Background:Macrophage-driven inflammation in adipose tissue contributes to chronic intermittent hypoxia (CIH)-induced metabolic disorders, but the underlying mechanisms remain unclear. Adiponectin (Ad), an abundant adipokine secreted by adipocytes, plays a crucial role in insulin sensitivity. We tested the hypothesis that CIH-induced macrophage inflammation requires adipocyte-derived paracrine signals and that Ad attenuates this process. Methods:Using a co-culture approach, we investigated the roles of adipocytes and Ad in CIH-induced macrophage inflammation. Direct co-culture involved physical interaction between iBMDM macrophages and 3T3-L1 adipocytes, while indirect co-culture used adipocyte-conditioned media. After CIH and Ad treatment, inflammatory factor levels in conditioned media were quantified. Statistical significance was set at P < 0.05. Results:CIH did not directly trigger inflammatory factor release from individually cultured iBMDM cells or 3T3-L1 adipocytes. However, CIH significantly increased inflammatory factor release in co-cultured cells. Ad alleviated the pro-inflammatory effect of adipocytes on macrophages under CIH conditions. Conclusion:CIH disrupts adipocyte function and promotes macrophage inflammation via paracrine mechanisms.

Background Airway remodeling is a critical driver of asthma progression and therapeutic resistance; however, treatment strategies that directly target and reverse this process are still lacking. There is growing evidence that tRNA-derived fragments (tRFs) sourced from Traditional Chinese Medicine (TCM) can modulate disease-associated genes and exert therapeutic effects. We specifically focused on Ginkgo biloba (G. biloba) because of its documented use in traditional practices for respiratory ailments and the reported lung-protective activities of its key bioactive components, such as ginkgolides and flavonoids. Yet, the function of G. biloba-derived tRFs in chronic respiratory conditions like asthma remains elusive, presenting a significant knowledge gap. Purpose This study aimed to investigate the therapeutic potential of tRFs from G. biloba in asthma and to elucidate their underlying mechanisms of action. Study Design Key targets involved in airway remodeling were systematically identified and mapped to G. biloba-derived tRFs. Functional validation was subsequently performed using both asthmatic mouse models and airway structural cells. Methods We employed an integrated approach combining multi-sample sequencing, bioinformatics analysis, and experimental validation to identify central mediators of airway remodeling and to pinpoint a core G. biloba-derived tRF. The therapeutic efficacy and mechanistic basis of this tRF were further evaluated in house dust mite (HDM)-induced asthmatic mice, as well as in transforming growth factor beta 1 (TGF-β1)-stimulated bronchial epithelial cells (BECs) and airway smooth muscle cells (ASMCs), with or without tRF treatment. Results Integrated analysis of human clinical samples, public transcriptomic datasets, and an original TCM RNA database identified prostate transmembrane protein, androgen induced 1 (PMEPA1) as a critical regulator of airway remodeling. PMEPA1 was found to exacerbate mitochondrial dysfunction and dysregulate mitophagy in BECs and ASMCs, thereby promoting their transition to pathological phenotypes and perpetuating chronic airway inflammation. A specific G. biloba-derived tRNA fragment, NO.6-tRF-5-1 (abbreviated as tRF_G6), was identified as a potent regulator of PMEPA1. Treatment with tRF_G6 mimics effectively suppressed PMEPA1 expression, which in turn alleviated airway remodeling and inflammation. By attenuating mitochondrial damage and preventing pathological phenotype shifts in airway structural cells, tRF_G6 disrupts the self-sustaining cycle of airway remodeling in asthma. Conclusion Our study reveals that a G. biloba-derived tRNA fragment attenuates asthma by targeting PMEPA1 and restoring mitochondrial function, thereby inhibiting airway remodeling. These results pinpoint PMEPA1 as a novel target and underscore the therapeutic potential of specifically targeting it with G. biloba-derived nucleic acids.

