Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease driven by a self-perpetuating "fibrotic niche," where monocyte-derived alveolar macrophages (Mo-AMs) regulate disease progression. Conventional single-target antifibrotics show limited efficacy in reversing established fibrosis and frequently cause dose-limiting toxicities, prompting the investigation of natural product-based therapeutics as multi-targeted investigational alternatives. This narrative review examines the mechanisms through which purified phytochemicals and multicomponent botanical formulas modulate the pulmonary fibrosis (PF) immune microenvironment. Moving beyond the classical M1/M2 dichotomy, we outline the spatiotemporal heterogeneity of macrophages and their bidirectional crosstalk with myofibroblasts. We summarize preclinical and experimental pharmacological interventions targeting macrophage reprogramming networks, detailing how natural monomers exhibit targeted immunomodulation, including immunometabolic shifts (e.g., covalent GAPDH inhibition to suppress glycolysis) and mechanotransduction blockade (e.g., Piezo1 inhibition by specific terpenoids). Concurrently, quality-controlled botanical formulas demonstrate potential synergistic effects in modulating microenvironmental homeostasis. Natural product-based therapeutics provide a promising investigational approach for modulating the fibrotic niche. To address the translational gap in this field, future research requires a methodological shift from theoretical network pharmacology to empirical validation using raw metabolomics and spatial transcriptomics, integrated with macrophage-targeted nano-delivery systems and rigorous chemical fingerprinting.

Post-acute infection syndrome (PAIS) remained underrecognized before the COVID-19 pandemic, which further increased exposure by introducing a novel global cause. The global burden of post-acute COVID syndrome (PACS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) alone is estimated at several tens of millions affected worldwide. Biomarker discovery is central to improving PAIS diagnosis and may provide therapeutic targets. This review summarizes current knowledge on biomarkers for PAIS, including PACS and ME/CFS.

A systematic literature search was conducted in PubMed and Web of Science. Inclusion criteria were: (1) studies including PAIS patients; (2) reporting laboratory or omics biomarkers; and (3) investigating biomarkers or pathomechanisms of PAIS. Although Guillain-Barré syndrome (GBS) is not PAIS, we have included it as a separate mechanistic comparator due to its prevalence in search results and its clinical and immunological similarities to PAIS.

A total of 142 studies analyzing PAIS biomarkers were included. GBS was analyzed separately and later compared with the other results. Overall, the reviewed studies employed heterogeneous approaches. While similar types of data were frequently investigated, analytical methods varied and often focused only on a subset of molecules. The results indicate that amino acid, energy, and lipid metabolism, microbiome, mitochondrial stress, and miRNA networks are affected. All pathways are connected via NF-κB.

PAIS is a multisystem disorder rooted in persistent immune activation, metabolic reprogramming, and systemic inflammation, driven not by active viral infection, but by dysregulated host responses. The NF-κB pathway serves as a unifying hub, connecting molecular, cellular, and clinical phenotypes. Our framework enables a shift from symptom-based to mechanism-based classification, paving the way for biologically grounded interventions.

This review synthesizes a broad spectrum of biomarkers in PAIS, integrating findings across pathogens and molecular levels rather than restricting to individual conditions or symptom clusters. This study highlights the differences and commonalities among pathogens and diseases that lead to post-acute sequelae, fills a critical knowledge gap, and provides a foundation for future research and clinical practice. Future studies incorporating multi-omics approaches, longitudinal designs, and larger patient cohorts are needed to validate specific biomarkers and advance the understanding of PAIS.

