The aim of the study was to optimize the coating formulation of sustained release pellets of loxoprofen sodium by the central composite design-response surface methodology(RSM plus CCD).In the formulation design using RSM plus CCD,independent variables were the ratio of HPMC to EC(X_1) in the sustained coating formulation and polymer load(weight gain,X_2) were selected as in dependent variables,and in vitro accumulated releases from the pellets at 1,4,and 8 h were dependent variables.Multilinear,two and three order quadratic models were used to estimate the relationship between the dependent and the independent variables,and to delineate RSM and overlay contour plots in order to select the optimal formulations in compliance to the hypothesized in vitro releases (%) at 1,4,and 8 h.The results showed that the relationship between dependent and independent variables was best fitted to three-order quadratic equation.The regression equation generated for the hypothesized in vitro cumulative releases(%) at 1,4,and 8 h were Q_(1h) =227.699 2-30.785 9X_1-43.395 4X_2 + 0.917 4X_1~2 +1.820 3X_2~2 +6.803 9X_1X_2-0.131 5X_1~2X_2-0.268 2X_1X_2~2,Q_(4h) =408.254 0-47.427 8X_1-75.229 2X_2 +3.304 0X_2~2 +12.357 3X_1X_2-0.111 8X_1~2X_2-0.5425X_1X_2~2,Q_(8h) =303.539 0-30.417 6X_1-45.114 0X_2 +2.064 4X_2~2 +6.865 0X_1X_2-0.3341X_1X_2~2,respectively.In the optimized coating formulation,the ratio of HPMC to EC was 4.0% and the polymer load 9.0%.Bias between observed and predicted values in vitro accumulated releases were negligible,indicating the high predictability of the selected models.Therefore,RSM plus CCD is applicable in the optimization of the coating formulation of loxoprofen sodium sustained-release pellets.

Objective To study the effect of post-hospital nursing intervention on blood pressure and medication compliance of hypertensive patients.Methods One hundred hypertensive patients were divided into the observation group and the control group in equal number by the random digits table.Those in the control returned regularly for consultations and took medicine under doctor’s supervision and those in the observation group received out-of-hospital nursing intervention apart from the nursing done to the controls. The blood pressure and medicine-taking compliance were assessed in 6 months.Result The observation group was significantly better than the control one in terms of blood pressure and medicine-taking compliance(both P<0.05).Conclusion The post-hospital systematic nursing intervention may help to control the blood pressure of hypertensive patients and enhance their medicine-taking compliance so as to improve the curative effect.

Objective To investigate the role of CD4 ~+ CD25~+ regulatory T lymphocytes (Treg)in modulating the cellular immune response and pathogenesis of murine pulmonary tuberculosis.Methods Inactivation of Treg was achieved by intraperitoneal injection anti-CD25 (clone PC61,50 μ/mouse) in PC61 group, and rat-IgG (50 μ/mouse) was injected intraperitoneally in control group. All the mice were inoculated intravenously with H37Rv 0. 1 mL (1 × 10~6 CFU) 3 days after Treg inactivation. The effects of Treg inactivation in different tissues were analyzed by flow cytometry. The cellular immune response, pulmonary histopathology and bacterial load were determined in vitro at different time points. The data were compared using homogeneity of variance F test and non-paired t test. Results In spleen, the percentages of Treg/CD4 T lymphocytes in PC61 group and control group were (21. 13± 3. 58)% and (30. 42± 4. 20)%, respectively at day 10 of inoculation (t = 2. 38, P < 0. 05), and those were (16. 12 ± 1. 26)% and ( 17. 34± 1. 62)%,respectively at day 30 of inoculation (t = 0. 84,P>0. 05). The percentages of Foxp3~+/CD4~+ T lymphocytes in PC61 group and control group were (32. 07 ± 3. 95)% and (60. 55 ± 5. 48)%,respectively at day 10 of inoculation (t = 5. 96, P<0. 05). Similar results were achieved in the peripheral blood. Bacillus calmette-guerin (BCG)-specific 1L-17 (ng/L) secreted by murine spleen cells in PC61 group and control group at day 10, 30 and 60 of inoculation were 5. 1± 0.9 vs 0, 43. 1± 10.0 vs5. 9± 2. 8 and 124.8 ± 5.8 vs 102. 5±8. 1, respectively (t = 7. 90, t=5. 10,t = 3. 19; all P<0.05); those of BCG-specific IFN-γ (ng/L) were 28. 4 ± 8. 2 vs 4. 0±1. 3, 685. 9± 128. 6 vs418. 7±20.4 and 310.9±119. 7 vs 32. 8±7. 5, respectively(tO = 4. 21,t = 8. 43, t = 3. 27; all P<0.05);those of TNF-a (ng/L) were 38. 6±5.0 vs 16. 3±4. 0, 112. 9 ±12. 3 vs 71. 5±12. 6 and 86. 2±8. 2vs0, respectively(t = 4. 95, t=3. 33,t/=14.8; all P<0. 05). The lung bacterial load at day 10 of inoculation in PC61 group was lower than that in control group (t = 4. 63, P < 0. 01), but the differences were not significant thereafter. The changes of lung histopathology at late stage of infection (day 120) in PC61 group were less severe than those in control group. Conclusions Murine Tregs increase dramatically after Mycobacterium tuberculosis infection. Treg could inhibit the specific cellular immunity against Mycobacterium tuberculosis, and therefore, may facilitate the persistent infection of Mycobacterium tuberculosis and development of tuberculosis.

