Multiple primary lung cancer: Updates and perspectives.

Management of multiple primary lung cancer (MPLC) remains challenging, partly due to its increasing incidence, especially with the significant rise in cases of multiple lung nodules caused by low-dose computed tomography screening. Moreover, the indefinite pathogenesis, diagnostic criteria, and treatment selection add to the complexity. In recent years, there have been continuous efforts to dissect the molecular characteristics of MPLC and explore new diagnostic approaches as well as treatment modalities, which will be reviewed here, with a focus on newly emerging evidence and future perspectives, hope to provide new insights into the management of MPLC and serve as inspiration for future research related to MPLC.

Advances in the Treatment of Pulmonary Nodules.

BACKGROUND: Early detection and accurate diagnosis of pulmonary nodules are crucial for improving patient outcomes. While surgical resection of malignant nodules is still the preferred treatment option, it may not be feasible for all patients. We aimed to discuss the advances in the treatment of pulmonary nodules, especially stereotactic body radiotherapy (SBRT) and interventional pulmonology technologies, and provide a range of recommendations based on our expertise and experience. SUMMARY: Interventional pulmonology is an increasingly important approach for the management of pulmonary nodules. While more studies are needed to fully evaluate its long-term outcomes and benefits, the available evidence suggests that this technique can provide a minimally invasive and effective alternative for treating small malignancies in selected patients. We conducted a systematic literature review in PubMed, designed a framework to include the advances in surgery, SBRT, and interventional pulmonology for the treatment of pulmonary nodules, and provided a range of recommendations based on our expertise and experience. KEY MESSAGES: As such, alternative therapeutic options such as SBRT and ablation are becoming increasingly important and viable. With recent advancements in bronchoscopy techniques, ablation via bronchoscopy has emerged as a promising option for treating pulmonary nodules. This study reviewed the advances of interventional pulmonology in the treatment of peripheral lung cancer patients that are not surgical candidates. We also discussed the challenges and limitations associated with ablation, such as the risk of complications and the potential for incomplete nodule eradication. These advancements hold great promise for improving the efficacy and safety of interventional pulmonology in treating pulmonary nodules.

Inhibition of fatty acid synthase protects obese mice from acute lung injury via ameliorating lung endothelial dysfunction.

BACKGROUND: Obesity has been identified as a risk factor for acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the underlying mechanisms remain elusive. This study aimed to investigate the role of fatty acid synthase (FASN) in lipopolysaccharide (LPS)-induced ALI under obesity. METHODS: A high-fat diet-induced obese (DIO) mouse model was established and lean mice fed with regular chow diet were served as controls. LPS was intratracheally instilled to reproduce ALI in mice. In vitro, primary mouse lung endothelial cells (MLECs), treated by palmitic acid (PA) or co-cultured with 3T3-L1 adipocytes, were exposed to LPS. Chemical inhibitor C75 or shRNA targeting FASN was used for in vivo and in vitro loss-of-function studies for FASN. RESULTS: After LPS instillation, the protein levels of FASN in freshly isolated lung endothelial cells from DIO mice were significantly higher than those from lean mice. MLECs undergoing metabolic stress exhibited increased levels of FASN, decreased levels of VE-cadherin with increased p38 MAPK phosphorylation and NLRP3 expression, mitochondrial dysfunction, and impaired endothelial barrier compared with the control MLECs when exposed to LPS. However, these effects were attenuated by FASN inhibition with C75 or corresponding shRNA. In vivo, LPS-induced ALI, C75 pretreatment remarkably alleviated LPS-induced overproduction of lung inflammatory cytokines TNF-α, IL-6, and IL-1ß, and lung vascular hyperpermeability in DIO mice as evidenced by increased VE-cadherin expression in lung endothelial cells and decreased lung vascular leakage. CONCLUSIONS: Taken together, FASN inhibition alleviated the exacerbation of LPS-induced lung injury under obesity via rescuing lung endothelial dysfunction. Therefore, targeting FASN may be a potential therapeutic target for ameliorating LPS-induced ALI in obese individuals.

Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis.

BACKGROUND: Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive. METHODS: Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed. RESULTS: Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized. CONCLUSIONS: Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN. Video Abstract.

HA-ADT suppresses esophageal squamous cell carcinoma progression via apoptosis promotion and autophagy inhibition.

Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer-related deaths. We have previously connected a non-sulfated glycosaminoglycan, hyaluronic acid (HA), with a common hydrogen sulfide (H2S) donor, 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH), to reconstruct a novel conjugate, HA-ADT. In this study, we determined the effect of HA-ADT on the growth of ESCC. Our data suggested that HA-ADT exerted more potent effects than sodium hydrosulfide (NaHS, a fast H2S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H2S-releasing donor) on inhibiting the viability, proliferation, migration, and invasion of human ESCC cells. HA-ADT increased apoptosis by suppressing the protein expressions of phospho (p)-Ser473-protein kinase B (PKB/AKT), p-Tyr199/Tyr458-phosphatidylinositol 3-kinase (PI3K), and p-Ser2448-mammalian target of rapamycin (mTOR), but suppressed autophagy through the inhibition of the protein levels of p-Ser552-ß-catenin, p-Ser9-glycogen synthase kinase-3ß (GSK-3ß), and Wnt3a in human ESCC cells. In addition, HA-ADT was more effective in terms of the growth inhibition of human ESCC xenograft tumor than NaHS and GYY4137. In conclusion, HA-ADT can suppress ESCC progression via apoptosis promotion and autophagy inhibition. HA-ADT might be efficacious for the treatment of cancer.

Feasibility and Safety of Endosonography-Guided Transvascular Needle Aspiration in the Diagnosis of Thoracic and Abdominal Lesions: A Meta-Analysis.

BACKGROUND: Endoscopic techniques, including endobronchial ultrasound (EBUS) and endoscopic ultrasound (EUS), are used as the initial approach for the diagnosis and staging of lung cancer and the diagnosis of thoracic and abdominal lesions. Historically, the transvascular approach has been avoided because of concerns about bleeding. OBJECTIVES: This article is a systematic review of studies evaluating the feasibility and safety of transvascular needle aspiration (TVNA) under the guidance of EBUS or EUS in the diagnosis of thoracic and abdominal lesions. METHODS: We performed a systematic search of the MEDLINE, Embase, and Cochrane databases to identify studies evaluating the application of EBUS/EUS-guided TVNA (EBUS/EUS-TVNA) for lesions located at the contralateral side of the vessel for which the transvascular approach was the best puncture path. We performed a meta-analysis of diagnostic yield estimations. We also reviewed the complications related to the procedure. RESULTS: Eleven observational studies were included in the final analysis. Meta-analysis yielded a pooled overall diagnostic yield of 82.10% (95% confidence interval, 0.74-0.89) for TVNA, with an I2 value of 52%. No publication bias was detected by Egger's test (p = 0.8528). The overall complications included minor bleeding, minor hematoma, pseudo-aneurysm of the aorta, hemoptysis, acute hypoxic respiratory failure, and moderate bleeding. The major complication rate was 2.71%. CONCLUSIONS: EBUS/EUS-TVNA is feasible and probably safe when performed by experienced endoscopists in carefully selected patients. In view of the potential risks associated with the transvascular approach, especially the development of hematoma and pseudoaneurysm, the fanning technique was avoided, and the area of aspiration should be assessed by EUS for 3 min after each aspiration. Most importantly, EBUS/EUS-TVNA should only be performed if the results will impact the clinical management.

MCAM abnormal expression and clinical outcome associations are highly cancer dependent as revealed through pan-cancer analysis.

MCAM (CD146) is a cell surface adhesion molecule that has been reported to promote cancer development, progression and metastasis and is considered as a potential tumor biomarker and therapeutic target. However, inconsistent reports exist, and its clinical value is yet to be confirmed. Here we took advantage of several large genomic data collections (Genotype-Tissue Expression, The Cancer Genome Atlas and Cancer Cell Line Encyclopedia) and comprehensively analyzed MCAM expression in thousands of normal and cancer samples and cell lines along with their clinical phenotypes and drug response information. Our results show that MCAM is very highly expressed in large vessel tissues while majority of tissues have low or minimal expression. Its expression is dramatically increased in a few tumors but significantly decreased in most other tumors relative to their pairing normal tissues. Increased MCAM expression is associated with a higher tumor stage and worse patient survival for some less common tumors but not for major ones. Higher MCAM expression in primary tumors may be complicated by tumor-associated or normal stromal blood vessels yet its significance may differ from the one from cancer cells. MCAM expression is weakly associated with the response to a few small molecular drugs and the association with targeted anti-BRAF agents suggests its involvement in that pathway which warrants further investigation.

Electromagnetically induced transparency based on a carbon nanotube film terahertz metasurface.

