With the advance of drug development and research techniques, the drug metabolic processes and mechanism can be more deeply achieved. As the drug metabolism and pharmacokinetics process are mediated by drug metabolizing enzymes and transporters, study of drug metabolizing enzymes and transporters has become an important part for drug development. The traditional immunoassays with low sensitivity and poor specificity can not reflect the accurate expression level of drug metabolizing enzymes and transporters. We now give a brief review on the quantitative study of drug metabolizing enzymes and transporters by mass spectrometry-based proteomic approach.
Enzymes ; chemistry ; Humans ; Inactivation, Metabolic ; Mass Spectrometry ; Membrane Transport Proteins ; chemistry ; Pharmacokinetics ; Proteomics

500 pmol/L were greater than those in any group.Conclusion Serum MMP-2 can be involved in left ventricular remodeling of HF,and measuring its concentration is helpful to judge the severity and prognosis of HF.

Objective To explore the effect of alfacalcidol soft capsules on immune function in patients with chronic obstructive pulmonary disease(COPD).Methods A total of 172 COPD patients were random-ly divided into the trial group ( n=86 ) and the control group ( n=86 ) . They all accepted the conventional treatment, but the patients in the trial group were given the treatment of alfacalcidol soft capsules 0.25μg? d -1 for 6 months.The difference of immune function ( CD3 +, CD4 +, CD8 +and CD4 +/CD8 +), pulmonary function [forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, diffusion capacity for carbon monoxide of lung/alveolar volume ( DLCO/VA ) ] and acute exacerbations of COPD during 6 months follow -up were compared between the two groups.Results The contrations of CD3 +, CD4 +, CD8 +and CD4 +/CD8 +after treatment in the trial group were significantly higher than that before treatment and control group (P<0.05).The FEV1,FEV1/FVC,DLCO/VA after treatment in the trial group were significantly higher than that before treatment and control group(P<0.05).There were no significant difference of CD3 +,CD4 +, CD8 +, CD4 +/CD8 +, FEV1, FEV1/FVC, DLCO/VA before and after treatment in the control goup(P>0.05).The rate of acute exacerbations of COPD in the trial group (9.30%)was sig-nificantly lower than that in the control group ( 25.58%) during 6 months follow-up.Conclusion Alfacalcidol soft capsules could improve the pulmonary function and reduce acute exacerbations by improving immune function of patients with COPD.

OBJECTIVETo study the genetic pathogenesis of myasthenia gravis (MG) caused by cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene polymorphisms and regulation function of transcription factor.

METHODSELISA assay was used to determine the expression level of serum sCTLA-4 in MG. Four single nucleotide polymorphisms (SNPs) of CTLA-4 at exon 1 +49, promoter -318, -1661, -1772 were analyzed by restriction fragment length polymorphism (RFLP). Transcription factor nuclear factor 1(NF-1) and c/EBPbeta binding site were confirmed by chromatin immunoprecipitation(CHIP) assay.

RESULTSIt was found that the frequencies of the GG+49 genotype and G+49 allele are higher in MG patients with thymoma than those in patients of thymic hyperplasia and normal thymus subgroups. T/C-318 is not correlated with MG. The frequency of CT-1772 genotype is significantly higher in MG patients, especially in MG patients with thymoma, when compared with that in healthy controls. Meanwhile, the frequency of the G-1661 allele and GG-1661 genotype is lower in MG patients. Linkage disequilibrium (LD) between each SNPs in promoter -1772, -1661, -318 and coding sequence 1 (CDS 1) +49 is apparent. sCTLA-4 levels in patients' sera are correlated with the haplotype and genotype. T/C-1772 and A/G-1661 SNPs change the sequence of transcription factor NF-1 and c/EBPbeta binding sites. DNA variants lose site-specific binding activity of transcription factor regulated by lectin ConA and PHA.

CONCLUSIONThere are strong positive linkages among four SNPs. C/T-1772 and A/G-1661 polymorphisms can result in inefficient transcription of CTLA-4 gene. T>C-1772 mutation also affects gene splicing. These SNPs may constitute a factor of susceptibility to disease.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antigens, CD ; Antigens, Differentiation ; blood ; genetics ; CCAAT-Enhancer-Binding Protein-beta ; genetics ; CCAAT-Enhancer-Binding Proteins ; genetics ; CTLA-4 Antigen ; Exons ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Myasthenia Gravis ; genetics ; immunology ; NFI Transcription Factors ; Point Mutation ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Thymoma ; genetics ; Thymus Hyperplasia ; genetics ; Thymus Neoplasms ; genetics ; Transcription Factors ; genetics

OBJECTIVETo investigate the chemical constituents of the bulbs of Bolbostemma panicultum.

