Objective:To explore the predictive value of key preoperative cardiopulmonary exercise testing (CPET) indicators for cardiopulmonary complications following thoracoscopic lung resection. Methods:Patients who underwent lung resection at the Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University were selected. Information was collected for patients who completed CPET using the incremental exercise protocol. Hospitalization information, postoperative complications and follow-up data were analyzed. Correlations between postoperative cardiopulmonary complications and preoperative CPET indices were analyzed to identify threshold values. Results:Among 376 thoracoscopic lung resection patients, 52 experienced at least one complication (13.8%). Comparison between the cardiopulmonary complications group (CCP) and no complications group (NCCP) revealed significant differences in age, extent of lung resection, and lymph node metastasis (P < 0.05). Core CPET indicators including peak heart rate (peak HR), peak oxygen uptake (peak VO2), peak VO2%pred, peak metabolic equivalent (peak MET), and maximal workload %pred were significantly lower in the CCP group (P < 0.05). The sensitivity and specificity of peak VO2%pred <70%, peak MET <5, and maximal workload %pred <80% all exceeded 60%, with negative predictive values surpassing 90%. Positive predictive values of peak VO2 < 15 mL/(min·kg), peak VO2%pred <60%, peak MET <4, and maximal workload %pred < 60% exceeded 30%. Using these cutoff values resulted in high diagnostic accuracy with odds ratios of 6.2, 4.0, 4.6, and 3.2, respectively. Conclusion:Key preoperative CPET indicators effectively evaluate postoperative complication risk in thoracoscopic lung resection patients. Peak VO2, peak VO2%pred, peak MET, and maximal workload %pred are associated with postoperative cardiopulmonary complications.

Background: Patients with chronic obstructive pulmonary disease (COPD) face a substantially elevated risk of developing lung cancer, significantly complicating their clinical management and prognosis. We therefore performed this study to investigate lung cancer incidence and risk factors in patients with COPD. Methods: Comprehensive searches were conducted in PubMed, Embase, and the Cochrane Library up to December 2024. To estimate lung cancer incidence in COPD, we applied a random-effects model with log transformation of raw data. Risk factors were quantified through pooled odds ratios (ORs) and 95% confidence intervals (CIs), also computed under a random-effects framework. Results: Twenty-six cohort studies involving 613,373 patients with COPD were selected for the meta-analysis. The incidence of lung cancer in patients with COPD was 6.0% (95% CI: 5.0-6.9; P<0.001). Moreover, older age (OR: 2.16; 95% CI: 1.15-4.05; P=0.02), current smoking (OR: 1.69; 95% CI: 1.42-2.00; P<0.001), and presence of emphysema (OR: 2.73; 95% CI: 2.02-3.69; P<0.001) were associated with increased risk of lung cancer in COPD patients. Subgroup analyses showed that the incidence of lung cancer in COPD patients was higher in retrospective cohort studies, studies conducted in Asia, those with sample sizes <5,000, follow-ups <5.0 years, and studies with low quality. Conclusions: This study identified the incidence and risk factors for lung cancer in patients with COPD. Regular screening is recommended for high-risk populations with COPD to improve patient outcomes.

In-hospital mortality risk varies substantially among patients with pulmonary fibrosis (PF). Existing prognostic models have primarily focused on long-term survival and have limited ability to capture early in-hospital mortality risk or incorporate worsening oxygenation, inflammatory burden, and treatment-escalation information. This study aimed to develop and internally validate an interpretable machine learning model for in-hospital mortality risk stratification using early admission clinical data and information on ventilatory support within 24 h after admission in hospitalized patients with PF. This retrospective cohort study included hospitalized patients with PF admitted to a tertiary hospital between January 2019 and December 2023. Candidate variables included demographic characteristics, comorbidities, disease subtype, clinical symptoms, laboratory tests, arterial blood gas analysis, modified Medical Research Council (mMRC) dyspnea score, and the use of invasive or noninvasive ventilation within 24 h after admission. Nested LASSO feature selection combined with repeated 10-fold cross-validation was used for model development and internal validation. The main candidate models included logistic regression (LR), naive Bayes (NB), support vector machine (SVM), random forest (RF), neural network (NN), multilayer perceptron (MLP), adaptive boosting (AdaBoost), and gradient boosting machine (GBM). A supplementary clinically simplified model based on LASSO prescreening, recursive feature elimination, and logistic regression (RFE_LR) was also developed. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), threshold-dependent classification metrics, calibration analysis, decision curve analysis, clinical impact curves, bootstrap internal validation, and SHAP interpretation. Additional analyses included pairwise AUC comparisons with Holm adjustment for multiple testing, alternative-threshold analyses, exploratory in-sample recalibration analyses, and sensitivity analyses related to noninvasive ventilation (NIV). A total of 547 patients were included, of whom 108 met the prespecified primary mortality outcome, corresponding to an event rate of 19.74

