Differential diagnostic value of simultaneous detection of CD69 and HLA-DR on host T and NK cells in QFT-TB assay for identifying active tuberculosis.

BACKGROUND: Interferon-gamma release assay (IGRA) for tuberculosis (TB) remains limited in its ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Activation markers on host T and NK cells are currently considered to be promising markers in the diagnosis of ATB. METHODS: This prospective observational study enrolled 213 participants and the participants were divided into ATB, LTBI, other lung-related diseases (ORD), and health control (HC) groups. CD69 and HLA-DR on T and NK cells were detected in QFT-TB assay, and a composite scoring system (TB-Flow) was created for the diagnosis of ATB. RESULTS: The expression of activation markers (CD69 and HLA-DR) were significantly increased in ATB. HLA-DR on NK cells, CD69 on T cells, and QFT-TB in the differential diagnosis of ATB and HC were all of good diagnostic value (AUC>0.90). In addition, the TB-Flow greatly improved the efficiency of differential diagnosis between ATB and LTBI (AUC=0.90, 95%CI: 0.84-0.96), with sensitivity and specificity of 79.17 % (95%CI: 64.60%-89.04 %) and 88.68 % (95%CI: 76.28%-95.31 %). CONCLUSIONS: CD69 and HLA-DR on host T and NK cells are promising markers in distinguishing different TB infection status. Our blood-based TB-Flow scoring system can distinguish ATB from LTBI with good diagnostic efficacy.

Expression of HLA-DR and KLRG1 enhances the cytotoxic potential and cytokine secretion capacity of CD3+ T cells in tuberculosis patients.

BACKGROUND: Human T cells play an important role in immunity against tuberculosis (TB) infection. Activating receptor HLA-DR and inhibitory receptor KLRG1 are critical regulators of T cell function during viral infection and tumorigenesis, but they have been less studied in TB infection. METHODS: In this study, we explored the relationship between CD3+ T cell expression of HLA-DR and KLRG1 receptors and function against TB infection. Flow cytometry was conducted to assess the immunomodulatory effects of HLA-DR and KLRG1 receptors on CD3+ T cells in patients with different TB infection status. RESULTS: We found activating receptors HLA-DR, NKG2C, CD57 and NKP46, and inhibitory receptors KLRG1 and KIR on CD3+ T cells in different TB infection status showed different distribution patterns; the cytotoxic potential and cytokine secretion capacity of CD3+ T cells after Mtb-specific antigen stimulation were significantly enhanced in TB infection groups. Further studies revealed HLA-DR+ T and KLRG1+ T cells expressed higher activating and inhibitory receptors than the negative population. In addition, the expression of cytotoxic potential and cytokine secretion capacity of HLA-DR+ T and KLRG1+ T cells was significantly higher than that of HLA-DR- T and KLRG1- T cells. CONCLUSIONS: Expression of HLA-DR and KLRG1 enhances the cytotoxic potential and cytokine secretion capacity of CD3+ T cells in TB patients, suggesting CD3+ T cells expressing HLA-DR and KLRG1 are important effector cell phenotypes involved in the host anti-TB infection. HLA-DR and KLRG1 expressed by CD3+ T cells may be potential predictive markers of TB disease progression and clinical immune assessment.

Diagnostic Value of CD25, CD69, and CD134 on Tuberculosis-Specific Antigen-Stimulated CD4+ T Cells for Tuberculous Pleurisy.

Rapid and accurate methods for the diagnosis of tuberculous pleurisy (TP) are urgently needed. Activation markers of tuberculosis (TB)-reactive T cells are considered promising for the diagnosis of active TB (ATB). Different activation indexes may play different roles in the progression of TB, but there are few reports on T cell activation indicators, except for HLA-DR. Hence, we evaluated the expression of early (CD25 and CD69) and late (CD134) activation markers on TB antigen-stimulated CD4+ T cells in populations with different TB infection status and investigated their diagnostic value for ATB, particularly, for TP. Moreover, we compared the differences in the diagnostic efficacy among the indexes from peripheral blood (PB) and pleural fluid (PF) for TP. The expression of each activation marker was significantly increased in TB-infected populations (patients with ATB and latent TB infection vs. healthy individuals; patients with TP vs. non-TP) and was significantly higher in the PF than in the PB of patients with TP. The diagnostic performance of the coexpressed activation markers was superior to that of single expression markers in the differential diagnosis of ATB and non-TB, with CD25+CD134+ showing the best diagnostic efficiency (AUC: 0.93, 95% CI, 0.87-0.99; sensitivity: 86.7%, 95% CI, 72.5%-94.5%; and specificity: 94.0%, 95% CI, 82.5%-98.4%). Except for TB-IGRA, the activation indexes were more accurate than conventional laboratory methods for ATB diagnosis. In addition, the expression of CD25+CD134+ in PB and PF was the best values for differential diagnosis of TP and NTP, with AUCs of 0.87 (95% CI, 0.77-0.96) and 0.95 (95% CI, 0.90-1.00), respectively. Our study provides information on the diagnostic value of different activation markers for TB and shows that the expression of CD25+CD134+ on CD4+ T cells in PF can serve as a potential marker for TP diagnosis.

