Folypolyglutamate synthetase(FPGS) catalyzes the addition of multiple glutamate molecules to compounds with the basic pteroylglutamate structure,such as polyglutamylation-dependent novel antifolates.As the antifolates like methotrexate require polyglutamation by FPGS for activation,FPGS has an established position in the cytotoxic action of methotrexate and has become a essential part in methotrexate resistance.Recent studies have indicated that decreased mRNA expression and activity of FPGS can cause reduction of methotrexate-polyglutamates accumulation,which have been observed as a dominant mechanism leading to methotrexate resistance.Furthermore,single nucleotide polymorphism in FPGS has been displayed significant associations with methotrexate sensitivity and susceptibility of deseases,though the detail mechanism is unknown.This paper is to review the relationship among FPGS enzyme activity,gene polymorphism and methotrexate drug sensitivity.

Objective To explore the predictive value of combined measurement of D-dimer (D-D),fibrinogen (FIB),and peripheral blood leukocyte count (PBLC) for the severity of acute pancreatitis (AP).Methods We collected the clinical data of 134 hospitalized patients who were diagnosed with AP in the General Hospital of Ningxia Medical University from January 2014 to January 2016.These patients were divided into mild acute pancreatitis (MAP) group (n =72) and severe acute pancreatitis (SAP) group (n =62).Also,these patients were divided into hyperlipidemic acute pancreatitis (HAP) group (n =43) and biliogenic acute pancreatitis (BAP) group (n =91).The initial measurements of D-D,FIB,and PBLC for the patients who were admitted to the hospital within 24 hours of onset and received no treatment before admission were collected.The t test was used for comparison of normally distributed continuous data,while the Mann-Whitney U test was used for non-normally distributed continuous data.The chi-square test was used for comparison of categorical data.In addition,the Spearman correlation test and Pearson correlation test were used for correlation analyses.The receiver operating characteristic (ROC) curve was used to analyze the predictive values of D-D,FIB,and PBLC for the severity of AP.Results Compared with the MAP group,the SAP group had significantly increased D-D and FIB levels in peripheral blood (Z =-3.171,P =0.002;t =-2.339,P =0.021).Compared with the HAP group,the BAP group had a significantly higher D-D level (Z =-4.178,P ＜ 0.001),an insignificantly higher FIB level (P ＞ 0.05),and a significantly lower PBLC (t =2.466,P =0.015).The areas under the ROC curve (AUCs) of D-D,FIB,and PBLC were 0.659,0.611,and 0.591,respectively,and D-D had a higher value than FIB and PBLC in predicting the severity of SAP.The AUC of a combination of D-D,FIB,and PBLC was 0.712.Plasma D-D and FIB levels were positively correlated with the severity of AP (r =0.275 and 0.192,P =0.001 and 0.026).Conclusions D-D,FIB,and PBLC are important for early judgment of the severity of AP,and a combination of the three markers has greater significance.

Objective To determine the relationship between plasma cytokeratin polypeptide 19 (CK 19) level and prognosis of patients with first occurrence of papillary thyroid carcinoma (PTC).Methods This prospective trial enrolled 60 patients with PTC.The plasma CK19 level was determined by ELISA and the other clinical data were collected on admission.All patients were followed up for 12 months.The patients were divided into recurrence group (27 patients) and non-recurrence group (33 patients) according to the results of follow-up.Results Single factor analysis showed that age,female,history of smoking,Graves disease,occupational exposure,the level of thyroid peroxidase antibody,thyroglobulin antibody,triglyceride and CK19 between two groups had significant difference (P ＜ 0.05).Multiple factors analysis showed that female,history of smoking,occupational exposure,the level of thyroid peroxidase antibody,thyroglobulin antibody and CK19 were independent risk factors for recurrence (P =0.01).The recurrence rate of CK19 ≥4.12 μg/L patients was 79.31％ (23/29),significantly higher than that in CK19 ＜4.12 μg/L patients [12.90％ (4/31)] (x2 =5.17,P ＜ 0.05).The recurrence rate of CK19 ≥ 4.12 μ g/L was significantly higher than that in CK19 ＜4.12 μ g/L (x2 =4.11,P ＜ 0.05).Conclusions The plasma CK19 level is an independent risk factor for recurrence of PTC patients.It can be used as a significant independent predictor for recurrence of PTC patients.

Objective To increase the solubility and relieve the mucous irritation of cantharidin (CA) by preparing cantharidin-hydroxypropyl-β-cyclodextrin (CA/HP-β-CD) inclusion complex.Methods The inclusion complex was prepared by co-evaporation method and characterized by differential scanning calorimetry (DSC),X-ray diffractometry (XRD),and nuclear magnetic resonance (NMR).Results The disappearance of CA as well as the shift of exothermic peaks shown in DSC results indicated the complexation phenomenon.XRD results showed that the crystalline CA pattern had disappeared,and in NMR results,H-5 shifted from δ 3.731to 3.695 after complexation and H-2 shifted from δ 3.626 to 3.598,which suggested that part of the drug had entered the HP-β-CD cavity to form an inclusion complex.The solubility increased 10.3 times after complexation and the mucous irritation of CA was relieved remarkably.Conclusion Through complexation with HP-β-CD,the solubility and dissolution rate of CA are improved significantly,and the irritation of musous is relieved.