Tropheryma whipplei detection by metagenomic next-generation sequencing in bronchoalveolar lavage fluid: A cross-sectional study.

Tropheryma whipplei is the bacterium associated with Whipple's disease (WD), a chronic systemic infectious disease primarily involving the gastrointestinal tract. T. whipplei can also be detected in different body site of healthy individuals, including saliva and feces. Traditionally, Tropheryma whipplei has a higher prevalence in bronchoalveolar lavage fluid (BALF) of immunocompromised individuals. Few studies have explored the significance of the detection of T. whipplei in BALF. Herein, we retrospectively reviewed 1725 BALF samples which detected for metagenomic next-generation sequencing (mNGS) from March 2019 to April 2022 in Zhuhai, China. Seventy BALs (70/1725, 4.0%) from 70 patients were positive for T. whipplei. Forty-four patients were male with an average age of 50 years. The main symptoms included cough (23/70), expectoration (13/70), weight loss (9/70), and/or dyspnea (8/70), but gastrointestinal symptoms were rare. Chronic liver diseases were the most common comorbidity (n=15, 21.4%), followed by diabetes mellitus (n=13, 18.6%). Only nine patients (12.9%) were immunocompromised. Twenty-four patients (34.3%) were finally diagnosed with reactivation tuberculosis and 15 patients (21.4%) were diagnosed with lung tumors, including 13 primary lung adenocarcinoma and two lung metastases. Fifteen patients (21.4%) had pneumonia. Among the 20 samples, T. whipplei was the sole agent, and Mycobacterium tuberculosis complex was the most common detected other pathogens. Among the non-tuberculosis patients, 31 (31/46, 67.4%) had ground glass nodules or solid nodules on chest CT. Our study indicates that T. whipplei should be considered as a potential contributing factor in some lung diseases. For non-immunocompromised patients, the detection of T. whipplei also needs attention. The mNGS technology improves the detection and attention of rare pathogens. In the future, the infection, colonization, and prognosis of T. whipplei in lung still need to be studied.

Enhanced Inhibitory Effect of DC-CIK Cells on Lung Adenocarcinoma via Anti-Tim-3 Antibody and Antiprogrammed Cell Death-1 Antibody and Possible Mechanism.

Objective: To investigate the effect and mechanism of blocking the signaling pathways of the T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and programmed death protein 1 (PD-1) in dendritic cell-cytokine induced killer (DC-CIK) cells on human lung adenocarcinoma A549 cells. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated and induced into mature DC-CIK cells by cytokines in vitro. After blocking the Tim-3 and PD-1 signaling transduction pathways with anti-Tim-3 and anti-PD-1 antibodies, DC-CIK cells were coincubated with A549 cells. The killing effect of DC-CIK cells against A549 cells was measured by a CCK-8 assay. The impact of DC-CIK cells on the invasion and migration ability of A549 cells was detected by the Transwell test. The apoptosis rate of DC-CIK cells and the ratio of CD4+, CD8+, and DC-CIK cell subsets were determined by flow cytometry. The cell proliferation of DC-CIK was detected by the CCK-8 assay. Results: The antibodies of anti-Tim-3 antibody and anti-PD-1 could block Tim-3+ and PD-1+ DC-CIK cells and could significantly increase the killing effect of DC-CIK cells on A549 cells. The number of A549 cells under the microporous membrane of the Transwell chamber was reduced considerably in invasion and migration tests. Anti-Tim-3 and anti-PD-1 antibodies significantly reduced apoptosis of DC-CIK cells. No significant differences were observed in the ratios of CD4+ and CD8+ DC-CIK cell subsets or the proliferation capacity of DC-CIK cells in each group. Conclusion: Blocking the Tim-3 and PD-1 signaling pathways of DC-CIK cells with antibodies can enhance the killing ability of DC-CIK cells in A549 cells and significantly suppress the invasion and migration ability of A549 cells. The potential mechanism may be related to reduced apoptosis of DC-CIK cells.

Effect of Exercise on Fatigue in Patients with Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Trials.

Background: Fatigue is a frequent debilitating symptom among patients with lung cancer. The effect of exercise on fatigue remains to be quantified. Objective: This review aimed to examine the effect of exercise on fatigue by synthesizing findings from randomized controlled trials (RCTs). Methods: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was conducted in five electronic databases from inception to March 2020. Only RCT was included. The primary outcome was fatigue and the secondary outcomes included depression, anxiety, quality of life, and functional capacity. Pooled weighted or standardized mean difference (WMD or SMD) with 95% confidence interval (CI) was calculated. Results: Eight RCTs were included. The exercise intervention was delivered in the supervised environment (n = 6) or free-living settings (n = 2). Exercise reduced the level of fatigue (SMD = -0.33; 95% CI = -0.54 to -0.13). Exercise also decreased depressive symptom (WMD = -1.57; 95% CI = -2.69 to -0.44) and anxiety (WMD = -1.39; 95% CI = -2.60 to -0.18). Exercise showed a moderate effect on the quality of life, with an SMD of 0.33 (95% CI = 0.08 to 0.58). Exercise intervention increased functional capacity as measured by the six-minute walk test by 20 meters (95% CI = 14.2 to 55.0), but the effect was not significant (p = 0.247). Conclusion: Exercise demonstrated a moderate effect on fatigue in patients with lung cancer. Exercise also improved depressive symptoms, anxiety, and quality of life; however, its impact on functional capacity was not significant. More clinical trials are warranted to explore the mechanisms underlying the impact of exercise on fatigue. Strategies improving adherence to exercise prescription should be developed to help these patients overcome potential challenges.

Sideroflexin1 as a novel tumor marker independently predicts survival in lung adenocarcinoma.

BACKGROUND: Targeted therapy for lung cancers is based on prognostic genes and needs more investigation. No study has yet evaluated the effects of Sideroflexin1 (SFXN1) on lung cancer. METHODS: Data were analyzed from large patient cohorts in the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). RESULTS: The mRNA and protein expression of SFXN1 is apparently upregulated in lung adenocarcinoma (LUAD) tissues. Among LUAD patients, upregulated SFXN1 mRNA expression can independently predict unfavorable overall survival (OS, P=0.006) and recurrence-free survival (RFS; P=0.003). In addition, detection data from DNA copy number alterations (CNAs) showed that 164 (32.03%) of the 512 cases had copy number loss (-2 and -1), while 121 (23.63%) of the cases had copy number amplification (+1 and +2). We also found a weak negative correlation between the methylation status of one CpG site (chr5: 174, 944, 791-174, 944, 793) and SFXN1 expression (P<0.0001). CONCLUSIONS: Upregulated SFXN1 mRNA expression can be a prognostic biomarker of unfavorable OS and RFS in patients with LUAD.