Objective To establish a fluorescent polymerase chain reaction (PCR) method for rapid, sensitive and specific determination of -88/-123 polymorphisms in Myxovirus resistance protein A (MxA) gene promoter so as to provide molecular biology tool for optimized interferon-a treatment in chronic hepatitis B patients. Methods Hepatitis B virus (HBV) genotyping,serum HBV DNA level,and- 88/- 123 polymorphisms in MxA gene promoter of patients who had been treated with interferon-α were detected. The statistical analysis was done by using SPSS software to understand the relationship between MxA gene polymorphisms and interferon-α treatment. Afterwards, an optimal fluorescent PCR system was established to determine -88/-123 polymorphisms in MxA gene promoter. The sensitivity and the specificity of this system were confirmed by DNA sequencing. P-value of chi square test, odds ratios of regression analysis and 95% confidence intervals were employed. Results Patients with- 88 G/T and - 123 C/A in the interferon-stimulated response element in MxA gene promoter were interferon-α sensitive, while patients with - 88 GIG and - 123 C/C were not interferon-α sensitive. The coincidence rate of this system was 99.65% in comparison with DNA sequencing.Conclusion MxA gene polymorphisms could be rapidly and sensitively determined by this fluorescent PCR system.

Objective This review was aimed to provide reference for production, management and use of laboratory animals by analyzing the test results on intestinal parasitic infections of mice and rats in different provinces from 1989 to 2013 in China.The results showed that the infection rates in clean and SPF mice and rats were reduced to 10%, being better than that in the past years, but the situation was still not optimistic for the control of flagellate parasites infections.

The oral colon-specific drug delivery system (OCDDS) has gained more attention from investigators in recent years since it can increase local drug concentration and reduce dosage and side effects.The type of colonspecific drug delivery system consists of enzyme dependent,pH dependent,time dependent,pressure dependent system and CODEDSTM.The development of many new materials and technology is very important for the preparation of new type of precise positioning colon-specific preparation.This article summarizes the advances in excipients and technique for oral colon-specific drug delivery system in recent years.It may provide a reference and a basis for the researchers concerned.

BACKGROUND: A lot of researches have proved that polyglicolide acid (PGA), as a stent material, has been successfully used to construct engineered tissues, such as cartilage, bone and tendons, in nude mice or even big mammal. Whether the incubation of vascular endothelial cells and smooth muscle cells in the polyglicolide acid may subcutaneously construct vessel-like structure in nude mice needs a further study.OBJECTIVE: To verify the feasibility of forming vessel-like structure in the nude mice by subcutaneous implantation of polyglicolide acid cocultured with vascular endothelial cells and smooth muscle cells derived from newborn umbilical vein.DESIGN: Contrast study.SETTING: Tissue Engineering Key Laboratory, Medical College, Shanghai Jiao Tong University.MATERIALS: This study was performed at Tissue Engineering Key Laboratory, Medical College, Shanghai Jiao Tong University from January to June 2002. Belly band was derived from newborn babies in our department of obstetrics & gynecology. The parturien provided the informed consent, and this study was approved by the local research ethics committee. Twenty-six nude mice (3-4 weeks old, clean grade, irrespective of gender) were selected in this study. The animal experiment received confirmed consent from the local ethic committee. Polyglicolide acid was provided by Albany International Research Co.METHODS: Vascular endothelial cells and smooth muscle cells derived from newborn umbilical vein were incubated on a piece of polyglicolide acid to produce cell-material compound. In addition, the compound covered around the silicone tube to form a tube-like structural substance. Subsequently, the tube-like structural substance was subcutaneously implanted in 20 nude mice, which were regarded as an experimental group. And then, polyglicolide acid alone was subcutaneously transplanted in the rest 6 nude mice, which was regarded as a control group.MAIN OUTCOME MEASURES: Gross observations of cell-material compound by 2 and 6 weeks after transplantation;HE staining and immunohistochemical staining.detection; expression of factor Ⅷ and α-smooth muscle actin.RESULTS: Twenty-six nude mice were included in the final analysis. ① Gross observation: At 2 weeks after implantation,both the experimental and control groups formed tubular structures, however, at 6 weeks after implantation, the tubular structure still remained in experimental group but not in the controls. ② Histological observation and immunohistochemical detection: The histological examination of the engineered vessel showed that at 2 weeks, the vessels in both group contained mainly undegraded PGA fibers, while at 6 weeks, the PGA fibers were almost completely degraded in both groups and in the control group only fibrous-like tissue formed. Contrastly, in experimental group a typical vascular structure formed, Masson's trichrome stain, which stains collagen green, smooth muscle fibers red and cells purple, showed significant amounts of stainable collagen and smooth muscle fibers in the wall of the engineered vessel, furthermore,immunohistochemistry examination revealed that there were an endothelial cell layer formed in the inner surface of the engineered vessel which was confirmed by positive staining of yon Willebrand factor, meanwhile, the smooth muscle cells in the wall of the engineered vessel were confirmed by the positive staining of smooth muscle α-actin.CONCLUSION: The subcutaneous implantation of polyglicolide acid cocultured with vascular endothelial cells and smooth muscle cells may form vessels, which are similar to normal vascular histological structure.

