Comparative analysis of clinical features of lower respiratory tract infection with respiratory syncytial virus and influenza virus in adults: a retrospective study.

BACKGROUND: Respiratory syncytial virus (RSV) infection in adults remains less recognized and understood, both socially and clinically, compared to influenza virus infection. This retrospective study aims to delineate and compare the clinical manifestations of adult RSV and influenza virus infections in the lower respiratory tract, thereby enhancing awareness of RSV lower respiratory tract infection and providing strategic insights for its prevention and treatment. METHODS: Clinical data from January 2019 to December 2020 were analyzed for 74 patients with RSV and 129 patients with influenza A/B virus lower respiratory tract infections who were admitted to respiratory or intensive care units. All patients had complete clinical data with positive IgM and negative IgG viral antibodies. Comparison parameters included onset timing, baseline data, clinical manifestations, supplementary examination results, treatment methods, and prognosis, while logistic regression was employed to ascertain the correlation of clinical features between the two patient groups. RESULTS: In comparison to the influenza group, the RSV group presented less frequently with fever at admission but exhibited a higher incidence of dyspnea and wheezing on pulmonary auscultation (P < 0.01). RSV infection was more prevalent among patients with underlying diseases, particularly chronic obstructive pulmonary disease (COPD) and demonstrated a higher probability of co-infections, most notably with Mycoplasma (P < 0.01). The RSV group had significantly higher lymphocyte counts (P < 0.01) and exhibited more incidences of pleural thickening, pulmonary fibrosis, and emphysema (P < 0.05). The use of non-invasive mechanical ventilation was more common, and hospital stays were longer in the RSV group compared to the influenza group (P < 0.05). Logistic multivariate regression analysis further revealed that age and tachypnea incidence were significantly higher in the RSV group (P < 0.05). CONCLUSION: Compared to influenza virus infection, adults with COPD are more susceptible to RSV infection. Moreover, RSV infection elevates the risk of co-infection with Mycoplasma and may lead to conditions such as pleural thickening, pulmonary fibrosis, and emphysema. The requirement for non-invasive mechanical ventilation is higher in RSV-infected patients, who also tend to have longer hospital stays. Therefore, greater awareness and preventive strategies against RSV infection are imperative.

Characterization of the fatty acid metabolism-related genes in lung adenocarcinoma to guide clinical therapy.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common cancer with a bad prognosis. Numerous investigations have indicated that the metabolism of fatty acids plays an important role in the occurrence, progression, and treatment of cancer. Consequently, the objective of the current investigation was to elucidate the role and prognostic significance of genes associated with fatty acid metabolism in patients diagnosed with LUAD. MATERIALS AND METHODS: The data files were acquired from The Cancer Genome Atlas database and GSE31210 dataset. Univariate Cox and least absolute shrinkage and selection operator regression analyses were conducted to establish a prognostic risk scoring model depending on fatty acid metabolism-associated genes to predict the prognosis of patients with LUAD. pRRophetic algorithm was utilized to evaluate the potential therapeutic agents. Gene set variation analysis combined with cell-type identification based on the estimation of relative subsets of RNA transcript and single-sample gene set enrichment analysis was used to determine the association between immune cell infiltration and risk score. Tumor immune dysfunction and exclusion algorithm was employed to predict immunotherapeutic sensitivity. RESULTS: To forecast the prognosis of patients with LUAD, a risk scoring model based on five genes associated with fatty acid metabolism was developed, including LDHA, ALDOA, CYP4B1, DPEP2, and HPGDS. Using the risk score algorithm, patients were divided into higher- and lower-risk categories. Patients classified as minimal risk showed superior prognosis than those with elevated risk. In addition, individuals in the higher-risk group had a proclivity toward chemoresistance and amenable to immunotherapy. CONCLUSION: The prognostic risk scoring model aids in estimating the prognosis of LUAD patients. It may also provide new insights into LUAD carcinogenesis and therapeutic strategies.

