Ebola virus, the cause of severe and fatal hemorrahagic fever in humans, belongs to filovirus family. This study was designed to establish a cell-based screening and evaluation system in the pharmacological study of antivirus compounds. Three reporter systems were established with recombinant pseudoviral luciferase of HIV core (pNL4-3.Luc.R(-)E(-)) packed with filovirus glycoprotein (EBOV-Zaire GP/HIV-luc, EBOV-Sudan GP/HIV-luc and Marburg GP/HIV-luc), which are required for virus entry of cells. The level of filovirus entry was determined by the expression of luciferase reporter gene in the infected cells. For screening of filovirus entry inhibitors, the vesicular stomatitis G packed pseudovirions (VSVG/HIV-luc) was used to determine the compound specificity. The results of known filovirus entry inhibitors demonstrated successful establishment of the new model systems, which would be useful in high throughput screening of anti-filovirus drugs in the future.
Antiviral Agents ; pharmacology ; Drug Evaluation, Preclinical ; methods ; Ebolavirus ; drug effects ; physiology ; Genes, Reporter ; Glycoproteins ; genetics ; Hemorrhagic Fever, Ebola ; Humans ; Luciferases ; Viral Proteins ; genetics ; Virus Internalization ; drug effects

OBJECTIVE:To promote the rational drug use in our hospital.METHODS:The in-patient and out-patient drug use in our hospital was monitored and analyzed.RESULTS:The income from pharmaceuticals accounted for 38% of the total income in our hospital and the drug use tend to be more rational after the practice of dynamic monitoring on drug use.CONCLUSION:Dynamic monitoring on drug use played a positive role on the rational use of drugs meanwhile it brings the proportion of drug consumption under effective control.

OBJECTIVE:To determine the dissolution of puerarin and 2,3,5,4'-tetrahydroxy-stibene-2-O-?-D-glycoside in Xinnaokang capsules.METHODS:The contents of puerarin and 2,3,5,4'-tetrahydroxy-stibene-2-O-?-D-glycoside were determined by HPLC and the dissolution rates of puerarin and 2,3,5,4'-tetrahydroxy-stibene-2-O-?-D-glycoside in Xinnaokang capsules were determined by basket-rolling method.RESUTLS:With water as releasing media,at a rotation rate of 100 r?min-1,the dissolution rate at 45 min was above 75% of the labeled amount.CONCLUSION:The method can be used for evaluation and control of the internal quality of Xinnaokang capsules.

9.0 mmol/L, and well controlled group if FPG0.05). However, in each group, the incidence rate of different algesic severity decreased with the increasing algesic severity. Conclusion EIP will occur in DM patients within a week after RCT. Well controlling of the blood glucose can reduce the incidence rate of EIP.

Background Scarring of the filtering bleb is a main cause of filtering surgical failure in glaucoma.It has been reposed that tetrandrine could suppress the proliferation of cultured human fibroblast of Tenons capsule in vitro and thus has the potential effect to prevent scarring after the filtering surgery. Objective Present study was to investigate the anti-cicatricial effect of tetrandrine drug delivery system(Tet DDS)during filtration surgery. Methods Filtration surgery was performed in bilateral eyes of 18 New Zealand white rabbits.The Tet DDS with 0.3 mg Tet,0.2 mg Tet or free-Tet were implanted subcunjunctially during the surgery.The filtering blebs were scored in 1 day,4,7,10,14 days after referring to the corneal thickness and bleb range under the slit-lamp biomicroscopy.The morphology of filtering bleb was assessed by in vivo confocal microscopy in 7 and 14 days after operation.The filtering bleb specimen was prepared in 7 and 14 days for the histopathological examination. Results The filtering bleb scores in Tet DDS implantation groups were significantly higher than those in free-Tet DDS group from 4 days through 14 days after trabeculectomy(P＜0.01),and the scores showed a considerably increase in 0.3 mg Tet DDS group compared with 0.2 mg Tet DDS group from 7 days through 14 days after trabeculectomy(P＜0.05).The filtering blebs of Tet DDS implantation groups were found with distinct subepithelial cystic spaces under the light microscopy and in vivo confocal microscopy on the 7th day and 14th day after surgery.Compared with free-Tet DDS group,the numbers of subepithelial mierocysts were much more(P＜0.01)and the area of microcysts was larger(P＜0.01)in Tet DDS group.The filtering tissue presented with more subepithelial microcysts and larger microcysts range in 0.3 mg Tet DDS group than 0.2 mg Tet DDS group in 7 and 14 days after operation(P＜0.05).The inflammatory cell infiltration wag milder in 0.3 mg Tet DDS group in comparison with 0.2 mg Tet DDS group and free-Ted DDS group.Conclusion Tet DDS has strong inhibitory effects on inflammatory cells activity and fibroblagt activity the early stage after filtering surgery and therefore improve the surgery success rate.

