Since its identification in 2001, human metapneumovirus (hMPV) has been recognized as an important cause of acute respiratory tract infection in all age groups. Although infection is often mild in healthy adults, hMPV can cause severe lower respiratory tract disease, including pneumonia, in young children, older adults, individuals with chronic diseases and immunocompromising conditions, and residents of long-term care facilities. Accumulating evidence demonstrates that hMPV contributes substantially to hospitalization, intensive care unit admission, and mortality in these high-risk populations. Globally, hMPV circulates seasonally, most commonly in late winter and spring, contributing to both community- and healthcare-associated respiratory infections; however, the COVID-19 pandemic disrupted established epidemiology, resulting in shifts in epidemic timing, off-season resurgences, genotype replacement, and increased overlap with other respiratory viruses, while also providing insights into viral interference and multivirus cocirculation. Clinical manifestations of hMPV overlap with other respiratory viruses, including influenza virus or SARS-CoV-2, and selective diagnostic practices contribute to under-recognition and under-testing. Although no specific antiviral therapies or licensed vaccines are currently available, identification of hMPV has important implications for diagnostic accuracy, prognosis, antimicrobial stewardship, and infection prevention, particularly in hospital and long-term care settings. This review summarizes current evidence on the virology, epidemiology, post-COVID-19 trends, clinical manifestations, outcomes, diagnosis, and prevention of hMPV, with a particular focus on adults and other high-risk populations. We also review the current landscape of hMPV vaccine development and its potential implications for clinical practice and public health.
The development and progression of respiratory diseases are influenced by both the local pulmonary microenvironment and the intestinal ecosystem. Research on the gut-lung axis has shown that diverse small-molecule metabolites produced or modified by the gut microbiota can cross the intestinal barrier and enter the systemic circulation, where they may modulate immune-cell response thresholds, functional polarisation, and inflammatory dynamics in the distal lung. The local respiratory microbiota may also contribute to the pulmonary metabolic microenvironment, although its role in metabolite production and immune regulation remains less clearly defined. This review summarises the metabolic features of the gut and respiratory microbiota, focusing on the production, systemic distribution, and immunomodulatory mechanisms of microbiota-associated metabolites, including short-chain fatty acids, other short-chain carboxylic acids, and amino acid-derived metabolites, with attention to their effects on respiratory immune-cell populations. These mechanisms include metabolite-sensing G protein-coupled receptor signalling, histone deacetylase inhibition, and aryl hydrocarbon receptor-dependent mucosal immune programmes. At the disease level, current evidence suggests that these metabolites mainly influence viral infections, bacterial infections, and chronic inflammatory lung diseases by regulating immune-response intensity, persistence, and tissue tolerance, rather than directly mediating pathogen clearance. Finally, this review discusses the key challenges and future directions for moving from associative studies to causal validation and translational applications.
Objective: To investigate the impact of the mismatch between respiratory event frequency and hypoxic burden on cardiovascular outcomes in patients with obstructive sleep apnea (OSA). Methods: This study enrolled 3 754 adult OSA patients from the Sleep Heart Health Study, a prospective cohort study. Respiratory event frequency and hypoxic burden were assessed using the apnea-hypopnea index (AHI) and the percentage of time spent with oxygen saturation below 90% (T90), respectively. Patients were stratified into three groups based on the tertile alignment of AHI and T90: the matched group (AHI and T90 in the same tertile), the AHI-dominant group (AHI in a higher tertile than T90), and the T90-dominant group (T90 in a higher tertile than AHI). The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction, heart failure, and