Identification and validation of autophagy-related gene expression for predicting prognosis in patients with idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fatal fibrotic pulmonary disease with unknow etiology. Owing to lack of reliable prognostic biomarkers and effective treatment measures, patients with IPF usually exhibit poor prognosis. The aim of this study is to establish a risk score prognostic model for predicting the prognosis of patients with IPF based on autophagy-related genes. Methods: The GSE70866 dataset was obtained from the gene expression omnibus (GEO) database. The autophagy-related genes were collected from the Molecular Signatures Database (MSigDB). Gene enrichment analysis for differentially expressed genes (DEGs) was performed to explore the function of DEGs. Univariate, least absolute shrinkage and selection operator (LASSO), as well as multivariate Cox regression analyses were conducted to identify a multi-gene prognostic model. Receiver operating characteristic (ROC) curve was applied to assess the prediction accuracy of the model. The expression of genes screened from the prognostic model was validated in clinical samples and human lung fibroblasts by qPCR and western blot assays. Results: Among the 514 autophagy-related genes, a total of 165 genes were identified as DEGs. These DEGs were enriched in autophagy-related processes and pathways. Based on the univariate, LASSO, and multivariate Cox regression analyses, two genes (MET and SH3BP4) were included for establishing the risk score prognostic model. According to the median value of the risk score, patients with IPF were stratified into high-risk and low-risk groups. Patients in high-risk group had shorter overall survival (OS) than low-risk group in both training and test cohorts. Multivariate regression analysis indicated that prognostic model can act as an independent prognostic indicator for IPF. ROC curve analysis confirmed the reliable predictive value of prognostic model. In the validation experiments, upregulated MET expression and downregulated SH3BP4 expression were observed in IPF lung tissues and TGF-ß1-activated human lung fibroblasts, which is consistent with results from microarray data analysis. Conclusion: These findings indicated that the risk score prognostic model based on two autophagy-related genes can effectively predict the prognosis of patients with IPF.

Downregulation of microRNA­423­5p suppresses TGF­ß1­induced EMT by targeting FOXP4 in airway fibrosis.

Airway fibrosis (AF) is a common disease that can severely affect patient prognosis. Epithelial­mesenchymal transition (EMT) participates in the pathophysiological development of AF and several studies have demonstrated that some microRNAs (miRNAs) contribute to the development of EMT. The aim of this study was to investigate the function of miR­423­5p in the EMT process and its possible underlying mechanism in BEAS­2B cells. The present study utilized the BEAS­2B cell line to model EMT in AF. Online tools, fluorescence in situ hybridization analysis and an RNA pull­down assay were used to identify potential target genes of miR­423­5p. In addition, immunohistochemistry, wound healing assays, Transwell migration assays, flow cytometry, enzyme­linked immunosorbent assay, reverse transcription­quantitative PCR, western blot analysis and immunofluorescence staining were used to determine the function of miR­423­5p and its target gene in the EMT process in AF. The results indicated that the miR­423­5p expression in AF tissues and BEAS­2B cells stimulated with 10 ng/ml TGF­ß1 for 24 h was significantly increased compared with that in the control group. Overexpression of miR­423­5p facilitated TGF­ß1­induced EMT in BEAS­2B cells; by contrast, downregulation of miR­423­5p suppressed TGF­ß1­induced EMT in BEAS­2B cells. Furthermore, forkhead box p4 (FOXP4) was identified as a potential target gene of miR­423­5p and changes in the miR­423­5p and FOXP4 expression were shown to significantly affect the expression of PI3K/AKT/mTOR pathway members. In summary, overexpression of miR­423­5P promoted the EMT process in AF by downregulating FOXP4 expression and the underlying mechanism may partly involve activation of the PI3K/AKT/mTOR pathway.

A Novel Hypoxia-Related Gene Signature with Strong Predicting Ability in Non-Small-Cell Lung Cancer Identified by Comprehensive Profiling.