BACKGROUND Irreversible airflow limitation is the hallmark of a progressive respiratory disorder known as chronic obstructive pulmonary disease (COPD). Depression and anxiety are common mental health problems that can happen with COPD and can make the disease worse. However, the extent to which they affect the rate of lung function decline is not yet known. AIM To examine how depression and/or anxiety, when present as comorbid conditions, affect the rate at which lung function declines each year in patients with COPD. METHODS From July 2022 to July 2025, 122 patients with stable COPD received continuous treatment and regular spirometric follow-up for up to three years at our hospital. We retrospectively analysed the data from these patients. Patients were assessed on two occasions, enabling the calculation of their yearly rate of lung function decline. Patients were divided into two groups. The first group was the control group. This included patients with COPD alone (n = 58). The second group was the comorbidity group. This included patients with COPD and depression and/or anxiety (n = 64). We used something called "linear mixed-effects models" to compare changes over time in something called "forced expiratory volume in one second (FEV1)". We also used something called "multivariate linear regression analyses" to find out what causes a faster decline in lung function. RESULTS At the start of the study, patients with depression and/or anxiety as well as the disease had a lower FEV1, FEV1% predicted, and FEV1/forced vital capacity ratios, and had more acute exacerbations and inhaled corticosteroid use than the control group (all P < 0.05). After the study, the yearly decrease in lung function was a lot higher in the group with both conditions than in the control group (52.4 +/- 10.8 mL/year vs 41.3 +/- 9.5 mL/year, P < 0.001). After adjustment for age, sex, body mass index, smoking status, and baseline lung function, faster FEV1 decline was found to be independently associated with comorbid depression/anxiety (beta = -10.92, 95% confidence interval: -17.35 to -4.49, P = 0.001). More detailed analysis showed that depression/anxiety was the biggest thing that made lung function get worse faster. CONCLUSION The rate of annual lung function decline in COPD was found to be independently accelerated by comorbidity, specifically depression and/or anxiety. This highlights the significance of incorporating psychological assessments and integrated management strategies during long-term follow-ups to decelerate disease progression.

Background: Interferon-induced transmembrane protein 1 (IFITM1) restricts virus infection. IFITM proteins are involved in Th2 cell differentiation in allergic asthma. The epithelial‒mesenchymal transition (EMT) regulates allergic airway remodeling. We sought to explore the functional contributions and underlying mechanisms of IFITM1 in the EMT associated with allergic asthma. Methods: The expression of IFITM1 was measured in pulmonary tissues from asthma patients and in a house dust mite (HDM)-induced murine asthma model. The mechanisms by which IFITM1 affects the EMT of airway remodeling were investigated in vitro and in vivo via the use of an IFNAR neutralizing antibody or Ifitm1 knockdown. Results: We demonstrated that airway IFITM1 was increased in patients with asthma. As expected, HDM exposure increased airway IFITM1 in an asthmatic murine model. The increase in IFITM1 was mediated through IFN-β stimulation and subsequent STAT1 signaling activation. Blocking IFNAR or knocking down Ifitm1 mitigated HDM-induced EMT and airway remodeling. Mechanistically, HDM exposure increased IFITM1 and TNC levels in airway epithelial cells, which promoted Th17 cell differentiation and IL-17A production. Conclusion: IFIMT1, which is upregulated in airway epithelial cells via the IFN-β and STAT1 signaling pathways, contributes to EMT during allergic airway remodeling and may serve as a potential treatment target for allergic asthma.

OBJECTIVES:To overcome the limitations of existing predictors for immune-related adverse events (irAEs) in advanced non-small cell lung cancer (NSCLC), including failure to account for competing mortality risks and non-linear interactions, we aimed to develop an accurate machine learning model for clinically significant irAEs (cs-irAEs, Grade ≥ 2). METHODS:We enrolled 332 patients with stage IIIB-IV NSCLC treated with PD-1/PD-L1 inhibitors, and randomly assigned to training (n = 232) and testing (n = 100) sets. The Fine-Gray model, adjusting for death as a competing event, estimated cs-irAE incidence. Least Absolute Shrinkage and Selection Operator (LASSO) regression selected predictors, followed by an Extreme Gradient Boosting (XGBoost) model compared to logistic regression. Model performance was assessed using under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, and SHapley Additive exPlanations (SHAP) values for interpretability. RESULTS:The 12-month cumulative incidence of cs-irAEs was 18.0% (95% CI, 14.0%-23.0%). Nine predictors were selected, including baseline neutrophil-to-lymphocyte ratio (NLR), body mass index, prior radiotherapy, and proton pump inhibitor use. The XGBoost model achieved an AUC of 0.871 (95% CI, 0.805-0.937) and a negative predictive value (NPV) of 87.9% in the testing set. SHAP analysis revealed a non-linear protective threshold for NLR > 4.0. A bedside nomogram was created using the six strongest predictors. CONCLUSION:This machine learning-based model accurately identified advanced NSCLC patients at risk for cs-irAEs. Its high NPV value helped identify low-risk patients, supporting optimized monitoring and resource allocation. Combining competing risk analysis with interpretable machine learning offers a stable tool for personalized toxicity management.

