Animals ; Calmodulin ; metabolism ; Epimedium ; Flavonoids ; pharmacology ; Gene Expression ; Hypothalamo-Hypophyseal System ; drug effects ; metabolism ; Male ; Pituitary-Adrenal System ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley

AIMTo evaluate the in vitro/in vivo correlation for three kinds of self-designed sustained-release nitrendipine formulations using deconvolution method.

METHODSThe characteristics of in vivo release were calculated by deconvolution method using the data of plasma concentration of three kinds of self-designed sustained-release nitrendipine formulations in healthy dogs, in which the in vivo results of nitrendipine solution after oral administrated to dogs were used as weight function. It was the compared with characteristics of in vitro release to assess the in vitro/in vivo correlations.

RESULTSThe good correlations of in vitro/in vivo were shown in three kinds of self-designed sustained-release nitrendipine formulations using deconvolution method.

CONCLUSIONThe deconvolution method exhibited advantage in evaluation of in vitro/in vivo correlation for self-designed sustained-release nitrendipine formulations.

Administration, Oral ; Animals ; Delayed-Action Preparations ; Dogs ; Methylcellulose ; analogs & derivatives ; Microspheres ; Nitrendipine ; administration & dosage ; blood ; pharmacokinetics ; Powders ; Silicone Gels ; Technology, Pharmaceutical ; methods

OBJECTIVEX-linked inhibitor of apoptosis protein (XIAP) To gastrointestinal (GI) investigate the expression of XAF1 and heat-shock transcription factors 1 èHSF1éand their relationship in human gastrointestinal cancers.

METHODSImmunoblotting was used to analyze the expression of HSF1 and XAF1 in either gastric or colon cancer tissue and GI cancer cell line. Transient expression of the HSF1-containing vector in GI cell lines and RNA interference were used to up/down-regulae the expression of the HSF1, and the subsequent expression of XAF1 was measured.

RESULTSThe expression of HSF1 was higher in GI cancers than in normal tissues. The expression of XAF1 and HSF1 was negatively correlated in GI cancer cell lines. Stress stimuli up-regulated the expression of HSF1 while the alteration of XAF1 expression was negatively correlated with HSF1 expression.

CONCLUSIONThe high expression of HSF1 in GI cancers is associated with suppressed expression of XAF1, which can be one of the mechanisms for low-expression of XAF1 and insufficient apoptosis in GI cancers.

Animals ; Base Sequence ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; Gastrointestinal Neoplasms ; genetics ; metabolism ; pathology ; Gene Expression Regulation, Neoplastic ; Heat Shock Transcription Factors ; Humans ; Intracellular Signaling Peptides and Proteins ; Neoplasm Proteins ; genetics ; Oxidative Stress ; genetics ; Temperature ; Transcription Factors ; genetics

OBJECTIVETo investigate the expressions of X-linked inhibitor of apoptosis protein (XIAP)-associated factor-1 (XAFI) and heat-shock transcription factor 1 (HSF1) and their relationship in human gastrointestinal cancers.

METHODSImmunoblotting was used to analyze the expressions of HSF1 and XAF1 in gastric and colon cancer tissues and in gastrointestinal cancer cells. The gastrointestinal cancer cells were tranfected with a eukaryotic expression vector containing HSF1 gene fragment or subjected to RNA interference to induce up- or down-regulation of HSF1 expression, and the consequence changes in XAF1 expression in the cells was measured. XAF1 expression was also assayed in the cells after stress stimulation for HSF1 expression.

RESULTSThe expression of HSF1 was higher in gastrointestinal cancer tissues than in normal tissues. The expression of XAF1 and HSF1 was inversely correlated in the cancer cell lines, and stress stimuli of the cells up-regulated the expression of HSF1 but down-regulated XAF1 expression.