revascularization. Cox regression analysis was used to explore the association between AHI-T90 matching status and MACE. Kaplan-Meier survival analysis was performed to compare the prognosis among the groups. Restricted cubic spline (RCS) analysis was used to evaluate the association between the relative difference of AHI and T90 and MACE. Results: The age of the participants was 65 (57, 74) years, and 1 997 (53.2%) were men. Among them, 1 745 (46.5%) patients exhibited an AHI-T90 mismatch. There were 2 009 patients in the matched group, 882 in the AHI-dominant group, and 863 in the T90-dominant group. During a mean follow-up of 10.3 years, 974 patients (25.9%) experienced MACE. Kaplan-Meier curves showed that the incidence of MACE was significantly higher in the mismatch groups compared to the matched group (both Plog-rank<0.05). Multivariable Cox regression analysis demonstrated that the AHI-dominant group (HR=1.173, 95%CI 1.004-1.369, P=0.044) and the T90-dominant group (HR=1.187, 95%CI 1.016-1.386, P=0.031) were independently associated with MACE. RCS revealed that the risk of MACE was lowest when the relative difference between AHI and T90 was minimal. Conclusion: Mismatch between respiratory event frequency and hypoxic burden represents a distinct OSA phenotype associated with a higher incidence of MACE. 目的： 探究呼吸事件频率与低氧负荷失匹配对阻塞性睡眠呼吸暂停（OSA）患者心血管预后的影响。 方法： 基于睡眠心脏健康研究的前瞻性队列，入选3 754例成年OSA患者。分别使用呼吸暂停低通气指数（AHI）和血氧饱和度低于90%累积时间占总睡眠时间百分比（T90）评价呼吸事件频率和低氧负荷，并根据二者的匹配情况将OSA患者分为匹配组（分别根据AHI和T90三分位数将患者进行分组，当二者处于相同三分位时定义为AHI-T90匹配）、AHI主导组（AHI处于较高三分位）和T90主导组（T90处于较高三分位）。主要结局为主要不良心血管事件（MACE），定义为心血管死亡、心肌梗死、心力衰竭和血运重建的复合结局。使用Cox回归探究AHI-T90匹配情况与MACE的关系，使用Kaplan-Meier生存分析比较组间预后差异。使用限制性立方样条评价二者相对差异对MACE的影响。 结果： 年龄65（57，74）岁，其中男性1 997例（53.2%）。1 745例（46.5%）存在AHI-T90不匹配。匹配组2 009例，AHI主导组882例，T90主导组863例。平均随访10.3年，3 754例OSA患者中共发生了974例MACE（25.9%）。Kaplan-Meier曲线显示，AHI主导组和T90主导组的MACE发生率均显著高于匹配组（Plog-rank均<0.05）。多因素Cox回归结果示，AHI主导组（HR=1.173，95%CI 1.004~1.369，P=0.044）和T90主导组（HR=1.187，95%CI 1.016~1.386，P=0.031）是MACE的独立影响因素。限制性立方样条图曲线显示，当AHI与T90相对差异最小时，OSA患者MACE风险最低。 结论： 呼吸事件频率和低氧负荷失匹配是一种特殊的OSA亚型，其发生心血管事件的风险较高。.
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in infants and immunocompromised adults, and secondary bacterial infections are recognized as important contributors to disease severity. Recent microbiome studies have shown that Haemophilus influenzae is frequently co-detected in severe RSV cases and ranks among the bacteria most closely correlated with disease severity; however, its causal role and underlying mechanisms remain unclear. Here, we used a murine model to examine the manner in which H. influenzae influences RSV-associated airway inflammation. We established a murine respiratory infection model by infecting mice with RSV and subsequently intratracheally inoculating them with live, ultraviolet (UV)-killed, or heat-killed nontypeable H. influenzae (NTHi). Body weight, viral and bacterial loads, bronchoalveolar lavage fluid (BALF) cytokine levels, and immune cell populations were analyzed. Live NTHi inoculation following RSV infection induced severe lower airway inflammation, characterized by pronounced body weight loss and lung injury along with increased CD8+ T-cell accumulation and enhanced interleukin (IL)-6 inflammatory mediator production in BALF. Additionally, CD8+ T-cell depletion modestly attenuated body weight loss, altered the recruited innate immune cell composition, and reduced BALF IL-6 levels. However, RSV-infected mice inoculated with UV- or heat-killed NTHi exhibited CD8+ T-cell accumulation without developing body weight loss, which suggested that CD8+ T-cell accumulation alone may be insufficient to drive full disease manifestation. In contrast to that observed for non-viable NTHi, live NTHi induced robust neutrophil recruitment along with strong production of inflammatory mediators. Additionally, BALF IL-6 levels showed a strong negative correlation with body weight; hence, IL-6 was identified as a potential marker associated with disease severity. This mouse model shows that pulmonary inoculation of live NTHi after RSV infection induces severe lower airway inflammation partially involving CD8+ T cells and that IL-6 is a potential biomarker associated with disease severity. Overall, this study suggests a novel pathological role for NTHi in the exacerbation mechanism of secondary bacterial infection in RSV infection.
