BackgroundBalloon pulmonary angioplasty (BPA) effectively treats chronic thromboembolic pulmonary hypertension (CTEPH); however, its effects on right ventricular (RV) remodeling remains unclear. This study investigates RV reverse remodeling patterns and key hemodynamic determinants in patients undergoing sequential BPA therapy.MethodsIn this retrospective study, 46 patients who underwent BPA at monthly intervals were included. Serial echocardiography was used to monitor cardiac structure and function, while right heart catheterization assessed hemodynamic parameters before and after treatment. Longitudinal changes were analyzed using mixed-effects models with piecewise assessment of early and late treatment phases.ResultsSignificant improvements in right ventricular structure and function were observed across BPA sessions. Notably, right atrial transverse diameter and tricuspid annular systolic velocity demonstrated early responses to BPA, with significant changes evident during the initial treatment phase. In longitudinal analyses, early treatment phases (baseline to BPA3) were characterized by marked reverse remodeling, including reductions in right atrial area (RAA), RV end-diastolic transverse diameter, and wall thickness, accompanied by improvements in tricuspid annular plane systolic excursion, enhanced RV function. Greater reductions in pulmonary vascular resistance (PVR) were associated with more pronounced RV reverse remodeling, particularly in RAA.ConclusionA temporal pattern of RV reverse remodeling is observed during serial BPA, characterized by substantial early improvements followed by a plateau in later sessions. These changes are closely associated with reductions in PVR, supporting a central role of afterload reduction in driving RV recovery. This pattern may help inform the optimization of BPA treatment strategies.

RNA viruses represent an integral component of human-associated environments and human health. However, the ecology of environmental RNA viruses remains largely unexplored. Here, we analyzed 2922 metatranscriptomic samples collected from urban and surrounding environments-including human-dense settings (e.g., transit hubs, hospitals, banks), alongside peri-urban settings - across 102 cities in 31 countries and constructed the Urban & Peri-urban RNA Virus Atlas (UPVAtlas), comprising 54,945 RNA viruses, 77% of which had not been previously observed. Phylogenetic reconstruction based on RNA-dependent RNA polymerases from UPVAtlas greatly expanded the evolutionary diversity of RNA viruses, leading to the identification of two potential candidate phyla, one candidate class, and several unclassified clades. Host association analyses further revealed the ecological complexity of environmental RNA viruses, with the diversity of vertebrate-related and ESKAPE pathogen-related viruses underscoring the importance of continued monitoring of urban environments for tracking RNA viral prevalence and dynamics, with direct relevance to future public health.

The 15-min city (15mC) framework has emerged as a transformative urban planning strategy to promote equitable access to essential urban services. However, existing studies predominantly focus on descriptive, static, and urban-core-based analyses of accessibility coverage, neglecting predictive insights into how this policy shift might impact systemic spatiotemporal disparities in suburban and peri-urban contexts. This study introduces a novel optimization-based evaluation framework that integrates temporal accessibility metrics to assess how different policy objectives—minimizing average travel time versus maximizing population coverage within 15-, 30-, and 45-min thresholds—shape spatial equity across urban-suburban gradients. Leveraging high-resolution data on COVID-19 testing sites in 10 Chinese megacities, we identify persistent suburban accessibility deserts, particularly under nighttime conditions, and quantify the implications of different planning strategies. Our findings reveal that proximity-driven goals, while effective in boosting 15-min coverage, often fail to mitigate temporal and spatial inequities, especially in underserved suburban areas. In contrast, efficiency-driven approaches not only enhance overall travel performance but also deliver disproportionate benefits to marginalized populations in peripheral zones. This study challenges proximity-centric assumptions embedded in current 15mC discourse and highlights the need for context-sensitive, temporally-aware equity metrics. Our methodological innovations offer transferable tools for equitable public service allocation and provide strategic guidance for suburban planning under both crisis and normal conditions.

