Utility of auto fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions.

BACKGROUND: Bronchoscopy is currently the most common technique for lung cancer diagnosis. Patients suspected of malignancy often undergo bronchoscopic examination, and biopsy is routinely used in patients with visible bronchial lesions. However, it is difficult to differentially diagnose lung cancer in patients with bronchial mucosal lesions. Thus, this study was conducted to investigate the utility of fluorescence-guided biopsy in suspected lung cancer patients with bronchial mucosal lesions. METHODS: We conducted a retrospective study in a single screening center to assess the sensitivity and specificity of fluorescence-guided biopsy compared with white light bronchoscopy (WLB) in patients with bronchial mucosal lesions. RESULTS: A total of 301 patients with bronchial mucosal lesions were enrolled in this study. The sensitivity for patients with fluorescence-guided biopsy was 60.3 % (95 % confidence interval [CI]: 53.1 %-67.1 %), which was higher than that of patients with WLB alone (45.2 %, 95 % CI: 38.2-52.4 %) (P = 0.0026). Additionally, compared with the WLB group, the fluorescence -guided biopsy group was found to have a significantly higher specificity (100 %, 95 % CI: 95.5-100 % versus 69.6 %, 95 % CI: 59.6-78.1 %), positive predictive value (100 %, 95 % CI: 96.1-100 % versus 74.3 %, 95 % CI: 65.5-81.7 %) and negative predictive value (56.3 %, 95 % CI: 48.8-63.6 % versus 39.4 %, 95 % CI: 32.3-47.0 %). CONCLUSION: Fluorescence-guided biopsy can serve as an important adjunct to WLB for the differential diagnosis of lung cancer in patients with bronchial mucosal lesions.

Disease-associated gut microbiome and critical metabolomic alterations in patients with colorectal cancer.

BACKGROUND: Gut microbiota plays a significant role in the colorectal cancer (CRC) process. Ectopic colonization of multiple oral bacteria is reportedly associated with CRC pathogenesis and progression, but the details remain unclear. METHODS: We enrolled a cohort of 50 CRC patients and 52 healthy controls from an East China population. Taxonomic and functional analysis of the fecal microbiota were performed using 16S rDNA (50 + 52 samples) and shotgun metagenomic sequencing (8 + 6 samples), respectively, with particular attention paid to gut-colonized oral bacteria. RESULTS AND CONCLUSIONS: The results showed more detected bacterial species but lower species evenness within the samples from CRC patients. To determine the specific bacteria enriched in each group, we analyzed their possible protective, carcinogenic, or opportunistic roles in the CRC process. Among the ectopic oral bacteria, we observed a significant increase in the abundance of Fusobacterium and decreased abundance of Prevotella and Ruminococcus in the CRC group. Main differences in the functional composition of these two groups were related to energy metabolism and biosynthesis, especially the glycolytic pathway. Furthermore, we validated the colonization of Fusobacterium nucleatum subsp. animalis within CRC tissues and studied its impact on the host intestinal epithelium and tumor cells. With high selectivity for cancerous tissues, this subspecies promoted CRC cell proliferation and induced potential DNA damage.

Early Identification of Fungal and Mycobacterium Infections in Pulmonary Granulomas Using Metagenomic Next-Generation Sequencing on Formalin fixation and paraffin embedding tissue.

BACKGROUND: The purpose of the study is to assess the etiology detection ability of Metagenomic Next-Generation Sequencing (mNGS) on formalin fixation and paraffin embedding (FFPE) tissue from postoperative biopsy specimens. METHODS: We prospectively enrolled specimens from patients undergone surgery biopsy due to undefinite diagnosis and pathologically indicated granulomatous lesions. FFPE tissues were tested by mNGS and histopathology. The etiology detection rate of mNGS was calculated and compared with histopathology.. RESULTS: Among the 69 cases eventually included, 41 (59.42%) were diagnosed with infectious granuloma. The overall fungi and mycobacteria etiology detection rates of mNGS in granuloma lesions was 87.80% (36/41). The mNGS increased the detection rate by 68.29% (28/41) compared with histopathology, the difference was statistically significant (χ2 = 28.97, P = 0.00). The detection rates of mNGS in fungal infections (12/12,100%) and in mycobacterium infections (22/27, 81.48%) were significant higher than those of histopathology (8/12, 66.67% and 0/27, 0.00%; both P = 0.00). Two (2/2.100%) cases of co-infection were detected at one time by mNGS. All mNGS-based clinical decisions were made within 2 days. CONCLUSIONS: The mNGS could accurately and quickly detect fungi and mycobacteria in FFPE specimens from postoperative granuloma specimens and identify the pathogens to the species level. CLINICAL TRIALS REGISTRATION: China Clinical Trial Registry ChiCTR2000035464.

