Case report: Endobronchial closure of postoperative bronchopleural fistula with embolization coil: a sandwich-like approach.

Background: Embolization Coil has been reported to effectively treat postoperative bronchopleural fistula (BPF). Little detailed information was available on computer tomography (CT) imaging features of postoperative BPF and treating procedures with pushable Embolization Coil. Objective: We aimed to specify the imaging characteristics of postoperative BPFs and present our experience treating them with the pushable Embolization Coil. Methods: Six consecutive patients (four males and two females aged 29-56 years) diagnosed with postoperative BPF receiving bronchoscopic treatment with the pushable Nester® Embolization Coil (Cook Medical, Bloomington, Indiana) were included in this single-center, retrospective study. Multiplanar reconstruction of multidetector CT scans was reviewed for the presence, location, size, and radiological complications of each BPF, including air collection, pneumothorax, bronchiectasis, and chest tube. Using standardized data abstraction forms, demographic traits and clinical outcomes were extracted from the medical files of these patients. Results: The underlying diseases for lung resection surgery were pulmonary tuberculosis (n = 3), lung adenocarcinoma (n = 2), and pulmonary aspergillosis (n = 1). All patients had air or air-fluid collection with chest tubes on radiological findings. Multiplanar reconstruction identified the presence of postoperative BPF in all patients. Five fistulas were central, located proximal to the main or lobar bronchus, while one was peripheral, distant from the lobar bronchus. Fistula sizes ranged from 0.8 to 5.8 mm. Subsequent bronchoscopy and occlusion testing confirmed fistula openings in the bronchial stump: right main bronchus (n = 1), right upper lobe (n = 2), and left upper lobe (n = 3). The angioplasty catheter-based procedure allows precise fistula occlusion "like a sandwich" with the pushable Embolization Coil. Five patients with BPF sizes ranging from 0.8 to 1.5 mm were successfully treated with a pushable Embolization Coil, except for one with a BPF size of 5.8 mm. No adverse events or complications were observed throughout follow-up, ranging from 29 to 1,307 days. Conclusion: The pushable Nester® Embolization Coil seems a minimally invasive, cost-effective, and relatively easy-to-perform bronchoscopic treatment for postoperative BPF with a size less than 2 mm. Further studies are required to ensure the use of pushable Embolization Coil in treating postoperative BPF.

Chinese expert consensus on cone-beam CT-guided diagnosis, localization and treatment for pulmonary nodules.

Cone-beam computed tomography (CBCT) system can provide real-time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Alteration of bacterial community composition in the sediments of an urban artificial river caused by sewage discharge.

Background: Urbanization has an ecological and evolutionary effect on urban microorganisms. Microorganisms are fundamental to ecosystem functions, such as global biogeochemical cycles, biodegradation and biotransformation of pollutants, and restoration and maintenance of ecosystems. Changes in microbial communities can disrupt these essential processes, leading to imbalances within ecosystems. Studying the impact of human activities on urban microbes is critical to protecting the environment, human health, and overall urban sustainability. Methods: In this study, bacterial communities in the sediments of an urban artificial river were profiled by sequencing the 16S rRNA V3-V4 region. The samples collected from the eastern side of the Jiusha River were designated as the JHE group and were marked by persistent urban sewage discharges. The samples collected on the western side of the Jiusha River were categorized as the JHW group for comparative analysis. Results: The calculated alpha diversity indices indicated that the bacterial community in the JHW group exhibited greater species diversity and evenness than that of the JHE group. Proteobacteria was the most dominant phylum between the two groups, followed by Bacteroidota. The relative abundance of Proteobacteria and Bacteroidota accumulated in the JHE group was higher than in the JHW group. Therefore, the estimated biomarkers in the JHE group were divided evenly between Proteobacteria and Bacteroidota, whereas the biomarkers in the JHW group mainly belonged to Proteobacteria. The Sulfuricurvum, MND1, and Thiobacillus genus were the major contributors to differences between the two groups. In contrast to JHW, JHE exhibited higher enzyme abundances related to hydrolases, oxidoreductases, and transferases, along with a prevalence of pathways associated with carbohydrate, energy, and amino acid metabolisms. Our study highlights the impact of human-induced water pollution on microorganisms in urban environments.

