Objective Enzyme triggered multi unit colon targeting mini tablet of indomethacin were prepared,in order to improve the target treatment of colon disease.Methods Different proportion of enteric layer and chitosan layer were screened to optimize the prescription.The colon targeting mini tablets were prepared by direct compression method.The drug release properties were investigated in different release medium.Rats were used to investigate the distribution of tissue in vivo.The Beagle dogs were used to study the pharmacokinetics and bioavailability.Results The optimum chitosan layer prescription:coating liquid concentration was 2％,plasticizer three citric acid ethyl ester (TEC) was 15％,an anti sticking agent amount of talc was 30％,coating weight was 5％;Enteric layer prescription:coating liquid solid content was 20％,plasticizer content of TEC was 5％,anti sticking agent talc powder dosage was 40％,coating weight was 3％.The chitosan multi unit colon targeted preparation seldom released in rat stomach and small intestine,released slowly in colon.The pharmacokinetics parameters in Beagle dogs were:Cmax =(3.25 + 0.672) mg·L-1,tmax =(2.00 + 0.014) h,AUC(0.∞) =(10.2 +0.871) mg·L-1 ·h,MRT (0-∞) =(2.82 + 0.180) h,CL =(2.46 + 0.202) L·h-1 ·kg-1.The release time of mini tablets for colon targeted was significantly prolonged and preserved stable blood concentration.Conclusion The enzyme triggered multi unit colon targeting mini tablet of indomethacin showed good target to colon and sustained release effect,providing an important reference for the development of preparation of indomethacin for the treatment of colon disease.

Objective: To analyze the characteristics, treatment and prognosis in patients with essential thrombocythemia (ET) combining myocardial infarction (MI).
Methods: A total of 10 patients with ET combining MI treated in our hospital from 2003-01 to 2015-07 were retrospectively studied. The basic clinical information with major admission complaints, previous history and peripheral platelet counts were recorded;echocardiograph, coronary angiography (CAG), application of anti-platelet drugs and platelet reductive therapy with the prognosis were recorded in all patients.
Results: There were 6 male and 4 female with a mean age of (55.3 ± 9.7) years, 7 patients with AMI and 3 with old MI. The platelet counts at admission were (500-599) × 109/L in 3 patients, (600-699) × 109/L in 1 patient, (700-799) × 109/L in 3 patients, (800-899) × 109/L in 1 patients, (900-999) × 109/L in 1 patient and more than 1000 × 109/L in 1 patient. Echocardiograph indicated that 5 patient had LVEF≤50%and 5 had LVEF>50%. CAG revealed that there were 9 cases with left anterior descending involved, 2 with circumlfex involved and 5 with right coronary involved. All patients received dual anti-platelet drugs before operation, 4 had hydroxyurea for (20-30) days before operation and no post-operative cardiovascular events occurred;6 patients without hydroxyurea medication and 1 of them was re-hospitalized for angina pectoris and 2 had progressed coronary lesions.
Conclusion: Application of platelet reductive therapy at before and after interventional treatment may improve the prognosis in patients with ET combining MI.

Objective To analyze the investigation data of the national schistosomiasis surveillance sites in 2015,so as to provide scientific evidences for schistosomiasis control,elimination and surveillance. Methods According to National Schisto-somiasis Surveillance Programme(version 2014),457 surveillance sites were selected,and the investigation data in residents, floating population,domestic animals and Oncomelania hupensis snails were collected and analyzed from four types of endemic counties. Results A total of 4468 seropositive cases were detected from 133350 residents,among which 4457 residents with seropositive results received the etiological tests,and 71 of them were identified with positive results. Most of them were fisher-men and farmers in the middle and old-aged group. The schistosomiasis infection rate was 0.05% in local population. Totally 977 seropositive cases were examined from 85047 migrant individuals,and 16 positive cases were found out from 966 individuals who took etiological tests,which showed the schistosomiasis infection rate was 0.02% in floating population. Imported cases were found among floating people in four provinces,namely Zhejiang,Hunan,Hubei and Anhui provinces. No acute schistoso-miasis cases were reported. A total of 13406 head of cattle received examinations and only 5 were determined as stool positives. The cattle infection rate was 0.04%. The snail survey covered an area of 22295.13 hm2 and snails were found in an area of 7426.63 hm2,including 3.47 hm2 newly detected area with snails. No schistosome-infected snails were found. Conclusions Based on the collected data from 457 national schistosomiasis surveillance sites of China,the Schistosoma japonicum infection rate is 0.05% in local population which maintains a stably descending trend. In floating population,there are imported schistosome-in-fected persons. Cattle are still a vulnerable species infected with schistosome. Although no infected snails are found,snails are widely distributed in endemic areas. Some provinces detect areas with snails for the first time or the reproduction of snails. The staff in endemic provinces should carry out the surveillance work according to National Schistosomiasis Surveillance Programme (version2014)to improve the surveillance system,and enhance the sensibility and effectiveness of surveillance work.