Urbanization exerts unprecedented pressure on the microbial community, with far-reaching implications for human health. While previous studies have documented microbial variations across the geographic urban-rural gradient, the temporal dynamics of microbial communities in response to urbanization remain poorly understood. Leveraging global datasets of 2,110 metagenomes spanning 45 cities on 6 continents and annual artificial impervious surface data (1985-2018), we investigated how microbial composition, diversity and functions correlate with urbanization age. Our results reveal that, with increasing urbanization age, there is a significant decline in microbial alpha diversity (P < 0.05), a pronounced compositional shift from nature-associated to human-associated microorganisms (P < 0.001), a rise in the total relative abundance of opportunistic human pathogens (P < 0.05) and a functional restructuring with potential human health implications. These findings provide empirical evidence of microbial community dynamics across the temporal urbanization process, offering actionable insights for urban planning (such as urban regeneration and renovation) and stage-targeted public health policies aimed at mitigating potential microbiome-related health risks in an increasingly urbanizing world.

BACKGROUND:The right ventricular free wall longitudinal strain to pulmonary arterial systolic pressure (RVFWLS/PASP) ratio is an emerging echocardiographic index for evaluating right ventricular-pulmonary artery (RV-PA) coupling. This study aimed to evaluate its prognostic significance and incremental value in risk stratification for patients with pulmonary arterial hypertension (PAH). METHODS:We conducted a retrospective-prospective cohort study of 149 adult PAH patients (87 idiopathic PAH and 62 connective tissue disease-associated PAH). RVFWLS was measured via speckle tracking echocardiography, and PASP was estimated using Doppler. The primary endpoint was event-free survival, defined as the first occurrence of all-cause mortality, lung transplantation, or rehospitalization for right heart failure. Kaplan-Meier and multivariate Cox regression analyses were performed to identify independent predictors. RESULTS:During a median follow-up of 32 months, 78 primary events occurred. Patients in the lower RVFWLS/PASP group (<0.246%/mmHg) exhibited significantly worse exercise capacity, higher NT-proBNP levels, and poorer hemodynamics compared with the higher group (≥0.246%/mmHg) (all p < 0.001). The event-free survival rate for the composite endpoint was significantly lower in the group with reduced RVFWLS/PASP compared with that observed in the higher RVFWLS/PASP group (log-rank p < 0.05). Multivariate Cox regression analysis demonstrated RVFWLS/PASP ≥ 0.246%/mmHg was independently predictive of reduced risk for the primary endpoint (HR = 0.46, 95%CI 0.23-0.93, p < 0.05). Moreover, RVFWLS/PASP facilitated additional risk stratification among patients classified as low risk based on established models (FPHN, COMPERA 2.0, and REVEAL Lite 2). CONCLUSIONS:RVFWLS/PASP is a robust, independent determinant of long-term prognosis in patients with PAH. As a noninvasive measure of RV-PA coupling, it provides significant incremental value for clinical risk assessment and treatment monitoring.

Mitochondrial dynamics play an indispensable role in maintaining the proliferation-apoptosis balance of pulmonary artery smooth muscle cells (PASMCs), a process closely linked to hypoxic pulmonary hypertension (HPH). P21-activated kinase 5 (PAK5) has been implicated in cancer-related mitochondrial dysfunction to induce cell proliferation/apoptosis and pulmonary hypertension (PH) shares numerous similarities with cancer, yet its pathophysiological role in HPH, and its mechanistic connection to mitochondrial fission remains unclear. Here, we demonstrated that PAK5 expression was upregulated in the lungs and pulmonary vasculature and mitochondrial fission was dysregulated following HPH injury. In tissue samples from PH patients, PAK5 expression positively correlated with pulmonary vascular remodeling. In vivo, PAK5-silenced mice exhibited significantly improved hemodynamic parameters and right ventricular function compared to control mice. In vitro, hypoxia-induced upregulation of PAK5 promoted dynamin-related protein 1 (Drp1) activation, leading to the occurrence of mitochondrial midzone division, reduced expression of the mitochondrial fusion protein Mfn1, and enhanced expression of proliferative proteins including PCNA, Cyclin A, and Cyclin D. Pharmacological or viral-induced PAK5 deficiency resulted in enhanced Mfn1 expression, reduced levels of Drp1, Mff, PCNA, Cyclin A, and Cyclin D, and consequently attenuated mitochondrial midzone division and excessive PASMC proliferation. Our findings indicate that PAK5 participates in the development of HPH by driving mitochondrial fission through Drp1, and this study provides a new potential therapeutic target for HPH.