Objective To compare the clinical efficacy and safety of pegylated interferon α-2a (Peg IFN α-2a) or adefovir dipivoxil(ADV) monotherapy and their combination therapy in HBeAg positive chronic hepatitis B (CHB) patients. Methods An open randomized controlled multicenter clinical trial was performed. One hundred and twenty cases with CHB were divided into 3 groups: Peg IFN α-2a monotherapy (group A), ADV monotherapy (group B) and Peg IFN α-2a plus ADV combination therapy (group C). The virological response (VR), serological response (HBeAg, HBsAg clearance and seroconversion), biochemical response (BR) and sustained response (SR) were tested at week 24 and 48 of therapy and week 48 of follow-up after end of treatment (EOT) for'evaluation of therapeutic effects, safety and drug resistance. The efficacy was compared using X2 test. Results At week 48 of treatment, the VR (HBV DNA ≤500 copy/mL) rates were 36. 8%(14/38), 37. 5%(15/40) and 62. 9% (22/35), respectively in groups A, B and C; that in group C was higher than those in groups A and B (X2 = 4. 933, 4. 801, respectively; both P < 0. 05); HBeAg seroconversion rates in three groups were 44. 7% (17/38), 17. 5% (7/40) and 51. 4% (18/35), respectively. At week 48 of follow-up,SR rates in three groups were 34. 2%(13/38), 15. 0%(6/40) and 48. 6% (17/35), respectively; those in groups C and A were higher than that in group B (X2 = 9. 894,P<0. 01;X2 =3. 903, P<0. 05, respectively). Conclusions VRs at week 24 and 48 of Peg IFN α-2a plus ADV combination therapy are better than Peg IFN α-2a or ADV monotherapy. SRs at week 48 of follow-up after Peg IFN α-2a monotherapy and combination therapy are both better than ADV monotherapy.

Objective To assess the efficacy and safety of peginterferon ( PegIFN) α-2b in treatment of HBeAg-positive chronic hepatitis B ( CHB).Methods Thirty two patients with HBeAg-positive CHB admitted in Peking University Shenzhen Hospital during November 2013 and January 2014 were recruited in the study.Patients were center randomly assigned into two groups : 22 patients in test group were treated with 180 μg PegIFN α-2b, 1 /w for 48 wk; 10 patients in control group were treated with 180 μg PegIFN α-2a (Pegasys), 1 /w for 48wk.All patients were followed up for 24wk after treatment.Virology markers, HBV DNA levels and liver functions were monitored regularly , and adverse events were observed . Fisher’s exact test was used to compare the efficacy and safety between two groups .Results There were no statistically significant differences between the control group and test group in ALT normalization rates , HBV DNA negative rates and HBeAg serological conversion rates both at the end of treatment and at the end of 24-wk follow-up (all P >0.05).Both groups had similar adverse effect incidence rates (P >0.05), but retina disease occurred in 7 cases of test group, which was not observed in control group .Conclusion Compared with PegIFN α-2a, PegIFN α-2b has similar efficacy and safety for patients with HBeAg -positive CHB.

Due to the non-targeted release and low solubility of anti-gastric cancer agent,apatinib(Apa),a first-line drug with long-term usage in a high dosage often induces multi-drug resistance and causes serious side effects.In order to avoid these drawbacks,lipid-film-coated Prussian blue nanoparticles(PB NPs)with hyaluronan(HA)modification was used for Apa loading to improve its solubility and targeting ability.Furthermore,anti-tumor compound of gamabufotalin(CS-6)was selected as a partner of Apa with reducing dosage for combinational gastric therapy.Thus,HA-Apa-Lip@PB-CS-6 NPs were constructed to synchro-nously transport the two drugs into tumor tissue.In vitro assay indicated that HA-Apa-Lip@PB-CS-6 NPs can synergistically inhibit proliferation and invasion/metastasis of BGC-823 cells via downregulating vascular endothelial growth factor receptor(VEGFR)and matrix metalloproteinase-9(MMP-9).In vivo assay demonstrated strongest anti-tumor growth and liver metastasis of HA-Apa-Lip@PB-CS-6 NPs adminis-tration in BGC-823 cells-bearing mice compared with other groups due to the excellent penetration in tumor tissues and outstanding synergistic effects.In summary,we have successfully developed a new nanocomplexes for synchronous Apa/CS-6 delivery and synergistic gastric cancer(GC)therapy.