Advances in molecular mechanisms of interaction between Mycobacterium tuberculosis and lung cancer: a narrative review.

OBJECTIVE: We systematically review the molecular mechanism of the interaction between lung cancer (LC) and tuberculosis (TB), and put forward the existing problems in order to provide suggestions for early intervention and future research direction. BACKGROUND: TB and LC are two global public health problems affecting human health. LC is the main cause of cancer-related death worldwide and TB is one of the leading causes of death among infectious diseases, especially in resource-poor areas. Previous studies have suggested that a history of TB may be associated with an increased risk of LC. With the improvement of LC treatment, the occurrence of pulmonary tuberculosis in the course of LC treatment is also frequently reported recently. METHODS: The molecular immunological mechanisms of interaction between LC and TB, and related epidemiological literature are reviewed. The research progress and problems to be solved are summarized. CONCLUSIONS: Chronic inflammation, immune abnormalities, scar formation, gene mutations and drug effects caused by TB may be associated with the occurrence of LC induced by abnormalities in various molecular pathways. LC and decreased immunity during treatment may also increase the risk of latent TB activation or new TB infection through immune pathways. Data on dual burden areas of TB and LC are still lacking, and more clinical studies are needed to elucidate the association.

The Evaluation and Validation of Blood-Derived Novel Biomarkers for Precise and Rapid Diagnosis of Tuberculosis in Areas With High-TB Burden.

Tuberculosis (TB) remains a highly contagious public health threat. Precise and prompt diagnosis and monitoring of treatment responses are urgently needed for clinics. To pursue novel and satisfied host blood-derived biomarkers, we streamlined a bioinformatic pipeline by integrating differentially expressed genes, a gene co-expression network, and short time-series analysis to mine the published transcriptomes derived from whole blood of TB patients in the GEO database, followed by validating the diagnostic performance of biomarkers in both independent datasets and blood samples of Chinese patients using quantitative real-time PCR (qRT-PCR). We found that four genes, namely UBE2L6 (Ubiquitin/ISG15-conjugating enzyme E2 L6), BATF2 (Basic leucine zipper transcriptional factor ATF-like), SERPING1 (Plasma protease C1 inhibitor), and VAMP5 (Vesicle-associated membrane protein 5), had high diagnostic value for active TB. The transcription levels of these four gene combinations can reach up to 88% sensitivity and 78% specificity (average) for the diagnosis of active TB; the highest sensitivity can achieve 100% by parallel of BATF2 and VAMP5, and the highest specificity can reach 89.5% through a combination of SERPIG1, UBE2L6, and VAMP5, which were significantly higher than 75.3% sensitivity and 69.1% specificity by T-SPOT.TB in the same patients. Quite unexpectedly, the gene set can assess the efficacy of anti-TB response and differentiate active TB from Latent TB infection. The data demonstrated these four biomarkers might have great potency and advantage over IGRAs in the diagnosis of TB.

The frequency and dynamics of CD4+ mucosal-associated invariant T (MAIT) cells in active pulmonary tuberculosis.