CONCLUSIONHSF1 expression is increased in gastrointestinal cancer tissues to result in suppressed expression of XAF1, which may be one of the reasons for the low expression of XAF1 in association with the defect of the apoptosis mechanisms in the cancer cells

Cell Line, Tumor ; Colonic Neoplasms ; genetics ; metabolism ; pathology ; DNA-Binding Proteins ; biosynthesis ; genetics ; Heat Shock Transcription Factors ; Humans ; Immunoblotting ; Intracellular Signaling Peptides and Proteins ; Neoplasm Proteins ; biosynthesis ; genetics ; RNA Interference ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Transcription Factors ; biosynthesis ; genetics ; Transfection

Objective To investigate the Gram-positive coccus resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Methods All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 1 974 pathogenic Gram-positive coccus from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,the prevalence of methicillin resistant Stapylococcus aureus(MRSA)and methicillin resistant Stapylococcus epidermidis(MRSE)were 36.4％and 79.9％respectively.No vancomycin insensitivity Staphylococcus was detected.Staphylococcus aureus were 100％susceptibility to linezolid and teicoplanin.Antibiotic resistance rate of Enterococcus faecalis and Enterococcus faecium to ampicillin were 3.1％and 92.9％.The detectation rate of vancomycin resistant Enterococcus(VRE)was 1.6％.Nonsusceptibility rate of Enterococcus faecalis to linezolid was 32.2％,two consecutive monitoring rises and nonsusceptibility rate of Enterococcus faecium(12.5％)was also significantly increased.The prevalence of penicillin non-susceptible Streptococcus pneumoniae(PNSSP)was 0.8％based on non-meningitis and parenteral administration criterion,decrease of nearly 30 percentage points from the previous surveillance.While for cases of oral penicillin,the rate was 71.8％,showing similar to last time.The results indicated that the number of strains with higher MIC value of penicillin(MIC ≥4 mg·L-1)decreased significantly.There were no significant differences of resistance rates of Stapylococcus aureus,Stapylococcus epidermidis,Enterococcus faecalis,Enterococcus faecium and Streptococcus pneumoniae among various groups such as different department,age,or specimen source.Conclusion VRE detection ratio stablized at a relatively low level.The number of Streptococcus pneumoniae with higher MIC value of penicillin decreased significantly compared with the previous monitoring.The increase of linezolidin-insensitive Enterococcus was noteworthy.

Objective To investigate the Gram-negative bacteria resistance in nationwide's tertiary hospitals and understand the trend of antimicrobial resistance.Method All the clinical isolates were collected from 19 hospitals and the minimal inhibitory concentrations(MICs)were tested using agar/broth dilution method recommended.Results A total of 4 066 pathogenic isolates from 19 tertiary hospitals in 19 cities nationwide over the period from July 2021 to June 2022 were studied.Based on the MIC results,Escherichia coli and Klebsiella pneumoniae showed extended spectrum β-lactamase(ESBLs)phenotype rates of 55.0％and 21.0％,respectively,ESBLs phenotype rate of Klebsiella pneumoniae keep going down.The ratios of carbapenems resistance Klebsiella pneumoniae increased by 5 percentage points compared with the previous monitoring.Carbapenems,moxalactam,sitafloxacin,β-lactam combination agents,fosfomycin trometamol,and amikacin displayed desirable antibacterial activity against Enterbacterales,susceptibal rates were above 75％.In addition,tigacycline,omacycline,colistin and fluoxefin maintained good antibacterial activity against their respective effective bacteria/species,and the bacterial sensitivity rates by more than 80％.Resistance rates of Pseudomonas aeruginosa and Acinetobacter baumannnii to imipenem were 26.3％and 72.1％and multidrug-resistant(MDR)detection rates were 41.1％and 77.3％,extensively drug-resistant(XDR)were 12.0％and 71.8％,respectively.Comparison of drug resistance rates from different wards,ages and specimen sources indicated that the proportion of resistance in Klebsiella pneumoniae and Acinetobacter baumannii isolated from intensive care unit(ICU)were significantly higher than non-ICU.Carbapenem resistance rates of Klebsiella pneumoniae isolated from ICU were more than 35％.Resistance rates of Haemophilus influenzae isolated in children to β-lactam,macrolide,clindamycin and ESBLs detection rate in Klebsiella pneumoniae isolated from children were more than those from adults and the old people,so bacterial resistance in children is an important problem in China.Conclusion ESBLs detection rate of Escherichia coli increased slightly after years of continuous decline.The proportion of carbapenem resistant Pseudomonas aeruginosa was stable,but the resistance rate of Klebsiella pneumoniae and Acinetobacter baumannii to carbapenems was still increased,which should be paid more attention.