Ficolin-A/2 Aggravates Severe Lung Injury through Neutrophil Extracellular Traps Mediated by Gasdermin D-Induced Pyroptosis.

Neutrophil extracellular traps (NETs) and pyroptosis are critical events in lung injury. This study investigated whether ficolin-A influenced NET formation through pyroptosis to exacerbate lipopolysaccharide (LPS)-induced lung injury. The expression of ficolin-A/2, NETs, and pyroptosis-related molecules was investigated in animal and cell models. Knockout and knockdown (recombinant protein) methods were used to elucidate regulatory mechanisms. The Pearson correlation coefficient was used to analyze the correlation between ficolins and pyroptosis- and NET-related markers in clinical samples. In this study, ficolin-2 (similar to ficolin-A) showed significant overexpression in patients with acute respiratory distress syndrome. In vivo, knockout of Fcna, but not Fcnb, attenuated lung inflammation and inhibited NET formation in the LPS-induced mouse model. DNase I further alleviated lung inflammation and NET formation in Fcna knockout mice. In vitro, neutrophils derived from Fcna-/- mice showed less pyroptosis and necroptosis than those from the control group after LPS stimulation. Additionally, GSDMD knockdown or Nod-like receptor protein 3 inhibitor reduced NET formation. Addition of recombinant ficolin-2 protein to human peripheral blood neutrophils promoted NET formation and pyroptosis after LPS stimulation, whereas Fcn2 knockdown had the opposite effect. Acute respiratory distress syndrome patients showed increased levels of pyroptosis- and NET-related markers, which were correlated positively with ficolin-2 levels. In conclusion, these results suggested that ficolin-A/2 exacerbated NET formation and LPS-induced lung injury via gasdermin D-mediated pyroptosis.

Gut microbiota-derived acetic acids promoted sepsis-induced acute respiratory distress syndrome by delaying neutrophil apoptosis through FABP4.

In patients with sepsis, neutrophil apoptosis tends to be inversely proportional to the severity of sepsis, but its mechanism is not yet clear. This study aimed to explore the mechanism of fatty acid binding protein 4 (FABP4) regulating neutrophil apoptosis through combined analysis of gut microbiota and short-chain fatty acids (SCFAs) metabolism. First, neutrophils from bronchoalveolar lavage fluid (BALF) of patients with sepsis-induced acute respiratory distress syndrome (ARDS) were purified and isolated RNA was applied for sequencing. Then, the cecal ligation and puncture (CLP) method was applied to induce the mouse sepsis model. After intervention with differential SCFAs sodium acetate, neutrophil apoptosis and FABP4 expression were further analyzed. Then, FABP4 inhibitor BMS309403 was used to treat neutrophils. We found CLP group had increased lung injury score, lung tissue wet/dry ratio, lung vascular permeability, and inflammatory factors IL-1ß, TNF-α, IL-6, IFN-γ, and CCL3 levels in both bronchoalveolar lavage fluid and lung tissue. Additionally, FABP4 was lower in neutrophils of ARDS patients and mice. Meanwhile, CLP-induced dysbiosis of gut microbiota and changes in SCFAs levels were observed. Further verification showed that acetic acids reduced neutrophil apoptosis and FABP4 expression via FFAR2. Besides, FABP4 affected neutrophil apoptosis through endoplasmic reticulum (ER) stress, and neutrophil depletion alleviated the promotion of ARDS development by BMS309403. Moreover, FABP4 in neutrophils regulated the injury of RLE-6TN through inflammatory factors. In conclusion, FABP4 affected by gut microbiota-derived SCFAs delayed neutrophil apoptosis through ER stress, leading to increased inflammatory factors mediating lung epithelial cell damage.