METHODThe compounds were isolated by column chromatography on silica gel, C18, Sephadex LH-20 separately and their structures were elucidated by chemical and spectroscopic technologies.

RESULTEight compounds were isolated and identified as maltol(I), emodin(II), cucurbitacin B(III), cucurbitacin E(IV), stigmasta-7, 22, 25-triene-3-ol(V), stigmasta-7, 22, 25-triene-3-nonadecanoic acid ester(VI), stigmasta-7, 22, 25-triene-3-O-beta-D-glucopyranoside(VII), stigmasta-7, 22, 25-triene-3-O-beta-D-(6'-palmitoyl) glucopyranoside(VIII).

CONCLUSIONI-VIII were obtained from this plant for the first time; VI and VIII are new compounds.

Cucurbitaceae ; chemistry ; Emodin ; chemistry ; isolation & purification ; Molecular Structure ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Saponins ; chemistry ; isolation & purification ; Stigmasterol ; analogs & derivatives ; chemistry ; isolation & purification ; Triterpenes ; chemistry ; isolation & purification

The bevacizumab and its glycoforms were analyzed by matrix-assisted laser desorption ionization-time of flight-time of flight-mass spectrometry (MALDI-TOF-MS), sodium dodecyl sulfate polyacrylamide gel electrophoresis ( SDS-PAGE) and short-gun strategy, with the sequence of unique peptide and seventeen glycoforms being characterized. The bevacizumab and its glycopeptides concentrations in mice plasma with different intravenous injection doses of bevacizumab were detected and the concentration-time curves were obtained by parallel reaction monitoring ( PRM) method based on liquid chromatography-tandem mass spectrometry (LC-MS / MS) technique. First, standard curves were created for quantification of mAb in mice plasma, which showed good linearity, with the correlation coefficient (R2 ) value of 0. 998 and the lower limit of quantification of 66 fmol. Detection results of high and low doses of the drug in the mice plasma samples showed that the drug concentration-time curve trend was consistent, e. g. the concentration was decreasing. However, the results of quantitation of seventeen glycoforms demonstrated that the metabolism of different glycoforms was different. The concentrations of most glycoforms increased first, whereas the metabolism afterwards differed by different glycoforms.

With the continuous development of science and technology,environmental pollution has become increasingly severe,which makes environmental monitoring crucial.In recent years,electrochemical sensing strategy has attracted wide attention due to its advantages such as low cost,easy operation and fast detection speed.However,the detection performance still faces many challenges such as low sensitivity,high limit of detection and poor selectivity.Metal-organic frameworks(MOFs)is a kind of ordered network porous crystal formed by the coordination bond of organic ligands and metal ions/ion clusters,which can be used to prepare high-performance electrode materials for construction of electrochemical sensors because of their characteristics of large specific surface area,adjustable pore size and diverse structure.However,the poor conductivity and stability of MOFs result in poor electrochemical detection performance,which seriously limits their extensive applications in the field of electrochemistry.Combining MOFs with other functional materials can not only overcome the inherent defects of MOFs but also have the superior properties of both MOFs and functional materials,and the synergistic effect between MOFs and functional materials is conducive to improving the detection performance.Therefore,MOFs composites have been widely used in the electrochemical detection of environmental pollutants.This paper reviewed the applications progress of electrochemical sensors based on MOFs composites(MOFs combine with carbon materials,conductive polymers,metal nanoparticles or MOFs)in detection of environmental pollutants(Pesticides,heavy metal ions,phenolic compounds and nitrites)in the past five years.The prospects and challenges of electrochemical sensors based on MOFs composites for detection of environmental pollutants were also discussed.

