Screening and clinical characteristics analysis of familial hypercholesterolemia in a tertiary public hospital.

Background and aims: Familial hypercholesterolemia (FH) is becoming a global burden. However, it remains underdiagnosed and undertreated worldwide. This study aimed to observe the screening rate of FH patients and department distribution among hospitalized patients using different diagnostic criteria. Methods: A total of 45,410 inpatients with LDL-C ≥3.5 mmol/L between 2008 and 2019 were included from The Second Affiliated Hospital of Nanchang University. Inpatients are diagnosed and divided into groups by Dutch Lipid Clinic Network (DLCN) criteria, Chinese-modified DLCN criteria and Chinese expert consensus (CEC) criteria. Results: There were 172, 1,076 and 115 inpatients included in the DLCN group, Chinese-modified DLCN group and CEC group, respectively (screening rates: 0.38%, 2.37% and 0.25%). These FH patients had a very high risk of atherosclerotic cardiovascular disease (ASCVD) (55.7%-74.4%), especially in the DLCN group and CEC group (70.4%-74.4%). More than half of the patients were in the Department of Cardiology, and other high-risk departments included Neurology, Nephrology, Vascular Surgery, Otolaryngology & Head Neck Surgery and Traditional Chinese Medicine (24.35%-31.51%). Overall, hypertension, coronary heart disease, carotid arteriosclerosis, hepatic cyst, arrhythmia, and nonalcoholic fatty liver disease were common accompanying diseases with FH. Conclusions: It is necessary to establish appropriate diagnostic criteria and more positive treatment strategies for the FH inpatient population. In addition, promoting awareness of FH among doctors from other departments is also necessary. Therefore, developing a comprehensive management strategy for FH disease is very important.

AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial.

Background: Inhibiting vascular endothelial growth factor (VEGF) function can improve the efficacy of immunotherapy by modulating the tumor immune microenvironment. AK112 is the first-in-class humanized IgG1 bispecific antibody targeting programmed death-1 (PD-1) and VEGF. This study aimed to evaluate the efficacy and safety of AK112 combined with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Methods: This open-label, multicenter, phase II clinical trial was conducted in 11 hospitals in China. Eligible participants were adults aged 18-75 years with locally advanced or metastatic NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, at least one measurable lesion, and an estimated life expectancy of at least 3 months. The participants were categorized into three cohorts based on prior therapy and functional genomic alterations. Patients in cohort 1 were previously untreated advanced NSCLC, had no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) gene modifications, and received AK112 combined with pemetrexed (500 mg/m2) for non-squamous (non-sq)-NSCLC or paclitaxel (175 mg/m2) for sq-NSCLC plus carboplatin (area under the curve of 5 mg/mL per min) for four cycles, followed by AK112 with pemetrexed for non-sq-NSCLC and AK112 alone for sq-NSCLC as maintenance therapy. The participants in cohort 2 had advanced NSCLC with EGFR-sensitive mutations, failed previous EGFR-tyrosine kinase inhibitor (TKI) therapy, and received pemetrexed plus AK112 and carboplatin for four cycles, followed by pemetrexed plus AK112 as maintenance therapy. The participants in cohort 3 had advanced NSCLC who failed systemic platinum-based chemotherapy and anti-PD-1/programmed death-ligand 1 (PD-L1) treatments and received AK112 plus docetaxel (75 mg/m2). Two dosages of AK112 (10 or 20 mg/kg) were examined in each cohort, and the drug was administered intravenously on day 1 of each 3-week treatment cycle. The primary endpoints were the investigator-assessed objective response rate (ORR) and safety. This study was registered with ClinicalTrials.gov (NCT04736823). Findings: Eighty-three patients were enrolled from February 2021 to August 2022 and received the study treatment. Cohorts 1, 2, and 3 had 44, 19, and 20 patients, respectively. The confirmed ORR was 53.5% (23/43) [95% CI, 36.9-67.1], 68.4% (13/19) [95% CI, 43.4-87.4], and 40.0% (8/20) [95% CI, 19.1-63.9] in cohorts 1, 2, and 3, respectively. In cohort 1, the median PFS was not reached, and the 12-month PFS rate was 59.1%. In cohorts 2 and 3, the median PFS were 8.5 [95% CI, 5.5-NE] and 7.5 [95% CI, 2.3-NE] months, and the 12-month PFS rates were 35.5% and 44.5%, respectively. The most common grade ≥3 treatment-related adverse events were decreased white blood cell count [7 (8.4%)], neutropenia [5 (6.0%)], thrombocytopenia [2 (2.4%)], anemia [4 (4.8%)], and myelosuppression [2 (2.4%)]. Interpretation: AK112 plus platinum-doublet showed promising antitumor activity and safety not only in first-line treatment of advanced NSCLC patients without driver mutation but also in patients with EGFR-functional mutation who failed previous EGFR-TKI therapy and advanced NSCLC patients who failed prior systemic platinum-based chemotherapy and PD-1/PD-L1 inhibitor treatments, suggesting a valuable potential new treatment option for this patient population. Funding: Akeso Biopharma, Inc., Zhongshan, China, and National Natural Science Foundation of China.