Pulmonary arterial hypertension (PAH) is a refractory cardiopulmonary disorder with a high mortality rate and few treatment options. Fisetin, a natural flavonoid, exhibits pleiotropic effects including anti-angiogenic, anti-proliferative, anti-inflammatory, and autophagy-modulating activities. To evaluate the therapeutic potential of Fisetin, we established two experimental models: a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and a platelet-derived growth factor (PDGF)-induced human pulmonary artery smooth muscle cell (PASMC) proliferation model. The therapeutic efficacy and underlying mechanisms of Fisetin were comprehensively assessed using a combination of in vivo and in vitro approaches, including right heart catheterization, masson’s trichrome and hematoxylin–eosin staining, immunohistochemistry, westernblot, immunofluorescence, ELISA, and transmission electron microscopy. Additionally, Protein–protein docking predicts interactions between proteins, whereas molecular docking predicts interactions between small molecules and proteins. Fisetin significantly ameliorated pulmonary vascular remodeling and reduced both right ventricular systolic pressure and the right ventricular hypertrophy index in monocrotaline (MCT)-induced PAH rats. The underlying mechanism may involve suppression of the TGF-β1/Smad2/3 pathway, which regulates autophagy, cell proliferation, migration, and inflammatory responses. In vitro, Fisetin exerted a dose-dependent suppressive effect on these molecular events. This study suggests that Fisetin may alleviate MCT-induced PAH rats by suppressing aberrant TGF-β1/Smad2/3 pathway activation. These findings provide experimental and theoretical support for Fisetin as a promising therapeutic candidate for PAH.

Pulmonary arterial hypertension (PAH) is a severe and progressive cardiovascular disease. While potential links between clonal hematopoiesis (CH) and cardiovascular diseases have been identified, the causal relationship between CH and PAH remains unclear. This study aims to investigate the causal effect of CH on the risk of PAH using a two-sample Mendelian randomization (MR) approach. We utilized genetic variants associated with CH as instrumental variables, identified from two large genome-wide association studies (GWAS) involving 359,088 participants in the discovery cohort and 184,121 participants in the validation cohort, all of European descent. We obtained GWAS summary statistics for PAH. The inverse-variance weighted (IVW) method was employed as the primary analysis, complemented by sensitivity analyses to assess the robustness of our findings. A bidirectional MR analysis was conducted to estimate the causation between CH and PAH. Our results indicate a causal effect of CH on the risk of PAH in the discovery cohort, with TET2 showing an IVW odds ratio (OR) of 1.200 (95

BackgroundLong COVID patients are prone to bronchial hyperresponsiveness and respiratory symptoms like coughing and breathing difficulties, often with positive bronchial provocation test (BPT) results.ObjectiveThis study aims to evaluate the diagnostic value of various lung function tests in patients with long-term COVID-19, explicitly focusing on positive BPT outcomes.MethodsOur study analyzed the BPT outcomes and various pulmonary function parameters of all 9,406 COVID-19 patients who met the inclusion criteria and visited our hospital between February 24, 2022, and April 28, 2024. Key indicators included forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow (PEF), and single-breath diffusing capacity for carbon monoxide (DLCOc SB). A logistic regression model was employed to identify factors influencing positive BPT results, while the receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of these indicators.ResultsA total of 4211 valid samples were analyzed, with 3388 patients (80.46%) testing positive for BPT. Significant differences were observed between positive and negative groups regarding age, gender, smoking status (all P < 0.05), and specific lung function indicators, including FVC, FEV1/FVC ratio, maximum of vital capacity (VC max), and DLCOc SB (all P < 0.001). Logistic regression identified age, MEF50, and DLCOc SB as independent factors influencing positive BPT results. The area under the ROC curve for all assessed factors was <0.700, indicating limited diagnostic value.ConclusionAge, the small airway function indicator MEF50, and the pulmonary diffusion function indicator DLCOc SB are independent influencing factors for BPT positivity in long-term COVID patients. However, baseline data and lung function indicators have limited utility for diagnosing positive BPT in this population, highlighting the complex nature of post-COVID respiratory symptoms.

