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Background. Lung adenosquamous carcinoma (LASC) is a special type of lung cancer. LASC is a malignant tumor with strong aggressiveness and a poor prognosis. Previous studies have revealed that microRNAs (miRNAs) are widely involved in the development of tumors by targeting mRNA. This study is aimed at identifying the key mRNAs and miRNAs of LASC and constructing miRNA-mRNA networks for deeply comprehending the latent molecular mechanisms. Methods. mRNA dataset (GSE51852) and miRNA dataset (GSE51853) were extracted and downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were picked out by the GEO2R web tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were conducted in the DAVID database. The protein-protein interaction (PPI) network was performed and analyzed by using the STRING database and Cytoscape software, respectively. TransmiR v2.0 was applied to predict potential transcription factors of miRNAs. The target genes of DEMs were predicted in the miRWalk database. Results. In comparison to normal tissues, a total of 1458 DEGs (511 upregulated and 947 downregulated) and 13 DEMs (5 upregulated and 8 downregulated) were screened out in LASC tissues. The PPI network of the DEGs displayed five key modules and seventeen hub genes. Six target genes of the DEMs were predicted, and five essential miRNA-mRNA regulatory pairs were established. Ensuingly, CENPF, one of the target genes, was also the hub genes of GSE51852, which was obtained from MCODE and cytoHubba and regulated by hsa-miR-205. Conclusions. We constructed the miRNA-mRNA regulatory pairs, which are helpful to study the potential regulatory mechanisms and find out promising diagnosis biomarkers and therapeutic targets for LASC.

To verify whether mesenchymal stem cells cocultured with tanshinone IIA may ameliorate Alzheimer's disease by inhibiting oxidative stress.Sixty male Sprague-Dawley rats were randomly divided into 4 groups named Sham, Aβ25-35, mesenchymal stem cells, and mesenchymal stem cells (tanshinone IIA). The rats were treated according to different groups. The neurobehavioral performance of Sprague-Dawley rats was evaluated via Morris water maze test. Histological changes were checked via hematoxylin-eosin staining. The levels of total antioxidant activity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and malondialdehyde in hippocampus were assayed by ELISA kit. The levels of Aβ, p-tau/tau, and p-AMP-activated protein kinase/AMP-activated protein kinase in hippocampus were checked by Western blot.Our research showed that the injection of mesenchymal stem cells (tanshinone IIA) into the hippocampus alleviated learning and memory deficits and reduced hippocampal neuronal injury in the Alzheimer's disease rats. Moreover, mesenchymal stem cells (tanshinone IIA) treatment suppressed oxidative stress, attenuated Aβ accumulation reduced Tau hyperphosphorylation, and enhanced the activity of AMP-activated protein kinase in the hippocampus of the Alzheimer's disease rats. However, there were almost no significant difference between the mesenchymal stem cells and Aβ25-35 groups.Mesenchymal stem cells (tanshinone IIA) transplantation may be a potential treatment for curing Alzheimer's disease, which may be related to the inhibition of oxidative stress.

Summary Background The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose of this meta-analysis was to summarize the available studies evaluating the association between levels of inflammatory factors and ARDS/ALI incidence. Methods We searched the PubMed, EmBase, and Cochrane databases for studies published up to July 2017. For each inflammatory factor, a random effects model was employed to pool results from different studies. Results We identified 63 studies that included 6243 patients in our meta-analysis. Overall, the results indicated that the levels of angiopoietin (ANG)-2 (standard mean difference, SMD: 1.34; P P = 0.012), IL‑6 (SMD: 0.66; P = 0.005), and tumor necrosis factor (TNF)-α (SMD: 0.98; P = 0.001) were significantly higher in patients with ARDS/ALI than in unaffected individuals. No significant differences were observed between patients with ARDS/ALI and unaffected individuals in terms of the levels of IL‑8 (SMD: 0.61; P = 0.159), IL-10 (SMD: 1.10; P = 0.231), and plasminogen activator inhibitor (PAI)-1 (SMD: 0.70; P = 0.060). Conclusions ARDS/ALI is associated with a significantly elevated levels of ANG‑2, IL-1β, IL‑6, and TNF‑α, but not with IL‑8, IL-10, and PAI‑1 levels.

