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.

OBJECTIVE：To prepare Imperatorin ultradeformable liposomes gel （IMP-UDLs-Gel），and to evaluate its quality. METHODS：Based on single factor test ，using 12 h accumulative penetration amount （Q12h）as evaluation index ，the proportion of carbomer 940，glycerol and propyl glycol in formulation of IMP-UDLs-Gel were investigated by orthogonal test. The optimal formulation was screened. The quality of IMP-UDLs-Gel prepared with the optimal formulation was evaluated. RESULTS ：The optimal formulation of IMP-UDLs-Gel included carbomer 940 proportion of 1％，glycerol proportion of 15％ and propyl glycol proportion of 10％. Q12 h of IMP-UDLs-Gel was （11.543±0.241）μg/cm2；the appearance was milky white and translucent ；the particle size was （93.13±1.68）nm，PDI was 0.268±0.012，Zeta potential was （－24.96±1.99）mV；pH was 7.32±0.03； viscosity was （45.37±1.27）g·s；steady flow was （0.727±0.002）μg·h/cm2，lag time was （4.358±0.175）h，apparent permeability coefficient was 1.392×10－3 cm/h，and it has good physical and optical stability. CONCLUSIONS ：The preparation method is stable and feasible ，and the prepared IMP-UDLs-Gel has good adhesion ，stability and transdermal property.

Objective To investigate the clinical characteristics of DCD donor-derived CRKP infection and bleeding in kidney transplantation,and to summarize the experience of diagnosis,treatment and prevention.Methods A retrospective analysis was carried out from July 2016 to December 2017 in hospital,containing clinical data of 4 cases of CRKP-infected DCD donors and 7 cases of kidney transplantation recipients.Results In the CRKP culture of 4 cases of DCD donors,1 case was positive for blood culture,1 case was positive for urine culture,1 case was positive for sputum culture,and 1 case was negative for blood,urine and sputum culture.The corresponding 7 recipients were all positive for blood culture after renal transplantation,4 cases were positive for urine culture,3 cases were positive for sputum culture,and 5 cases were positive for perirenal drainage.Of the 7 patients,4 cases had renal artery hemorrhage,1 of them was died.The average bleeding time was 17.75 days after operation (14-19 days).In 7 patients with renal transplantation,CRP increasd.And in 3 cases of deaths,CRP was stably higher than normal.Meanwhile,CRP in 4 surviving patients gradually decreased to the normal range after effective anti-infection treatment.All 7 patients were treated with carbapenems;2 patients were dead without avibactam therapy;and 5 cases were treated with avibactam and carbapenems and survived,1 case died and 1 case had good renal function recovery.Conclusion Positive CRKP in blood,urine and sputum of DCD donors can lead to CRKP infection in kidney transplant recipients.Even if the body fluids of donors are all negative,the false negative results could not be excluded.Persistent or increased high-level CRP after operation is an early warning on CRKP infection.And CRP can be used as an indicator for evaluating the effectiveness of anti CRKP therapy.The combination of avibactam and carbapenem antibiotics is an effective regimen in the treatment of DCD donor-derived CRKP.

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.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

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.

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.

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 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.

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.