COL8A1 Promotes NSCLC Progression Through IFIT1/IFIT3-Mediated EGFR Activation.

Activation of EGFR is a major risk factor for non-small cell lung cancer (NSCLC). Understanding the molecular events promoting EGFR activation can help us gain more insights into the progression of NSCLC. In this study, we demonstrate that collagen type VIII alpha 1 chain (COL8A1), an extracellular matrix component, was overexpressed in NSCLC. In NSCLC cells, knockdown of COL8A1 suppressed cell growth, cycle progression, and migration, and induced cell apoptosis. While COL8A1 overexpression promoted cell proliferation and inhibited cell apoptosis. In addition, we found that COL8A1 depletion reduced interferon response signaling and downregulated (IFIT1) and interferon-induced proteins with tetratricopeptide repeats 3 (IFIT3). Moreover, we indicated that COL8A1 could upregulate IFIT1 and IFIT3 mediated EGFR activation in vitro and in vivo. Lastly, there was a positive correlation among COL8A1, IFIT1, and IFIT3 expression, and EGFR activity in patients with NSCLC. Overall, our data demonstrate that COL8A1 contributes to NSCLC proliferation and invasion through EGFR activation, dependent on IFIT1 and IFIT3 expression.

Plasmonic Bismuth Nanoparticles: Thiolate Pyrolysis Synthesis, Size-Dependent LSPR Property, and Their Oxidation Behavior.

Plasmonics, especially the localized surface plasmon resonance (LSPR) in non-noble metal bismuth nanoparticles (Bi NPs), and its spectral features and applications have stimulated increasing research interest in recent years. However, the lack of mature methods to prepare Bi NPs with a well-controlled size and/or shape significantly limits the experimental investigations concerning the LSPR optical properties. Herein, we realize the size-tunable synthesis of nearly monodisperse spherical Bi NPs through a thiolate pyrolysis reaction in solution. The instantaneous thermolysis of a layered molecular intermediate, bismuth dodecanethiolate [Bi(SC12H25)3], results in a classical LaMer mechanism for the nucleation and growth of Bi NPs, allowing for a precise size control from 65 to 205 nm in the average diameter. The diameter tunability enables a systematic study on the size dependence of LSPR optical properties of Bi NPs, and we observe rich ultraviolet-visible-near-infrared spectral responses arising from the LSPR absorption and scattering of Bi NPs as their size varies, which will greatly benefit the light harvesting and manipulation in the solar spectrum. Furthermore, we find that a complete oxidation occurs to Bi NPs under air flow at the temperature when they melt and accordingly generate metastable tetragonal-phase ß-Bi2O3 NPs that show an optical band gap of 2.15 eV and interesting temperature-dependent ß â†’ α → δ → (γ + ß) polymorphic transitions.

Inhibition of HDAC1 alleviates monocrotaline-induced pulmonary arterial remodeling through up-regulation of miR-34a.