Lung carcinoma with diffuse cysts repeatedly misdiagnosed as pulmonary infections and lymphoid interstitial pneumonia: A case report.

INTRODUCTION: Diffuse cystic lung diseases comprise a heterogeneous group of pulmonary disorders, with most cases being benign and malignant instances being rare. CASE REPORT: We present an unusual case of lung adenocarcinoma characterized by the progressive diffusion of cystic lesions. The patient, initially diagnosed with a pulmonary infection and lymphoid interstitial pneumonia, underwent repeated misdiagnoses. Ultimately, the diagnosis was confirmed using radial endobronchial ultrasound-guided-transbronchial cryobiopsy (rEBUS-TBCB). A 44-year-old male was admitted to the hospital with a persistent cough and expectoration of bloody sputum for over 6 months. Thoracic computed tomography revealed widespread cystic lesions and nodules. Despite multiple misdiagnoses, rEBUS-TBCB successfully confirmed the presence of lung adenocarcinoma and identified an echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) E13:A20 gene rearrangement. The patient was subsequently transferred to a local hospital for oral targeted drug therapy, which resulted in a favorable response. CONCLUSION: In conclusions, transbronchial lung biopsies often provide inadequate specimens for confirming diffuse cystic lung diseases. In contrast, the utilization of rEBUS-guided TBCB offers superior diagnostic capabilities, as it enables the collection of larger lung biopsies with higher diagnostic yields and fewer complications compared to surgical lung biopsy.

Re-UNet: a novel multi-scale reverse U-shape network architecture for low-dose CT image reconstruction.

In recent years, the growing awareness of public health has brought attention to low-dose computed tomography (LDCT) scans. However, the CT image generated in this way contains a lot of noise or artifacts, which make increasing researchers to investigate methods to enhance image quality. The advancement of deep learning technology has provided researchers with novel approaches to enhance the quality of LDCT images. In the past, numerous studies based on convolutional neural networks (CNN) have yielded remarkable results in LDCT image reconstruction. Nonetheless, they all tend to continue to design new networks based on the fixed network architecture of UNet shape, which also leads to more and more complex networks. In this paper, we proposed a novel network model with a reverse U-shape architecture for the noise reduction in the LDCT image reconstruction task. In the model, we further designed a novel multi-scale feature extractor and edge enhancement module that yields a positive impact on CT images to exhibit strong structural characteristics. Evaluated on a public dataset, the experimental results demonstrate that the proposed model outperforms the compared algorithms based on traditional U-shaped architecture in terms of preserving texture details and reducing noise, as demonstrated by achieving the highest PSNR, SSIM and RMSE value. This study may shed light on the reverse U-shaped network architecture for CT image reconstruction, and could investigate the potential on other medical image processing.

Recombinant Slit2 attenuates tracheal fibroblast activation in benign central airway obstruction by inhibiting the TGF-ß1/Smad3 signaling pathway.

Airway fibrosis is among the pathological manifestations of benign central airway obstruction noted in the absence of effective treatments and requires new drug targets to be developed. Slit guidance ligand 2-roundabout guidance receptor 1 (Slit2-Robo1) is involved in fibrosis and organ development. However, its significance in airway fibrosis has not yet been reported. The study explored how the recombinant protein Slit2 functions in transforming growth factor-ß1 (TGF-ß1)-mediated airway fibrosis in vivo and in vitro. In this study, Slit2 expression initially increased in the tracheal granulation tissues of patients with tracheobronchial stenosis but decreased in the fibrotic tissue. In primary rat tracheal fibroblasts (RTFs), recombinant Slit2 inhibited the expression of extracellular matrices such as Timp1, α-SMA, and COL1A2, whereas recombinant TGF-ß1 promoted the expression of Robo1, α-SMA, and COL1A2. Slit2 and TGF-ß1 played a mutual inhibitory role in RTFs. Slit2 supplementation and Robo1 downregulation inhibited excessive extracellular matrix (ECM) deposition induced by TGF-ß1 in RTFs via the TGF-ß1/Smad3 pathway. Ultimately, exogenous Slit2 and Robo1 knockdown-mediated attenuation of airway fibrosis were validated in a trauma-induced rat airway obstruction model. These findings demonstrate that recombinant Slit2 alleviated pathologic tracheobronchial healing by attenuating excessive ECM deposition. Slit2-Robo1 is an attractive target for further exploring the mechanisms and treatment of benign central airway obstruction.

