Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

Objective To investigate the value of the Wells score and D-dimer assay in assisting pulmonary perfusion imaging (PPI) for the diagnosis of acute pulmonary embolism (APE). Methods One hundred twenty-one patients with suspected APE were studied from January, 2006 to December, 2008. All patients underwent the Wells score, the quantitative D-dimer assay, chest X-ray photography, and PPI. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of PPI with the assistance of Wells score and D-dimer assay were calculated. Results Fifty (41.3%) patients were diagnosed with APE. PPI combined with chest X-ray photography (Q/X scan) showed positive results in 49 patients. The sensitivity, specificity, positive predictive value and negative predictive value of the Q/X scan were 86.0% (43/50), 91.5% (65/71), 87.8% (43/49) and 90.3% (65/72), respectively. With assistance of Wells score >4 and D-dimer≥0. 5 mg/L, Q/X scan had a positive predictive value of 100.0% (29/29), for patients with Wells score ≤4 and D-dimer<0.5 mg/L, the negative predictive value for Q/X scan was 100.0% (41/41). Conclusion Combined with Wells score and D-dimer assay, PPI can make accurate diagnosis of APE.

A model for screening the yeast which can ferment xylose to produce the ethanol was constructed.An ethanol yeast was obtained using the lignocellulose as substrate production the ethanol.By malt extract medium pre-culturing,soil samples use the plate with xylose as sole carbon source as the primary screening,then finally screen by the potassium dichromate color-displaying method.A strain named Y2-3 was screened from the soil.Phenotypic analysis including morphology and physiology and biochemical characteristics and 26D1/D2 sequence analysis were carried out.Based on taxonomy results,the Y2-3 was identified as Pichia caribbica.The strain Y2-3 ferments using xylose as sole carbon source: biomass 23.5 g/L,xylose utilization rate 94.7 %,ethanol final yield 4.57 g/L;using mixture sugar:biomass 28.6 g/L,xylose utilization rate 94.2 %,glucose utilization rate 95.6%,ethanol final yield 20.6 g/L.Pichia caribbica is a yeast which can utilize xylose and mixture sugar as substrate.It established the foundation for further research fermentation of ethanol by yeast using lignocellulose.

Abstract: Objective To understand the mental health literacy level of residents in Hainan Province, and to provide evidence for promoting mental health promotion and improving the mental health literacy level of residents. Methods Multi-stage random sampling method was used to investigate The National Mental Health Literacy Questionnaire among 6 895 residents in 12 districts including Changjiang, Chengmai, Dongfang, Ledong, Lingshui, Haikou Longhua District, Haikou Meilan District, Qionghai, Sanya, Tunchang, Wenchang and Wuzhishan. Results　In the survey 6 895 residents in 12 counties, cities, districts of Hainan Province, 365 of them reached the standard of mental health with the standard rate of 5.3%. The mental health knowledge score was (54.00±17.02) with the standard rate of 7.7%; the self-assessment score was (26.11±3.99) with the standard rate of 75.9%; the score of mental health skill was (26.22±7.25) with the standard rate of 44.8%. The mental health literacy level of medical workers was the highest, with the standard rate of 13.5% (112/830), and the mental health literacy level of farmers was the lowest, with the standard rate of 0.8% (13/1 647). The results of unconditional Logistic regression showed that the factors entering the regression model included educational background (OR=2.268), personal monthly income (OR=1.129), gender (OR=1.302), household registration (OR=0.776), and whether they had participated in mental health related courses OR training (OR=0.511). The higher the educational background and personal monthly income, the higher the psychological quality. The mental health of women was higher than that of men, and that of urban was higher than that of rural, and those who had participated in mental health related courses were higher than those who had not. Conclusions The mental health literacy level of Hainan residents is at a low level, and the influencing factors are multifaceted. It is suggested to strengthen the mental health monitoring comprehensively and carry out rich health education service mode for different groups.

