1.Study the influence on detection activity of coagulation factors Ⅸ in human prothrombin complex concentrates
Jingrui LI ; Xiaoxin GAO ; Yuchi HU
Chinese Journal of Biochemical Pharmaceutics 2017;37(4):426-428
Objective To study the influence factors on detection coagulation factors Ⅸ activity in human prothrombin complex concentrates(PCC).MethodsUsing Chinese Pharmacopoeia(2010)as reference,factor Ⅸ deficient plasma from different manufacturers,different types of instruments,different methods of heparin neutralization,different sample pretreatment methods were used to determine the activity of coagulation factor Ⅸ in PCC.The influence on the results of coagulation factor Ⅸ was analyzed.ResultsThere was a significant difference between factor Ⅸ deficient plasma from different manufacturers for the activity of coagulation factors Ⅸ(P<0.05).There was no significant difference between the results of coagulation factor Ⅸ measured by different types of Automatic Coagulation Analyzer.When the dilution ratio was more than 60 times,the neutralization of heparin had little effect on the coagulation factor Ⅸ activity.When the dilution ratio is less than 60 times,the detection results of coagulation factor Ⅸ by neutralization of heparin are higher than no neutralization of heparin,and the difference is significant(P<0.05).Samples for pre-temperature or not and whether dissolution for 15minutes or not,the coagulation factor Ⅸ activity showed no significant difference.Conclusion The coagulation factor Ⅸ activity in PCC was affected by factor Ⅸ deficient plasma from different manufacturers,different dilution times of heparin neutralization method and sample pre-treatment methods.It must be paid attention to in the detection process.Strengthen the quality control of the factor deficient plasma and the standardization of operation process are necessary.The External Quality Assessment for the detection of coagulation factors in PCC products should be edtablished.
2.Establishment of a double antibody sandwich ELISA for detection of human IL-37
Yan JIA ; Yuchi GAO ; Siping LI ; Xin WANG ; Chen CHEN ; Shiyan YU ; Zegang ZHUANG ; Junai ZHANG ; Zhangquan CHEN ; Junfa XU
Chinese Journal of Immunology 2017;33(9):1346-1349,1354
Objective:To establish a double antibody sandwich ELISA assay for detection of human IL-37 in serum.Methods: Mouse anti-human IL-37 monoclonal antibody was used as capturing antibody,rabbit anti-human IL-37 polyclonal antibodies served as detection antibody,HRP labeled goat anti-rabbit IgG employed as second antibody and recombinant human IL-37 protein used as reference standard for the establishment of a doubleantibody sandwich ELISA.The working conditions were optimized,such as sensitivity,linear range,reproducibility and evaluated the serum IL-37 in patients with Dengue fever.Results: The sensitivity of the established ELISA method was 1.465 μg/L approximately.Likewise,the linearity range of this method was about (1.465-46.875) μg/L.Further,the co efficient of variation (CV) of inter-batch and intra-batch in this study were 6.6% and 11.7%,respectively.Notably,this method could be used in the detection of IL-37 in serum of the patients with Dengue fever,showing that the level of IL-37 in Dengue fever patients was much higher than that in healthy controls.Conclusion: The double antibody sandwich ELISA assay for the detection of human IL-37 was successfully established,which can be apply to detect of human IL-37 in clinical samples.
3.Detection of IL-35 in plasma in the patients with active tuberculosis complicated with bronchiectasis and its clinical significance
Bin KONG ; Ganbin LIU ; Wenyu XIANG ; Yuanbin LU ; Yuchi GAO ; Dongzi LIN ; Junai ZHANG ; Jincheng ZENG ; Lailong YI ; Junfa XU
International Journal of Laboratory Medicine 2015;(16):2289-2291,2294
Objective To detect plasma interleukins-35 (IL-35 )level in the patients with active tuberculosis complicated with bronchiectasis and to analyze its clinical significance.Methods Peripheral blood of patients with active tuberculosis from depart-ment of Dongguan 6th People′s hospital were collected,assigned to the active tuberculosis complicated with bronchiectasis group and active tuberculosis group.The healthy volunteers served as the control group.The plasma IL-35 level was measured by ELISA, and peripheral blood neutrophils and lymphocytes were detected by hematology analyzer.Results The levels of plasma IL-35 signif-icantly increased in both patients with active tuberculosis complicated with bronchiectasis and patients with active tuberculosis.The level of plasma IL-35 of patients with active tuberculosis complicated with bronchiectasis was significantly higher than that of the patients with active tuberculosis.The absolute value and percentage of peripheral blood neutrophils of patients with active tubercu-losis complicated with bronchiectasis were significantly higher than those of healthy volunteers.However,the percentage of periph-eral blood lymphocytes of patients with active tuberculosis complicated with bronchiectasis was significantly lower than that of healthy volunteers.Pearson correlation analysis showed that the absolute value of peripheral blood neutrophils of patients with ac-tive tuberculosis was positively correlated to the level of plasma IL-35.Conclusion IL-35 may play an important role in the progres-sion of active tuberculosis complicated with bronchiectasis.The determination of IL-35 may be helpful to the diagnosis of patients with active tuberculosis complicated with bronchiectasis.
4.Discovery of a series of dimethoxybenzene FGFR inhibitors with 5pyrrolo2,3-pyrazine scaffold: structure-activity relationship, crystal structural characterization and study.
Peng WEI ; Bo LIU ; Ruifeng WANG ; Yinglei GAO ; Lanlan LI ; Yuchi MA ; Zhiwei QIAN ; Yuelei CHEN ; Maosheng CHENG ; Meiyu GENG ; Jingkang SHEN ; Dongmei ZHAO ; Jing AI ; Bing XIONG
Acta Pharmaceutica Sinica B 2019;9(2):351-368
Genomic alterations are commonly found in the signaling pathways of fibroblast growth factor receptors (FGFRs). Although there is no selective FGFR inhibitors in market, several promising inhibitors have been investigated in clinical trials, and showed encouraging efficacies in patients. By designing a hybrid between the FGFR-selectivity-enhancing motif dimethoxybenzene group and our previously identified novel scaffold, we discovered a new series of potent FGFR inhibitors, with the best one showing sub-nanomolar enzymatic activity. After several round of optimization and with the solved crystal structure, detailed structure-activity relationship was elaborated. Together with metabolic stability tests and pharmacokinetic profiling, a representative compound () was selected and tested in xenograft mouse model, and the result demonstrated that inhibitor was effective against tumors with FGFR genetic alterations, exhibiting potential for further development.