• [Development of core outcome set for efficacy evaluation of traditional Chinese medicine treatment of early-stage respiratory virus infection with external cold and internal heat syndrome].
    3 weeks ago
    This study constructed a core outcome set(COS) for traditional Chinese medicine(TCM) treatment of early-stage external cold and internal heat syndrome in respiratory viral infections, aiming to provide a reference for selecting outcomes in related clinical studies. A literature review was conducted to collect outcomes related to the early-stage external cold and internal heat syndrome in respiratory viral infections under TCM treatment from randomized controlled trials, systematic reviews, guidelines, and registered clinical trial protocols. Supplementary searches were performed in high-impact journals for systematic reviews on conventional medicine treatments for respiratory viral infections, as well as on the official websites of the Center for Drug Evaluation of the National Medical Products Administration and the US Food and Drug Administration, to develop the initial outcome pool. Two rounds of the Delphi surveys using a 9-point Likert scale were conducted to evaluate the importance of outcomes. The final outcomes were determined through a face-to-face expert consensus meeting. A total of 31 clinical studies, five systematic reviews, two guidelines, five registered clinical trial protocols, and eight new drug evaluation guidelines were included. After standardizing and sorting the outcomes, a pool of 34 outcomes was established. After two rounds of Delphi surveys, 17 outcomes were initially included. After the expert consensus meeting, 10 core outcome indicators were finally determined, including rate of progression to severe cases, time to major symptom improvement, time to resolution of all symptoms, dosage of antipyretic and analgesic medications, incidence of adverse events, time to viral clearance, mortality rate, quality of life, length of hospital stay, and time to normalization of body temperature.
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  • [Evidence map analysis of clinical research on treatment of community-acquired pneumonia with Chinese patent medicines in recent ten years].
    3 weeks ago
    This study summarized clinical research on the application of Chinese patent medicines for the treatment of community-acquired pneumonia(CAP) through an evidence mapping method to elucidate the distribution of evidence and the current state of research in this field. Databases, including CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched, covering the period from January 2014 to August 2024. Randomized controlled trial(RCT), systematic review/Meta-analysis, and guideline/expert consensus of Chinese patent medicines for CAP in the past 10 years were included, and the characteristics of evidence distribution were presented by a combination of text and charts. A total of 243 publications were included, including 222 RCTs, 14 systematic reviews/Meta-analyses, 2 network Meta-analyses, and 5 guidelines/expert consensus. The overall number of publications in this field showed a fluctuating downward trend. Most of the included RCTs were small in size, with sample sizes ranging from 61 to 100 cases, and the common course of treatment was 7, 10, or 14 days. Traditional Chinese medicine(TCM) syndrome type was reported in only 47 publications. A total of 37 Chinese patent medicines were involved, with Tanreqing Injection receiving the highest level of attention. The combination of quinolones and β-lactams was the measure most commonly taken for intervention. There was a wide range of outcome indicators, with high attention paid to signs and symptoms, physical and chemical tests, and safety events. There were problems such as a lack of attention to the distinction between primary and secondary outcome indicators, insufficient attention to the indicators with TCM characteristics, a lack of uniformity and standardization for the names of outcome indicators, and less use of economic indicators. In terms of quality assessment, most RCTs were rated as "unknown risk of bias" due to unspecified allocation concealment or blinding. Most systematic reviews/Meta-analyses were of "very low quality", and the guidelines/expert consensus lacked standardization in the rigor of their development and application. The results showed that the quality of clinical research on Chinese patent medicines for CAP was generally low. In the future, the design of clinical protocols should be further optimized, and more large-sample, multicenter, long-term follow-up studies should be conducted. Moreover, a core set of outcome indicators with TCM characteristics should be established, and the quality of systematic review/Meta-analysis and guideline/expert consensus literature should be improved so that more high-quality evidence for the treatment of CAP with Chinese patent medicines will be provided.
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  • Chronic Rhinosinusitis Optimisation of Nasal Outcomes and Scores (CHRONOS): An Italian Delphi Consensus on Long-Term Management with Biologics.
    3 weeks ago
    This review synthesizes current evidence and expert consensus on the long-term management of severe chronic rhinosinusitis with nasal polyps (CRSwNP) treated with biologics, as established by the Italian CHRONOS project.

