Lung function benefits of traditional Chinese medicine Qiju granules against fine particulate air pollution exposure: a randomized controlled trial.

Introduction: Multiple targets are considered as the causes of ambient fine particulate matter [aerodynamic diameters of < 2.5 µm (PM2.5)] induced lung function injury. Qiju granules are derived from the traditional Chinese medicine (TCM) formula known as Qi-Ju-Di-Huang-Wan (Lycium, Chrysanthemum, and Rehmannia Formula, QJDHW), which has been traditionally used to treat symptoms such as cough with phlegm, dry mouth and throat, and liver heat. This treatment approach involves attenuating inflammation, oxidative stress, and fibrosis response. This study investigated the effects of Qiju granules on protecting lung function against PM2.5 exposure in a clinical trial. Methods: A randomized, double-blinded, and placebo-controlled trial was performed among 47 healthy college students in Hangzhou, Zhejiang Province in China. The participants were randomly assigned to the Qiju granules group or the control group based on gender. Clinical follow-ups were conducted once every 2 weeks during a total of 4 weeks of intervention. Real-time monitoring of PM2.5 concentrations in the individually exposed participants was carried out. Data on individual characteristics, heart rate (HR), blood pressure (BP), and lung function at baseline and during the follow-ups were collected. The effects of PM2.5 exposure on lung function were assessed within each group using linear mixed-effect models. Results: In total, 40 eligible participants completed the scheduled follow-ups. The average PM2.5 level was found to be 64.72 µg/m3 during the study period. A significant negative correlation of lung function with PM2.5 exposure concentrations was observed, and a 1-week lag effect was observed. Forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), maximal mid-expiratory flow (MMEF), forced expiratory flow at 75% of forced vital capacity (FVC) (FEF75), forced expiratory flow at 50% of FVC (FEF50), and forced expiratory flow at 25% of FVC (FEF25) were significantly decreased due to PM2.5 exposure in the control group. Small airway function was impaired more seriously than large airway function when PM2.5 exposure concentrations were increased. In the Qiju granules group, the associations between lung function and PM2.5 exposure were much weaker, and no statistical significance was observed. Conclusion: The results of the study showed that PM2.5 exposure was associated with reduced lung function. Qiju granules could potentially be effective in protecting lung functions from the adverse effects of PM2.5 exposure. Clinical Trial Registration: identifier: ChiCTR1900021235.

Effects of Ipratropium Bromide Combined with Traditional Chinese Medicine Intervention on the Pulmonary Function and Psychological Status of Patients with Chronic Obstructive Pulmonary Disease.

Recently, most scholars have advocated multidisciplinary comprehensive intervention measures for chronic obstructive pulmonary disease (COPD) to improve lung function, relieve symptoms of dyspnea, and improve quality of life. Traditional Chinese medicine (TCM) has rich experience in the treatment of various respiratory system diseases and the rehabilitation of their syndrome differentiation. In this study, total 68 patients with COPD from November 2019 to November 2021 in the hospitals were divided into the control group, ipratropium bromide (IB)-treated group, and IB + TCM-treated group for clinical efficacy observation and to explore the effect of IB combined with TCM on the pulmonary function and psychological status of COPD patients. Patients in the control group were subjected to routine oxygen inhalation, cough and expectorant, and antiviral treatments, while the patients in the IB-treated group were treated with IB and those received in the control group. Patients in the IB + TCM-treated group were treated with IB and TCM intervention. All patients were treated for a month. The results showed that after different interventions, the levels of FEV1, FEV1% pred, FVC, and PEF (P < 0.05) were significantly increased in all the groups, while levels of TNF-α, IL-6, IL-8, and CRP in serum as well as Hamilton Anxiety Scale and Hamilton Depression scores were significantly decreased. Compared with the control group and IB-treated group, the IB + TCM-treated group presented the greatest changes on all abovementioned indicators and the lowest total incidence of adverse reactions, indicating the biggest improvement of IB + TCM on the symptoms of COPD patients. Therefore, the combination of IB and TCM intervention effectively improved the pulmonary function and psychological status of COPD patients and could be used as an important adjunct for COPD treatment.

Intralobular pulmonary sequestration in the middle lobe supplied by a right internal mammary artery: a case report.

