[Summary] Type 2 diabetes is usually associated with overweight or obesity,hypertension,hyperlipidaemia and increased cardiovascular risk.Most of the anti-diabetic drugs mainly work on glucose-lowering,therefore would not bring benefits to the multiple metabolic abnormalities.In this article,the multiple effects of the anti-diabetic drug liraglutide on body weight,blood pressure,blood lipids,and cardiovascular system were summarised.

Accumulated clinical trials have demonstrated the clinical efficacy of statins,which is closely associated with the magnitude of LDL-C reduction,in primary and secondary prevention of cardiovascular diseases.The concept of intensive LDL-C lowing has been widely accepted.Although statins are classified as a group of drugs with documented safety and tolerability,the potential risk profile in liver and skeleton muscle under the intensive treatment with large dose has drawn great attention.

On the basis of complete blockade of endothelin-A (ET-A) receptor,the hemodynamic effects of further removal of endothelin-B receptor mediated effect with endothelin converting enzyme is not clear.We studied forearm vasodilation (with plethysmography) during a maximally effective dose of an ET-A receptor antagonist alone (brachial artery infusion of BQ123,36μg/min*100mL tissue for 25min) and during double blind,randomized,additional endothelin converting enzyme inhibition (phosphoramidon,20μg/min*100mL tissue for 15min,n=6) or placebo (n=6) in 12 patients with severe congestive heart failure (CHF).Baseline clinical characteristics in terms of age,NYHA grade,LVEF and medications are comparable between the two groups.As a study control,we carried out the same protocol in 12 normal volunteers.Forearm blood flow (FBF) increased similarly in patient with CHF and in normal volunteers after BQ123 over the 45 min observation period.There were significant further increases of FBF in both study populations after phosphoramidon infusion.While in placebo treated CHF patients during the additional 45min observation period,there is a decrease of FBF by a mean of 30% (mean difference between Phosph and Pla 57%,95% CI 43 to 72%,P＜0.001),which was greater than that in normal subjects.In patients with severe CHF as well as in normal volunteers,endothelin converting enzyme inhibition results in further vasodilation on the basis of ET-A receptor blockade alone,which suggests that ET-B receptor may play a role in maintaining vascular tong in human beings.

HDL or apolipoprotein A-Ⅰ,the major protein of HDL particles,protect host against vascular endothelial dysfunction.HDL binding to scavenger receptor-BI activates eNOS for increasing NO.SR-BI and Endothelial lipase(EL) play a critical role in the regulation of plasma HDL.Incubation of HDL with vascular endothelial cells promotes prostacyclin synthesis.Some proteins such as paraoxonase that cotransport with HDL in plasma,have antioxidant properties.HDL inhibits TNF-? dependent expression of adhesion molecules in vascular endothelial cells and interferes with apoptosis,proliferation and migration of vascular endothelial cells.

European Society of Cardiology guidelines on diagnosis and treatment of heart failure are among the mostly authorized international directing documents,applied widely in clinical practice,epidemiological researches and randomized clinical trials.The guidelines published in 2008 combined chronic and acute hear failure and made significant modifications in the definition,classification,diagnosis,pharmacological and non-pharmacological treatment of heart failure.Simplification of the recommendations and enhancement of the guidelines implication are also point of focusing.This article represents a brief review of the new guidelines,together with comparison with the previous edition and analysis of recommendations based on local clinical practice,to enhance the standardized management of heart failure in China. Abstract:Summ ary:European Soc iety of Card iology gu idelines on d iagnosis and treatm ent of heart failure are among the mostly au-thorized international d irecting docum ents,app lied w idely in c lin ical practice,ep idem iological researches and random ized c lin ical trials.The gu idelines pub lished in 2008 comb ined chron ic and acute hear failure and m ade sign ificant mod ifica-tions in the defin ition,c lassification,d iagnosis,pharm acological and non-pharm acological treatm ent of heart failure.S imp li-fication of the recomm endations and enhancem ent of the gu idelines imp lication are also point of focusing.Th is artic le re-presents a brief review of the new gu idelines,togetherw ith comparison w ith the previous ed ition and analysis of recomm en-dations based on local c lin ical practice,to enhance the standard ized m anagem ent of heart failure in Ch ina.