Objective: To explore the value of echocardiography in the diagnosis and follow-up of cardiac thrombosis in children with Mycoplasma pneumoniae pneumonia. Methods: This was a case series analysis. Children diagnosed with Mycoplasma pneumoniae pneumonia combined with cardiac thrombosis at the Children's Hospital of Shandong University from November 2015 to December 2023 were enrolled. Echocardiographic findings were collected, with emphasis on sonographic characteristics of cardiac thrombi, changes in thrombus size after treatment, and thrombus resolution. Results: A total of 22 children (15 males; aged 6.2±2.2 years) were included. Echocardiography showed right ventricular thrombi in 20 cases (91%), including 19 in the right ventricular inflow tract and 1 in the right ventricular outflow tract; a thrombus in the main pulmonary artery in 1 case (5%); and a thrombus in the proximal left inferior pulmonary vein in 1 case (5%). Among the 22 patients, 1 (5%) underwent surgical thrombectomy, and the remaining received anticoagulation therapy. During the 12-month follow-up, 1 patient receiving anticoagulation was lost to follow-up; in the remaining 20 patients, thrombi gradually decreased in size, and disappeared completely in 17 cases. Conclusions: In children with Mycoplasma pneumoniae infection complicated by cardiac thrombosis, echocardiography can clearly delineate thrombus location, size, and post-treatment changes. It is the preferred imaging modality for diagnosing cardiac thrombosis associated with Mycoplasma pneumoniae infection.

The concurrent circulation of influenza A virus (IAV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has unveiled complex host-pathogen interactions governed by temporal dynamics of innate immune activation. This narrative review synthesizes evidence from human air-liquid interface (ALI) epithelial models, animal studies (hamster, ferret), clinical cohorts, and randomized controlled trials (2015-2026) to delineate the molecular mechanisms underlying viral interference between these two major respiratory pathogens. Prior IAV infection induces a robust type I/III interferon (IFN) response and broad interferon-stimulated gene (ISG) upregulation that restricts subsequent SARS-CoV-2 replication within a critical 24-72 h temporal window. Conversely, SARS-CoV-2 employs a multi-layered immune evasion strategy that blunts IFN induction, providing minimal heterologous protection. Simultaneous co-infection tends to exacerbate disease severity. Host genetic determinants, including OAS1 and TLR7 variants, modulate interference capacity. Therapeutically, early pegylated IFN-λ shows clinical benefit, while experimental evidence from in vitro and animal models suggests oseltamivir may paradoxically reduce IAV-induced interference. These findings underscore the need for multi-pathogen diagnostics, temporally informed clinical decision-making, and IFN-based therapeutic strategies during co-circulation periods.

High-mobility group box 1 (HMGB1) has been implicated in matrix remodeling and fibrotic disorders; however, its role in tuberculosis (TB)-associated pleural fibrosis remains unknown. Pleural fluid levels of HMGB1 and matrix metalloproteinase-1 (MMP-1) in patients with TB pleural effusion (TBPE, n = 36) or transudative pleural effusion (TPE, n = 14) were measured. The effects of Mycobacterium tuberculosis H37Ra (MTBRa) on HMGB1 and MMP-1 expression and their effects on mesothelial-mesenchymal transition (MMT) in human pleural mesothelial cells (PMCs) were assessed. The levels of HMGB1 and MMP-1 were significantly higher in TBPE than in TPE. Elevated HMGB1 and MMP-1 levels in TBPE were positively correlated and both factors were significantly associated with post-TB residual pleural thickening (RPT), particularly in patients with RPT ≥ 10 mm. Colocalized expression of HMGB1 and MMP-1 was also observed in the pleural mesothelium of TBPE patients. MTBRa significantly induced HMGB1 expression in PMCs through activation of the JNK/AP-1 signaling pathway, leading to MMT, enhanced collagen synthesis, and upregulation of MMP-1. Furthermore, silencing of MMP-1 markedly attenuated HMGB1-triggered MMT response. Collectively, HMGB1 promotes pleural fibrogenesis through JNK/AP-1-dependent and MMP-1-mediated MMT, suggesting that targeting the HMGB1/MMP-1 axis may represent a potential therapeutic strategy for TB-related pleural fibrosis.

