miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.

Benign airway stenosis (BAS) means airway stenosis or obstruction that results from a variety of non-malignant factors, including tuberculosis, trauma, benign tumors, etc. In consideration of the currently limited research on microRNAs in BAS, this study aimed to explore the role and mechanism of miR-34c-5p in BAS. The expression of miR-34c-5p in BAS granulation tissues showed a significant down-regulation compared with the normal control group. Moreover, miR-34c-5p mimics suppressed the proliferation and differentiation of human bronchial fibroblasts (HBFs) and the epithelial-mesenchymal transition (EMT) of human bronchial epithelial cells (HBE). Conversely, miR-34c-5p inhibitors aggravated those effects. A dual-luciferase reporter assay confirmed that miR-34c-5p can target MDMX rather than Notch1. The over-expression of MDMX can reverse the inhibiting effect of miR-34c-5p on HBFs proliferation, differentiation and EMT. Furthermore, the expressions of tumor protein (p53) and PTEN were down-regulated following the over-expression of MDMX. In addition, the expressions of PI3K and AKT showed an up-regulation. In conclusion, miR-34c-5p was down-regulated in BAS and may inhibit fibroblast proliferation differentiation and EMT in BAS via the MDMX/p53 signaling axis. These findings expand the understanding of the role of miR-34c-5p and will help develop new treatment strategies for BAS.

Safety and efficacy of a novel transbronchial radiofrequency ablation system for lung tumours: One year follow-up from the first multi-centre large-scale clinical trial (BRONC-RFII).

BACKGROUND AND OBJECTIVE: Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi-centre, large-scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours. METHODS: The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1-year survival rates, were evaluated. RESULTS: This study included 126 patients (age range: 23-85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12-month follow-up, the complete ablation rate and intrapulmonary progression-free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground-glass nodules (GGNs) were superior to those of the patients with solid nodules (12-month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow-up period. CONCLUSION: Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs.

Social participation in older people with hearing impairment in Chinese community: A latent profile analysis.

OBJECTIVES: Hearing impairment may lead to increased communication difficulties for older people, making their social participation less optimistic. However, there is little research on the social participation of older people with hearing impairment, especially based on the characteristics of their social participation. This study aimed to identify different social participation profiles in older people with hearing impairment and to explore sociodemographic characteristics, disease-related characteristics and psychosocial factors with different social participation profiles. METHODS: A cross-sectional study of 300 older people with hearing impairment using the sociodemographic questionnaire, the Impact on Participation and Autonomy Questionnaire, the Lubben Social Network Scale-6, Medical Outcomes Study Social Support Survey and Geriatric Depression Scale-15 from May to August 2023 in a community of Beijing, China. Latent profile analysis was used to analyse the latent profiles of social participation in elderly with hearing impairment. Multiple logistic regression was used to explore the predictors of different profiles. RESULTS: The social participation of older people with hearing impairment in the community can be classified into three potential profiles: Profile 1 - high social participation group (76.05 %), Profile 2 - moderate social participation group (17.34 %), Profile 3 - low social participation group (6.61 %). Age, types of chronic diseases, self-reported health, severity of hearing impairment, social network, social support and depression were predictors of different profiles. CONCLUSIONS: Nurses should pay attention to the characteristics, depression, social network and support of older people with different hearing impairment to improve social participation in different profiles. IMPLICATIONS AND RECOMMENDATIONS: This was the first study exploring latent profiles of social participation in older people with hearing impairment. Insights from this study are useful for gerontological nursing to distinguish different profiles and further identify the characteristics of different profiles in older people with hearing impairment by characterizing the level of social participation in the community and better implement interventions according to profiles.

Social network and related factors in older people with sensory impairment in the community: Using principal component analysis.

AIM: Older people with sensory impairment are more likely to have smaller and weaker social network due to their reduced ability, which lowers their quality of life. However, there is little research on the social network in older people with sensory impairment, especially the related factors. The aim of the study was to explore the related factors of social network and to provide evidence for the improvement of social network to promote successful aging in older people with sensory impairment. METHODS: A cross-sectional study was conducted among 374 participants for hearing and vision assessment and questionnaire survey in a community, Beijing. Data were collected and analyzed by principal component analysis (PCA) and multiple logistic regression using IBM SPSS 25.0 software. RESULTS: PCA showed that there were six risk factors whose eigenvalues >1 were extracted, with a total variance of 56.555%. Multiple logistic regression analysis of principal component indicated that five factors including physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor, were statistically significant (p < 0.05). CONCLUSIONS: The social network of older people with sensory impairment is relatively poor. Physical health factor, social interaction factor, psychological status factor, lifestyle factor, and family condition factor may be related factors. Medical staff should pay attention to physical, psychological and social characteristics of older people, especially with sensory impairment, to carry out necessary measures to improve social network and avoid social isolation.