In this work, we present a study of bright-bright mode electromagnetically induced transparency based on carbon nanotube films terahertz metasurface consisting of an array of two asymmetric split rings. Under the excitation of terahertz wave, the electromagnetically induced transparency window can be obviously observed. The simulation results agree with the theoretical results. The formation mechanism of the transparent window in bright-bright mode electromagnetically induced transparency is further analyzed. Moreover, the sensing performance of the proposed terahertz metasurface is investigated and the sensitivity can reach to 320 GHz/RIU. To verify the slow light characteristics of the device, the group delay of the terahertz metasurface is calculated and the value is 2.12 ps. The proposed metasurface device and the design strategies provide opportunities for electromagnetically induced transparency applications, such as sensors, optical memories, and flexible terahertz functional devices.

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.

Identification of the determinants of tRNA function and susceptibility to rapid tRNA decay by high-throughput in vivo analysis.

Sequence variation in tRNA genes influences the structure, modification, and stability of tRNA; affects translation fidelity; impacts the activity of numerous isodecoders in metazoans; and leads to human diseases. To comprehensively define the effects of sequence variation on tRNA function, we developed a high-throughput in vivo screen to quantify the activity of a model tRNA, the nonsense suppressor SUP4oc of Saccharomyces cerevisiae. Using a highly sensitive fluorescent reporter gene with an ochre mutation, fluorescence-activated cell sorting of a library of SUP4oc mutant yeast strains, and deep sequencing, we scored 25,491 variants. Unexpectedly, SUP4oc tolerates numerous sequence variations, accommodates slippage in tertiary and secondary interactions, and exhibits genetic interactions that suggest an alternative functional tRNA conformation. Furthermore, we used this methodology to define tRNA variants subject to rapid tRNA decay (RTD). Even though RTD normally degrades tRNAs with exposed 5' ends, mutations that sensitize SUP4oc to RTD were found to be located throughout the sequence, including the anti-codon stem. Thus, the integrity of the entire tRNA molecule is under surveillance by cellular quality control machinery. This approach to assess activity at high throughput is widely applicable to many problems in tRNA biology.

A Holistic Review of the State-of-the-Art Microfluidics for Exosome Separation: An Overview of the Current Status, Existing Obstacles, and Future Outlook.

Exosomes, a class of small extracellular vesicles (30-150 nm), are secreted by almost all types of cells into virtually all body fluids. These small vesicles are attracting increasing research attention owing to their potential for disease diagnosis and therapy. However, their inherent heterogeneity and the complexity of bio-fluids pose significant challenges for their isolation. Even the "gold standard," differential centrifugation, suffers from poor yields and is time-consuming. In this context, recent developments in microfluidic technologies have provided an ideal system for exosome extraction and these devices exhibit some fascinating properties such as high speeds, good portability, and low sample volumes. In this review, the focus is on the state-of-the-art microfluidic technologies for exosome isolation and highlight potential directions for future research and development by analyzing the challenges faced by the current strategies.

Multi-band terahertz resonant absorption based on an all-dielectric grating metasurface for chlorpyrifos sensing.

Perfect metasurface absorbers play a significant role in imaging, detecting, and manipulating terahertz radiation. We utilize all-dielectric gratings to demonstrate tunable multi-band absorption in the terahertz region. Simulation reveals quad-band and tri-band absorption from 0.2 to 2.5 THz for different grating depths. Coupled-mode theory can explain the absorption phenomenon. The absorption amplitude can be precisely controlled by changing the pump beam fluence. Furthermore, the resonant frequency is sensitive to the medium's refractive index, suggesting the absorber may be of great potential in the sensor detection field. The experimental results exhibit a high detectivity of pesticides.

Conservation of location of several specific inhibitory codon pairs in the Saccharomyces sensu stricto yeasts reveals translational selection.

Synonymous codons provide redundancy in the genetic code that influences translation rates in many organisms, in which overall codon use is driven by selection for optimal codons. It is unresolved if or to what extent translational selection drives use of suboptimal codons or codon pairs. In Saccharomyces cerevisiae, 17 specific inhibitory codon pairs, each comprised of adjacent suboptimal codons, inhibit translation efficiency in a manner distinct from their constituent codons, and many are translated slowly in native genes. We show here that selection operates within Saccharomyces sensu stricto yeasts to conserve nine of these codon pairs at defined positions in genes. Conservation of these inhibitory codon pairs is significantly greater than expected, relative to conservation of their constituent codons, with seven pairs more highly conserved than any other synonymous pair. Conservation is strongly correlated with slow translation of the pairs. Conservation of suboptimal codon pairs extends to two related Candida species, fungi that diverged from Saccharomyces ∼270 million years ago, with an enrichment for codons decoded by I•A and U•G wobble in both Candida and Saccharomyces. Thus, conservation of inhibitory codon pairs strongly implies selection for slow translation at particular gene locations, executed by suboptimal codon pairs.