Objective To investigate the inhibitory effect of carbon-coated iron nanoparticles carrying cisplatin on the growth of NCI-H446 lung cancer cells and expressions of Caspase 3 and Survivin mRNA.Methods NCI-H446 lung cancer cells were treated with iron-carbon nanoparticles and/or cisplatin.The cell viability was detected by MTT method,and the mRNA expressions of Caspase 3 and Survivin were measured with RT-PCR.Results Cisplatin could inhibit the growth of NCI-H446 lung cancer cells,and the inhibitory effect was stronger when it was combined with the iron-carbon nanoparticles.The cells had apoptosis.The mRNA expression of Caspase 3 of NCI-H446 lung cancer cells was remarkably enhanced after treatment with iron-carbon nanoparticles combined with cisplatin,while the mRNA expression of Survivin was notably weakened (P＜0.05).Conclusion Carbon-coated iron nanoparticles carrying cisplatin could significantly increase the chemotherapy sensitivity of cisplatin on NCI-H446 lung cancer cells and enhance the therapeutic efficacy of chemotherapy drugs.

AIMTo investigate the preparation of diclofenac sodium pulsatile release pellets (DS-PRP), the release in vitro and the pharmacokinetics of the drug.

METHODSDiclofenac sodium (DS) core pellets prepared by extrusion-spheronization technology were coated in a mini-fluidized bed spray coater with swelling material as the inner coating swelling layer and ethylcellulose aqueous dispersion as the outer coating controlled layer. The effects of formulation and medium on pulsatile release of DS were investigated under release rate test. Pharmacokinetic and bioavailability study in eight human subjects were performed by HPLC method.

RESULTSThe delayed-release time and release rate of DS from DS-PRP were influenced obviously by the swelling material, the concentration of SDS in medium, the coating level of the inner swelling layer and the outer controlled layer. In vitro, the delayed-release time T0.1 was 3.1 h, and the pulsed-release time T0.1-0.2 was 1.2 h. In vivo, the delayed-release time Tlag was 2.8 h, and the bioavailability was (91 +/- 12)%.

CONCLUSIONThe release of drug from DS-PRP was shown to be in pulsed way both in vitro and in vivo.

Adult ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; pharmacokinetics ; Biological Availability ; Cellulose ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; Diclofenac ; administration & dosage ; pharmacokinetics ; Humans ; Hydrogen-Ion Concentration ; Male ; Random Allocation ; Sodium Dodecyl Sulfate ; chemistry

Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons underlying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.
Ebolavirus ; metabolism ; Flow Cytometry ; Glycoproteins ; metabolism ; Hepatitis A Virus Cellular Receptor 1 ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Membrane Glycoproteins ; metabolism ; Membrane Proteins ; metabolism ; Protein Binding ; Receptors, Virus ; metabolism ; Surface Plasmon Resonance ; Viral Envelope Proteins ; metabolism ; Viral Proteins ; metabolism

Adiponectin is an adipocyte-derived secretory protein. It was found to be associated with insulin resistance, inflammation and arteriosclerosis. To further study the biological function and expression of adiponection in vivo, adipoenctin gene knock-out and LacZ gene knock-in mouse model was constructed. Gene targeting strategy was designed to replace part of exon 2 and exon 3 of adiponectin gene with full length LacZ gene in frame with remaining upstream ATG and signal peptide sequence of exon 2. The targeting vector (Adipo-LacZ-XpPNT) was constructed and verified by restriction enzyme digestion and sequencing. CJ7 ES cells were transfected with targeting vector linearized by NotⅠ digestion, selected in the medium containing both G418 and ganciclovoir. Resistant clones were screened by PCR and further confirmed by Southern blot for correct homologous recombinants. Chimera mice were obtained by routing microinjection of homologous recombined ES cells into blastocysts. After mating, mice heterozygous and further homozygous for adiponectin knockout and LacZ gene knock-in were established. Expression of both endogenous adiponectin and exogenous LacZ gene in mouse tissues and sera were detected by RT-PCR, Northern-blot, Western blot and ELISA. The results show that adiponectin was disrupted at both mRNA and protein levels. LacZ gene is expressed exclusively in adipose tissue of mutant mice. Its expression profile is identical to endogenous adiponection. Unexpectedly, LacZ activity could not be detected in both adipose tissue and serum although LacZ protein can be detected in adipose tissue but not in serum of mutant mice. In conclusion, mice homozygous for adiponectin knockout and LacZ gene knock-in have been successfully constructed. Mutant mice display LacZ expression profile identical to endogenous adiponectin albeit neither LacZ activity nor protein can be detected in serum of mutant mice.

