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.

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

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.

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

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

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

In order to obtain nucleotides aptamers bind to IgE, 80 bp nucleotides single-stranded DNA library containing 40 random nucleotides was designed and synthesized. Oligonucleotides that bind to human Cepsilon3-Cepsilon4 protein were isolated from ssDNA pools by the systematic evolution of ligands by exponential enrichment (SELEX) method using nitrocellulose filters as screening medium. Through the optimization of critical PCR and asymmetric PCR parameters including annealing temperature, cycles, and molar ratios of target protein and ssDNA etc, a suitable screening system was established. The aptamers of Cepsilon3-Cepsilon4 protein with high affinity and high specificity were identified by ELISA with biotin-streptavidin-horseradish peroxidase system, and its primary sequence and second structure were analyzed by DNAMAN package and DNA folding sever after being cloned and sequenced. Moreover, target protein was bound to one aptamer and another aptamer modified with biotion together forming a sandwich-like complex, which was captured in microwell to detect IgE concentration using the optimal combination in the sandwich method named enzyme-linked aptamers sorption assay (ELASA). The method could be used for the quantitative detection of human IgE, and whose sensitivity reached to 120 ng x mL(-1).
Aptamers, Nucleotide ; chemistry ; genetics ; isolation & purification ; Base Sequence ; DNA, Single-Stranded ; chemistry ; Humans ; Immunoglobulin epsilon-Chains ; chemistry ; genetics ; Oligonucleotides ; chemistry ; SELEX Aptamer Technique ; methods ; Sensitivity and Specificity

OBJECTIVETo investigate the variance and drug resistance of pathogenic bacteria isolated from children with infectious diseases seen between 2001 and 2006 in Chengdu area.

METHODSA total of 2888 pathogenic bacterial strains isolated from children in Chengdu Children's Hospital from 2001 to 2006 were analyzed. Tests were performed according to the guidelines of National Committee for Clinical Laboratory Standards (NCCLS) of the United States.

RESULT(1) Of the 2888 strains, 1845 (63.9%) were Gram negative bacteria. The main pathogenic bacteria included Escherichia coli (Ec, 718 strain, 24.9%), Hemophilus (H, 476 strain, 16.5%), Streptococcus pneumoniae (Sp, 412 strain, 14.3%), Klebsiella pneumoniae (Kp, 369 strain, 12.8%), Staphylococcus aureus (Sa, 353 strain, 12.2%), Staphylococcus epidermidis (Se, 278 strain, 9.6%), Pseudomonas aeruginosa (Pa, 146 strain, 5.1%) and other non-zymocyte (Onz, 136 strain, 4.7%). (2) The common pathogens found in blood specimen were 158 strain, which included Se (78 strain, 49.4%), Ec (23 strain, 14.6%), Kp (17 strain, 10.8%), Sa (14 strain, 8.9%), Onz (14 strain, 8.9%), Sp (7 strain, 4.4%) and Pa (5 strain, 3.2%). (3) The number of common pathogens isolated from patients with lower respiratory tract infection was 2018, including Ec (441 strains, 21.9%), H (430 strains, 21.3%), Sp (368 strains, 18.2%), Kp (253 strains, 12.5%), Sa (207 strains, 10.3%), Se (149 strains, 7.3%), Pa (97 strains, 4.8%) and Onz (73 strains, 3.6%). (4) There were 120 strains of common pathogens isolated from urine specimens, including Ec (78 strains, 65%), Kp (25 strains, 20.8%), Onz (7 strains, 5.8%), Pa (5 strains, 4.2%) and Se (5 strains, 4.2%). (5) There were 497 strains of common pathogens found in pus specimens, including Ec 167 strains, (33.6%), Sa (126 strains, 25.4%), Se (46 strains, 9.3%), H (44 strains, 8.9%), Onz (37 stains, 7.4%), Kp (31 strains, 6.2%), Sp (26 strains, 5.2%) and Pa (20 strain, 4.0%). The trend of drug resistance of pathogenic bacteria to antibiotics deteriorated. The proportion of methicillin-resistant Staphylococcus aureus (MRSA) was 6.7% and the methicillin-resistant coagulase-negative Staphylococci (MRCNS) rate was 20% in 2001 - 2003. The total proportion of extended-spectrum beta-lactamase stains (ESBL(S)) in Ec and Kp was 21.8%, and the rate of beta-lactamase production stains of Hemophilus influenzae (Hi) was 19.4% in 2001 - 2003.The proportion of MRSA was 17.2% and the MRCNS rate was 70.2%, the total proportion of ESBL(S) in Ec and Kp was 43.8%, and the rate of beta-lactamase producing stains of Hi was 39.7% in 2004 - 2006.

CONCLUSIONThe distribution of common pathogenic bacteria seen in Chengdu Children's Hospital has changed and the trend of drug resistance of pathogenic bacteria to antibiotics deteriorated in recent three years. Regionally monitoring the changes in pathogenic bacteria and the trend of drug resistance to antibiotics is paramount in guiding the pediatric clinical treatment.

Anti-Bacterial Agents ; pharmacology ; Bacterial Infections ; epidemiology ; microbiology ; Child ; China ; epidemiology ; Drug Resistance, Multiple, Bacterial ; drug effects ; Humans ; Microbial Sensitivity Tests

OBJECTIVETo summarize lessons learned from an outbreak of severe acute respiratory syndrome (SARS) in China during the spring of 2004.

METHODSData of SARS cases were officially reported by Beijing Municipal Center for Disease Control and Prevention (BCDC) and Anhui Provincial Center for Disease Control and Prevention (APCDC) and results of epidemiological investigations were collected and analyzed.

RESULTSThree generations of 11 cases of SARS were identified during the outbreak. Initial two cases were most likely to be infected in Diarrhea Virus Laboratory of National Institute of Virology, China Centers for Disease Control and Prevention and main mode of transmission was direct contact with SARS patients. Delay in detecting initial case resulted in spread of the illness at hospitals and communities with two generations of secondary cases.

CONCLUSIONSSARS outbreak in 2004 has yielded following lessons for public health globally. (1) Lab bio-safety programs should be made and should be strictly abided by. Studies in highly pathogenic viruses such as SARS coronavirus should be utmost cautious. (2) Management systems of occupational exposure to virus and disease surveillance need to be strengthened to take all risk factors into account so as to detect potential patients with infectious disease as early as possible.

China ; epidemiology ; Disease Outbreaks ; Female ; Humans ; Male ; Occupational Exposure ; prevention & control ; Occupational Health ; Retrospective Studies ; Severe Acute Respiratory Syndrome ; epidemiology ; prevention & control ; transmission