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OBJECTIVE@#To screen new serum metabolic biomarkers for different drug resistance profiles of pulmonary tuberculosis (TB) and explore their mechanisms and functions.@*METHODS@#We collected serum samples from TB patients with drug sensitivity (DS), monoresistance to isoniazid (MR-INH), monoresistance to rifampin (MR-RFP), multidrug resistance (MDR), and polyresistance (PR). The metabolites in the serum samples were extracted by oscillatory and deproteinization for LC-MS/MS analysis, and the results were normalized by Pareto-scaling method and analyzed using Metaboanalyst 4.0 software to identify the differential metabolites. The differential metabolites were characterized by function enrichment and co-expression analysis to explore their function and possible pathological mechanisms.@*RESULTS@#Compared with the DS group, 286 abnormally expressed metabolites were identified in MR-INH group, 362 in MR-RPF group, 277 in MDR group and 1208 in PR group by LC-MS/MS analysis. Acetylagmatine ( < 0.05), aminopentol ( < 0.05), and tetracosanyl oleate ( < 0.05) in MR-INH group; Ala His Pro Thr ( < 0.001) and glycinoprenol-9 ( < 0.05) in MR-RFP group; trimethylamine ( < 0.05), penaresidin A ( < 0.05), and verazine ( < 0.05) in MDR group; and PIP (18:1(11Z)/ 18:3(6Z, 9Z, 12Z)) ( < 0.001), Pro Arg Trp Tyr ( < 0.001), N-methyldioctylamine ( < 0.001), and phytolaccoside E ( < 0.05) in PR group all showed significant differential expressions. Significant differential expressions of phthalic acid mono-2-ethylhexyl ester ( < 0.05) and eicosanoyl-EA ( < 0.05) were found in all the drug resistant groups as compared with DS group.@*CONCLUSIONS@#Acetylagmatine, aminopentol, tetracosanyl oleate, Ala His Pro Thr, glycinoprenol-9, trimethylamine, penaresidin A, verazine, PIP(18:1(11Z)/18:3(6Z, 9Z, 12Z)), Pro Arg Trp Tyr, N-methyldioctylamine, phytolaccoside E, phthalic acid mono-2-ethylhexyl ester, and eicosanoyl-EA are potentially new biomarkers that indicate monoresistance, multi-drug resistance and polyresistance of Mycobacterium tuberculosis. The combined use of these biomarkers potentially allows for assessment of drug resistance in TB and enhances the diagnostic sensitivity and specificity.
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Humans , Biomarkers , Chromatography, Liquid , Tandem Mass Spectrometry , Tuberculosis, Multidrug-Resistant , Tuberculosis, PulmonaryABSTRACT
Objective To study serum IL-22 levels in patients with pulmonary tuberculosis and diabetes mellitus (PPTDM) and to analysis their clinical significance.Methods ELISA was used to detect serum IL-22 levels in 30 cases PPTDM pa-tients,30 cases pulmonary tuberculosis (PTB)patients,30 cases diabetes mellitus (DM)patients and 30 cases healthy vol-unteers (HV).Results Serum IL-22 levels of PPTDM patients (54.4±4.81 pg/ml)were significantly lower than those in diabetes mellitus (DM)patients (72.36±5.12 pg/ml)and healthy volunteers (HV)(68.32±3.08 pg/ml)(t=2.557,P =0.013;t=2.437,P =0.018),respectively.There was no significantly different of serum IL-22 levels between PPTDM and PTB patients (t=1.190,P =0.239).Serum IL-22 levels of diabetes mellitus coincident with pulmonary tuberculosis (DM-PTB)patients (64.62±8.59 pg/ml)were significantly higher than those in pulmonary tuberculosis coincident with diabetes mellitus (PTB-DM)patients (44.21±2.68 pg/ml)(t=2.267,P =0.031).Conclusion IL-22 may play an important role in PPTDM development.
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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.
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Objective To analyze the dynamic changes of white blood cells in patients with cavitary pulmonary tuberculosis (CPTB) during chemotherapy procedure ,and explore immunological indexes which could evaluate the curative effect and prognosis . Methods 85 cases of patients with CPTB (CPTB group) and 100 healthy people conducted physical examination (control group) were enrolled in this study ,The immunological indexes of white blood cells were detected and compared between CPTB group and control group ,and dynamic changes of white blood cells were analyzed in patients with CPTB .Results Compared with the control group ,absolute lymphocyte count and percentage of lymphocyte were decreased in the CPTB group before chemotherapy ,while the total white blood cells count ,absolute neutrophil count and percentage of neutrophil ,absolute monocyte count and percentage of monocyte were increased in the CPTB group before chemotherapy ,there were statistically significant differences between the two groups(P<0 .05) .Except the absolute lymphocyte count ,other indexes were statistically increased or decreased during chemothera‐py procedure .Conclusion After chemotherapy ,the immunological reactions induced by lymphocyte are under inhibitory state .The dynamic changes of white blood cells could reflect the state of cellular immunity in patients with CPTB during chemotherapy ,which could be helpful for the evaluation of curative effect and prognosis .