ObjectiveTo investigate the value of 18F-FDG SPECT myocardial imaging in evaluating haemodynamic change,treatment outcome and prognosis for idiopathic pulmonary arterial hypertension (IPAH).MethodsAll 24 patients with IPAH underwent 18 F-FDG SPECT myocardial imaging.Right ventricle/left ventricle (RV/LV)-FDG uptake was calculated by ROI method drawing over the central areas of left and right ventricular free walls.All patients underwent right heart catheterization within 3 days after imaging studies.Mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) were recorded.After six month pharmaceutical treatment,15 IPAH patients were re-examined with 18F-FDG SPECT myocardial imaging followed by repeated right heart catheterization within 3 days.Plasma N-terminal pro-brain naturetic peptide (NT-proBNP) and endothelin-1 ( ET-1 ) were measured in 17 patients using electrochemiluminescent immunoassay and enzyme immunoassay respectively.All patients were followed up for 12 months at least.Correlations between RV/LV-FDG uptake and mPAP and PVR were determined by simple linear regression analysis.Change of RV/LV-FDG before and after treatment was calculated using Student's t-test.Survival in groups with RV/LV FDG uptake ≥ 1.15 and RV/LV-FDG uptake ＜ 1.15 were compared using Log-rank test.ResultsSignificant correlations were found between RV/LV-FDG uptake and mPAP (r =0.562,P ＜ 0.01 ),and between RV/LV-FDG uptake and PVR ( r =0.574,P ＜ 0.01 ).There were no significant correlation between RV/LV-FDG uptake and NT-proBNP( r =0.18 1,P ＞ 0.05 ),but a significant correlation between RV/LV-FDG and ET-1 was observed (r =0.669,P ＜ 0.01 ).The RV/LV-FDG uptake in patients with positive treatment outcome ( n =6) decreased from 1.38 ± 0.52 to 0.92 ±0.26 (t =4.018,P ＜ 0.05) after 6 months treatment.In contrast,no significant change of RV/LV-FDG uptake was seen in those patients (n =9) with negative treatment outcome ( t =1.861,P ＞ 0.05 ).The mean follow-up time was (21 ±8) months.Mean survival time for the patients with RV/LV- FDG uptake ≥ 1.15was 28 months (95％ confidence interval:24-32 months),which was significantly lower than 34 months survival (95％ confidence interval:33-35 months) for the patients with RV/LV-FDG ＜ 1.15 (x2 =3.956,P ＜0.05 ).Conclusions Detection of right ventricle myocardial glucose metabolism level with 18F-FDG SPECT may be a practical method for evaluating haemodynamic change,treatment outcome and prognosis of IPAH.

Objectives: To investigate the relationships between the stability of carotid plaque and serum Lp-PLA2, A-FABP levels in hypertensive postmenopausal women. Methods: 195 postmenopausal women with hypertension were selected and divided into non-plaque group, stable plaque group and unstable plaque group according to the results of carotid intima-media thickness (IMT) and plaque types derived from color doppler ultrasonography. In addition, 40 healthy postmenopausal women were recruited as normal control group. The serum Lp-PLA2 and A-FABP levels of all subjects were measured. Lp-PLA2 and A-FABP levels were compared among four groups by One-Way ANOVA. Spearman correlation analysis and multiple logistic regression analysis were also performed. Results: Plaque group included 123 subjects (unstable plaque group: 29 cases; stable plaque group: 94 cases), and non-plaque group included 72 subjects. The average serum A-FABP level was significantly higher in unstable plaque group [(172.60±33.70) ng/L] than in non-plaque group[(133.04±29.49) ng/L], P<0.05. Serum Lp-PLA2 level was similar between the four groups, P>0.05. Serum A-FABP level was positively correlated with the carotid plaque (r=0.3446, P=0.0049);serum Lp-PLA2 level was not correlated with the carotid plaque (r=0.2058, P=0.0996). Multiple logistic regression analysis showed that high A-FABP level was associated with stable plaque in hypertensive postmenopausal women (P=0.040, OR=1.017, 95%CI: 1.001~1.033), which was also associated with unstable plaque in this population (P=0.003, OR=1.031, 95%CI: 1.010~1.052). Conclusions: The level of A-FABP is a determinant responsible for the occurrence and stability of carotid plaque among hypertensive postmenopausal women. There was no correlation between Lp-PLA2 level and the stability of carotid plaque in this patient cohort.

OBJECTIVETo investigate the expression and mutation of Mad1, Mxi1 and Rox genes in leukemia cells.

METHODSExpression and mutation of Mad1, Mxi1 and Rox genes in bone marrow mononuclear cells (BMMNC) from 26 de novo acute leukemia (AL) patients, and in peripheral blood mononuclear cells (PBMNC) from 30 healthy volunteers, as well as in 7 human leukemic cell lines were analyzed by reverse transcription-polymerase chain reaction (RT-PCR), single strand conformational polymorphism (SSCP) and DNA sequencing.

RESULTSRT-PCR showed that all the above cells expressed Mad1, Mxi1 and Rox mRNA. SSCP revealed four polymorphisms: two in Mad1, one each in Mxi1 and Rox. DNA sequencing detected nine missense mutations: two in Mad1 in AL patients, four in Mxi1 (three in AL patients and one in KG-1 cell line), and three in Rox in AL patients. The mutations of Mad1, Mxi1 and Rox mRNA were detected in 2, 3 and 3 patients, respectively.

CONCLUSIONIt is for the first time to demonstrate the mutations of Mad1, Mxi1 and Rox genes in AL patients suggesting these mutated genes involve in the pathogenesis of leukemia.

