Background:Asthma affects approximately 334 million people worldwide. Accumulating evidence indicates that gut dysbiosis exacerbates airway inflammation through the gut-lung axis. In the present study, using an OVA-induced murine model of asthma, we investigated whether Huanglong Zhixiao Formula (HLZXF) restores gut lung homeostasis by reshaping the gut microbiota and enhancing intestinal barrier function, thereby attenuating pulmonary pathological changes. Methods:Female BALB/c mice were randomly assigned to three groups (n = 15 per group): Control (C), Asthma Model (MX), and HLZXF-treated (ZG) groups. Asthma was induced by OVA sensitization and challenge over a 6-week period. The ZG group received daily oral gavage of HLZXF, 1 h prior to each OVA challenge. Fecal samples were collected for metagenomic sequencing. Lung and intestinal tissues were excised for HE and IHC staining of tight junction proteins, including Claudin, Occludin, and ZO-1. Alpha and beta diversity analyses were conducted to evaluate the composition and structure of the gut microbiota. Results:We analyzed the structure of the gut microbiota, detected the expression levels of intestinal barrier-related proteins, and assessed inflammatory injury in the lungs and intestines. Results demonstrated that HLZXF significantly ameliorated gut microbiota dysbiosis in asthmatic mice, as evidenced by the significant enrichment of Heminiphilus faecis and Paramuribaculum intestinale. Additionally, certain fungal taxa, such as Piromyces finnis and Rhizopus arrhizus, were significantly enriched in the ZG group. HLZXF also significantly upregulated the expression levels of the tight junction proteins Claudin, Occludin, and ZO-1 in intestinal tissues, thereby promoting the repair of the intestinal mucosal barrier. Furthermore, HLZXF significantly attenuated inflammatory cell infiltration and tissue injury in the lungs and intestines, alleviated alveolar septal thickening, and enhanced the integrity of the intestinal mucosal barrier. Conclusion:This study elucidates the potential therapeutic mechanisms of HLZXF in the treatment of asthma from the perspective of gut microbiota and intestinal barrier function. It highlights that HLZXF can attenuate pulmonary inflammation by regulating the balance of gut microbiota and enhancing intestinal barrier function.
Introduction The Chinese continent is grappling with a rising prevalence of chronic obstructive pulmonary disease (COPD) in conjunction with the growing threat of climate change and its associated extreme temperature. This systematic review aims to assess the relationship between extreme temperature exposures (heat and cold exposure) and COPD health outcomes in Chinese populations. Methods and analysis This study will assess the relationship between extreme temperature exposures and COPD health outcomes through a systematic review and meta-analysis. Observational studies meeting the inclusion criteria will be included, and the Population-Exposure-Comparator-Outcome-Study (PECOS) research design standard will be adopted to examine how extreme temperatures impact COPD-related mortality and morbidity including hospitalizations and acute exacerbations. A literature search will be conducted across multiple databases, including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), WANGFANG Data, VIP and Sinomed. We will evaluate the reporting quality, methodological quality and evidence quality of these observational, cohort, and cross-sectional studies using Risk of Bias in Non-randomized Studies-of Environmental Exposure (ROBINS-E) assessment tool, and integrate the evidence within the GRADE framework. Additionally, the analysis of outcomes will be performed using the narrative synthesis and R software. Ethics and dissemination Ethical approval is not required for this review. The results of this study will be disseminated through publication in a peer-reviewed journal. Study protocol registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261281322 , identifier (CRD420261281322).