Noncanonical JAK1/STAT3 interactions with TGF-ß modulate myofibroblast transdifferentiation and fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with limited survival. Janus kinases (JAKs), tyrosine kinases that transduce cytokine-mediated signals, are known to be involved, but their specific roles in lung fibrosis are not well defined. In this study, the interactions between JAK1/signal transducers and activators of transcription (STAT)3 signaling and transforming growth factor-beta (TGF-ß)-induced fibroblast responses were investigated using both pharmacological and siRNA approaches in human normal and IPF-derived lung fibroblasts. We found that JAK1 directly interacts with the TGF-ß receptor I subunit (TßRI), and silencing JAK1 promotes myofibroblast transdifferentiation. However, the suppression of JAK1 signaling in vitro and in vivo using an inhibitor (upadacitinib) did not alter lung fibroblast activation or fibrosis development. STAT3 was constitutively active in cultured primary lung fibroblasts; this STAT3 activation required JAK1 and repressed myofibroblast transdifferentiation. Loss of phosphorylated STAT3 following transcriptional JAK1 silencing promoted myofibroblast transdifferentiation. In contrast, transcriptional silencing of unphosphorylated STAT3 suppressed TGF-ß signaling, decreased SMAD3 activation, and reduced myofibroblast transdifferentiation and ECM production. Taken together, these observations support a role for JAK1/STAT3 as a direct regulator of TGF-ß signaling in lung fibroblasts. Modulation of JAK1/STAT3 signaling in lung fibroblasts represents a noncanonical approach to regulating TGF-ß-induced fibrosis and suggests the potential for a novel approach to treat pulmonary fibrosis.

Diagnostic value of LungPoint navigation combined with EBUS-GS & ROSE in peripheral pulmonary nodules.

Background & objectives: Recently, there has been a surge to develop new devices and techniques for the diagnosis of peripheral pulmonary lesions such as the combination of LungPoint navigation and endobronchial ultrasound with a guide sheath (EBUS-GS). The present study aimed to explore the diagnostic value of LungPoint navigation in combination with EBUS-GS and rapid on-site evaluation (ROSE) particularly for peripheral pulmonary nodules. Methods: Patients (n=108) with pulmonary nodules (10 mm ≤ nodal diameter ≤30 mm) presenting to Henan Provincial People's Hospital were detected using chest computed tomographic (CT) scanning and bronchoscopy. All patients were evaluated using LungPoint navigation, EBUS-GS and ROSE techniques to evaluate the positive rate of combined diagnosis using the three methods. Results: A total of 108 patients participated in this study and successfully underwent all the three procedures. Of these, 82 patients were accurately diagnosed, making the overall diagnostic rate of 75.9 per cent for combined LungPoint navigation, EBUS-GS, and ROSE analyses. Further subgroup analysis of the diagnostic rate of the three combined techniques were conducted based on the size of the nodules which showed a diagnostic rate of 65.3 per cent for 10 mm ≤ nodule diameter ≤20 mm and 85.7 per cent for 20 mm ≤ nodal diameter ≤30 mm. Of the 108 patients, 85 had solid nodules and 23 had ground-glass nodules; the positive rate of diagnosis of solid nodules was the highest. The patients ultimately were diagnosed with lung cancer with a positive rate of 83.5 per cent. The sensitivity, specificity and positive and negative predicted values for ROSE were 90.3, 78.3, 84.8 and 83.6 per cent, respectively. Interpretation & conclusions: The combined use of the three techniques can effectively shorten the duration of the total diagnosis period and improve the safety of diagnosis without affecting the detection rate.

A novel humanized model of rheumatoid arthritis associated lung disease.

Cigarette smoking has been implicated in the pathogenesis of seropositive rheumatoid arthritis (RA), as well as RA-associated lung disease. Fibrotic interstitial lung disease as well as emphysema occur in RA and cause substantial morbidity. We used arthritis-susceptible HLA-DQ8 transgenic mice to generate RA-associated lung disease. Mice were exposed to cigarette smoke (CS) prior to induction of arthritis, and subsequently injected with a low dose of bleomycin intra-tracheally to induce lung injury. Exposure of arthritic mice to both CS and bleomycin led to a significant reduction in lung compliance consistent with development of diffuse lung disease. Morphologic evaluation of the lung demonstrated areas of emphysematous change and co-existent fibrosis, consistent with a combined pattern of fibrosis and emphysema. These changes were accompanied by inflammatory cell infiltration and upregulation of fibrosis-associated genes. This humanized mouse model can serve as a valuable research tool to understand the pathogenesis of RA associated lung disease.