Rationale:Asthmatic cough may not respond well to corticosteroids. The underlying mechanisms and heterogeneity of cough variant asthma (CVA) remain poorly understood. The objectives of the present study were to explore airway immunological mechanisms and identify molecular endotypes in CVA by analysing sputum transcriptomics, clinical and pathophysiological characteristics. Methods:RNA sequencing and cytokine measurement were performed on sputum samples from newly diagnosed patients with CVA (n=72), classic asthma (CA) (n=28) and healthy controls (HC) (n=28). Patients with CVA were treated and followed-up for 6 months. Results:The majority of differentially expressed genes in CVA versus HC overlapped with those identified in CA versus HC. However, the type 2 immunity co-expression network in CVA was lower than that in CA. Based on sputum transcriptomics profiles, two endotypes of CVA were identified: mixed-inflammatory CVA (n=40) and pauci-inflammatory CVA (n=32). Mixed-inflammatory CVA showed higher inflammation-related gene set signatures compared to both pauci-inflammatory CVA and HC. Mixed-inflammatory CVA also showed elevated levels of eosinophils, neutrophils, type 2, type 1 and type 3 cytokines in sputum compared to HC. Conversely, pauci-inflammatory CVA had slightly elevated sputum eosinophils, but no significant gene signatures and cytokine differences compared to HC. During 6 months' follow-up, pauci-inflammatory CVA showed a trend of less complete resolution in cough (56.2% versus 80.0%, p=0.0553) compared to mixed-inflammatory CVA. Kaplan-Meier analysis found significantly higher cough persistence in pauci-inflammatory versus mixed-inflammatory CVA. Conclusions:CVA exhibits overlapping but distinct airway transcriptomics profiles compared to CA. Two distinct molecular endotypes are identified in CVA, presenting different clinical and pathophysiological features.

Ethnopharmacological Relevance Lianhua Qingke (LHQK), a traditional Chinese medicine, has shown efficacy in treating acute and chronic bronchitis and bronchiolitis. However, the specific mechanism underlying the therapeutic effects of LHQK on severe pneumonia is not clear. Aim of the study Severe pneumonia remains a critical health challenge, particularly in cases progressing to sepsis and septic shock, where host immune responses become dysregulated or dysfunctional. This study aims to evaluate the immunomodulatory effects of LHQK in severe pneumonia. Materials and Methods This research examined LHQK's therapeutic and immunomodulatory mechanisms in patients with severe pneumonia and a lipopolysaccharide (LPS)-induced mouse model of severe pneumonia. Patients with severe pneumonia were randomized into three groups: basal treatment, LHQK-Low dose (12 tablets/day), and LHQK-High dose (24 tablets/day). BALB/c mice were categorized into four groups: control, model, LHQK-Low dose (3.7 mg/kg), and LHQK-High dose (7.4 mg/kg). Clinical efficacy was evaluated by assessing parameters including the value and rate of change in APACHE II score, improvement in chest X-ray or CT, partial pressure of oxygen (PO2), oxygen saturation in arterial blood (SaO2), oxygenation index (OI), and the length of hospitalization after 7 days of treatment. The viscosity of sputum was measured by viscosimeter. Moreover, lung histopathology, airway barrier integrity, and immune cells in BALF, were assessed using hematoxylin and eosin staining, immunostaining, and Wright-Giemsa staining. Cytokine levels were measured using Luminex assay and Olink, while pulmonary immune cell patterns were analyzed using multiplex fluorescence and Cytometry by Time-Of-Flight (CyTOF). Results In comparison to the basal treatment group of patients, LHQK treatment exhibited a reduction in the severity of severe pneumonia and inflammatory status, as evidenced by observations on Chest X-ray or CT scans. Additionally, LHQK treatment led to an elevation in OI, PO2, and SaO2 levels, and notably, a decreased duration of hospitalization. Further analysis revealed that LHQK enhanced the integrity of the airway epithelial barrier, reduced the viscosity of sputum, and significantly decreased inflammatory cells infiltration. The application of Luminex and Olink assay further confirmed the inhibitory impact of LHQK on the cytokine storm in mice. Moreover, multiplex fluorescence and CyTOF analysis demonstrated that LHQK effectively suppressed the activation of monocyte derived macrophages, neutrophils, and Treg cells, while preserved the levels of alveolar macrophages, B cells, and CD4+ and CD8+ T lymphocytes, therefore restoring immune homeostasis within the lung of severe pneumonia. These findings significantly substantiate the potential clinical application of LHQK in severe pneumonia treatment. Conclusion LHQK demonstrates therapeutic efficacy in severe pneumonia by maintaining structural integrity, suppressing cytokine storms, enhancing intrinsic immunity, reversing T cell exhaustion, and correcting lung immune disorders. These findings significantly substantiate LHQK's potential clinical application in severe pneumonia treatment.