Ling Gong,1,2,* Chunyan Wu,2,* Mingjie Lu,2 Chengyan Huang,2 Yongqian Chen,2 Zhu Li,2 Guichuan Huang,2 Daishun Liu,2 Xiaoping Tang1,3 1The First Clinical Medical College, Jinan University, Guangzhou, 510632, People’s Republic of China; 2Department of Respiratory Medicine, The First People’s Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi, 563000, People’s Republic of China; 3Infectious Disease Department, Guangzhou Eighth People’s Hospital (the Affiliated Hospital ofGuangzhou Medical University), Guangzhou, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Daishun LiuDepartment of Respiratory Medicine, The First People’s Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), No. 98 Fenghuang Road, Zunyi, Guizhou, 563000, People’s Republic of ChinaEmail ldslwtg@126.comXiaoping TangThe First Clinical Medical College, Jinan University, 601 W. Huangpu Avenue, Guangzhou 510632, Guangdong, China; Guangzhou Eighth People’s Hospital, Guangzhou Medical University, No. 627 Dongfeng East Road, YueXiu District, Guangzhou, Guangdong, 510060, People’s Republic of ChinaEmail txpdoc@126.comObjective: 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.Keywords: hospitalized children, respiratory syncytial virus infection, incidence, clinical characteristics

Objective: A number of recent clinical studies have identified a relationship between elevated expressions of 14-3-3 and poorer patient prognosis in the context of several cancers. The present meta-analysis was therefore conducted to gain an enhanced understanding of the prognostic importance of 14-3-3 levels in cancer patients. Methods: Two reviewers independently systematically reviewed the Web of Science, Embase, and PubMed databases to identify published, suitable studies through October 2019. The correlation between the level of 14-3-3 and cancer patient survival were assessed based upon pooled HR (hazard ratios) and 95% CI (confidence intervals) derived from chosen studies. Results: In total we were able to identify 22 eligible studies that had enrolled 2676 patients in the present meta-analysis. Assessment of these studies revealed that elevated 14-3-3 level correlated significantly with poorer OS (overall survival) (HR : 1.93, 95% CI : 1.42-2.61) in cancer patients. This was true even when studies were analyzed in subgroups according to tumor type, sample size, analysis type, and method of HR determination. With respect to disease-free survival (DFS), the pooled HR for cancer patients expressing high levels of 14-3-3 was 1.89 (95% CI: 1.56-2.30). Patients with elevated 14-3-3 expression also exhibited reduced CSS (cancer-specific survival) (HR: 3.47, 95% CI: 2.12-5.69).Conclusions: The outcomes indicate that higher level of 14-3-3 correlates with poorer patient prognosis in a range of cancer types.Keywords: Meta-analysis, Prognosis, 14-3-3 Proteins C Continuous...

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-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in A549 cells. Mechanically, TGF-β1 upregulated β-catenin and the phosphorylation of glycogen synthase kinase-3β, which was blocked by silencing S100A2 in vitro. Furthermore, lithium chloride (activator of the Wnt/β-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.

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.

Purpose To determine the ultrasound imaging characteristics of participants with bronchial anthracofibrosis (BAF) and identify clinical markers for prevention and treatment. Methods We randomly selected 1,243 participants (including 113 with BAF) who underwent bronchoscopy and treatment at our institution from April 2018 to October 2019. BAF was classified as flat, deep seated retracted, or mucosal protrusion type, based on microscopy. Ultrasound probes were used to determine the maximum thickness of the tube wall and submucosa. The average values of the submucosal and bony tissue areas of the BAF subtypes were compared. Results The BAF group included 13 participants with a history of tuberculosis (11.5%) and 57 with biofuel exposure (50.4%). The average exposure time was 17.4 ± 6.2 years; BAF accounted for 10% of bronchoscopies performed. The maximum tube-wall thicknesses of the deep-seated retracted (17.3 ± 5.7) and black protruding (19.3 ± 5.4) groups were significantly greater than that of the flat group (12.5 ± 5.0; P P P P > 0.05). Conclusion Differences in BAF airway remodeling among the different subtypes may lead to varying clinical symptoms. Analyzing the characteristics of BAF airway remodeling and the regulatory pathway may provide new clues for treatment.

