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 We compared the effect of three anesthetic procedures on the establishment of and recovery effect on the young minipig models of skull defect,and explore an optimal anesthetic procedure for long-lasting surgical experiment in minipigs.Methods Thirty 3-month old Guizhou minipigs (male∶female=1∶1) were randomly divided into three groups,10 in each group.The group A was given with midazolam and ketamine i.p.,the group B received lumianning II i.p.,and the group C received midazolam combined with ketamine and lumianning II i.p.The induction time of anesthesia,the first anesthesia maintenance time,the first anesthesia maintenance period after additional use of anesthetics,the second time anesthesia maintenance period after additional use of anesthetics,the recovery period,the number of times of additional intraoperative use of anesthetics,cumulative amount of anesthetics used,and the adverse reaction and mortality rates of the animals after anesthesia were observed and analyzed.Results The anesthesia induction time in the group B was significantly longer than that in the groups A and C (P<0.05 for both).The anesthesia maintenance time and the anesthesia maintenance after first and second additional use of anesthetics in the groups A were significantly longer than those of the groups A and B (P<0.05 for both).The recovery periods in groups A and C were shorter than that of the group B (P<0.05 for both).The number of times of additional intraoperative use of anesthetics,the total dose of anesthetics,the adverse reaction and mortality rates in the group C were significantly lower than those of the groups A and B (P<0.05 for both).Conclusions The combination of midazolam with ketamine and lumianning II is a simple,easy to control the anesthesia depth,and a safe method to anesthetize young minipigs in long-lasting surgical experiment.