BACKGROUND: It has been found that up-regulation of histone deacetylases 1 (HDAC1) is involved in the development of pulmonary arterial hypertension (PAH). However, it is still unclear whether inhibition of HDAC1 suppresses the development of PAH via restoring miR-34a level in monocrotaline (MCT)-induced PAH rats. METHODS: PAH rat models were induced by intraperitoneal injection of MCT. HDAC1 was suppressed by intraperitoneal injection of the class I HDAC inhibitor MS-275, and miR-34a was over-expressed via tail vein injection of miR-34a agomiR. RESULTS: HDAC1 protein was significantly increased in MCT-induced PAH rats; this was accompanied with down-regulation of miR-34a and subsequent up-regulation of matrix metalloproteinase 9 (MMP-9)/tissue inhibitor of metalloproteinase 1 (TIMP-1) and MMP-2/TIMP-2. Administration of PAH rats with MS-275 or miR-34a agomiR dramatically abolished MCT-induced reduction of miR-34a and subsequent up-regulation of MMP-9/TIMP-1 and MMP-2/TIMP-2, finally reduced extracellular matrix (ECM) accumulation, pulmonary arterial remodeling, right ventricular systolic pressure (RVSP) and right ventricle hypertrophy index (RVHI) in PAH rats. CONCLUSIONS: HDAC1 contributes to the development of MCT-induced rat PAH by suppressing miR-34a level and subsequently up-regulating the ratio of MMP-9/TIMP-1 and MMP-2/TIMP-2. Inhibition of HDAC1 alleviates pulmonary arterial remodeling and PAH through up-regulation of miR-34a level and subsequent reduction of MMP-9/TIMP-1 and MMP-2/TIMP-2, suggesting that inhibition of HDAC1 might have potential value in the management of PAH.

Primary intratracheal schwannoma misdiagnosed as severe asthma in an adolescent: A case report.

BACKGROUND: Primary intratracheal schwannoma is an extremely rare type of benign airway tumor, especially in adolescents. The presenting symptoms are typically prolonged cough and wheezing that can be misdiagnosed as asthma in adolescent patients. CASE: A 16-year-old adolescent girl admitted to a local hospital with symptoms of an irritating cough and wheezing was diagnosed with bronchial asthma and treated with budesonide and formoterol. Over the next year, the patient's wheezing and coughing symptoms gradually worsened and the antiasthma treatment was ineffective. One week prior to this admission, the patient developed dyspnea after catching a cold and was transferred to our hospital with a diagnosis of severe asthma. However, chest computed tomography and bronchoscopy showed a mass in the trachea. Primary intratracheal schwannoma was diagnosed by biopsy. Her symptoms were relieved by endoscopic resection by electrosurgical snaring combined with argon plasma coagulation. No relapse occurred during an 18 mo follow-up. CONCLUSION: Primary intratracheal schwannoma should be considered in the differential diagnosis in adolescents with recurrent asthma-like attacks.

m6A RNA Methylation Regulators Participate in the Malignant Progression and Have Clinical Prognostic Value in Lung Adenocarcinoma.

Abnormal methylation of N6 adenosine (m6A) in RNA plays a crucial role in the pathogenesis of many types of tumors. However, little is known about m6A RNA methylation in lung adenocarcinoma. This study aimed to identify the value of m6A RNA methylation regulators in the malignant progression and clinical prognosis of lung adenocarcinoma. The RNA-seq transcriptome data and corresponding clinical information of lung adenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Then the identification of differentially expressed m6A RNA methylation regulators between cancer samples and normal control samples, different subgroups by consensus expression of these regulators and the prognostic signature were achieved using R software with multiple corresponding packages. The results showed that the expression levels of HNRNPC, YTHDF1, KIAA1429, RBM15, YTHDF2, and METTL3 in cancer group were significantly up-regulated (P < 0.05), while expression levels of FTO, ZC3H13, METTL14, YTHDC1 and WTAP in cancer group were significantly down-regulated (P < 0.05) compared with control group. Two subgroups identified by consensus expression of these regulators were closely related to the clinicopathological features, clinical outcomes and malignancy of lung adenocarcinoma. In addition, a 3-gene risk signature including KIAA1429, RBM15, and HNRNPC was constructed and the lung adenocarcinoma patients in TCGA database were divided into high-risk group and low-risk group based on the median risk score. In conclusion, the prognostic signature-based risk score calculated according to the expression levels of KIAA1429, RBM15, and HNRNPC, was not only strongly associated with clinical outcomes and clinicopathological features, but also an independent prognostic factor in lung adenocarcinoma.