Background: Nanog has been found to be overexpressed in various cancers. However, the association between Nanog expression and prognosis or clinicopathological features is still controversial. Therefore, this meta-analysis was conducted to identify whether Nanog expression was associated with prognosis or clinicopathological characteristics in non-small cell lung cancer (NSCLC). Methods: We searched Embase, PubMed, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure database (CNKI), and the Wanfang database for articles. Pooled hazard ratios (HR), odds ratios (OR), and corresponding 95% confidence intervals (CI) were utilized to evaluate the relationship between Nanog expression and prognosis or clinicopathological characteristics in NSCLC. Results: The results showed that high expression of Nanog was significantly associated with poor overall survival (OS) (HR=1.95, 95% CI: 1.38-2.75, P=0.000). Additionally, high Nanog expression was significantly correlated with tumor differentiation (OR=3.18, 95% CI: 1.69-5.98, P=0.000) and TNM stage (OR=1.78, 95% CI: 1.28-2.47, P=0.001). However, no significant relationship was observed between Nanog expression and other clinicopathological features, including gender (OR=0.95, 95% CI: 0.69-1.33, P=0.783), age (OR=0.78, 95% CI: 0.57-1.07, P=0.119), tumor size (OR=0.87, 95% CI: 0.26-2.95, P=0.824), and lymph node metastasis (OR=1.29, 95% CI: 0.94-1.77, P=0.121). Conclusion: High Nanog expression was associated with poor prognosis in patients with NSCLC, and Nanog may serve as a prognostic predictor in NSCLC.

To determine the ultrasound imaging characteristics of patients with bronchial anthracofibrosis (BAF) and identify clinical markers for prevention and treatment. We randomly selected 1243 participants (113 with BAF) who underwent bronchoscopy and received treatment at our institution between April 2018 and October 2019. BAF was classified as flat, deep-seated retracted, or black mucosal protruding based on microscopic findings. Ultrasound probes were used to determine the maximum thickness of the tube walls and submucosa. The average values of the submucosal and bony tissue areas in the BAF subtypes were compared. The BAF group included 13 participants with a history of tuberculosis (11.5%) and 57 participants with biofuel exposure (50.4%). The average exposure time was 17.4 ± 6.2 years; BAF accounted for 10% of the bronchoscopies performed. The maximum tube-wall thicknesses of the deep-seated retracted (17.3 ± 5.7) and black mucosal protruding (19.3 ± 5.4) groups were significantly greater than those of the flat group (12.5 ± 5.0; P.05). The maximum thicknesses of the submucosa in the deep-retracted (9.8 ± 3.0) and black mucosal protruding (14.5 ± 5.0) groups were significantly greater than that of the flat group (6.6 ± 3.5; P.05). The ratios of bone tissue in the flat and black mucosal protruding groups were 33.3 ± 9.3% and 34.9% ± 12.1%, respectively. The ratio in the deep-seated retracted group (65.2% ± 8.7%) was significantly reduced (P.05). The flat group showed no significant change (P.05). Differences in BAF airway remodeling among different subtypes may lead to varying clinical symptoms. Analyzing the characteristics of BAF airway remodeling and the regulatory pathway may provide new clues for treatment.

BackgroundLung 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.MethodsThe mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset.ResultsBased 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.ConclusionA 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.

Transforming growth factor‑β1 (TGF‑β1)‑induced epithelial‑mesenchymal 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 miR‑483‑5p in PF remains unclear. Therefore, the present study investigated the potential effect of miR‑483‑5p on TGF‑β1‑induced EMT in PF. It was found that the expression of miR‑483‑5p was upregulated in both PF tissue and A549 cells treated with TGF‑β1, whereas expression of Rho GDP dissociation inhibitor 1 (RhoGDI1) was downregulated. miR‑483‑5p mimic transfection promoted TGF‑β1‑induced EMT; by contrast, miR‑483‑5p inhibitor inhibited TGF‑β1‑induced EMT. Also, miR‑483‑5p mimic decreased RhoGDI1 expression, whereas miR‑483‑5p inhibitor increased RhoGDI1 expression. Furthermore, dual‑luciferase reporter gene assay indicated that miR‑483‑5p directly regulated RhoGDI1. Moreover, RhoGDI1 knockdown eliminated the inhibitory effect of the miR‑483‑5p inhibitor on TGF‑β1‑induced EMT via the Rac family small GTPase (Rac)1/PI3K/AKT pathway. In conclusion, these data indicated that miR‑483‑5p inhibition ameliorated TGF‑β1‑induced EMT by targeting RhoGDI1 via the Rac1/PI3K/Akt signaling pathway in PF, suggesting a potential role of miR‑483‑5p in the prevention and treatment of PF.

