Histone deacetylase (HDAC1) has a high expression in many cancer cells and curcumin can inhibit the growth of cancer cells. This paper was designed to investigate the expression of HDAC1 of Raji cells and the effect of curcumin on their proliferation and apoptosis. Raji cells were treated with 3.125-50 micromol/L curcumin for 8-48 h and the growth inhibition rates of Raji cells were measured by MTT. The expression of HDAC1 on Raji cells were examined by mRNA, Western blot at 24 h various concertrations (1.6-50 micromol/L). Curcumin could selectively inhibit the proliferation of Raji cells in a dose- and time-dependent manner, with the inhibition rate being 52.47 %-82.18 % (P<0.01). The up-regulation of HDAC1 expression was observed within 24 h after the treatment with curcumin as shown by RT-PCR and Western blot. With the increase of concentration, the expression was down-regulated in a dose- dependent manner. It is concluded that the expression of HDAC1 plays an important role in the proliferation and apoptosis of Raji cells and curcumin can inhibit the growth of Raji cells at various concentrations and promote the apoptosis of Raji cells.

OBJECTIVE: To prepare bezafibrate osmotic pump tablets(BOPT) and optimize its formulation by central composite design-response surface methodology(CCDRSM).METHODS: The amount of polyoxyethylene(PEO) N80 which used as an adjuvant of Bezafibrate osmotic pump tablets(A),the amount of Na2CO3(B),and the coating weight increase(C) were used as 3 factors for investigation,and the cumulative release amount at 1 h and 6 h respectively,and the linear correlation coefficient(r) of the cumulative release amount versus time were taken as indexes.The formulation of BOPT was optimized by CCDRSM and the optimized formulation was verified.RESULTS: The optimized formulation obtained was as follows: A 40 mg,B 20 mg,and C 29 mg.The tablets prepared in optimized formulation demonstrated good release behavior,with the absolute value of deviation of each index being less than 5%.CONCLUSION: The CCDRSM can be applied to optimize the formulation of BOPT and the established model is of satisfactory predictive value.

Objective To improve the different diagnosis between autoimmune pancreatitis(AIP) and pancreatic cancer(PC) by a retrospective analysis of clinical symptoms and serological features.Methods The analysis included 36 patients who had postoperative pathological,serological findings consistent with Asian AIP standards and 95 patients who had postoperative pathological consistent with PC pathological standards.All patients were admitted by the surgery department of our hospital from January,2003 to October,2011.A retrospective comparative analysis of the clinical manifestations,serology data of these AIP and PC patients was conducted.And summary the differential diagnosis characteristics of AIP and pancreatic cancer in the clinical symptoms,the serology.Results The features of different diagnosis:(1) The age of patients with PC was higher than AIP((60.9 ±9.0) years vs.(53.56 ± 14.6) years,t =3.48,P ＜0.05),and AIP preferred to male groups (x2 =2.88,P =0.09).(2) The clinical features of AlP and PC with the age characteristics were easily confused.Both clinical features were relatively typical in younger age which could be found earlier and relatively insidious in the older age which might be found with delay.(3) AIP were often complicated by biliary system inflammations(AIP =47.2％,PC =12.6％,x2 =18.12,P ＜ 0.05),while PC were usually complicated by the cysts in liver and kidney (PC =29.5％,AIP =0,x2 =13.50,P ＜ 0.05).(4) The high titer in CA199 had a higher value in the diagnosis of PC (concentration:group AIP =20.51 (9.55,86.5) kU/L,group PC =326.50 (94.38,10393.00) kU/L; positive rate:group AIP =35.70％ (10/28),group PC =86.70％ (65/75),P =0.000).The high titers in amylase (concentration:group AIP =103.50 (72.00,252.00) U/L,group PC =46.50 (21.65,96.90) U/L; positive rate:group AIP =45.00％ (9/20),group PC =19.40％ (7/36),P =0.043),lipase(concentration:group AIP =340.50(152.05,495.80) U/L,group PC =107.40(23.40,177.26) U/L,P =0.005 ; aspartate aminotransferase (positive rate:group AIP =75.00％ (27/36),group,PC =55.90％ (52/93),P =0.046) andγ-glutamyltranspeptidase (positive rate:group AIP =79.40％ (27/34),group PC =57.10％ (52/91),P =0.022) had higher values in the diagnosis of AIP.The significant increases in CA199 were not the basis which excluding AIP.Conclusion AIP as a unique type of chronic pancreatitis can be distinguished from PC on distinctive clinical,serological characteristics.

To increase the dissolution rate and extent of valsartan, valsartan nanosuspensions have been prepared. Controlled precipitation assisted with sonication is utilized to prepare valsartan nanosuspensions, the concentration of the drug, stabilizer and costablizer had a great effect on the stability of the preparation according to the pre-experiment. So the method of central composite design-response surface is used to optimize the prescription based on the above three factors and the particle size as the response value. The software Origin 8.0 is used to draw the view of the three-dimensional effects and 2D contour map, to get the optimal prescription area. Valsartan nanosuspensions were prepared. The mean diameter and zeta potential are about 216.6 nm and -57.7 mV, respectively. Compared with the microsuspensions and commercial preparation, the dissolution of valsartan nanosuspensions was faster and the bioavailability can be enhanced to some extent.

