Objectives: To design the mutants of peptide antibiotics hPAB ? based on its molecular structure. Methods: The three dimension structure of hPAB ? was constructed by protein homology modeling method. The mutant molecules were designed and generated by PCR and inserted into pQE CP4 expression plasmid. The recombinant plasmids were identified by PCR and DNA sequencing and then transformed into Escherichia coli JM109 to express target fusion proteins. Results:Peptide hPAB ? shows one ? helical and three ? sheet in its structure. Its ? helical regions seem play a key role in the formation of active oligomer. Aside from positioning Thr 7 and Lys 10 into contact positions, the orientation of the ? helix is conserved about the oligome core, forming a ridge around it. Additionally, the dipoles of the helices would overlap to create a positively charged region near the core. These dipoles may be offset, however, by the presence of Asp 4 at the base of the helix. Two mutant molecules, hPAB ? 38 and hPAB ? 34, were designed by deleting N or/and C terminal 2～5 amino acid residues based on hPAB ? structure. The recombinant plasmids containing the mutants gene can express interest fusion proteins in E. coli JM109 successfully. Conclusions: Design, cloning and expression of the mutants of peptide antibiotics hPAB ? lay down the foundation for screening of the mutant of shorter peptide chain and having high or same antimicrobial activity.

OBJECTIVE To investigate the inhibitory effect of eight lignan compounds of Fructus Schisandrae chinensis in vitro on carboxylesterase 2 (CES2) and to estimate the herb-drug interaction (HDI) risks of strong CES2 inhibitors selected from the above compounds. METHODS Fluorescein diacetate (FD) was employed as a specific fluorescent probe of CES2. The residual activity of CES2 was detected in human liver microsomes after the intervention with deoxyschizandrin, schisanhenol, schisantherin E, schisandrol A, schisandrol B, gomisin J, gomisin G, and gomisin O at 37℃ for 10 min, respectively. 1% DMSO served as control. Residual activity of CES2 was assessed with metabolite production of FD detected by fluorescent intensity, combined with IC50 values of the above compounds to predict HDI risks between lignans and CES2-metabolizing drugs. RESULTS Compared with control group, the activity of CES2 was significantly inhibited by deoxyschizandrin and schisanhenol (P<0.01), with IC50 values of 8.06 μmol · L- 1 and 8.91 μmol · L- 1, respectively. The other six lignans compounds exhibited mild inhibitory effect on CES2. HDI risk prediction of deoxyschizandrin or schisanhenol indicated that exposure of CES2-metabolizing drugs might increase 11.24 and 0.40 times, respectively. CONCLUSION Deoxyschizandrin and schisanhenol exhibit strong inhibitory effects against CES2 in vitro so that potential HDI risks should be taken into account during administration of drugs containing Fructus Schisandrae chinensis.

Objective To determine the effects of individual antibiotic and immunosuppressive regime on postoperative infection in liver transplant recipients. Method There were 31 cases of liver transplantation from March 2001 to May 2005. The recipients received individual antibiotic and immunosuppressive regime based on the drug susceptibility testing and monitoring of blood drug concentration. The incidence and pattern of infection and the mortality in these recipients were analyzed retrospectively. Results There were 15 episodes of infection during recipients' staying in hospital. The common etiologies were Enterobacter cloacae, pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, and Staph. epidermidis. According to the drug sensitive test, targocid/tienam and tazocin were mostly used in antibiotic regime for treatment of postoperative infection. With monitoring of blood concentration, appropriate application of immunosuppressive agents decreased the incidence of infection from 86.7% before 2003 to 48.4% after 2003 (P0.05). Conclusion Individual application of antibiotic and immunosuppressive regime leads to the suppression of infections and other complications in liver transplant recipients.