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.

Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke.

This review aimed to evaluate the level of fatigue in adults with type 2 diabetes measured by the validated Diabetes Symptom Checklist (DSC)and related factors. Ten studies were included. Both DSC (n = 4) and the revised (n = 6) have been used to measure fatigue. When the latter was used (n = 1082), the pooled level of fatigue was 1.77 (on a 0–5 scale). When the former was used (n = 674), the pooled level of fatigue was 1.73 (on a 0–10 scale). Participant demographics (e.g., gender), health information (e.g., BMI), and diabetes-specific factors (e.g., A1C and diabetes distress) were associated with fatigue. Fatigue was negatively related to self-care behaviors. The prevalence of significant fatigue remains unclear due to a lack of a cut-off point of the instrument. Future research is warranted to identify the threshold for clinically significant fatigue and investigate the causal relationship. Nurses are recommended to perform a routine assessment of fatigue.

The novel coronavirus disease 2019 (COVID-19) is an acute infectious disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, the World Health Organization has confirmed that COVID-19 is a global infectious disease pandemic. This is the third acute infectious disease caused by coronavirus infection in this century, after sudden acute respirator syndrome and Middle East respiratory syndrome. The damage mechanism of SARS-CoV-2 is still unclear. It is possible that protein S binds to angiotensin-converting enzyme 2 receptors and invades alveolar epithelial cells, causing direct toxic effects and an excessive immune response. This stimulates a systemic inflammatory response, thus forming a cytokine storm, which leads to lung tissue injury. In severe cases, the disease can lead to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulation dysfunction, and multiple organ dysfunction syndromes. Patients with severe COVID-19 have a relatively high mortality rate. Currently, there are no specific antiviral drugs for the treatment of COVID-19. Most patients need to be admitted to the intensive care unit for intensive monitoring and supportive organ function treatments. This article reviews the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment methods of severe COVID-19 and puts forward some tentative ideas, aiming to provide some guidance for the diagnosis and treatment of severe COVID-19.

Background：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 been reported yet. In this study, we explored the potential role of S100A2 in PF and its potential molecular mechanisms. Methods: First, we analyzed S100A2 expression of patients with PF by retrieving RNA-sequencing datasets from Gene Expression Omnibus (GEO) database. Next, we detected the expression of S100A2 in patients with PF using quantitative real time PCR (qRT-PCR). Then, S100A2 expression was determined with or without the treatment of transforming growth factor-β1 (TGF-β1) in A549 cells. Epithelial-mesenchymal transition (EMT) biomarkers, including E-cadherin，vimentin, and α smooth muscle actin (α-SMA), were identified using qRT-PCR and western blot. Finally, the relevant signalling pathway indicators were detected by western blot. Results: Increased expression of S100A2 was first observed in lung tissues of PF patients. Meanwhile, we found that downregulation of S100A2 inhibited the TGF-β1-induced EMT in A549 cells. Mechanically, TGF-β1 up-regulated β-catenin and phosphorylation of GSK-3β, which was blocked by silencing S100A2 in vitro. Conclusion: These findings demonstrate that downregulation of S100A2 alleviate pulmonary fibrosis via inhibiting EMT. S100A2 is a promising potential target for further understanding the mechanism and developing strategy for the treatment of PF and other EMT-associated disease.

