OBJECTIVE:To prepare nifedipine sustained-release hydrogels and to study their drug release in vitro.METHODS:Nifedipine sustained-release hydrogels were prepared by complex coacervation.An orthogonal experiment was performed with chitosan,concentration of sodium alginate,mixing speed and the volume ratio of chitosan solution to sodium alginate solution as factors.Meanwhile,the dissolution rate of the prepared hydrogels was determined by basket-rotating method,and pH-sensitivity of the released drug in different pH medium was investigated.RESULTS:The optimal technical condition was as follows:the concentration of chitosan was 0.4% and that of sodium alginate was 1.5%;the mixing speed was 160 r?min-1;the volume ratio of chitosan solution to sodium alginate solution was 6:1.The dissolution rate of sustained-release hydrogels containing nifedipine was 13.43% in simulated gastric fluid(pH 1.5) at 4 hours,which stood at 52.30% at 4 hours and 81.72% at 12 hours in simulated intestinal fluid(pH 6.8).CONCLUSION:The sustained-release hydrogels of nifedipine showed remarkable sustained-release properties and strong pH sensibility in vitro.

Objective To study the expression of the excision repair cross complementing 1 ( ERCC1 ) and thymidylate synthase ( TS) in gastric cancer and to investigate the correlation between the ERCC 1 and TS ex-pression with the efficacy of FOLFOX adjuvant chemotherapy in gastric cancer patients .Methods A total of 73 gastric cancer patients received modified FOLFOX adjuvant chemotherapy .Real-time PCR was used to investi-gate the expression of ERCC 1 and TS in gastric cancer tissue .We also studied their correlation and association with prognosis .Results ERCC1 and TS expressed in gastric cancer tissues with the positive rate were 42 .5%(31/73)and 61.6%(45/73).There was no significant correlation between the ERCC 1 or TS expression and the clinical features .In this study ,the median of RFS and MST were 16 months and 27 months in patients with ER-CC1-negtive expression,9 months and 16months in patients with ERCC1-positive expression,the median of RFS and MST were significantly different in the two groups (P=0.000,P=0.002).There were no statistical differences on TS expression pattern in either median of RFS or MST (P=0.10,P=0.71).Conclusion The ex-pression of ERCC1 may be useful in prediction of the clinical outcome in gastric cancer patients who treated with FOLFOX7 adjuvant chemotherapy .Patients with ERCC1-negtive expression may benefit from the therapy .

Objective To evaluate prescribing antibiotics in medical patients visiting the polyclinic at 2008 Beijing Olympic Village for its further reasonable use. Methods Clinical prescriptions for all the medical patients at the polyclinic were reviewed retrospectively. Consistency between antibiotics prescriptions and their indications formulated before 2008 Beijing Olympic Games was evaluated, as well as related factors for their overuse. Results In total, 1537 patients visited the polyclinic and 1233 recipes were prescribed,with 956 patients (62. 2% ) with infections, including 809 (52. 6% ) of respiratory infections. One hundred and forty-nine of 1537 patients (9. 7% ) were treated with antibiotics, accounting for 12. 1 percent of all prescriptions, and 43 cases (28.9%) were identified as antibiotics overuse, including 39 cases with respiratory infections. Prevalence of antibiotics overuse was significantly more for patients of domestic employees than that for non-employees (34. 6% vs. 14.3% , P <0. 01 ), with art independent association between them (OR 3.07, 95% CI 1.11 - 8. 50). Conclusions Although the polyclinic has successfully reduced unnecessary antibiotics use, their overuse remains to be reduced, and physicians' strict adhesion to indications for antibiotics use and patient education are essential for their rational use in primary care of China.