Targeted resequencing showing novel common and rare genetic variants increases the risk of asthma in the Chinese Han population.

BACKGROUND: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals. METHODS: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma-related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next-generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls). RESULTS: First, we identified 18 potentially functional rare loss-of-function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single-nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant (p < 9.1 × 10-4 ) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle- and high-risk subjects had a 2.0-fold (95% CI: 1.621-2.423, p = 2.624 × 10-11 ) and 6.0-fold (95% CI: 3.623-10.156, p = 7.086 × 10-12 ) increased risk of asthma, respectively, compared with low-risk subjects. CONCLUSION: This study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals.

A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis in Southern Han Chinese.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD-ILD) has not been determined. METHODS: A two-stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD-ILD cases, and 225 controls). RESULTS: We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212-4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376-4.128, p = 0.002 in stage two). However, we did not observe this association in CTD-ILD (OR = 1.401, 95% CI = 0.790-2.485, p = 0.248). CONCLUSION: Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD-ILD.

Widespread temperature sensitivity and tRNA decay due to mutations in a yeast tRNA.

Microorganisms have universally adapted their RNAs and proteins to survive at a broad range of temperatures and growth conditions. However, for RNAs, there is little quantitative understanding of the effects of mutations on function at high temperatures. To understand how variant tRNA function is affected by temperature change, we used the tRNA nonsense suppressor SUP4oc of the yeast Saccharomyces cerevisiae to perform a high-throughput quantitative screen of tRNA function at two different growth temperatures. This screen yielded comparative values for 9243 single and double variants. Surprisingly, despite the ability of S. cerevisiae to grow at temperatures as low as 15°C and as high as 39°C, the vast majority of variants that could be scored lost half or more of their function when evaluated at 37°C relative to 28°C. Moreover, temperature sensitivity of a tRNA variant was highly associated with its susceptibility to the rapid tRNA decay (RTD) pathway, implying that RTD is responsible for most of the loss of function of variants at higher temperature. Furthermore, RTD may also operate in a met22Δ strain, which was previously thought to fully inhibit RTD. Consistent with RTD acting to degrade destabilized tRNAs, the stability of a tRNA molecule can be used to predict temperature sensitivity with high confidence. These findings offer a new perspective on the stability of tRNA molecules and their quality control at high temperature.

Cancer survivors' experiences with financial toxicity: A systematic review and meta-synthesis of qualitative studies.

OBJECTIVE: The aim of this study was to synthesize qualitative research evidence on cancer survivors' experiences with financial toxicity (FT). METHODS: We carried out a systematic review of qualitative studies using a meta-aggregation approach. Papers published prior to 31 August 2019, were collected from electronic databases, including PubMed/MEDLINE, MEDLINE (Ovid), EMBASE (Ovid), CINAHL (EBSCO), Web of Science, ProQuest Dissertations and Theses, and Cochrane Library (Wiley). RESULTS: Six synthesized findings were derived from 14 studies covering cancer patients' awareness of FT, cancer-related expenditures, and the risk factors, impacts, coping strategies, and unmet needs related to FT. CONCLUSIONS: Cancer survivors incur FT; however, their awareness of FT is limited. Cancer-related FT has multiple impacts on survivors' lives. Although cancer survivors try to cope with FT through adjustments, they still have unmet needs for the management of FT. Nurses and social workers can play a critical role in helping survivors manage FT by increasing pre-awareness of FT, strengthening emotional empowerment, and providing personalized informative support.

Long non-coding RNA-HAGLR suppressed tumor growth of lung adenocarcinoma through epigenetically silencing E2F1.

Emerging evidence indicates that long noncoding RNAs (LncRNAs) are new players in gene regulation but their mechanisms of action are mainly undocumented. In this study, we investigated LncRNA alterations that contribute to lung cancer by analyzing published microarray data in Gene Expression Obminus (GEO) and The Cancer Genome Atlas RNA (TCGA) sequencing data. Here, we reported that HAGLR (also called HOXD-AS1) was frequently down-regulated in lung adenocarcinoma (LUAD) tissues, and decreased HAGLR expression was clinically associated with shorter survival of LUAD patients. Preclinical studies using multiple LUAD cells and in vivo mouse model indicated that HAGLR could attenuate LUAD cell growth in vitro and in vivo. Mechanistically, HAGLR could physically interact with DNMT1, and recruit DNMT1 on E2F1 promoter to increase local DNA methylation. Overall, our study demonstrated that HAGLR promoted LUAD progression by recruiting DNMT1 to modulate the promoter methylation and expression of E2F1, which expanded potential therapeutic strategies for LUAD treatment.

