Animals ; Bone Marrow ; metabolism ; Cell Division ; physiology ; Hematologic Diseases ; therapy ; Hematopoiesis ; physiology ; Hematopoietic Stem Cells ; cytology ; Humans ; Renin-Angiotensin System ; physiology

OBJECTIVE:To prepare and characterize celecoxib-loaded PLGA nanoparticles. METHODS:Emulsification-solvent evaporation method was adopted to prepare celecoxib-loaded PLGA nanoparticles. With encapsulation efficiency and particle size as the indexes,Plackett-Burman design was preferred to screen the formulation and variables which had a significant effect on the property of nanoparticles. And then Box-Behnken response surface method was used to further optimize selected variables including mass concentration of PLGA,ultrasonic power and ultrasonic time,followed by verification. Malvern particle size analyzer was used to determine the particle size distribution of nanoparticles and Zeta potential of nanoparticle by the optimal formulation technol-ogy,and transmission electron microscope was used to observe the morphology of the nanoparticles,and their drug release in vitro behavior and stability(25,5 ℃)were also observed. RESULTS:The optimal formulation and technology was as follows as PLGA mass concentration of 30.0%,ultrasonic power of 180 W and ultrasonic time of 8 min. For the prepared nanoparticles,encapsula-tion efficiency and particle size were (85.7 ± 4.1)% and (226.1 ± 36.1) nm (n=3) respectively;particle size distribution was (176.2±41.2)nm,polydispersity index was 0.211±0.021,and Zeta potential was(-37.3±1.6)mV. Under the electron micro-scope,the nanoparticles were homogeneous in particle size and distributed spheroidally,with 24 h accumulative release of 52.4%. They were stable within 3 months at 5℃. CONCLUSIONS:Celecoxib-loaded PLGA nanoparticles have been prepared successfully.

Objective:To prepare celecoxib nanostructured lipid carriers and investigate the characteristics of tissue distribution in rats. Methods:Celecoxib nanostructured lipid carriers were prepared by a melt-emulsion ultrasonication and low temperature-solidifi-cation method. The physicochemical properties of nanostructured lipid carriers were studied, such as particle size distribution, zeta po-tential and morphology. The concentration of celecoxib in different tissues was determined after tail vein injection of celecoxib nano-structured lipid carriers in rats. Results:The obtained celecoxib nanostructured lipid carriers were spherical with the average particle size of (103. 5 ± 32. 6) nm and zeta potential of ( -37. 3 ± 5. 1) mV. The re of celecoxib nanostructured lipid carriers in liver, spleen, brain and muscle respectively was 3. 43, 2. 99, 2. 38 and 2. 93 times higher than that of celecoxib injection. Conclusion:The biodistribution of celecoxib is changed by the nanostructured lipid carriers. Celecoxib nanostructured lipid carriers have the characteris-tics of liver, spleen and muscle targeting, which is benefit to improving the efficacy.

Objective:To prepare celecoxib nanosuspension ( CXB-NSs) and study the pharmacokinetics of CXB-NSs in rats. Methods:CXB-NSs were prepared by an anti-solvent precipitation and high pressure homogenization method. The particle size, polydispersion index ( PdI) and zeta potential of the nanosuspension were studied. Totally 12 Wistar rats were randomly divided into CXB-NSs group and CXB suspension group, and gastric drug dose was 100 mg·kg-1 . CXB concentration in plasma was determined by HPLC and the pharmacokinetic parameters were calculated by 3P97 software. Results: The particle size, polydispersion index, zeta potential of CXB-NSs was (442. 5 ± 61. 9) nm, 0. 312 ± 0. 057 and ( -31. 6 ± 3. 9) mV, respectively. AUC (0-t) of CXB suspension and CXB-NSs was (5.13 ±0.77) and (13.51 ±3.18) mg·L-1·h, half time (t1/2) was (12.31 ±1.91) and (12.73 ±1.83) h, Tmax was (2. 48 ± 0. 37) and (1. 41 ± 0. 27) h and Cmax was (0. 94 ± 0. 31) and (2. 38 ± 0. 25) mg·L-1 , respectively. Conclusion:CXB-NSs can remarkably increase bioavailability in rats.