    Accumulating real-world and clinical trial data confirm the sustained efficacy and safety of biologics targeting type 2 inflammation, enabling durable control and remission in a significant proportion of patients. Personalized dosing regimens, including dose-spacing strategies, appear feasible. The CHRONOS project provides practical guidance for optimizing long-term biologic therapy in severe CRSwNP. Response assessment should combine subjective and objective measures, especially for olfactory testing. Biologics may be considered before surgery only in selected complex cases. Dose-spacing strategies may be appropriate in stable patients but require multidisciplinary oversight in those with comorbid asthma. Adverse events are uncommon. The concept of disease modification is endorsed, recognizing biologics' potential to alter the natural history of CRSwNP.
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  • [The role of NGF and its receptor TrkA in bronchial asthma and research on targeted therapy for severe asthma using nebulized anti-NGF microspheres].
    3 weeks ago
    Objective To investigate the role of nerve growth factor (NGF) and its high-affinity receptor tyrosine kinase A (TrkA) in the pathogenesis of bronchial asthma (BA), and to evaluate their association with asthma severity and type 2 T helper (Th2) inflammatory factors, and to validate the intervention efficacy and mechanism of nebulized targeted therapy using poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with anti-NGF antibodies in severe asthma. Methods Serum samples were collected from asthma patients of varying severity and non-asthmatic individuals. Levels of NGF, TrkA, interleukin 4(IL-4), IL-5, and IL-13 were measured. An ovalbumin (OVA)-induced severe asthma mouse model was established and randomly divided into blank control, severe asthma, conventional antibody therapy, and nebulized anti-NGF microsphere groups. Differences in inflammatory factors in bronchoalveolar lavage fluid (BALF), lung tissue pathology, and NGF/TrkA/NF-κB protein expression levels were compared among groups via ELISA, pulmonary function testing, HE/Masson staining, and Western blot analysis. Results Clinical testing revealed elevated serum NGF (82.52±4.01 vs 22.92±5.25)pg/mL and TrkA (53.93±8.97 vs 15.76±3.60)pg/mL levels in the severe asthma group compared to the non-asthmatic control group; IL-4 (44.23±9.88 vs 20.88±3.90)pg/mL, IL-5 (147.1±14.92 vs 47.13±5.63)pg/mL, and IL-13 (106.9±11.64 vs 51.93±8.55)pg/mL levels were significantly elevated. In animal experiments, the nebulized anti-NGF microsphere group exhibited significantly lower levels of IL-4 (36.08±6.08 vs 87.35±9.13)pg/mL, IL-5 (35.41±4.52 vs 81.53±4.94)pg/mL, and IL-13 (36.37±4.57 vs 92.37±6.53)pg/mL. Forced expiratory volume in one second(FEV1) (84.68±5.33 vs 60.87±3.93)% increased, and airway hyper reactivity(AHR) (152.8±7.36 vs 233.8±8.77)% decreased. Pulmonary tissue pathological damage and collagen deposition were alleviated. Western blot analysis revealed that relative protein levels of NGF, TrkA, and NF-κB in lung tissues of mice treated with nebulized anti-NGF microspheres were lower than those in the severe asthma group. Conclusion The NGF/TrkA signaling pathway is closely associated with asthma severity. Nebulized anti-NGF microsphere therapy effectively targets the lungs, inhibits the NF-κB pathway, alleviates airway inflammation, and significantly improves pulmonary function.
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  • Clinical characteristics, treatments and outcomes of hospitalised COVID-19 patients across pandemic waves at a tertiary acute care hospital in Narita, Japan: a single-centre retrospective observational study.
    3 weeks ago
    This study aims to describe the characteristics of hospitalised COVID-19 patients in a tertiary care hospital close to an international airport in Japan and to compare these characteristics among different waves during the pandemic.

    Retrospective observational study.

    Tertiary care centre in Japan.

    All patients diagnosed with COVID-19 who were hospitalised between January 2020 and April 2022 were included.

    Clinical characteristics, characteristics of admission, treatments and outcomes were investigated and compared among six pandemic waves.

    A total of 827 patients were included. The median age was 58.0 years. More than half of the patients (58.3%) had at least one comorbidity. The majority of patients (89.0%) were domestically infected patients admitted under the Infectious Diseases Law, while the remaining patients (11.0%) were those diagnosed during airport quarantine and admitted under the Quarantine Act. Hospital-acquired COVID-19 infection occurred in 7.0% of cases, and mainly during the sixth wave. Overall, some form of oxygen therapy, high-flow oxygen devices, invasive mechanical ventilation (IMV) and extracorporeal membrane oxygenation was provided in 46.3%, 10.4%, 4.5% and 1.5% of cases, respectively. Only 1.8% of patients were treated in the intensive care unit (ICU), and 59.5% of patients on IMV were managed in the non-ICU ward. The in-hospital mortality rate was 5.8%. Median age, percentages of some comorbidities, vaccination coverage, medications for COVID-19, types of supportive care and ICU admissions differed significantly among waves.