Background: Non-small-cell lung cancer (NSCLC) is the most common malignant tumor among males and females worldwide. Hypoxia is a typical feature of the tumor microenvironment, and it affects cancer development. Circular RNAs (circRNAs) have been reported to sponge miRNAs to regulate target gene expression and play an essential role in tumorigenesis and progression. This study is aimed at identifying whether circRNAs could be used as the diagnostic biomarkers for NSCLC. Methods: The heterogeneity of samples in this study was assessed by principal component analysis (PCA). Furthermore, the Gene Expression Omnibus (GEO) database was normalized by the affy R package. We further screened the differentially expressed genes (DEGs) and differentially expressed circular RNAs (DEcircRNAs) using the DEseq2 R package. Moreover, we analyzed the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of DEGs using the cluster profile R package. Besides, the Gene Set Enrichment Analysis (GSEA) was used to identify the biological function of DEGs. The interaction between DEGs and the competing endogenous RNAs (ceRNA) network was detected using STRING and visualized using Cytoscape. Starbase predicted the miRNAs of target hub genes, and miRanda predicted the target miRNAs of circRNAs. The RNA-seq profiler and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Then, the variables were assessed by the univariate and multivariate Cox proportional hazard regression models. Significant variables in the univariate Cox proportional hazard regression model were included in the multivariate Cox proportional hazard regression model to analyze the association between the variables of clinical features. Furthermore, the overall survival of variables was determined by the Kaplan-Meier survival curve, and the time-dependent receiver operating characteristic (ROC) curve analysis was used to calculate and validate the risk score in NSCLC patients. Moreover, predictive nomograms were constructed and used to predict the prognostic features between the high-risk and low-risk score groups. Results: We screened a total of 2039 DEGs, including 1293 upregulated DEGs and 746 downregulated DEGs in hypoxia-treated A549 cells. A549 cells treated with hypoxia had a total of 70 DEcircRNAs, including 21 upregulated and 49 downregulated DEcircRNAs, compared to A549 cells treated with normoxia. The upregulated genes were significantly enriched in 284 GO terms and 42 KEGG pathways, while the downregulated genes were significantly enriched in 184 GO terms and 25 KEGG pathways. Moreover, the function analysis by GSEA showed enrichment in the enzyme-linked receptor protein signaling pathway, hypoxia-inducible factor- (HIF-) 1 signaling pathway, and G protein-coupled receptor (GPCR) downstream signaling. Furthermore, six hub modules and 10 hub genes, CDC45, EXO1, PLK1, RFC4, CCNB1, CDC6, MCM10, DLGAP5, AURKA, and POLE2, were identified. The ceRNA network was constructed, and it consisted of 4 circRNAs, 14 miRNAs, and 38 mRNAs. The ROC curve was constructed and calculated. The area under the curve (AUC) value was 0.62, and the optimal threshold was 0.28. Based on the optimal threshold, the patients were divided into the high-risk score and low-risk score groups. The survival rate in the high-risk score group was lower than that in the low-risk score group. The expression of SERPINE1, STC2, and LPCAT1; clinical stage; and age of the patient were significantly correlated with the high-risk score. Moreover, nomograms were established based on the risk factors in multivariate analysis, and the median survival time, 3-year survival probability, and 5-year survival were possibly predicted according to nomograms. Conclusion: The ceRNA network associated with NSCLC was identified, and the hub genes, circRNAs, might act as the potential biomarkers for NSCLC.

Integrated Trinity Test With RPA-CRISPR/Cas12a-Fluorescence for Real-Time Detection of Respiratory Syncytial Virus A or B.

Respiratory syncytial virus (RSV) is a common virus that causes respiratory infection, especially severe respiratory infection in infants and young children, the elderly people over 65 years old, and people with weak immunity. Currently, RSV infection has no effective vaccine and antiviral treatment. The number of deaths due to RSV infection increases every year. Moreover, RSV A infection occurs in a large number and has severe clinical symptoms and complications than RSV B infection. Therefore, the development of a simple, rapid, and inexpensive detection method with high amplification efficiency, high sensitivity, and specificity is very important for the diagnosis of RSV A or RSV B infection, which can help in the early clinical medication and prevent the progress of the disease. Therefore, we developed an integrated trinity test with an RPA-CRISPR/Cas12a-fluorescence (termed IT-RAISE) assay system to detect RSV A or RSV B. The characteristic of the IT-RAISE system is that after target recognition, the reporter single-stranded DNA (ssDNA) is cleaved by Cas12a that is activated by different crRNAs to detect the generated fluorescent signal. This method is simple and helps in adding all reagents rapidly. It is a high-sensitive method that can detect 1.38 × 101 copies/µl of the target sequences, and it can distinguish RSV A or RSV B infection within 37 min. In addition, clinical specimens were detected for IT-RAISE system. It was found that the sensitivity and specificity of RSV A were 73.08 and 90%, respectively, and those of RSV B were 42.86 and 93.33%, respectively. The cost of ONE specimen for IT-RAISE system was approximately $ 2.6 (excluding rapid RNA extraction and reverse transcription costs). IT-RAISE system has good clinical application prospects for detecting RSV A or RSV B infection; it is a simple, rapid, and inexpensive method with high amplification efficiency, high sensitivity, and high specificity. The IT-RAISE system might also detect other viral or bacterial infections.

Efficacy and Safety of Cryobiopsy vs. Forceps Biopsy for Interstitial Lung Diseases, Lung Tumors, and Peripheral Pulmonary Lesions: An Updated Systematic Review and Meta-Analysis.