[Bronchial Mucoepidermoid Carcinoma in Children and Its Misdiagnosis:Report of One Case].

Bronchial mucoepidermoid carcinoma is a rare malignancy with varied disease courses.The symptoms are non-specific and mostly related to infection and airway obstruction secondary to the tumor.Bronchial mucoepidermoid carcinoma is difficult to be distinguished from pneumonia,tracheobronchitis,chronicobstructive pulmonary disease,asthma,and other respiratory diseases in its early stage.The age of onset is mostly between 20 and 55 years,and the disease is rarely seen in children.Confirmation of bronchial mucoepidermoid carcinoma depends on bronchoscopy and pathological biopsy,and this disease is often missed and misdiagnoed.

Impact of Radiographic Bronchiectasis in COPD.

BACKGROUND: COPD and bronchiectasis frequently coexist, which creates an emerging phenotype with a worse prognosis. However, the impact of bronchiectasis on the natural history of COPD has not been fully evaluated and is still controversial. This meta-analysis was performed to clarify the associations of the presence of bronchiectasis with the prognosis and quality of life of patients with COPD. METHODS: A systematic review and meta-analysis was performed following a search of medical databases, and included articles published up to April 2019. The following outcome measures were analyzed: age, sex, smoking history, body mass index, exacerbation rate, lung function, inflammatory biomarkers, albumin, colonization by potentially pathogenic microorganisms, Pseudomonas aeruginosa isolates, Haemophilus influenzae isolates, hospital admissions, and mortality. RESULTS: A total of 415,257 subjects with COPD from 18 observational studies were eligible; bronchiectasis was present in 25,929 subjects (6.24%). The coexistence of COPD and bronchiectasis occurred more often in older subjects with lower body mass index. The presence of bronchiectasis in the subjects with COPD increased the risk of daily sputum production (odds ratio [OR] 1.80, 95% CI 1.24-2.61), exacerbation (weighted mean difference [WMD] 0.72 times, 95% CI 0.59-0.85), frequent hospital admissions (WMD 0.35 times, 95% CI 0.21-0.49), and follow-up (>3 years) mortality (OR 2.26, 95% CI 0.95-5.36). The subjects with COPD and bronchiectasis showed poorer pulmonary function (FEV1/FVC: WMD -3.37%, 95% CI -5.63 to -1.11), lower albumin (Standardized mean difference [SMD] -0.17, 95% CI -0.26 to -0.08), elevated C-reactive protein (SMD 0.40, 95% CI 0.06-0.74), a greater proportion of chronic colonization by potentially pathogenic microorganisms (OR 6.65, 95% CI 4.44-9.95), and a higher isolation rate of P. aeruginosa (OR 5.13, 95% CI 4.89-5.38) or H. influenzae (OR 1.90, 95% CI 1.29-2.79) than the subjects with COPD without bronchiectasis. CONCLUSIONS: This meta-analysis confirmed the significant associations of the presence of bronchiectasis with the natural history, disease course, and outcomes in COPD. The COPD-bronchiectasis phenotype had adverse effects on subjects' health condition and prognosis.

Application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of non-small-cell lung cancer: A protocol for a systematic review.

BACKGROUND: Ruling out distant metastases, non-small cell lung cancer (NSCLC)treatment depends on the results of mediastinal node staging (N staging). Several diagnostic methods play central roles in mediastinal N staging. This study is intended to evaluate the existing diagnostic methods and report quality, and to search for the best method for staging mediastinal lymph nodes. METHODS: We searched PubMed, Embase, and the Cochrane Library to identify relevant studies, including randomized controlled trials and retrospective studies. These studies report the application of computed tomography, positron emission tomography-computed tomography, magnetic resonance imaging, endobronchial ultrasound, and mediastinoscopy in the diagnosis of mediastinal lymph node staging of NSCLC. The quality of the literature was assessed using the Quality Assessment of Diagnostic Accuracy Study 2. The true positive, false positive, true negative, and false negative of each study was extracted. The corresponding sensitivity, specificity, and other indicators were calculated and the Summary Receiver Operating curve was established. Then, head-to-head and indirect comparison meta-analyses will be conducted. RESULTS: The results of this study will be published in a peer-reviewed journal. CONCLUSION: This study will provide basis for mediastinal lymph node staging of non-small cell lung cancer. PROSPERO REGISTRATION NUMBER: CRD42019145667.