Cough hypersensitivity is increasingly recognized as a key mechanism underlying chronic cough across diverse etiologies. The Cough Hypersensitivity Questionnaire (CHQ) was developed to systematically assess characteristic triggers and abnormal sensory perceptions; however, its structural and clinical relevance across respiratory diseases remains unclear. We prospectively enrolled 300 adults with chronic cough from multiple respiratory centers. Participants completed four cough-related questionnaires: the Numeric Rating Scale (NRS), Leicester Cough Questionnaire (LCQ), Cough Assessment Test (COAT), and CHQ. Spearman correlation and network analyses were used to evaluate associations between CHQ items and other cough-related measures, including subgroup analyses by disease etiology. The CHQ demonstrated variable associations with conventional instruments and differing patterns across respiratory diseases. Triggers such as perfume and smoke correlated with LCQ hypersensitivity items, while the sensation item "urge to cough" exhibited broad correlations across physical, psychological, and social domains. Socially mediated triggers (e.g., talking) aligned with LCQ social interference items. In contrast, items such as hot air, dampness, laughter, and eating/drinking had minimal external associations. Internal CHQ correlations were sparse, and no significant associations were observed between CHQ and NRS, indicating a dissociation between hypersensitivity features and perceived severity. Disease-specific analyses suggested differing patterns, with broader associations observed in asthma and bronchiectasis compared with chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. The CHQ captures distinct and heterogeneous dimensions of cough hypersensitivity that are not adequately reflected by conventional cough measures, suggesting its potential utility for characterizing clinically relevant multidimensional aspects of chronic cough.
Cardiorespiratory fitness predicts health and longevity. The gold-standard test for V̇O₂-peak, the cardiopulmonary exercise test (CPET), is difficult to conduct in older adults, and alternative methods offer low to moderate accuracy. This project compared a new method, seismocardiography, to CPET in older adults. It was hypothesized that seismographic V̇O₂-peak estimates would strongly correlate with CPET-derived V̇O₂-peak. Thirty-six healthy older adults (aged 65-75 years; 19 female) completed the seismocardiography assessment (Seismofit®) of resting V̇O₂-peak and a CPET on a cycle ergometer. Two criteria were used to support the attainment of maximal oxygen uptake (V̇O₂-peak) during the ramp exercise test: (1) a V̇O₂ plateau, defined as an increase in oxygen uptake of less than 150 mL·min⁻¹ despite a further increase in work rate during the final phase of the incremental protocol, and (2) a respiratory exchange ratio (RER) > 1.15. The V̇O₂-peak estimation at rest was performed over 40 s with participants lying supine while wearing a Seismofit® chest sensor (VentriJect, Hellerup, Denmark). Concordance between measurements was assessed using correlations and Bland-Altman plots, and paired t-test evaluated mean differences between Seismofit and CPET-derived V̇O₂-peak. The sample had a mean age of 70 ± 3.0 years and BMI of 25.7 ± 2.8 kg/m². For all participants, a significant positive correlation was observed between Seismofit® and measured V̇O₂-peak (r = 0.57, p < 0.001). When restricting the analysis to the 27 participants with validated V̇O₂-peak, a strong significant positive association between the methods was found (r = 0.80, p < 0.001). For all participants, Seismofit significantly overestimated V̇O₂-peak (t = 4.48, df = 35, p < 0.001). This study demonstrated that Seismofit show a moderate-to-strong association with CPET measurements in older adults. Seismofit, however, systematically overestimated V̇O₂-peak. For Seismofit to be integrated into large-scale cohort studies and experimental research, the methodology used for older adults needs further development.
Acute respiratory infections, including SARS-CoV-2, remain a leading cause of childhood morbidity and mortality in low- and middle-income countries (LMICs), yet the underlying immune determinants of disease severity are poorly understood. The increased susceptibility to SARS-CoV-2 could be related to a decreased antibody or altered inflammatory response. We conducted a cohort study of South African children hospitalised with acute respiratory infections, and collected mucosal and serum samples over time. Nasopharyngeal aspirates (NPAs) or swabs were tested for viral pathogens by multiplex PCR. Antibody levels, neutralising capacity, and inflammatory proteome profiles were assessed. In the cohort (median age 7.31 months, IQR 2.9-31.7), 67 children (54%) were SARS-CoV-2 positive at enrolment. Substantial baseline anti-spike IgG was detected in both SARS-CoV-2-positive (68% serum, 58% saliva) and negative (40% serum, 36% saliva) patients, irrespective of disease severity. Lower expression of salivary inflammatory proteins was associated with severe disease (p < 0.05), independent of SARS-CoV-2 status. Disease severity was associated with differences in mucosal inflammatory protein expression rather than antibody levels, irrespective of SARS-CoV-2 status. These findings highlight the potential value of salivary biomarkers for understanding mucosal immune regulation and identifying children at risk of severe respiratory infection outcomes in LMICs.