Background: Cryobiopsy has emerged as a novel alternative to conventional forceps biopsy for the diagnosis of interstitial lung diseases (ILDs), lung tumors, and peripheral pulmonary lesions (PPLs). This study aims to compare cryobiopsy and forceps biopsy for the diagnosis of these lung pathologies with respect to efficacy and safety by performing a meta-analysis of updated evidence. Methods: A number of databases, such as PubMed, Embase, Web of Science, the Cochrane Library, OVID, CNKI, and Wanfang database, were searched for eligible studies. Randomized and non-randomized comparative studies investigating the efficacy and safety of cryobiopsy vs. forceps biopsy for lung pathologies were included. Pooled results were calculated as an odds ratio (OR) or standardized mean difference (SMD) with 95% CI. Results: A total of 39 studies, such as 9 RCTs with 3,586 biopsies (1,759 cryobiopsies and 1,827 flexible forceps biopsies) were analyzed. Cryobiopsy was associated with a significant increase in the diagnostic rates of ILDs (OR, 4.29; 95% CI, 1.85-9.93; p < 0.01), lung tumors (OR, 3.58; 95% CI, 2.60-4.93; p < 0.01), and PPLs (OR, 1.70; 95% CI, 1.23-2.34; p < 0.01). Cryobiopsy yielded significantly larger specimens compared with flexible forceps biopsy (SMD, 3.06; 95% CI, 2.37-3.74; p < 0.01). The cryobiopsy group had a significantly higher (moderate to severe) bleeding risk than the forceps group (OR, 2.17; 95% CI, 1.48-3.19; p < 0.01). No significant difference was observed in the incidence of pneumothorax between the groups (OR, 0.90; 95% CI, 0.44-1.85; p = 0.78). Conclusion: Our results demonstrate that cryobiopsy is a safe and efficacious alternative to conventional forceps biopsy.

Downregulation of miR­483­5p inhibits TGF­ß1­induced EMT by targeting RhoGDI1 in pulmonary fibrosis.

Transforming growth factor­ß1 (TGF­ß1)­induced epithelial­mesenchymal transition (EMT) serves a significant role in pulmonary fibrosis (PF). Increasing evidence indicates that microRNAs (miRNAs or miRs) contribute to PF pathogenesis via EMT regulation. However, the role of miR­483­5p in PF remains unclear. Therefore, the present study investigated the potential effect of miR­483­5p on TGF­ß1­induced EMT in PF. It was found that the expression of miR­483­5p was upregulated in both PF tissue and A549 cells treated with TGF­ß1, whereas expression of Rho GDP dissociation inhibitor 1 (RhoGDI1) was downregulated. miR­483­5p mimic transfection promoted TGF­ß1­induced EMT; by contrast, miR­483­5p inhibitor inhibited TGF­ß1­induced EMT. Also, miR­483­5p mimic decreased RhoGDI1 expression, whereas miR­483­5p inhibitor increased RhoGDI1 expression. Furthermore, dual­luciferase reporter gene assay indicated that miR­483­5p directly regulated RhoGDI1. Moreover, RhoGDI1 knockdown eliminated the inhibitory effect of the miR­483­5p inhibitor on TGF­ß1­induced EMT via the Rac family small GTPase (Rac)1/PI3K/AKT pathway. In conclusion, these data indicated that miR­483­5p inhibition ameliorated TGF­ß1­induced EMT by targeting RhoGDI1 via the Rac1/PI3K/Akt signaling pathway in PF, suggesting a potential role of miR­483­5p in the prevention and treatment of PF.

Virtual bronchoscopic navigation versus non-virtual bronchoscopic navigation assisted bronchoscopy for the diagnosis of peripheral pulmonary lesions: a systematic review and meta-analysis.

BACKGROUND: Image-guided bronchoscopy techniques such as virtual bronchoscopic navigation (VBN) has emerged as a means of assisting in the biopsy of peripheral pulmonary lesions. However, the role of VBN-assisted (VBNA) bronchoscopy in the diagnosing of peripheral pulmonary lesions (PPLs) has not been well established. This meta-analysis investigated the diagnostic yield of VBN-assisted versus non-VBN-assisted (NVBNA) bronchoscopy for PPLs. METHODS: PubMed, Embase, Cochrane library, and Web of Sciences databases were searched up to and including August 2020 to identify randomized controlled trials (RCTs) evaluating the performance of VBNA compared with an NVBNA group. Results were expressed as risk ratio (RR) or mean difference (MD) with accompanying 95% confidence interval (CI). RESULTS: Six RCTs with 1626 patients were included. The overall diagnostic rate was similar in the VBNA (74.17%) and NVBNA (69.51%) groups, with risk ratio of 1.07 (95% CI: 0.98-1.17). However, in the VBNA group, the total examination time was significantly shorter (MD = -3.94 min, 95% CI: -6.57 to -1.36; p = 0.003) than in the NVBNA group. VBNA had superior diagnostic yield than NVBNA for PPLs ⩽ 20 mm (RR = 1.18, 95% CI: 1.05-1.32). In addition, diagnostic yield according to nature of lesion, lesion location in the lung lobe, distance from the hilum, bronchus sign and complications were similar between VBNA and NVBNA groups. CONCLUSION: VBNA bronchoscopy did not increase overall diagnostic yield in patients with PPLs compared with NVBNA bronchoscopy. The superiority of VBNA over NVBNA was evident among patients with PPLs ⩽ 20 mm. Future multicenter RCTs are needed for further investigation.The reviews of this paper are available via the supplemental material section.