Advanced navigation technology enables endobronchial brachytherapy for peripheral lung cancer: An old technique plays a new role.

PURPOSE: To investigate the feasibility of super-selectively endobronchial brachytherapy in the treatment of peripheral lung cancer guided by advanced navigation technology. METHODS AND MATERIALS: Six patients with peripheral lung tumors successfully underwent treatment with super-selectively endobronchial brachytherapy guided by advanced navigation technology following pathway planning and were subsequently followed up to assess survival and treatment-related toxicities. RESULTS: The endobronchial applicators were successfully placed inside the tumors of all patients using advanced navigation techniques according to the pretreatment plan, and brachytherapy was delivered at curative doses after evaluation using radiotherapy planning software. None of the patients showed local progression of the treated lesions during the follow-up for a duration ranging from 11 months to 35 months, with a median follow-up time of 23 months. The patient with the longest follow-up, nearly 3 years, exhibited a stable condition. After undergoing endobronchial brachytherapy, patients predominantly experienced localized fibrosis as indicated. No significant alterations in cardiopulmonary function were detected during the follow-up, and no other adverse effects were found. CONCLUSIONS: The use of endobronchial brachytherapy for the curative treatment of peripheral lung cancers is feasible. Furthermore, the development of novel bronchial navigation techniques has the potential to broaden the application of endobronchial brachytherapy.

Endobronchial optical coherence tomography helps to estimate the cartilage damage of the central airway in TBTB patients.

Purpose: At present, there are few examination methods used to evaluate tracheobronchial cartilage damage. In our study, we explored whether endobronchial optical coherence tomography (EB-OCT) can be used to estimate central airway cartilage damage in tracheobronchial tuberculosis (TBTB) patients. Methods: In our study, we used the OCTICS Imaging system to perform EB-OCT scanning for TBTB patients. The thickness of the central airway wall and cartilage was measured by the OCTICS software system workstation. Results: There were 102 TBTB patients included in our study cohort. Their EB-OCT images of the central airway cartilage showed that abnormal cartilage manifests as thinning of the cartilage, cartilage damage, cartilage destruction, and even cartilage deficiency. The cartilage morphology becomes irregular and discontinuous. Some parts of the cartilage become brighter in grayscale. The intima of the cartilage is thickened and discontinuous, and the boundary with submucosa and mucosa is unclear. Conclusion: Our study conducted EB-OCT examination of the central airway cartilage of TBTB patients in vivo for the first time. EB-OCT helps to estimate the cartilage damage of the central airway in TBTB patients to some extent.

[Theory and application of pulse diagnosis at Renying and Cunkou regions].

Renying and Cunkou pulse diagnostic method is one of the important parts of the pulse diagnosis in Huangdi Neijing (Inner Canon of Yellow Emperor) and has been controversial since its proposal. This article takes WANG Shu-he's diagnostic operation as the evidence, and is in reference of the statement, "Cun region (the region ahead of Guan region of Cunkou) determines the human life, that on the left hand refers to Renying, while on the right hand is Qikou". The pulse conditions on the left and right hands represent yin and yang. If Renying pulse on the left is greater, the diseases are in yang meridians, while if Cunkou pulse on the right is bustling, the diseases are in yin meridians. By comparing the pulse condition and strength, as well as the pulse beating (rapid and urgent) between Guan region and region ahead of Guan on the same side, the conditions of three yang and three yin meridians are detected. In treatment, based on the records of Renying and Cunkou pulse diagnosis in Huangdi Neijing, the principles are proposed for reinforcing and reducing methods on hand and foot meridians of yin and yang. Five-shu points and yuan-source points are taken as the main acupoints in acupuncture treatment. During treatment, the changes in pulse conditions should be emphasized specifically and those at Renying and Cunkou regions are the criteria for judging qi arrival and qi regulation.

