OBJECTIVETo investigate the effect of hypoxia on the human pulmonary artery smooth muscle cells two pore domain potassium channels TASK-1 and the regulation of non-receptor tyrosine kinase c-Src in this process.

METHODSThe cultured human pulmonary artery smooth muscle cells (hPASMCs) were divided into: normal group, hypoxia 30 minute group, hypoxia 6 hours group and hypoxia 48 hour group, and hypoxia 48 hour + PP2 group, hypoxia 48 hour + PP3 group, hypoxia 48 hour + bpV group. Flow cytometry was used to analyze the cell cycle, RT-PCR and Western blot technique were carried out to detect the expression changes of TASK-1 mRNA and protein in different groups.

RESULTS(1) Cell Cycle Show: Compared with normal control group, with prolonged hypoxia, the percentages of hPASMCs in S phases of cell cycle were increased. While compared with hypoxia 48 hour group, the percentages of hypoxia 48 hour + PP2 group hPASMCs in S phases of cell cycle were decreased. The expression of TASK-1 mRNA on hPASMCs in acute hypoxia 6 hour group was increased, while the expression of TASK-1 protein on hPASMCs in the acute and chronic hypoxia group was decreased, and the expression of TASK-1 mRNA on hPASMCs in the chronic hypoxia group was decreased; After pre-incubation of a potent and selective inhibitor of the Src family of protein tyrosine kinases PP2, the expression of TASK-1 mRNA and protein in hypoxia 48 hour group was increased, however after pre-incubation of the inhibitor of the Src family of protein tyrosine phosphatase bpV, the expression of TASK-1 protein in hypoxia 48 hour group was decreased.

CONCLUSIONHypoxia promotes human pulmonary artery smooth muscle cell proliferation, and non-receptor tyrosine kinase c-Src may participate in the expression of two pore domain potassium channels TASK-1 regulated by hypoxia. Therefore, we hypothesized that TASK-1 channels and c-Src participatein the acute and chronic hypoxic human pulmonary vasoconstriction.

Cell Hypoxia ; Cell Proliferation ; Cells, Cultured ; Humans ; Myocytes, Smooth Muscle ; cytology ; Nerve Tissue Proteins ; metabolism ; Potassium Channels, Tandem Pore Domain ; metabolism ; Pulmonary Artery ; cytology ; RNA, Messenger ; Vasoconstriction ; src-Family Kinases ; metabolism

OBJECTIVETo study the protective effect of hyperoxia solution on acute lung injury caused by phosgene poisoning by observing the changes of PaO2 and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity in serum and Glutathione (GSH/GSSG) contents in lung tissues.

METHODSThe rabbits were divided into normal control group, hyperoxia solution (H0) and balance salt (BS) groups. Group HO and Group BS inhaled phosgene and the former was given intravenously hyperoxia solution (which was replaced by balance salt solution in Group BS). The content of MDA and the activity of SOD in serum were observed at different time points, the amount of GSH and GSSG in lung tissue were also measured.

RESULTS(1) The serum MDA contents increased and PaO2, SOD activity decreased significantly in Group HO and Group BS along with time increasing as compared with control group. The contents of GSH in lung tissue decreased in two groups compared with that in control group, however the contents of GSSG ascended instead. (2) At 3 and 8 h of the experiment, PaO2 of Group HO [(9.91 +/- 0.49), (9.15 +/- 0.46) mm Hg respectively] were significantly higher than those of Group BS [(9.03 +/- 0.76), (8.11 +/- 0.57) mm Hg respectively] (P < 0.01). The contents of MDA of Group HO (3.66 +/- 0.35), (5.31 +/- 0.15) micromol/L respectively] were lower than those of Group BS [(4.32 +/- 0.26), (7.4 +/- 0.33) micromol/L respectively] (P < 0.01). SOD activity in Group HO [(237.37 +/- 29.96), (208.10 +/- 18.80) NU/ml respectively] were higher than those of Group BS [(195.02 +/- 21.44), (144.87 +/- 21.26) NU/ml respectively] (P < 0.05 or P < 0.01). The content of GSSG lung tissue in Group HO (423.67 +/- 38.21) micromol/L were lower than those of Group BS (523.85 +/- 43.14) mol/L (P < 0.01). There were no significant differences in the content of GSH in lung tissues between Group HO and group BS.

CONCLUSIONHyperoxia solution can reduce acute lung injury of rabbits following phosgene poisoning.