A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma.

BACKGROUND: Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. METHODS: The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. RESULTS: Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. CONCLUSION: A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.

Clinical significance of serum transforming growth factor-ß1 and procollagen type I N-propeptide in post-tuberculosis tracheobronchial stenosis.

Non-invasive strategies for monitoring post-tuberculosis (TB) tracheobronchial stenosis (PTTS) are clinically important but currently lacking. Transforming growth factor-ß1 (TGF-ß1) and procollagen type I N-propeptide (PINP) have been identified as markers of fibrosis. The present study aimed to investigate the clinical significance of serum TGF-ß1 and PINP in PTTS. Serum samples were collected from 119 patients with tracheobronchial TB after the condition was treated for at least 6 months (59 patients with airway stenosis and 60 patients with no stenosis). Serum TGF-ß1 and PINP levels were measured using ELISA and compared between the groups. Relationships between serum TGF-ß1 and PINP levels and clinical characteristics, interventional bronchoscopy and outcomes of airway stenosis were analysed. The correlation between TGF-ß1 and PINP, and their diagnostic efficacy for airway stenosis were also analysed. The TGF-ß1 and PINP levels in the airway stenosis group were higher than those in the non-stenosis group. Furthermore, airway stenosis with atelectasis or mucus plugging was associated with higher TGF-ß1 levels, and airway stenosis with atelectasis, mucus plugging, right main bronchus stenosis or severe airway tracheal stenosis was associated with higher PINP levels. In addition, TGF-ß1 and PINP levels increased after interventional bronchoscopy therapy and airway stenosis with recurrent stenosis was associated with higher baseline levels of both markers. Finally, TGF-ß1 levels were positively correlated with PINP levels in patients with airway stenosis. The area under the receiver operating characteristic curve of TGF-ß1 and PINP for distinguishing airway stenosis from non-stenosis cases was 0.824 (95% CI: 0.748-0.900) and 0.863 (95% CI: 0.796-0.930), respectively. Therefore, TGF-ß1 and PINP are potential biomarkers that may be useful for diagnosing and monitoring PTTS.

Analysis of Incidence and Clinical Characteristics of RSV Infection in Hospitalized Children: A Retrospective Study.

OBJECTIVE: To investigate the incidence and clinical characteristics of hospitalized children with respiratory syncytial virus (RSV) infection, and to provide evidence for the importance of preventive strategies and improvements in supportive care of RSV infection. METHODS: This retrospective study included children under 14 years who received throat swab test and were diagnosed with RSV infection from January 2019 to December 2020. Throat swabs and intravenous blood were the main sources of samples, which were obtained within 24 hours of hospitalization. Direct immunofluorescence assay was used to diagnose RSV infection. RESULTS: Among the 448 hospitalized children with RSV infection, males (71.9%) showed the highest proportion, the highest incidence was found in children<6 months old (45.3%), and 76.6% of them had pneumonia. Pharyngeal redness, cough, expectoration, and mental fatigue were the most common symptoms in hospitalized children of all ages. More than 60% of hospitalized children had increased lymphocyte count, aspartate aminotransferase, creatine kinase-MB form, lactate dehydrogenase, and α-HBDH levels. The rates of myocardial damage, respiratory failure, stay in the intensive care unit (ICU), use of mechanical ventilation, and absorption of oxygen were higher in children<6 months old. Except for children who were 37-60 months old, the percentage of length of hospital stay≥7 days in the other age groups was greater than 62.0%. Except for children who were 0-28 days old and>61 months old, the other age groups showed a re-hospitalization situation due to re-infection with RSV. In hospitalized children diagnosed with RSV infection from throat swabs, we also performed the RSV IgM test and found that 59.2% of them were positive, 8.0% of them were weakly positive, and 32.8% of them were negative. CONCLUSION: This study analyzes the incidence and clinical characteristics of hospitalized children with RSV infection, which provides evidence for the importance of preventive strategies and improvements in supportive care of RSV infection.

miR­320a­3P alleviates the epithelial­mesenchymal transition of A549 cells by activation of STAT3/SMAD3 signaling in a pulmonary fibrosis model.