BACKGROUND: Pulmonary sequestration (PS) is a rare congenital malformation that is more common in the left lower lobe, and the thoracic aorta is the most common arterial supply. CASE PRESENTATION: We describe a case of a 67-year-old man with a chief complaint of intermittent cough and hemoptysis who had been diagnosed by multidetector computed tomography angiography with right middle lobe intralobular pulmonary sequestration supplied by a right internal mammary artery. Finally, he underwent middle pulmonary lobectomy with normal postoperative recovery. DISCUSSION: This is a rare intralobular pulmonary sequestration case for a feeding artery from the right internal mammary. Multidetector computed tomography angiography should be performed for diagnosis and preoperative evaluation once pulmonary sequestration is suspected.

Transcriptome-Wide m6A Methylome and m6A-Modified Gene Analysis in Asthma.

N6-methyladenosine (m6A) modification is one of the most prevalent RNA modification forms and is an important posttranscriptional mechanism for regulating genes. In previous research, we found that m6A regulator-mediated RNA methylation modification was involved in asthma; however, the specific modified genes are not clear. In this study, we systematically evaluated the transcriptome-wide m6A methylome and m6A-modified genes in asthma. Here, we performed two high-throughput sequencing methods, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and RNA sequencing (RNA-seq) to identify key genes with m6A modification in asthma. Through difference analysis, we found that 416 methylation peaks were significantly upregulated and 152 methylation peaks were significantly downregulated, and it was mainly distributed in 3' UTR. Furthermore, compared with the control group, there were 2,505 significantly upregulated genes and 4,715 significantly downregulated genes in the asthma group. Next, through a combined analysis of transcriptome and differential peaks, 14 differentially expressed genes related to RNA methylation modification were screened. Finally, through 87 health controls and 411 asthma cases from the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes) program, we verified three m6A-modified key genes (BCL11A, MATK, and CD300A) and found that they were mainly distributed in exons and enriched in 3' UTR. Our findings suggested that intervening in m6A-modified genes may provide a new idea for the treatment of asthma.

Effects of Vitamin D on Respiratory Function and Immune Status for Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.

Background: Many studies have demonstrated that vitamin D has clinical benefits when used to treat patients with chronic obstructive pulmonary disease (COPD). However, most of these studies have insufficient samples or inconsistent results. The aim of this meta-analysis was to evaluate the effects of vitamin D therapy in patients with COPD. Methods: We performed a comprehensive retrieval in the following electronic databases: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journals Database (VIP). Two trained reviewers identified relevant studies, extracted data information, and then assessed the methodical quality by the Cochrane risk of bias assessment tool, independently. Then, the meta-analyses were conducted by RevMan 5.4, binary variables were represented by risks ratio (RR), and continuous variables were represented by mean difference (MD) or standardized mean difference (SMD) to assess the efficacy of vitamin D therapy in patients with COPD. Then, publication bias assessment was conducted by funnel plot analysis. Finally, the quality of evidence was assessed by the GRADE system. Results: A total of 15 articles involving 1598 participants were included in this study. The overall results showed a statistical significance of vitamin D therapy in patients with COPD which can significantly improve forced expiratory volume in 1 second (FEV1) (MD: 5.69, 95% CI: 5.01-6.38,P < 0.00001,I2 = 51%) and FEV1/FVC (SMD:0.49, 95% CI: 0.39-0.60,P < 0.00001,I2 = 84%); and serum 25 (OH)D (SMD:1.21, 95% CI:1.07-1.34,P < 0.00001,I2 = 98%) also increase CD3+ Tcells (MD: 6.67, 95% CI: 5.34-8.00,P < 0.00001,I2 = 78%) and CD4+ T cells (MD: 6.00, 95% CI: 5.01-7.00,P < 0.00001,I2 = 65%); and T lymphocyte CD4+/CD8+ ratio (MD: 0.41, 95% CI: 0.20-0.61,P = 0.0001,I2 = 95%) obviously decrease CD8+ Tcells(SMD: -0.83, 95% CI: -1.05- -0.06,P < 0.00001,I2 = 82%), the times of acute exacerbation (RR: 0.40, 95% CI: 0.28-0.59,P < 0.00001,I2 = 0%), and COPD assessment test (CAT) score (MD: -3.77, 95% CI: -5.86 - -1.68,P = 0.0004,I2 = 79%). Conclusions: Our analysis indicated that vitamin D used in patients with COPD could improve the lung function (FEV1 and FEV1/FVC), the serum 25(OH)D, CD3+ T cells, CD4 + T cells, and T lymphocyte CD4+/CD8+ ratio and reduce CD8+ T cells, acute exacerbation, and CAT scores.

Emodin inhibiting neutrophil elastase-induced epithelial-mesenchymal transition through Notch1 signalling in alveolar epithelial cells.