[Diagnostic value of serum procalcitonin in identifying the etiology of non-responding community-acquired pneumonia after initial antibiotic therapy].

OBJECTIVE: This study was to investigate the diagnostic value of serum procalcitonin(PCT) in identifying the etiology of non-responding community-acquired pneumonia (CAP) after initial antibiotic therapy. METHODS: A retrospective analysis was performed for 232 hospitalized CAP patients admitted to the People's Hospital of Zhengzhou University during June 2013 and January 2014. Early treatment failure was defined as the presence of persistent fever (>38 °C) and/or clinical symptoms (malaise, cough, expectoration, dyspnea) or deterioration after at least 72 h of initial antimicrobial treatment, or development of respiratory failure requiring mechanical ventilation, or septic shock. Bronchoscopy or transthoracic lung biopsy was performed in case of early treatment failure when indicated. Serum level of PCT was detected by double antibody sandwich method. The differences between 2 or more groups were compared using 2-independent student t test, one-way ANOVA; Mann-Whitney U test, Kruskal-Wallis rank sum test, or χ(2) test. Risk factors and odds ratios for nonresponsiveness were analyzed by setting up a Logistic regression model. The diagnostic values of PCT were determined by receiver operating characteristic curves (ROC curves). RESULTS: Of the 232 CAP patients enrolled, 124 were male and 108 were female, with an average age of (46 ± 20) years. Thirty-six patients failed to respond to the initial antibiotic therapy. As shown by Logistic regression analysis, the risk factors for treatment failure included hypoalbuminemia, type 2 diabetes, previous history of splenectomy , PSI 4-5 grade, and lung infiltration ≥ 3 lobes. The most common causes of non-responsiveness were antimicrobial insufficiency (n = 23), and misdiagnosis of noninfectious mimics of pneumonia (n = 11), with 2 cases of unidentified etiology. The serum PCT level in admission was 0.19 (0.07-0.66) µg/L in the antimicrobial insufficiency subgroup, which was significantly higher than that in the misdiagnosis subgroup [0.06(0.05-0.08)µg/L; P < 0.01]. The antimicrobial insufficiency subgroup included 11 cases of bacterial infection (5 of G(+) cocci and 6 of G(-) bacilli) and 12 cases of nonbacterial infection; their PCT levels were 0.66(0.19-5.80) µg/L and 0.08(0.05-0.20) µg/L, respectively (P < 0.01). There was no statistically significant difference among PCT levels of the 4 subgroups of nonbacterial infections (4 tuberculosis, 3 fungi, 3 atypical pathogens, 2 viruses) (F = 3.025, P = 0.094). The cut-off values of PCT were >0.13 µg/L and >0.115 µg/L for differentiating non-responsiveness originated from bacterial infection or other causes, and infection vs non-infection, which yielded a sensitivity of 100% (11/11) and 65% (14/23) , specificity of 83% (19/23) and 91% (10/11) , and AUC of 0.955 and 0.802, respectively. CONCLUSIONS: Antibiotic failure to cover the microbial pathogens, infectious complications and misdiagnosis are the most common causes of early treatment failure in patients with CAP. Serum PCT level fails to predict non-responsiveness, but is suggestive of bacterial infections in hospitalized CAP patients with early treatment failure.

Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema.

Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair. In this study, a murine model of CS-induced emphysema was used to determine whether nebulized PEP can influence the development of CS-induced emphysema through the mitigation of oxidative stress and inflammation in the lung. Nebulization of PEP effectively delivered the PEP vesicles into the alveolar region, with evidence of their uptake by type I and type II alveolar epithelial cells and macrophages. Lung function testing and morphometric assessment showed a significant attenuation of CS-induced emphysema in mice treated with nebulized PEP thrice weekly for 4 weeks. Whole lung immuno-oncology RNA sequencing analysis revealed that PEP suppressed several CS-induced cell injuries and inflammatory pathways. Validation of inflammatory cytokines and apoptotic protein expression on the lung tissue revealed that mice treated with PEP had significantly lower levels of S100A8/A9 expressing macrophages, higher levels of CD4+/FOXP3+ Treg cells, and reduced NF-κB activation, inflammatory cytokine production, and apoptotic proteins expression. Further validation using in vitro cell culture showed that pretreatment of alveolar epithelial cells with PEP significantly attenuated CS extract-induced apoptotic cell death. These data show that nebulization of exosomes like PEP can effectively deliver exosome cargo into the lung, mitigate CS-induced emphysema in mice, and suppress oxidative lung injury, inflammation, and apoptotic alveolar epithelial cell death.

Ficolin A knockout alleviates sepsis-induced severe lung injury in mice by restoring gut Akkermansia to inhibit S100A4/STAT3 pathway.

Acute lung injury (ALI) is a life-threatening disease with high morbidity and mortality. Our previous results demonstrated that Ficolin A (FcnA) protected against lipopolysaccharide (LPS)-induced mild ALI via activating complement, however the mechanism of severe lung damage caused by sepsis remains unclear. This study aimed to investigate whether FcnA modulated gut microbiota to affect the progression of sepsis-induced severe ALI. Fcna-/- and Fcnb-/- C57BL/6 mice were applied to establish the ALI model by injection of LPS intraperitoneally. Mice were treated with antibiotics, fecal microbiota transplantation (FMT), and intratracheal administration of recombinant protein S100A4. Changes in body weight of mice were recorded, and lung injury were assessed. Then lung tissue wet/dry weight was calculated. We found knockout of FcnA, but not FcnB, alleviated sepsis-induced severe ALI evidenced by increased body weight change, decreased wet/dry weight of lung tissue, reduced inflammatory infiltration, decreased lung damage score, decreased Muc-2, TNF-α, IL-1ß, IL-6, and Cr levels, and increased sIgA levels. Furthermore, knockout of FcnA restored gut microbiota homeostasis in mice. Correlation analysis showed that Akkermansia was significantly negatively associated with TNF-α, IL-1ß, and IL-6 levels in serum and bronchoalveolar lavage fluid (BALF). Moreover, knockout of FcnA regulated gut microbiota to protect ALI through S100A4. Finally, we found knockout of FcnA alleviated ALI by inhibiting S100A4 via gut Akkermansia in mice, which may provide further insights and new targets into treating sepsis-induced severe lung injury.

Combination of the Archimedes Navigation System and cryobiopsy in diagnosis of diffuse lung disease.

OBJECTIVE: To evaluate the efficacy of the Archimedes Navigation System (Broncus Medical, San Jose, CA, USA) for guidance during transbronchial cryobiopsy and the incidence of complications in patients with diffuse lung disease. METHODS: High-resolution computed tomography and transbronchial cryobiopsy were used to evaluate eight patients with diffuse lung disease. The Archimedes Navigation System was used before cryobiopsy to obtain the best path with which to avoid large vessels. Three to five cryobiopsy specimens were taken from each sampled segment. RESULTS: Preoperative planning using the Archimedes Navigation System was successfully performed on all eight patients. The probe-to-pleura distance was approximately 10 mm. No cases of pneumothorax occurred, one patient developed moderate bleeding, two developed minor bleeding, and five developed minimal bleeding that stopped spontaneously. A final diagnosis was obtained for seven patients, and ongoing follow-up was being conducted for the last patient at the time of this writing. CONCLUSIONS: This is the first report of combining navigation technology with cryobiopsy to diagnose diffuse lung disease. The Archimedes Navigation System, which provides real-time guidance, is helpful in pre-cryobiopsy planning and diagnosis of diffuse lung disease. Moreover, this system can reduce the pneumothorax rate and bleeding risk by avoiding large vessels.

Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis.

Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNFα with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNFα/NF-κB signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment.

