Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease driven by fibroblast activation and extracellular matrix deposition. Endothelial-to-mesenchymal transition (EndMT) critically contributes to vascular injury and fibrotic remodeling in IPF. Legumain (LGMN), a lysosomal cysteine protease involved in excessive extracellular matrix processing and signaling modulation, has been implicated in vascular remodeling and fibrosis. This study aimed to investigate whether LGMN influences pulmonary fibrosis by regulating the EndMT process. Independent transcriptomic analyses revealed LGMN is significantly upregulated in IPF and associated with poor prognosis. Publicly available single-cell RNA sequencing datasets identify endothelial cells as a major source of elevated LGMN in human IPF and murine fibrosis, with LGMN expression positively correlating with disease severity. Our studies demonstrated that LGMN knockdown in endothelial cells inhibited EndMT and enhanced migratory and tube formation capabilities; conversely, LGMN overexpression promoted EndMT and suppressed these functions. Transcriptomic profiling indicated that LGMN knockdown significantly influenced the p38 MAPK signaling pathway. To validate the mechanism, pharmacological inhibition of p38 MAPK reduced EndMT and partially reversed LGMN overexpression-induced EndMT. In conclusion, these results indicate LGMN promotes pulmonary fibrosis by activating the p38 MAPK pathway to regulate EndMT, suggesting its potential as a therapeutic target for pulmonary fibrosis.

Efficient regeneration of the alveolar epithelium is essential for restoring lung function after injury, yet the mechanisms that govern alveolar type II cell (AT2) behavior remain insufficiently defined. Here, we identify the m⁶A RNA demethylase Alkbh5 as a pivotal regulator of AT2 cell activation and lineage progression. Conditional deletion of Alkbh5 in AT2 cells markedly enhances their proliferation and differentiation across diverse lung injury contexts-including fibrotic (bleomycin), inflammatory (LPS), mechanical (pneumonectomy), and oxidative (BHT) insults. Loss of Alkbh5 increases m⁶A modification on Amphiregulin (Areg) transcripts, stabilizing its mRNA and elevating Areg expression specifically within transitional AT2 populations. The resulting amplification of EGFR signaling drives accelerated AT2-to-AT1 differentiation and epithelial repair. Supplementation of recombinant Areg phenocopies the regenerative effects of Alkbh5 deletion, whereas Areg neutralization abrogates these responses, establishing Areg as a key downstream effector of Alkbh5. Importantly, ALKBH5 ablation or pharmacologic inhibition in human ESC-derived alveolar organoids similarly promote proliferation, differentiation, and AREG upregulation, demonstrating evolutionary conservation of this regulatory axis. Together, our findings reveal an Alkbh5-Areg-EGFR circuit that orchestrates alveolar epithelial regeneration and suggest new therapeutic opportunities for enhancing lung repair following injury.

Inflammatory bowel disease (IBD)-associated pulmonary injury is one of the frequently underestimated extraintestinal manifestations in clinical practice. It can present as subclinical pulmonary function abnormalities, radiographic changes, or overt inflammatory pulmonary diseases and often overlaps with infection- and treatment-related pulmonary toxicity, complicating early recognition and differential diagnosis. Growing evidence indicates that IBD-associated pulmonary injury is not an isolated pulmonary event but rather a cross-organ pathological process jointly driven by disruption of the intestinal mucosal barrier, dysbiosis, and aberrant microbial metabolites, systemic inflammation, and abnormal immune cell trafficking. This article provides a comprehensive review of current basic and clinical research evidence regarding intestinal barrier dysfunction, bidirectional gut-lung axis regulation, immune remodeling mediated by microbial metabolites, such as short-chain fatty acids (SCFAs), and the mechanisms and differential diagnosis of drug-induced pulmonary injury in IBD treatment. Existing studies suggest that SCFAs, tryptophan metabolites, immune cell homing, and alterations in the local pulmonary microbiota may represent key regulatory nodes in IBD-associated pulmonary injury; however, prospective studies integrating intestinal inflammatory activity, circulating biomarkers, pulmonary phenotypes, and drug exposure are still lacking. In the future, emphasis should be placed on establishing a stratified diagnostic framework for distinguishing pulmonary involvement intrinsic to the disease, infection, and drug-induced pulmonary injury, and on evaluating precision intervention strategies targeting microbial function, metabolite supplementation, and barrier repair to advance the translational application of mechanistic research on IBD-associated pulmonary injury into clinical practice.