Background Complete occlusion of pulmonary artery branches is challenging for percutaneous transluminal pulmonary angioplasty (PTPA) in chronic thromboembolic pulmonary hypertension (CTEPH) patients. Case Summary We report 2 CTEPH patients (a 30-year-old woman and a 63-year-old woman) with complete occlusion of right A8a and left A7 branches, respectively. In case 1, a Sion guidewire was advanced retrogradely via an intrapulmonary collateral from the adjacent A8b branch, successfully crossing the occlusion followed by balloon dilation. In case 2, the retrograde wire could not re-enter the proximal trunk; it was left as an intraluminal landmark to guide an antegrade Pilot 50 wire, achieving recanalization. Both cases were technically successful without complications. Discussion Retrograde wiring via intrapulmonary collaterals is feasible and can facilitate recanalization of occluded pulmonary arteries during PTPA. Take-Home Message In selected CTEPH patients, intrapulmonary collaterals provide a retrograde route to recanalize occluded pulmonary arteries during PTPA.

To compare plasma levels of miR-126-3p between patients with essential hypertension (EH) and healthy individuals, and to investigate its correlation with renin–angiotensin–aldosterone system (RAAS) biomarkers. 29 healthy controls and 71 EH patients were enrolled. Total RNA, including miRNA, was extracted from plasma. Relative expression of miR-126-3p was determined by qRT-PCR. The discriminative ability of miR-126-3p and a combined panel was evaluated using ROC curves. The relative expression of miR-126-3p was significantly higher in the EH group (3.20 ± 2.15) than in the healthy group (1.54 ± 1.27, P < 0.001). Spearman correlation showed a significant negative correlation between miR-126-3p and serum ACE2 activity (r = − 0.205, p = 0.041). The AUC of a combined indicator (miR-126-3p, AngII, LDL-C, TC) was 0.859 (95% CI: 0.769–0.950, P < 0.001). Stepwise regression identified AngII, TC, LDL-C, and miR-126-3p as significant (P < 0.05), although collinearity was within an acceptable range (VIF < 5). miR-126-3p is significantly upregulated in the peripheral blood of EH patients and correlates negatively with ACE2. The combined panel shows moderate exploratory discriminative ability. However, due to the absence of continuous blood pressure data, no claim of added value over blood pressure measurement can be made. The potential role of miR-126-3p in modulating the RAAS counter‑regulatory axis requires further validation.

Pulmonary arterial hypertension (PAH) has a poor prognosis despite available treatments. TPN171H, structurally modified from traditional Chinese medicine (Epimedium), was reported to have a high affinity for phosphodiesterase type 5 and exhibited anti-inflammatory and vasodilatory effects in preclinical studies. This phase 2a randomized trial (NCT04483115) evaluated the hemodynamic effects and safety of TPN171H in PAH. Sixty patients with PAH were randomly assigned to receive placebo, TPN171H (2.5, 5, or 10 mg) or tadalafil (20 or 40 mg) and evaluated for hemodynamic changes for 24 h. The primary endpoint was the maximum change (%) in pulmonary vascular resistance (PVR) from baseline. The key secondary endpoint was the change (%) in PVR to systemic vascular resistance (SVR) ratio at each observation point from baseline. Compared to the placebo group, the least square mean differences in the maximum change in PVR were -16.8% (95% CI, -29.1 to -4.5, p = 0.008) in TPN171H 5 mg, -15.4% (95% CI, -28.2 to -2.7, p = 0.019) in tadalafil 20 mg, and -13.3% (95% CI, -25.6 to -0.9, p = 0.036) in the tadalafil 40 mg group. Moreover, TPN171H 5 mg, but none of the tadalafil doses, showed a significant reduction in PVR/SVR ratio at 2 h (p = 0.026), 3 h (p = 0.030), and 5 h (p = 0.046) compared to the placebo group. No serious adverse events occurred. TPN171H 5 mg demonstrated favorable acute hemodynamic effects and an acceptable short-term safety profile in this exploratory trial, supporting further evaluation in adequately powered trials.