BackgroundThe relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose of this meta-analysis was to summary the available studies evaluated the association between levels of inflammatory factors and ARDS/ALI incidence.MethodsWe searched the PubMed, EmBase, and Cochrane databases for studies published in or before July 2017. For each inflammatory factor, a random effects model was employed to pool results from different studies.ResultsWe identified 63 studies that included 6,243 patients in our meta-analysis. Overall, the results indicated that the levels of angiopoietin (ANG)-2 [standard mean difference (SMD): 1.34; P < 0.001], interleukin (IL)-1β (SMD: 0.92; P = 0.012), IL-6 (SMD: 0.66; P = 0.005), and tumour necrosis factor (TNF)-α (SMD: 0.98; P = 0.001) were significantly higher in patients with ARDS/ALI than in unaffected individuals. No significant differences were observed between patients with ARDS/ALI and unaffected individuals in terms of the levels of IL-8 (SMD: 0.61; P = 0.159), IL-10 (SMD: 1.10; P = 0.231), and plasminogen activator inhibitor (PAI)-1 (SMD: 0.70; P = 0.060).ConclusionsOur findings indicated that ARDS/ALI were associated with elevated levels of ANG-2, IL-1β, IL-6, and TNF-α, but not with IL-8, IL-10, and PAI-1 levels.

Objects: This study aimed to analyze the clinical manifestations, sources, and treatment methods used in patients with a bronchial foreign body. Methods: We analyzed the basic characteristics, clinical signs, CT imaging presentations, pathological manifestations, pathological biopsy results, fiberoptic bronchoscopic surgical techniques, and interventional therapeutic approaches in seven patients with a bronchial foreign body. Results: Among the seven patients with a bronchial foreign body, there were three males and four females. Of the patients, five patients were over 50 years old. Duration of time since onset varied, ranging between six hours and 30 days. One patient had finger pulse oxygen saturation below 90%. Foreign body was the cause of presentation in all seven cases. Computed tomographic scans were normal in one patient, one patient showed a left lung disease, and five patients showed a right lung disease. The presence of the foreign body could be seen in only one patient. Pathological biopsies identified a chili peel in one case, a duck bone in one case, a tooth in one case, and peanuts in three cases. In the seventh patient, a pen cap was found without a pathological biopsy. Using fiberoptic bronchoscopy, the foreign bodies were found and removed in all patients. We also performed bronchial stenosis in three patient, bronchial stenosis with granulation tissue formation in two patients. Conclusion: Neglected foreign bodies in the bronchi could cause various complications and seriously affect the patient's health.

BackgroundEpithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF.MethodsHuman lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting.ResultsStimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA. ConclusionsThese results suggest that IL-32 induces EMT in A549 cells by triggering ER stress. These results suggest that IL-32 may be a novel marker for IPF.

Purpose To estimate the prevalence of common respiratory pathogens among children with community acquired pneumonia (CAP) in Zunyi City, Guizhou, China, and to assess whether the presence of common respiratory pathogens in patients is associated with disease severity. Patients and methods This retrospective study assessed the prevalence of common respiratory viruses and bacteria in the upper respiratory tract of among infants and children aged 1 month to 5 years hospitalized with radiologically confirmed CAP between April 2017 and March 2018. Direct immunofluorescence assay and bacterial culture were used to identify viruses and bacteria in the upper airway specimens, respectively. The association between severe CAP and the presence of pathogens was determined using multivariate logistic regression models. Results Of the 685 patients enrolled, 583 cases had viral and/or bacterial pathogens detected, which included the presence of only viral pathogens, only bacterial pathogens and mixed viral and bacterial pathogens in 34.3%, 29.7% and 36.0% of cases, respectively. Respiratory syncytial virus (RSV) was the most common viral pathogen, with a prevalence rate of 39.9% (273/685). Haemophilus influenzae was the most commonly detected bacterial pathogen, with a prevalence rate of 15.3% (105/685). The presence of RSV (adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.3-2.8) and Staphylococcus aureus (aOR 13.7; 95% CI 5.5-33.9) in children with CAP was associated with severe pneumonia. Conclusions In a cohort of Zunyi infants and children hospitalized with CAP, RSV was the most common pathogen. This article is protected by copyright. All rights reserved.