Social support and posttraumatic growth: A meta-analysis.

BACKGROUND: The beneficial role of social support on posttraumatic growth (PTG) has been assumed by theoretical models and established in some studies. However, there are inconsistent findings and little knowledge on moderators. The present study aims to investigate the overall effect size of the relationship and identify factors affecting the association. METHODS: Six electronic databases were searched. Newcastle-Ottawa Quality Assessment Scale (NOS) were used to evaluate the quality of studies. Study quality, study design, trauma type, PTG measure, social support measure, continent, publishing language, sample size, gender, religion, and age were analyzed as moderators. Meta-regression was conducted with the significant differential predictors in moderator analysis. RESULTS: The meta-analysis included 217 samples and a total of 47,940 participants from both longitudinal and cross-sectional studies. There was a medium positive effect size between social support and PTG in random effect model, r = 0.418, p < .001. The meta-regression analysis indicated that the association between social support and PTG was stronger among caregivers (vs. other traumatized samples), Chinese, older individuals and studies with smaller sample size. LIMITATIONS: Only survey results were included in the analysis. The retrospective self-report may limit a more objective assessment of the relations. In addition, 87 % of the studies were cross-sectional, which may influence the estimation of a valid effect size. CONCLUSIONS: Regarding the medium positive association between social support and PTG, it is important to enhance social support for trauma survivors. It will be especially effective for caregivers, Chinese, and older people.

Host biomarkers other than interferon gamma in QFT-TB supernatants for identifying active tuberculosis.

Interferon gamma release assays (IGRAs) for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). The objective of our study was to evaluate the value of additional cytokines/chemokines other than interferon gamma (IFN-γ) as biomarkers to identify different TB infection status. A total of 128 subjects were enrolled to detect the quantification of IL-2, IP-10, MCP-1 and RANTES in the supernatants of QuantiFERON®-TB (QFT-TB). Area under the curve (AUC) was used to evaluate the diagnostic efficiency. Notably, Mycobacterium tuberculosis (Mtb) induced cytokines/chemokines of ATB patients were significantly higher than those of the LTBI, other lung related diseases (ORD) and healthy controls (HC). Moreover, ROC analysis indicated that all cytokine/chemokine parameters detected were more capable of distinguishing ATB from LTBI than IFN-γ, especially IL-2. The diagnostic model including TB specific IL-2 and RANTES improved the performance in distinguishing ATB from LTBI, which was superior to single cytokines/chemokines in QFT-TB supernatants. Our results suggest that the combination of Mtb specific cytokines/chemokines has great prospects in the diagnosis of ATB, and the diagnostic model based on IL-2 and RANTES can be used as an alternative to distinguish ATB from LTBI.

Evaluating the diversity of circulating natural killer cells between active tuberculosis and latent tuberculosis infection.

Tuberculosis (TB) is a leading global public health problem; however, the mechanisms underlying the immunopathology of TB progression are not well understood. It is currently believed that Mycobacterium tuberculosis (Mtb) infection can modify natural killer (NK) cell phenotypic signatures. Hence, our study was designed to investigate the diversity of circulating NK cells in patients with different TB infection status. NK subsets, as well as their expression of activating and inhibitory receptors between active TB (ATB) and latent TB infection (LTBI) were evaluated. There were significant differences in NK cell phenotypes between ATB, LTBI and healthy controls. Notably, the proportion of KLRG1 in NK cells (P = 0.036), as well as in their subsets CD56DimCD16+ (P = 0.046) and CD27+ (P = 0.027) NK cells, increased significantly in LTBI group than in ATB group; while Mtb specific IFN-γ+CD56BrightCD16Dim NK cells expressed higher KLRG1 in ATB than in LTBI (P = 0.027). However, the expression of activating receptor NKG2D in NK subsets showed no significant difference among the study groups. Our results suggest that different TB infection status are coupled with the diversity of NK cell compartments, and the expression of KLRG1 in NK cells may be a specific phenotype that modulates the progression of TB from latent to active.

Study on the value of small dense low-density lipoprotein in predicting cardiovascular and cerebrovascular events in the high-risk stroke population.