Objective To investigate and evaluate the iodine nutritional status of school-age children in Yi county of Heibei Province,and to provide scientific basis for the development of control measures to iodine deficiency disorders.Methods Retrospectinely analyzed school-age children urinary iodine monitoring results of Yi County of Hebei Province from 1998 to 2011.One township was selected randomly in each of the five directions (east,west,south,north and center) from 1998 to 2011.One elementary school was randomly chosen in each of the five townships.And at least 20 urine samples of 8-10 years old children were randomly collected in each school selected.Urinary iodine contents were determined through arsenic cerium catalytic spectrophotometric method.Urinary iodine determination standard according to The Standard of Iodine Deficiency Disorders Elinination (GB 16006-2008) and The Iodine Deficiency Disorders Elinination Guide.Results A total of 1725 children urinary samples were collected from 1998 to 2011,urinary median was 243.26 μg/L,each of the median urinary iodine was higher than 100 μg/L.The ratio of urinary iodine less than 100 μg/L was ＜ 50％ over the years,and less than 50 μg/L was ＜ 20％.Overall,the highest value of urinary iodine stayed at approximately 200 μg/L,showing positively skewed distribution that was skewed to the right.Urinary iodine level was compared among different ages,gender and ethnicity,and the difference was not statistically significant(P ＞ 0.05).Conclusions In recent years,the iodine intake of school-age children of Yi County can meet the body needs,and the iodine nutrition is at an appropriate level.

Objective To evaluate the efficacy and safety of the unilateral and bilateral drainage in hilar malignant biliary obstruction with a meta?analysis of relevant studies. Methods A systematic electronic search with keywords “ biliary stent”, “hilar tumor” and “malignant biliary obstruction” was independently performed by two reviewers in major electronic databases of Pubmed, EMBASE, Cochrane Library and Web of Science. A meta?analysis was conducted using Revman 5?? 1 software. Results Six studies were included with a total number of 558 patients, of whom 307 patients underwent unilateral biliary drainage and 251 pa?tients bilateral drainage. There was no significant difference in early complications ( OR = 1?? 03,95% CI:0?? 58?1?? 81,P = 0?? 93), later complications (OR = 0?? 98,95%CI:0?? 46?2?? 07,P = 0?? 95), operation success rate (OR= 1?? 42,95%CI:0?? 76?2?? 66,P = 0?? 28),drainage efficacy or median survival time between the two groups. Compared with unilateral biliary drainage, bilateral biliary drainage had a longer time of stent patency (MD = - 29?? 12,95% CI:- 38?? 55?- 19?? 70,P< 0?? 001). Conclusion Both unilateral and bilateral biliary drainage are safe and effective for hilar malignant biliary obstruction, but more high quality clinical researches are needed.

Objective To explore the effects of vinblastine on abcb4 tumor resistance gene expression in early development zebrafish and lay an important foundation for multi-drug resistant antineoplastic screening in zebrafish model.Methods Zebrafish embryos of 0.5~1.5 hours post-fertilization were exposured to different concentrations of vinblastine, and then calculated the IC50 of vinblastine.Zebrafish embryos of 0.5~1.5 hours post-fertilization were treated with different concentrations of vinblastine and embryo culture medium respectively, and then observed zebrafish embryo development in 24~120 hours post-fertilization and recorded the number of death, hatch and malformation.Evaluating the impact of vinblastine on abcb4 gene expression in zebrafish with quantitative real-time PCR and whole-mount in situ hybridization by collecting zebrafish embryos exposed to different concentrationsof vinblastine.Results Vinblastine IC50 in zebrafish embryos was 3.08 μmol/L.The mRNA level of abcb4 gene in vinblastine treated embryos was significantly increased compared to blank control group.Moreover, abcb4 gene positive hybridization signals were found in the small intestine of zebrafish embryos after 120 hours post-fertilization and also found in the brain and heart of zebrafish embryos by the method of whole-mount in situ hybridization.Conclusions Vinblastine can significantly increase the expression level of abcb4 tumor resistancegene in early development zebrafish embryos, which indicates that zebrafish can be used as a tumor resistant drug screening model.

Objective To investigate clinical efficacy and safety of endoscopic multiband mucosec-tomy(EMBM)for esophageal submucosal tumors(SMTs).Methods Data of 51 patients with SMTs diag-nosed between Jan 2012 and Aug 2014 were retrospectively studied.Of the 51 patients,33 patients(34 le-sions)received EMBMand 18 patients received endoscopic submucosal resection(ESMR).The operation success rates,complete resection rates,procedure time,complications and the follow-up of group EMBMand group ESMR were compared.Results All of 51 cases had successful endoscopic treatment with no perfora-tion,infection or obvious bleeding.Follow-up showed no recurrence after operation.Compared with group ESMR,group EMBM had higher complete resection rate [97.1% (33 /34)VS 61.1% (11 /18 ),P =0.010],shorter operation time[(6.3 ±1.8)min VS (21.4 ±3.8)min,P =0.001]and lower complication rate[6.1%(2 /33)VS 27.8%(5 /18),P =0.024].Conclusion EMBM is simple,safe and effective for treating SMTs originating from muscularis mucosa or submucosa which are less than 2.0 cm in diameter.

