustained inhibition of xanthine oxidase in vivo under combined administration. This study comprehensively evaluated the target occupancy process of three effective components in different ways of administration in vivo by UPLC-MS, concentration-response method, SPR technology and xanthine oxidase target occupancy model, which would provide a new research idea and method for screening active ingredients in traditional Chinese medicine.
Chromatography, Liquid ; Chrysanthemum ; Flavonoids ; Kinetics ; Pharmaceutical Preparations ; Tandem Mass Spectrometry ; Xanthine Oxidase/metabolism*