Directed evolution was conducted to improve the thermostability of lipase from Rhizopus chinensis CCTCC M201021. Mutations were introduced by two rounds of error-prone PCR and mutant lipase was selected by fast-blue RR top agar screening. Two positive variants were selected in the first-round and four in the second-round screening process. Ep2-4 was proved as the most thermostable lipase and its DNA sequencing revealed three amino acid substitutions: A129S, P168L and V329A. Compared with the parent, its half-life at 60 degrees C was 5.4- times longer and T50 was 7.8 degrees higher. Purified lipase of Ep2-4 was characterized and the result shows that its thermostability improved without compromising enzyme activity. According to the mimicked protein structure, mutation A129S formed a hydrogen bond with Gln133 and improved the thermostability by increasing the hydrophilicity and polarity of protein; mutation P168L by forming a hydrophobic bond with the nearby Leu164.
Cloning, Molecular ; Directed Molecular Evolution ; methods ; Enzyme Stability ; genetics ; Hot Temperature ; Industrial Microbiology ; Lipase ; chemistry ; genetics ; Mutation ; Pichia ; genetics ; metabolism ; Polymerase Chain Reaction ; methods ; Protein Engineering ; methods ; Rhizopus ; enzymology

Objective To study the prognostic value of initial arterial lactate level and to explore the relationship between early arterial lactate and the outcome of patients with acute paraquat poisoning by analyzing the clinical data of 235 cases.Methods A total of 235 patients with acute paraquat poisoning were admitted to the Emergency Intensive Care Unit (EICU) from January 2009 to June 2012.Demographics,clinical and laboratory findings were compared between the survivors and non-survivors.Receiver operating characteristic (ROC) curves were used to identify the optimal cut-off points for initial arterial lactate level.Results Totally 235 patients with average age of (33.6 ± 11.5) years old (ranging from 18 to 74),89 male and 146 female.The median estimated amount of 20％ paraquat ingested was 55 mL,(ranging from 10 to 280,IQR:27 mL,77 mL),the median length of time between paraquat ingestion and the arrival at the emergency department was 4.5 h (ranging from 0.5 to 10.5,IQR:2.3 h,6.8 h).The overall mortality rate was 74.0％ (174/235) during a 28 days follow-up period,only 61 of 235 patients survived.The initial arterial lactate level was higher in non-survivors than that in survivors (2.79 ± 0.76) mmol/L vs.(1.62 ± 0.48) mmol/L,P =0.028).Correlation analyses showed that the initial arterial lactate level was associated with increased risk of 28-day mortality (r =0.26,P =0.004),and as the initial lactate increased,the survival time of non-survivors shortened (F =3.246,P =0.037).Using the ROC curve analysis,the initial arterial lactate level had an area of 0.799 (95％ CI:0.745-0.866) and the cut-off point of concentration was 2.57 mmol/L for prediction of prognosis in patients with acute paraquat poisoning (sensitivity 85.2％,specificity 79.6％,the best Youden index was 0.648).The initial arterial lactate level was higher in patients died from circulatory failure rather than from respiratory failure (5.22 ± 1.46) mmol/L vs.(1.87 ± 0.62) mmol/L,P =0.042.And the survival time of patients died from circulatory failure was shorter than that from respiratory failure (4.1 ± 1.3) d vs.(11.6 ± 3.2)d,P =0.023.With the ROC curve analysis,the initial arterial lactate level had an area of 0.882 (95％ CI:0.805-0.941) and the cut-off point of concentration was 3.65 mmol/L for prediction of prognosis of patients died from circulatory failure (sensitivity 87.6％,specificity 82.5％,the best Youden index was 0.701).Conclusions The initial arterial lactate level may be one of early indicators of prognosis in patients with acute paraquat poisoning and it had high potential in predicting the outcome of patients died from circulatory failure.