Chronic obstructive pulmonary disease (COPD) is a global public health challenge and a major cause of death. The lactate dehydrogenase to albumin ratio (LAR) is a simple and practical indicator of disease prognosis, but its prognostic value in acute exacerbation of COPD (AECOPD) remains unclear. Therefore, we aimed to explore the prognostic value of LAR for the short-term all-cause mortality risk in patients with AECOPD. This retrospective cohort study included 654 patients with AECOPD from the MIMIC-IV database. LAR was analyzed after natural logarithm transformation and the patients were divided into three groups. The clinical outcome was the 1-month and 3-months all-cause mortality. The relationship between LAR and all-cause mortality was assessed using Kaplan–Meier survival analysis and a Cox regression model. Generalized additive models were employed to identify non-linear relationships, and a subgroup analysis was performed to determine the stability of the results. The study showed that LAR levels significantly and positively correlated with short-term all-cause mortality in patients with AECOPD. Compared to the low LAR group, patients in the medium LAR group had a significantly increased 1-month all-cause mortality risk, with a hazard ratio (HR) of 1.74 (95

Objective:To provide further data support for the treatment of COVID-19 by conducting a comprehensive analysis of reports on dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), which detects the functional vitamin K status post COVID-19 infection, using meta-analysis. Methods:This study conducted a comprehensive review and analysis of relevant research on dp-ucMGP detection in patients infected with COVID-19 through meta-analysis. The article collection period ranged from January 2024 to April 2024. Results:A total of 6 articles were included in this study. Baseline data analysis showed that the age of patients in the COVID-19 infected group was greater than that of the non-infected control group (p = 0.030); similarly, the age of patients in the severe infection group was also greater than that of the mild infection group (p = 0.003). In the analysis of underlying diseases, statistical differences were found between the Severe group and Mild group in the presence of CVD (p = 0.010). A total of 5 studies conducted dp-ucMGP detection in both the COVID-19 infected group and the control group. The results showed that the expression of dp-ucMGP was higher in the infected group than in the control group (p < 0.001). Subgroup analysis revealed that the expression of dp-ucMGP in the severe infection group was also higher than that in the mild infection group (p < 0.001). Conclusion:COVID-19 infected patients exhibit Low Vitamin K Status, which correlates positively with the severity of infection. Supplementation of vitamin K during COVID-19 infection may potentially mitigate the progression toward severe infection, necessitating further support from clinical data.