AIM:To demonstrate the relationship between hormones in follicular fluid and the expression of LH receptor in granulosa cells(GC) in anovulatory women with polycystic ovary syndrome(PCOS).METHODS: Follicles were obtained from 12 women with PCOS and 15 women with normal menstrual period through surgery at time between day 7 and day 10 of menstrual cycle.The accumulations of estrogen(E2),progesterone(P),luteinizing hormone(LH),follicle stimulating hormone(FSH) and insulin in follicular fluid were determined by a automatism chemiluminescent microparticle immunoassay(CMIA) for the quantitative determination.The accumulation of androstenediol(A) was determined by ELISA.The amounts of the mRNA expressions of LH receptors from GC and theca cells(TC) respectively were measured by RT-PCR using ?-actin as intra-control simultaneously.RESULTS: The levels of LH [(3.8?2.1 vs 1.7?0.8)IU/L,P

Objective To understand the dynamics of DC subsets in chronic HIV-infected patients during antiretroviral therapy (ART).Methods Seventeen treatment-naive chronic HIV-infected patients were enrolled in our study,and blood was collected at week 0,4,12,24,48 and 60 of ART.Additional 15 HIV-uninfected age-matched healthy adults and 15 long term non-progressors(LTNP) were recruited as controls.CD4+T cell counts and viral loads were examined routinely.The counts of DC subsets were measured by flow cytometry and IFN-α plasma levels were measured by ELISA.Data analysis was performed using SPSS version 16.0.Results ( 1 ) Before ART,mDC ( percentage and absolute count) in ⅢⅤ-infected group were significantly lower than those in healthy group and LTNP group,P＜0.001 in both groups.After 60 weeks of ART,mDC in HIV-infeeted group were significantly increased,and there were no significant differences compared with healthy controls and LTNP group.(2) pDC and IFN-α plasma levels remained relatively stable during ART,and similar to those in healthy controls and LTNP group.(3)Significant associations were found for DC subsets and CD4+ T cell counts before ART.mDC subsets at week 12,24,60 post ART were positively correlated with CD4+ T cell counts,and negntively correlated with virus load.Changes in mDC at week 8 post ART positively correlated with the changes in CD4+T cells at week 60 post ART,and negatively correlated with the changes in virus load at week 60 post ART.Conclusion The counts of mDC significantly reduced in HIV-infected patients,increased after ART,and positively correlated with CD4+ T cell counts.The findings suggest that mDC may play an important role in controlling HIV infection,mDC may serve as an early predictor for immune reconstitution in the initiation of ART.

Two simple and sensitive high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) methods were developed and validated for the determination of fenticonazole in human plasma after percutaneous and intravaginal administration. Mifepristone was used as an internal standard (IS), and simple protein precipitation by acetonitrile containing 2%acetic acid was utilized for extracting the analytes from the plasma samples. Chromatographic separation was performed on a Kinetex XB-C18 column. The quantitation was performed by a mass spectrometer equipped with an electrospray ionization source in multiple reactions monitoring (MRM) positive ion mode using precursor-to-product ion transitions of m/z 455.2–199.1 for fenticonazole and m/z 430.2–372.3 for mifepristone. The validated linear ranges of fenticonazole were 5–1000 pg/mL and 0.1–20 ng/mL in plasma for the methods A and B, respectively. For the two methods, the accuracy data ranged from 85% to 115%, the intra- and inter-batch precision data were less than 15%, the recovery data were more than 90%, and no matrix interference was observed. The methods A and B were successfully validated and applied to the pharmacokinetic studies of fenticonazole gel in Chinese healthy volunteers after percutaneous and intravaginal administration, respectively.