Serum Surfactant Protein D is a Potential Biomarker for Chronic Obstructive Pulmonary Disease: a Systematic Review and Meta-analysis.

BACKGROUND: A number of studies have been conducted to investigate the association between serum surfactant protein D (SP-D) concentration and chronic obstructive pulmonary disease (COPD) risk. However, the results are inconsistent. This systematic review and meta-analysis aim to investigate whether serum SP-D concentration is a potential biomarker for COPD diagnosis. METHODS: We searched Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), and Wanfang Database from inception through July 18, 2018. The standardized mean difference (SMD) with 95% confidence interval (CI) was used to investigate the effect sizes. RESULTS: Seventeen eligible studies from a total of 4,639 subjects were finally included in this systematic review and meta-analysis. The results indicated that serum SP-D levels in COPD patients were significantly higher than those in controls (SMD = 1.01, 95% CI = 0.62 - 1.41, p < 0.001). We also found that serum SP-D concentration in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients was significantly higher than that in stable COPD patients (SMD = 1.50, 95% CI = 0.92 - 2.08, p < 0.001), and serum SP-D concentration was higher in smokers than in nonsmokers in healthy population (SMD = 1.50, 95% CI = 0.35 - 2.64, p = 0.025). CONCLUSIONS: The current systematic review and meta-analysis indicates that serum SP-D levels may be a promising biomarker for COPD. In particular, increased serum SP-D levels appear to be associated with acute exacerbation of COPD and smoking in healthy population.

A Machine Learning Method for Identifying Lung Cancer Based on Routine Blood Indices: Qualitative Feasibility Study.

BACKGROUND: Liquid biopsies based on blood samples have been widely accepted as a diagnostic and monitoring tool for cancers, but extremely high sensitivity is frequently needed due to the very low levels of the specially selected DNA, RNA, or protein biomarkers that are released into blood. However, routine blood indices tests are frequently ordered by physicians, as they are easy to perform and are cost effective. In addition, machine learning is broadly accepted for its ability to decipher complicated connections between multiple sets of test data and diseases. OBJECTIVE: The aim of this study is to discover the potential association between lung cancer and routine blood indices and thereby help clinicians and patients to identify lung cancer based on these routine tests. METHODS: The machine learning method known as Random Forest was adopted to build an identification model between routine blood indices and lung cancer that would determine if they were potentially linked. Ten-fold cross-validation and further tests were utilized to evaluate the reliability of the identification model. RESULTS: In total, 277 patients with 49 types of routine blood indices were included in this study, including 183 patients with lung cancer and 94 patients without lung cancer. Throughout the course of the study, there was correlation found between the combination of 19 types of routine blood indices and lung cancer. Lung cancer patients could be identified from other patients, especially those with tuberculosis (which usually has similar clinical symptoms to lung cancer), with a sensitivity, specificity and total accuracy of 96.3%, 94.97% and 95.7% for the cross-validation results, respectively. This identification method is called the routine blood indices model for lung cancer, and it promises to be of help as a tool for both clinicians and patients for the identification of lung cancer based on routine blood indices. CONCLUSIONS: Lung cancer can be identified based on the combination of 19 types of routine blood indices, which implies that artificial intelligence can find the connections between a disease and the fundamental indices of blood, which could reduce the necessity of costly, elaborate blood test techniques for this purpose. It may also be possible that the combination of multiple indices obtained from routine blood tests may be connected to other diseases as well.

Identification of potential diagnostic and therapeutic target genes for lung squamous cell carcinoma.

