Objective To evaluate the protective effect of the activator of silent information regulator 2-related enzymes 1(SIRT1),SRT1720,on liver injury induced by acetaminophen(APAP)in mice and explore its mechanism. Methods Forty male C57BL/6J mice were randomly divided into normal control group,SRT1720 treatment group,APAP treatment group,and APAP + SRT1720 treatment group,with 10 mice in each group. Mice in SRT1720 and APAP + SRT1720 groups were given SRT1720(30 mg/kg body mass)by intragastric administration,while normal saline of equal volume was given by intragastric administration in control and APAP groups,once a day for 5 days;On the 6th day,mice in APAP and APAP + SRT1720 groups were injected i. p. with APAP(325 mg/kg body mass),while those in control and SRT1720 groups with equal volume of normal saline. After 24 hours,the peripheral blood was taken and the serum was separated,which were detected for the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)by the corresponding kits;The liver tissue of mice was taken aseptically,observed for the pathological changes by HE staining,detected for the mRNA transcription levels of GRP78,PERK,eIF2 α,ATF4 and CHOP genes related to PERK-eIF2α-CHOP signaling pathway by RT-qPCR and detected for the relative expression levels of these corresponding proteins and Caspase12 protein by Western blot. Results Compared with normal control group,the serum ALT and AST levels of mice in APAP group significantly increased(t = 55. 21 and34. 29 respectively,each P < 0. 01);significant necrosis of hepatocytes was observed in liver tissue,the structure of hepatic lobules changed significantly,and the swelling and deformation of hepatocytes in some areas were serious;the mRNA transcription and relative protein expression levels of GRP78,PERK,eIFα,ATF4 and CHOP genes increased significantly(t = 9. 85～33. 89,each P < 0. 05)and the relative expression level of Caspase12 protein increased significantly(t = 11. 78,P < 0. 01). Compared with APAP group,the serum ALT and AST levels of mice in APAP + SRT1720 group decreased significantly(t = 42. 92 and 18. 02 respectively,each P < 0. 01);the degree of hepatocyte injury was obviously reduced and the number of swollen and deformed cells also significantly decreased;the mRNA transcription and relative protein expression levels of GRP78,PERK,eIF2α,ATF4 and CHOP decreased significantly(t = 6. 19～22. 43,each P < 0. 05)and the expression level of Caspase12 protein showed no significant decrease(t = 0. 34,P > 0. 05). Conclusion SRT1720improved APAP-induced liver injury in mice,possibly by inhibiting PERK-eIF2α-CHOP signaling pathway in endoplasmic reticulum stress(ERS).

Objective To establish a method for the determination of molecular weight of meningococcal polysaccharide and polysaccharide-protein conjugates by size exclusion chromatography-multiangle laser-light scattering(SEC-MALLS), and to verify and apply the method, so as to improve the quality control level of meningococcal vaccines.Methods A SEC-MALLS method was established to detect the molecular weight of polysaccharide and polysaccharide-protein conjugates of meningococcus. The chromatographic conditions were as follows: 0. 9% sodium chloride solution as the mobile phase; Shodex OHpak LB-806 HQ(300 mm × 8. 0 mm, 13 μm) as the column; the flow rate at 0. 5 mL/min; the column temperature at 35 ℃. The systematic applicability, accuracy, precision and durability of the method were verified, and the samples from different manufacturers were detected by this method. In addition, the correlation between SEC-MALLS and the existing pharmacopoeia quality standard methods was analyzed.Results Except for STD P-100, the relative error and precision between the measured and marked values of weight-average molecular weight(Mw) of STD P-50 to STD P-800 were less than 5. 0%, indicating that the pullulan standard could be used as the systematic adaptive sample. The RSDs of reproducibility and intermediate precision were not more than 5. 0%. The polysaccharide and polysaccharide-protein conjugates had good stability within 48 h after preparation. The average Mw of polysaccharides from group A, C, Y and W135 were 257. 5, 377. 3, 399. 7and 305. 5 kDa, while the polysaccharide-protein conjugates of group A and group C were 6 438 and 23 360 kDa, respectively. Among the 71 batches of polysaccharide samples, the results of group A and group C in five batches exceeded the trend, and the inner-and inter-batch differences of other batches were within the range of mean ± 3 SD. Except the KDvalue of polysaccharide in group Y had a certain negative correlation with Mw, there was no significant correlation between the two methods in the remaining polysaccharide and polysaccharide-protein conjugates.Conclusion SEC-MALLS can directly determine the molecular weight of polysaccharide and polysaccharide-protein conjugates of meningococcal vaccine with the advantages of fast, accurate and simple operation, and can reflect the molecular structure information to a certain extent,which is conducive to improve the quality control of this key quality parameter.