Objective To investigate the effect of hydrogen on endoplasmic reticulum stress during hypoxiareoxygeuation(H/R)in PC12 cells.Methods PC12 cells were randomly divided into 4 groups:normal control group(group NC),positive control group(group PC),H/R group and hydrogen group(group H).In group NC.the cells were cuhnred routinely for 25 h.In group PC,the cells were cultured routinely for 1 h and then in RPM1-1640 culture medium saturated with hydrogen for 24 h.In H/R group,the cells were exposed to 1 h of hypoxia followed by 24 h of reoxygenation.In group H,the cells were exposed to 1 h of hypoxia and then reoxygenated in RPMI-1640 culture medium saturated with hydrogen for 24 h.Hypoxia-reperfusion was produced by 1 h exposure of cells to 5％ CO2 in an incubator at 37 ℃ in RPMI-1640 culture medium containing Na2S2O4 with the final concentration of 5.0 mmoI/L,followed by 24 h reoxygenation in the normal RPMI-1640 culture medium.The relative rate of cell proliferation was detected by WST-1,The concentration of MDA was determined by thiobarbituric acid method.The expression of caspase-3 was determined by immuno-histochemistry.The expression of activating transcription factor-4(ATF4)mRNA and C/EBP homologous protein(CHOP)mRNA was determined by RTPCR.Results Compared with groups NC and PC,the relative rate of cell proliferation was significantly decreased,MDA concentration was significantly increased,and the expression of caspase-3,ATF4 mRNA and CHOP mRNA was up-regulated in group H/R,and the expression of ATF4 mRNA and CHOP mRNA was up-regulated in group H(P ＜ 0.05).There was no significant difference in the relative rate of cell proliferation,MDA concentration,and the expression of caspase-3,ATF4 mRNA and CHOP mRNA between groups NC and PC(P ＞ 0.05).Compared with group H/R,the relative rate of cell proliferation was significantly increased,MDA concentration was significantly decreased,and the expression of caspase-3,ATF4 mRNA and CHOP mRNA was down-regulated in group H(P ＜ 0.05).Conclusion Hydrogen can decrease cell apoptosis and attenuate H/R injury to PC12 cells through inhibiting endoplasmic reticulum stress.

Objective To detect and explore the expression and clinical significance of dual specificity tyrosine phosphorylation regulated kinase1b (Dyrk1b) in the specimens and cells of cervical lesions. Methods (1)All the data were collected from 75 patients with cervical cancer and 52 cases with squamous intraepithelial lesion(SIL)admitted in the First Affiliated Hospital of Dalian Medical College during Jan. 2011 to Dec. 2013 and confirmed by pathological examination, included 60 cases of stageⅠand 15 cases of stageⅡ, 12 cases with low-grade squamous intraepithelial lesion(LSIL)and 40 cases with high-grade squamous intraepithelial lesion(HSIL). While, 28 cases with chronic cervicitis were chosen as the control group. The protein expression of Dyrk1b was detected by immunohistochemistry among the four groups.(2)The expression of Dyrk1b in HeLa and SiHa cells were detected by western blot method and the expression of Dyrk1b protein were also detected after treatment of AZ191 (5, 10 μmol/L) for 48 hours in HeLa and SiHa cells.(3)The cellular survival and proliferation of HeLa and SiHa cells treated by different concentrations of AZ191(2.5, 5, 10, 25, 50, 100 μmol/L)for 48 hours were detected by methyl thiazolyl tetrazolium (MTT) assay.(4)The rate of apoptosis of HeLa and SiHa cells was detected by flowcytometry after treatment of AZ191 (5, 10μmol/L) for 48 hours. Results (1)The positive rates of Dyrk1b protein in chronic cervicitis, LSIL, HSIL and cervical squamous cancer by immunohistochemistry were 11%(3/28), 1/12, 42%(17/40)and 71%(53/75), respectively. The expression of Dyrk1b in cervical squamous cancer and HISL were higher than those in LSIL and chronic cervicitis (P<0.01), there were significant difference between cervical squamous cancer and HSIL, or between HSIL and LSIL(all P<0.05), while there were not significant difference between LSIL and chronic cervicitis(P>0.05). Expression of Dyrk1b was correlated with stromal invasion depth of cervical cancer (P<0.05), but not with age, clinical stage, lymph node metastasis, and serum squamous cell carcinom antigen(SCC-Ag)levels (all P>0.05). (2) Dyrk1b protein was expressed in different levels in HeLa and SiHa cells, and the expression of Dyrk1b was decreased gradually as the increased of the concentration of AZ191 in both HeLa and SiHa cells by treatment of AZ191 for 48 hours. (3) Different concentration of AZ191 treated on cervical cancer cells could inhibit the cellular proliferation and induce cell apoptosis in a concentration-dependent manner(P<0.01), concomitant to the decreased cell survival rate. The apoptosis rate of HeLa and SiHa were increased significantly after 10μmol/L AZ191-treatment for 48 hours, but no any difference induced by 5 μmol/L AZ191-treatment compared to control group. Also,there was no any difference between Hela and SiHa cells in either inhibitory effect or apoptosis rate induced by AZ191. Conclusions Dyrk1b is over-expressed in either specimens or cells of cervical cancer. The expression of Dyrk1b protein in cervical lesions is increased as the progression of disease. Dyrk1b inhibitor AZ191 could inhibit cellular proliferation and induce apoptosis in a concentration-dependent manner in cervical cancer cells.

