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Summary Objectives: The aim of this study is to investigate the clinical usefulness of metagenomic Next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples to discriminate pulmonary tuberculosis (PTB) from Non-TB community-acquired pneumonia (CAP) in PTB suspects. Methods: We investigate the performance of mNGS on BALF samples from 110 PTB suspects, in comparison with conventional microbiological testing (solid media culture, acid-fast bacilli staining (AFS), Xpert) of BALF or sputum samples and final clinical diagnosis. Results: We finally clinically diagnosed 48 cases of pulmonary tuberculosis patients and 62 cases of non-tuberculosis patients. Comparing to the final clinical diagnosis, mNGS produced a sensitivity of 47.92%, which was similar to that of Xpert (45.83%) and culture (46.81%), but much higher than that of AFS (29.17%) for TB diagnosis in BALF samples. Apart from detecting Mycobacterium tuberculosis, mNGS also identified mixed infections in PTB patients, including 3 fungal cases and 1 bacteria case. Meanwhile, mNGS efficiently identified 14 of 22 (63.63%) cases of non-tuberculous mycobacteria (NTM), 7 cases of fungi, 1 case of viral infection, and other common bacterial pathogens in Non-PTB group. Finally, mNGS identified 67.23% infection cases within 3 days, while the conventional methods identified 49.58% infection cases for over 90 days. Conclusion: Our data show that mNGS of BALF represents a potentially effective tool for the rapid diagnosis of PTB suspects.

Background Sudden exacerbations and respiratory failure are major causes of death in patients with severe coronavirus disease 2019(COVID-19) pneumonia, but indicators for the prediction and treatment of severe patients are still lacking. Methods A retrospective analysis of 67 collected cases was conducted and included approximately 67 patients with COVID-19 pneumonia who were admitted to the Suzhou Fifth People’s Hospital from January 1, 2020 to February 8, 2020. The epidemiological, clinical and imaging characteristics as well as laboratory data of the 67 patients were analyzed. Results The study found that fibrinogen (FIB) was increased in 45 (65.2%) patients, and when FIB reached a critical value of 4.805 g/L, the sensitivity and specificity、DA, helping to distinguish general and severe cases, were 100 and 14%、92.9%, respectively, which were significantly better than those for lymphocyte count and myoglobin. Chest CT images indicated that the cumulative number of lung lobes with lesions in severe patients was significantly higher than that in general patients (P Conclusions Based on the retrospective analysis, FIB was found to be increased in severe patients and was better than lymphocyte count and myoglobin in distinguishing general and severe patients. The study also suggested that hormone treatment has no significant effect on COVID-19.

Background: Pneumonia (COVID-19) caused by the novel coronavirus (2019-nCoV) outbreak attracted global attention. However, early prognostic biomarkers on clinical outcomes about COVID-19 patients is not clear by now. Methods: We collected the clinical data of the 85 COVID-19 patients confirmed in the local hospital. The patients' clinical baseline data, serological data, outcome data were retrospectively analyzed. This study aimed to figure out monitoring values for early prediction of clinical outcome. Results: Dynamic monitoring of laboratory examination indicators during hospitalization showed that the second week is a critical time window of disease progression. Beginning on the 8th day, severely reduced lymphocytes accompanied by a severe increase in inflammation indicators and abnormally high fibrinogen occurred in serious patients. Plasma fibrinogen was increased (5.23 vs 3.87 g/L, P < 0.001), and lymphocyte count (0.71 vs 1.42 109/L, P < 0.0001) was significantly reduced. On the 8th day of disease course, when the lymphocyte count was lower than 1.23×109/L, the time of negative conversion of viral nucleic acid was prolonged (P = 0.051), and imaging showed that the chest CT absorption time was prolonged (P < 0.01). When fibrinogen was greater than 4.24, the time to viral nucleic acid negative conversion was prolonged (P < 0.01), and imaging showed that chest CT absorption time was prolonged (P < 0.001).Conclusion: the Lymphocyte count might be related to clinical outcome events. It could act as laboratory indicators of disease severity.