Pulmonary fibrosis (PF) is a common, chronic and incurable lung disease, in which the lungs become scarred over time. MicroRNAs (miRNAs/miRs) serve key roles in various biological processes, including cell proliferation, differentiation, apoptosis and the regulation of epithelial­mesenchymal transition (EMT) process. The aim of the present study was to investigate the underlying mechanism of miR­320a­3p as a potential therapeutic target for PF. Clinical samples and microarray datasets collected from various databases were used to evaluate the expression of miR­320a­3p in PF. A549 cells were used to construct an EMT model of PF. A dual­luciferase reporter assay system was used to identify target genes of miR­320a­3p. Western blot analysis and immunofluorescence staining were used to determine the roles of miR­320a­3p and its target genes in the EMT process in PF. The present study found that, compared with lung tissue of healthy control subjects, the expression of miR­320a­3p in lung tissue of PF patients was significantly reduced. The expression levels of miR­320a­3p decreased in TGF­ß1­stimulated A549 cells in a time­ and concentration­dependent manner. The overexpression of miR­320a­3p suppressed EMT markers induced by TGF­ß1 in A549 cells and STAT3 was identified as a potential target gene of miR­320a­3p. Furthermore, the expression changes of miR­320a­3p and STAT3 were found to significantly affect the expression of phosphorylated SMAD3 in TGF­ß1­stimulated A549 cells. Briefly, overexpression of miR­320a­3p could inhibit the EMT process in PF by downregulating STAT3 expression. The mechanism mediating these effects may partly involve crosstalk between the SMAD3 and STAT3.

Specific Lung Squamous Cell Carcinoma Prognosis-Subtype Distinctions Based on DNA Methylation Patterns.

BACKGROUND Lung squamous cell carcinoma (LUSC) is one of the major types of non-small-cell lung cancer. Epigenetic alterations, such as DNA methylation, have been recognized to be closely associated with the tumorigenesis and progression. MATERIAL AND METHODS In this study, we investigated the prognosis subgroups and assessed their correlation with clinical characteristics in LUSC using a methylation array acquired from The Cancer Genome Atlas (TCGA) database. RESULTS A total of 196 DNA methylation sites exhibited a significant association with patient prognosis, and patients were further stratified into 7 prognosis subgroups based upon the consensus clustering. The patients in every subgroup were different in terms of prognosis and TNM stage. In addition, we found these 196 significant methylation sites corresponded to 258 genes. The function enrichment analysis revealed that these 258 genes enriched in biological pathways were closely related to cancers, such as DNA methylation and demethylation, cell cycle DNA replication, regulation of signal transduction by p53 class mediator, and genetic imprinting. Subsequently, we determined the levels of methylation sites in 7 subgroups, and found 24 intra-subgroup-specific methylation sites. Meanwhile, we selected 3 subgroups-specific methylation sites to construct the prognosis model for LUSC patients using multivariate Cox proportional risk regression model analysis. This model can effectively predict the prognosis of LUSC patients. CONCLUSIONS Our study identified a new classification of LUSC into 7 prognosis subgroups on the basis of DNA methylation data in TCGA, which demonstrated that molecular subtypes are independent factor for prognosis in LUSC. This may provide a more detailed explanation for LUSC heterogeneity. Additionally, this classification will contribute to discovery of new biomarkers of LUSC and provide more accurate subdivision of LUSC. Furthermore, these specific DNA methylation sites and corresponding genes can serve as biomarkers for early diagnosis, accurate therapy, and prognosis prediction.

S100A2 Silencing Relieves Epithelial-Mesenchymal Transition in Pulmonary Fibrosis by Inhibiting the Wnt/ß-Catenin Signaling Pathway.

Pulmonary fibrosis (PF) is a progressive and lethal disease with poor prognosis. S100A2 plays an important role in the progression of cancer. However, the role of S100A2 in PF has not yet been reported. In this study, we explored the potential role of S100A2 in PF and its potential molecular mechanisms. Increased expression of S100A2 was first observed in lung tissues of PF patients. We found that downregulation of S100A2 inhibited the transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in A549 cells. Mechanically, TGF-ß1 upregulated ß-catenin and the phosphorylation of glycogen synthase kinase-3ß, which was blocked by silencing S100A2 in vitro. Furthermore, lithium chloride (activator of the Wnt/ß-catenin signaling pathway) effectively rescued S100A2 knockdown-mediated inhibition of EMT in PF. In conclusion, these findings demonstrate that downregulation of S100A2 alleviated PF through inhibiting EMT. S100A2 is a promising potential target for further understanding the mechanism and developing a strategy for the treatment of PF and other EMT-associated diseases.