BACKGROUND:Chronic intermittent hypoxia (CIH) is a key pathogenic mechanism of obstructive sleep apnea (OSA). OSA is an independent risk factor for insulin resistance (IR) in non-obese individuals, yet its underlying mechanisms remain unclear. Dysfunctional visceral adipose tissue (vWAT) is a central driver of insulin resistance and is closely associated with IR. Adiponectin (Ad), secreted by adipose tissue, plays a crucial role in metabolic regulation through insulin sensitization and anti-inflammatory effects. This study investigates how CIH induces IR and how Ad alleviates this effect by modulating macrophage polarization in visceral white adipose tissue (vWAT). METHODS:This study successfully established a lean murine CIH-IR model. C57BL/6J mice were divided into three groups: standard control (NC), CIH, and CIH supplemented with Ad (CIH + Ad), with 10 mice in each group. We evaluated systemic glucose homeostasis using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) index and assessed macrophage infiltration in the white adipose tissue of both epididymides (eWAT) through immunofluorescence (IF) staining, flow cytometry, and ELISA. Additionally, we further investigated these pathways and examined key proteins in the insulin signaling pathway using RNA sequencing (RNA-seq), KEGG pathway enrichment analysis, and Western blot (WB). RESULTS:The CIH group showed a significant decrease in serum Ad levels, along with a corresponding increase in HOMA-IR, compared to the NC group. When Ad was administered to CIH mice, HOMA-IR decreased. Transcriptomic sequencing identified all the differentially expressed genes (DEGs) in eWAT among the three groups. KEGG pathway enrichment and WB analyses revealed the PI3K-AKT pathway as the key driver of functional changes in eWAT. The macrophage count and proportion in the eWAT of mice in the CIH group were significantly higher than in the NC and CIH + Ad groups, and the M1/M2 macrophage ratio was also notably increased. Levels of TNF-α, IL-6, and IL-1β in eWAT were considerably higher in the CIH group compared to both the NC and CIH + Ad groups. CONCLUSION:CIH may impair insulin signaling pathways in mouse eWAT by promoting M1 polarization of eWAT macrophages, which is likely a key mechanism of CIH-induced insulin resistance. Additionally, it is hypothesized that Ad alleviates CIH-induced insulin resistance in mice by regulating eWAT macrophage polarization and restoring insulin signaling pathways.

Severe asthma poses a significant challenge in clinical management due to its poor responsiveness to conventional therapies and worse overall prognosis. Identifying differentially expressed genes (DEGs) between severe asthma and non-severe asthma, exploring potential therapeutic targets, and intervening in these targets could offer new strategies to overcome the treatment bottleneck in severe asthma and improve clinical outcomes. Bioinformatics analysis first revealed that DEGs between severe and non-severe asthma were predominantly enriched in the longevity-regulating pathway, which is closely linked to cellular senescence. Subsequent in vitro experiments confirmed a heightened level of cellular senescence in severe asthma. Notably, ADCK5 was identified as a highly expressed senescence-related marker in severe asthma, exhibiting both strong predictive value for the condition and a clear association with cellular senescence. Finally, through high-throughput compound screening, molecular docking, and experimental validation, Leucokinin VIII acetate (Leucokinin 8) was found to inhibit ADCK5 expression and reduce excessive cellular senescence. In summary, ADCK5 emerges as a critical gene involved in airway senescence in severe asthma, and Leucokinin 8 may offer therapeutic potential by targeting ADCK5 to alleviate airway senescence, thus improving severe asthma outcomes.