ObjectiveTo investigate the risk factors for portal vein thrombosis (PVT) in cirrhotic patients with esophageal varices, and to establish a nomogram for predicting the risk of PVT. MethodsA retrospective analysis was performed for the clinical data of 283 cirrhotic patients with esophageal varices who attended Shandong Provincial Hospital Affiliated to Shandong University from December 2013 to December 2018, and according to imaging findings, the patients were divided into PVT group with 119 patients and non-PVT group with 164 patients. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. A multivariate logistic regression analysis was used to screen out independent risk factors; a nomogram was established and validated based on the results of the multivariate logistic regression analysis, and C-index and calibration curve were used to evaluate its performance. ResultsThe univariate analysis showed that compared with the non-PVT group, the PVT group had significantly higher Child-Pugh class (χ2=9.388, P=0.009), proportion of patients with a history of splenectomy (χ2=26.805, P＜0.001), white blood cell count (Z=-2.248, P=0.025), platelet count (Z=-3.323, P=0.001), D-dimer(Z=-6.236, P＜0.001), and spleen thickness (Z=-2.432, P=0.015) and a significantly lower level of triglyceride (TG) (Z=-4.150, P＜0.001). The multivariate logistic regression analysis showed that a reduction in TG (odds ratio ［OR］=0.441, 95% confidence interval ［CI］: 0.190-0.889), an increase in D-dimer (OR=1.151, 95%CI: 1.041-1.272), prolonged prothrombin time (PT) (OR=1160, 95%CI: 1.025-1.313), and a history of splenectomy (OR=2.933, 95%CI: 1.164-7.389) were independent risk factors for PVT in cirrhotic patients with esophageal varices. In addition, a nomogram was established based on the results of the multivariate regression analysis, with a C-index of 0.745, and the calibration curve showed good consistency between the observed and predicted values for the development of PVT. ConclusionA reduction in TG, an increase in D-dimer, prolonged PT, and a history of splenectomy are independent risk factors for PVT in cirrhotic patients with esophageal varices, and the nomogram developed based on these results can provide a quantitative and intuitive tool for clinicians to assess the risk of PVT.

Objective    To explore the role of increased preoperative ventricular-arterial stiffening in hypertensive infants with coarctation of the aorta (CoA). Methods    A retrospective study was conducted in 314 infants with CoA (CoA group, 193 males and 121 females, aged 5.4±2.2 months), and 314 infants receiving tumor chemotherapy with normal cardiovascular function and without pneumonia (control group, 189 males and 125 females, aged 4.4±3.8 months), who were admitted to our hospital from 2015 to 2017. The clinical data of the two groups were compared. Results    There were statistical differences in effective aortic elastance index (Eai), effective left ventricular end-systolic elasticity index (Eesi), ventricle-artery coupling index (VACi), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and ratios of left ventricular hypertrophy, dilation and systolic dysfunction between the two groups (P<0.05). Compared with non-hypertensive CoA infants, CoA infants with hypertension had higher Eai, Eesi, NT-ProBNP level and proportion of left ventricular hypertrophy (P<0.05). Compared with concomitant ventricular septal defect, infants with isolated CoA had higher Eai, Eesi, NT-proBNP level, incidence of hypertension and higher proportion of left ventricular hypertrophy, dilation and systolic dysfunction (P<0.05). Eai and Eesi were positively correlated with NT-proBNP level, left ventricular hypertrophy and fractional shortening of left ventricle (P<0.05), while Eai and Eesi were negatively correlated with left ventricular end diastolic volume index, left ventricular end systolic volume index and concomitant ventricular septal  defect (P<0.05). Hypertension was related to preoperative left ventricular hypertrophy, Eai, Eesi and NT-ProBNP. Eai was an independent risk factor for hypertension. Conclusion    Preoperative ventricular-arterial stiffening is increased in infants with aortic coarctation, which is related to the occurrence of hypertension. Isolated CoA shows more significant increase in ventricular-arterial stiffening, higher ventricular overload and incidence of hypertension.