The transition of alveolar type II epithelial cells into fibroblasts has been reported to cause and/or aggravate pulmonary fibrosis (PF), which is characterized by fibroblast proliferation, an enhanced production and accumulation of ECM (extracellular matrix), alveolar wall damage and functional capillary unit loss. Traditional Chinese medicine Emodin has been reported to inhibit TGF-ß-induced epithelial-mesenchymal transition (EMT) in alveolar epithelial cells through Notch signalling. In the present study, neutrophil elastase (NE, also known as ELA2) treatment promoted EMT, Notch1 cleavage (NICD/Notch1 ratio increase) and NICD nuclear translocation in RLE-6TN cells and A549 cells. The promotive roles of NE treatment in these events were significantly reversed by Notch1 knockdown. Traditional Chinese medicine Emodin treatment remarkably inhibited the enzyme activity of NE, suppressed EMT, Notch1 cleavage and NICD nuclear translocation within RLE-6TN and A549 cells, while NE treatment significantly reversed the effects of Emodin. Moreover, in RLE-6TN, the effects of NE on EMT, Notch1 cleavage and NICD nuclear translocation were remarkably attenuated by Emodin treatment and more attenuated by the combination of Emodin and neutrophil elastase inhibitor Sivelestat or notch signal pathway inhibitor DAPT. In conclusion, we revealed the involvement of NE-induced Notch1 cleavage in the functions of Emodin suppressing NE-caused EMT in RLE-6TN cells and A549 cells. This novel mechanism of Emodin inhibiting EMT might extend the application of Emodin in PF treatment.

Primary colorectal diffuse large B-cell lymphoma initially presenting with pleural effusion: report of one case and review of literature.

Gastrointestinal (GI) diffuse large B-cell lymphoma (DLBCL) is one of the frequently reported histologic subtypes of non-Hodgkin lymphoma (NHL) that occur in the GI tract. However, the presentation of quite different clinical manifestations, morphologic characteristics, immunophenotypes, and molecular biologic features is challenging for its diagnosis. Herein, we describe a rare case of primary colorectal DLBCL that occurred in a 59-year-old immunocompetent Chinese female who attended our respiratory clinic for the third time with an asymptomatic pleural effusion and pleural thickening. In her clinical setting, there was no history of trauma or travel, and no evidence of infections, connective tissue diseases, or malignancies such as pleural mesothelioma. Lymphoma was highly suspected for the enlargement of systemic lymph nodes and the multiple polypoid appearance in the rectum found by endoscopy examination. In a repeated colonoscopy, immunohistochemical and molecular features of the multiple "polyps" allowed diagnosis of colorectal diffuse large B-cell NHL. To our knowledge, this is the first case of a verified diagnosis of pleural effusion associated with a primary colorectal DLBCL. The purpose of this report is to alert clinicians that when we evaluate the causes of unexplained pleural effusion, lymphoma should be considered, particularly when the available examination data cannot be corroborated by clinical manifestations.

Determining Pharmacological Mechanisms of Chinese Incompatible Herbs Fuzi and Banxia in Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study.

Aconiti Lateralis Radix Praeparata (Fuzi) and Pinelliae Rhizoma (Banxia) are among the 18 incompatible medications that are forbidden from use in one formulation. However, there is increasing evidence implying that this prohibition is not entirely correct. According to the theory of Chinese traditional medicine, they can be used for the treatment of chronic obstructive pulmonary disease (COPD). Thus, we analyzed the possible approaches for the treatment of COPD using network pharmacology. The active compounds of Fuzi and Banxia (FB) were collected, and their targets were identified. COPD-related targets were obtained by analyzing the differentially expressed genes between COPD patients and healthy individuals, which were expressed using a Venn diagram of COPD and FB. Protein-protein interaction data and network regarding COPD and drugs used were obtained. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted. The gene-pathway network was constructed to screen the key target genes. In total, 34 active compounds and 47 targets of FB were identified; moreover, 7,153 differentially expressed genes were identified between COPD patients and healthy individuals. The functional annotations of target genes were found to be related to mechanisms such as transcription, cytosol, and protein binding; furthermore, 68 pathways including neuroactive ligand-receptor interaction, Kaposi sarcoma-associated herpesvirus infection, apoptosis, and measles were significantly enriched. FOS CASP3, VEGFA, ESR1, and PTGS2 were the core genes in the gene-pathway network of FB for the treatment of COPD. Our results indicated that the effect of FB against COPD may involve the regulation of immunological function through several specific biological processes and their corresponding pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of herb-opponents FB.