To study the in situ intestinal absorption kinetics of flrubiprofen in rats, the absorption of flurbiprofen in small intestine (duodenum, jejunum and ileum) and colon of rats was investigated using in situ single-pass perfusion method and the drug content was measured by HPLC. The effects of drug concentration on the intestinal absorption were investigated. The K(a) and P(app) values of flurbiprofen in the small intestine and colon had no significant difference (P > 0.05). Drug concentration (4.0, 10.0 and 16.0 mg x L(-1)) had no significant influence on the K(a) values (P > 0.05). However, when concentration was 4.0 mg x L(-1) and 10.0 mg x L(-1), significant effect on the P(app) values (P < 0.05) was found, but significant effect on the P(app) values was not shown between 10.0 mg x L(-1) and 16.0 mg x L(-1) (P > 0.05). The K(a) and P(app) values of flurbiprofen on the perfusion flow rate had significant difference (P < 0.05). Flurbiprofen could be absorbed at all segments of the intestine in rats and had no special absorption window. The absorption of flurbiprofen complies with the facilitated diffusion in the general intestinal segments, and accompany with the cytopsistransport mechanism probably. The perfusion flow rate had significant effect on the K(a) and P(app).

Histone deacetylase (HDAC1) has a high expression in many cancer cells and curcumin can inhibit the growth of cancer cells. This paper was designed to investigate the expression of HDAC1 of Raji cells and the effect of curcumin on their proliferation and apoptosis. Raji cells were treated with 3. 125-50 μmol/L curcumin for 8-48 h and the growth inhibition rates of Raji cells were measured by MTT. The expression of HDAC1 on Raji cells were examined by mRNA, Western blot at 24 h various concertrations (1.6-50 μmol/L). Curcumin could selectively inhibit the proliferation of Raji cells in a dose- and time-dependent manner, with the inhibition rate being 52.47 %-82.18%(P＜0.01).The up-regulation of HDAC1 expression was observed within 24 h after the treatment with curcumin as shown by RT-PCR and Western blot. With the increase of concentration, the expression was down-regulated in a dose- dependent manner. It is concluded that the expression of HDAC1 plays an important role in the proliferation and apoptosis of Raji cells and curcumin can inhibit the growth of Raji cells at various concentrations and promote the apoptosis of Raji cells.

Objective: To investigate whether CD137-CD137L signaling could affect the secretion of mouse vascular smooth muscle cells (VSMCs) -derived exosomes through autophagy mediated Rab7 pathway. Methods: Primary thoracic aorta VSMCs from C57BL/6J mouse were obtained by tissue block adherence method. VSMCs between the third to fifth passages were used and VSMCs were divided into 4 groups: control group, CD137 agonist group, lentivirus control group, Rab7 lentiviral interference group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in lentivirus control group were treated with lentiviral followed by recombinant protein of CD137L (10 μg/ml), VSMCs in Rab7 lentiviral interference group were treated with Rab7 lentiviral intervention followed by recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of LC3Ⅱ, p62, Rab7, CD9, CD81 and Hsc70. Fluorescence microscopy was used to track the changes of autophagy in cells infected with mRFP-GFP-LC3. Transmission electron microscope was used to observe the morphology and size of VSMCs-derived exosomes. The nanoparticle tracking analysis(NTA) was used to detect the concentration and size of exosomes in each group. Results: (1) The expressions of Rab7, LC3Ⅱ and p62 protein in VSMCs of CD137 activation group were significantly higher than those in control group (all P<0.05). The expressions of Rab7, LC3Ⅱ and p62 protein in Rab7 lentivirus interference group was lower than in CD137 activation group (all P<0.05), while the expressions were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (2) The total number of fluorescent spots and yellow fluorescent spots in the VSMCs of the CD137 activation group were higher than those in the control group (all P<0.05), and the number of yellow fluorescent spots was higher than that of the red fluorescent spots in the VSMCs of the CD137 activation group ((50.3±0.9) vs. (10.3±1.5)/cell). The total numbers of fluorescent spots and yellow fluorescent spots in VSMCs of Rab7 lentivirus interference group were lower than those of CD137 activation group (both P<0.05), and the number of red fluorescent spots in VSMCs was higher than that of yellow fluorescent spots ((40.7±4.0) and (10.7±1.2)/cell) in the Rab7 lentiviral interference group. The total numbers of fluorescent spots and yellow fluorescent spots in the VSMCs were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (3) Under transmission electron microscopy, the size of the VSMCs-derived exosomes was about 30-150 nm. The exosome markers (CD9, CD81) could be detected in vesicles by Western blot. NTA results showed that the concentration of VSMCs-derived exosomes was significantly higher in the CD137-activated group than in the control group (P<0.05), which was significantly lower in the Rab7 lentiviral interference group than in the CD137-activation group (P<0.05) and was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of Hsc70 protein in exosomes secreted by CD137 activation group was higher than that in the control group (P<0.05). The expression of Hsc70 protein in exosomes was lower in Rab7 lentivirus interference group than in the CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of LC3Ⅱ protein in exosome was higher in CD137 activation group than in control group (P<0.05), which was lower in Rab7 lentivirus interference group than in CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). Conclusion The CD137-CD137L signaling may affect the secretion of mouse VSMCs-derived exosomes through modulating the Rab7 pathway mediated autophagy.