Combined pulmonary fibrosis and emphysema-associated pulmonary hypertension (CPFE-PH) has emerged as a distinct third category of PH, yet its detailed clinical-hemodynamic profile, pathological features, and comparative outcomes remain poorly defined. This study aims to characterize the phenotype of CPFE-PH and compare it with chronic obstructive pulmonary disease-related PH (COPD-PH) and idiopathic interstitial pneumonia-related PH (IIP-PH). In this multicenter cohort study, we analyzed 113 patients with CPFE-PH, 277 with COPD-PH, and 78 with IIP-PH, all diagnosed by right heart catheterization. Clinical, physiological, imaging, pathological, treatment response, and survival data were statistically compared across groups. CPFE-PH patients were older, predominantly male smokers, and exhibited preserved ventilatory function but severely reduced diffusing capacity (DLCO 31.6

To the Editor: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but serious condition characterized by obstruction of the pulmonary arteries due to thromboembolic events and subsequent vascular remodeling, which leads to pulmonary hypertension (PH). Classified as Group 4 in the 2022 PH guidelines by the European Society of Cardiology and the European Respiratory Society, CTEPH poses significant risks, including progressive PH, right ventricular dysfunction, and mortality if left untreated. Despite established diagnostic and treatment guidelines, the exact national prevalence of CTEPH remains largely unknown due to the absence of organized registries, with estimates ranging from 3 to 30 cases per million people. Although CTEPH is commonly thought to follow acute pulmonary embolism (PE), epidemiological data reveal a discrepancy; studies suggest that only 0.1% to 3.8% of PE patients may develop CTEPH.[1,2] Recent reports indicate that 65.6% of CTEPH patients have a history of acute PE, although this proportion varies across regions.[3] Treatment options include pulmonary endarterectomy (PEA), riociguat, and balloon pulmonary angioplasty (BPA). CTEPH significantly impacts patients' quality of life, causing symptoms such as shortness of breath and fatigue, which lead to increased healthcare utilization and economic burden. In China, limited awareness and delayed diagnosis further complicate the management of CTEPH, underscoring the need for studies that address the disease's burden and enhance recognition among healthcare providers. Therefore, this systematic review aimed to estimate the prevalence of CTEPH using data from PE patients and to investigate the characteristics and management patterns of CTEPH in the Chinese population. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered in the PROSPERO database (Ref. CRD42024510051). An electronic search of databases, including PubMed, EMBASE, Web of Science, Cochrane, the Chinese Biomedical Database (CBM), China National Knowledge Infrastructure (CNKI), and the Wanfang Digital Resource Database, was conducted in August 2023. No restrictions were applied regarding language or publication status. Due to the limited epidemiological evidence, we applied Gall's methodology (2017) to indirectly calculate the prevalence of CTEPH in the general Chinese population.[4] This approach involved estimating overall CTEPH prevalence based on the proportion of CTEPH among PE patients, the prevalence of PE in the general population, and the proportion of CTEPH cases associated with prior PE. Diagnosis of PE and CTEPH was based on the definitions used in the original studies. Inclusion criteria varied between the prevalence and characteristics investigations. For the prevalence study, we included observational studies involving the general population and PE patients in China, which reported PE prevalence, the proportion of CTEPH among PE patients, and the number of CTEPH cases with and without a history of PE. For the characteristics investigation, we included prognostic and cross-sectional studies on CTEPH patients in China, focusing on venous thromboembolism (VTE) history, comorbidities, demographics, risk factors, disability rates, and treatment patterns. Exclusion criteria included interventional studies, case reports, abstracts, reviews, conference proceedings, and literature not published in English or Chinese. Both study selection and data extraction were performed by two independent reviewers, with discrepancies resolved through discussion. For dichotomous outcomes, rates were extracted, and pooled proportions with 95% confidence intervals (CIs) were calculated using a random-effects model in R software (version 4.3.1, https://www.r-project.org/). For continuous outcomes, means and standard deviations (SDs) were pooled similarly. The prevalence of CTEPH was estimated using the following formula: Zprevalence of CTEPH =P1proportion of CTEPH following PE×P2prevalence of PE P3proportion of CTEPH cases with a history of PE These proportions were obtained through meta-analysis. For characteristics related to comorbidities and treatment, the results were described narratively. Heterogeneity was assessed using the Cochrane Q test and I2 statistic, with substantial heterogeneity indicated by an I2 ≥50% and a P-value <0.1 from the Q test. Publication bias was evaluated using a funnel plot and Egger's test, but only when there were more than 10 studies. The risk of bias in studies estimating CTEPH prevalence was independently assessed by two reviewers using the Joanna Briggs Institute (JBI) critical appraisal checklist for prevalence studies. Ultimately, 31 studies on CTEPH and 5 studies on PE were included [Supplementary Figures 1 and 2, https://links.lww.com/CM9/C403]. To estimate the prevalence of CTEPH in China, 18 studies were analyzed [Supplementary reference list 1, https://links.lww.com/CM9/C403]. The quality assessment revealed that 83% (15/18) of studies lacked an appropriate sample frame, 50% (9/18) did not enroll an adequate sample size, and 78% (14/18) failed to measure the condition reliably [Supplementary Table 1, https://links.lww.com/CM9/C403]. The pooled proportion of CTEPH following PE (P1) was found to be 5.36% (95% CI: 3.04–7.67%, Supplementary Figure 3, https://links.lww.com/CM9/C403), based on seven studies involving 1843 patients. Two prevalence representations of PE were identified: P2a (0.09% among hospitalized patients, from five studies, 95% CI: 0.08–0.10%, Supplementary Figure 4, https://links.lww.com/CM9/C403) and P2b (0.0071% among the general population, from one study). The proportion of CTEPH cases with a history of PE (P3) was 56.50% (95% CI: 48.61–64.38%, Supplementary Figure 5, https://links.lww.com/CM9/C403). Using these values, the overall prevalence of CTEPH was estimated at 85 cases