The purpose of this study was to identify potential molecular markers of lung squamous cell carcinoma (LUSC). Three datasets containing LUSC mRNA sequencing data were downloaded from the Gene Expression Omnibus, The Cancer Genome Atlas and the Gene Expression Profiling Interactive Analysis databases. These datasets were used to identify significantly differentially expressed genes (DEGs) in LUSC. A protein-protein interaction network of the DEGs was constructed followed by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and overall survival analyses of the DEGs. A total of 37 DEGs between LUSC and normal tissues were identified, including 26 downregulated genes and 11 upregulated genes. Biological Process enrichment analysis revealed that the DEGs were mainly enriched in 'cell adhesion', 'cell-matrix adhesion', 'anatomical structure morphogenesis', 'ECM-receptor interaction' and 'focal adhesion'. Overall survival analysis demonstrated that transcription factor 21, α-2-macroglobulin, acyl-CoA synthetase long chain family member 5, integrin subunit ß8, meiotic nuclear divisions 1 and secretoglobin family 1A member 1 were significantly associated with the occurrence and development of lung cancer, and these genes were selected as hub genes. The results obtained in the present study may aid the elucidation of the molecular mechanisms involved in the development of LUSC and may provide potential targets for LUSC treatment.

Biomarkers for detecting malignant pleural mesothelioma: Protocol for a reanalysis of published data based on systematic reviews of diagnostic test accuracy.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a highly invasive tumor caused primarily by asbestos exposure. In recent decades, the incidence of MPM has shown an increasing trend, posing a great threat to human health. Although there is currently no effective way to treat MPM, patients can survive for more than 5 years if the tumor is removed early. Several systematic reviews (SRs) have evaluated the diagnostic value of biomarkers for diagnosing MPM. However, no studies have been conducted to analyze the quality of these SRs and it remains unclear which biomarker is the excellent diagnostic test. This study aims to assess the methodological quality of the SRs and reanalyze the published data based on SRs to find the optimal biomarker for the early diagnosis of MPM. METHODS: A systematic search will be performed in PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify SRs reporting value of biomarkers for detecting MPM. We will evaluate the risk of bias of the included SRs according to the Assessment of Multiple Systematic Reviews-2 (AMSTAR-2) instrument. Standard pairwise meta-analysis and adjusted indirect comparison will be used to compare the diagnostic value of different biomarkers. RESULTS: The results of this study will be submitted to a peer-reviewed journal for publication. CONCLUSION: This study will reanalyze the published data based on SRs to find a biomarker with the superior diagnostic performance for the diagnosis of MPM. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews. PROSPERO REGISTRATION NUMBER: CRD42019125880.

Comparison of value of biomarkers in diagnosing lung cancer: An overview of systematic reviews protocol.

BACKGROUND: In both sexes combined, lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death. Furthermore, the incidence rate is increasing in many countries. Many lung cancer patients have a poor prognosis because they are usually diagnosed at an advanced stage. Therefore, there is an urgent need to develop effective methods for early diagnosis of lung cancer. Some systematic reviews have evaluated the value of biomarkers for diagnosing lung cancer. However, it remains unclear which biomarker has superior performance for early and accurate detection of lung cancer. This overview aims to assess the methodological and reporting quality of available systematic reviews and to find an optimal biomarker for diagnosing lung cancer. METHODS: We searched PubMed, Embase.com, the Cochrane Library of Systematic Reviews, and Web of Science to identify relevant systematic reviews including randomized controlled trials, cross-sectional studies, case-control studies, or cohort studies that reported the value of biomarkers for diagnosing lung cancer. The methodological quality will be assessed using AMASAR-2 checklist, and the reporting quality will be assessed using PRISMA-DTA checklist. Bubble plot will be generated to map the biomarkers, methodological and reporting quality. The pairwise meta-analysis and indirect comparisons will be performed using STATA 13.0. RESULTS: The results of this study will be published in a peer-reviewed journal CONCLUSION:: This overview will provide comprehensive evidence of different biomarkers for the diagnosis of lung cancer. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is an overview based on published systematic reviews.

Prediction of target genes for miR-140-5p in pulmonary arterial hypertension using bioinformatics methods.