Inducible bronchus-associated lymphoid tissue (iBALT), the tertiary immune organ in the lungs, has been implicated in various pulmonary diseases. The formation and roles of iBALTs in neutrophilic allergic asthma, however, remain largely unexplored. In our study, iBALTs were located near bronchi and vessels in a neutrophilic asthma murine model induced by house dust mite (HDM) extract and lipopolysaccharide (LPS). Repeated sensitization promoted the formation of iBALTs, which disappeared 2 weeks after the last HDM challenge. We disrupted the function of B-cell chemokines (C-X-C motif chemokine ligand 13, CXCL13). The CXCL13 neutralizing antibody prevented the formation of iBALTs but failed to relieve airway inflammation. Bulk RNA-seq revealed elevated MMP-12 in pulmonary B lymphocytes, a major population in iBALTs. MMP408, a specific MMP-12 inhibitor, reduced iBALT formation. Moreover, a modified AAV-6 (adeno-associated virus-6) targeting MMP-12 in B lymphocytes blocked iBALTs and ameliorated neutrophilic airway inflammation. These results indicate that MMP-12 produced by B lymphocytes promotes the aggregation of B lymphocytes, promotes the formation of iBALTs, and further exacerbates inflammation in neutrophilic allergic asthma.

Background Severe asthma is a heterogeneous airway inflammatory disease presenting with varying clinicophysiological characteristics and response to treatments. The objectives of the present study were to determine the clinical phenotypes of the Chinese C-BIOPRED cohort and their link to the sputum proteome. Methods Partition-around-medoids clustering was applied to a training set of 362 nonsmoking, smoking or ex-smoking severe asthma patients, and nonsmoking mild–moderate asthma patients using eight clinicophysiological variables, with validation performed in the remaining 181. Results Three stable clusters were defined, with Cluster T1 composed of predominantly female patients with severe nonsmoking asthma experiencing frequent exacerbations with moderate airflow obstruction, and Cluster T3 of elderly male patients with smoking/ex-smoking late-onset severe asthma and severe airflow obstruction and a moderate number of exacerbations. Cluster T2 was composed of nonsmokers with a mild–moderate airflow obstruction and no previous exacerbations. Validation clusters (V1, V2 and V3) were similar to the training set clusters. Differentially expressed proteins in sputum supernatants measured by liquid chromatography with tandem mass spectrometry pointed to differences in the complement and coagulation cascade pathway between Cluster 1 (T1 and V1) and Cluster 3 (T3 and V3), as well as between Cluster 2 (T2 and V2) and Cluster 3. Galectin 10 was upregulated in Cluster 1 compared with Cluster 2, and correlated with exacerbations, fractional exhaled nitric oxide, blood and sputum eosinophil count and oral corticosteroid dose in Cluster 1. Conclusion The clinical clusters were differentiated by smoking status, degree of airflow obstruction and exacerbation history, and by sputum complement and coagulation pathways, and galectin 10 levels.

The study aimed to describe the clinical features of psittacosis pneumonia and identify risk factors associated with severe psittacosis pneumonia. We retrospectively collected data from patients with psittacosis pneumonia, confirmed by metagenomic next-generation sequencing (mNGS) from January 2022 to June 2024 and analyzed differences between severe and non-severe groups. A total of 24 patients (eight severe/16 non-severe) were diagnosed with psittacosis, and 33.3% had severe psittacosis pneumonia. The levels of white blood cells (WBCs), neutrophils, neutrophil-to-lymphocyte ratio (NLR), hypersensitive C-reactive protein (hs-CRP), and procalcitonin (PCT) and the detection rate of fungi by mNGS were significantly higher in the severe group than in the non-severe group. The length of stay and omadacycline use were longer in patients of the severe group when compared to the non-severe group. Receiver operating characteristic (ROC) curves indicated that NLR had a better predictive value of severe conditions than PCT and hs-CRP. Patients with psittacosis pneumonia have a high rate of severe disease, and NLR may be a useful tool to promptly ascertain the severity of the disease and optimal therapies for better outcomes. IMPORTANCE:This study explores the clinical features of psittacosis pneumonia and identifies key factors that may predict the severity of the disease. By analyzing data from 24 patients diagnosed using metagenomic next-generation sequencing (mNGS), the research uncovers important differences between severe and non-severe cases. The study finds that patients with severe psittacosis pneumonia have elevated levels of white blood cells (WBCs), neutrophils, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (hs-CRP), and procalcitonin (PCT), as well as a higher detection rate of fungi. Notably, the NLR emerges as a strong predictor of severe disease, suggesting its potential as an early diagnostic tool. These findings provide valuable insights that can help healthcare providers identify high-risk patients more quickly, allowing for timely interventions and improved management of the disease. Ultimately, this research could lead to better outcomes by guiding treatment decisions and enhancing our understanding of psittacosis pneumonia.