Objective To evaluate the reliability of gas sampling from the distal end of the tracheal tube for partial pressure of end-tidal CO2 (PETCO2) monitoring in neonates.Methods A total of 50 fullterm neonates,scheduled for elective abdominal surgery under general anesthesia,aged 1-28 days,weighing 2.55-4.00 kg,of ASA physical status Ⅰ or Ⅱ,were randomly divided into 2 groups (n =25 each) using a random number table:gas samples collected from proximal end of tracheal tube group (group P) and gas samples collected from distal end of tracheal tube group (group D).Epidural catheters of 1 mm in external diameter were used.One end of the catheter was connected to a tube for carbon dioxide sampling,and the other end was inserted into the endotracheal tube and advanced toward the distal hole of the tube.At 15 min of mechanical ventilation,blood samples were collected from the radial artery for record of PETCO2 and for blood gas analysis.Consistency test was performed between PETCO2 and partial pressure of arterial CO2 (PaCO2).Results PET CO2 was significantly lower than PaCO2 in the two groups.There was no significant difference in PaCO2between the two groups.PETCO2 was significantly higher in group D than in group P.Kappa was significantly higher in group D than in group P.Conclusion Gas sampling from the distal end of the tracheal tube is more reliable than gas sampling from the proximal end in monitoring PETCO2 in the neonates.

OBJECTIVE: To study synergistic effect of Vitamin C (VitC) combined with arsenic trioxide (As2 O3)-on human laryngocarcinoma Hep-2 cell line apoptosis. METHOD: Human laryngocarcinoma cell line Hep-2 was cultured in vitro, and incubated with As2 O3 or jointly with VitC. The inhibition ability of Hep-2 cells was determined by methyl thiazolyl tetrazolium (MTT) assay, while the apoptosis was mensurated by the flow cytometry with Annexin-V/PI. RESULT: Compared with the use of As2 O3 separately, the combination of As2 O3 and VitC could increase the inhibition ability and the apoptosis rate of Hep-2 cells markedly (P < 0.05). CONCLUSION Combination of As2 O3 with VitC could markedly increase arsenic trioxide (As2 O3)-induced apoptosis of Hep-2 cells.
Apoptosis ; drug effects ; Arsenic Trioxide ; Arsenicals ; pharmacology ; Ascorbic Acid ; pharmacology ; Cell Line, Tumor ; Drug Synergism ; Humans ; Oxides ; pharmacology

Objective: To screen the best genetic engineering bacterium for the production of peptide antibiotic hPAB-? and evaluate its fermentation level in bottle. Methods:After analysis of the interest fusion protein expression levels of 8 recombinant bacteria containing 1-8 copies of human peptide antibiotic hPAB-? expressing plasmid respectively,2-5 copies expressing bacteria were chosen for the further study of their bacteria yield,expression forms of the target protein, dissolution of the inclusion bodies and the efficiency of fusion protein purification by affinity chromatography, then the best engineering bacterium with the certain copies of interest peptide expressing plasmid was screened out and its optimal fermentation parameters in bottle were also studied. Results:The recombinant bacterium transformed by 3 copies of interest peptide expressing plasmid was the best candidate for its bacteria yield (3.153 g/L) and fusion protein expression level (27.7%) were the highest among 1-8 copies candidates. The inclusion bodies of 3 copies target fusion protein could be easily dissolved by 8 mol/L urea and captured by Ni-NTA column. The elution of the fusion protein could be directly cleaved to monomer by adding 2 mol/L hydroxylamine, adjusting pH to 9.0 and incubating at 45℃ for 2 h. The optimal fermentation conditions of the selected recombinant bacteria were: culture the organisms with modified M9-CAA media at 37℃ and 160 r/min to (A 600 )≈2.5, then add IPTG to the final concentration 100 ?mol/L to induce the expression of target fusion protein for 5 h. Conclusion:The engineering bacterium containing 3 copies interest peptide recombinant expressing plasmid is the best candidate for the production of peptide antibiotic hPAB-?,and its fermentation parameters are confirmed.