ABSTRACT Background Pre‐Omicron studies identified chronic obstructive pulmonary disease (COPD) as a significant risk factor for adverse COVID‐19 outcomes. Given Omicron's altered pathogenicity and widespread population‐level immunity, the association between COPD and COVID‐19 outcomes warrants reassessment in light of the variant's distinct clinical profile. We evaluated whether COPD remained a risk factor for poor clinical outcomes among hospitalized patients with SARS‐CoV‐2 infection during Omicron predominance. Methods We conducted a two‐center retrospective cohort study of 1176 adults hospitalized with confirmed Omicron infection between January 2022 and December 2023 in Northern China. Patients were stratified by pre‐existing COPD status. To address confounding by treatment selection, inverse probability weighting (IPW) was applied based on the likelihood of receiving inhaled corticosteroids. Multivariable logistic regression models, adjusted for comorbidities, disease severity (as measured by the PSI), inflammatory markers (CRP, D‐dimer, NLR, LDH), and treatment regimens, were used to evaluate the associations between COPD and in‐hospital outcomes. Results Among 1176 patients (337 COPD; 839 non‐COPD), COPD patients had significantly lower PSI scores and lower levels of systemic inflammation despite a higher prevalence of respiratory comorbidities. In unadjusted models, COPD was associated with reduced odds of mortality (OR 0.52), respiratory failure (OR 0.24), and ventilatory support. However, after IPW adjustment, these associations were no longer statistically significant (mortality: adjusted OR 0.90, 95% CI 0.22–3.74, p = 0.887). Conclusions COPD was not independently associated with increased risk of mortality, respiratory failure, or ventilatory support in hospitalized Omicron‐infected patients after rigorous adjustment for confounding. These findings suggest a shifting risk profile for COPD during Omicron predominance, likely influenced by variant tropism, treatment effects, and altered inflammatory responses. Future prospective studies are warranted to validate these findings and explore the mechanisms underlying this observed shift.

This study evaluated the causal relationship between matrix metalloproteinases (MMPs) and pulmonary embolism using data from the genome-wide association study (GWAS) of pulmonary embolism from the UK Biobank and a GWAS dataset of MMPs based on 5,457 Icelanders aged 65 years and older. MR-Egger, MR-PRESSO, Cochran’s Q, and leave-one-out were used for sensitivity analysis. The Mendelian randomization (MR) analysis, based on the IVW analysis, indicated an elevated risk for pulmonary embolism in association with MMP19 (OR = 1.0009, 95%CI: 1-1.0017, P = 0.041), consistent with the weighted median method results (P = 0.015). In addition, despite the negative result from the IVW method (P = 0.554), the weighted median analysis suggested a reduced risk for pulmonary embolism related to MMP12 (OR = 0.9992, 95%CI: 0.9984-1, P = 0.038). No causal associations were found for the other MMPs (including MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP13, MMP14, MMP16, MMP17, and MMP20) on pulmonary embolism (all P > 0.05). The reverse MR analysis revealed no causal associations between pulmonary embolism as exposure and MMPs as outcomes. Sensitivity analyses confirmed the robustness of these findings. In conclusion, this MR analysis revealed the potential causal relationship between MMPs and pulmonary embolism, suggesting that measuring MMPs could help identify people at higher risk of pulmonary embolism, but further research is needed.

The ratio of hemoglobin (Hb) to red blood cell distribution width (RDW), known as HRR, functions as an innovative indicator related to prognosis. However, whether HRR can predict the mortality for pulmonary embolism (PE) patients remains ambiguous. A retrospective cohort study was conducted using the MIMIC IV database (3.0), All patients were categorized into four groups based on the HRR. We investigated the association between HRR and PE mortality. Cox regression models were used to evaluate these associations, while restricted cubic spline (RCS) regressions assessed potential nonlinear relationships. In addition, six machine learning models, including random survival forest (RSF), conditional Inference Tree(ctree), gradient boosting machine (gbm), nearest neighbors (nn), and extreme gradient boosting (xgboost), were applied, with Shapley additive explanation (SHAP) are used to determine the importance of characteristics. 2,272 PE patients were eligible for analysis. Our study identified both age and HRR levels (both with OR > 1, P < 0.05) as significant predictors of 30-day and 365-day mortality in PE patients admitted to the ICU. In Cox regression analysis, both age and HRR (both with HR > 1, P < 0.05) also emerged as prognostic risk factors for 30-day and 365-day mortality in this patient population. KM analysis demonstrated that patients with PE who were older or had increased HRR levels while hospitalized or in the ICU exhibited considerably reduced survival rates in comparison to younger individuals or those with lower HRR levels (P < 0.0001). Additionally, the RCS analysis revealed a pronounced nonlinear association between HRR levels and the risk of mortality. Validation set, coxph (ROC: 0.772) demonstrated superior predictive accuracy for these endpoints. identifying HRR as a vital component of mortality. A lower HRR correlates with high mortality rate in patients with PE patients. This model could serve as a useful tool for guiding mortality, assisting in clinical decision-making and improving patient management outcomes.