Background The inflammatory response driven by macrophages in adipose tissue is a key contributor to CIH-induced metabolic disorders. The precise mechanism underlying CIH-induced inflammation in adipose tissue macrophages remains elusive. Adiponectin (Ad) is a highly abundant adipokine secreted by adipocytes that plays a crucial role in insulin sensitivity. Methods This study aims to elucidate the pivotal roles of adipocytes and Ad in CIH-induced macrophage inflammation using a co-culture cell approach. The direct co-culture method involved the physical interaction between iBMDM cells and 3T3-L1 adipocytes, while the indirect co-culture method utilized adipocyte-conditioned media as the culture medium for macrophages. Following CIH treatment and Ad intervention, the expression levels of inflammatory factors in the conditioned media of each cell group were quantified. Statistical significance was defined as P < .05. Results Results showed CIH did not directly cause the release of inflammatory factors in individually cultured iBMDM cells and 3T3-L1 adipocytes; however, it significantly increased the release of inflammatory factors in co-cultured cells. Ad alleviates the pro-inflammatory effect of adipocytes on macrophages under CIH conditions. Conclusion CIH could disrupt adipocyte function and promote macrophage inflammation through paracrine mechanisms. ### Competing Interest Statement The authors have declared no competing interest. * Ad : Adiponectin CIH : Chronic Intermittent Hypoxia OSA : Obstructive Sleep Apnea IRS-1 : Insulin Receptor Substrate 1 BMDMs : bone marrow-derived macrophages DMEM : Dulbecco’s Modified Eagle Medium FBS : fetal bovine serum ELISA : Enzyme-linked immunosorbent assay iBMDM : immortalized bone marrow-derived macrophage O2 : oxygen CO2 : carbon dioxide N2 : nitrogen

Amyloidosis is a rare and heterogeneous disorder that is characterized by abnormal accumulation of amyloid protein deposits in the extracellular matrix. ANCA-associated vasculitis (AAV) is a life-threatening autoimmune disease, which often leads to death due to diffuse alveolar hemorrhage (DAH), renal failure, and infection. Herein, we report the first clinical case of tracheobronchial amyloidosis (TBA) coexisting with AAV. TBA was diagnosed in a 27-year-old female who presented with recurrent cough and hemoptysis. Three years later, she was readmitted with worsening symptoms, including blood-filled blisters on all four limbs. A serological workup resulted in positive proteinase-3 antineutrophil cytoplasmic antibody (PR-3 ANCA). She was diagnosed as AAV according to the American Rheumatism Association (ACR) standard. During hospitalization, the patient was transferred to Respiratory Intensive Care Unit (RICU) due to DAH. Her condition improved following non-invasive ventilator-assisted breathing and hormone shock. Upon discharge, she continued treatment with prednisone and cyclophosphamide for AAV. During the follow-up period, ANCA levels remained negative until one year after her last discharge, when PR3-ANCA returned to positive levels, and the patient was considered as relapse of AAV, while her TBA remained unchanged. In this case, we speculate that TBA is a crucial factor in triggering AAV. Neutrophil extracellular traps (NETs) may present a bridge connecting amyloidosis and AAV, which synergistically cause tissue damage.