Disruption of the CCDC43-FHL1 interaction triggers apoptosis in gastric cancer cells.

The coiled-coil domain-containing protein 43 (CCDC43) is essential to promote gastric cancer (GC) proliferation and invasion, while four and a half LIM domains 1 (FHL1) involves GC cells apoptosis. We attempted to address inter-relationship between CCDC43 and FHL1 in modulating GC cells growth and apoptosis. Levels of protein expression were assessed by western blot, immunofluorescence. Using EdU, plate colony formation, Matrigel invasion and animal models, we evaluated the function in vitro and in vivo. Apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. Reciprocal co-immunoprecipitation (co-IP) analyses indicated that CCDC43 physically interacted with FHL1. The expression of CCDC43 was negatively correlated with FHL1. Moreover, up-regulation of CCDC43 resulted in FHL1 level decline, and the reverse is also true. CCDC43 expressed jointly with FHL1 group significantly decreases the ability of the growth, metastasis and invasion of GC cells compared with that of the CCDC43 group. Furthermore, siRNA-mediated repression of CCDC43 results in dissociation from FHL1 and causes suppression of GC cell proliferation and metastasis. CCDC43 repression mediates the stability of FHL1 protein. In addition, CCDC43 interacts with FHL1. Knockdown of CCDC43 plus FHL1 overexpression inhibits proliferation and migration and induces apoptosis of GC cells in vitro and vivo.

Genomic analysis provides insights into the transmission and pathogenicity of Talaromyces marneffei.

Talaromyces marneffei (T. marneffei) is a medically important opportunistic dimorphic fungus that infects both humans and bamboo rats. However, the mechanisms of transmission and pathogenicity of T. marneffei are poorly understood. In our study, we combined Illumina and PacBio sequencing technologies to sequence and assemble a complete genome of T. marneffei. To elucidate the transmission route and source, we sequenced three additional T. marneffei isolates using Illumina sequencing technology. Variations among isolates were used to develop a multilocus sequence typing (MLST) system comprising five housekeeping genes that can be used to discriminate between isolates derived from different sources. Our analysis revealed that human and bamboo rat share identical genotypes in these five loci. Thus, we hypothesized that T. marneffei is transmitted to humans through inhalation of spores in the surrounding environment into the lungs and that the bamboo rat can serve as an important natural reservoir for pathogens. Furthermore, we also identified temperature-dependent polyketide synthases, non-ribosomal peptide synthetases and secreted proteins as putative pathogenicity-related factors. In addition, we identified antifungal drug targets that can be investigated in future studies to elucidate the mechanisms underlying drug resistance. In summary, our study presents the basic features of the T. marneffei genome and provides insights into the transmission and pathogenicity of T. marneffei, which warrant fundamental experimental research.

Enhanced activation of circulating plasmacytoid dendritic cells in patients with Chronic Obstructive Pulmonary Disease and experimental smoking-induced emphysema.

Plasmacytoid dendritic cells (pDCs) are key cells bridging the innate with adaptive immunity. However, the phenotypic characteristics of circulating pDCs and its role in smoking related-Chronic Obstructive Pulmonary Disease (COPD) remain largely unknown. The aim of this study was analyzed the phenotype of circulating pDCs and the expression of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells in patients with COPD by using multi-colour flow cytometry. The cytokine profiles in peripheral blood from all subjects were measured by ELISA. The influence of cigarette smoke on pDCs was evaluated in an experimental mouse model of emphysema. Circulating pDCs in patients with COPD and in mice exposed to cigarette smoke expressed high levels of co-stimulatory molecules CD40 or CD86 accompanied by exaggerated IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells. In vitro, cigarette smoke directly promoted pDCs maturation and release of IFN-α, IL-6 and IL-12, subsequently inducing differentiation of IFN-γ producing CD8+T cells and IL-17-producing CD8+T cells from mouse naïve CD8+T cells. These data suggested that circulating pDCs display an enhanced activation phenotype in patients with COPD and in experimental smoking mouse model of emphysema, which might contribute to exaggerated IFN-γ producing CD8+T and IL-17-producing CD8+T cell-mediated immune responses.