Objective To develop a convolution neural network (CNN) model to classify multi?sequence MR images of the prostate. Methods ResNet18 convolution neural network (CNN) model was developed to classify multi?sequence MR images of the prostate. A deep residual network was used to improve training accuracy and test accuracy. The dataset used in this experiment included 19 146 7?sequence prostate MR images (transverse T1WI, transverse T2WI, coronal T2WI, sagittal T2WI, transverse DWI, transverse ADC, transverse PWI), from which a total of 2 800 7?sequence MR images was selected as a training set. Three hundred and eighty eight 7?sequence MR images were selected as test sets. Accuracy was used to evaluate the effectiveness of ResNet18 CNN model. Results The classification accuracy of the model for transverse DWI, sagittal T2WI, transverse ADC, transverse T1WI, and transverse T2WI was as high as 100.0% (44/44,52/52), and the accuracy for transverse PWI was also as high as 96.7% (116/120). The accuracy for coronal T2WI was 77.5% (31/40). 0.8% (1/120) of transverse PWI was incorrectly assigned to transverse T2WI, and 2.5% (3/120) incorrectly assigned to sagittal T2WI. 15.0% (6/40) of coronal T2WI was incorrectly assigned to transverse T2WI, and 7.5% (3/40) to sagittal T2WI. Conclusion The experimental results show the effectiveness of our deep learning method regarding accuracy in the prostate multi?sequence MR images detection.

Objective To explore the mechanism by which CD137 signal regulates the aging of vas-cular smooth muscle cells(VSMCs).Methods Thirty 8-week-old male C57BL/6J mice were ran-domly divided into a young group(8 weeks old)and an aged group(80 weeks old),with 30 mice in each group.After corresponding periods of feeding,the mice were euthanized,and the plasma and aortic blood vessels were isolated.In the cell experiments,normal VSMCs were divided into a control group,bleomycin(BLM)group,combined agonist group,and combined inhibitor group.The cellular senescence level of VSMCs was assessed using a cellular senescence β-galactosidase staining kit.Western blotting and PCR were employed to examine the expression of senescence-related proteins in tissues and cells,while ELISA was utilized to measure the expression of senes-cence-related inflammatory factors.Results The expression of CD137 and γ-H2AX in the aorta was significantly higher,while that of PCNA was obviously lower in the aged group than the young group(P＜0.05).The plasma level of CD137 was notably higher in the aged group than the young group(154.0±4.1 pg/ml vs 98.0±2.3 pg/ml,P＜0.05).Compared with the normal control group,there were significantly more aged VSMCs in the BLM group(P＜0.05).While,treatment of combined agonist resulted in larger amount of aged VSMCs when compared with the BLM group(P＜0.05),which was reversed by combined inhibitor treatment(P＜0.05).The levels of TNF-α,IL-6 and IL-1β were significantly elevated in the BLM group than the normal control group(P＜0.05).The combined agonist group had even higher levels of TNF-α,IL-6,and IL-1βthan the BLM group(P＜0.05),but the levels were decreased in the combined inhibitor group(P＜0.05).Compared with the normal control group,the expression of Bcl-2,γ-H2AX,P53,and P21 were significantly increased in the BLM group,combined agonist group,and combined inhibi-tor group,while that of PCNA was significantly decreased(P＜0.05).Compared with the BLM group,the expression of P53 and P21 in the combined agonist group showed an increase(P＜0.05),and the expression of P53 was significantly decreased in the combined inhibitor group(P＜0.05).Conclusion CD137 signal regulates the P53/P21 pathway to promote VSMC aging.

The drug formulation design of self-emulsifying drug delivery systems (SEDDS) often requires numerous experiments, which are time- and money-consuming. This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches. 4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods. Random forest (RF) showed the best prediction performance with 91.3% for accuracy, 92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation. The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy (89.51%). The central composite design (CCD) was used to screen the best ratio of oil-surfactant-cosurfactant. Finally, molecular dynamic (MD) simulation was used to investigate the molecular interaction between excipients and drugs, which revealed the diffusion behavior in water and the role of cosurfactants. In conclusion, this research combined machine learning, central composite design, molecular modeling and experimental approaches for rational SEDDS formulation design. The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.