Purpose: The roles and mechanisms of long noncoding RNAs (lncRNAs) in T helper 2 (Th2) differentiation from allergic asthma are poorly understood. We aimed to explore a novel lncRNA, LincR-protein phosphatase 2 regulatory subunit B' gamma (PPP2R5C), in Th2 differentiation in a mouse model of asthma. Methods: LincR-PPP2R5C from RNA-seq data of CD4+ T cells of asthma-like mice were validated and confirmed by quantitative reverse transcription polymerase chain reaction, northern blotting, nuclear and cytoplasmic separation, and fluorescence in situ hybridization (FISH). Lentiviruses encoding LincR-PPP2R5C or shRNA were used to overexpress or silence LincR-PPP2R5C in CD4+ T cells. The interactions between LincR-PPP2R5C and PPP2R5C were explored with western blotting, chromatin isolation by RNA purification assay, and fluorescence resonance energy transfer. An ovalbumin-induced acute asthma model in knockout (1(O) mice (LincR-PPP2R5C 1(O, CD4 conditional LincR-PPP2R5C 1(O) was established to explore the roles of LincR-PPP2R5C in Th2 differentiation. Results: LncR-PPP2R5C was significantly higher in CD4+ T cells from asthmatic mice ex vivo and Th2 cells in vitro. The lentivirus encoding LincR-PPP2R5C suppressed Th1 differentiation; in contrast, the short hairpin RNA (shRNA) lentivirus decreased LincR-PPP2R5C and Th2 differentiation. Mechanistically, LincR-PPP2R5C deficiency suppressed the phosphatase activity of the protein phosphatase 2A (PP2A) holocomplex, resulting in a decline in Th2 differentiation. The formation of an RNA-DNA triplex between LincR-PPP2R5C and the PPP2R5C promoter enhanced PPP2R5C expression and activated PP2A. LincR-PPP2R5C 1(O and CD4 conditional 1(O decreased Th2 differentiation, airway hyperresponsiveness and inflammatory responses. Conclusions: LincR-PPP2R5C regulated PPP2R5C expression and PP2A activity by forming an RNA-DNA triplex with the PPP2R5C promoter, leading to Th2 polarization in a mouse model of acute asthma. Our data presented the first definitive evidence of lncRNAs in the regulation of Th2 cells in asthma.

Background: As a pivotal pathway of programmed cell death, necroptosis significantly contributes to the pathogenesis of respiratory disorders. However, its role in asthma is not yet fully elucidated. Therefore, this study aimed to identify markers associated with necroptosis, evaluate their functions in asthma, and explore potential therapeutic agents targeting necroptosis for the management of asthma. Methods: Firstly, machine learning algorithms, including Least Absolute Shrinkage and Selection Operator (LASSO), Random Forest, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were utilized to identify necroptosis-related differentially expressed genes (NRDEGs) in asthma patients compared to healthy controls. Concurrently, the expression of NRDEGs was validated using external datasets, Western blot, and quantitative real-time polymerase chain reaction (qPCR). Secondly, the clinical relevance of NRDEGs was assessed through Receiver Operating Characteristic (ROC) curve analysis and correlation with clinical indicators. Thirdly, the relationship between NRDEGs and pulmonary immune cell infiltration, as well as the signaling interactions between different cells types, were analyzed through immune infiltration and single-cell analysis. Fourthly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), were conducted to elucidate the functional roles of NRDEGs. Finally, compounds targeting NRDEGs were screened, and their binding affinities were evaluated using molecular docking studies. Results: In asthma, necroptosis is activated, leading to the identification of four NRDEGs: NLRP3, PYCARD, ALOX15, and VDAC3. Among these, NLRP3, PYCARD, and ALOX15 are upregulated, whereas VDAC3 is downregulated in asthma. Comprehensive clinical evaluations indicated that NRDEGs hold diagnostic value for asthma. Specifically, NLRP3 was inversely correlated with forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), while VDAC3 showed an inverse correlation with sputum neutrophils. Conversely, ALOX15 expression was positively correlated with fractional exhaled nitric oxide (FeNO) levels, as well as sputum eosinophils, blood eosinophils, and blood IgE levels. Subsequent immune infiltration analysis revealed associations between NRDEGs and activated dendritic cells, mast cells, and eosinophils. Single-cell RNA sequencing (scRNAseq) further confirmed the communication signals between myeloid dendritic cells, fibroblasts, neutrophils, and helper T cells, predominantly related to fibrosis and immune-inflammatory responses. Pathway enrichment analysis demonstrated that NRDEGs are involved in ribosomal function, oxidative phosphorylation, and fatty acid metabolism. Finally, resveratrol and triptonide were identified as potential therapeutic agents targeting the proteins encoded by NRDEGs for asthma treatment. Conclusions: The necroptosis pathway is activated in asthma, with NRDEGs-namely PYCARD, NLRP3, ALOX15, and VDAC3-correlated with declines in lung function and airway inflammation. These genes serve as reliable predictors of asthma risk and are involved in the regulation of the immune-inflammatory microenvironment. Resveratrol and triptolide have been identified as promising therapeutic candidates due to their potential to target the proteins encoded by these genes.

