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Objective:To explore the expression and clinical significance of immunosuppressive receptor T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) on the peripheral blood mononuclear cells (PBMC) in silicosis patients with Mycobacterium tuberculosis infection. Methods:August 2018, a total of 78 patients with silicosis (all were quarry workers in Sanmen County, Zhejiang Province) were enrolled and divided into silicosis combined with active pulmonary tuberculosis group (APTB group), silicosis combined with latent tuberculosis infection group (LTBI group), and simple silicosis with non-tuberculosis infection group (non-TB group). Flow cytometry was used to analyze the expressions of TIGIT, programmed death-1 (PD-1) and transcription factor T-bet on PBMC from patients. Mann-Whitney U test and Pearson correlations analysis were used for statistical analysis. Results:Among the 78 patients, eight were in the APTB group, 24 in the LTBI group, and 46 in the non-TB group. The expressions of PD-1 and TIGIT on CD8 + T cells in the APTB group (29.45%(16.78%) and 65.40%(12.12%), respectively) were significantly higher than those in the LTBI group (17.40%(11.17%) and 48.30%(28.75%), respectively; U=23.500 and 43.500, respectively, P=0.000 8 and 0.020 5, respectively) and non-TB group (15.95%(12.46%) and 45.30%(19.75%), respectively; U=64.000 and 69.000, respectively, P=0.002 3 and 0.003 8, respectively), and the differences were all statistically significant. The expression of TIGIT was positively correlated with PD-1 on CD8 + T cells in silicosis patients ( r=0.434 3, P<0.01). The proportion of PD-1 + TIGIT + CD8 + T cells in the APTB group (19.90%(22.67%)) was significantly higher than those in the non-TB group (11.55%(11.29%), U=76.500, P=0.007 1) and LTBI group (11.55%(10.53%), U=41.000, P=0.015 4), while the proportion of PD-1 -TIGIT -CD8 + T cells in the APTB group (30.60%(12.90%)) was significantly lower than non-TB group (48.90%(18.98%), U=58.000, P=0.001 3) and LTBI group (47.20%(24.59%), U=41.000, P=0.015 4). The differences were all statistically significant. The expression of T-bet on the peripheral blood CD8 + T cells in the APTB group (29.45%(16.78%)) was higher than that in the non-TB group (15.95%(12.46%)) and the LTBI group (17.40%(11.17%)), and the differences were both statistically significant ( U=46.500 and 46.000, respectively, P=0.000 3 and 0.028 3, respectively). The expression of T-bet on CD8 + T cells was positively correlated with TIGIT on CD8 + T cells ( r=0.456 7, P<0.01). The expression of T-bet on PD-1 + TIGIT + CD8 + T cells in the APTB group (65.40%(12.12%)) was higher than those in the LTBI group (48.30%(28.75%), U=23.500, P=0.000 8) and non-TB group (45.30%(19.75%), U=65.000, P=0.002 6), and the differences were both statistically significant. Conclusion:The immunosuppressive receptor PD-1 and TIGIT are highly expressed on CD8 + T cells in silicosis patients with active pulmonary tuberculosis, which indicates CD8 + T cells exhaustion in these population, while the highly co-expression of T-bet suggests the exhausted subsets may have reversed potentiality.
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Objective To retrospectively analyze the clinical and laboratory characteristics of patients with positive blood culture results for Mycobacterium tuberculosis (M.tb).Methods The clinical laboratory database of patients suspected with disseminated tuberculosis from January 2009 to January 2017 in Huashan Hospital affiliated with Fudan University were collected and analyzed.The clinical manifestations,laboratory characteristics and outcomes between disseminated tuberculosis patients with positive blood culture (positive blood culture group) for M.tb and negative results (negative blood culture group) were compared.T test,Mann-Whitney U test and Fisher exact test were used for statistical analysis.Results A total of 5 589 patients suspected with M.tb infection had peripheral blood culture for mycobacterium.Positive blood culture for M.tb was found in 26 disseminated tuberculosis patients,while 6 patients finally identified as nontuberculous mycobacterium (NTM) with species identification,and 22 disseminated tuberculosis patients with negative blood culture results were enrolled during the same period as control.The mean age ([49.1 ± 10.1] years old vs [38.3 ± 17.1] years old,t =2.460,P =0.018),the proportion of diagnosed with fever of unknown origin at admission (FUO) (65.0% [13/20] vs 13.6% [3/22],P =0.001),the proportion of diagnosed with focal infection (30.0% [6/20] vs 86.4% [19/22],P =0.001),the proportion of patients with other diseases (75.0%[15/20] vs 22.7% [5/22],P =0.002),the proportion of patients with hematological diseases (35.0% [7/20] vs 4.5% [1/22],P =0.018) and the proportion of patients with tumor (20% [4/20] vs 0[0/22],P =0.043) in the positive blood culture group were significantly different from those in the negative blood culture group.Laboratory examinations of the percentage of neutrophils,the percentage of lymphocytes,the percentage of monocytes,the value of neutrophil/lymphocyte,the level of hemoglobin,the level of erythrocyte sedimentation rate,the level of C-reactive protein,the level of procalcitonin and the positive rate of T-SPOT.TB in positive blood culture groups were significantly different from those in negative blood culture group (all P < 0.05).Conclusions Peripheral blood M.tb culture is more likely to be positive for those elder disseminated tuberculosis patients with hematological diseases or tumors,and those with increase of neutrophil counts and inflammation markers but reduction of lymphocyte counts and hemoglobin.
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Objective To investigate the prevalence of tuberculosis among silicosis patients and silica exposure patients,and to analysis the risk factors of tuberculosis among these population.Methods A total of 1 227 silica exposure patients from Wenling,Zhejiang were enrolled in this field study.Basic demographic information was collected and chest X-ray was taken for each patient.Sputum was collected for Mycobacterium tuberculosis culture and strain identification. In univariate analysis,t test was performed for continuous variables andχ2 test for categorical variables.In multivariate analysis,the odds ratio (OR )was calculated along with a 95 % confidence interval (CI )by binary Logistic regression. Results A total of 1 204 silica exposure patients had full basic information and 99.8% were male patients with mean age of (59.4 ± 6.8 )years.The patients in phase 0 + to phase Ⅲ were 172 (14.3%),255 (21 .2%),160 (13.3%)and 617 (51 .2%),respectively.The tuberculosis prevalence rate was about 7.3% among these population.The risk factors for tuberculosis including phase Ⅱ silicosis (OR =2.96, 95 %CI :1 .05 -8.32,P =0.04)and phase Ⅲ silicosis (OR=3.88,95 %CI :1 .58-9.56,P <0.01),and contacting with tuberculosis patients (OR=4.14,95 %CI :1 .91 -8.98,P <0.01).Patients complicated with tuberculosis lacked specific symptoms,but fever and weight loss were more frequent.Conclusion Tuberculosis is highly prevalent in silicotic patients,especially in patients with phase Ⅱ/Ⅲ silicosis and in patients with tuberculosis contact history.