The pharmacokinetics and tissue distributions of the novel paclitaxel microemulsion based on the L-OH lipid complex made in our laboratory were studied in this article with the commercial paclitaxel injection in cremophor as reference preparation by injected intravenously with single dose of 5 mg x kg(-1) in rats. LC-MS/MS method was used to determine the drug concentration in plasma and calculate the pharmacokinetic parameters. [3H]-paclitaxel was used to reveal the tissue distributions of different organs in 0.5 h, 3 h, 24 h and 120 h. The results indicated that the AUC of the emulsion group descended to 42.55%, with the CLz and Vz increased by 2.27 times and 3.81 times respectively. Tissue distribution results revealed that the emulsion showed a significantly increase in liver and spleen with a peak concentration up to 5 times; a slightly increase was observed in lung with no statistical differences; a significantly decrease in heart, kidney, gastrointestinal tract, bone marrow, aorta, thymus, pancreas, fat, muscle, skin, seminal vesicle, reproductive organs and brain with a drop of 40%-80%. These results indicated that paclitaxel microemulsion based on L-OH lipid complexes can remarkably reduced the blood exposure, accelerate plasma clearance rate and increase distribution volume. The fact that paclitaxel microemulsion tended to be uptake by reticuloendothelial system (RES) contributed to the target in liver, spleen and lung, and help to reduce the toxicity in blood, heart, kidney and gastrointestinal tract.

Objective To explore the effectiveness of ipsilateral autologous semitendinosus ten don graft in treatment of lateral ankle ligament injuries and ankle instability. Methods Two patients including one male (25 years old) and one female (17 years old) with chronic lateral instability of the ankle were enrolled in the study. Both patients had the history of repeated ankle sprain in supination position and had grade Ⅲ injury of the lateral ankle ligament according to the American College of Foot and Ankle Surgeons Grading System. Anterior drawer test and talar tilt test were all positive. The stress-inversion radiograph demonstrated the average inclination of the talus for 21 ° and the lateral radiograph demonstrated anterior dislocation of the talus. The chronic ankle instabilities in two patients were treated by using the ipsilateral autologous semitendinosus tendon graft to reconstruct the lateral ankle ligament. Results The two patients were followed up for mean eight months, which revealed that the active and passive range of motion was good, with no pain or swelling. The anterior drawer test and talar tilt test were all negative. The stress-inversion radiograph demonstrated that the average inclination of the talus was less than 5°, with no anterior dislocation of the talus. According to the Mazur grading system, the clinical outcome was excellent in one patient and good in one. The two patients were satisfied with the stability of the ankle. Conclusions ( 1 ) Lateral ankle ligament injury is a common cause of chronic ankle instability,even the ankle osteoarthritis. ( 2 ) Brostr(o)m method can attain satisfactory result for fresh lateral injury of the ankle, but not for the old injuries. ( 3 ) Ipsilateral autologous semitendinosus tendon graft is simpleand effective for treatment of lateral ankle ligament injuries and chronic ankle instability and may play an important role in the treatment of lateral ankle instability and prevention of the occurrence of ankle osteoarthritis.

Objective To investigate the effect mechanism of sanguinarine on the proliferation,apoptosis,invasion and migration abilities of cervical cancer cells.Methods MTT,flow cytometer,cell scratch test and Transwell chamber assay were respectively used to detect the cellular proliferation,apoptosis,migration and invasion abilities after sanguinarine action.The expression levels of E-Cadherin,PTEN,β-catenin and MMP2 protein of cervical cancer cells after sanguinarine action were detected by Western blot.Results 0.6,0.8 μmol/L sanguinarine had the inhibitory effect on the proliferation of cervical cancer cells.After 0.8μmol/L sanguinarine action for 48 h,cervical cancer HeLa and Siha cells apoptosis rate were up to (45.68± 2.26)％ and(31.89 ± 3.80)％ respectively.0.8 μmol/L sanguinarine action for 3 h,cervical cancer cells HeLa and Siha adhesion rates were only (67.45 ± 2.13)％and(73.59± 2.61)％.0.8 mol/L sanguinarine action for 16 h,the invasion numbers of cervical cancer Hela and Siha cell were (39.64 ±1.98) and (43.87 ± 2.83) respectively.The expression amount of E-Cadherin and PTEN in cervical cancer cells after sanguinarine action was increased,while the expression amount of E-Cadherin and PTEN was weakened.Conclusion Sanguinarine has the proliferation inhibiting and apoptosis promoting effect on cervical cancer cells,its mechanism may be related to adhesion protein E-Cadherin,β-catenin and PTEN,MMP2.