Disease severity and clinical outcomes of community-acquired pneumonia caused by non-influenza respiratory viruses in adults: a multicentre prospective registry study from the CAP-China Network.

Although broad knowledge of influenza viral pneumonia has been established, the significance of non-influenza respiratory viruses in community-acquired pneumonia (CAP) and their impact on clinical outcomes remains unclear, especially in the non-immunocompromised adult population.Hospitalised immunocompetent patients with CAP were prospectively recruited from 34 hospitals in mainland China. Respiratory viruses were detected by molecular methods. Comparisons were conducted between influenza and non-influenza viral infection groups.In total, 915 out of 2336 adult patients with viral infection were enrolled in the analysis, with influenza virus (28.4%) the most frequently detected virus, followed by respiratory syncytial virus (3.6%), adenovirus (3.3%), human coronavirus (3.0%), parainfluenza virus (2.2%), human rhinovirus (1.8%) and human metapneumovirus (1.5%). Non-influenza viral infections accounted for 27.4% of viral pneumonia. Consolidation was more frequently observed in patients with adenovirus infection. The occurrence of complications such as sepsis (40.1% versus 39.6%; p=0.890) and hypoxaemia (40.1% versus 37.2%; p=0.449) during hospitalisation in the influenza viral infection group did not differ from that of the non-influenza viral infection group. Compared with influenza virus infection, the multivariable adjusted odds ratios of CURB-65 (confusion, urea >7 mmol·L-1, respiratory rate ≥30 breaths·min-1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) ≥3, arterial oxygen tension/inspiratory oxygen fraction <200 mmHg, and occurrence of sepsis and hypoxaemia for non-influenza respiratory virus infection were 0.87 (95% CI 0.26-2.84), 0.72 (95% CI 0.26-1.98), 1.00 (95% CI 0.63-1.58) and 1.05 (95% CI 0.66-1.65), respectively. The hazard ratio of 90-day mortality was 0.51 (95% CI 0.13-1.91).The high incidence of complications in non-influenza viral pneumonia and similar impact of non-influenza respiratory viruses relative to influenza virus on disease severity and outcomes suggest more attention should be given to CAP caused by non-influenza respiratory viruses.

Experimental pulmonary fibrosis was suppressed by microRNA-506 through NF-kappa-mediated apoptosis and inflammation.

Fibrosis in the lungs usually occurs in the initial phase of acute respiratory distress syndrome (ARDS), which exacerbates poor prognosis among patients. MicroRNAs (miRs) have the ability to modulate the expression profiles of many genes, thus essentially altering cell phenotypes. We hypothesize that miRs may be involved in the development of lung fibrosis in mice. In this study, mice were treated with lipopolysaccharide (LPS) to establish the lung fibrosis animal model. Hematoxylin and eosin (H&E) staining and western blot (WB) were performed to confirm the successful establishment of the model. Quantitative PCR (qPCR) and WB were utilized to monitor the expression of miRs and proteins. A dual-luciferase reporter assay was used to detect the interaction between miR and genes. We observed miR-506 downregulation in lung tissues during lung fibrosis after ARDS rat modeling by LPS exposure. We also observed that its expression level was similar to that observed in TGF-ß1-induced human MRC-5 cells. The proportion of apoptotic cells decreased, while levels of inflammatory cytokines were upregulated in lung tissues during lung fibrosis and in fibroblasts after TGF-ß1 treatment. In order to elucidate the possible role of miR-506, it was overexpressed in mice with ARDS. It was revealed that miR-506 significantly ameliorated the degree and spread of pulmonary damage stimulated by LPS. miR-506 also induced apoptosis in vivo and in vitro, while also ameliorating the inflammatory response. Notably, p65, a subunit of NF-κB, acts as a target of miR-506. p65 expression was downregulated in TGF-ß1-treated MRC-5 cells upon transfection with miR-506 mimic. Indeed, the 3'-UTR of human p65 contained functional human miR-506-responsive sequences. LPS induction and TGF-ß1 stimulation in mice led to p65 upregulation. In addition, p65 knockdown in the ARDS mouse model partially ameliorated the severity of lung lesions, induced apoptosis and reduced inflammation in lung tissue. Our findings revealed that miR-506 could be an important modulator of apoptosis and inflammation and a regulator of lung fibrosis.