The relationship between C3a-C3aR, IL-1β, and the acute exacerbation of chronic obstructive pulmonary disease is still unclear. This study aims to explore the expression levels of C3aR in peripheral blood WBCs and the concentrations of C3a, C3aR, and IL-1β in plasma in healthy controls and patients with chronic obstructive pulmonary disease (COPD).WBCs C3aR level in the peripheral blood, the concentrations of C3a, C3aR, and IL-1β in plasma were measured in 60 patients with acute exacerbation of COPD (AECOPD), 30 patients with stable COPD (SCOPD), and 30 healthy controls. The baseline characteristics and clinical data collected from enrolled patients, including age, gender, laboratory indicators, and lung function. We analyzed the correlation between C3a, C3aR, IL-1β, and lung function indicators (forced expiratory volume in the first second as a percentage of predicted value, FEVThe white blood cell count (WBC), neutrophil/lymphocyte ratio (NLR), and C-reactive protein (CRP) of patients in COPD were higher than in healthy controls (P 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in AECOPD were higher than in SCOPD and healthy controls (P 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3aR, and IL-1β in AECOPD combined with respiratory failure were higher than in the non-respiratory failure group (P 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in AECOPD with high-risk were higher than in the low-risk group (P 0.05). The peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in AECOPD were negatively correlated with FEVThe peripheral blood WBCs C3aR mRNA and plasma C3a, C3aR, and IL-1β in COPD patients were significantly related to the risk of disease deterioration. The C3a-C3aR axis may be involved in airway inflammation in patients with COPD.

Inorganic pyrophosphatase (PPA1) promotes tumor progression in several tumor types. However, the underlying mechanism remains elusive. Here, we disclosed that PPA1 expression is markedly upregulated in lung carcinoma tissue versus normal lung tissue. We also found that the non-small cell lung cancer (NSCLC) cell lines show increased PPA1 expression levels versus normal lung cell line control. Moreover, the knockdown of PPA1 promotes cell apoptosis and inhibits cell proliferation. Whereas, the ectopic expression of PPA1 reduces cell apoptosis and enhances cell proliferation. Most interestingly, the expression of mutant PPA1 (D117A) significantly abolishes PPA1-mediated effect on cell apoptosis and proliferation. The underlying mechanism demonstrated that TP53 expression deficiency or JNK inhibitor treatment could abolish PPA1-mediated NSCLC progression. In summary, the aforementioned findings in this study suggest a new pathway the PPA1 mediates NSCLC progression either via TP53 or JNK. Most important, the pyrophosphatase activity is indispensible for PPA1-mediated NSCLC progression. This may provide a promising target for NSCLC therapy.

Arsenic trioxide (As2O3) induces cell apoptosis and reduces the invasive and metastatic activities in various cancer types. However, the role of As2O3 in ovarian cancer angiogenesis remains unclear. In this study, we investigated the role of As2O3 in ovarian cancer angiogenesis and found that a low concentration of As2O3 causes no effects on epithelial ovarian cancer cell viability or apoptosis. Moreover, we found that As2O3-treated epithelial ovarian cancer cells demonstrate a reduced tube formation of endothelial cells in Matrigel. In addition, As2O3-treated epithelial ovarian cancer cells show a decreased VEGFA, VEGFR2 and CD31 mRNA expression. As per the underlying mechanisms involved in As2O3 treatment, we found that As2O3 inhibits VEGFA and VEGFR2 expression that thereby inhibits the VEGFA-VEGFR2-PI3K/ERK signaling pathway. This leads to a suppression in both VEGFA synthesis and angiogenesis-related gene expression. A decreased VEGFA synthesis and secretion also inhibits the VEGFA-VEGFR2-PI3K/ERK signaling pathway in human umbilical vein endothelial cells (HUVECs). In summary, our results may provide strategies for the use of As2O3 in the prevention of tumor angiogenesis.

