Aim To explore the effects of Shp2 on cig-arette smoke extract (CSE)-induced epithelial-mesen-chymal transition (EMT). Methods The effects of CSE on TGF-β1 levels in epithelial cells were meas-ured by Q-PCR and ELISA. Immunofluorescent stai-ning was used to assess the expressions of CSE-induced EMT-related markers. The activation of CSE-induced Shp2,Smad2 was investigated by Western blot. Re-sults CSE induced Shp2 phosphorylation in a concen-tration-dependent manner in A549 cells. PHPS1 inhib-ited the increase in mRNA and protein expression of TGF-β1 induced by CSE. PHPS1 regulated the expres-sions of CSE-induced EMT markers (down-regulation of E-cadherin,up-regulation expression of Vimentin and α-SMA). The inhibition of either Shp2 inhibitor or Shp2 siRNA decreased Smad2 phosphorylation induced by CSE. Conclusions CSE initiates EMT through the Shp2 / Smad2 signaling pathway,which is activated by CSE through TGF-β1 generation. It is suggested that Shp2 might be a possible new target for COPD and lung cancer therapy.

Animals ; Cell Line ; Hepatic Stellate Cells ; drug effects ; metabolism ; pathology ; Plasminogen Activator Inhibitor 1 ; biosynthesis ; Rats ; Transforming Growth Factor beta1 ; pharmacology

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

OBJECTIVETo analyze the effect of long-term exposure to paint or hair dye on chromosomal aberration of early embryos.

METHODSWe analyzed 2 cases of fetal or infantile chromosome aberration in which the parents experienced long-term exposure to paint and hair dye.

RESULTThe chromosomal mutations were detected in one 3-month-old infant and one 21-week-old fetus, and the karyotypes were 46,XX,del(2)(pter'q31) and 46,XX, t(4;12;15), respectively. Their parents worked with long-term exposure to paint and hair dye and developed such symptoms as dizziness, headache, and insomnia. The chromosomes of the parents remained normal, but the micronuclei of the lymphocytes and plasma lead level were increased with decreased WBC, platelet, and HGB.

CONCLUSIONLong exposure to paint or hair dye can cause poison and affect the normal growth of early embryos, leading eventually to gene and chromosomal mutation of the embryos.

Adult ; Chromosome Aberrations ; drug effects ; Female ; Hair Dyes ; toxicity ; Humans ; Infant ; Karyotyping ; Paint ; toxicity

The antisense approach and RT-PCR were used to study the effects of muscarinic receptors on the scores of morphine-withdrawal syndrome and the expression of NMDA receptor subtypes (NR(1A) and NR(2A)) mRNA in rat spinal cord and brainstem. The concentrations of glutamate in periaqueductal grey (PAG) of morphine-withdrawal rats were determined by capillary electrophoresis with laser-induced fluorescence detection. The data showed that the NR(1A) and NR(2A) mRNA levels were increased significantly in the spinal cord and brainstem 1 h after the injection of naloxone (4 mg/kg, i.p.) in morphine-dependent rats. Moreover, in morphine-dependent rats pretreated (i.p.) with scopolamine (0.5 mg/kg), or pirenzepine (10 mg/kg), MK801 (0.125 mg/kg), L-N-nitroarginine methylester (10 mg/kg) 30 min before naloxone injection, the NR(1A) and NR(2A) mRNA levels were significantly lower than those of 1 h morphine-withdrawal rats. Intrathecal injection of NR(1A) or M(2) receptor antisense oligonucleotides (A-oligo, 4 microg/per rat) 24 h prior to naloxone challenge could block the morphine withdrawal symptoms including wet dog shaking, irritability, salivation, diarrhea, chewing and weight loss. Meanwhile, in morphine-dependent rats the NR(1A) mRNA levels in the spinal cord and brainstem were down-regulated by intrathecal injection of M(2) receptor A-oligo. The glutamate concentrations in PAG microdialysis were increased to a maximal level 15 min after naloxone injection. The glutamate response was inhibited by pretreatment with M(2) receptor A-oligo but not by M(1) A-oligo. The results suggest that the expression of NMDA receptors and the release of glutamate in brainstem are involved in the processes of morphine withdrawal and that the NMDA receptor expression is possibly regulated by the muscarinic receptors during morphine withdrawal.
Animals ; Brain Stem ; metabolism ; Glutamic Acid ; metabolism ; Male ; Morphine ; adverse effects ; Periaqueductal Gray ; metabolism ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Muscarinic ; physiology ; Receptors, N-Methyl-D-Aspartate ; biosynthesis ; genetics ; Spinal Cord ; metabolism ; Substance Withdrawal Syndrome ; genetics ; metabolism

OBJECTIVEThe aim of this study was to develop a new perimembranous VSD occluder and to evaluate it.

METHODSThe shape of VSD occluder was designed as fabric frame "I" shape that comprised two types: symmetric and asymmetric. The safety, efficacy, feasibility and complication were tested in 22 animal models and in 58 VSD patients in clinical trial. The device were compared with Amplatzer occluder in this study.

RESULTSThe new perimembranous VSD occluder was passed the national material test. In animal study, artificial VSD were all occluded by using the new devices with no complication in follow up except one pig expresented wound infection. In clinical trial, all 58 VSD cases were healing with the new device. One patient suffered with atria-ventricular block 5 days after procedure and was free from AV block with medicine therapy. Compared with Amplatzer perimembranous VSD occluder, the new devices had lower frequency of residual shunt.