Overexpression of Napsin A resensitizes drug-resistant lung cancer A549 cells to gefitinib by inhibiting EMT.

Lung cancer is one of the most common malignant tumors and also the leading cause of cancer-related deaths in the world. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI), such as gefitinib, have been used in the therapy of lung cancer. However, the acquisition of drug resistance is a major limitation in the clinical efficiency of EGFR-TKIs. Epithelial-mesenchymal transition (EMT) has been demonstrated to be an underlying mechanism of acquired resistance. A previous study has reported that Napsin A expression can inhibit EMT in lung cancer cells. The present study therefore investigated the effect of Napsin A on the sensitivity of EGFR-TKI-resistant lung cancer cells. First, a drug-resistant lung cancer cell line was generated using the EGFR-TKI gefitinib on A549 cells (termed here A549-GFT). EMT was demonstrated to be induced in the drug resistant A549-GFT cells, evidenced by reduced E-cadherin expression and increased Vimentin expression compared with control A549 cells. Next, Napsin A was overexpressed in the cells by transfection of the Napsin A-expression vector, PLJM1-Napsin A. Western blot analysis confirmed that the protein expression levels of Napsin A were significantly elevated in the Napsin A-overexpressing cells. Cell proliferation and apoptosis assays were performed to evaluate the effect of Napsin A overexpression on resistant A549 cells. The results of MTT assay demonstrated that Napsin A overexpression inhibited the proliferation of A549 and drug-resistant A549-GFT cells and that the proliferation of Napsin A-overexpressing A549-GFT cells was significantly inhibited by gefitinib treatment compared with control A549-GFT cells. The results from the Annexin V/propidium iodide double staining apoptosis assay indicated that Napsin A overexpression enhanced gefitinib-induced apoptosis in A549-GFT cells. Additionally, EMT was reversed following Napsin A expression in A549-GFT cells, as evidenced by the restoration of E-cadherin and downregulation of Vimentin expression. Further investigation demonstrated that Napsin A overexpression resulted in inhibition of focal adhesion kinase, a critical factor in integrin signaling, in the resistant A549-GFT cells. These data suggested that Napsin A resensitized the drug-resistant A549-GFT cells to gefitinib, possibly by reversing EMT via integrin signaling inhibition. Therefore, Napsin A combined with a TKI may be a more effective treatment strategy for lung cancer.

Napsin A is negatively associated with EMT­mediated EGFR­TKI resistance in lung cancer cells.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR­TKI) have been used as a standard therapy for patients with lung cancer with EGFR­activating mutations. Epithelial­mesenchymal transition (EMT) has been reported to be associated with the development of EGFR­TKI resistance, which limits the clinical efficacy of EGFR­TKI. Therefore, investigating the resistance­associated mechanism is required in order to elucidate an effective therapeutic approach to enhance the sensitivity of lung cancer to EGFR­TKI. In the present study, EGFR­TKI erlotinib­sensitive H358, H322 and H441 lung cancer cells, erlotinib­moderately sensitive A549 cells, and erlotinib­insensitive HCC827 cells with EGFR­mutation (exon 19 deletion) were used to detect the mRNA and protein expression of the EMT­associated proteins E­cadherin and vimentin, and napsin A, by reverse transcription­quantitative polymerase chain reaction analysis and western blotting. It was observed that the E­cadherin expression level in erlotinib­sensitive cells was increased compared with the moderately sensitive A549 cells and HCC827 cells; however, vimentin exhibited opposite expression, suggesting a correlation between EMT and erlotinib sensitivity in lung cancer cells. The napsin A expression level was observed to be positively associated with erlotinib sensitivity. In addition, napsin A highly­expressingH322 cells were used and napsin A­silenced cells were constructed using small interfering RNA (siRNA) technology, and were induced by transforming growth factor (TGF)­ßl. It was observed that TGF­ßl partially induced the alterations in E­cadherin and vimentin expression and the occurrence of EMT in napsin A highly­expressing cells, while TGF­ßl significantly induced EMT via downregulation of E­cadherin and upregulation of vimentin in napsin A­silenced cells; cell proliferation and apoptosis assays demonstrated that TGF­ßl induced marked resistance to erlotinib in napsin A­silenced cells compared with napsin A­expression cells. These data indicated that napsin A expression may inhibit TGF­ßl­induced EMT and was negatively associated with EMT­mediated erlotinib resistance, suggesting that napsin A expression may improve the sensitivity of lung cancer cells to EGFR­TKI through the inhibition of EMT.