Objective To evaluate the efficacy and safety of interferon alpha (IFNα) combined with adefovir dipivoxil (ADV) for patients with chronic hepatitis B (CHB) non-responding to 24-week IFNα monotherapy.Methods Sixty CHB patients admitted to the First Affiliated Hospital of Xiamen University during 2009 and 2012 were enrolled in the study.All patients recieved IFNα monotherapy for 24 weeks and had no response.The patients were randomly divided into 3 groups by number table with 20 cases in each group.The experimental group was treated with IFNα combined with ADV,the control group 1 continued IFNα monotherapy,and the control group 2 shifted to ADV monotherapy.Virological,serological and biochemical responses were compared,and adverse reactions were observed.SPSS 19.0 software was used for data analysis.Results After 24 weeks of treatment,there was no statistical difference in HBV DNA loads,ALT levels and titers of HBeAg and HBsAg among three groups (F =0.985,0.717,0.985 and 0.717,P ＞ 0.05).And no HBeAg seroconversion was observed.After 48 weeks of treatment,the experimental group had higher HBV DNA negative conversion rate,ALT normalization rate and HBeAg conversion rate than control group 1 (x2 =10.00,3.956 and 4.800,P ＜ 0.05),but no statistically significant difference was found in HBeAg negative conversion rate (x2 =0.693,P ＞ 0.05).There was no significant difference in HBV DNA and HBeAg negative conversion rates between experimental group and the control group 2 (x2 =1.026,1.905 and 0.156,P ＞0.05),but the HBeAg conversion rate in experimental group was significantly higher than that in control group 2 (x2 =4.800,P ＜ 0.05).No HBsAg negative or serological conversion was observed,and there was no significant difference in titers of HBsAg among three groups (F =1.935,P ＞ 0.05).No adverse reaction was observed.Conclusion For patients nonresponding to IFNα monotherapy,combination of IFNα and ADV can achieve higher ALT normalization rate,HBeAg conversion rate and HBV DNA negative conversion rate,and improve the overall efficacy of CHB antiviral therapy.

Objective To observe the effects and study the underlying mechanism of siRNA targeting PARP1 on the proliferation of androgen independent prostate cancer PC3 cell line.Methods Three specific siRNA sequences targeting PARP1 were designed and synthesized.And two sequences which had better interfering effect on the expression of PARP1 were evaluated and selected through lipofectamine transfection,RT-PCR and Western Blot.The effect of PARP1 silencing on the proliferation of PC3 cells was observed with MTS assay and the levels of the phosphorylation of Akt and GSK3β were detected by Western Blot.Results Compared to the blank control group,the transfected group with the negative control sequence had no significant impact on the expression of PARP1,however the transfected group with siRNA-1706,-2003 or-2907 could significantly suppress the mRNA and protein expression of PARP1.The mRNA inhibition rate reached to(52.07 ± 4.65)％,(44.38 ± 9.15)％ and(22.05 ± 6.65)％,respectively;and the protein inhibition rate reached to(86.86 ± 4.94)％,(83.30 ± 7.18)％ and(63.05 ± 10.19)％,respectively.The siRNA-1706 and-2003 could significantly inhibit the proliferation of PC3 cells;the inhibition rate was(38.93 ± 3.87)％ and(34.93 ± 1.21)％.And they also could down-regulate the intracellular levels of phosphorylated Akt and GSK3β in PC3 cells.Conclusion PARP1-targeted siRNA can significantly suppress the expression of endogenous PARP1 and inhibit the proliferation of PC3 cells,which is related to the inhibition of Akt activity and the activation of GSK3 β.

Objective To explore the expression and clinical significance of constitutive androstane receptor(CAR)in placenta syntrophoblast from patients with intrahepatic cholestasis of pregnancy(ICP).Methods Placenta were collected from women with ICP who delivered from April 2009 to March 2010 in First Affiliated Hospital of Chongqing Medical University.According to the severity of ICP,patients were classified into mild ICP group(n=10)and severe ICP group(n=10).Ten healthy pregnant women who delivered in the same period were chosen as control group.The location of CAR protein in placenta was studied by immunohistochemical streptavidin-biotin complex(SABC)method.CAR mRNA level was determined by reverse transcription(RT)-PCR technique and CAR protein expression level was determined by western blot.Results(1)CAR was located in the placenta syncytiotrophoblastic cells in control group and mild ICP group,showed light tan when stained,and was mainly in the cytoplasm.In severe ICP group,CAR was also located in placenta syncytiotrophoblastic cells but mainly in the nucleolus,showed dark tan when stained.(2)The mRNA expressions of CAR in control group,mild ICP group,severe ICP group were 0.06 ±0.03,0.07 ±0.03 and 0.56±0.03.respectively.CAR in severe ICP group was significantly higher than those in control group and mild ICP group(P＜0.05).The difference of mRNA between control group and mild ICP group wag not statistically significant(P＞0.05).(3)The CAR protein levels in control group,mild ICP group,severe ICP group were 0.74±0.03,0.79±01 03 and 1.02±0.04,respectively.CAR protein expression in the severe ICP group was significantly higher than the other two groups(P＜0.05).And there was no statistical significance between mild group and control group(P＞0.05).Conclusion In ICP women.especially severe ICP patients,the CAR expression in placenta syncytiotrophoblastic cells increased appreciably,which may be involved in the maintenance of placenta barrier function and protection in ICP pathogenesis.