Background: The Chinese government has pay attention about tuberculosis infection among medical staff in infectious disease hospitals, but the effects have not yet been reported. This study will explore latent infection and immune function in the medical staff and systematically analyze the associated influencing factors. Methods: Ninety-four medical staffs were enrolled and 20 medical staffs were defined as low risk group and others were high risk group. We used IFN-γ release assay and flow cytometry to analyze the latent TB infection status and immune function. Logistic regression analyses were performed to identify the independent risk factors of latent TB infection. Results: This study explored and compared the infection status of medical workers and found that the rate of positive TB-IGRA results was higher among high risk group than in low risk group. Working environment, occupational history and work type were risk factors for TB infection in hospital. This study also found that high risk group had higher IFN-γ expression and a lower ratio of CD4+ to CD8+ T cells and further analysis found that this immune disorder is associated with wards and occupations. Conclusions: This study through rigorous sample collection and analysis found the risk factors of latent tuberculosis infection in health care workers. This finding may provide a theoretical basis to be used by the countries with a high TB burden to further improve their strategies for the prevention of TB infections in hospitals and may give an indication for improving the personal health of medical staff in infectious disease hospitals.

The numbers of IL-27-producing CD4(+) T cells and the concentration of soluble IL-27 have been found to be increased in tuberculous pleural effusion (TPE). The objective of the present study was to explore the mechanism by which IL-27(+)CD4(+) T cells are recruited into the pleural space, and to explore the impact of IL-27 on pleural mesothelial cells (PMCs).The expression profiles of chemokine receptor (CCR) were determined by flow cytometry. The chemoattractant activity of chemokines CCL20 and CCL22 for IL-27(+)CD4(+) T cells in vitro was observed. Effects of IL-27 on wound healing, proliferation and apoptosis of PMCs were also investigated.IL-27(+)CD4(+) T cells in TPE expressed high level of CCR6, medium level of CCR4, and low levels of CCR2, CCR3, CCR5, CCR7, CCR10, and CXCR3. Recruitment of IL-27(+)CD4(+) T cells into TPE could be induced by pleural CCL20 and CCL22. By activating STAT3 signaling, IL-27 significantly improved wound healing and promoted proliferation of PMCs, and completely prevented apoptosis of PMCs induced by IFN-γ.After being recruited into pleural space by CCL20 or/and CCL22, these pleural IL-27-producing CD4(+) T cells may play important roles in tuberculosis immunity by affecting PMC functions.

Th22 cells have been reported to be involved in human cancers. However, differentiation and immune regulation of Th22 cells in malignant pleural effusion (MPE) remain unknown. We noted that Th22 cell numbers were increased in MPE, and that IL-22 substantially promoted the proliferation and migratory activity of A549 cells. Moreover, IL-22 could strongly facilitate intercellular adhesion of A549 cells to pleural mesothelial cell monolayers. Our data revealed that the increase in Th22 cells in MPE was due to pleural cytokines and chemokines, and that Th22 exerted an important immune regulation on cancer cells in human pleural malignant environment.

IL-22-producing helper T cells (Th22 cells) have been reported to be involved in tuberculosis infection. However, differentiation and immune regulation of Th22 cells in tuberculous pleural effusion (TPE) remain unknown.To elucidate the mechanism by which Th22 cells differentiate and recruit into the pleural space.The distribution and phenotypic features of Th22 cells in both TPE and blood were determined. The impacts of proinflammatory cytokines and antigen presentation by pleural mesothelial cells (PMCs) on Th22-cell differentiation were explored. The chemoattractant activity of chemokines produced by PMCs for Th22 cells was observed.Th22 cells were significantly higher in TPE than in blood. IL-1β, IL-6, and/or tumor necrosis factor-α promoted Th22-cell differentiation from CD4(+) T cells. It was found that PMCs expressed CCL20, CCL22, and CCL27, and that TPE and PMC supernatants were chemotactic for Th22 cells. This activity was partly blocked by anti-CCL20, anti-CCL22, and anti-CCL27 antibodies. IL-22 and IL-17 significantly improved PMC wound healing. Moreover, PMCs were able to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation by presenting tuberculosis-specific antigen.The overrepresentation of Th22 cells in TPE may be due to pleural cytokines and to PMC-produced chemokines. Our data suggest a collaborative loop between PMCs and Th22 cells in TPE. In particular, PMCs were able to function as antigen-presenting cells to stimulate CD4(+) T-cell proliferation and Th22-cell differentiation.