OBJECTIVE:To provide reference for the selection and management of compound drugs. METHODS:The variet-ies and frequency of compound drugs recorded in the national drug reimbursement list and drug reimbursement list supplementary varieties in provinces (regions and municipalities) were statistically analyzed,and Spearman test method was used to conduct the correlation analysis for the variety and local economic development level. RESULTS:There were totally 126 varieties of compound drugs recorded in the national drug reimbursement list,covering 19 categories. The varieties of compound drugs in class B supple-mentary drug lists of 28 provinces (regions and municipalities) ranged from 19 to 50;for the supplementary lists of compound drugs in 24 provinces(regions and municipalities),the varieties ranged from 12 to 117. Almost 50% of the compound drugs were recorded in only 1 province(region and municipality),and most compound drugs recorded 1-4 time(s)in provinces(regions and municipalities). There was no significant relationship between the varieties number of supplementary compound drugs and the per capita GDP in a province(region and municipality)(P>0.05,r=-0.180). CONCLUSIONS:The supplementary variety of com-pound drugs in a region has little relationship with the local economic development level. The work progress of recoding the com-pound drugs varies a lot,with large differences in number and high dispersion. It is necessary to clarify the definition of compound drug at a national level,develop unified management policies,standardize the selection criteria for compound drugs and guarantee the clinical medication requirements of patients.

ObjectiveTo investigate the mechanism of Baihuan Xiaoyao Decoction （Xiaoyaosan added with Lilii Bulbus and Albiziae Cortex） in alleviating depression-like behaviors of juvenile rats by regulating the polarization of microglia. MethodSixty juvenile SD rats were randomized into normal control， model， fluoxetine， and low-， medium-， and high-dose （5.36， 10.71， 21.42 g·kg^-1， respectively） Baihuan Xiaoyao decoction groups. The rat model of juvenile depression was established by chronic unpredictable mild stress （CUMS）. The sucrose preference test （SPT） was carried out to examine the sucrose preference of rats. Forced swimming test （FST） was carried out to measure the immobility time of rats. The open field test （OFT） was conducted to measure the total distance， the central distance， the number of horizontal crossings， and the frequency of rearing. Morris water maze （MWM） was used to measure the escape latency and the number of crossing the platform. The immunofluorescence assay was employed to detect the expression of inducible nitric oxide synthase （iNOS， the polarization marker of M1 microglia） and CD206 （the polarization marker of M2 microglia）. Real-time polymerase chain reaction was employed to determine the mRNA levels of iNOS， CD206， pro-inflammatory cytokines ［tumor necrosis factor （TNF）-α， interleukin （IL）-1β， and IL-6］ and anti-inflammatory cytokines （IL-4 and IL-10） in the hippocampus. Western blotting was employed to determine the protein levels of iNOS and CD206 in the hippocampus. The levels of IL-4 and IL-6 in the hippocampus were detected by enzyme-linked immunosorbent assay. ResultCompared with the normal control group， the model rats showed a reduction in sucrose preference （P<0.05）， an increase in immobility time （P<0.05）， decreased motor and exploratory behaviors （P<0.05）， and weakened learning and spatial memory （P<0.05）. In addition， the model rats showed up-regulated mRNA and protein levels of iNOS and mRNA levels of IL-1β， IL-6， and TNF-α （P<0.05）. Compared with the model group， Baihuan Xiaoyao decoction increased the sucrose preference value （P<0.05）， shortened the immobility time （P<0.01）， increased the motor and exploratory behaviors （P<0.05）， and improved the learning and spatial memory （P<0.01）. Furthermore， the decoction down-regulated the positive expression and protein level of iNOS， lowered the levels of TNF-α， IL-1β， and IL-6 （P<0.01）， promoted the positive expression of CD206， and elevated the levels of IL-4 and IL-10 （P<0.01） in the hippocampus of the high dose group. Moreover， the high-dose Baihuan Xiaoyao decoction group had higher sucrose preference value （P<0.01）， shorter immobility time （P<0.01）， longer central distance （P<0.01）， stronger learning and spatial memory （P<0.01）， higher positive expression and protein level of iNOS （P<0.01）， lower levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， lower positive expression and mRNA level of iNOS （P<0.05）， and higher levels of IL-4 and IL-10 （P<0.05， P<0.01） than the fluoxetine group. ConclusionBaihuan Xiaoyao decoction can improve the depression-like behavior of juvenile rats by inhibiting the M1 polarization and promoting the M2 polarization of microglia in the hippocampus.