Leukemia inhibitory factor (LIF) is a tumor promoter in several cancer types. However, the role of LIF in non‑small cell lung cancer (NSCLC) remains to be explored. The present study explored the hypothesis that LIF is important for NSCLC development by measuring LIF expression and its downstream signal transducer and activator of transcription 3 (STAT3) phosphorylation in tumor samples derived from patients with NSCLC. The association between LIF expression and clinical features was analyzed in two cancer subtypes. The effects of LIF on cell proliferation, migration and invasion were also evaluated in a NSCLC‑derived cell line, A549. LIF mRNA and protein expression levels were significantly higher in tumor tissues compared with those in the corresponding adjacent and normal lung tissues. Regarding NSCLC subtypes, LIF expression was significantly higher in adenocarcinoma than in squamous cell carcinoma tissues. It was also found that phosphorylated‑STAT3 levels were higher in tumor tissues compared with those in the corresponding adjacent and normal lung tissues, which was in agreement with the LIF expression levels in NSCLC tissues. Clinically, overexpression of LIF was positively correlated with aggressive tumor characteristics, including lymph node metastasis and advanced tumor stage. In A549 cells, LIF treatment enhanced cell proliferation, migration and invasion. LIF also increased STAT3 phosphorylation in A549 cells, and the STAT3 inhibitor Stattic decreased A549 cell migration and invasion following LIF stimulation. The present results demonstrate that LIF is overexpressed in NSCLC, and that LIF can promote NSCLC development through activation of the STAT3 signaling pathway. The present study indicates that LIF may serve as a potential prognostic marker for NSCLC.
To evaluate the value of lung ultrasonography score (LUS) on assessing extravascular lung water (EVLW) and prognosis in patients with acute respiratory distress syndrome (ARDS).The clinical data of 46 patients meeting ARDS Berlin definition admitted to intensive care unit (ICU) of Ningbo Yinzhou People's Hospital from July 2016 to December 2019 were retrospectively collected. The general data, vital signs, blood lactic acid (Lac), oxygenation index (OI), LUS, extravascular lung water index (EVLWI), sequential organ failure assessment (SOFA) score, clinical pulmonary infection score (CPIS) and the length of ICU stay were collected. According to the prognosis of patients during ICU treatment, the patients were divided into survival group and non-survival group, and the clinical characteristics between the two groups were compared. The correlation between LUS and OI, EVLWI, SOFA, and CPIS were analyzed by Pearson correlation analysis. Receiver operator characteristic (ROC) curve was plotted to determine the prognostic value of LUS for ARDS patients during ICU treatment.Forty-six patients were enrolled in the analysis, of whom 32 patients survived (69.6%), and 14 patients died (30.4%) during ICU treatment. There was no significant difference in gender, age, left ventricular ejection fraction (LVEF) or heart rate (HR) between the two groups. Compared with the survival group, the mean arterial pressure (MAP) and OI in the non-survival group were significantly lowered [MAP (mmHg, 1 mmHg = 0.133 kPa): 57.48±33.34 vs. 85.45±19.56, OI (mmHg): 74.50±18.40 vs. 233.06±28.28, both P < 0.05], while Lac, LUS, EVLWI, SOFA and CPIS were significantly increased [Lac (mmol/L): 6.78±2.56 vs. 2.21±1.42, LUS score: 23.57±2.03 vs. 15.58±2.24, EVLWI (mL/kg): 22.93±2.56 vs. 12.96±2.18, SOFA score: 20.21±3.35 vs. 12.43±2.97, CPIS score: 8.07±1.38 vs. 4.59±1.04, all P < 0.01], and the length of ICU stay was significantly shortened (days: 9.33±3.28 vs. 16.89±4.12, P < 0.05]. Pearson correlation analysis showed that a significant negative linear correlation was found between LUS and OI (r = -0.823, P < 0.01), and positive linear correlations were found between LUS and EVLWI, SOFA, CPIS (r values were 0.745, 0.614, 0.757, respectively, all P < 0.01). ROC curve analysis showed that both LUS and EVLWI could predict the prognosis of ARDS patients during ICU treatment, and the areas under ROC curve (AUC) of LUS and EVLWI were 0.936 and 0.991, respectively. When the cut-off of LUS score was 20.5, the sensitivity and specificity were 85.7% and 81.2% respectively.LUS score has a good correlation with EVLWI monitored by pulse index continuous cardiac output (PiCCO), which can reflect lung water content. LUS score can be used as an early prognostic indicator for ARDS patients.