Objective To construct a new human-derived consensus interferon α(cIFNα)sequence and verify its antiviral effect.Methods Total 57 human-derived IFNα sequences were synthesized,and the conservative amino acid preference at each site was selected by software comparison analysis.A new cIFN sequence,hIC,was synthesized into pUC-57 vector and connected with pCK to construct eukaryotic expression vector pCK-hIC,which was transfected into 293T cells to express the target protein hIC.A549 cells were incubated with the target protein before and after infection with enhanced green fluorescent protein vesicular stomatitis virus(VSV-EGFP).The effect of hIC on VSV-EGFP replication was analyzed by fluorescence observation,crystal violet staining and flow cytometry in vitro,and the downstream gene expression of IFN was verified by qPCR.Results The plasmid pCK-hIC was constructed correctly as verified by double enzyme digestion and sequen-cing.The expressed hIC protein,with a relative molecular mass of about 27 000,significantly reduced the fluorescence expression of VSV-EGFP,significantly inhibited virus proliferation and activated the expression of interferon-stimulated gene 15(ISG15),2′-5′-oligoadenylate synthetase 1(OAS1)and interferon-inducible transmembrane protein(IFITM).Conclusion The hIC has good antiviral effect,which lays a foundation for the follow-up research and development.

China is the country with the biggest diabetic population in the world.Diabetes has become a heavy financial burden for diabetic patients,families,and society.This article briefly described pharmacoeconomic concepts and analysis methods,and systemically reviewed literatures in health economic data of DPP-4 inhibitors,in the hope of providing a new perspective for clinicians,researchers,and health care policy makers.

Obesity is associated with numerous metabolic abnormalities, including insulin resistance and type 2 diabetes. Losing weight is an effective way of improving insulin sensitivity, thus decreasing the risk of obesityassociated diabetes and chronic cardiovascular disease. There is evidence that Liraglutide, as a human glucagon-like peptide-1 ( GLP-1 ) analogue, either using alone or combining with other glucose-lowering drugs, has effect on improving glycemic control, protecting β-cell function, and reducing body weight via inhibiting feeding behavior and delaying gastrointestinal motility. Therefore, liraglutide is a new option for treating type 2 diabetes patients.