per million in hospitalized populations (Za) and 6.74 cases per million in the general population (Zb), translating to approximately 9729 individuals with CTEPH in China [Table 1]. Table 1 - Definitions and values of variables in formula used to calculate prevalence of CTEPH among general population in China. Variable Definition Rate (95% CI) Source Sample size P1 Proportion of CTEPH following PE 5.36% (95% CI 3.04 to 7.67%) Gong 2015, Yang 2015, Bian 2015, Guo 2016, Xi 2016, Xu 2022, Xu 2016 1843 P2a Prevalence of PE among hospitalized population 0.09% (95% CI 0.08 to 0.10%) Yang 2011, Li 2016, Liu 2011, Wang 2017, Zhang 2019 55,028,750 P2b Prevalence of hospitalized PE among general population 0.0071% Zhang 2019 NA P3 Proportion of CTEPH cases with a history of PE 56.50% (95% CI 48.61 to 64.38%) Deng 2020, Du 2019, Han 2013, Shu 2007, Wang 2018, Xie 2019 1221 Za Prevalence of CTEPH among hospitalized population 85 cases per million (95% CI 42 to 128 cases per million) P1×P2a/P3 NA Zb Prevalence of CTEPH among general population 6.74 cases per million P1×P2b/P3 NA CI: Confidence interval; CTEPH: Chronic thromboembolic pulmonary hypertension; NA: not applicable; PE: Pulmonary embolism; SD: Standard deviation; SE: Standard error. For references of studies listed in Source column, please see Supplementary reference list 1, https://links.lww.com/CM9/C403. 95% CI of prevalence of CTEPH among general population calculated using delta method SE=p22p32Var(p1)+p12p32Var(p2)+p12p22Var(p3)p34 95% CI: Z ± 1.96SE. The 30 studies provided insights into the baseline clinical characteristics of CTEPH patients [Supplementary references list 2, https://links.lww.com/CM9/C403]. The average age was 57.55 years, with 47.02% of patients being female. The mean body mass index (BMI) was 23.99 kg/m2, and 39.02% had a history of smoking. Notably, 56.50% had a history of PE, while 61.38% were classified as World Health Organization (WHO) functional class III/IV, with an average time from symptom onset to diagnosis of 24.63 months [Supplementary Table 2, https://links.lww.com/CM9/C403]. Egger's tests for mean age, BMI, female proportion, smoking history, and WHO functional class III/IV showed no significant publication bias across the studies (P >0.05, Supplementary Figures 6–10, https://links.lww.com/CM9/C403). Common comorbidities included diabetes mellitus (2.00–33.33%), hypertension (8.33–75.00%), coronary heart disease (6.35–16.67%), and chronic obstructive pulmonary disease (COPD, 2.78–27.27%). Comorbidities associated with the onset of CTEPH included varicose veins in the lower limbs (63.64%) and deep vein thrombosis (DVT; 31.25% to 96.88%; Supplementary Table 3, https://links.lww.com/CM9/C403). Additionally, common risk factors identified for CTEPH included pulmonary artery systolic pressure (PASP) and intermediate- to high-risk PE [Supplementary Table 4, https://links.lww.com/CM9/C403]. Mortality rates associated with CTEPH were reported in seven studies, ranging from 6.94% to 45.45%. Among these, three studies reported additional estimated survival rates: 1-year survival rate was from 93.3% to 97.1%, 3-year survival rate was from 84.6% to 93.3%, 5-year survival rate was from 73.4% to 86.9%, 7-year survival rate was 82.0%, and 8-year survival rate was 66.6%, respectively [Supplementary Table 5, https://links.lww.com/CM9/C403]. Unfortunately, data on disability rates and socioeconomic burdens were not available. Treatment patterns revealed that 11.11% to 35.14% of patients received PEA, and 10.29% to 40.95% were treated with BPA. Medical therapy alone was documented in 30.29% to 88.89% of cases. Among patients using specific medications, a significant proportion received a combination of conventional anticoagulants and other therapies [Supplementary Table 6, https://links.lww.com/CM9/C403]. Compared to global trends of 3 to 30 cases per million, our study found a higher prevalence of CTEPH among hospitalized patients in China. This discrepancy may stem from prior studies that primarily focused on acute PE cases, while CTEPH can also develop from sub-acute and chronic PE, as well as in individuals without a history of PE. Our analysis included a broader range of PE patients, although it may overestimate the prevalence of CTEPH due to the higher likelihood of inpatient cases. Furthermore, the estimation of prevalence in the general population is based on a single study, which requires further validation through larger epidemiological investigations. Our study also reveals a significant delay in diagnosis, with many patients presenting at advanced stages of the disease. This underscores the urgent need to increase awareness for early detection of CTEPH. The absence of standardized guidelines for multimodal therapy, coupled with limited evidence on approved medications such as riociguat, underscores the need for improved treatment strategies and further research in this area. Several limitations of our study should be noted. First, the imprecision inherent in the calculation formula, along with notable heterogeneity due to diverse patient characteristics and study designs, may have impacted the results. Additionally, the lack of tailored prevalence studies further complicates the accuracy of our findings. Risk factor analysis was based on descriptive data rather than pooled data, which hinders a more precise predictive assessment of these factors. The relatively small sample sizes in the studies examining risk factors may contribute to data instability, emphasizing the need for caution in interpreting the results. This also highlights the importance of future research involving larger sample sizes. In conclusion, our study highlights the complexity of the CTEPH landscape in China, stressing the need for greater awareness, specialized databases, and enhanced clinical standards. Ongoing studies are expected to provide further insights into the management patterns and outcomes of CTEPH in the Chinese population. Acknowledgements The authors would like to acknowledge Miss Xue Zhou, Miss Yang Zhang, and Dr. Sitong Dong from Systematic Review Solutions Ltd for their medical writing and editorial support, which was funded by MSD China. Funding This study was supported by the National Key Research and Development Program of China (No. 2023YFC2507200), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (No. 2021-I2M-1-049), National High Level Hospital Clinical Research Funding (No. 2022-NHLHCRF-LX-01-0203), and National Natural Science Foundation of China (Nos. 82241029, 81970058). Conflicts of interest Y Wu and J Zou are employees of MSD China, while Jean-François Richard is an employee of Merck & Co. The other authors declare no competing interests.