Acute Lung Injury ; etiology ; metabolism ; pathology ; Animals ; Glutathione Peroxidase ; metabolism ; Hyperoxia ; Lung ; drug effects ; metabolism ; pathology ; Malondialdehyde ; analysis ; Oxygen ; administration & dosage ; pharmacology ; Phosgene ; poisoning ; Rabbits ; Superoxide Dismutase ; metabolism

To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model, make a correlation analysis on concentration-time and effect-time curves, and explore RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate, tripterine and high-dose T. wilfordii could down-regulate RORγt, IL-17, STAT3, IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.
Animals ; Arthritis, Rheumatoid ; drug therapy ; immunology ; Biomarkers ; Female ; Interleukin-17 ; antagonists & inhibitors ; genetics ; Interleukin-6 ; genetics ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Tripterygium ; Triterpenes ; pharmacokinetics ; pharmacology

OBJECTIVETobacco smoking results in increased platelet aggregability, which suggests that low-dose aspirin used in common clinical practice may not effectively inhibit platelet activity in smokers with coronary heart disease (CHD). This review was performed to assess the effect of aspirin on platelet aggregation in patients with CHD.

DATA SOURCESWe performed an electronic literature search of MEDLINE (starting from the beginning to March 15, 2009) using the term "smoking" or "tobacco" paired with the following: "platelet", "aspirin" or "coronary heart disease".

STUDY SELECTIONWe looked for review articles regarding the effect of tobacco smoking on platelet activity and on the anti-platelet efficacy of aspirin in healthy people and patients with CHD. The search was limited in "core clinical journal". In total, 1321 relevant articles were retrieved, and 36 articles were ultimately cited.

RESULTSTobacco smoking results in increased platelet aggregability, which can be inhibited by low-dose aspirin in the healthy population. However, in patients with CHD, the increased platelet aggregability can not be effectively inhibited by the same low-dose of aspirin. A recent study indicated that clopidogrel or an increased dose of aspirin can effectively inhibit the increased platelet aggregability induced by tobacco smoking in patients with CHD.

CONCLUSIONSIt is important for patients with CHD to quit smoking. For the current smoker, it may be necessary to take larger doses of aspirin than normal or take an adenosine diphosphate receptor inhibitor along with aspirin to effectively inhibit the increased platelet activity.

Aspirin ; therapeutic use ; Coronary Disease ; drug therapy ; Drug Interactions ; Humans ; Platelet Aggregation Inhibitors ; therapeutic use ; Smoking ; adverse effects

In this study, we observed the levels of adrenomedullin (ADM) and proadrenomedullin N-terminal 20 peptide (PAMP) in myocardium and aorta of spontaneously hypertensive rats (SHRs) in comparison with Wistar-kyoto (WKY) rats. Contents of ADM and PAMP were measured by radioimmunoassay (RIA) in plasma, myocardium and aorta. The amount of Pro-ADM mRNA of myocardium and aorta was determined by competitive quantitative reverse transcription polymerase chain reaction (RT-PCR). In SHRs the amounts of Pro-ADM mRNA of myocardium and aorta were 66.7% (P<0.01) and 73% (P<0.01) higher than those in WKY rat, respectively. In SHRs, the levels of ADM in plasma, myocardium and aorta were 29%, 76.7% and 79% (all P<0.01) higher than those in WKY rats, respectively. The level of PAMP in SHRs was increased by 42.5% in plasma (P<0.01), 47.2% in myocardium (P<0.0.1) and 27.3% in aorta (P<0.05) compared to WKY rats, respectively. In addition, the ratio of ADM content to PAMP content in SHRs group was increased compared with that in WKY group (2.0+/-0.25 vs 1.64+/-0.3 and 2.2+/-0.18 vs 1.56+/-0.28, in myocardium and aorta, respectively, P<0.01). These results suggest that ProADM gene expression is up-regulated and the increase in ADM and PAMP is different in SHRs. The significance of inconsistency of increase in ADM and PAMP in SHRs needs to be further investigated.
Adrenomedullin ; genetics ; metabolism ; Animals ; Aorta ; metabolism ; Female ; Male ; Myocardium ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Inbred SHR ; Rats, Inbred WKY ; Up-Regulation

Objective To learn the changes of blood lead levels and serum biochemical parameters of the school agechildren from different areas. Methods All research objects, the school age children, were from three different areasrespectively, including a mountainous area (L area), an island area (H area) where there is not history of Pb pollution,and an industry area (N area) in relation to Pb pollution. The morning urine and peripheral venous blood samples werecollected from the school age children. Pb in blood (PbB), δ-aminoaevulinic acid in urine (ALA), Ca2+, BUN, Cr inserum, and Thyroid Stimulating Hormone (TSH), thyroxin (T4), free thyroxin (FT4) levels were detected. ResultsPbB levels [M was 36.0 ppb] of the school age children from N area were significantly higher than that of L area [22.0 ppb] andH area [23.8 ppb]. On the contrary, serum Ca2+ levels of the school age children from N area were significantly lower than thatof L area and H area. Serum T4 of N area was significantly lower than that of L area and H area. Serum FT4 of H area wassignificantly higher than that of L area and N area. And TSH of N area and H area were both obviously lower than that of L area.But all of these thyroxin indexes were in the range of normal values. Conclusion It should be widely concerned that thesignificant elevation of PbB levels may have a negative impact on school age children in the future.