Hypoxic pulmonary hypertension (HPH) lacks effective treatments. The research is designed to examine the effectiveness of Notoginsenoside R1 (NGR1) in addressing HPH and to explore its molecular mechanisms. Under hypoxic conditions, we created a rat model of HPH and treated the animals with NGR1. We assessed the therapeutic effects of NGR1 on HPH through hemodynamic measurements and pulmonary artery vascular remodeling. We employed transcriptomic analysis to evaluate gene expression changes in HPH rats. We conducted untargeted metabolomics to examine how NGR1 influences the metabolic profile of HPH rats. NGR1 treatment significantly improved hemodynamic parameters and ameliorated pulmonary artery vascular remodeling in HPH rats. Transcriptomic analysis identified Pck1 as the most significantly altered gene. NGR1 intervention significantly improved the expression of vascular remodeling-related proteins. NGR1 reversed the expression of glycolysis-related genes. NGR1 reduced the levels of glycolysis-related metabolites. Further analysis revealed that NGR1 treatment decreased PFKL, HK2, and LDHA protein expression and lowered lactate levels in lung tissue. Our findings demonstrate that NGR1 effectively alleviates the pathological features of HPH in rats. NGR1 inhibits hypoxia-induced glycolysis-mediated pulmonary artery remodeling, mitigates vascular endothelial damage, and suppresses the abnormal proliferation of smooth muscle cells and fibroblasts.

BackgroundMetagenomic next-generation sequencing (mNGS) enables simultaneous sequencing of DNA fragments for comprehensive pathogen identification. Pneumonia in immunocompromised patients—characterized by atypical clinical manifestations and rapid progression—poses diagnostic challenges. Conventional microbiological testing (CMT), which relies on pathogen culture and serological assays, is limited by prolonged turnaround times and suboptimal detection rates. This study was performed to evaluate the clinical utility of mNGS through comparative analysis with CMT in detecting pathogens among immunocompromised patients with pneumonia.MethodsWe conducted a retrospective cohort study of 146 immunocompromised patients with suspected pneumonia. The mNGS and CMT results were systematically analyzed. Pathogen detection rates and microbial spectrum concordance were visualized using pie and bar charts. Diagnostic performance was compared using McNemar’s test and Kappa (κ) statistics for inter-method agreement. The sensitivity, specificity, accuracy, and area under the curve were calculated for pathogen-specific evaluations.ResultsmNGS demonstrated superior detection efficacy, identifying pathogens in 98 cases versus 50 by CMT, with 48 overlapping positives. The microbial spectrum showed substantial differences: mNGS detected 73 bacterial, 46 fungal, and 45 viral pathogens, whereas CMT identified 38 bacterial, 27 fungal, and 21 viral agents. mNGS outperformed CMT across all infection types, including single-pathogen infections (bacterial, fungal, or viral only) and mixed infections (bacterial + fungal, bacterial + viral, fungal + viral, or bacterial + fungal + viral). Bacterial and fungal detections showed low inter-method concordance, while viral detection exhibited moderate agreement (κ = 0.510, p < 0.001). Notably, mNGS achieved significantly higher detection rates for Enterococcus faecalis and Pneumocystis jirovecii in intensive care unit (ICU)-admitted patients with severe pneumonia (p < 0.05). Clinical outcomes improved in 45 patients following mNGS-guided therapeutic adjustments.ConclusionsmNGS and CMT demonstrate complementary strengths in bacterial and fungal detection in immunocompromised patients with pneumonia. mNGS provides enhanced diagnostic accuracy for key pathogens such as E. faecalis and P. jirovecii, particularly in severe and ICU-admitted cases. As a high-throughput diagnostic tool, mNGS may improve pathogen detection and clinical management in immunocompromised populations.