Human melatonin receptor type 1/2 (MTR1/MTR2) are widely distributed throughout the body and play essential roles in regulating cardiovascular physiology. However, the therapeutic potential of agomelatine (AGM), a melatonin analog and nonselective MTR1/MTR2 agonist, in pulmonary arterial hypertension (PAH) remains unclear. The present investigation was designed to evaluate the ameliorative potential of AGM on pulmonary vascular remodeling in a SU5416/hypoxia (SuHx)-induced PAH rat model, and to elucidate the concomitant mechanistic pathways. Our experimental data demonstrated that AGM treatment significantly diminished right ventricular systolic pressure, mitigated right ventricular hypertrophy, and attenuated medial wall thickening of pulmonary arteries. Notably, immunofluorescence staining further revealed predominant localization of MTRs within the smooth muscle layer of pulmonary arteriole. In vitro, AGM significantly suppressed hypoxia-evoked proliferative and migratory responses in human pulmonary artery smooth muscle cells (PASMCs). Mechanistically, AGM enhanced mitochondrial reactive oxygen species generation and facilitated mitophagic flux, as corroborated by upregulated LC3-II protein expression, diminished p62 abundance, and increased mitochondrial-lysosomal colocalization. Transcriptomic analysis identified unc-51 like autophagy activating kinase 1 (ULK1) as a pivotal mediator of AGM-induced mitophagy. Genetic silencing of ULK1 abrogated the cytoprotective efficacy of AGM against hypoxia-evoked PASMC dysfunction. Further investigation revealed that AGM upregulated Sirtuin 1 (SIRT1) expression, leading to forkhead box protein 1(FoxO1) deacetylation. In contrast, inhibition of SIRT1 resulted in increased FoxO1 acetylation, which subsequently downregulated ULK1 expression and impaired mitophagy. Collectively, these findings establish that AGM exerts therapeutic effects in PAH by enhancing ULK1-dependent mitophagy through modulation of the SIRT1/FoxO1 signaling axis, underscoring its potential as a novel therapeutic candidate for PAH.