Objective: To analyze the current status of allergic adverse reactions caused by non-ionic iodinated contrast media in patients with coronary angiography (CAG).
Methods: A total of 1 225 patients who received non-ionic iodinated contrast media for CAG in our hospital from 2011-02 to 2013-09 were retrospectively studied. There were 52 patients suffered from allergic adverse reactions including 47 (90.38%) male and 5 (9.62%) female. The allergic reaction to iodixanol, iohexol, iopamidol and iopromide were in 34, 3, 3 and 12 patients respectively. The clinical symptoms and outcomes of allergic reaction in 4 iodinated contrast media were analyzed.
Results: There were 40/52 (76.92%) patients with mild allergic reaction, 11(21.15%) with moderate and 1 (1.92%) with severe reaction. 13 patients had the reaction within 1 hour of contrast media injection and 39 had the reaction between 1 hour to 3 days of contrast media injection. There 34 patients were cured by symptomatic and anti-allergic treatment, 1 patient was rescued from allergic shock and no death occurred.
Conclusion: Application of non-ionic iodinated contrast media in CAG is safe, while closely observe the allergic adverse reaction with the in time and symptomatic treatment is very important in clinical practice.

OBJECTIVETo observe the effect of curcumin on the expression of PI3K (phosphatidylinositol-3-kinase, PI3K) and p-P3 K (phosphated phosphatidylinositol-3-kinase, p-PI3K) in the hippocampus of Alzheimer's disease (AD) model (APP/PS1 double transgenic) mice.

METHODA total of 60 three-month-old APP/PS1 double transgenic mice were randomly divided into model group, rosiglitazone group(10 mg . kg-1 . d-1) and curcumin large(400 mg . kg-1 . d-1), medium(200 mg- kg-1 . d-1) and small(100 mg . kg-1 . d-1) dose group. Twelve C57BL/6J mice in the same age and genetic background as APP/PS1 double transgenic mice were used as normal control group. All the 6 groups of mice were intragastrically administered for 3 months. After 3 months, the expression of PI3K and p-PI3K were detected by immunohistochemistry and Western blot.

RESULTThe expression of PI3K and p-PI3K positive cells in hippocampus CA1 region significantly decreased in model group compared with normal control group (P < 0. 05) , while compared with model group, PI3K and p-PI3K positive cells of all the curcumin intervention groups increased to varying degrees in hippocampus CA1 region,especially the middle dose group(P <0. 01). Besides,Western blot results of the curcumin high dose group were also increased obviously (P <0. 05).

CONCLUSIONCurcumin can recover the decreased PI3K and p-PI3K and improve the insulin-signaling transmission in the hippocampus of APP/PS1 double transgenic mice. The mechanism of curcumin maybe by regulating the insulin signal transduction to treat AD.

Alzheimer Disease ; drug therapy ; genetics ; metabolism ; Animals ; Curcumin ; pharmacology ; therapeutic use ; Disease Models, Animal ; Hippocampus ; drug effects ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Thiazolidinediones ; pharmacology ; therapeutic use

Objective To investigate the feasibility and effect of visualization teaching method using HC visual laryngoscope for the standardized training of endotracheal intubation in emergency department.Methods Forty standard-trainee doctors were divided into two groups randomly.20 standard-trainee doctors in team N were taught using the conventional teaching method of emergency medicine for the standardized training of endotracheal intubation,and the other 20 standard-trainee doctors in team HC were taught by visualization teaching method using HC visual laryngoscope.After 1 month training,comparisons of the success rate of tracheal intubation in airway management simulator,the time consumed for intubation and the number of attempt on successful intubation cases,and the satisfaction score with the teaching mode scored by standard-trainee doctors between the two groups were done.Results The one-attempt success rate and the success rate of tracheal intubation in airway management simulator by the standard-trainee doctors in group HC were significantly higher than those in group N (40％ vs.10％,85％ vs.55％),while the number of attempt and the time consumed for successful intubation were significantly less than those in group N[(1.65±0.61) vs.(2.27±0.66),(79.00±8.35) s vs.(89.36±12.03) s).The satisfaction score with this teaching mode and teaching effect of standard-trainee doctors in group HC were significantly higher than those in group N (8.10±0.74 vs.6.55±1.05,8.15±0.80 vs.6.85±0.91).Conclusions The visualization teaching method with application of HC visual laryngoscope for standardized training of endotracheal intubation in emergency department could improve the success rate and efficiency of tracheal intubation in airway management simulator for standard-trainee doctors,and this teaching method may be better than the conventional teaching method on teaching mode presenting some feasibility.