Snail/FOXK1/Cyr61 Signaling Axis Regulates the Epithelial-Mesenchymal Transition and Metastasis in Colorectal Cancer.

BACKGROUND/AIMS: Metastasis is the primary cause of colorectal cancer (CRC)-related death. However, the molecular mechanisms underlying metastasis in CRC remain unclear. METHODS: We evaluated mRNA and protein expression levels by quantitative real-time reverse transcription PCR, western blotting, immunofluorescence, tissue microarrays, and immunohistochemistry assays. We also assessed the migration and invasion abilities of CRC cells in vitro by wound healing assays, invasion and migration assays, western blot analysis, and immunofluorescence. Tumor metastasis was evaluated in nude mice in vivo. RESULTS: A positive correlation was observed between the expression patterns of Forkhead box k1 (FOXK1) and Snail in CRC. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Snail directly bound to and activated the human FOXK1 gene promoter. Moreover, the Snail-FOXK1 axis promote epithelial mesenchymal transition (EMT)-mediated CRC cell invasion and metastasis. FOXK1 and Snail expression levels were correlated with tumor progression and served as significant predictors of overall survival in patients with CRC. Furthermore, overexpression of FOXK1 induced the EMT by upregulating the expression of cysteine-rich angiogenic inducer 61 (Cyr61). Luciferase assays showed that Cyr61 was a direct transcriptional target of FOXK1. Down regulation of Cyr61 decreased FOXK1-enhanced "CRC cell" migration, invasion, and metastasis. Additionally, FOXK1 expression was positively correlated with Cyr61 expression and was associated with poor prognosis. CONCLUSIONS: The Snail/FOXK1/Cyr61 signaling axis regulates the EMT and metastasis of CRC.

The FOXK1-CCDC43 Axis Promotes the Invasion and Metastasis of Colorectal Cancer Cells.

BACKGROUND/AIMS: The CCDC43 gene is conserved in human, rhesus monkey, mouse and zebrafish. Bioinformatics studies have demonstrated the abnormal expression of CCDC43 gene in colorectal cancer (CRC). However, the role and molecular mechanism of CCDC43 in CRC remain unknown. METHODS: The functional role of CCDC43 and FOXK1 in epithelial-mesenchymal transition (EMT) was determined using immunohistochemistry, flow cytometry, western blot, EdU incorporation, luciferase, chromatin Immunoprecipitation (ChIP) and cell invasion assays. RESULTS: The CCDC43 gene was overexpressed in human CRC. High expression of CCDC43 protein was associated with tumor progression and poor prognosis in patients with CRC. Moreover, the induction of EMT by CCDC43 occurred through TGF-ß signaling. Furthermore, a positive correlation between the expression patterns of CCDC43 and FOXK1 was observed in CRC cells. Promoter assays demonstrated that FOXK1 directly bound and activated the human CCDC43 gene promoter. In addition, CCDC43 was necessary for FOXK1- mediated EMT and metastasis in vitro and vivo. Taken together, this work identified that CCDC43 promoted EMT and was a direct transcriptional target of FOXK1 in CRC cells. CONCLUSION: FOXK1-CCDC43 axis might be helpful to develop the drugs for the treatment of CRC.

Identification of key genes in human airway epithelial cells in response to respiratory pathogens using microarray analysis.

BACKGROUND: Airway epithelium is the primary target for pathogens. It functions not only as a mechanical barrier, but also as an important sentinel of the innate immune system. However, the interactions and processes between host airway epithelium and pathogens are not fully understood. RESULTS: In this study, we identified responses of the human airway epithelium cells to respiratory pathogen infection. We retrieved three mRNA expression microarray datasets from the Gene Expression Omnibus database, and identified 116 differentially expressed genes common to all three datasets. Gene functional annotations were performed using Gene Ontology and pathway analyses. Using protein-protein interaction network analysis and text mining, we identified a subset of genes functioned as a group and associated with infection, inflammation, tissue adhesion, and receptor internalization in infected epithelial cells. These genes were further identified in BESE-2B cells in response to Talaromyces marneffei by Real-Time quantitative PCR (qRT-PCR). In addition, we performed an in silico prediction of microRNA-target interactions and examined our findings. CONCLUSIONS: Using bioinformatics analysis, we identified several genes that may serve as biomarkers for the diagnosis or the surveillance of early respiratory tract infection, and identified additional genes and miRNAs that warrant further fundamental experimental research.

Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells.

BACKGROUND: Neutrophil extracellular traps (NETs) represent a distinct strategy by which neutrophils trap, confine and eliminate invading microorganisms. Emerging evidence suggests that NETs exert a deleterious effect to the host in the absence of microbial stimuli. However, the role of NETs in smoking-related lung diseases remains to be elucidated. OBJECTIVES: To evaluate the formation of NETs in the context of chronic inflammation induced by cigarette smoking and explore its potential role in an experimental mouse model of emphysema. METHODS: The formation and degradation of NETs in cigarette smoke exposed mice was assessed with a fluorescence microscope. The potential influences of NETs on plasmacytoiddendritic cells were also investigated. RESULTS: NETs were more prone to formation by polymorphonuclearneutrophils but defective in degradation in cigarette smoke exposed mice. Cigarette smoke extract (CSE) served as an important facilitator that triggered neutrophils to undergo NETosis in vitro. Furthermore, CSE-induced NETs were capable of driving plasmacytoiddendritic cell maturation and activation, thereby initiating a T-cell-mediated immune response. CONCLUSIONS: NETs may represent a critical connection between innate and adaptive immune responses under conditions of chronic inflammation induced by cigarette smoke exposure.

Dendritic cells induce Tc1 cell differentiation via the CD40/CD40L pathway in mice after exposure to cigarette smoke.

Dendritic cells and CD8(+) T cells participate in the pathology of chronic obstructive pulmonary disease, including emphysema, but little is known of the involvement of the CD40/CD40L pathway. We investigated the role of the CD40/CD40L pathway in Tc1 cell differentiation induced by dendritic cells in a mouse model of emphysema, and in vitro. C57BL/6J wild-type and CD40(-/-) mice were exposed to cigarette smoke (CS) or not (control), for 24 wk. In vitro experiments involved wild-type and CD40(-/-) dendritic cells treated with CS extract (CSE) or not. Compared with the control groups, the CS mice (both wild type and CD40(-/-)) had a greater percentage of lung dendritic cells and higher levels of major histocompatability complex (MHC) class I molecules and costimulatory molecules CD40 and CD80. Relative to the CS CD40(-/-) mice, the CS wild type showed greater signs of lung damage and Tc1 cell differentiation. In vitro, the CSE-treated wild-type cells evidenced more cytokine release (IL-12/p70) and Tc1 cell differentiation than did the CSE-treated CD40(-/-) cells. Exposure to cigarette smoke increases the percentage of lung dendritic cells and promotes Tc1 cell differentiation via the CD40/CD40L pathway. Blocking the CD40/CD40L pathway may suppress development of emphysema in mice exposed to cigarette smoke.

Combination of erythromycin and dexamethasone improves corticosteroid sensitivity induced by CSE through inhibiting PI3K-δ/Akt pathway and increasing GR expression.

Corticosteroid insensitivity, which is induced by cigarette smoke extract (CSE), is a significant barrier when treating chronic obstructive pulmonary disease (COPD). Erythromycin (EM) has been shown to have an anti-inflammatory role in some chronic airway inflammatory diseases, particularly diffuse panbronchiolitis and cystic fibrosis. Here, we explored whether the combination therapy of EM and dexamethasone (Dex) reverses corticosteroid insensitivity and investigated the molecular mechanism by which this occurs. We demonstrated that the combination of EM and Dex restored corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) from COPD patients and U937 cells after CSE exposure. Moreover, pretreatment with 10, 50, or 100 µg/ml EM reversed the HDAC2 protein reduction induced by CSE exposure in a dose-dependent manner. U937 cells exposed to CSE show a reduction in histone deacetylase (HDAC) activity, which was potently reversed by EM or combination treatment. Although 10 and 17.5% CSE increased phosphorylated Akt (PAkt) expression in a concentration-dependent manner, preapplication of EM and the combination treatment in particular blocked this PAkt increase. Total Akt levels were unaffected by CSE or EM treatments. Furthermore, the combination treatment enhanced glucocorticoid receptor (GR)α expression. Our results demonstrate that the combination therapy of EM and Dex can restore corticosteroid sensitivity through inhibition of the PI3K-δ/Akt pathway and enhancing GRα expression.