    This study suggests that patient characteristics, vaccination coverage, standard of treatment and severity of illness changed across waves during the COVID-19 pandemic. Intensive care delivery in non-ICU wards was unavoidable due to limited ICU capacity, which may be a key consideration when preparing for future pandemics.
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  • Association of influenza viral genetic information with severity markers in patients hospitalised with influenza: multicentre retrospective cohort study.
    3 weeks ago
    The objective of this study was to determine the association between viral subtype/clade and disease severity.

    Multicentre retrospective cohort study.

    This study used data from the Global Influenza Hospital Surveillance Network (GIHSN). The dataset comprised hospitalised influenza patients with viral sequencing data across 14 countries, collected from August 2022 through October 2023.

    A total of 761 hospitalised patients were enrolled during the study period, and 745 patients were included in the analysis. We excluded patients with missing data on explanatory or outcome variables, those infected with viral clades represented by fewer than 11 sequences, and those enrolled at study sites contributing fewer than 5 patients.

    Disease severity was defined by admission to intensive care unit (ICU), receipt of non-invasive oxygen supplementation, 3-variable definition (ICU, mechanical ventilation or death) or 4-variable definition (3-variable plus oxygen supplementation).Outcomes were analysed in association with subtype or clade using the mixed-effects logistic regression models, adjusting for age group, sex, underlying medical conditions, influenza vaccination status, antiviral use, country income level and epidemic period, while study site was included as a random effect.

    745 patients were included: 263 A(H1N1)pdm09, 380 A(H3N2), 102 B/Victoria. A(H1N1)pdm09 infection was associated with increased odds of ICU admission (adjusted ORs (aORs) 2.5, 95% CI 1.1 to 5.8) compared with A(H3N2). 6B.1A.5a.2a.1 clade of A(H1N1)pdm09 was associated with increased severity compared with 6B.1A.5a.2a clade (aOR 3.0, 95% CI 1.0 to 9.5) and (aOR 5.4, 95% CI 1.6 to 18.3) for the 3-variable and 4-variable definitions respectively. Among A(H3N2), the (3C.2a1b.2a.)2b clade showed a trend toward increased severity using the 4-variable definition compared with the 2a.1b clade (aOR 2.9, 95% CI 0.8 to 10.0).

    This analysis highlights the differential impact of influenza subtypes and clades on disease severity in hospitalised patients. Future research should investigate the role of specific viral mutations of these clades in modulating immune evasion or disease severity. These findings reinforce the GIHSN's critical role in global surveillance. Ongoing genomic surveillance is crucial for understanding the clinical impact of emerging influenza variants and informing public health responses.
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  • Unmasking the dilemma: Public health, safety, and the challenges of anonymity in emergency management and homeland security.
    3 weeks ago
    Masks occupy a unique and dual role in society, functioning as both critical tools for public health protection and enablers of anonymity, which can be exploited for deviant or criminal purposes. Historically, masks have evolved from their origins in plague prevention to modern applications in medical, public health, and societal contexts. While essential during health crises such as the coronavirus disease 2019 pandemic, their use also reveals unintended consequences, including fostering riskier behavior through the Peltzman Effect and enabling anonymity-driven disassociation described by Deindividuation Theory. This article explores the complexities of mask usage at the intersection of public health and safety. It examines how masks, while mitigating disease transmission, can embolden individuals to take greater risks or evade accountability in public disturbances and criminal activities. Through historical and contemporary case studies-including the 1918 influenza pandemic, the Ku Klux Klan's use of masks, and modern legislation like New York's 2024 Mask Transparency Act-the article underscores the need for nuanced policies that balance public health objectives with security concerns. Integrating behavioral theories with legal and emergency management strategies, it advocates for a multifaceted approach to mask policy that addresses both their protective role and potential for misuse, ultimately fostering a safer and more resilient society.
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  • Antineutrophil Cytoplasmic Antibodies Contribute to Airway Inflammation via Induction of Neutrophil Extracellular Traps in Children With Bronchiolitis Obliterans.
    3 weeks ago
    It was found that the levels of antineutrophil cytoplasmic antibodies (ANCA) are elevated and linked to disease severity of bronchiolitis obliterans (BO) in children. This study aims to explore the mechanism of ANCA in the process of BO.