Despite the presence of licensed vaccines and therapeutics, influenza viruses remain a major public health concern, as they cause seasonal respiratory infections and pose a pandemic threat through the emergence of zoonotic strains. Although neutralizing antibodies elicited by seasonal vaccination constitute a primary defense against infection, their protective capacity is often limited because they frequently target the epitopes that are highly susceptible to structural changes through viral evolution. To overcome this challenge, broadly protective antibodies have been intensively investigated in both humans and animal models. These antibodies recognize conserved epitopes and confer protection through multiple mechanisms beyond conventional neutralization. Recent advances in antibody discovery technologies and structural biology have enabled high-resolution mapping of conserved epitopes and the on-target antibodies that bind them. Furthermore, although broadly protective antibodies are typically elicited only at low frequencies following standard vaccination, several settings have been reported in which their induction is enhanced. Those findings increase the feasibility of epitope-focused vaccine strategies for enhancing the breadth and durability of antibody responses. In this review, we summarize current knowledge of broadly protective flu antibodies and discuss how mechanistic and structural insights can guide the development of next-generation influenza vaccines that offer broad-spectrum protection against antigenically diverse viruses.

Mycoplasma pneumoniae is the primary pathogen of community-acquired bacterial pneumonia in humans. Children and adolescents are particularly susceptible, and a dry cough is the most common clinical symptom. In severe cases, this may progress to acute respiratory distress syndrome. To determine the anti-M. pneumoniae and anti-inflammatory activities of a novel pleuromutilin derivative, 22-(4-((2-furan-1-yl)acetamido)phenyl)thio) deoxypleuromutilin (p-furoylamphenmulin, or PFAPM).

We utilized M. pneumoniae-infected mice to conduct in vivo pharmacokinetic (PK) and pharmacodynamic (PD) studies. The recommended dose was calculated based on PK/PD analysis, and treatment trials were performed at this dose to validate the fitted outcomes and investigate the anti-inflammatory effects.

The PK/PD results indicated that PFAPM exhibited an absorption half-life (T1/2ka) of 0.07 h and an elimination half-life (T1/2kel) of 0.87 h, with corresponding AUC values ranging from 1.18 to 8.33 μg·h/mL at doses of 10-80 mg/kg. When the mycoplasma load decreased by 3 log10 cfu/mL, the corresponding AUC48h/MIC and Cmax/MIC values were 7617.62 h and 1256.76, respectively, at a dose of 67.66 mg/kg. ELISA and flow cytometry analysis revealed that drug treatment significantly reduced cytokines and inflammatory cells associated with T helper 1 (Th1) and T helper 2 (Th2) immune responses.

AUC48h/MIC was the best parameter to describe the PK/PD relationship. The bactericidal effect was achieved at a dose of 67.66 (∼68) mg/kg. Pleuromutilins can reduce Th1 and Th2 inflammation.

Evidence describing paediatric COVID-19 and influenza co-infection is limited because influenza circulation was minimal during the early COVID-19 pandemic. We used the National Clinical Cohort Collaborative, a multicentre electronic health record repository, to describe the characteristics and clinical outcomes of paediatric COVID-19 and influenza co-infections in the United States from March 2020-April 2024. We defined co-infection as COVID-19 and influenza identified <7 days apart. We reported demographics, pre-existing diagnoses, and clinical outcomes and used generalized estimating equation models. We defined clinical outcomes as Severe/Moderate disease (hospitalization, critical care, or death) versus emergency department/outpatient encounters. We repeated analyses using varying co-infection definitions to assess robustness of findings. Among 1.53 million patients, 10,277 were co-infected, and 647 (6%) were hospitalized. Co-infections occurred predominantly among children aged <12 years. The most common pre-existing diagnoses were obesity (24%), asthma (10%), and congenital/genetic conditions (5%). The risk for Severe/Moderate disease was greatest among persons aged 0-4 years (adjusted risk ratio (aRR) 3.05; 95% confidence interval (CI): 2.35-3.97) and those with ≥2 pre-existing diagnoses (aRR 2.89; 95% CI: 2.43-3.43). Similar distributions of disease severity were observed across varying co-infection definitions. This study provides a large-scale epidemiological characterization of paediatric COVID-19 and influenza co-infection and successfully implemented a practical EHR-based co-infection case definition for future analyses.

