Deep vein thrombosis (DVT) is a serious complication of fractures. The incidence of ankle fracture which occurs most frequently intra-articular is 200/100 000, about 3.9%of all fractures. Domestic and foreign reports of ankle fractures and DVT were allocated and analyzed to review their correlation. Furthermore, different methods of rou-tined thromboprophylaxis was discussed. DVT incident after ankle fractures and the necessity of routined thromboprophy-laxis were reviewed. DVT incidence after ankle fractures was low and routine thromboprophylaxis was not necessary to all ankle fracture patients except the ones who had risk factors of thrombosis which could induce DVT.

Model-informed drug development (MIDD) in the development of pediatric drugs is drawing more and more attention due to the insufficiency of subjects, lack of research on ontogeny, and the limitation of ethic. The core of MIDD used for dose selection includes the population pharmacokinetic (PopPK) model and physiologically based pharmacokinetic (PBPK) model, as well as model-based simulation and prediction. PBPK model has the advantage of predicting the optimal pediatric dose before the clinical trials and has the ability of extrapolation from adult model to pediatric model. PopPK model characterizes the pediatric PK feature based on the analysis of clinical data and can be used to explore the significant covariates, which is a power tool for individualized medicine in children. With their own advantages and disadvantages, PBPK and PopPK model should be jointly used in the pediatric drug development to refine the dose regimen for children at different ages. In this study, the pediatric drug development of rivaroxaban was taken as an example to introduce the combined application of PBPK model and PopPK model in the design and validation of pediatric dose regimen in Phase Ⅰ, Ⅱ and Ⅲ trials, which may provide reference to MIDD in other pediatric drug development.

Objective To evaluate the effects of different doses of propofol or isoflurane on the cochlear blood flow (CBF) in guinea pigs.Methods Fifty-four adult male guinea pigs,aged 3 months,weighing 400-500 g,were randomly divided into 6 groups (n =9 each).In P1,P2 and P3 groups,propofol was infused for 115 min at 10,20 and 40 mg· kg-1 · h-1,respectively,after a loading dose of 5 mg/kg was injected over 5 min.In S1,S2 and S3 groups,isoflurane was inhaled for 120 min with end-tidal concentrations of 1％,2％ and 3 ％,respectively.Mean arterial pressure and CBF were recorded before administration (baseline,T1) and during the period of drug administration.Distortion product otoacoustic emission (DPOAE) was measured at T1,at the end of administration (T2) and 1 h after administration (T3).Five animals in each group were sacrificed and organs of Corti were harvested for observation of morphology of out hair cells by scanning electron microscopy.Results Propofol decreased MAP and increased CBF and DPOAE amplitude in a dose-dependent manner.Isoflurane decreased MAP and CBF in a dose-dependent manner.1％ isoflurane increased DPOAE amplitude,however,2％ and 3％ isoflurane decreased it and caused damage to out hair cells.Conclusion Propofol induces an increase in CBF in guinea pigs,while high concentration of isoflurane induces a decrease in CBF.Isoflurane inhibits CBF autoregulation,which makes CBF more sensitive to perfusion pressure,thus causing damage to hearing function.This is the reason why high concentration of isoflurane induces a decrease in CBF.

Objective To investigate the effects of deletion of adenosine A2A receptors on peripheral leukocytes on cerebral white matter lesions induced by chronic cerebral hypoperfusion.Methods Twenty-four wild type(WT) male mice were given a ? irradiation of 12.5Gy,followed by receiving bone marrow cells tail vein from female A2A receptor knocked out(KO) mice via tail vein,were assigned as KO→WT group,while those received bone marrow cells from WT female mice were assigned as WT→WT group(n=20).The efficiency of reconstitution of bone marrow cells in recipient mice was assessed 7 weeks after transplantation by PCR and immunofluorescent technique.Then,the recipient mice were subjected to bilateral common carotid artery stenosis with internal diameter of 0.18mm by external banding using microcoils at 8 weeks after transplantation.On 7d,14d and 30d after the surgery,corpus callosum,fiber bundles of Caudoputamen and optic tract were harvested from the cerebral white matter,and stained with Kluver-Barrera staining for observing the changes in nerve fibers,and with GFAP and CD11b immunohistochemistry staining for observing the proliferation of microglia and astrocytes.Results At 7 weeks after successful transplantation,the genotype of sex chromosome in peripheral leukocytes of the male recipient mice was changed into female pattern.The expression rate of A2A receptor was 9.73%?2.05% in KO→WT group and 93.82%?11.24% in WT→WT group,with significant difference between the two groups(P