Acute respiratory distress syndrome (ARDS) is a complex and heterogeneous clinical syndrome characterized by diffuse alveolar damage, severe hypoxemia, and a high risk of respiratory complications. Among these, the Macklin effect has emerged as an early radiological sign associated with the subsequent development of barotrauma. Although several genetic and molecular factors have been implicated in ARDS susceptibility and progression, their potential contribution to the biological processes underlying Macklin effect development remains largely unexplored. This review aims to examine current evidence on genetic susceptibility factors, molecular biomarkers, and multi-omics signatures involved in ARDS pathophysiology, with particular attention to mechanisms that may increase alveolar fragility and predispose to the development of the Macklin effect. A narrative review of the literature was conducted, focusing on studies investigating genetic polymorphisms, inflammatory pathways, transcriptomic profiles, proteomic biomarkers, and metabolomic alterations associated with ARDS severity, tissue injury, and pulmonary complications. Available evidence indicates that genetic variants involved in innate immunity, inflammatory signaling, and endothelial barrier regulation, including polymorphisms in TLRs, IL-1B, TNF-α, and S1PR3, contribute to interindividual variability in ARDS susceptibility and clinical outcomes. Multi-omics studies have identified several biomarkers, including TIMP1, MMP8, PTX3, and CCL2, that are consistently associated with dysregulated inflammation, extracellular matrix remodeling, immune cell recruitment, and epithelial-endothelial barrier dysfunction. These mechanisms are biologically plausible contributors to progressive alveolar injury and increased susceptibility to air leak syndromes. In parallel, molecular profiling studies have identified distinct ARDS subphenotypes associated with differences in disease severity, ventilator dependence, and mortality. To date, no genetic or molecular biomarkers have been specifically validated as predictors of Macklin effect development. Nevertheless, the available literature supports the existence of molecular pathways linking inflammation, tissue remodeling, and barrier dysfunction to processes that may facilitate alveolar rupture and air dissection. Further prospective studies integrating molecular profiling, radiological findings, and clinical outcomes are needed to determine whether these candidate biomarkers can improve risk stratification and prediction of barotrauma in patients with ARDS.
The human nasopharynx is colonized by a diverse community of commensal microbiota linked to many respiratory diseases, yet their associations with the host remain unclear. In this study, we introduced a dual-transcriptomics analysis strategy, which can characterize the host transcriptome and microbiome from nasal samples simultaneously. We applied this workflow to a local SARS-CoV-2 cohort with 76 asymptomatic infected patients, among whom 52 (68.42%) developed symptomatic infection during a 1-week follow-up period. Nasal swabs were collected from all 76 patients at enrollment and from 73 patients at one-week later follow-up. We detected a median of 8.94% reads that did not map to the human genome across all 149 samples, among which around half (median 49.68%) were successfully mapped to microbiome genome. Meta-transcriptomic analysis detected significantly higher SARS-related coronavirus loads in samples from the symptomatic group at enrollment (P = 0.004), and both groups showed decreased loads one week later (symptomatic, P = 0.001; asymptomatic, P = 0.035). Compared with benchmarking 16 S rRNA sequencing on 53 samples, our computational strategy showed high correlation of relative abundance in all top 20 genera (median Rho = 0.90, Pmax < 0.001). A total of 670 bacteria species were identified to show a relative abundance ≥ 0.01% in at least 10% samples. Differential abundance analysis identified 76 species (DASs) from six phyla with significantly decreased abundance in samples from the symptomatic group (log2(fold change or FC) < -1 and adjusted P < 0.05) compared to the asymptomatic group at enrollment. Integrating these symptom-associated DASs with host's gene expression using an expression quantitative trait bacteria (eQTB) model, we found 45 symptom-associated DASs identified at enrollment were significantly associated with one to 14 genes (adjusted P < 0.05). GSEA showed a series of symptom-associated DASs were significantly correlated with pathways related to olfactory function, keratinocyte differentiation, and DNA methylation. In summary, our dual-transcriptomic analysis strategy effectively characterized host-microbiome associations, offering insights into microbial contributions to respiratory diseases.