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

Background Chronic thromboembolic pulmonary hypertension (CTEPH) presents challenges due to its complex pathobiology. Although numerous studies have reported heterogeneous cell types by single-cell RNA sequencing, the atlas and characteristics of plasma cells remain poorly understood. Objectives To identify the altered phenotype and differentiation patterns of plasma cells in CTEPH. Methods We performed single-cell RNA sequencing on pulmonary endarterectomy tissue from 5 patients and 6 normal pulmonary arteries. Serum immunoglobulins (Igs) were measured using protein electrophoresis among 273 CTEPH patients, 259 idiopathic pulmonary arterial hypertension (IPAH) patients, and 251 healthy controls. Results The percentage of plasma cells was significantly increased from less than 1% in healthy controls to 15% in CTEPH patients. We identified 1 B cell cluster and 5 distinct mature plasma cell clusters, including IGHG1, HSPA1A, AHNAK, IGLC3, and IGKV4. Notably, the AHNAK and IGLC3 subclusters are newly identified. GeneSwitches analysis indicated early activation of IGHG1 and early deactivation of HLA-DPA1. The trajectory of AHNAK cluster was earlier than that of IGLC3 cluster, with an enrichment for pathways responsive to lipopolysaccharide. The IGLC3 cluster revealed lower differentiation potential and was predominantly associated with Ig production. Furthermore, Igα2 levels in CTEPH patients were lower than in controls but higher than in IPAH patients. Significantly, Igγ levels were markedly elevated in CTEPH patients compared with IPAH patients and controls, better distinguishing CTEPH patients from controls and IPAH patients. Conclusion Plasma cells of CTEPH had a distinctive landscape and heterogeneity. The newly identified clusters represented excessive Ig production but lacked immune response function. These findings highlight that targeted plasma cells can be used to develop novel CTEPH treatments.