Atypical carcinoid: A rare finding of a man with mediastinal mass: A case report.

The present case report describes a case of mediastinal atypical carcinoid and a favorable outcome linked with the treatment. Mediastinal atypical carcinoid is a rare and aggressive type of neuroendocrine tumor. A 56-year-old man was admitted at the Respiratory Department due to intermittent tightness of the chest for 1 month. An initial diagnosis of a mass in the left anterior mediastinum was conducted using CT scan and immunohistochemistry. Laboratory data revealed the following values: Neuron Specific Enolase of 62.13 ng/ml (reference range, 0-40 ng/ml); CYFRA21 of 3.01 ng/ml (reference range, 0-3.3 ng/ml); CEA of 4.22 (0-6.5) ng/ml; SCC of 0.5 (0-1.5) ng/ml; CA125 of 67.24 (0-35) U/ml; AFP of 23 (0-25) U/ml; CRP of 96.7 (0-10) mg/l; PCT <0.05 (0-0.05) ng/ml; and ESR of 48 (0-20) mm/h. Tissue pathology revealed tumor cells with small cell pattern, and cell proliferation activity was 10%. Combined chemotherapy with bevacizumab (0.4 g, qd, once every 21 days) and capecitabine (0.15 g, Bid, Po) and timozolamine (0.34 mg, qd, po) was administered for 6 cycles. After the patient was given chemotherapy, the symptoms and CT exhibited improvement. On March 11, 2018, the lesion progressed into the lymph and pleura. The patient was commenced on radiotherapy and new chemotherapeutic regimen etoposide (0.5 g)-carboplatin (0.4 g)-bevacate (0.4 g). Another CT scan was performed after a month which revealed a substantial decrease in tumor size. Hence, a CT scan was performed for this patient who further revealed a decrease in tumor size. Currently patients are treated with bevacizumab maintenance therapy. Further studies of conservative treatment of chemotherapy and radiotherapy may provide a treatment to improve atypical carcinoid.

Protein expression shift and potential diagnostic markers through proteomics profiling of tuberculous pleurisy biopsy tissues.

OBJECTIVES: Tuberculous pleurisy is a common type of tuberculosis (TB), but its diagnosis is challenging. This study aimed to profile the protein expression of this disease and identify new diagnostic makers. METHODS: Biopsy tissues from patients with tuberculous pleurisy and controls were taken through thoracoscopy, and proteins were extracted for Tandem Mass Tag Mass Spectrometry. Differential protein expression was performed between patients and controls, and the identified proteins were analyzed for pathway enrichment. Selected proteins were further validated in another set of samples using a more quantitative method. RESULTS: A total of 5101 proteins were detected and quantified in a discovery set of patients and controls. Overall protein expression was quite different between patients and controls. Most proteins were down-expressed, while a minority were overly expressed in the patient samples. At p value < 0.05 and absolute fold change >2, 295 proteins were found to be up-expressed and 608 down-expressed. The top enriched pathways included ECM-receptor interaction, complement and coagulation cascades and focal adhesion. All 19 selected candidates were validated in an independent set of patient and control samples. CONCLUSION: This unbiased proteomics approach not only provided unique insights into protein expression and pathways, but also discovered potential diagnostic markers for tuberculous pleurisy.

STAT3-induced long noncoding RNA LINC00668 promotes migration and invasion of non-small cell lung cancer via the miR-193a/KLF7 axis.

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in non-small cell lung cancer (NSCLC) progression. Recently, a newly identified lncRNA, LncRNA LINC00668 (LINC00668), was reported to be involved in the regulation of progression of several tumors. However, the expression pattern and biological function of LINC00668 in NSCLC remains largely unclear. In this study, we found that LINC00668 expression was significantly up-regulated in both NSCLC tissues and cell lines. we also showed that LINC00668 upregulation was induced by transcription factor STAT3. Clinical investigation demonstrated that high expression level of LINC00668 was associated with advanced TNM stage, histological grade and lymph node metastasis. Moreover, multivariate analysis confirmed LINC00668 expression level to be an independent prognostic indicator for overall survival of NSCLC patients. Functional assays indicated that knockdown of LINC00668 suppressed NSCLC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic studies indicated that LINC00668 is a direct target of miR-193a, leading to down-regulation in the expression of its target gene KLF7. Our findings suggested that STAT3-induced LINC00668 contributed to NSCLC progression through upregulating KLF7 expression by sponging miR-193a, and may serve as a prognostic biomarker and a potential target for NSCLC.