Azvudine and mortality in patients with coronavirus disease 2019: A retrospective cohort study.

OBJECTIVES: Several studies have found that azvudine (FNC) can inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication both in vivo and in vitro. However, the effect of FNC on the risk of death in patients with coronavirus disease 2019 (COVID-19) is unclear. This study aims to investigate the effect of FNC on the risk of death in patients with coronavirus disease 2019 (COVID-19). METHODS: Charts of consecutive patients hospitalized at five hospitals in Chongqing with confirmed COVID-19. The primary outcome of the study was 28-day mortality. Secondary outcomes were: ICU admission rates, length of hospital and ICU stay, and also the range of mechanical ventilation days when admission. We compared primary outcome in patients who received FNC with those in patients who did not, using a multivariable model with inverse probability weighting according to the propensity score. RESULTS: We included 1,110 patients in our study cohort. Of the 236 patients treated with FNC, 30 died within 28 days (12.7%), and of the 874 patients not treated with FNC, 206 died within 28 days (23.6%). In the crude, unadjusted analysis, a significant beneficial effect of FNC in terms of the 28-day mortality (OR 0.472, 95% CI 0.312-0.714; p < 0.001) in the overall population was detected. The adjusted odds ratio by multivariate analysis was (OR 0.498, 95% CI 0.287-0.864; p = 0.013). In the multivariate analysis with inverse probability weighting according to the propensity score, a significantly beneficial effect of FNC in terms of the 28-day mortality was further confirmed (OR 0.754, 95% CI 0.614-0.925; p = 0.007). Moreover, multivariable propensity-score analyses with matching also yielded similar results (OR 0.438, 95% CI 0.246-0.778; p = 0.005). CONCLUSION: Our results reveal that in patients with COVID-19, FNC administration was associated with a significantly reduced 28-day mortality.

GATA6 promotes fibrotic repair of tracheal injury through NLRP3 inflammasome-mediated epithelial pyroptosis.

Tracheal injury is a challenging emergency condition that is characterized by the abnormal repair of the trachea. GATA6, a well-established transcription factor, plays a crucial role in tissue injury and epithelial regenerative repair. This study aims to evaluate the role of GATA6 in NF-κB-mediated NLRP3 inflammasome activation and pyroptosis after tracheal injury. Tracheal tissues and serum samples were collected from clinical patients and a rat model of tracheal injury. Upon GATA6 knockdown or overexpression, BEAS-2B and rat tracheal epithelial (RTE) cells were treated with lipopolysaccharides and nigericin before being co-cultured with primary tracheal fibroblasts. The changes of NLRP3 inflammasome activation and pyroptosis and their underlying mechanisms were detected. Additionally, the role of GATA6 downregulation in tracheal injury was verified in rats. GATA6 expression and NLRP3 inflammasome activation were upregulated following tracheal injury in the epithelium of granulation tissues. GATA6 silencing inhibited NLRP3 priming, NLRP3 inflammasome activation, and pyroptosis in BEAS-2B and RTE cells. Mechanistically, GATA6 was determined to have bound to the promoter region of NLRP3 and synergistically upregulated NLRP3 promoter activity with NF-κB. Furthermore, GATA6 overexpression promoted epithelial-mesenchymal transition via modulating the NF-κB/NLRP3 pathway. Epithelial NLRP3 inflammasome activation triggered ECM production in fibroblasts, which was suppressed by GATA6 knockdown and induced by GATA6 overexpression. Finally, the downregulation of GATA6 alleviated NLRP3 inflammasome-mediated pyroptosis induced by tracheal injury in rats, thereby reducing tracheal stenosis, inflammation, and fibrosis. GATA6 promotes fibrotic repair in tracheal injury through NLRP3 inflammasome-mediated epithelial pyroptosis, making it a potential biological therapeutic target for tracheal injury.