Adolescent ; Adult ; Aged ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; genetics ; metabolism ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Female ; Humans ; Leukemia ; genetics ; metabolism ; Male ; Middle Aged ; Mutation ; Nuclear Proteins ; genetics ; metabolism ; Polymorphism, Single-Stranded Conformational ; Repressor Proteins ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

Objective To analyze the relationship between prevalence of metabolic syndrome (MS) and behavior habits such as smoking,alcohol intake,physical activity,sleeping hours.Methods A multi-stage stratified cluster sampling was conducted in 31 provinces,autonomous regions,and municipalities in China according to the program of National Nutrition and Health Survey.Questionnaire survey,interview,physical examination,measurement of biochemical indices,and dietary investigation were done.In total,4937 men aged 18 to 45 years old were selected.Results The MS prevalence was 6.9%(329/4937).The rate of drinking was 49.4% and smoking rate was 54.4%.The percentage of sleeping was hours from 7 to 8 was 70.5%.The percentage of spending time on physical activity over 420 minutes/week was as high as 41.9%.Data from single logistic regression showed volume of smoking more than 600 packs and alcohol intake were associated with high risk of MS and no significantly associations were found between MS and the duration of physical activity and the sleeping time.Multivariate logistic regression showed that the risk of MS in smokers with the volume more than 600 packs age increased significantly as compared to nonsmokers with the odds ratio as 1.443 (95%CI:1.044-1.993 ) and 1.765 (95%CI:1.150-2.708) in smokers with volume from 600 to 899 packs age,and more than 900 packs age respectively.Compared to the nondrinkers,the odds ratios were 1.525 (95%CI:1.135-2.048),2.322(95%CI:1.671-3.255) and 2.033 (95%CI:1.478-2.796) in subjects volume of alcohol dranking as 1 to 2 times per week,3 to 4 times per week and more than 5 times per week respectively.Conclusion Tobacco and alcohol were associated with high risks of MS.

Objective To investigate the relationship between expressions of mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF) and pathological grading of meningiomas. Methods Seventy-six specimens of meningiomas, performed resection in our hospital from January 1995 to August 2010, were chosen, in which, 40 were of WHO grade Ⅰ, 24 of WHO grade Ⅱ, and 12 of WHO grade Ⅲ. The expressions of mTOR and VEGF were immunohistochemically studied with SABC method. Results The protein expressions of mTOR and VEGF mainly located in cytoplasm of meningioma cells, and these proteins were granular materials colored from pale yellow to dark yellow. The expressions of mTOR and VEGF were significantly different among meningiomas of grade Ⅰ,Ⅱ and Ⅲ (P<0.05);the expressions of mTOR and VEGF had a positive correlation (r=0.440, P=0.000). Conclusion The expressions of mTOR and VEGF are positively correlated with the tumor grades.

BACKGROUNDThe synovial fluid concentrations of adiponectin are significantly higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA). Accumulating evidence suggests that adiponectin may be an inducer of inflammation in arthritis, but the mechanism remains unclear. The objectives of this study were to compare the expression levels of adiponectin receptors in rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF), evaluate the roles of adiponectin receptors in adiponectin-induced prostaglandin E(2) (PGE(2)) production, and then investigate the effects of a nonsteroidal anti-inflammatory drug (NSAID) and a cyclooxygenase (COX)-2-selective inhibitor on adiponectin-induced PGE(2) release.

METHODSThe expressions of adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA and protein in synovial fibroblasts from seven patients with RA and eight patients with OA undergoing total knee replacement were evaluated by real-time polymerase chain reaction, immunofluorescence microscopy and Western blotting analysis. Adiponectin-induced PGE(2) production was detected by enzyme-linked immunosorbent assay. RNA interference against the AdipoR1 and AdipoR2 genes was performed to investigate the effects of the adiponectin receptors on adiponectin-induced PGE(2) production in both RASF and OASF.

RESULTSAdipoR1 and AdipoR2 mRNA and protein were expressed by both RASF and OASF. Compared with OASF, RASF exhibited higher levels of AdipoR1, but there was no significant difference for AdipoR2. Adiponectin induced the production of PGE(2) by the synovial fibroblasts in a concentration-dependent manner, and this was more obvious in RASF. RNA interference showed that the difference may be mediated by the diverse distribution of AdipoR1. The adiponectin-induced PGE(2) production was efficiently relieved by the NSAID and COX-2-selective inhibitor.

CONCLUSIONThe present findings suggest that AdipoR1 may mediate the difference in adiponectin-induced PGE(2) production in RASF and OASF.

Adiponectin ; pharmacology ; Arthritis, Rheumatoid ; metabolism ; Blotting, Western ; Cells, Cultured ; Dinoprostone ; metabolism ; Female ; Fibroblasts ; drug effects ; metabolism ; Humans ; Immunoassay ; Male ; Microscopy, Fluorescence ; Middle Aged ; Osteoarthritis ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Receptors, Adiponectin ; genetics ; metabolism ; Synovial Membrane ; cytology