Vaccination is a principal method of infectious disease prevention, but its association with rheumatoid arthritis (RA) remains controversial. This study assessed vaccine‑associated RA using the Vaccine Adverse Event Reporting System (VAERS). Data from 1990 to 2026 were extracted. Descriptive statistics, Weibull fitting, and disproportionality analysis using four methods, including the reporting odds ratio (ROR), along with subgroup analyses by age, sex, and pre‑/post‑COVID, were performed. Among 11,532,185 reports, 34,498 RA‑related adverse events (AEs) (0.03%) involved 5006 subjects. Females comprised 77.9% and 18-65 predominated. Serious outcomes occurred in 13.48%. Most AEs (47.49%) were musculoskeletal. 47.0% occurred within 7d (median 5.4), indicating early failure. The COVID‑19 vaccine had the most reports (n = 24,266) but a weak signal (ROR = 1.25); the Lyme disease vaccine (ROR = 27.81), the rubella vaccine (ROR = 5.69), and the anthrax vaccine (ROR = 3.90) exhibited the strongest signals. Subgroup signals: Lyme disease vaccine except 2021-2026; rubella vaccine only in females/≤17; anthrax vaccine in 18-64. RA‑related vaccine AEs are extremely rare, mainly musculoskeletal and within 1 week. High COVID‑19 volume did not align with its weak signal, while strong signals for the Lyme disease, rubella, and anthrax vaccines reflected specific populations. No strong disproportionality signal was found. However, VAERS is passive, cannot establish causality or confirm safety.

Uvular necrosis is an uncommon complication following oesophagogastroduodenoscopy (OGD). We report a case involving a male in his 20s who developed uvular necrosis following a routine OGD performed under conscious sedation. The patient presented three days postprocedure with a worsening sore throat and odynophagia. Examination revealed an erythematous uvula with a necrotic tip. He was managed conservatively with simple analgesia, topical lidocaine and oral antibiotics with eventual full resolution of symptoms with no lasting sequelae. This case highlights a rare yet significant complication of OGD, emphasising the importance of clinician awareness, conservative management and patient reassurance.

Fixed drug eruption is a distinctive cutaneous adverse drug reaction characterised by the recurrence of well-demarcated lesions at the same anatomical site following re-exposure to the offending drug, with residual hyperpigmentation after resolution. Antimicrobials are common triggers, although fluoroquinolones are less frequently implicated. A man in his 30s developed multiple well-defined hyperpigmented patches involving the upper lip, upper limbs and foot within 24 hours of receiving levofloxacin for a lower respiratory tract infection. The lesions were pruritic, non-tender and recurrent at previously affected sites. Clinical findings and a clear temporal relationship supported the diagnosis of fixed drug eruption. Withdrawal of levofloxacin and symptomatic treatment resulted in gradual resolution with post-inflammatory hyperpigmentation. Causality assessment using the Naranjo scale suggested a probable association. This case highlights the importance of recognising fixed drug eruption caused by commonly prescribed antibiotics and the role of careful drug history taking and adverse drug reaction reporting.

Seasonal influenza imposes a substantial global health burden. The COVID-19 pandemic, accompanied by widespread non-pharmaceutical interventions (NPIs), profoundly disrupted respiratory virus circulation, offering a unique opportunity to assess their broader epidemiological impact. This study aimed to quantify changes in influenza burden between the pre-pandemic and intra-pandemic periods. Within the RESPINOW project, we conducted a systematic review following PRISMA guidelines. Studies reporting absolute influenza case counts before and during the pandemic were included. Data extraction and quality assessment were performed using a modified NHLBI tool for before-after studies. Influenza cases were normalized by reporting period length, and relative changes were estimated using incidence rate ratios. Subgroup analyses explored age, setting, hemisphere, human development index, influenza transmission zones, WHO regions, and viral strains. Of 20,676 screened records, 115 studies from 98 countries were included. Globally, influenza incidence declined by -92% (95% CI: -94 to -90) following the onset of the pandemic. Reductions varied geographically, ranging from near-elimination in several countries to more modest declines (e.g., South Korea: -61%, 95% CI: -79 to -26). Decreases were observed across all transmission zones and WHO regions, with descriptively larger reductions observed in high-income countries (-96%, 95% CI: -98 to -94) than in low-income settings (-82%, 95% CI: -88 to -73). Age-specific declines appeared smaller among young children (< 6 years: -66%, 95% CI: -79 to -45) compared with adults aged 18-64 years (-80%, 95% CI: -90 to -63). Influenza A appeared to decline more strongly than influenza B. The COVID-19 pandemic was associated with an unprecedented global reduction in influenza incidence. Data limitations and the need for robust epidemiological indicators highlight the importance of strengthened, integrated global surveillance to inform future pandemic responses.