To evaluate pathogen spectrum and epidemiological dynamics of acute respiratory infections (ARI) in Nankai District, Tianjin, during the post-pandemic era (2024-2025). Retrospective surveillance study. A total of 1853 ARI specimens were retrospectively collected from two sentinel hospitals during weeks 1-52 of 2024-2025. Multiplex PCR was used to detect 31 pathogens. Statistical analyses were performed using SPSS 25.0. The overall positivity rate was 39.61% (734/1853). Viral pathogens predominated (66.02%), followed by bacterial (23.53%) and atypical pathogens (10.45%). The top five pathogens were SARS-CoV-2 (8.90%), Haemophilus influenzae (6.31%), influenza A H3N2 (5.02%), Mycoplasma pneumoniae (4.75%), and influenza A H1N1 (3.99%). Males showed higher co-infection rates than females (P = 0.020). Positivity rates were highest in the 35-59 (48.19%) and 18-34 age groups (47.43%). M. pneumoniae primarily affected children aged 4-17 years, whereas SARS-CoV-2 was more prevalent in adults. Spring and winter exhibited the highest positivity rates, with summer the lowest (22.17%). Significant inter-annual differences were observed (P < 0.001). 2024 showed "immunity debt"-driven compensatory outbreaks with atypical pathogens, while 2025 returned to viral dominance (64.64%), particularly H3N2. Post-pandemic ARI demonstrates pronounced de-dominance and multi-pathogen co-circulation, with notable age, seasonal, and inter-annual specificity. Continuous comprehensive surveillance is essential for optimizing clinical diagnostics and public health strategies.
At the end of 2019, severe acute respiratory syndrome (SARS) caused by the novel coronavirus SARS-CoV-2 emerged in China, representing one of the most significant global health threats of the twenty-first century. This study aimed to evaluate the phenotypic and cellular activation of epithelial cells in tracheal aspirate samples from patients with severe COVID-19. A total of 48 samples were collected from 28 mechanically ventilated patients and analyzed using flow cytometry and conventional microscopy. The results revealed a high prevalence of basal, ciliary, undifferentiated cells, and pneumocytes displaying morphological abnormalities. Samples were classified into hypocellular and hypercellular profiles based on total cell counts. These profiles were associated with clinical outcomes, with hypercellular samples more frequently observed in patients who died. Hypercellular samples exhibited increased frequencies of basal, undifferentiated cells and pneumocytes, as well as a greater presence of CD45⁺ cells with elevated HLA-DR expression, indicating an influx of activated leukocytes and antigen-presenting cells. In contrast, hypocellular samples showed a higher proportion of CD45⁻PanCK⁺ cells, reflecting a predominance of epithelial cells. Hypercellular samples also demonstrated increased EpCAM⁺PanCK⁺ epithelial cells with more expression of Spike in the context of intense inflammation. ICAM-1 expression was elevated in CD45⁺ cells from hypercellular samples, while reduced in CD45⁻ cells. Finally, a superior connectivity was found for networks of correlations of hypercellular samples, especially amongst the compartments of cells expressing EpCAM. Together, these findings identify two distinct cellular profiles that may serve as prognostic indicators in severe COVID-19.
Pompe disease is a lysosomal disorder associated with respiratory muscle weakness and a high risk of sleep-disordered breathing (SDB). The impact of enzyme replacement therapy (ERT) on respiratory parameters remains insufficiently analyzed. The aim of the study was to retrospectively review the polysomnographic/polygraphic (PSG/PG) characteristics and longitudinal trajectories of 22 children with Pompe disease in an era of universal access to ERT in France. Nineteen patients had Infantile-Onset Pompe disease (IOPD) and three had Late-Onset Pompe disease (LOPD). For the IOPD subgroup, the median age at diagnosis was 2 (0-8) months and ERT was started at 2.5 (0.5-10) months. Seven patients had mild obstructive sleep apnea (OSA) with one patient having associated hypercapnia and one patient had moderate OSA. For the LOPD subgroup, the median age at diagnosis was 36 (0-48) months and ERT was started at 39 (0-52) months. One patient had moderate OSA with hypercapnia. Of the IOPD patients, after their baseline PSG/PG, two patients were weaned from NIV and two patients were initiated on long-term NIV. Among the LOPD patients, one patient continued NIV after his baseline PSG/PG. Regarding follow-up PSG/PG for the IOPD patients, one patient was successfully weaned from NIV, and one continued long-term NIV. Our findings suggest that, in a cohort of patients receiving ERT, nocturnal respiratory function is largely preserved, and that early diagnosis and prompt initiation of ERT may mitigate the progression of respiratory disease, which has historically been associated with a poor prognosis.