According the present complicated and lacks of high-leveled automation ground operation supporting system, based on the concept of ICAO'S A-SMGCS (advanced surface movement guidance and control systems) and the existed facilities of the airport, this paper focuses on the research of a new ground operation supporting system in accordance with A-SMGCS, including the basis system hardware, the surveillance ground monitoring subsystem and the lighting subsystem, etc. The system is capable of not only detecting and predicting the traffic conflicts on the ground but also providing solutions and suggestions. Meanwhile the system can help controllers to arrange and use the airport resources so as to reduce the ground holding time and delay time.

IL-17–producing CD4+ T (Th17) cells have been found to be increased in some human cancers; however, the possible implication of Th17 cells in regulating antitumor responses in malignant pleural effusion (MPE) remains to be elucidated. In the current study, distribution and phenotypic features of Th17 cells in both MPE and peripheral blood from patients with lung cancer were determined by flow cytometry or double immunofluorescence staining. The impacts of cytokines on Th17 cell generation and differentiation were explored. The chemoattractant activity of chemokines CCL20 and CCL22 for Th17 cells in vitro was also observed. It was found that the increased Th17 cells could be found in MPE compared with blood. The in vitro experiments showed that IL-1β, IL-6, IL-23, or their various combinations could promote Th17 cell generation and differentiation from naive CD4+ T cells. MPE was chemotactic for Th17 cells, and this activity was partly blocked by anti-CCL20 and/or CCL22 Abs. Our data also showed that the accumulation of Th17 cells in MPE predicted improved patient survival. It could be concluded that the overrepresentation of Th17 cells in MPE might be due to Th17 cell differentiation and expansion stimulated by pleural proinflammatory cytokines and to recruitment of Th17 cells from peripheral blood induced by pleural chemokines CCL20 and CCL22. Furthermore, the accumulation of Th17 cells in MPE predicted improved patient survival. These data provide the basis for developing immune-boosting strategies based on ridding the cancer patient of this cell population.

The clock synchronization is the key technology in distributed control system. This paper investigates the method to adjust computer clock frequency and time in embedded control system based on Ethernet. This paper also analyses the basic working principle of the IEEE 1588 Precision Time Protocol. In particular, it outlines the working principle of the free PTPd that is the software only implementations of the IEEE 1588 Precision Time Protocol. In the ARM-Linux environment, it presents a clock synchronization method to achieve high precise clock synchronization in distributed control system using PTPd. The results indicate that it is able to synchronize distributed clocks with the accuracy less than 500 microseconds using PTPd without the support of specialized hardware.

Programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and PD-L2 have been demonstrated to be involved in tuberculosis immunity, however, the expression and regulation of PD-1/PD-Ls pathways in pleural mesothelial cells (PMCs) and CD4(+) T cells in tuberculous pleural effusion (TPE) have not been investigated. Expression of PD-1 on CD4(+) T cells and expressions of PD-L1 and PD-L2 on PMCs in TPE were determined. The impacts of PD-1/PD-Ls pathways on proliferation, apoptosis, adhesion, and migration of CD4(+) T cells were explored. Concentrations of soluble PD-l, but not of soluble PD-Ls, were much higher in TPE than in serum. Expressions of PD-1 on CD4(+) T cells in TPE were significantly higher than those in blood. Expressions of PD-Ls were much higher on PMCs from TPE when compared with those from transudative effusion. Interferon-γ not only upregulated the expression of PD-1 on CD4(+) T cells, but also upregulated the expressions of PD-Ls on PMCs. Blockage PD-1/PD-Ls pathways abolished the inhibitory effects on proliferation and adhesion activity of CD4(+) T cells induced by PMCs. PD-1/PD-Ls pathways on PMCs inhibited proliferation and adhesion activity of CD4(+) T cells, suggesting that Mycobacterium tuberculosis might exploit PD-1/PD-Ls pathways to evade host cell immune response in human.

IL-9-producing CD4(+) T cells (Th9 cells) have been reported to be involved in inflammation and immune diseases. However, the involvement of Th9 cells in malignancy has not been investigated.To elucidate the mechanism by which Th9 cells differentiate in malignant pleural effusion (MPE) and to explore the immune regulation of Th9 cells on lung cancer cells.Distribution of Th9 cells in relation to Th17 and Th1 cells in both MPE and blood were determined. The effects and mechanisms of proinflammatory cytokines and regulatory T cells on differentiation of Th9 cells in vitro were explored. The impacts and signal transductions of IL-9, IL-17, and IFN-γ on lung cancer cell lines were also investigated.The numbers of Th9, Th17, and Th1 cells were all increased in MPE when compared with blood. The increase in Th9 cells in MPE was due to the promotion by cytokines and regulatory T cells. By activating STAT3 signaling, both IL-9 and IL-17 substantially promoted the proliferation and migratory activity of lung cancer cells, whereas IFN-γ, which activated STAT1 signaling, was noted to suppress lung cancer cell proliferation and migration. IFN-γ could induce lung cancer cell apoptosis. Moreover, IL-9 and IFN-γ, but not IL-17, could strongly facilitate intercellular adhesion of lung cancer cells to pleural mesothelial cell monolayers.Our data revealed that Th9 cells were increased in MPE and that Th9 cells exerted an important immune regulation on lung cancer cells in human tumor environment.