IL-11 drives the phenotypic transformation of tracheal epithelial cells and fibroblasts to enhance abnormal repair after tracheal injury.

Tracheal stenosis (TS) is a multifactorial and heterogeneous disease that can easily lead to respiratory failure and even death. Interleukin-11 (IL-11) has recently received increased attention as a fibrogenic factor, but its function in TS is uncertain. This study aimed to investigate the role of IL-11 in TS regulation based on clinical samples from patients with TS and a rat model of TS produced by nylon brush scraping. Using lentiviral vectors expressing shRNA (lentivirus-shRNA) targeting the IL-11 receptor (IL-11Rα), we lowered IL-11Rα levels in the rat trachea. Histological and immunostaining methods were used to evaluate the effects of IL-11Rα knockdown on tracheal injury, molecular phenotype, and fibrosis in TS rats. We show that IL-11 was significantly elevated in circulating serum and granulation tissue in patients with TS. In vitro, TGFß1 dose-dependently stimulated IL-11 secretion from human tracheal epithelial cells (Beas-2b) and primary rat tracheal fibroblasts (PRTF). IL-11 transformed the epithelial cell phenotype to the mesenchymal cell phenotype by activating the ß-catenin pathway. Furthermore, IL-11 activated the atypical ERK signaling pathway, stimulated fibroblasts proliferation, and transformed fibroblasts into alpha-smooth muscle actin (α-SMA) positive myofibroblasts. IL-11-neutralizing antibodies (IL-11NAb) or ERK inhibitors (U0126) inhibited IL-11 activity and downregulated fibrotic responses involving TGFß/SMAD signaling. In vivo, IL-11Rα knockdown rats showed unobstructed tracheal lumen, relatively intact epithelial structure, and significantly reduced granulation tissue proliferation and collagen fiber deposition. Our findings confirm that IL-11 may be a target for future drug prevention and treatment of tracheal stenosis.

Characteristics analysis of 157 cases of central airway stenosis due to tracheobronchial tuberculosis: A descriptive study.

Background: Tracheobronchial stenosis, particularly central airway stenosis, which frequently results in severe complications such as lung damage, occurs in patients with tracheobronchial tuberculosis (TBTB). Objectives: To analyze the clinical characteristics of patients with central airway stenosis due to tuberculosis (CASTB). Methods: Retrospective analysis was performed on the clinical features, radiological features, bronchoscopic features and treatment of 157 patients who were diagnosed with CASTB in two tertiary hospitals in Chongqing, China, from May 2020 to May 2022. Results: CASTB mostly occurs in young patients and females. Patients with CASTB exhibited different symptoms repeatedly during the disease, especially varying degrees of dyspnea, prompting many patients to undergo bronchoscopic intervention and even surgery. Patients with cicatricial strictures constituted the highest proportion of the TBTB subtype with CASTB and 35.7% of the patients with CASTB were found to have tracheobronchomalacia (TBM) under bronchoscopy. CASTB and TBM mainly involved the left main bronchus. Patients with lower levels of education had higher rates of TBM. Patients with TBM manifested shortness of breath more frequently than patients without TBM. Patients with TBTB who had undergone bronchoscopic interventions have a higher rate of TBM. Conclusions: Despite mostly adequate anti-tuberculosis chemotherapy, patients with TBTB can present with CASTB involving severe scarring stenosis, bronchial occlusion, tracheobronchomalacia and even destroyed lung.

GATA6 triggers fibroblast activation and tracheal fibrosis through the Wnt/ß-catenin pathway.