Heilongjiang Province shares a 2,981-km border with the Russian Federation and runs the largest land-port network in China. The sheer volume and diversity of cross-border movement at these ports complicates infectious disease surveillance and control. Although some individual ports and pathogens have been examined separately, a province-wide integrated analysis spanning all 18 border port municipalities has been absent. This study aimed to characterise the notifiable-disease burden across those municipalities and to identify the diseases warranting priority attention. Individual case records of notifiable infectious diseases reported between 1 January 2014 and 31 December 2023 were retrieved from China's National Infectious Disease Reporting Information Management System. We computed constituent ratios, crude incidence rates, and disease rankings. Joinpoint regression yielded annual percent change (APC) and average annual percent change (AAPC) estimates. Seasonality was characterised by the direct average seasonal index method. Between-group differences were evaluated with χ² or Fisher's exact tests. A two-tailed P < 0.05 was the threshold for statistical significance, and population denominators came from the Heilongjiang Provincial Statistical Yearbook. Over the decade, 64,865 statutorily notifiable cases (out of 70,244 total reported cases) were recorded, corresponding to a mean annual incidence of 220.30 per 100,000. Respiratory diseases (37.99%) and bloodborne and sexually transmitted diseases (33.68%) jointly accounted for 71.67% of the burden. The five leading diseases were pulmonary tuberculosis (23.56%), hepatitis B (15.81%), influenza (9.85%), syphilis (9.35%), and hand, foot and mouth disease (6.48%). Overall incidence was statistically stable across the period (AAPC 1.85%, 95% CI - 0.18% to 3.93%; P > 0.05), though respiratory diseases trended upward (AAPC 6.61%, P < 0.05) while enteric and zoonotic and vector-borne diseases declined significantly (P < 0.05). Monthly incidence peaked in March (seasonal index 131%) and December (128%). Males outnumbered females (male-to-female ratio 1.51:1; rising to 3.01:1 for zoonotic and vector-borne diseases). The 15-59-year age group contributed 57.54% of cases. Farmers (31.86%), homemakers and the unemployed (23.17%), and students (10.52%) were the principal occupational groups affected. The highest cumulative incidence was observed in Mishan, Suifenhe, Mohe, Muling, and Tongjiang. Respiratory infections should receive heightened prevention efforts in the winter-spring season, whereas bloodborne and sexually transmitted infections call for sustained, risk-focused measures throughout the year. Working-age adults-farmers and homemakers in particular-represent the primary target population. Mishan and Suifenhe warrant reinforced surveillance, and a strengthened China-Russia cross-border joint-prevention mechanism is needed.
Neoadjuvant immunotherapy combined with chemotherapy (NICT) improves tumor downstaging in locally advanced hypopharyngeal squamous cell carcinoma (LA-HSCC), but the effect of response-adapted surgery on outcomes is unclear. This study evaluated the efficacy and safety of NICT and compared minimally invasive versus open surgery on the basis of treatment response. We retrospectively analyzed 79 patients with stage III-IVB HSCC who received NICT. Treatment response was assessed per RECIST 1.1, and surgery was tailored accordingly. The objective response rate was 84.81%, and the pathological complete response rate was 59.49%. Grade ≥ 3 treatment-related adverse events occurred in 11.39% of patients. Following NICT, 73.4% of patients underwent transoral minimally invasive surgery, 17.7% partial laryngectomy, and 8.8% total laryngectomy, resulting in a laryngeal preservation rate of 91.14%. With a median follow-up of 15 months, there were no significant differences in progression-free or overall survival between surgical groups. However, the minimally invasive group had significantly better 1-year respiratory (89.66% versus 35.71%, p < 0.001) and phonatory (70.69% versus 0%, p < 0.001) function preservation compared to the open surgery group. Multivariate analysis confirmed that minimally invasive surgery independently predicted improved respiratory function. NICT enables high response and organ preservation in LA-HSCC, and minimally invasive surgery achieves comparable survival with superior functional outcomes, supporting its use in a personalized treatment approach.