BACKGROUND:Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE:To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS:MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting β2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/μL; <300/μL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS:Of 695 patients randomized, 473 had baseline bEOS ≥300/μL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/μL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS:MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

AbstractThis study examined the levels of soluble CD146 (sCD146) in plasma samples from patients with chronic obstructive pulmonary disease (COPD) and assessed the relationship between sCD146 and the severity of COPD. A total of 97 COPD patients were recruited from 20 medical centers in Jiangsu, China, including 13 stable subjects and 84 exacerbated subjects. The plasma sCD146 level in exacerbated subjects (28.77 ± 10.80 ng/mL) was significantly lower than that in stable subjects (38.84 ± 15.00 ng/mL). In the high sCD146 group, the proportion of subjects with modified Medical Research Council (mMRC) scores of 0–1 was higher, the proportion of subjects with the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 4 was lower, and the proportion of subjects with ≥1 hospitalizations in the past year was lower. The plasma sCD146 level was negatively correlated with the COPD Assessment Test (CAT) score (r = −0.2664, p = 0.0087). Logistic regression analysis showed that sCD146 was an independent risk factor for acute exacerbation of COPD (AECOPD). Receiver operating characteristic (ROC) analysis suggested that sCD146 combined with sex, age, pulmonary function, and acute exacerbations in the past year had clinical value for the accurate identification of AECOPD, with an area under the ROC curve (AUC) of 0.908 (95% CI: 0.810–1.000, p < 0.001). In addition, there was a significant negative correlation between plasma sCD146 and S100A9 (r = −0.3939, p < 0.001).

Objective:To investigate the clinical characteristics and prognostic factors of primary pulmonary mucinous adenocarcinomas (PPMAs).Methods:It was an cohort study involving 78 patients with pathologically confirmed PPMA who were treated in the First Affiliated Hospital with Nanjing Medical University from January 2009 to December 2019 and selected by non-random sampling method.The clinical data, treatment course and follow-up results were collected.Follow-up ended on December 31, 2021.Kaplan-Meier method (Log-Rank test) was used for plotting survival curves.Multiple Cox regression model was used to analyze the independent risk factors affecting the survival of PPMA.Results:A total of 78 patients with the mean age of onset of (60.1±11.8) years were recruited.Most patients (67.9%, 53/78) did not have smoking history.Forty-eight patients (61.5%) had primary lung tumor-related symptoms, including cough, expectoration, chest tightness, dyspnea, chest pain and fever.Chest CT scans showed peripheral type and central type in 59 cases (75.6%) and 19 cases (24.4%), respectively.There were 54 cases (69.2%) and 24 cases (30.8%) of nodular type and pneumonia type, respectively.Tumor markers associated with lung cancer increased in 69.7% (46/66) patients.Stratified by tumor staging, there were 31 cases (39.7%) of stage Ⅰ, 14 cases (17.9%) of stage Ⅱ, 16 cases (20.5%) of stage Ⅲ and 17 cases (21.8%) of stage Ⅳ.Immunohistochemical tests were performed in 35 patients, including 31 with positive cytokeratin 7 (CK7), 17 with positive thyroid transcription factor 1 (TTF-1), 12 with positive Napsin A and 8 with positive Villin.PPMA-related driver gene mutations were mainly KRAS mutations (15/46, 31.3%).Radical surgery was performed in 55 (70.5%) patients.By the end of follow-up, 31 cases (39.7%) died and 47 cases (60.3%) survived.The median follow-up time was 40.5 months.The median overall survival time of was 96.0 months, and the 1-, 3-, 5-, 7-year cumulative survival rate was 86%, 71%, 62%, and 52%, respectively.Distant metastasis occurred in 26 cases (33.3%), of which, bone metastasis (16 cases) was the most common.All stage Ⅰ PPMA patients underwent radical resection and no relapse reported.There were significant differences in sex, age, smoking history, symptoms associated with primary lung tumor, tumor markers (carcinoembryonic antigen [CEA], cytokeratin fragment antigen 21-1 [CYFRA21-1]), radiologic features and the tumor, node, metastasis (TNM) staging in PPMA patients with different survival status ( P<0.05).Multiple Cox regression model analysis was conducted with survival outcome as the dependent variable, while sex, age, smoking history, symptoms, CEA, CYFRA21-1, imaging findings and TNM staging as covariates.The results showed that symptoms associated with primary lung tumor, elevated CEA, elevated CYFRA21-1, pneumonitis and TNM staging were independent risk factors affecting the survival of PPMA patients. Conclusions:PPMA is more common in the middle-aged and elderly people.The clinical manifestations are non-specific, while the chest CT manifestations are mainly peripheral type and nodular type.KRAS mutations are the frequent driving gene mutations in PPMA patients.Primary lung tumor related symptoms, elevated CEA, elevated CYFRA2-1, pneumonia type and TNM staging are independent factors affecting the prognosis of PPMA patients.