This study aimed to investigate the drug susceptibility of wild-type and mutant avian influenza A (H7N9) virus neuraminidase (NA) to oseltamivir and zanamivir. Codon optimized DNA of H7N9 (A/ Hangzhou/1/2013) NA was synthesized and constructed into the pcDNA3.1/His vector (NA(H7N9-WT)). Mutant NA(H7N9-H274Y) and NA(H7N9-R292K) plasmids were constructed by directed mutagenesis PCR using NA(H7N9-WT) plasmid as the template followed by sequencing. NA plasmids were transfected into 293T cells and cell lysates containing NAs were collected 48 h post-transfection. Wild-type and mutant NAs were analyzed by Western blotting and their activities were tested by the 4-MUNANA-based assay. All three NAs were expressed and enzymatic activities were confirmed. The effects of oseltamivir and zanamivir on all three NAs were then tested. It showed that the half maximal inhibitory concentrations (IC50s) of oseltamivir carboxylate on NA(H7N9-WT), NA(H7N9-H274Y) and NA(H7N9-R292K) were 1.6 nM, 15.1 nM, and > 1 000 nM with fold changes of 9 and > 625, respectively. The IC50 values of zanamivir on NA(H7N9-WT), NA(H7N9-H274Y), and NA(H7N9-R292K) were 1.1 nM, 1.4 nM, and 38.0 nM with fold changes of 1.3 and 34, respectively. These results indicated that oseltamivir and zanamivir could significantly inhibit NA(H7N9-WT). NA(H7N9-R292K) showed high-level resistance to both drugs (34-fold and 625-fold) and NA(H7N9-H274Y) was sensitive to both (1.3-fold and 9-fold). These results indicated that both oseltamivir and zanamivir could be used for patients infected with the H7N9 virus. However, when patients carried the H7N9 virus with a NA R292K mutation, other medications would be preferred over oseltamivir or zanamivir.
Antiviral Agents ; pharmacology ; Humans ; Influenza A Virus, H7N9 Subtype ; drug effects ; enzymology ; genetics ; Influenza, Human ; virology ; Microbial Sensitivity Tests ; Mutation ; Neuraminidase ; antagonists & inhibitors ; genetics ; metabolism ; Oseltamivir ; pharmacology ; Viral Proteins ; antagonists & inhibitors ; genetics ; metabolism ; Zanamivir ; pharmacology

Biomedical Research ; Dental Research ; Humans ; Taste ; Taste Buds ; cytology

Objective To evaluate the efficacy of hydromorphone for patient-controlled intravenous analgesia (PCIA) after hip replacement in elderly patients.Methods Seventy patients, aged 65-75 yr, weighing 40-70 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , undergoing elective unilateral hip replacement, were randomly divided into either analgesia with hydromorphone group (group H, n =35) or analgesia with fentanyl group (group F, n=35).After a loading dose of 20 μg/kg of hydromorphone was injected at the beginning of skin closure, a PCA pump was connected, and the PCIA solution contained hydromorphone 0.25 mg/kg and tropisetron 10 mg in 120 ml of normal saline in group H.After a loading dose of 1 μg/kg of hydromorphone was injected at the beginning of skin closure, a PCA pump was connected, and the PCIA solution contained fentanyl 25 μg/kg and tropisetron 10 mg in 120 ml of normal saline in group F.The PCA pump was set up with a 0.5 ml bolus dose, a 15 min lockout interval and the background infusion at a rate of 2 ml/h in both groups.Tramadol 0.5 mg/kg was injects intravenously as rescue analgesic, and visual analogue scale score was maintained ≤ 3.The Ramsay sedation score,the number of attempts and the number of tramadol administration were recorded at 24 and 48 h after operation.The adverse effects within 48 h after operation and patient's satisfaction with analgesia were recorded.Results There was no significant difference in the Ramsay sedation score, the number of attempts and the number of Tramadol administration between H and F groups.Compared with group F, the incidence of adverse effects such as postoperative nausea, vomiting, respiratory depression, drowsiness, urinary retention, was significantly decreased, and the level of satisfaction with analgesia was increased in group H.Conclusion Hydromorphone provides accurate efficacy for PCIA after hip replacement in elderly patients, with fewer adverse effects and higher level of patient' s satisfaction.