Viral vaccine development requires both mechanistic understanding of protective immunity and translational study designs that connect preclinical data with human outcomes. Animal models remain important for early assessment of safety, immunogenicity and protective efficacy, but their predictive value depends on the question being asked, the pathophysiology of infection, the immune mechanisms expected to mediate protection, and the biomarkers chosen to bridge animal and human data. This review focuses on viral vaccines and examines innate and adaptive mechanisms of vaccine-induced protection, including B cell and antibody responses, Fc-mediated functions, Fc glycosylation, T cell memory and CD8+ cytotoxic responses. We discuss common reasons for clinical failure and show how preclinical endpoints can be classified as human-counterpart, surrogate or comparative/mechanistic readouts. Influenza and COVID-19 examples illustrate how different models can be combined across discovery, challenge, transmission and late-stage bridging studies. Emerging tools such as systems serology, omics, AI/ML and new approach methods can improve candidate prioritization, but their value depends on assay standardization, biological validation and cautious interpretation. A mechanism-driven model cascade, paired with human-relevant immunological readouts, can improve preclinical interpretation and reduce the risk of advancing candidates that are unlikely to succeed in clinical trials.

To investigate the role and mechanism of miR-146b-5p in pulmonary vascular remodeling in neonatal rats with bronchopulmonary dysplasia-associated pulmonary hypertension (BPD-PH) induced by hyperoxia.

Thirty-two Sprague-Dawley neonatal rats were randomly assigned to normoxia group, BPD-PH group, overexpression group, and inhibitor group (n=8 per group). The normoxia group was raised in 21% oxygen, while the other groups were exposed to 85.0%±0.5% hyperoxia to induce BPD-PH. The overexpression group received tail vein injection of ADV1-miR-146b-5p adenovirus; the inhibitor group received miR-146b-5p inhibitor injections. After 14 days, adenovirus transfection efficiency in lung tissue was confirmed by confocal microscopy. Right ventricular systolic pressure (RVSP) was measured by direct manometry. Right ventricular hypertrophy index (RVHI) was calculated by weighing isolated ventricular tissues. Hematoxylin-eosin staining was used to assess pulmonary vascular morphology, and medial thickness percentage (MT%) and medial area percentage (MA%) of pulmonary vessels were calculated. Mitochondrial ultrastructure of pulmonary vascular endothelial cells was observed by transmission electron microscopy (TEM). Iron deposition in lung tissue was detected by DAB Prussian blue staining and ferrous ion colorimetric assay. Quantitative real-time PCR was used to measure mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and acyl-CoA synthetase long-chain family member 4 (ACSL4). Protein expression levels of these molecules were detected by Western blotting.

Compared with the normoxia group, the BPD-PH group showed significantly increased RVSP, RVHI, MT%, and MA% (P0.05), swollen mitochondria, increased iron deposition, downregulated mRNA and protein expression of Nrf2, GPX4, and SLC7A11, and upregulated expression of ACSL4 (P0.05). Compared with the BPD-PH group, the overexpression group exhibited further increases in RVSP, RVHI, MT%, and MA%, severe mitochondrial swelling, significantly elevated iron deposition, decreased Nrf2, GPX4, and SLC7A11 mRNA and protein levels, and increased ACSL4 expression (P0.05). In contrast, the inhibitor group demonstrated decreased RVSP, RVHI, MT%, and MA%, alleviated mitochondrial swelling, reduced iron deposition, upregulated mRNA and protein levels of Nrf2, GPX4, and SLC7A11, and downregulated mRNA and protein levels of ACSL4 (P0.05).

Overexpression of miR-146b-5p promotes pulmonary vascular remodeling in neonatal rats exposed to hyperoxia, likely through inhibition of the Nrf2/GPX4 signaling pathway and regulation of ferroptosis.

A cluster sample survey of the point-prevalence of microbiologically confirmed pulmonary tuberculosis (MCPTB) in the population above 14 years of age in India, by the Indian Council of Medical Research, revealed unexpectedly wide geographic variations across states, with a distinct and intriguing pattern: coastal states consistently had lower prevalence rates than land-locked states. The odds of having a prevalence rate above the mean are 46 times higher for land-locked compared to coastal states. The lowest rate was in Kerala, a state with a long seacoast, and the highest in Delhi National Capital Region, landlocked and far from any seacoast. We hypothesize that constant air exchange with sea air without any Mycobacterium tuberculosis, has led to lower risk of infection, eventually expressed as lower prevalence of MCPTB. Understanding this determinant of geographic variation provides valuable insights for strategies aimed at controlling tuberculosis.