BACKGROUND: Lipid management in people at high risk of stroke is an important measurement to prevent the occurrence of stroke. The study aims to investigate the association between sdLDL and cardiovascular and cerebrovascular events in high-risk stroke populations. METHODS: This was a prospective study. Screened from 15,933 individuals aged >40 years in April 2013 and followed up at 3rd, 6th, 12th, and 24th months, 823 participants met the screening criteria and were investigated for clinical data and biochemical parameters. RESULTS: A total of 286 subjects had varying degrees of carotid stenosis, and 18 subjects experienced cardiovascular and cerebrovascular events during the two-year follow-up period. There was no positive correlation between sdLDL and carotid stenosis. Carotid stenosis and extent of carotid stenosis involvement did not predict cardiovascular and cerebrovascular events in patients with high-risk stroke, while sdLDL did. The sdLDL level in the events group was significantly higher than those in the no event group (p = 0.002). In the events group, the risk of events in the fourth quartile of sdLDL was 10.136 times higher than in the first quartile (HR = 10.136, 95% CI: 1.298-79.180, p = 0.027). CONCLUSIONS: sdLDL was positively correlated with the incidence of cardiovascular and cerebrovascular events, which can predict the occurrence of an event and provide a scientific basis for early prevention.

Construction of Ag2O-modified g-C3N4 photocatalyst for rapid visible light degradation of ofloxacin.

The design of stable and highly efficient photocatalysts had emerged as an economic and promising way for eliminating harmful pharmaceutical pollutants. In this study, a series of Ag2O-modified g-C3N4 composites with different Ag2O amounts (denoted as Ag2O-CNx) were fabricated via a facile reflux condensation methodology. Ofloxacin (OFL) was chosen as a model pollutant to evaluate the degradation efficiency of the photocatalytic system. The optimal photocatalytic activity was achieved with Ag2O-CN1.0, which reached up to 99.1% removal of OFL after 15-min reaction and the pseudo-first-order constant was 0.469 min-1, approximately 42 times higher than that of g-C3N4. Considering the complexity of the actual environment, the important influential factors such as catalyst dosage, initial OFL concentration, solution pH, and natural organic matter on the OFL degradation were systematically investigated. Additionally, Ag2O-CN1.0 showed good stability and recyclability in multiple cycle experiments. The feasible photodegradation mechanism of OFL was proposed with radical scavenger experiments, and the degradation products were determined. Furthermore, the enhanced photocatalytic activity could be ascribed to not only the high photogenerated charge separation efficiency and the surface plasmon resonance effect of metallic Ag, but also the p-n heterojunction formed between Ag2O and g-C3N4. Therefore, Ag2O-CN1.0 was a treatment material possessing great application prospects for eliminating OFL in wastewater.

Band gap tuning of g-C3N4 via decoration with AgCl to expedite the photocatalytic degradation and mineralization of oxalic acid.

A series of functional organic-metal AgCl-decorated graphitic carbon nitride (AgCl-CNx) composites were synthesized and applied for the degradation of oxalic acid (OA) under visible light. The highest photocatalytic activity was achieved with AgCl decoration ratio of 1.0 (denoted as AgCl-CN1.0). The pseudo-first-order constant for OA degradation was 0.0722 min-1 with the mineralization efficiency of 90.80% after 60 min reaction in the photocatalytic process with AgCl-CN1.0. A variety of characterization techniques including Brunauer-Emmett-Teller, X-ray diffraction, scanning electron microscope, transmission electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectra, ultraviolet-visible diffuse reflectance spectra, photoluminescence, and Mott-Schottky were utilized to elucidate the physicochemical, microstructure, and optical properties contributing to the improvement of the photocatalytic performance. The results showed that AgCl-CN1.0 had an oblate flaky erythrocyte-like structure with a moderate band gap energy of ~3.00 eV. In addition, the effects of the key parameters (i.e., AgCl-CN1.0 dosage, initial OA concentration, solution pH, and presence of natural organic matter) on OA degradation were systematically investigated. Radical scavenger experiments indicated that photogenerated holes, electrons, superoxide anion radicals, and hydroxyl radicals were the dominant reactive species. Moreover, AgCl-CN1.0 exhibited excellent stability and reusability for OA degradation without detectable Ag+ release in the solution over multiple reaction cycles. The efficient OA mineralization could be mainly ascribed to the moderate specific surface area, increased numbers of active sites, and effective interfacial charge transfer of AgCl-CN1.0. Overall, the AgCl-CN1.0 composite was demonstrated to be a highly efficient, stable, and recoverable photocatalyst.