Gentiana dahurica Fisch. is a traditional herb widely used in Chinese and Mongolian medicine for the management of respiratory disorders such as cough, sore throat, and "lung heat". Its historical application provides a strong rationale for investigating its potential in the management of COPD. Its application in Mongolian medicine for 'lung heat' syndrome provides a direct ethnopharmacological basis for exploring its anti-COPD potential. This study primarily aimed to evaluate the anti-COPD effects of G. dahurica flowers and elucidate its underlying molecular mechanisms, with a particular focus on the regulatory effects of its bioactive components on inflammatory signaling pathways. Chemical profiling was performed using HPLC-Q-Exactive-MS. A laboratory-induced COPD model was established in mice using LPS and cigarette smoke extract (CSE), followed by a 12-week treatment with G. dahurica extract. Assessments included lung function tests, histopathology, qPCR, and proteomic analysis. In vitro validation was performed on LPS-stimulated cultures, involving two distinct lung cell types: human BEAS-2B and mouse MLE-12. Fifty compounds were identified in the extract. Treatment significantly alleviated pulmonary inflammation and improved lung function in mice. Proteomic analysis revealed inhibition of the NF-κB signaling pathway. Additionally validated by downregulation of inflammatory genes. Isoorientin and luteolin were confirmed as key active compounds mediating these effects. G. dahurica flowers ameliorate COPD progression via suppressing the NF-κB signaling pathway, which provides a solid molecular basis for its traditional application in the treatment of respiratory disorders. These findings suggest that G. dahurica flowers hold great potential as a promising therapeutic agent for COPD intervention.
To identify clinical and epidemiological predictors of mortality among patients hospitalized with laboratory-confirmed influenza in Brazil during 2024, and to evaluate the association of vaccination and antiviral therapy with clinical outcomes. We conducted a nationwide retrospective cohort study using the Brazilian SIVEP-Gripe surveillance database. All hospitalized patients with RT-PCR-confirmed influenza and known outcomes were included. Multivariable logistic regression was initially performed to explore predictors of mortality. To more rigorously assess the association between COVID-19 booster vaccination and mortality, a propensity score-based inverse probability of treatment weighting (IPTW) approach was applied, with weights truncated at 10. E-values were calculated to assess robustness to unmeasured confounding. A total of 15,995 hospitalized influenza cases were included, with an overall case fatality rate of 12.1%. Influenza A predominated (88.0%) and was associated with higher mortality than Influenza B. In IPTW-weighted models, COVID-19 booster vaccination remained independently associated with reduced mortality (OR 0.90, 95% CI 0.84-0.97; p = 0.007). Additional risk factors included dyspnea, respiratory distress, and low oxygen saturation, as well as comorbidities such as obesity, diabetes, liver disease, and immunosuppression. Protective factors included influenza vaccination (OR 0.77) and oseltamivir use (OR 0.81). The model demonstrated good discrimination (AUC = 0.81, 95% CI 0.80-0.82). The E-value for the booster association was 1.46, indicating moderate robustness to unmeasured confounding. Influenza mortality in Brazil is primarily driven by age, comorbidities, and clinical severity at presentation, but is significantly mitigated by vaccination and antiviral therapy. The observed association between COVID-19 booster vaccination and reduced mortality suggests a possible heterologous immune effect, although causality cannot be established. These findings support integrated immunization strategies targeting multiple respiratory pathogens.
Posterior rib fractures represent severe thoracic trauma and are associated with a higher risk of complications due to their proximity to vital intrathoracic structures, including the intercostal vessels and lungs. Surgical stabilization of rib fractures (SSRF) has emerged as an operative strategy to restore chest wall stability, improve respiratory mechanics, and reduce pain. However, evidence specifically addressing posterior rib fractures remains limited, and current understanding is largely extrapolated from studies involving general rib fracture populations. This literature review evaluates the principles, operative techniques, effectiveness, and limitations of SSRF in posterior rib fractures, with an emphasis on surgical timing, technical challenges, and postoperative rehabilitation. Current evidence suggests that SSRF may reduce respiratory complications and improve outcomes in selected patients. Studies report reductions in pneumonia incidence and up to a 95% decrease in tracheostomy requirements in patients with flail chest. Surgical timing also influences outcomes, with pneumonia reported in 18% of patients undergoing SSRF within 72 h compared with 58% in those receiving delayed stabilization. SSRF may provide clinical benefits in appropriately selected patients with rib fractures. However, evidence specifically addressing posterior rib fractures remains limited, and further high-quality studies are required to clarify optimal indications and surgical strategies.