Medical Thoracoscopy for the Management of Exudative Pleural Effusion: A Retrospective Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of medical thoracoscopy in the diagnosis and treatment of exudative pleural effusion. METHODS: A total of 82 patients with exudative pleural effusion underwent medical thoracoscopy under local anesthesia and mild sedation. The clinical characteristics, pleural fluid routine and biochemical tests, pleural biopsy, and outcomes were retrospectively evaluated. RESULTS: Among 82 patients, the color and transparency of pleural fluid and the levels of white blood cells (WBC), lactate dehydrogenase (LDH), neutrophil proportion, lymphocyte proportion, adenosine deaminase (ADA), and glucose were different among tuberculosis (TB), malignant (M), acute and chronic inflammation (ACI), and purulent (P) cases. Furthermore, 70% of M cases had a low positive rate of exfoliated cells in the sputum and pleural fluid, and more than 90% of TB cases had low positive rates of anti-tuberculosis antibodies and acid-fast bacilli in the sputum and pleural fluid. Pleural biopsy showed that 11% of cases were M, 74.4% were TB, 11% were ACI, and 3.6% were P. Medical thoracoscopy showed that 66.7% of ACI cases had pleural adhesions, 34.4% of TB cases had moderate and 34.4% of TB cases had severe pleural adhesions, 100% of M and TB cases had pleural surface nodules and 77.8% of ACI cases had pleural surface nodules, 49.2% of TB cases showed encapsulated pleural effusion, and 33.3% of M cases showed encapsulated pleural effusion. CONCLUSION: Medical thoracoscopy has high feasibility and accuracy in the diagnosis and treatment of exudative pleural effusion.

CAVIN2 is frequently silenced by CpG methylation and sensitizes lung cancer cells to paclitaxel and 5-FU.

Aim: To explore the biological functions and clinical significance of CAVIN2 in lung cancer. Materials & methods: Methylation-specific PCR was used to measure promoter methylation of CAVIN2. The function of CAVIN2 was tested by Cell Counting Kit-8, colony formation, Transwell, flow cytometric analysis, acridine orange/ethidium bromide, chemosensitivity assay and xenograft assay. Results: CAVIN2 is significantly downregulated by promoter methylation in lung cancer. CAVIN2 overexpression inhibits lung cancer cell migration and invasion. Furthermore, ectopic expression of CAVIN2 inhibits cell proliferation in vivo and in vitro by inducing G2/M cell cycle arrest, which sensitizes the chemosensitivity of lung cancer cells to paclitaxel and 5-fluorouracil, but not cisplatin. Conclusion: CAVIN2 is a tumor suppressor in non-small-cell lung cancer and can sensitize lung cancer cells to paclitaxel and 5-fluorouracil.

Lower expression of LINC00092 in lung adenocarcinoma might mean poorer prognosis: A study based on data mining and bioinformatics.

The mechanisms that underlie long non-coding RNA 00092 (LINC00092) in lung adenocarcinoma (LUAD) remain unclear. In this study, by mining the Cancer Genome Atlas and Gene Expression Omnibus databases and using bioinformatics tools, we try to elucidate the function of LINC00092 in LUAD.The the Cancer Genome Atlas and gene expression Omnibus microarray datasets were used to analyze and evaluate the expression of LINC00092 in LUAD and its clinical significance. Clinical samples were collected and the relative expression level of LINC00092 were identified by quantitative real time polymerase chain reaction. The LINC00092 related genes were identified by Multi Experiment Matrix, The Atlas of ncRNA in Cancer and the database of RNA-Binding Protein specificities. The predicted genes were then sent to the Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes pathway analysis.The expression of LINC00092 was significantly decreased in LUAD tissues compared to non-tumor tissues (standard mean difference =-1.10, 95% confidence interval: -1.87 to -0.32, P < .001, random). Low expression of LINC00092 was associated with the poor overall survival (hazard ratio = 1.32, 95% confidence interval: 1.08-1.62, P < .05, fixed) and high pathological stage (P < .05). The relative expression level of LINC00092 in clinical samples were significantly lower in LUAD tissues compared with adjacent normal tissues. (P < 0.05) 61 LINC00092 related genes were identified; the Kyoto Encyclopedia of Genes and Genomes analysis showed that the most significant signaling pathways were: NF-κB, HIF-1 and ErbB signaling pathways.In this study, we found that the decrease of LINC00092 expression was involved in LUAD tumorigenesis and metastasis, and the depletion of LINC00092 was associated with a poor prognosis in patients with LUAD. The mechanisms that underlie LINC00092 in LUAD might be related to the NF-κB, HIF-1 and ErbB signaling pathways.