Urban expansion, with multifaceted urban form changes, has been proved to have profound impact on environmental quality and population health. While existing research has widely explored the link between urban form and respiratory health, most evidence comes from intra-city comparisons within single metropolitan areas, highlighting a need for more representative, nationwide studies. To address this gap, we systematically examined associations between urban expansion characteristics and lung cancer incidence across 180 Chinese cities, using structural equation models with air pollution exposure as a mediator. Our findings indicated that urban expansion characterized by a larger total urban area (β = 0.204, p = 0.014), higher urban population density (β = 0.191, p = 0.004), greater patch density (β = 0.240, p = 0.002), higher annual growth rate (β = 0.266, p < 0.001), and increased urban cropland mixing (β = 0.415, p < 0.001) was associated with higher levels of air pollution exposure, which in turn contributed to elevated lung cancer incidence (β = 0.235, p < 0.001 for females; β = 0.214, p < 0.001 for males). Compared with prefecture-level cities, total urban area, annual growth rate, and urban cropland mixing had a larger marginal impact on lung cancer incidence in county-level cities. Our nationwide analysis shows urban expansion characteristics – specifically larger scale, higher density, faster expanding speed, and cropland mixing – significantly elevate lung cancer risk through increased air pollution exposure, with stronger effects in county-level cities. These results provide exploratory evidence that may inform the development of health-oriented urban policies and land use interventions, not only in China but also in other rapidly urbanizing developing countries.

Background:Combined post-capillary pulmonary hypertension (Cpc-PH) is a severe form of pulmonary hypertension associated with high morbidity and mortality. Early identification and intervention are crucial but challenging due to the invasive right heart catheterization (RHC). This study aimed to develop and validate a non-invasive diagnostic model, the Predictive Echocardiography Cpc-PH Score (PECS), using echocardiographic parameters to facilitate detection of Cpc-PH. Methods:A retrospective analysis encompassing 198 patients with suspected PH-LHD, admitted from July 2010 through December 2023, was executed. Patients were divided into Cpc-PH and Ipc-PH/No-PH groups based on RHC in accordance with the 7th World Symposium on Pulmonary Hypertension criteria for PECS model construction. Chi-square and L1-regularized backward elimination refined predictive indicators. Model efficacy and stability were appraised via receiver operating characteristic and 5-fold cross-validation. Results:The PECS model, incorporating a suite of indicators including valvular heart disease, left atrial systolic diameter, interventricular septal thickness, mitral valve E/Em ratio, left ventricular fractional shortening, and tricuspid regurgitation velocity, demonstrated good predictive performance, achieving an area under characteristic (AUC) of 0.761 (95% CI: 0.692-0.823, P < 0.001). It demonstrated a sensitivity of 66.7%, specificity of 72.0%, a positive predictive value of 72.9%, a negative predictive value of 65.7%, and an overall accuracy of 69.2%. A total of 5-fold cross-validation confirmed these findings, yielding an AUC of 0.752 ± 0.070. Conclusion:The PECS model provides a non-invasive and precise approach to diagnosing Cpc-PH, potentially acting as a practical screening tool.