Blunt cerebrovascular injury (BCVI) is a rare but potentially devastating complication of pediatric blunt trauma. Delayed or missed diagnosis may result in ischemic stroke, permanent neurological deficits, or death. To avoid missed injuries, many trauma centers apply liberal computed tomography angiography (CTA) screening strategies, although this may expose children to substantial and potentially unnecessary radiation. Several adult- and pediatric-derived screening tools have been proposed, but their applicability in pediatric trauma populations remains controversial. This study aimed to evaluate the incidence of BCVI, imaging utilization, and the diagnostic performance of pediatric BCVI screening approaches in a German Level I trauma center cohort.

This retrospective observational cohort study included pediatric trauma patients aged 0-15 years who underwent CT imaging following blunt trauma between January 2005 and December 2020 at a Level I trauma center in Germany. Patients were identified through systematic review of electronic medical records and radiological databases. BCVI was defined as traumatic injury to the carotid or vertebral arteries detected by CTA or magnetic resonance imaging (MRI). Demographic, clinical, imaging, and outcome data were collected retrospectively. The McGovern score was calculated for patients with sufficient available data and evaluated using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic (ROC) analysis. Additionally, the theoretical applicability of PECARN and Scandinavian pediatric head trauma guidelines was explored to assess potential reductions in CT utilization.

A total of 956 pediatric trauma patients underwent CT imaging, of whom 668 (70%) additionally received CTA. BCVI was diagnosed in 6 patients, corresponding to an incidence of 0.6%. Five injuries were identified by CTA and one by MRI. All BCVI patients presented with focal neurological deficits at initial evaluation. The McGovern score could be calculated in 896 patients. Using a cutoff value of ≥ 3 points, all BCVI cases were correctly identified, resulting in a sensitivity of 100%, specificity of 83.8%, PPV of 4.0%, and NPV of 100%. ROC analysis demonstrated excellent discriminative ability with an area under the curve of 0.960 (95% CI 0.923-0.989). However, the small number of BCVI cases limited statistical power. Theoretical application of PECARN and Scandinavian guidelines suggested that a substantial proportion of CT examinations may have been avoidable.

BCVI is an uncommon but clinically significant injury in pediatric blunt trauma. Despite its low incidence, CTA utilization was high in our cohort, raising concerns regarding potential overuse of imaging and radiation exposure. Pediatric-specific screening tools such as the McGovern score may help identify low-risk patients while maintaining high sensitivity. However, larger prospective multicenter studies are required to validate pediatric BCVI screening strategies and optimize the balance between early diagnosis and radiation avoidance.

Targeted therapies have transformed the treatment landscape for patients with chronic lymphocytic leukemia (CLL). These therapies include the selective B-cell lymphoma-2 (BCL-2) inhibitor venetoclax and Bruton's tyrosine kinase (BTK) inhibitors (e.g., ibrutinib, acalabrutinib, zanubrutinib). Especially in a setting of long-term care, safety and tolerability are important considerations. Although generally well tolerated, targeted therapies for relapsed and refractory CLL are associated with potentially treatment-limiting untoward effects, often within weeks to months of initiating therapy. These include myelosuppression (e.g., neutropenia); tumor lysis syndrome, infection, and gastrointestinal effects with venetoclax; as well as cardiovascular diseases (e.g., hypertension, atrial fibrillation/flutter) and infection (e.g., pneumonia) with BTK inhibitors. Instrumental to management of these adverse effects are effective risk assessment, stratification, and modification; prophylaxis; and regimen modifications, with appropriate measures to minimize pharmacokinetic interactions.