Prognostic and clinicopathological significance of long noncoding RNA MALAT-1 expression in patients with non-small cell lung cancer: A meta-analysis.

BACKGROUND: Although expression of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) in tumor tissues has been assessed in several malignancies. However, the association between lncRNA MALAT-1 expression and prognosis or clinicopathological feature remains controversial. Therefore, we conducted a meta-analysis to verify whether lncRNA MALAT-1 expression was associated with prognosis or clinicopathological features in patients with non-small cell lung cancer (NSCLC). METHODS: We searched Embase, PubMed, Web of Science, Cochrane library, The Chinese National Knowledge Infrastructure, and Wanfang databases from inception to March, 1, 2020. The language restrictions were Chinese and English. The published literature on lncRNA MALAT-l expression and prognosis or clinicopathological characteristics of NSCLC patients was statistically analyzed. Combined hazard ratios (HRs), odds ratios (OR), and 95% confidence intervals (95% CIs) were used to evaluate the effects of lncRNA MALAT-l on the prognosis and clinicopathological features of NSCLC. RESULTS: Fifteen studies with 1477 NSCLC patients were enrolled. The results showed that the elevated expression of lncRNA MALAT-l in tumor tissues was associated with shorter overall survival (OS) (HR: 2.20, 95% CI: 1.53-3.16; P = 0.000). Additionally, high lncRNA MALAT-l expression was also significantly associated with gender (OR: 0.69, 95% CI: 0.51-0.93; P = 0.014), tumor size (OR: 1.87, 95% CI:1.13-3.09; P = 0.016), lymph node metastasis (LNM) (OR: 2.87, 95% CI:1.05-7.83, P = 0.04), tumor differentiation (OR: 1.60, 95% CI:1.17-2.20; P = 0.003), and tumor-node-metastasis (TNM) stage (OR: 0.42, 95% CI: 0.25-0.70; P = 0.001). There was no significant relationship between lncRNA MALAT-l expression and other clinicopathological features including age (OR: 1.03, 95% CI: 0.79-1.34; P = 0.830), number of tumors (OR: 1.02, 95% CI: 0.63-1.64; P = 0.943), vascular invasion (OR: 1.23, 95% CI: 0.50-3.05; P = 0.652), and recurrence (OR: 1.98, 95% CI: 0.67-5.85; P = 0.214). CONCLUSION: The overexpression of lncRNA MALAT-l in NSCLC tissues was correlated with OS, gender, tumor size, LNM, tumor differentiation, and TNM stage. Thus, lncRNA MALAT-l may serve as a prognostic factor for NSCLC.

Clinicopathological and prognostic value of S100A4 expression in non-small cell lung cancer: a meta-analysis.

BACKGROUND: Numerous published studies have shown that S100A4 is frequently overexpressed in various human cancers. However, the association between S100A4 expression and prognosis or clinicopathological parameters in non-small cell lung cancer (NSCLC) remains unclear. Therefore, a meta-analysis was performed to identify the significance of S100A4 in NSCLC. METHODS: Systematic literature search was conducted using PubMed, Embase, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure database (CNKI), and the Wanfang database to obtain relevant articles. A combined hazard ratio (HR) and its corresponding 95% confidence interval (CI) were used to evaluate the association between S100A4 expression and prognosis in NSCLC patients. Pooled odds ratio (OR) and 95% CI were calculated to assess the association between S100A4 expression and clinicopathological features in NSCLC. RESULTS: NSCLC patients with overexpression of S100A4 had a worse prognosis than patients with low expression of S100A4 (HR = 1.77, 95% CI: 1.55-2.02, P<0.001). Additionally, overexpression of S100A4 was significantly correlated to patients' age (OR = 0.67, 95% CI: 0.49-0.91, P=0.010), tumor differentiation (OR = 2.20, 95% CI: 1.69-2.85, P<0.001), lymph node metastasis (LNM) (OR = 3.70, 95% CI: 2.25-6.06, P<0.001), Tumor-Node-Metastasis (TNM) stage (OR = 3.08, 95% CI: 2.10-4.53, P<0.001), and pathological subtype (OR = 1.77, 95% CI: 1.09-2.88, P=0.020). However, there was no association between S100A4 expression and other clinicopathological features in NSCLC, including gender, tumor size, and smoking. CONCLUSION: S100A4 overexpression was associated with tumor progression and poor prognosis in NSCLC patients. Hence, S100A4 might serve as a potential prognostic biomarker in NSCLC.