Retrospective analysis of 14 cases of disseminated Penicillium marneffei infection with osteolytic lesions.

BACKGROUND: Penicillium marneffei disseminates hematogenously and can infect most organs, though infection leading to osteolysis is extremely rare. We describe the clinical and laboratory features, management, and outcomes of patients with penicilliosis marneffei (PSM) with osteolytic lesions. METHODS: This retrospective study was conducted between January 1, 2003 and May 1, 2014 at the First Affiliated Hospital of Guangxi Medical University. Patients who presented with culture and/or histopathologic proof of disseminated PSM within osteolytic lesions were included. RESULTS: P. marneffei infection was diagnosed in 100 patients (65 HIV-infected and 35 HIV-negative). Fourteen patients, all HIV-negative, (14/35, 40%) had osteolytic lesions. The most common comorbidity was diabetes mellitus, though previous glucocorticoid therapy, ß-thalassemia, breast cancer, and Langerhans cell histiocytosis also occurred. Five patients had no comorbidity. Fever, malaise, ostealgia, weight loss, and anemia were the most common symptoms, followed by cutaneous lesions, lymphadenopathy, hepatosplenomegaly, cough, sputum, and stethalgia. Ostealgia, joint pain, and joint disorders were also recorded. White blood cell and neutrophil counts were increased (mean 22.3 ± 7.4 × 10(9) cells/L; mean 18.84 ± 4.5 × 10(9) cells/L, respectively). The most common sites were the vertebrae, skull and femur, ribs and ilium, though the clavicle, scapula, humerus, and tibia were also involved. Radiography and computed tomography (CT) showed multiple radiolucencies with moth-eaten bone destruction, periosteal proliferation, bone fracture, and surrounding soft-tissue swelling. Emission CT showed significantly increased uptake in many skeletal regions. Positron emission tomography/CT showed generalized lymphadenopathy, bone metabolic activity, and bone destruction. The (18) F-FDG standard uptake value was increased in the entire skeleton (mean 6.16). Twelve patients received antifungal therapy, four of whom died during treatment, and eight recovered, though four of these eight relapsed within 3-24 months. Two patients discontinued treatment because of severe multiple organ failure and died. CONCLUSIONS: Osteolysis is often overlooked in HIV-negative individuals with disseminated P. marneffei infection. However, P. marneffei involving the bone and leading to osteolysis may indicate severe systemic disturbance, and is characterized by a poor prognosis, high recurrence rate, and the need for prolonged antifungal treatment.

Decreased IL-27 Negatively Correlated with Th17 Cells in Non-Small-Cell Lung Cancer Patients.

The presence of Th17 cells and IL-27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL-27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL-27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL-27 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL-27 in the peripheral blood was examined by real-time quantitative polymerase chain reaction (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL-17 and RORγt. IL-27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL-27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.

Treatment of Disseminated Talaromyces marneffei with Tracheal Infection: Two Case Reports.

Talaromyces marneffei infection involving the trachea presents as diffuse irregular nodules that grow on the tracheal lumen and/or rarely present as concurrent severe eosinophilia. Herein, we report two patients without HIV infection whose main tracheal and/or principal bronchi were involved by T. marneffei infection, which manifested as diffuse proliferative nodules. In case 1, the infection primarily affected the main trachea, resulting in structural cartilage damage, tracheal stenosis, and tracheal absence. In case 2, there were diffuse proliferative nodules in the trachea and bronchi with marked eosinophilia. The final diagnosis was made based on a positive culture from bronchiolar lavage fluid, skin, and tracheal polyps. Case 1 was administered antifungal treatment combined with surgery, but relapse occurred during a 3-month follow-up period. Case 2 was treated by intravenous liposomal amphotericin B combined with atomized inhaled liposomal amphotericin B, and he later showed improvement; there was no relapse during the 12-month period of antifungal treatment. Importantly, atomized inhaled amphotericin B antifungal treatment for T. marneffei infection has never been previously reported.

[Lung involvement of 3 cases of idiopathic sweet syndrome and literature review].