The expression of microRNA (miR)-140-5p is known to be reduced in both pulmonary arterial hypertension (PAH) patients and monocrotaline-induced PAH models in rat. Identification of target genes for miR-140-5p with bioinformatics analysis may reveal new pathways and connections in PAH. This study aimed to explore downstream target genes and relevant signaling pathways regulated by miR-140-5p to provide theoretical evidences for further researches on role of miR-140-5p in PAH. Multiple downstream target genes and upstream transcription factors (TFs) of miR-140-5p were predicted in the analysis. Gene ontology (GO) enrichment analysis indicated that downstream target genes of miR-140-5p were enriched in many biological processes, such as biological regulation, signal transduction, response to chemical stimulus, stem cell proliferation, cell surface receptor signaling pathways. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis found that downstream target genes were mainly located in Notch, TGF-beta, PI3K/Akt, and Hippo signaling pathway. According to TF-miRNA-mRNA network, the important downstream target genes of miR-140-5p were PPI, TGF-betaR1, smad4, JAG1, ADAM10, FGF9, PDGFRA, VEGFA, LAMC1, TLR4, and CREB. After thoroughly reviewing published literature, we found that 23 target genes and seven signaling pathways were truly inhibited by miR-140-5p in various tissues or cells; most of these verified targets were in accordance with our present prediction. Other predicted targets still need further verification in vivo and in vitro.

Activation of PPARγ inhibits HDAC1-mediated pulmonary arterial smooth muscle cell proliferation and its potential mechanisms.

The downstream targets of histone deacetylase 1 (HDAC1) mediation of platelet-derived growth factor (PDGF)-induced pulmonary arterial smooth muscle cell (PASMC) proliferation are still unclear, and it is also unknown whether activation of peroxisome proliferator-activated receptor γ (PPARγ) modulates HDAC1 and its down-stream targets in PASMCs. The present study aims to address these issues. Our results showed that PDGF dose- and time-dependently induced PASMC proliferation, and this was accompanied by an increase of HDAC1 and cyclin-dependent kinase 4 (CDK4) protein expression as well as a reduction of microRNA-124 (miR-124). Pre-silencing of HDAC1 with small interfering RNA (siRNA) abolished PDGF-induced miR-124 down-regulation, CDK4 protein up-regulation, and PASMC proliferation. In addition, over-expression of miR-124 reversed CDK4 protein elevation and PASMC proliferation caused by PDGF. We further found that pre-incubation of PASMCs with pioglitazone, an agonist of PPARγ receptors, significantly increased PPARγ expression and activity, and blocked PDGF-stimulated cell proliferation by regulating HDAC1-mediated miR-124 and CDK4 expression. Our study indicates that HDAC1/miR-124/CDK4 axis plays an important role in PDGF-induced PASMC proliferation, and activation of PPARγ inhibits PASMC proliferation by acting on HDAC1 pathway.

[Progress in sleep-disordered breathing in idiopathic pulmonary fibrosis].

Idiopathic pulmonary fibrosis (IPF) is one of the most common idiopathic interstitial pneumonia. The main symptoms for IPF are dry cough and exertional shortness of breath, which is worsen gradually with the development of pulmonary fibrosis. Patients with IPF often suffer from sleep disordered breathing (SDB). Sleep architecture for these patients including the sleep efficiency, deep sleep, rapid eye movement sleep and arousal index, are changed, which seriously affects the quality of life. In the absence of effective therapies, optimizing the quality of life may become a major therapeutic target for IPF. The diagnosis and treatment of SDB can significantly improve the quality of life for patients with IPF.

Sildenafil versus continuous positive airway pressure for erectile dysfunction in men with obstructive sleep apnea: a meta-analysis.

OBJECTIVE: To evaluate the effectiveness of sildenafil versus continuous positive airway pressure (CPAP) for patients with erectile dysfunction (ED) and obstructive sleep apnea (OSA). METHODS: This is a meta-analysis of a randomized controlled trial. The main outcome measures for effectiveness were the percentage of successful intercourse attempts, International Index of Erectile Function (IIEF) domain scores (erectile function, EF) and the satisfaction levels of the patients and their partners with the treatment for ED. RESULTS: Two randomized controlled trials totaling 70 patients were included. Meta-analysis results are as follows: after 12 weeks of treatment, patients under sildenafil demonstrated a significant advantage over under CPAP in terms of the percentage of successful intercourse attempts [OR = 3.24, 95% CI (2.37-4.43)], EF scores [WMD = 3.57, 95%CI (1.68-5.45)], and the satisfaction levels of the patients and their partners with the treatment for ED [OR = 3.56, 95% CI (1.27-9.98)]. CONCLUSION: Current clinical studies might confirm that both therapeutic methods were safe and effective, but sildenafil was superior to CPAP in the treatment of ED in men with OSA. We conclude that new therapeutic agents or a combination of the two methods should be studied further.