Objective To investigate celecoxib self-microemulsifying drug delivery system (CXB-SMEDDS) that was developed to increase the dissolution rate and oral bioavailability of celecoxib.Methods The formulation of CXB-SMEDDS was optimized by pseudo-ternary phase diagrams analysis.The appearance, morphology, particle size distribution and in vitro drug release behavior of CXB-SMEDDS were investigated after diluted by water.The bioavailability of CXB-SMEDDS was determined by oral administration to rats compared with CXB suspension.Results An optimized formulation was selected: Medium chain triglycerides as oil phase, Tween 20 as surfactant, Transcutol HP as cosurfactant.The ratio of oil phase, surfactant and cosurfactant was 2∶9∶9.Upon mixing with water, CXB-SMEDDS formed a clear and transparent microemulsion solution with homogeneous small spherical under transmission electron microscopy.For particle size of CXB-SMEDDS was found to be (57.6±14.2) nm.The in vitro dissolution test indicated a significant improvement in release characteristics of CXB.The AUC of CXB-SMEDDS and CXB suspension were (5.54±0.94) and (3.32±0.59) mg·L-1·h, respectively.The relative bioavailability was 166.9%.Conclusion The SMEDDS can significantly increase celecoxib dissolution in vitro and bioavailability in vivo.

Although previous reports showed drug-eluting stent (DES) could effectively inhibit neointima formation, in-stent restenosis (ISR) remains an important obstacle. The purpose of this study was to investigate different effects of paclitaxel on proliferation and cell cycle regulators between vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs) of rats in vitro. The cultured VSMCs and VECs of rats from the same tissues were examined by using immunohistochemistry, flow cytometry and Western blotting in control and paclitaxel-treated groups. The results showed paclitaxel could effectively inhibit proliferation of VSMCs and VECs. However, as compared with VECs, proliferation of VSMCs in paclitaxel-treated group decreased less rapidly. The percentage of cells in G0-G1 and G2-M phases was reduced, and that in S phase increased after treatment for 72 h. The expression of cyclin D1 and B1, p27 and PCNA in VSMCs of paclitaxel-treated group was up-regulated, but that of p21 down-regulated as compared with VECs. It is concluded that there are significant differences in the expression of cell cycle regulators and proliferation rate between paclitaxel-treated VSMCs and paclitaxel-treated VECs, suggesting that the G1-S checkpoint regulated by paclitaxel may play a critical role in the development of complications of DES, which provides new strategies for treatments of ISR.

Objective To investigate the usefulness of 99Tcm-MDP whole body bone scan in bone malignant fibrous histiocytoma (BMFH).Methods Fifteen patients (11 males,4 females,age ranged from 23 to 60 years,average age (50.4±12.8) years) who had documented BMFH and underwent 99Tcm-MDP whole body bone scan were retrospectively analyzed.The appearance of increased uptake,decreased uptake or defect in radioactivity on bone was considered as positive.The typical scintigraphic manifestations of BMFH were summarized and compared to other radiological imaging data.Results All 15 patients showed positive results.The lesions involved femoral in 10 cases(66.7％),46.7％(7/15) of which was distal femur.The lesions also involved sacrum,tibia,humerus,radius each in 1 case and multiple lesions in 1 case.Among 27 lesions found,63.0％ (17/27) showed strong increased radioactivity together with reduced or defect area and 37.0％ (10/27) showed strong increased radioactivity only.X-ray found 20 lesions.Twelve cases underwent CT and 7 cases underwent MRI.Abnormal spots showed on CT and MRI were also positive on the whole body bone scan.Conclusions The most common site of BMFH is femur,especially distal femur.BMFH lesions are presented as strong increased radioactivity together with sparse and defect area on bone scan.The whole body bone scan may be an auxiliary examination to evaluate whether there are multiple bone lesions and bone metastasis.