Objective To analyze the status of research secretary team in Anzhen hospital and to put forward suggestions to improve the current situation of the team.Methods Factors such as the setting of research secretary duties,implementation mode,status of research secretary team building on hospital clinical departments,and existing problems were analyzed.Results The team building of research secretary reduced the department directors' burden,standardized the daily management,and partly improved work efficiency through co-ordination.But the inadequate maintenance of of scientific research strength was needed to be proved.Conclusions Improving the selection scheme of research secretary,setting up the system of rewards and penalties,Strengthening exchanges on a regular basis may sharpens research secretary professional ability and the quality,accelerate the hospital's research developments.

Objective To investigate elderly patients with thoracic radiotherapy nausea result after risk factors associated with radiation pneumonitis.Methods The clinical data of a total of 440 cases of cancer patients with chest radiation therapy during January 2010-January 2014 were collected retrospectively.Of them,76 cases of radiation pneumonitis after radiotherapy were compared with other patients.The unconditional Logistic regression analysis was used to analyze the relationship of radiation pneumonitis and different factors including smoking,pulmonary dysfunction,combination with chemotherapy,radiation dose,and radiation sites.Results Elderly incidence of radiation pneumonitis was 17.27％.Multivariate Logistic regression analysis revealed the chi-square value of smoking,pulmonary dysfunction,combined with chemotherapy,radiation dose,and radiation sites was significant correlation (x2 =16.936,19.633,11.531,17.133,10.178,P ＜0.05),and the correlation degree was gradually decreased from pulmonary dysfunction,radiation dose,smoking,combined chemotherapy,to radiation site.Conclusions Elderly patients with thoracic malignancies after radiotherapy had more radiation pneumonitis,which was related to smoking,previous chemotherapy PO2 ＜ 80％,combined with chemotherapy,radiation dose ≥ 55 Gy,and low-lung radiation.The correlation degree was gradually decreased from chemotherapy before PO2 ＜ 80％,the radiation dose ≥55 Gy,smoking,combined chemotherapy,to low-lung radiation.

The numbers of application and granted funds for NSFC were analyzed statistically in Capital Medical University Affiliated Beijing Anzhen Hospital from 2009 to 2012.This paper retrospectively analyzed the development recurrent features of scientific research and put forward some suggestions.Meanwhile,it revealed the prospects of scientific research in our hospital.

A rapid analytical method for the determination of dezocine and pethidine in hair samples using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established.After cleaned hair was extracted by grinding with methanol and ultrasonic, the final solution was analyzed by UPLC-MS/MS.The targets were gradient eluted on a Waters Acquity BEH C18 (2.1 mm × 100 mm, 1.7 μm) column with 0.1% formic acid-water and methanol as mobile phase at a flow rate of 0.4 mL/min.The ESI+ ion source and multiple reaction monitoring (MRM) were used to select the qualitative and quantitative ion pairs of dezocine and pethidine.Dezocine and pethidine showed good linearity in the range of 0.01-8 ng/mg, with the limit of detection of 0.005 ng/mg and the LOQs of 0.01 ng/mg.The accuracy, precision, matrix effect, extraction recovery, and stability all met the requirements.The established method is simple, rapid, and accurate for the qualitative and quantitative determination of dezocine and pethidine in hair, which can be applied in the case analysis of dezocine and/or pethidine abuse.