MAIT cells are unconventional innate-like T lymphocytes contributing to host immune protection against Mycobacteria tuberculosis (Mtb) infection. CD4- MAIT cells play a major role in immune protection against tuberculosis (TB), however, the role of CD4+ MAIT cells was elusive due to their low abundance. We firstly investigated the frequency and functions of CD4+ MAIT cells in pulmonary tuberculosis (PTB) patients before and after anti-TB treatment. We found that the frequency of Mtb-reactive CD4+ MAIT cells and IFN-γ, granzyme B (GrzB), CD69 expression on them were increased while LAG-3+ cells of them were decreased in PTB patients. After the treatment, the frequency of Mtb-reactive CD4+ MAIT cells and CD69, IFN-γ, GrzB expression on them were decreased while LAG-3 increased. The results indicated the expression profile is distinct between CD4+ MAIT cells and CD4- MAIT cells in PTB patients, the increased IFN-γ and GrzB expression of CD4+ MAIT cells play a role in anti-TB immunity.

Diagnostic yield of Xpert MTB/RIF on contrast-enhanced ultrasound-guided pleural biopsy specimens for pleural tuberculosis.

BACKGROUND: A 3-year prospective study was conducted to evaluate the efficacy of Xpert MTB/RIF (Xpert) in the diagnosis of pleural tuberculosis (pTB) on contrast -enhanced ultrasound (CEUS)-guided pleural biopsy specimens. METHOD: Patients suspected with pTB were prospectively enrolled to receive CEUS-guided biopsy. Specimens (pleural tissue and fluid) were submitted for Xpert and other routine examinations. Surgical thoracoscopy was performed on undiagnosed cases. RESULT: A total of 316 patients were enrolled, including 280 cases of pTB (definite 195, possible 85) and 36 cases of non-pTB. The sensitivity of Xpert was 69.64% (195/280) in biopsy specimens, which was significantly higher than that in pleural effusion specimens (p < 0.01). In 195 definite cases, the highest sensitivity of 100% (195/195) and NPV of 29.75% (36/121) were achieved by Xpert on biopsy specimens. Xpert-positive results were obtained in 149 culture-negative cases and 90 histopathological MTB PCR-negative cases. The incidence of necrosis by CEUS in Xpert-positive pTB was significantly higher than that in Xpert-negative pTB (χ2 = 72.41; p < 0.01). No serious complications occurred. CONCLUSION: Xpert achieved highly diagnostic sensitivity in pTB through CEUS-guided biopsy sampling, especially on necrotic lesions, which was proven to be efficient, minimally invasive and safe.

The Role of ß-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis.

ß-Catenin is a key molecule of canonical Wnt/ß-catenin pathway. Its roles and expression profiles in T cells of tuberculosis (TB) remain unclear. The aim of this study was to explore the role of ß-catenin in CD4+ T cells and its expression characteristics in patients with pulmonary tuberculosis (PTB). In this study, CD4+ T cell-specific ß-catenin conditional knockout mice (ß-CAT-cKO mice) were aerosol infected with Mycobacteria tuberculosis (Mtb) H37RV with wild-type mice as controls. Four weeks after infection, the mRNA expression of IFN-γ, TNF-α, and TCF-7 in the lungs of mice was measured. CD4, CD8, ß-catenin, IFN-γ, and TNF-α in mononuclear cells from the lungs and spleens were measured by flow cytometry, and the pathological changes of lungs were also observed. Patients with PTB were enrolled, with blood samples collected and PBMCs isolated. The expressions of ß-catenin, IFN-γ, TNF-α, and PD-1 in CD4+ and CD8+ T cells were measured by flow cytometry. Results showed a decreased frequency of and reduced IFN-γ/TNF-α mRNA expression and secretion by CD4+ T cells in the lungs of infected ß-CAT-cKO mice compared with infected wild-type controls, and only slightly more inflammatory changes were observed in the lungs. ß-catenin expressions in CD4+ and CD8+ T cells were significantly decreased in blood cells of patients with severe PTB compared with those in mild PTB. The stimulation of peripheral blood mononuclear cells (PBMCs) with lithium chloride (LiCl), a stimulant of ß-catenin, resulted in the increase in CD4+ T cell frequency, as well as their secretion of IFN-γ and TNF-α. ß-Catenin demonstrated a moderately positive correlation with PD-1 in CD4+ T cells. ß-Catenin along with PD-1 and IFN-γ in CD4+ T cells had a high correlation with those in CD8+ T cells. In conclusion, ß-catenin may be involved in the regulation of Th1 response and CD4+ T cell frequency in TB.