OBJECTIVE: To analyze the clinical features of idiopathic sweet's syndrome (SS) that involves the lung. METHODS: A retrospective analysis was carried out on clinical data of 3 cases of patients with idiopathic SS that involves the lung who were admitted in the First Affiliated Hospital of Guangxi Medical University from August 2012 to December 2013. And relevant literatures were reviewed. RESULTS: Among the literatures reported between 1981 and 2014, there were a total of 39 SS cases involving the lung from both home and abroad, where 31 cases were accompanied with other diseases (i.e. blood diseases); the rest 8 cases without comorbidities were diagnosed as idiopathic SS, which were included into the analysis plus the 3 cases of this group. Among 11 cases, 6 cases were male while 5 cases were female, with the average age of 47 years old (25-72 years old). The patients all had the symptoms of fever, cough and dyspnea; painful and red pseudo-blisters rashes, pulmonary rale, hypoxemia and pulmonary exudative shadow. 3 cases had swollen lymph nodes. Rashes appeared before lung involvement in 6 cases while after lung involvement in 5 cases. In 11 cases, white blood cells, neutrophils, ESR and CRP were all significantly increased. Pulmonary CT showed unilateral or bilateral pulmonary invasive exudates and consolidation with pleural reaction. 3 cases showed restrictive ventilatory dysfunction. BAF fluid (9/9 cases) was given priority to neutrophils. Pulmonary pathology (9/9 cases) showed neutrophils-infiltrating interstitial pneumonia or organizing pneumonia, which were in accordance with the rash pathology (11/11 cases). 11 cases all had been misdiagnosed as invalid antibiotic treatment on pneumonia; where 9 cases were healed by glucocorticoid while 2 cases died. CONCLUSIONS: Idiopathic SS involving the lung is rare in clinical, which can appear before or after rash. Idiopathic SS is often misdiagnosed as bacterial pneumonia. Clinical features include the unknown increase of mature neutrophils, fever, dyspnea, and even respiratory failure, lung exudative or consolidation shadows, swollen lymph nodes and red and painful pseudo-blisters rashes. The involved area is often infiltrated by numerous neutrophils. The glucocorticoid has special effects, but easy to relapse, can also cause death.

A case of Penicillium marneffei infection involving the main tracheal structure.

BACKGROUND: Penicillium marneffei is the only dimorphic member of the genus and is an emerging pathogenic fungus that can cause fatal systemic mycosis. Penicillium marneffei disseminates hematogenously to other locations. Penicillium marneffei infection most commonly involves the skin, lungs, and reticuloendothelial system, including the bone, bone marrow, joints, lymph nodes, pericardium, liver, and spleen. Involvement of the mesenteric and central nervous systems has also been reported. Infection involving the trachea has not been previously reported. CASE PRESENTATION: We herein report a previously healthy 28-year-old male farmer from Guangxi Province without HIV who became infected with P. marneffei. The infection primarily affected the trachea, resulting in structural damage to the cartilage, tracheal stenosis, and tracheal absence. The infection also involved the lungs and lymph nodes. After antifungal treatment and surgery, his symptoms, signs, and lung imaging findings showed significant improvement. This is the first such case report. CONCLUSION: Penicillium marneffei infection in normal hosts is characterized by an insidious onset, various clinical manifestations, and common misdiagnosis, leading to high mortality rates. Penicillium marneffei hematogenously disseminates throughout the whole body. This is the first reported case of P. marneffei infection involving the main trachea with subsequent structural damage to the tracheal cartilage, severe tracheostenosis, and tracheal absence.

Treatment of mixed and refractory post-tuberculosis tracheobronchial stenosis with L-shaped silicone stents: case series and a literature review.

The two patients included in the study had mixed and refractory post-tuberculosis tracheobronchial stenosis (PTTS), having experienced unsuccessful interventional therapies such as balloon dilation and V-shaped stent placement before the operation. Following the secure placement of L-shaped silicone stents, examinations with a fiberbronchoscope during the first and third months post-operation revealed a significant reduction in bronchial mucosa inflammation for both patients. Additionally, the opening diameter of the upper and lower branch segments increased, and chest CT scans indicated a noticeable absorption of left pulmonary lesions. Three months post-operation, fiberbronchoscopy confirmed the stable fixation of the stent without any movement. The patients exhibited substantial improvements in pulmonary function, dyspnea index, and blood gas analysis, with no reported adverse complications. After 7 months, a follow-up fiberbronchoscope for one case revealed excellent stent fixation. Simultaneously, the chest CT scan indicated favorable re-expansion. The placement of L-shaped silicone stents proves effective in preventing displacement, alleviating airway stenosis or obstruction, and ensuring the safety and efficacy of PTTS treatment - particularly in cases where V-shaped silicone stent placement has failed. To our knowledge, this is the first study describing the L-shaped silicone stent in two patients with PTTS.