Abstract Objectives Chronic obstructive pulmonary disease (COPD) patients have higher laryngopharyngeal reflux (LPR)‐related symptom incidence. But LPR treatment is empirical. We aimed to determine the frequency of LPR, diagnosed by 24‐hour Dx‐pH monitoring, among acute exacerbations of COPD (AECOPD) patients with Reflux Symptom Index (RSI) ≥13 and investigate proton pump inhibitor (PPI) treatment effect on LPR, COPD symptoms, and pulmonary function. Methods From January 2016 to September 2017, 102 AECOPD patients with RSI ≥13 were enrolled. COPD assessment test (CAT), mMRC dyspnea scale, pulmonary function tests, and 24‐hour Dx‐pH monitoring were performed. The Ryan score was evaluated by using the Dx‐pH DataView Lite software, which identifies patients with abnormal pharyngeal pH environments. Associations among RSI, pulmonary function test results, and Ryan score parameters were evaluated. The abovementioned assessments were reperformed after treatment, and pre‐ and posttreatment data were compared. Results Of the 102 eligible patients, 49 (48.04%) were diagnosed with LPR based on Ryan score. Percentage of the forced expiratory volume at 1 second (FEV1%) was significantly worse in Ryan‐positive than in Ryan‐negative AECOPD patients. There were significant negative correlations between FEV1% and Ryan score ( r = −0.394, P < 0.001), FEV1% and % time below pH threshold ( r = −0.371, P < 0.001) in upright position but not in supine position. There was no significant correlation between RSI and Ryan score parameters. There were significant improvements in RSI, mMRC, CAT, and FEV1% in Ryan‐positive AECOPD patients after PPI and basic treatments. Conclusion Study results indicate unreliability of RSI threshold for LPR diagnosis. Combination of symptoms, endoscopic findings, and 24‐hour Dx‐pH monitoring is recommended for LPR diagnosis and PPI treatment decisions, especially in difficult‐to‐control or severe COPD patients.
Bacterial infection of the lower respiratory tract is believed to play a major role in the pathogenesis of chronic obstructive pulmonary disease (COPD) and acute exacerbations of COPD (AECOPD). This study investigates the potential relationship between AECOPD and the load of six common bacterial pathogens in the lower respiratory tract using real-time quantitative PCR (RT-qPCR) in COPD patients.Protected specimen brush (PSB) and bronchoalveolar lavage fluid (BALF) samples from the lower respiratory tract of 66 COPD patients and 33 healthy subjects were collected by bronchoscopy. The load of Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae, and Moraxella catarrhalis were detected by RT-qPCR.High Klebsiella pneumoniae, Pseudomonos aeruginosa, Haemophilus influenzeae and Moraxella catarrhalis burden were detected by RT-qPCR in both PSB and BALF samples obtained from stable COPD and AECOPD patients compared with healthy subjects. The load of the above four pathogenic strains in PSB and BALF samples obtained from AECOPD patients were significantly higher compared with stable COPD patients. Finally, positive correlations between bacterial loads and inflammatory mediators such as neutrophil count and cytokine levels of IL-1β, IL-6 and IL-8, as well as negative correlations between bacterial loads and the forced expiratory volume in one second (FEV1) % predicted, forced vital capacity (FVC) % predicted, and FEV1/FVC ratio, were detected.These findings suggest that increased bacterial loads mediated inflammatory response in the lower respiratory tract and were associated with AECOPD. In addition, these results provide guidance for antibiotic therapy of AECOPD patients.
Circular RNAs represent a new class of noncoding RNAs involved in the development of cancer. However, little is known about their role in non-small cell lung cancer (NSCLC).We examined hsa_circ_0003998 levels in 60 NSCLC tissues by quantitative real-time polymerase chain reaction and analyzed the clinicopathologic significance of hsa_circ_0003998 expression. The effect of small interfering RNA-mediated hsa_circ_0003998 knockdown on proliferation and invasion was analyzed in A549 and H1299 cells in vitro. Moreover, the target genes of hsa_circ_0003998 were further explored by bioinformatic analysis, dual luciferase reporter assays, and rescue experiments.Hsa_circ_0003998 upregulation was associated with larger tumor size and lymph node metastasis and also correlated with shorter overall survival of NSCLC patients. Functional experiments showed knockdown of hsa_circ_0003998 restrained cell proliferation and invasion in NSCLC cells. In particular, hsa_circ_0003998 upregulated the expression of miR-326 target gene Notch1 through sponging miR-326. Furthermore, the tumor-inhibiting effect of hsa_circ_0003998 silencing was blocked by miR-326 inhibitor.hsa_circ_0003998/miR-326/Notch1 pathway regulates the progression of NSCLC.
Recent studies have implied that miRNAs act as crucial modulators for epithelial‐to‐mesenchymal transition (EMT). We found that miR‐134 expression correlated with invasive potential and EMT phenotype of NSCLC cells. Functional assays demonstrated that miR‐134 inhibited EMT in NSCLC cells. In addition, we showed that Forkhead Box M1 (FOXM1) is a direct target of miR‐134. Knockdown of FOXM1 reversed EMT resembling that of miR‐134 overexpression. We further found that FOXM1 was involved in TGF‐β1‐induced EMT in A549 cells. These findings suggest that miR‐134 acts as a novel EMT suppressor in NSCLC cells.
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