Objective To study the effects of APBV (airway pressure release ventilation) / BIPAP(bipha-sic positive airway pressure) on lung recmitment/open maneuvers in piglets with acute lung injury. Method The model of acute lung injury (ALI) was induced by E. coll. intraperitoneal injection in piglets. Based APRV/BI-PAP model, the different pressure combinations (Phigh/Plow) of RMs increased gradually, such as RMI(30/15),RM2(35/20), RM3(40/25), RM4(45/30),RM5(50/35), RM6(55/40), RM7(60/45) cmH2O. The effects of stepwise RMs were studied by computed tomography (CT) at iaspiratory phase. Meantime the oxygen index (PaO2/FiO2), hemodynamic parameter and mean pressure of airway (Pmean) were continuously observed. The piglets were killed when RiMs finished and pulmonary pathological examination were done routinely by optical microscope. Data was analyzed by self-contrast method, using SPSS 11.5 software package. Results were expressed as mean ± standard deviation (x±s). Multiple comparisons were made with One-way ANOVA. Pearson correlative analysis was used to describe the relativity of PaO2/FiO2 and the collapsed alveolar area. Changes were considered as statistically significant if P value was less than 0.05. Results Eight piglets with ALl model were successfully made and all of them showed different degree of alveolar collapse under chest CT scan. During RMs their PaO2/FiO2 increased obviously (P<0.05) were decreased obviously (P<0.05) too, specially after RM2 finished (P<0. 05). But the alveolar over-inflatian could be found in some non-diseased area. The heart rate (HR) increased and mean artery blood pressure (MAP) decreased significantly while the pressure combinations (Phigh/Plow) of RMs were added gradual]y ( P<0.05). Meantime the Pmean and Ppeak inspiratory pressure (PIP) of airway and central venous pressure (CVP) were increased significantly ( P<0.05). But when RMs were finished,all of these indexes were hack to the levels of pre-RMs. Even there were no barowaumas happened, such as pneumothorax and pneumomedistinum, the alveolar overdistention and interruption of the alveolar separation still could be seen by pathologic examination. Conclusions RMs could be done well by APRV/BIPAP. Phigh/Plow (35/20cmH2O) would be the best pressure combination with more efficacy of RMs and less influence on hemodynamics,airway pressure indexes and others. When the effect of RMs was satisfied enough, setting Phigh/Plow to 30/15cmH2O for 20 mitt may maintain the good efficacy of RMs.

Objective To investigate the molecular mechanism for change in permeability in brain microvascular endothelial cells (bEnd.3) induced by lipopolysaccharide (LPS). Methods Monolayers of bEnd.3 were exposed to LPS,in the presence or absence of exoenzyme C3 transferase. We monitored the monolayer barrier integrity by transendothelial electrical resistance assay (TEER),activity of RhoA by pull down assay,NF-κB by luciferase reporter assay,and F-actin dynamic structure by Rhodamine-phalloidin staining. Results Incubation of monolayers with LPS caused substantial barrier hyperpermeability. Under the had been treated for 3 and 12 h with LPS (P＜0.05). Such effects could be inhibited partly by pretreatment of RhoA inhibitor exoenzyme C3 transferase. LPS activated RhoA and NF-κB at 0.5 h. The C3 transferase could significantly reverse the NF-κB activation (P＜0.05). The F-actin rearrangments displayed in a time-dependent manner and occurred originally after the stimulation of LPS for 3 h,which could be diluted by the pretreatment of C3 transferase as well. Conclusion LPS induces the disruption of F-actin cytoskeleton and brain microvascular endothelial barrier integrity,in part,through RhoA and NF-κB activation. The mechanism underlying this pathophysiological effect of RhoA is to influence the disruption of the F-actin cytoskeleton by regulating NF-κB activites.

Objective To evaluate the long-term prognosis and safety of ABO-incompatible (ABO-I) liver transplantation on type-O patients with acute severe liver disease,analyze and compare the effects and main complications between different donor blood types,and investigate corresponding treatment measures.Methods The clinical data of 65 cases of emergency orthotopic liver transplantation (OLT) for type-O patients with acute severe liver disease from January 2014 to January 2017,including 41 cases of ABO-compatible (ABO-C) OLT and 24 cases of ABO-incompatible OLT (7 with type-A donor,9 with type-B donor,and 8 with type-AB donor) were retrospective analyzed.Results The model for end-stage liver disease (MELD) score in the ABO-incompatible group was 32.5±5.5,significantly higher in the ABO-compatible group (23.3±8.9) (P=0.001).The data of the other perioperative factors showed no statistically significant difference between two groups.The cumulative survival rate in the ABO-compatible group was 87.8 % (36/41),not significantly different from that in the ABO-incompatible group [87.5% (21/24),P=0.924].The 57 cases who had survived after perioperative period were followed up for 4-37 months (mean 18 months).Significantly higher incidence of hepatic artery and biliary complications was found in ABO-incompatible group (P=0.005,and P<0.001,respectively).The incidence of hepatic artery complication and biliary complication in ABO-incompatible group was 29.2% (7/24) and 37.5% (9/24),and that in ABO-compatible group was 4.9% (2/41) and 0 (0/41),respectively.The rate of acute rejection in the ABO-incompatible group and ABO-compatible group was 9.8% (4/41) and 4.2% (1/24) (P=0.463).The infection rate in the ABO-compatible group and ABO-incompatible group was 24.3% (10/41) and 29.2%(7/24),respectively (P=0.598).Conclusion The different donor blood types including ABO-compatible and ABO-incompatible liver transplantation program on type-O patients with acute severe liver disease have a favorable outcome.The long-term cumulative survival rate between two groups shows no significant difference.With the help of effective immunosuppression and intensive perioperative management,ABO-incompatible liver transplantation is an acceptable option to cure type-O patients with acute liver failure in emergency.The incidence of hepatic artery and biliary complications was lower in ABO-compatible group than in ABO-incompatible group.For the type-O patients with ABO-incompatible liver transplantation,the use of rituximab and plasma exchange to decrease the antibody titers of recipients is essential to prevent and cure the hepatic artery and biliary complications.