The objective of the study is to explore the role of respiratory syncytial virus Toll-like receptor 3 (TLR3)-mediated immune response in the pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). A total of 20 AECOPD patients and 10 normal volunteers were studied. TLR3 was detected by RT-PCR, and respiratory syncytial virus (RSV) was detected by nested RT-PCR. Then, A549 cells were infected by RSV at different time points and at different viral titers. TLR3 mRNA was detected by RT-PCR, the protein of TLR3 and interferon regulatory factor 3 (IRF3) were detected by western blot, and IRF3 protein localization was detected by immunofluorescence. Interferon-β (IFN-β) and interleukin-6 (IL-6) were detected by ELISA. A total of 4 (20%) of the 20 AECOPD patients sampled were infected with RSV. The forced expiratory volume in 1 second (FEV1) percentage was lower in the AECOPD patients infected with RSV compared to those not infected (P = 0.03). The expression of IL-6 in the two groups was diametrically opposite (P = 0.04). The AECOPD group (n = 20) showed an increase in TLR3 mRNA compared with that of the control group (n = 10) (P = 0.02). The RSV-infected AECOPD group (n = 4) showed an obvious increase in TLR3 mRNA compared with that of the control group (P = 0.03). There was a significant correlation between severity of reduction in lung function at exacerbation and the increasing expression of TLR3 in AECOPD patients. The TLR3 signaling pathway was activated in lung epithelial cells. TLR3 mRNA/protein levels were increased in A549 infected with RSV compared with those of the control group. IRF3 protein also increased along with the occurrence of nuclear transfer in A549 infected with RSV. IFN-β and IL-6 were also increased in the RSV-infected A549 cells compared with those of the control (P = 0.00 and 0.00, respectively). Increased TLR3 expression in AECOPD patients is associated with declining lung function. TLR3 may be a risk factor for RSV-infected AECOPD patients.

The present study examined differential expression levels of DNA damage repair genes in COLO 205 colorectal cancer cells, with the aim of identifying novel biomarkers for the molecular diagnosis and treatment of colorectal cancer. COLO 205-derived cell spheres were cultured in serum-free medium supplemented with cell factors, and CD133+/CD133− cells were subsequently sorted using an indirect CD133 microbead kit. In vitro differentiation and tumorigenicity assays in BABA/c nude mice were performed to determine whether the CD133+ cells also possessed stem cell characteristics, in addition to the COLO 205 and CD133− cells. RNA sequencing was employed for the analysis of differential gene expression levels at the mRNA level, which was determined using reverse transcription-quantitative polymerase chain reaction. The mRNA expression levels of 43 genes varied in all three types of colon cancer cells (false discovery rate ≤0.05; fold change ≥2). Of these 43 genes, 30 were differentially expressed (8 upregulated and 22 downregulated) in the COLO 205 cells, as compared with the CD133− cells, and 6 genes (all downregulated) were differentially expressed in the COLO 205 cells, as compared with CD133+ cells. A total of 18 genes (10 upregulated and 8 downregulated) were differentially expressed in the CD133− cells, as compared with the CD133+ cells. By contrast, 6 genes were downregulated and none were upregulated in the CD133+ cells compared with the COLO 205 cells. These findings suggest that CD133+ cells may possess the same DNA repair capacity as COLO 205 cells. Heterogeneity in the expression profile of DNA damage repair genes was observed in COLO 205 cells, and COLO 205-derived CD133− cells and CD133+ cells may therefore provide a reference for molecular diagnosis, therapeutic target selection and determination of the treatment and prognosis for colorectal cancer.

Rationale. Most cases of cystic fibrosis occur in Europe, with only a few occurring in Asia. Pulmonary cystic fibrosis is not a rare disease, but in children it is a potentially life-threatening condition. Children suffering from pulmonary cystic fibrosis rarely survive to adulthood, and responses to treatment are generally poor. The most common cause of cystic fibrosis is a genetic mutation on chromosome 7. Patient concerns. A 15-year-old boy with healthy parents suffered from a recurrent cough and expectoration for nearly 10 years. Six years previously, a definitive diagnosis of pulmonary cystic fibrosis and hepatic cirrhosis was made at the Beijing Children’s Hospital. The first occurrence of hematemesis occurred 1 year ago. The main symptoms, which caused this period of hospitalization, were cough, expectoration, and hematemesis. Diagnoses. The underlying cause was finally determined to be the cystic fibrosis transmembrane conductance regulator gene (p.G970D). After genetic and sweat testing performed at the Beijing Children’s Hospital in 2012, a definitive diagnosis of cystic fibrosis was made. Interventions. The patient was administered hemostatic treatment, antibiotics, and cough relief and sputum reduction therapy. Outcomes. The patient’s condition rapidly improved and continued to remain stable, though future relapse is possible following respiratory tract infections. Lessons. This case indicates that in the case of any child that presents a recurrent cryptogenic cough and expectoration, whether accompanied by hematemesis or not, pulmonary cystic fibrosis should be considered. In order to determine underlying causes and prepare for cystic fibrosis transmembrane conductance regulator modulator therapy, genetic and sweat testing are recommended to be conducted if available.