Successful treatment of severe airway narrowing due to tuberculosis using special L-shaped silicone stentsThis article tells the story of two patients who suffered from a complex lung condition called post-tuberculosis tracheobronchial stenosis (PTTS). Imagine your airways - the tubes that carry air to your lungs - getting severely scarred and narrowed due to a past bout with tuberculosis. These two patients had tried previous treatments like balloon dilation (where a small balloon is inflated inside the narrowed airway to widen it) and using V-shaped stents (flexible supports placed in the airway to keep it open), but these methods didn't provide lasting relief. In this innovative approach, doctors used L-shaped silicone stents specifically designed to fit in the affected parts of the patients' airways. After placing these stents, regular checks showed remarkable improvements. The swelling in the airway lining reduced significantly, and the openings leading to the upper and lower parts of the lungs got wider. Chest X-rays (CT scans) even showed that the patient's left lung was healing well. Three months later, the stents stayed firmly in place, and neither patient experienced any problems. Breathing became easier, lung function tests improved, and blood tests showed better oxygen levels. Seven months down the line, one patient continued to do extremely well, with the stent securely fixed and the chest scan showing good lung expansion. This groundbreaking study shows that using L-shaped silicone stents can effectively treat PTTS when other methods fail. Not only do they stay in place, preventing blockages, but they also safely and effectively alleviate narrowing of the airways. It's the first time such L-shaped stents have been used successfully in PTTS patients, offering new hope for those facing similar challenges.

Down-regulation of miR-21-5p by pirfenidone to inhibit fibroblast proliferation in the treatment of acquired tracheal stenosis.

OBJECTIVE: Treatment options for acquired tracheal stenosis (ATS) are limited due to a series of pathophysiological changes including inflammation and cell proliferation. Micro ribonucleic acid-21-5p (miR-21-5p) may promote the excessive proliferation of fibroblasts. However, various types of fibrosis can be prevented with pirfenidone (PFD). Currently, the effect of PFD on miR-21-5p and its biological function has not been clarified. In this study, PFD was evaluated as a potential treatment for ATS by inducing fibroblast proliferation in lipopolysaccharide (LPS)-induced fibroblasts by targeting miR-21-5p. METHODS: For 48 h, 1 g/ml LPS was used to generate fibroblasts in vitro, followed by the separation of cells into four groups: control, PFD, mimic, and mimic + PFD. The Cell Counting Kit-8 (CCK-8) technique was adopted to measure the proliferation of fibroblasts. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) were used to measure the relative expressions of tumor necrosis factor-α (TNF-α), transforming growth factor-ß1 (TGF-ß1), drosophila mothers against decapentaplegic 7 (Smad7) and collagen type I alpha 1(COL1A1) messenger RNA (mRNA) and proteins, respectively. RESULTS: (1) At 0, 24, 48, and 72 h, fibroblast growth was assessed using the CCK-8 method. Compared with the control group, the mimic group showed the highest fibroblast viability, and the PFD group showed the lowest fibroblast viability. However, fibroblast viability increased in the mimic + PFD group but decreased in the mimic one. (2) RT-qPCR and WB showed that the mimic group exhibited a significant up-regulation in the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins but a down-regulation in the relative expression of Smad7 mRNA and protein compared with the control one. In the PFD group, the results were the opposite. Nevertheless, the relative expressions of TNF-α, TGF-ß1, and COL1A1 mRNA and proteins were increased, whereas that of Smad7 mRNA was decreased in the mimic + PFD group. The change was less in the mimic group. CONCLUSION: PFD may have a preventive and curative effect on ATS by inhibiting fibroblast proliferation and the fibrotic process and possibly through down-regulating miR-21-5p and up-regulating Smad7 and its mediated fibrotic and inflammatory responses.