Objective To study the curative effect of behavior therapy(military training and growth eduction)on conduct disorder of adolescent inpatients. Methods Using a random grouping and control-study method，87 inpatients with conduct disorder were divided into the study group and the control group. On the basis of drug therapy，the study group adopted the behavior therapy(military training and growth education),and was assessed 1 week and 12 weeks after admission using Achenbach's Child Behavior Checklist(CBCL). The assessment results were statistically treated. Results After 12 weeks of behavior tllerapy. the CBCL scores of the study group and the control group were(13.46±3.28)and(18.41±4.26)in anxiety and obsession,(8.65±3.34)and(12.57 4-3.28)in schizophrenia like，(11.87±3.21)and(14.85±3.55)in depression and withdrawn，(8.62±3.67)and(15.74±2.21)in immaturity，(9.23±2.41)and(15.62±2.51)in violation of discipline，(15.24±3.62)and(26.54±3.11)in aggressiveness，(7.16±3.32)and(11.89±2.65)in hyperactive syndrome. There Was a statistical meaning between the two groups(P<0.01).In addition，there Was a statistical meaning between before and after the therapy in the study group(P<0.01). Conclusions Behavior therapy(military training and growth education)is an effective method in the treatment of conduct disorder of adolescent inpatients.

Objective To explore the influencing factors of urinary tract infection in patients with spinal cord injury in rehabilitation period, so as to provide the basis to minimize urinary tract infection.Methods The patients' information and the incidence of urinary tract infection (UTI) during the rehabilitation period of 503 cases of spinal cord injury admitted to the First Affiliated Hospital of PLA General Hospital from January 2013 to December 2015 were retrospectively analyzed. Logistic regression analysis was used to analyze the influencing factors of UTI in patients with spinal cord injury during rehabilitation period.Results The degree of injury, the site of injury, the way of urination, and the course of the disease were the factors affecting the incidence of UTI in the patients with spinal cord injury during the rehabilitation period (P<0.05). Conclusions The degree of injury, the location of injury, the way of micturition and the duration of disease are the influencing factors of UTI in patients with spinal cord injury during rehabilitation. As the course of disease goes on, we need to choose intermittent catheterization as a way of micturition according to the bladder function of patients with spinal cord injury.

OBJECTIVETo investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).

METHODSEquilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions.

RESULTSThe binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16∓2.82)%, (33.42∓4.21)%, and (34.61∓3.42)%, and those of and Rb1 were (50.13∓2.34)%, (51.23∓3.23)%, and (53.11∓3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13∓2.72)%, (21.42∓3.22)%, and (25.45∓3.52)%, and those of Rb1 to (40.13∓3.24)%, (41.25∓4.15)%, and (43.11∓3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA.

CONCLUSIONClopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.

OBJECTIVETo investigate the relationship between plasma cytochrome P450 3A4 (CYP3A4) 894C>T gene polymorphism and the risk of recurrence of adverse cardiac events after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS).

METHODSA total of 275 patients with ACS received standard dual antiplatelet therapy and PCI. Platelet aggregation rate (PAR) was detected in each patient before and 7 days after administration of the anti-platelet drugs. Single nucleotide polymorphism of CYP3A4 gene 894C>T was detected with PCR and microarray technique. The number of coronary artery lesions was determined by PCI and the Gensini score was calculated. The patients were followed up for 3-12 months after discharge.

RESULTSNo significant difference was found in CYP3A4 gene polymorphism between patients with clopidogrel resistance (CR group) and those without CR (NCR group) (P>0.05). Multivariate logistic regression analysis showed that CYP3A4 gene 894C>T polymorphism was not correlated with CR in patients with ACS (OR 1.359, P>0.05). During the follow-up, the incidence of cardiovascular events was significantly higher in CR group than in NCR group (P<0.05), but this difference was not related to the mutation type of 894C>T locus of CYP3A4 gene.

CONCLUSIONThe CYP3A4 gene 894C>T polymorphism is not associated with the effect of anti-platelet therapy and the risk of cardiovascular event in patients with ACS following PCI.

Acute Coronary Syndrome ; therapy ; Alleles ; Blood Platelets ; Cytochrome P-450 CYP3A ; genetics ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation ; Platelet Aggregation Inhibitors ; therapeutic use ; Platelet Function Tests ; Polymorphism, Single Nucleotide ; Ticlopidine ; analogs & derivatives ; therapeutic use