COVID-19 is primarily a respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can enter host airway epithelial cells through angiotensin-converting enzyme 2 (ACE2) receptors. Emerging SARS-CoV-2 variants are a roadblock to irradicating the disease. Given recombinant human annexin A5 (Anx5) inhibits proinflammatory responses, improves survival in sepsis models and binds to several receptors and lipids, we hypothesized that Anx5 impedes SARS-CoV-2 viral entry and lessens disease severity. To assess SARS-CoV-2 Spike-receptor binding domain (RBD) and ACE2 interactions with Anx5, the recombinant proteins were expressed and isolated, and interactions were evaluated using solution NMR, microscale thermophoresis, steady-state fluorescence and size-exclusion chromatography coupled to multi-angle light scattering. Remarkably, we found that Anx5 binds to both the Spike-RBD and ACE2. Further, Anx5 induced extensive 15N-Spike-RBD amide resonance broadening, most concentrated in the region that engages with ACE2 and least enriched on the opposite face, highlighting the ACE2 interface as the primary site of Anx5 binding. Finally, we demonstrate that Anx5 inhibits SARS-CoV-2 pseudoviral entry and reduces viral burden while enhancing survival in SARS-CoV-2-infected mammalian cells. Collectively, our findings demonstrate that Anx5 directly engages both Spike-RBD and ACE2, inhibits SARS-CoV-2 pseudoviral entry and reduces viral burden while enhancing survival of infected mammalian cells, supporting further investigation of Anx5 as a multi-functional anti-SARS-CoV-2 therapeutic.
Acute lung injury (ALI) is a severe inflammatory lung disorder characterized by disruption of the alveolar-capillary barrier and impaired gas exchange, often progressing to acute respiratory distress syndrome and respiratory failure. Current treatments are largely supportive with limited efficacy, underscoring the need for novel therapeutic strategies. This review summarizes current evidence on extracellular vesicles (EVs) in ALI and evaluates their potential as therapeutic agents and biomarkers. A comprehensive literature review was conducted focusing on the biological functions, mechanisms of action, and translational potential of EVs in ALI. EVs are key mediators of intercellular communication in ALI. They exert anti-inflammatory, antioxidant, and pro-regenerative effects through transfer of bioactive cargo, thereby modulating immune responses, preserving endothelial and epithelial barrier integrity, and promoting tissue repair. EVs derived from mesenchymal stem cells and endothelial progenitor cells demonstrate protective effects against lung injury and vascular dysfunction in preclinical studies. In addition, EVs hold promise as natural drug delivery systems due to their low immunogenicity and ability to cross biological barriers, as well as potential biomarkers for ALI. EVs represent a promising cell-free therapeutic platform for ALI, with applications in immunomodulation, tissue repair, drug delivery, and diagnosis. However, further mechanistic studies and rigorous translational validation are required to support clinical application.
Climate and air pollution are associated with pediatric allergic diseases; however, their relative impacts remain poorly understood, particularly in subtropical climates. This study quantified and compared the contributions of meteorological variables and air pollutants to childhood allergic rhinitis (AR), asthma and atopic dermatitis (AD). We analyzed 1,516,996 pediatric hospital visits in Chongqing, China (2014-2019, 2023-2024), including AR (n = 456,807), asthma (n = 775,181), and AD (n = 285,008). Using distributed lag non-linear models, we examined associations with temperature, humidity, atmospheric pressure, wind speed, PM₂.₅, PM₁₀, NO₂, SO₂, CO, and O₃, comparing effect magnitudes through standardized coefficients and attributable disease burdens. Temperature demonstrated the strongest associations across all diseases, with opposing effects: positive associations with respiratory allergies (AR: RR = 1.25, 95% CI: 1.16-1.35 at 30 °C, attributing 84,640 cases [18.5% of total burden]; asthma: RR = 1.10, 95% CI: 1.05-1.16 at 32 °C, attributing 58,058 cases [7.5%]) versus inverse association with AD (RR = 0.75, 95% CI: 0.68-0.83 at 30 °C, associated with 58,270 fewer cases [20.4% reduction]). Seasonal analyses demonstrated marked heterogeneity: summer concentrated AR burden (temperature attributing 18,896 cases, 22.3% of annual burden), while winter concentrated asthma NO₂ effects (21,558 cases, 11.1% of winter burden). Individual air pollutants showed substantially smaller effects than temperature. Temperature demonstrated stronger short-term associations with childhood allergic disease burden than individual air pollutants in subtropical settings. Disease-specific environmental susceptibility patterns (opposing temperature effects for respiratory versus dermatological allergies) necessitate tailored prevention strategies. These results support integrating climate adaptation measures alongside air quality management in pediatric environmental health policies, with season-specific interventions during high-burden periods.