目的:分析以肺部症状为首发表现的黑色素瘤分化相关基因蛋白5(melanoma differentiation-associated gene 5,MDA5)抗体阳性皮肌炎(dermatomyositis,DM)患者的临床特征与预后.方法:回顾性选取2017年8月—2021年10月南京医科大学第一附属医院收治的MDA5抗体阳性DM患者57例为研究对象,根据临床首发表现分为肺部首发组(n=15)和非肺部首发组(n=42),比较两组一般临床资料、实验室检查结果、影像学表现和预后情况.结果:肺部首发组患者血清铁蛋白(serum ferritin,SF)、C反应蛋白(C-reactive protein,CRP)水平明显高于非肺部首发组,肌酸激酶(creatine kinase,CK)水平明显低于非肺部首发组(P＜0.05).肺部首发组患者的胸部CT征象以斑片状影为主,其次为磨玻璃影、网格影、实变影,小叶间隔增厚、结节影、蜂窝肺和胸腔积液等征象较少.多因素Logistic回归分析结果显示,SF、CK水平是MDA5抗体阳性DM患者以肺部症状为首发表现的独立危险因素(P＜0.05).两组患者发病后6个月内的累积生存率比较,差异有统计学意义(P＜0.05).结论:以肺部症状为首发表现的MDA5抗体阳性DM患者治疗方案以糖皮质激素+免疫抑制剂为主,患者预后较差,其临床表现及影像学特征具有多样性;SF、CK水平与MDA5抗体阳性DM患者以肺部症状为首发表现相关,或可成为实验室监测指标之一.

Objective: To evaluate the influencing factors of poor treatment adherence in patients with uncontrolled asthma in China. Methods: From April 2017 to April 2018, all asthma patients with uncontrolled asthma and poor compliance in 32 third-class hospitals in 28 provinces and cities of China mainland included in the "National Mobile Asthma Assessment and Management Project" were selected as the subjects. A total of 923 patients were enrolled in the study including 388 males and 535 females. By analyzing the baseline data of the patients at the initial visit when enrolled, the influencing factors of poor adherence of adult asthma was analyzed by inter-group comparison and χ2 test. Results: Poor compliance in asthma was related to the following factors: age from 59 to 68 years old, course of disease more than 20 years, low education level, non-local follow-up, having obstructive ventilation dysfunction and low awareness of the disease[P values were 0.026(t=1.20), 0.004(t=3.97), 0.001(t=4.92), 0.003(t=3.98), 0.032(t=1.22) and 0.001(t=4.99), respectively]. Totally, 243 patients (26.33%) answered all the questions about asthma correctly. Their medication adherence rating scale (MARS-A) scores were significantly higher than those who answered incompletely correctly (36.23±5.85 vs. 31.77±5.74, P=0.001). Conclusions: The adherence of adult asthma patients was affected by individual and external environment factors. Clinicians should choose individualized methods based on the characteristics of patients. Patient education should be strengthened to improve patients' awareness of the disease at the same time.