The objective of the present study was to investigate the presence of interleukin (IL)-27 in pleural effusions and to evaluate the diagnostic significance of pleural IL-27. The concentrations of IL-27 were determined in pleural fluids and sera from 68 patients with tuberculous pleural effusion, 63 malignant pleural effusion, 22 infectious pleural effusion, and 21 transudative pleural effusion. Flow cytometry was used to identify which pleural cell types expressed IL-27. It was found that the concentrations of pleural IL-27 in tuberculous group were significantly higher than those in malignant, infectious, and transudative groups, respectively. Pleural CD4(+) T cells, CD8(+) T cells, NK cells, NKT cells, B cells, monocytes, macrophages, and mesothelial cells might be the cell sources for IL-27. IL-27 levels could be used for diagnostic purpose for tuberculous pleural effusion, with the cut off value of 1,007 ng/L, IL-27 had a sensitivity of 92.7% and specificity of 99.1% for differential diagnosing tuberculous pleural effusion from non-tuberculous pleural effusions. Therefore, compared to non-tuberculous pleural effusions, IL-27 appeared to be increased in tuberculous pleural effusion. IL-27 in pleural fluid is a sensitive and specific biomarker for the differential diagnosing tuberculous pleural effusion from pleural effusions with the other causes.

Bevacizumab is a recombinant humanized monoclonal antibody against vascular endothelial growth factor which has been used in conjunction with other anti-cancer agents in the treatment of patients with many cancers. It remains controversial whether bevacizumab can prolong survival in cancer patients. This meta-analysis was therefore performed to evaluate effect of bevacizumab on survival in cancer patients. PubMed, EMBASE, and Web of Science databases were searched for English-language studies of randomized controlled trials comparing bevacizumab with control therapy published through February 8, 2012. Progression-free survival, overall survival, and one-year survival rate were analyzed using random- or fixed-effects model. Thirty one assessable randomized controlled trials were identified. A significant improvement in progression-free survival in cancer patients was attributable to bevacizumab compared with control therapy (hazard ratio, 0.72; 95% confidence interval, 0.68 to 0.76; p

Purpose: The aim of this study was to explore the presence of the chemokines CCL22 and CCL17 in malignant pleural effusion, and the chemoattractant activity of these chemokines on CD4-positive CD25-positive Foxp3-positive regulatory T cells infiltrating into the pleural space.Experimental Design: The concentrations of CCL22 and CCL17 in both pleural effusions and sera from 33 patients with lung cancer were determined. Flow cytometry was done to determine T lymphocyte subsets in cell pellets of pleural effusion. Pleural cells were analyzed for the expression of CCL22 and CCL17. The chemoattractant activity of CCL22 for regulatory T cells in vitro and in vivo was also observed.Results: The concentration of CCL22 in malignant pleural effusion was significantly higher than that in the corresponding serum. Pleural fluid from lung cancer patients was chemotactic for regulatory T cells, and this activity was partly blocked by an anti-CCL22, but not by an anti-CCL17 antibody. Intrapleural administration of CCL22 of patients produced a marked progressive influx of regulatory T cells into pleural space.Conclusions: Compared with serum, CCL22 seemed to be increased in malignant pleural effusion, and could directly induce regulatory T cell infiltration into the pleural space in patients with malignant effusion.

Ye, Z.-J., Q. Zhou, Y.-Y. Gu, S.-M. Qin, W.-L. Ma, J.-B. Xin, X.-N. Tao, and H.-Z. Shi. 2010. Generation and differentiation of IL-17–producing CD4+ T cells in malignant pleural effusion. J. Immunol. 185: [6348–6354][1]. The images published in [Fig. 5A][2] were mistakenly selected from