    Plasma from BO patients (n = 40) and healthy controls (n = 11) was analyzed for ANCA and neutrophil extracellular traps (NETs) components. Plasma IgG from ANCA-positive BO children and normal controls were used to stimulate neutrophils, measuring reactive oxygen species (ROS) and NETs production. Small airway epithelial cells (SAECs) were exposed to NETs, assessing viability by CCK8 and cytokine release by ELISA. The IgG treated neutrophils were co-cultured with SAECs, and cytokines were measured by ELISA.

    The levels of ANCA and NETs components including dsDNA, neutrophil elastase (NE) and myeloperoxidase (MPO) in the plasma of BO children were significantly higher than those of healthy controls. ANCA-positive IgG induced neutrophils produce ROS and NETs. The cell viability of SAECs was significantly reduced upon treatment with NETs in a concentration-dependent manner. The levels of IL-8, IL-17, TNF-α, and TGF-β secreted by SAECs treated with NETs were increased significantly, and the degree of increase was positively correlated with the concentration of NETs. The co-culture of neutrophils stimulated by ANCA IgG with SAECs significantly increased the expression of cytokines including IL-8, IL-17, TNF-α, and TGF-β.

    NETs induced by ANCA may exacerbate airway inflammation in children with BO.
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  • [Advances in exosomal proteomics for biomarkers and traditional Chinese medicine treatment of lung diseases].
    3 weeks ago
    Lung diseases such as lung cancer, chronic obstructive pulmonary disease(COPD), and pulmonary fibrosis(PF) urgently require new treatment strategies due to their complex pathological mechanisms and the limitations of existing therapies. Traditional Chinese medicine(TCM) has a long history and proven efficacy in treating lung diseases, characterized by a "multi-component, multi-target, and multi-pathway" treatment approach, but its molecular mechanisms still require systematic analysis. Exosomes, as key mediators of intercellular communication, participate in disease progression and serve as specific biomarkers by delivering proteins, nucleic acids, and metabolites. Tumor-derived exosomes drive the formation of the pre-metastatic microenvironment and immune suppression in lung cancer, while inflammatory cell-derived exosomes exacerbate airway damage in COPD. Additionally, fibroblast-derived exosomes aberrantly activate the Wnt pathway, promoting the progression of PF. Exosome proteomics provides a crucial breakthrough for elucidating the mechanisms of TCM in treating lung diseases, revealing the synergistic intervention of TCM on inflammation and tumor metabolism through high-throughput identification of key proteins regulated by TCM. Furthermore, dynamic changes in exosome proteins can quantitatively assess drug efficacy and resistance mechanisms. Technologically, 4D proteomics combined with single-vesicle membrane protein analysis can accurately analyze the heterogeneity of TCM-induced exosome subpopulations, advancing the precise validation of the "components-targets-efficacy" treatment approach in TCM and accelerating its clinical translation. Looking ahead, integrating multi-omics analysis will systematically reveal the molecular networks through which TCM formulas regulate disease targets via exosome proteins, providing comprehensive solutions for the diagnosis and treatment of lung cancer, COPD, and PF, from mechanism elucidation to clinical translation.
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  • [Clinical strategies of classical formulae in treatment of chronic obstructive pulmonary disease].
    3 weeks ago
    Chronic obstructive pulmonary disease(COPD) is one of the top three leading causes of death worldwide and can be divided into acute exacerbation and stable phases. Acute exacerbation of COPD(AECOPD) is the main trigger of disease progression and mortality in COPD patients, while the stable phase is a chronic and continuous stage of the disease. With continuous updates to relevant guidelines, modern medicine has achieved certain therapeutic effects in the treatment of COPD. However, long-term use of antibiotics and glucocorticoid drugs tends to drug resistance and may cause adverse reactions. Traditional Chinese medicine(TCM) attaches great importance to syndrome differentiation and has unique advantages in the treatment of lung diseases, following the principle of "treating the symptoms in acute conditions and the root in chronic ones". According to TCM theory, the pathological location of COPD is the lungs and is related to the spleen and kidneys. The disease is characterized by deficiency in origin and excess in manifestations, with phlegm and deficiency as the main pathogenesis factors. During the acute exacerbation phase, phlegm is the predominant factor, running through the disease course, and often mixed with heat, dampness(turbidity), cold, or blood stasis. These may appear in various combinations, leading to syndromes such as phlegm-heat obstructing the lungs, phlegm-turbidity blocking the lungs, external cold with internal fluid retention, and phlegm-blood stasis blocking the lungs. In the stable phase, deficiency is predominant, commonly involving deficiencies of the lungs, spleen, and kidneys. This article explored the clinical strategies of classical formulae in the treatment of COPD in recent years based on COPD staging and pathogenic factors and presented two medical cases for peer reference and discussion.
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