Objective To investigate the effect of hydromorphone postconditioning on ischemiareperfusion (I/R) injury in isolated rat hearts and the role of mitochondial permeability transition pore (mPTP).Methods Male Sprague-Dawley rats, aged 2-3 months, weighing 250-320 g, were used in the study.The rats were heparinized and anesthetized with intraperitoneal 10％ chloral hydrate 350 mg/kg.The hearts were excised, and perfused in a Langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 36.5-37.5 ℃.Forty isolated rat hearts were randomly divided into 4 groups (n=10 each)using a random number table: control group (group C), group I/R, hydromorphone postconditioning group (group H), and hydromorphone postconditioning + mPTP opener lonidamine group (group HL).Group C was continuously perfused with K-H solution for 120 min.Group I/R was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group I/R was perfused with K-H solution for another 30 min.Group H was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group H was perfused with K-H solution containing 0.3 μmol/L hydromorphone for 10 min, and then with K-H solution for 50 min.Group HL was perfused with K-H solution for 30 min, the perfusion was then suspended for 30 min, and group HL was perfused with K-H solution containing 0.3 μmol/L hydromorphone and 30 μmol/L lonidamine for 10 min, and then with K-H solution for 50 min.At 30 min of equilibration (T0), and 30 and 60 min of reperfusion (T2,3), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP) , ±dp/dtmax, heart rate (HR), and coronary flow (CF) were measured.The concentrations of lactic dehydrogenase (LDH), creatine kinase-MB (CK-MB) , and troponin-T (Tn-T) in the coronary effluent were determined at T0 and T3.The coronary effluent was collected at T0 and 15 min of reperfusion (T1),nicotinamide-adenine dinucleotide (NAD+) concentrations were measured using enzyme-linked immunosorbent assay to reflect the degree of mPTP opening.The myocardial infarct size was determined at T3 by TTC staining.Results Compared with group C, LVDP, HR, ±dp/dtmax and CF were significantly decreased, and LVEDP was increased at T2,3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were increased in group I/R (P＜0.05).Compared with I/R and HL groups, LVDP, ±dp/dt CF and HR were significantly increased, and LVEDP was decreased at T2,3, and the concentrations of LDH, CK-MB and Tn-T in the coronary effluent, myocardial infarct size at T3, and NAD+ concentrations in the coronary effluent at T1 were decreased in group H (P＜0.05).Conclusion Hydromorphone postconditioning can reduce myocardial I/R injury in isolated rat hearts, and the mechanism is related to inhibition of mPTP opening.

Objective To evaluate the significance of fiberoptic bronchoscopic brush cytology in the diagnosis and histological classification of lung carcinoma.Methods Data of 309 patients with lung carcinoma were retrospectively analyzed.Both bronchoscopic cytology and histology diagnosis were available.The positive rate of bronchoscopic cytology and tissue biopsy were calculated respectively.The classification accuracy of cytological diagnosis for lung carcinoma was evaluated.In tissue biopsy standard,evaluated the significance of bronchoscopic cytology in diagnosis and histological diagnosis.Results The positive rate of bronchoscopic cytology and tissue biopsy were 86.1％ (266/309) and 83.8％ (259/309),respectively.Bronchoscopic cytology combined with bronchial biopsy could obviously improve the positive rate to 94.2％ (291/309) in lung carcinoma diagnosis.Taking the tissue biopsy histological type as a standard,the cytotyping accuracy for brush method was 85.1％(74/87) in squamous carcinoma,82.4％(108/131) in adenocarcinoma and 100％(11/11) in small cell carcinoma for higher.However,the accuracy in diagnosing poorly differentiated carcinomas was only 12.2％ (5/ 41).Conclusion Fiberoptic bronchoscopic brush cytology plays an stable and important role in diagnosing lung carcinomas and histological type determination.However,it has limited use in diagnosing poorly differentiated carcinomas.