Objective To observe behavioral characteristics and pathologic changes of chronic cerebral hypoperfusion in mice. MethodsTotally 62 adult C57BL/6 mice were subjected to either sham-operation (n=31) or bilateral common carotid artery stenosis using external microcoils with an inner diameter of 0.18 mm(n=31). At 30 d after the stenosis, the animals of the 2 groups (8 mice for each group) underwent behavioral test of 8-arm radial maze. In 7, 14 and 30 d, the rest mice were sacrificed for their brain tissue samples which were examined with Kluver-Barrera staining and immunohistochemical assay for markers of microglia and astroglia, glial fibrillary acidic protein (GFAP) and CD11b. In 14 d after the model establishment, Evans blue dye extravasation test was performed for the blood-brain barrier function. ResultsThe model group made significantly more errors than sham-operated group in 8-arm radial maze test at 30 d after the surgery. White matter lesions occurred and the proliferation of activated microglia and astroglia were observed in white matter in model mice after 14 and 30 d bilateral common carotid artery stenosis. The disruption of blood-brain barrier function of model mice was indicated in the evans blue extravasation test at 14 d after bilateral common carotid artery stenosis. ConclusionCognitive impairment, white matter lesions and glial activation are successfully induced after bilateral common carotid artery stenosis in mice model of chronic cerebral hypoperfusion.

Objective To investigate the effect of adenosine A2A receptor deficiency on the ischemic neuronal injury and its potential mechanism.Methods Transient(2 h)cerebral ischemia was induced by the middle cerebral artery occlusion(MCAO)in mice.Adenosine A2A receptor knockout(A2ARKO)mice and their wild-type littermates(A2ARWT)were divided into 2-hour cerebral ischemia group,cerebral ischemia with 22-hour reperfusion group and cerebral ischemia with 46-hour reperfusion group.Cerebral infarction volume was measured by image analysis of brain sections stained with cresyl violet(CV).Brain water content was evaluated with the dry-wet weighing method.The expression of calbindin D-28k(CB)and aquaporin-4(AQP4)in ischemic brain was determined with immunohistochemical methods.Results The cerebral infarction volumes in 2-hour cerebral ischemia group,cerebral ischemia with 22-hour reperfusion group and cerebral ischemia with 46-hour reperfusion group of A2ARKO mice were lesser than those in the corresponding groups of A2ARWT mice.Compared with A2ARWT mice,A2ARKO mice had more CB,lesser AQP4 expressions and lesser brain water contents.Conclusion Adenosine A2A receptor deficiency exerts the protection against ischemic brain injury both in the acute phase and reperfusion phase,and attenuates brain edema caused by cerebral ischemia,which may be due to the inhibition of intracellular calcium overload and AQP4 expression.

Objective To investigate the effect of intrathecal(IT)different concentrations of ozone(O_3) on pain threshold,motor function and cerebral spinal fluid(CSF)malondialdehyde(MDA)concentration and superoxide dismutase(SOD)activity and determine if ozone is toxic to central nervous system(CNS).Methods Thirty New Zealand white rabbits of both sexes aged 3-5 months,weighing 2.5-3.0 kg were randomly divided in 5 groups(n=6 each):groupⅠcontrol;groupⅡpure O_2;groupⅢO_2-O_3 30;groupⅣO_2-O_3 50 and groupⅤO_2-O_3 80.The animals were anesthetized with intraperitoneal pentobarbital.Cerebello-medullary cistern was punctured for IT administration of O_2 and O_3.In groupⅡ2 ml of pure oxygen(O_2)(for medical use)was injected IT.In groupⅢ,ⅣandⅤ2 ml of ozone(O_3)30,50 and 80 mg?L~(-1) was injected IT respectively.Ozone was manufactured by ozone generator(Ozoneline Co,Italy).Before and one day after IT O_3 paw withdrawal latency to heat(PWHL)and to mechanical stimulation(yon Frey filament)(PWML)were measured and motor function was assessed(1=normal,4=severe motor dysfunction and weakness).CSF was obtained at 1,2,4 h after IT O_3 for determination of MDA concentration and SOD activity.Results IT administration of the 3 concentrations of ozone did not affect pain threshold and motor function,but significantly increased SOD activity.MDA concentration decreased significantly at 4 h after IT O_2 or ozone administration in groupⅡ,ⅢandⅣ,but increased significantly at 1 and 2 h after IT ozone in groupⅤ.SOD/MDA was significantly increased at 1,2 and 4h after IT ozone in groupⅢandⅣ,but decreased at 1 and 2 h after IT ozone in groupⅤ.Conclusion IT ozone is toxic to CNS.