Objective To investigate the clinical factors dominant in the efficacy of lung recruitment maneuver (RM) with high-level positive end-expiratory pressure (PEEP) under pressure control ventilation in patients with 2009 influenza A (H1N1)-associated acute respiratory distress syndrome (ARDS) by analyzing the clinical data of 24 patients treated with mechanical ventilation.Methods A retrospective study was carried out in a 16-bed capacity emergency intensive care unit (EICU) of the First Affiliated Hospital of China Medical University from October 2009 to January 2010.Twenty-four patients with influenza-associated ARDS were included.During pressure control ventilation,when SpO2 persisted lower than 88％ for more than 30 min,RM with high-level PEEP was initiated to normalize lung volume at 30 cmH2O for 60 s.The RM was responded as SpO2 increased more than 3％ within 15 min; otherwise,the increase below 3％ in SpO2 would be considered non-responded.Variations in respiratory mechanics,oxygen metabolism and hemodynamic parameters were measured before and after RM.Results Of 24 patients with influenza-associated ARDS,16 survived and 8 deceased.The median duration of mechanical ventilation (DMV) in EICU was 5.5 days (range from 3.5 to 12.0 days).During the entire study period,a total of 158 RMs with high-level PEEP were done,including 76 (48.1％) responded RMs (the responded group) and 82 (51.9％) non-responded RMs (the non-responded group).In survivor group,the ratio of effective RM was higher than in nonsurvivors group (66.2％ vs.33.3％,P ＜ 0.01).Compared with the data before RM,HR was increased (92.6 ± 11.8) vs.(73.0 ± 12.6),P =0.038 and MAP was decreased (66.1 ±9.3) mmHg vs.(73.9 ± 11.4) mmHg,P=0.049 during RM,and these difference were not statistically significant at 3 min after RM.The decrease in SpO2 after 134 procedures of RMs in 85.9％ patients,and the minimum value of SpO2 occurred at (2.1 ±0.6) min after RM.In the responded group,the maximum SpO2 were higher than that before RM by (6.9 ± 1.6) ％ occurred at (12.7 ±2.6) min after RM.Compared with the data before RM,SpO2 were increased (90.4 ± 4.4) ％ vs.(86.7 ± 7.6) ％,P =0.047) in responded group at 30 min after RM.The initial PEEP level in the responded group was lower than that of the non-responded group (8.6 ± 3.4) cmH2O vs.(11.3 ±4.2) cmH2O,P=0.028.The initial mean DMV in the responded group was also shorter than that in the non-responded group (4.1 ± 3.1) d vs.(5.8 ± 2.5) d,P =0.011.Furthermore,the initial dynamic lung-thorax compliance (Cdyn) was obviously higher in the responded group than that in the non-responded group (30.8 ±6.2) mL/cmH2O vs.(26.1 ±5.1) mL/cmH2O,P=0.038.Conclusion The lung RM with high-level PEEP may cause temporary hemodynamic changes and the initial PEEP level,DMV,and Cdyn may be potential factors influencing the efficacy of lung RM.

Objective To compare the induction of L1 and L2 ?-lactamase stenotraphomonas maltoptilia by common antimicrobial agents, including imipenem, meropenem, cefotaxime and ceftazidime, and to survey the modulation of L1 and L2 ?-lactamase expression. Methods One clinical strain of S. maltophilia was isolated and identified with VITEK automatic microbic system. L1 and L2 ?-lactamase genes were amplified, cloned and sequenced by PCR method. Minimal inhibitory concentrations (MICs) of four antimicrobial agents against the clinical isolates were determined by agar dilution method. Two hours after being induced by different concentrations of four antimicrobial agents, total RNA was extracted, and RT-PCR method was used to determine the induction of L1 and L2 ?-lactamase by different concentrations (0.25, 1 or 4?MIC) of common antimicrobial agents. Electrophoresis strips of L1 and L2 ?-lactamase were quantified by Image J software. Results The clinical isolates of S. maltophilia with simultaneous production of L1 and L2 ?-lactamse were identified. When different concentrations of four antimicrobial agents were used as inductors, electrophoresis strips of L1 and L2 amplicons were not found in strains of blank control and those in which imipenem, meropenem or cefotaxime (4?MIC) was added to the culture mediam, while light electrophoresis strips were exhibited by the isolates with ceftazidime (0.25, 1 or 4?MIC) or cefotaxime (0.25?MIC) added to the medium. The strongest electrophoresis strips and the strongest expression were found in the isolates with cefotaxime (1?MIC) added to the medium. Conclusions Clinical common antimicrobial agents, e.g. ceftazidime and cefotaxime, are able to induce production of L1 and L2 ?-lactamase, and cefotaxime (1?MIC) is the strongest inductor. Cefotaxime can exert an effect on transcription of L1, L2 genes simultaneously, implying that a significant overlap might exist between the mechanism of modulation of two ?-lactamases.

Human resources are the principle factor for survival and sustainable development of hospital libraries, the paper analyzes the status of human resources of hospital libraries in Shandong province where it could reveal the factors that effect human resources construction in hospital libraries, and then puts forward that hospital libraries should be under the management of information department,the leader of library should establish people-oriented concept for human resources construction and the developing trends of human resources construction should be established.