Diagnostic Significance of Mycobacterium tuberculosis T-cell Assays for Active Tuberculosis.

BACKGROUND: Active tuberculosis (TB) with negative results of sputum smear is difficult to be identified. Till now, there is no effective and noninvasive diagnostic method. This study evaluated the diagnostic power of Mycobacterium tuberculosis T-cell (T.SPOT®.TB) assays for active TB. METHODS: We retrospectively screened 450 suspected TB patients that were hospitalized in the Respiratory Department of Henan Province People's Hospital from June 2015 to June 2016. The patients were divided into the active, previous, and non-TB groups according to their final diagnosis. We evaluated the diagnostic value of the T-SPOT®.TB assay by constructing receiver operating characteristic (ROC) curves and calculating the optimal diagnostic cutoff value. In addition, we compared the levels of A antigen (ESAT-6) and B antigen (CFP-10) in active TB. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of T-SPOT®.TB for active TB were 89.78%, 63.16%, 0.56, 0.92, 2.47, and 0.16, respectively. For active TB, the area under the ROC curve (AUC) of the A antigen (0.89) was higher than that of the B antigen (0.86). The AUC of the A antigen for active TB was largest at a cutoff value of 13.5 spot-forming cells (SFCs) per 2.5 × 105 peripheral blood mononuclear cells (PBMCs). The AUC of the A and B antigens was 0.60 and 0.58 for previous TB. The levels of A and B antigen in the active TB group were significantly different from those in the previous- and non-TB groups (A antigen: χ2 = 105.41, P< 0.01 and B antigen: χ2 = 91.03, P< 0.01; A antigen: χ2 = 12.99, P< 0.01 and B antigen: χ2 = 8.56, P< 0.01, respectively). There were no significant differences in the levels of A and B antigens between the non-TB group and previous TB group (A antigen: χ2 = 1.07, P> 0.05 and B antigen: χ2 = 0.77, P> 0.05). CONCLUSIONS: T-SPOT®.TB has high sensitivity and specificity for the diagnosis of active TB at a cutoff value of 13.5 SFCs per 2.5 × 105 PBMCs and is not influenced by previous TB.

IL-33 levels differentiate tuberculous pleurisy from malignant pleural effusions.

Tuberculous pleural effusions (TPEs) and malignant pleural effusions (MPEs) are difficult to differentiate between in certain clinical situations. Interleukin (IL)-33 is a cytokine that participates in inflammatory responses and may have a role in pleural effusions. The present study aimed to investigate the concentrations and potential differential significance of IL-33 in patients with TPE and MPE. IL-33 levels in pleural effusion and serum samples were detected using sandwich enzyme-linked immunosorbent assay in 23 patients with TPE and 21 patients with MPE. The concentration of IL-33 (mean ± standard deviation) in the TPE patients (22.962±0.976 ng/l) was significantly higher than that in the MPE patients (12.603±5.153 ng/l; P<0.001; z=-4.572); however, there was no significant difference in the serum level of IL-33 in the patients with TPE compared with those with MPE (P>0.05). The concentration of IL-33 in the pleural effusions was positively correlated with that in the serum samples in each group (TPE: r=0.563, P=0.05; MPE: r=0.535, P<0.05). The cut-off value of pleural IL-33 for TPE was 19.86 ng/l, which yielded a sensitivity of 0.869, a specificity of 0.905 and an area under the corresponding receiver operating characteristic curve of 0.903. The present study identified that the level of pleural IL-33 is significantly increased in TPEs and may serve as a novel biomarker to differentiate between patients with TPE and MPE.