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Purpose To investigate estrogen receptor ( ER ) , progesterone receptor ( PR ) expression in PTEN-deficient endometrial carcinoma and to analysis the relationship of PTEN, ER and PR protein expression with histological grade, pathological staging and muscle invasive. Methods Immunohistochemistry EnVision was used to detect the expression of PTEN, ER and PR protein in 100 ca-ses of endometrial carcinoma. Results The rate of PTEN-deficient endometrial carcinoma was 52. 0% (52/100). The expression rate of ER, PR protein on PTEN-deficient endometrial carcinoma was 15. 4% (8/52), 19. 2% (10/52), respectively. And the expression rate of ER, PR protein on PTEN over-expression endometrial carcinoma was 72. 7% (8/11), 63. 6% (7/11), respectively. The rate of PTEN, ER and PR expression types shown PTEN-ER-PR- was 42. 0% (42/100), which was higher than other types (P <0. 05). Different PTEN, ER and PR expression types were well correlated with histological grade and pathological staging (P<0. 05), but not with muscle invasive. Conclusion Combined detection of PTEN, ER and PR may have an important reference value for prog-nosis and treatment of endometrial carcinoma.
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AIM:To investigate the effect of mesalazine treatment on regulation of Th1, Th17 and Treg cells in mice with dextran sulfate sodium ( DSS)-induced ulcerative colitis ( UC) .METHODS:The expression of IL-17, IFN-gam-ma and Foxp3 in the peripheral blood mononuclear cells ( PBMC) and intestinal mucosa lamina propria mononuclear cells ( LPMC) of DSS-induced UC mice was detected by flow cytometry analysis.The effect of mesalazine treatment on regulaiton of Th1, Th17 and Treg cells in the mice with DSS-induced ulcerative colitis was examined.RESULTS:The expression of IL-17, IFN-γand Foxp3 on CD4 +T cells were significantly higher in the PBMC of DSS-induced mice than those in control group.CD4+IFN-γ+T cells and CD4 +Foxp3 +T cells were higher in LPMC than those in control group, except CD4+IL-17 +T cells.Moreover, the Th1, Th17 and Treg cells were higher in DSS group than those in control group in LPMC.How-ever, only Tregs was higher in PBMC.Pre-treatment with mesalazine significantly decreased the number of Th17, Th1 and Treg cells of UC model mice both in PBMC and LPMC.CONCLUSION: The Th1, Th17 and Tregs cells in DSS-induced mice were significantly higher than those in control mice, suggesting that CD4 +T cell subsets play an important role in the pathogenesis of UC.Mesalazine may play a role in the treatment of UC by regulating the Th1, Th17 and Tregs cells.
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Objective To stduy the expression of PTEN ,P27 and BAG-1 in endometrial carcinoma ,and to analysis the clinical significance .Methods The expression of PTEN ,P27 and BAG-1 in 102 cases of endometrial carcinoma ,90 cases of endometrial hy-perplasia and 44 cases of normal endometrium tissue were detected by immunohistochemistry .Results PTEN and P27 in endome-trial carcinoma and hyperplasia tissue showed lower expression ,BAG-1 showed high expression in them .The expression of PTEN and BAG-1 were well correlated to histology degree and muscular infiltration .BAG-1 expression also had a well correlated to clinical stage .In this study ,we had not find a correlated between the expression of P27 and clinical and pathology characteristic of patien . PTEN expression had a Pearson relevance to P27 or BAG-1 expression ,but there was no correlation between P27 and BAG-1 .Con-clusion PTEN and P27 in endometrial carcinoma and hyperplasia tissue showed lower expression ,BAG-1 showed high expression in them .PTEN ,P27 and BAG-1 might play a role in the development of endometrial cancer .
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Objective To investigate the expression of IL-17 in the serum and T cells of the patients with breast cancer and its correlation with breast cancer functional indicators.Methods The flow cytometry analysis was adopted to detect the percentage of peripheral blood CD3 + CD4 + IL-17 + T cells in breast cancer patients;the ELISA method was used to detect serum IL-17 content;the chemiluminescence immunoassay was used to detect CA153 and CA125 levels.The correlation between IL-17 with various indi-cators was analyzed.Results The percentage of CD3 + CD4 + IL-17 + T cell in peripheral blood of the breast cancer patients had sta-tistically significant difference compared with the healthy control group(P <0.05);serum IL-17 level had statistically significant difference compared with the healthy control group(P <0.05);serum IL-17 level was positively correlated with the percentage of CD3 + CD4 + IL-17 + T cells and the CA153 level;IL-17 level had no significant correlation with serum CA125 level.Conclusion The IL-17 expression level is associated with breast cancer.