OBJECTIVE:To observe clinical efficacy and safety of Qizhi qushi jianpi prescription in the treatment of chronic synovitis of knee joint in middleaged and elderly patients after debridement under arthroscope. METHODS:A total of 80 mid-dleaged and elderly inpatients with chronic synovitis of knee joint were selected and randomly divided into treatment group and con-trol group,with 40 cases in each group. Clinical efficacy,VAS,swelling score of modified Cincinnati knee joint score system, Lysholm score of knee joint function,the occurrence of ADR were observed in 2 groups. RESULTS:Total effective rate of treat-ment group(92.5%)was significantly than that of control group(77.5%),with statistical significance(P<0.05). Before debride-ment under arthroscope,there was no statistical significance in VAS score of knee joint,swelling score and Lysholm score between 2 groups(P>0.05). On the first day after surgery,VAS score of 2 groups decreased significantly,and there was statistical signifi-cance compared to before surgery (P<0.05). One month after surgery,VAS score of 2 groups decreased significantly,and the treatment group was significantly lower than the control group,with statistical significance(P<0.05). Swelling score of knee joint 1 month after surgery and Lysholm score 3 months after surgery increased significantly in 2 groups,and the treatment group was significantly higher than the control group,with statistical significance(P<0.05). 5 patients of treatment group suffered from stom-ach discomfort,and the symptom was relieved after adding the ingredient of comforting stomach and removing dampness through diuresis. CONCLUSIONS:Qizhi qushi jianpi prescription is effective for chronic synovitis of knee joint in middleaged and elderly patients after debridement under arthroscope,and can relieve pain, remove swelling and recover knee joint function with good safety.

OBJECTIVETo observe application value of multispectral animal living imaging technology in rats model of osteoarthritis.

METHODSFifteen male SD rats weighed (180 +/- 20) g (3 months old) were received intra-articular injection of iodoacetic acid for establishing osteoarthritis. Articular cavity of left knee of rats were injected into 50 microl iodoacetic acid. The same volume of sterile saline was injected into right knee articular cavity as control. X-ray living imaging and bone mineral density were observed at 2 and 4 weeks after establishment of model. After 4 weeks,rats were sacrificed and their bilateral joints were collected and determined histologically based on Collins classification and Kellgren-Lawrence classification.

RESULTSOsteoarthritis model was successfully established, compared with control group, model group showed typical manifestation of osteoarthritis, including irregular cartilage surface,osteophyte formation,joint deformity and cartilage defect,and combined with significant decrease of bone density (P < 0.01), while the decrease was not obvious in proximal tibia (P < 0.05). After 2 weeks, knee joints in model group was classified as Collins grade 1 and Kellgren-Lawrence grade 2,then classified as Collins grade 4 and Kellgren-Lawrence grade 3 after 4 weeks,control group showed smooth articular surface,normal joint space and intact cartilage surface, knee joints was classified as Collins and Kellgren-Lawrence grade 0, and bone density of distal femur and proximal tibia were normal.

CONCLUSIONMultispectral animal living imaging technology could be used in dynamic observation of living imaging and detection of bone density in the animal model of osteoarthritis, and it is significant for evaluation of osteoarthritis model, and its realted tesearch.

Animals ; Bone Density ; Disease Models, Animal ; Humans ; Knee Joint ; diagnostic imaging ; Male ; Osteoarthritis ; diagnosis ; diagnostic imaging ; physiopathology ; Radiography ; Rats ; Rats, Sprague-Dawley

A nicotine-degrading bacterial strain Z7 was isolated from tobacco growing soil at Zhangjiajie region in Hunan Province.The morphology,physiological and biochemical characteristics of strain Z7 were studied and the results showed that characteristics of this strain were essentially consistent with Agrobacterium radiobacter/tumefaciens.This strain degraded nicotine optimally at 30℃ and initial pH 7.0.It was able to utilize nicotine as its sole carbon source,and it could degrade 71% of nicotine under the optimized incubation conditions for 48 h.Meanwhile,the color of culture medium turned from yellowy to green and dark green,then it turned to brown.This strain might have potential applications in tobacco industry.