Objectives:Pulmonary arterial hypertension (PAH) is a severe heart-lung condition characterized by complex changes in the pulmonary vasculature, known as pulmonary vascular remodeling (PVR). Gypenosides (Gyp) possesses a range of pharmacological properties, including anti-inflammatory and anti-oxidant effects. This study aims to explore the impact of Gyp on pulmonary vascular remodeling, particularly in relation to its potential to counteract inflammation, oxidative stress, and apoptosis. Materials and Methods:Twenty-four rats were randomly divided into four groups. MCT was administered via intraperitoneal injection at a 55 mg/kg dose to establish a PAH model. Gyp (150 mg/kg/day, Ig) was administered for 28 days, after which all lung tissues from the rats were isolated. Results:The findings indicated that Gyp had a substantial positive impact on the hemodynamics of rats with PAH induced by MCT, including reductions in mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP). Additionally, it exhibited inhibitory effects on right ventricular hypertrophy and pulmonary vascular remodeling in these PAH-afflicted rats. MCT elevated the concentration of MDA (P<0.01 in the lung) while reducing the levels of SOD and GSH-PX (P<0.0001). Furthermore, MCT enhanced the expression of IL-6, TNF-α, and IL-1β (P<0.0001), as well as the mRNA expression of NF-κB (P<0.001) and the Bcl2 level (P<0.0001), while it lowered the expression of Bax (P<0.0001). Conversely, Gyp treatment effectively mitigated all of these alterations. Conclusion:This study represents the initial investigation showing that Gyp treatment attenuates PVR by inhibiting oxidative stress, inflammation, and apoptosis, providing a foundation for further research.

AIM:To explore the prognostic value of the first 24-h urine output (UO) after admission in patients with acute pulmonary embolism (APE) in the intensive-care unit (ICU) for short- and long-term all-cause mortality risk. METHODS:This retrospective cohort study used the MIMIC-IV database. Patients with APE were divided into 4 teams (T1-T4) by their first 24-h UO after admission: T1 (UO ≤ 400 ml), T2 (400＜UO ≤ 800 ml ), T3 (800＜UO ≤ 2500 ml), and T4 (UO＞2500 ml). The primary endpoints were the three-month and one-year all-cause mortality rates. The relationship between UO and mortality was assessed using Kaplan-Meier survival curves and Cox proportional hazards models. RESULTS:This study included 2012 patients with APE, of whom 50.75% were female. Compared to the T3 group, patients in the T1 and T2 groups had higher all-cause mortality rates. Kaplan-Meier survival curves showed that patients in the T1 and T2 groups had a higher risk of death, while those in the T4 group seemed to have a lower risk of death (P＜0.001). The results remained stable in all three adjusted models and subgroup analyses. A restricted cubic spline analysis (RCS) revealed that the risk of all-cause mortality gradually decreased with an increase in UO, showing an "L"-shaped relationship. A UO of ＜1283 ml increased the risk of death in patients. Subgroup analysis indicated that the first 24-h UO was associated with 3-month and 1-year all-cause mortality rates in most subgroups of patients. CONCLUSIONS:The first 24-h UO after admission is an important indicator for the prognosis of APE patients. A lower 24-h UO is strongly related to a higher risk of short-term and long-term all-cause mortality in ICU patients with APE.

Pulmonary arterial hypertension(PAH)is a chronic and pro-gressive cardiovascular disease,which eventually leads to heart failure and premature death in the absence of effective treatment.Due to its complex pathogenesis,as well as the limited available therapeutic options,PAH has been always associated with high rates of disability and mortality worldwide and remains a signifi-cant global health concern[1].Given the substantial burden that PAH imposes on both patients and the healthcare system,in-depth exploration of this condition is of utmost necessity.Herein,we used the Global Burden of Disease(GBD)2021 database[2]to assess the global epidemiologic characteristics and long-term changes in the burden of PAH.We aimed to provide a valu-able reference and foundation to promote PAH,and facilitate development of public health policies.