Tracheal fibrosis is a key abnormal repair process leading to fatal stenosis, characterized by excessive fibroblast activation and extracellular matrix (ECM) deposition. GATA6, a zinc finger-containing transcription factor, is involved in fibroblast activation, while its role in tracheal fibrosis remains obscure. The present study investigated the potential role of GATA6 as a novel regulator of tracheal fibrosis. It was found that GATA6 and α-smooth muscle actin (α-SMA) were obviously increased in tracheal fibrotic granulations and in TGFß1-treated primary tracheal fibroblasts. GATA6 silencing inhibited TGFß1-stimulated fibroblast proliferation and ECM synthesis, promoted cell apoptosis, and inactivated Wnt/ß-catenin pathway, whereas GATA6 overexpression showed the reverse effects. SKL2001, an agonist of Wnt/ß-catenin signaling, restored collagen1a1 and α-SMA expression which was suppressed by GATA6 silencing. Furthermore, in vivo, knockdown of GATA6 ameliorated tracheal fibrosis, as manifested by reduced tracheal stenosis and ECM deposition. GATA6 inhibition in rat tracheas also impaired granulation proliferation, increased apoptosis, and inactivated Wnt/ß-catenin pathway. In conclusion, our findings indicate that GATA6 triggers fibroblast activation, cell proliferation, and apoptosis resistance in tracheal fibrosis via the Wnt/ß-catenin signaling pathway. Targeting GATA6 may represent a promising therapeutic approach for tracheal fibrosis.

Asymmetric spillover between economic policy uncertainty and exchange rate volatility: A global network connectedness perspective.

This study employs the network connectedness approach to examine the risk spillover between the economic policy uncertainty (EPU) and exchange rate volatility (ERV) of 21 countries. Using monthly data from January 1997 to August 2022, we find that the spillover effect of ERV on EPU is greater than that of the inverse. In addition, the spillover effect of EPU on ERV is mainly concentrated in the foreign exchange markets of developing countries. This finding indicates that the foreign exchange markets of developing countries are more susceptible to shocks of global economic risk, and the spreading of risk contagion between EPU and ERV mainly follows the pathway "increase in global ERV → rising global EPU → further intensified volatility in the foreign exchange markets of developing countries." A rolling-window analysis shows that the spillover between global EPU and ERV is time-varying. The cross-market spillovers between EPU and ERV in the post-crisis period continued to rise and further increased sharply after the outbreak of the COVID-19 pandemic.

Multiresolution Discriminative Mixup Network for Fine-Grained Visual Categorization.

Fine-grained visual categorization (FGVC) is a challenging task because there are many hard examples existing between fine-grained classes which differ subtly in particular local regions. To address this issue, many methods have recourse to high-resolution source images and others adopt effective regularization like "mixup" or "between class learning." Despite their promising achievements, mixup tends to cause the manifold intrusion problem which would result in under-fitting and degradation of the model performance and high-resolution input inevitably leads to high computational costs. In view of this, we present a multiresolution discriminative mixup network (MRDMN). Different from standard mixup, the proposed discriminative mixup strategy mixes discriminative regions linearly instead of entire images to avoid manifold intrusion, which makes it learn the local detail features more effectively and contributes to more precise categorization. Furthermore, an innovative resolution-based distillation strategy is designed to transfer the multiresolution detail feature representations to a low-resolution network, which speeds up the testing and boosts the categorization accuracy simultaneously. Extensive experiments demonstrate that our proposed MRDMN remarkably outperforms most competitive approaches with less computation time on the CUB-200-2011, Stanford-Cars, Stanford-Dogs, Food-101, and iNaturalist 2017 datasets. The codes are in https://github.com/aztc/MRDMN.

Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting ß2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD. METHODS: Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke. RESULTS: A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% versus 1.3%; relative risk 1.42, 95% CI 1.11-1.81) and triple therapy (1.6% versus 1.4%; relative risk 1.29, 95% CI 1.03-1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power. CONCLUSION: Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.

Management of stent-related tracheoesophageal fistula in complex post-tuberculosis tracheobronchial stenosis: A case report.