Foreign Bodies ; Humans ; Male ; Maxillary Sinus ; Middle Aged

Objective To study military medical graduates' psychological elastic characteris-tics and the key influencing factors. Methods A comparative study of 817 graduate students and 597 undergraduate students in a military academy was conducted by using positive negative emotions, pos-itive and negative cognitive bias and Mental Resilience Scale. Independent sample t-test, single factor analysis of variance, correlation analysis, and step-wise regression analysis were conducted by SPSS 18.0 for data analysis. Results ①Resilience scores of postgraduate students were significantly lower than those of undergraduate students (76.01 ±11.43 vs. 80.00 ±10.26, t=-6.76, P<0.01). Resilience scores of military postgraduates were significantly higher than those of local postgraduates (77.18 ± 11.59 vs. 74.97±11.19, t=2.77, P<0.05). Resilience scores of female postgraduates were significantly lower than those of males (74.79 ±10.83 vs. 76.94 ±11.78, t=2.68, P<0.05), reflected in factors of tenacity and strength. ②Resilience and its factors were positively related to positive affect and atten-tion to positive information (r=0.448~0.625, P<0.01), while negatively related to negative affect and attention to negative information (r=-0.206~-0.448, P<0.01). ③Regression analysis showed that posi-tive and negative emotion, attention to positive and negative information can significantly predict re-silience, accounting for the variance of 53.7%. ④Positive and negative affect partially mediated the relationship between attention to positive information and positive affect and resilience. Conclusion Attention to positive information and positive affect may be potential targets for intervention to enhance the level of resilience among military medical postgraduate students.

Objective To evaluate the efficacy of discriminant function analysis for pericolic infiltration in colorectal cancer on enhanced 64-slice spiral CT and to improve the diagnostic accuracy and specificity of pericolic infiltration. Methods Dynamic enhanced 64-slice spiral CT was performed in 49 colorectal cancer patients (49 masses in total) before surgery. One or two slices were selected for each mass, with a total of 96 slices. The 96 slices were classified into two groups (pericolic infiltration or nonpericolic infiltration group) according to pathological data. Discriminant analysis was performed on the CT values between the mass and the corresponding pericolic tissue 5 mm from the mass at different time points as follows; 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, and 75 s. The discriminant function was calculated, and the pericolic infiltration determined by discriminant function and CT morphology were compared with the pathological results. The CT values in pericolic and non-pericolic infiltration groups at different enhancement time points were assessed using analysis of variance. Results The mean CT values ranged from (43. 6 ±7. 8) HU to (52. 3 ±0. 8) HU in the pericolic infiltration group, and ranged from (100.4±20.3)HU to(116.2±21.4)HU in the non.perieolic infiltration group.At 20 s and 40 s,the mean CT vshle8 were(43.6±27.8)HU and(50.9±27.8)HU in the perleolic infiltration group, (102.0±16.9)HU and(116.2 ±21.4)HU in the non-perieolic infiltration group,respectively.The mean CT value in the pericolic infiltration group was significantly lower than that in the non-pericolic infiltration group at all contrast enhancement time points(F=6.278,P<0.01).A diseriminant function Was obtained as follows:D=-3.450+0.023Xl±0.017X2-0.00lX12-0.001X22+0.002X1×X2. Based on the CT morphology of colorectal cancer,69 slices were identified correctly and 27 slices were fulsely interpreted.the sensitivity.speeificity and accuracy for perieolic infiltration determination were 82.5%,64.3%and 71.9%.respectively.Based on diseriminant function,85 slices were identified correctly and 11 slices were falsely interpreted.the sensitivity,specificity and accuracy were 85.0%.91.1%and 88.5%,respectively.Conclusion The discriminant function with dynamic enhanced 64-slice spiral CT can improve the diagnostic accuracy and specificity of perieolic infiltration in eolorectal cancer patients.