Objective To explore potential predictive biomarkers for preeclampsia by analyzing the expression and characteristics of vascular-related inflammatory proteins in the serum of preeclamptic pregnant women.Methods A case-control study was conducted from Sep 2017 to Sep 2018 in the Obstetrics and Gynecology Hospital,Fudan University.Preeclamptic pregnant women and normotensive pregnant controls during the same period were recruited.The concentration of 12 vascular inflammation-related proteins in the patients'serum was determined by multiplex flow cytometry.The vascular-related inflammatory molecules were subjected to differential analysis by non-parametric t-test to obtain preeclampsia-related vascular inflammatory proteins.Finally,high-risk preeclampsia pregnancy serum samples from the biobank were retrieved.Serum concentrations of preeclampsia-related vascular inflammatory proteins were determined,and receiver operating characteristic(ROC)curve analysis was conducted for preliminary predictive assessment of preeclampsia.Results This study conducted a quantitative analysis of serum vascular inflammatory proteins in 39 cases of preeclampsia and 43 cases of control pregnant women,detecting 10 vascular inflammatory proteins expressed in maternal serum.Among these,myoglobin and vascular cell adhesion molecule-1(VCAM-1)exhibited significant elevation in the serum of preeclamptic pregnant women,while matrix metalloproteinase-9(MMP-9)showed a marked decrease.ROC curve analysis revealed that in 96 high-risk early pregnancy women,the area under the curve(AUC)for VCAM-1 reached 0.802,whereas myoglobin and MMP-9 did not significantly predict the occurrence of preeclampsia.Conclusion Preeclampsia patients exhibit abnormal expression of serum inflammatory proteins,among which VCAM-1 may be a potential biological marker for early pregnancy preeclampsia risk prediction.

Inherited afibrinogenemia is a rare autosomal recessive bleeding disease characterized by complete absence of fibrinogen in blood. To identify the genotype in a Chinese family with inherited afibrinogenemia, the samples of peripheral blood were collected from 6 members of 3 generations. The activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (Fg, clauss) were tested. Fg was also analyzed by using immunoturbidimetry method. DNAs of six members were extracted by using a DNA extract kit. All the exons and exon-intron boundaries of the three fibrinogen genes were amplified by using PCR and analyzed by direct sequencing. The results showed that the parents of proband were 3 degree consanguinity. A homozygous c.934_935insA in FGA was found in proband which results in the change of protein p.Ser312fsX42. The parents, grandmother, maternal grandmother and father's sister were all detected with heterozygous mutation which was same as that in proband. In conclusion homozygous c.934_935insA in FGA is a cause of inherited afibrinogenemia and a novel mutation being reported.
Afibrinogenemia ; etiology ; genetics ; Child ; Exons ; Female ; Fibrinogen ; genetics ; Frameshift Mutation ; Heterozygote ; Humans ; Male ; Pedigree

BACKGROUNDDrug treatment for secondary hyperparathyroidism caused by chronic renal failure may be available at the early stage of the disease, but it is not as effective for serious patients. The aim of the study was to evaluate the effect of total parathyroidectomy combined with forearm autotransplantation in the uremic patients with secondary hyperparathyroidism.

METHODSFrom September 1999 through September 2006, parathroidectomy and autotransplantation was performed in 20 patients. The coherence between the results of preoperative parathyroid ultrasonography and surgical exploration were compared. The serum calcium concentration and intact parathyroid hormone (iPTH) were monitored preoperatively, intraoperatively, and postoperatively.

RESULTSA total of 71 hyperplastic parathyroid glands were resected in the 20 patients. The accordance rate of parathyroid localization between B-ultrasonography and intraoperative exploration was 94.4%. The average iPTH value was (110.90 +/- 67.42) ng/L, (433.80 +/- 243.72) ng/L, (48.80 +/- 42.69) ng/L, (229.04 +/- 172.68) ng/L and (232.39 +/- 224.05) ng/L at day 1, 2, 3, 7, 30 after operation respectively. The clinical symptoms were ameliorated and the levels of serum calcium concentration were controlled within the normal range after operation. Recurrent secondary hyperparathyroidism had happened in 1 case, 4 years postoperatively because of the development of autograft hyperplasia, and in another case 2 years postoperatively due to remnant of neck parathyroid glands. The clinical symptoms were all alleviated after re-operation. No surgical complication had occurred in any of the patients.

CONCLUSIONSThe total parathyroidectomy with forearm autotransplantation is feasible, safe, and effective for patients with secondary hyperparathyroidism in the short term. The long-term effects should be further investigated.

Adult ; Aged ; Calcium ; blood ; Female ; Follow-Up Studies ; Forearm ; Humans ; Hyperparathyroidism, Secondary ; blood ; surgery ; Male ; Middle Aged ; Parathyroid Glands ; diagnostic imaging ; transplantation ; Parathyroid Hormone ; blood ; Parathyroidectomy ; methods ; Transplantation, Autologous ; Ultrasonography