CONCLUSIONThe new perimembranous VSD occluder is a safe and effective perimembranous VSD interventional apparatus, and the effect of the new occluders seems not worse than that of the Amplatzer ones.

Adolescent ; Adult ; Animals ; Balloon Occlusion ; instrumentation ; methods ; Cardiac Catheterization ; methods ; Child ; Child, Preschool ; Equipment Design ; Female ; Heart Septal Defects, Ventricular ; surgery ; Humans ; Male ; Prosthesis Implantation ; Swine ; Treatment Outcome ; Young Adult

Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Female ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; epidemiology ; virology ; Male ; Middle Aged

OBJECTIVEThis study aims to establish and evaluate the methodology of isolated rabbit eye (IRE) test.

METHODSIRE test was performed according to modifications of the in vitro toxicology (INVITTOX) Protocol No.85: Rabbit enucleated eye test by European Centre for the Validation of Alternative Methods (ECVAM), and then 26 chemicals and 26 cosmetic products were tested in both in vitro IRE and in vivo Draize tests. A statistical analysis was conducted to determine the relevance of the IRE test to the data generated in the Draize test.

RESULTSIRE test was established successfully in our laboratory. It was shown that ranking correlation and class concordance were fairly well between the IRE test and the Draize test for 26 reference chemicals (Fisher's Exact Test χ(2)=51.314, P<0.001; McNemar P=0.261; Gamma=0.960, P<0.001; Kappa=0.843, P<0.001) and 26 cosmetic products (Fisher's Exact Test χ(2)=15.522, P<0.001; McNemar P=0.311; Gamma=0.967, P<0.001; Kappa=0.611, P<0.001).

CONCLUSIONIRE test was established successfully for in vitro testing of eye irritation as an alternative to Draize test.

Animal Testing Alternatives ; Animals ; Cosmetics ; toxicity ; Eye ; drug effects ; Irritants ; toxicity ; Rabbits ; Toxicity Tests ; methods

OBJECTIVETo investigate the prevalence of chronic obstructive pulmonary disease (COPD) and its risk factors in population over 40 years old in northern part of Guangdong province.

METHODSUsing uniform scheme, procedures and questionnaire, a cluster-randomized-sampling survey for the population aged over 40 years in a rural area of Shaoguan in the northern part of Guangdong province was performed. Spirometry was performed for every participant, followed by a bronchodilatation test when bronchial obstruction was present.

RESULTSThere were 1468 cases with complete data from 1498 people aged >or= 40 years including 640 males, 828 females with an average age of 54.3 years old. The total prevalence of COPD was 12.0%. The prevalence of COPD in males was significantly higher than that in females (18.3% vs. 7.1%, P < 0.01). Only 80.7% of the patients with COPD presented one or more symptoms as cough, phlegm, or dyspnoea. Underdiagnosis of COPD would be quite serious. Only 26.1% of the cases was previously diagnosed to have chronic bronchitis, emphysema, or COPD. Smoking was an important risk factor to COPD and 78.4% of the patients with COPD were smokers. However, relation of biomass and COPD called for further investigation.

CONCLUSIONPrevalence of COPD was much higher than expected in the northern part of Guangdong while smoking was an most important risk factor of COPD. Lung function test seemed to be of great importance to COPD diagnosis, especially in the earlier period of COPD.

Adult ; China ; epidemiology ; Female ; Humans ; Male ; Mass Screening ; Middle Aged ; Prevalence ; Pulmonary Disease, Chronic Obstructive ; epidemiology ; Risk Factors ; Sex Factors ; Smoking ; adverse effects ; Surveys and Questionnaires

OBJECTIVETo investigate the expression of PDGF receptor-beta and its correlation with extracellular matrix in hepatic tissue during hepatic fibrosis.

METHODSThe model of hepatic fibrosis in rats was induced by carbon tetrachloride. PDGF receptor-beta subunit, collagen I, collagen III and a-SMA in hepatic tissues of these rats were examined using immunohistochemistry. The correlation between PDGF receptor-beta subunit and collagen I, III was analyzed using SAS software after the results of immunohistochemistry were semi-quantified.

RESULTSPDGF receptor-beta subunit and a-SMA were not detected in normal controls. Collagen I and III were distributed in the portal tracts and beneath the endothelia of the central veins and of the Disse spaces. Two weeks after CCl4 injection, the PDGF receptor-beta and a-SMA were detected, and the expression of collagen I and III increased. At the end of 4 and 6 weeks, the above four proteins were further increased. Two weeks after CCl4 injection, PDGF receptor-beta had no apparent correlation with collagen I and III. However, PDGF receptor-beta had a significant correlation with collagen I and III 2 weeks later, and the correlation coefficient was 0.74 and 0.60 respectively at 4 weeks, and 0.83 and 0.67 respectively at 6 weeks. PDGF receptor-beta had a significant correlation with a-SMA during the whole process of hepatic fibrosis and the correlation coefficient was 0.62, 0.69 and 0.81, respectively at the time of 2, 4 and 6 weeks after CCl4 injection.

CONCLUSIONThe PDGF receptor-beta was overexpressed during the process of hepatic fibrosis development, and it significantly correlated with collagen I and collagen III.

Animals ; Carbon Tetrachloride ; Carbon Tetrachloride Poisoning ; Collagen Type I ; biosynthesis ; genetics ; Collagen Type III ; biosynthesis ; genetics ; Extracellular Matrix ; metabolism ; Liver ; metabolism ; Liver Cirrhosis, Experimental ; chemically induced ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Receptor, Platelet-Derived Growth Factor beta ; biosynthesis ; genetics