Background: The covered self-expandable metallic stents (SEMS) have been used to manage benign tracheobronchial stenosis, especially the complex post-tuberculosis (TB) tracheobronchial stenosis (PTTS) with cartilage destruction or malacia. This procedure could lead to stent-related tracheoesophageal fistula (TEF). Case presentation: A 21-year-old woman, who had one covered Y-shaped SEMS inserted to manage complex PTTS 2 years ago, presented with dyspnea and frequent coughing on drinking water. The bronchoscopy confirmed extensive granulation tissue hyperplasia and a TEF on the upper edge of the covered SEMS. The covered SEMS was removed in three steps, and another fully covered Y-shape SEMS (Microtech Co., Ltd., Nanjing, China) was inserted to restore patency in the tracheobronchial tree and occlude the TEF orifice. Recombinant bovine basic fibroblast growth factor (rbFGF) (6,000 IU/time) was sprayed into and around the fistula through the V-System single-use cannula via the flexible bronchoscope every other week. The patient showed sustained clinical and radiographic improvement, and the TEF healed. Conclusion: We presented a three-step bronchoscopic approach to managing a stent-related TEF in a patient with complex PTTS. Subsequently, regular bronchoscopic debridement of granulation tissue developing on the upper edge of SEMS is necessary to maintain the stent patency and reduce the risk of recurrent stent-related TEF. A fully covered SEMS associated with the local administration of rbFGF seems to offer an alternative simplified one-stage procedure for the temporary management of TEF combined with complex PTTS in non-surgical candidates.

GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts.

Benign tracheobronchial stenosis (BTS) is a fatal and incurable disease. Epithelial repair and matrix reconstruction play an important role in the wound repair process. If the interstitial context is not restored and stabilized in time, it can lead to pathological fibrosis. Here we attempted to identify cytokines that are involved in promoting wound repair. Growth differentiation factor 15 (GDF15) is a cytokine secreted by tracheal epithelial cells, which is indispensable for the growth of epithelial cells and inhibits the overgrowth of fibroblasts. GDF15 can counteract transforming growth factor-ß (TGFß1) stimulation of epithelial-mesenchymal transition (EMT) in tracheal epithelial cells and inhibit fibroblast activation via the TGFß1-SMAD2/3 pathway. In a rat model of tracheal stenosis, GDF15 supplementation alleviated the degree of tracheal stenosis. These results suggest that GDF15 prevents fibroblast hyperactivation and promotes epithelial repair in injured trachea. GDF15 may be a potential therapy to improve benign tracheobronchial stenosis.

Knockdown of SOX9 alleviates tracheal fibrosis through the Wnt/ß-catenin signaling pathway.

Trachealfibrosis is an important cause of tracheal stenosis without effective treatments, and new drug targets need to be developed. The role of SOX9 in the injury and repair of the trachea is unknown; this study aims to investigate the role of SOX9 in the regulation of tracheal fibrosis based on clinical samples from patients with tracheal injury and a model of tracheal fibrosis produced by tracheal brushing in rats. The results showed that the expressions of SOX9 and mesenchymal and ECM-related indicators were increased in the injury and fibrosis of the trachea in patients and rats. Serum SOX9 levels exhibited a sensitivity of 83.87% and specificity of 90% in distinguishing patients with tracheal fibrosis from healthy volunteers when the cut­off value was 13.24 ng/ml. Knockdown SOX9 can markedly inhibit granulation tissue proliferation, reduce inflammation and ECM deposition, promote epithelial regeneration and granulation tissue apoptosis, and attenuate the tracheal fibrosis after injury. Additionally, RNA sequencing showed that the proliferation, migration, and ECM deposition of tracheal granulation tissue were related to the activation of Wnt pathway, activation of the ß-catenin, and p-GSK3ß after injury can be inhibited by the knockdown of SOX9. In summary, SOX9 is upregulated in tracheas fibrosis and may be a novel factor to promote tracheal fibrosis progression. Inhibiting SOX9 may be used to prevent and treat tracheal fibrosis in the future. KEY MESSAGE : The expression of SOX9 is upregulated the process of injury and repair of the tracheal fibrosis. Knocking down SOX9 can attenuate tracheal fibrosis after injury by inhibiting inflammation response, granulation tissue proliferation, ECM deposition, and promoting granulation tissue apoptosis. The Wnt/ß-catenin-SOX9 axis is activated during tracheal injury and fibrosis, and inhibition of SOX9 can partially alleviate tracheal fibrosis. SOX9 may act as a new diagnostic and therapeutic target in patients with tracheal fibrosis in the future.