Objective To investigate the effects of different anesthesia methods on cerebral oxygen metabolism in patients with severe traumatic brain injury.Methods Forty-five patients with severe traumatic brain injury from March 2011 to March 2013 were divided into propofol intravenous anesthesia group(group A),sevoflurane inhalation anesthesia group(group B) and intravenous inhalational anesthesia group (group C) by random digits table method with 15 cases each.The mean artery pressure (MAP),heart rate (HR) before anesthesia,immediately after tracheal intubation,2 minutes after intubation,10 min and 30 min after operation set and operation end were observed.The oxygen content of jugular venous (SjvO2),jugular bulb venous oxygen content (Da-jvO2) and cerebral metabolic rate for oxygen (CERO2) before anesthesia induction,immediately finish anesthesia induction,30 min and 1 h after operation set and operatin end were calculated.Results The SjvO2 values in three groups were at 30 min,1 h after operation set and operation end was higher than that before anesthesia induction (group A:0.662 ±0.077,0.689 ±0.067,0.685 ±0.066 vs.0.623 ±0.083; group B:0.661 ±0.074,0.681 ±0.072,0.661 ±0.069 vs.0.598 ±0.092; group C:0.715 ± 0.072,0.743 ± 0.070,0.713 ± 0.075 vs.0.631 ± 0.078),and there was significant difference (P ＜ 0.05).The Da-jvO2 values,CERO2 at 30 min,1 h after operation set and operation end was lower than that before anesthesia induction in three groups [group A:Da-jvO2:(41.2 ± 6.3),(41.6 ± 8.1),(44.2 ± 6.3) ml/L vs.(49.2 ± 9.2) ml/L,CERO2:(33.0 ± 1.9)％,(32.7 ± 2.0)％,(32.3 ± 1.9)％ vs.(36.0 ±2.3)％; group B:Da-jvO2:(41.8 ± 5.6),(40.2 ± 6.9),(41.8 ± 5.6) ml/L vs.(51.3 ± 8.6) ml/L,CERO2:(33.2 ±2.1)％,(33.0 ±2.6)％,(32.8 ±2.1)％ vs.(34.7 ±3.1)％ ; group C:Da-jvO2:(39.5 ±6.8),(38.7 ±7.0),(40.2 ±6.8) ml/L vs.(48.8 ±9.7) ml/L,CERO2:(31.8 ±2.9)％,(31.5 ±3.1)％,(32.9 ±2.3)％ vs.(35.1 ± 2.9)％],and there was significant difference (P ＜ 0.05).And group C was decreased more significantly (P＜0.05).There was no significant difference in MAP,HR among three groups (P＞0.05).Conclusion Propofol intravenous anesthesia and sevoflurane inhalation anesthesia can effectively reduce perioperative cerebral metabolic rate of oxygen,and the balanced anesthesia has better cerebral protection with the stable hemodynamic.

Hyperoxia-induced lung injury in neonatal is a common complication after the clinical high oxygen therapy. There is not specific and effective prevention and treatment. Recent research suggests that many factor play an important role in the repair and protection of hyperoxia-induced lung injury in neonatal, such as growth factor, bone marrow mesenchymal stem cells,erythropoietin, anti-chemokine and anti-oxidation. The article reviews the molecular systems mechanisms in the pathologic process of hyperroxia-induced lung injury in neonatal.

1,25-dihydroxyvitamin D3 plays a role in the regulation of T cells, B cells, macrophages,dendritic cells,and keratinocytes. 1,25-dihydroxyvitamin D3 is linked to many autoimmune diseases, including rheumatoid arthritis,juvenile diabetes, Crohn's disease, multiple sclerosis. It may have potential as a treatment for autoimmune diseases, however, additional research will focus on better quantify dosage and course of treatment.

Acute leukemia is one of the most common cancers among children.The biological mechanisms leading to leukemia have not been fully clarified until now.Experiments were improved that most patients developing acute leukemia had abnormal chromosomes,including TEL/AML-l,BCR/ABL,PML/RAR-α fusion genes,which would be potential clinical biomarkers.Many genetic polymorphisms have effect on acute lymphoblastic leukemia susceptibility,which were containing genes involved in folate metabolism pathways,cytochrome P450,glutathione-S-transferase enzymes and quinone oxidoreductase-1.As the results of the studies,alcohol,tobacco,TNF-α and IFN-γ might be risk factors to the disease.Furthermore infection and IRF-3 were reported to reduce the occurrence of acute leukemia.Finally,as more is learned about the molecular pathology,it may be possible to develop new therapeutic agents which are specifically targeted to treat childhood acute leukemia.

Thl7 cells represent a new subset of CD4+ effector T cells which constitute the main subsets of CD4 T cells together with Th1,Th2 and Treg ce1ls.IL-17 is the main secretory product of Th17 cells,which plays important regulatory roles in autoimmune diseases,infectious diseases and tumors.Therefore,Th17 cells and related cytokines may provide promising targets and approaches for the treatment of diseases.