BACKGROUND:Global population aging exacerbates the challenges of multimorbidity and polypharmacy in older adults. Clinical practice guidelines are essential for addressing these issues. This systematic review aims to evaluate the quality of existing guidelines and synthesize their recommendations based on the Ariadne principles, to inform future guideline development and clinical practice. METHODS:We searched nine databases and five guideline repositories (e.g., PubMed, Web of Science, Cochrane Library, CNKI, WHO) up to August 2025. Guidelines and consensus documents focusing on multimorbidity or polypharmacy in older adults, published in English or Chinese, were included. Each guideline was evaluated using four validated tools: AGREE II (methodological quality), RIGHT (reporting completeness), AGREE-REX (recommendation credibility and applicability), and GLIA (implementation feasibility). Recommendations were categorized and synthesized according to the Ariadne principles, with independent screening and data extraction and consensus resolution of discrepancies. RESULTS:The multidimensional appraisal of the 21 included guidelines revealed consistent weaknesses. According to AGREE II, the domains of Scope and Purpose (81.9 %) and Clarity of Presentation (61.1 %) demonstrated the highest median scores, whereas Rigor of Development (16.7 %) and Applicability (8.3 %) scored the lowest. Based on the RIGHT checklist, overall reporting completeness was 43.2 %, with the Evidence (0.0 %) and Quality Assurance (0.0 %) domains being particularly underreported. AGREE-REX evaluation indicated limited implementability at the individual recommendation level (12.5 %), and GLIA, while suggesting moderate implementability at the guideline level (65.4 %), identified frequent barriers in the domains of Measurable Outcomes (100.0 %) and Innovation Requirements (66.7 %). Thematically, most guidelines addressed interaction assessment (n = 15, 71.4 %), but far fewer incorporated patient preferences (n = 9, 42.9 %) or monitoring strategies (n = 9, 42.9 %). Only three guidelines (14.3 %) fully adhered to all five steps of Ariadne principles. CONCLUSION:Current guidelines for older adults with multimorbidity or polypharmacy exhibit substantial weaknesses in methodological rigor, reporting completeness, and implementation feasibility. Synthesis based on the Ariadne principles revealed an imbalanced pattern of recommendations, with a predominant focus on medication safety rather than patient-centered and longitudinal care management. Future guideline development should strengthen methodological processes, systematically integrate patient perspectives, and co-design practical implementation strategies to better support personalized care for an aging population.
BackgroundChronic obstructive pulmonary disease (COPD) is one of the most common chronic respiratory diseases worldwide. Recurrent acute exacerbations severely impact patients' quality of life and impose a significant economic burden. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines recommend acupuncture as an adjunctive therapy for patients with advanced COPD. However, evidence regarding its efficacy during the acute exacerbation phase remains insufficient, particularly from high-quality clinical trials. This study aims to evaluate the efficacy and safety of electroacupuncture in treating patients with acute exacerbation of COPD (AECOPD), establish a standardized electroacupuncture treatment protocol for AECOPD, and preliminarily explore the association between electroacupuncture and airway mucus hypersecretion.MethodsThis is a multicenter, randomized, sham-controlled trial. A total of 336 eligible patients with AECOPD will be recruited and randomly allocated in a 1:1 ratio to either an electroacupuncture group or a sham acupuncture group. Participants will receive treatment once daily for 7 consecutive days and will then be followed up for 13 weeks. The primary outcome measure is the COPD Assessment Test (CAT). Secondary outcomes include the Cough and Sputum Assessment Questionnaire (CASA-Q), the modified Medical Research Council Dyspnea Scale (mMRC), clinical symptom and sign scores, the number of exacerbations, and arterial blood gas. All rating scales will be evaluated at baseline, 4 days after treatment, 7 days after treatment, 5 weeks of follow-up and 13 weeks of follow-up. Arterial blood gas analysis and alveolar lavage fluid collection will be performed at baseline and after 7 days of treatment. The number of acute exacerbations during the follow-up period will be recorded at 5 and 13 weeks of follow-up. Adverse events related to acupuncture will be recorded throughout the study period.ConclusionThis study will evaluate the efficacy and safety of electroacupuncture in treating patients with AECOPD, establish a standardized electroacupuncture treatment protocol for AECOPD, and preliminarily explore the association between electroacupuncture and airway mucus hypersecretion.Clinical trial registrationClinicalTrials.gov [NCT06869525].
There are few data regarding the duration, long-term prognosis of persistent cough post coronavirus disease 2019 (COVID-19). The break of COVID-19 Omicron mutant infection provides an opportunity to investigate the long-term outcome of postinfectious cough and its risk factors. In this multicenter prospective study, we recruited patients aged ≥ 18 years with cough duration ≥ 3 weeks after COVID-19 infection during early stage of 2023 in respiratory clinics, cough assessments and laboratory investigations were conducted. Patients underwent two follow-up visits at 12 weeks and 52 weeks. A total of 1650 patients were enrolled, with an average age of 42.2 ± 14.4 years and 63.3
Nowadays, features derived from Mel-filter banks are predominately used in combination with various deep learning models for state-of-the-art cough detection task. However, these handcrafted features are based on prior knowledge about speech perception, not inherently designed for cough sound at hand and thus may neglecting the potential of critical information. Instead, this paper introduces a learnable front-end (LEAF) layer over the raw sound samples for cough detection. Akin to Mel-scale filters, the LEAF module is comprised of a bank of learnable bandpass filters followed by learnable pooling and compression to reduce temporal resolution and dynamic range, respectively. In a data-driven fashion, the LEAF is optimized jointly with the remaining deep learning back-end model, potentially resulting with a representation better adapted to the specific cough task. Experimental results conducted on a large real-world cough dataset (COUGHVID) demonstrate the performance consistently outperform their counterparts trained on comparable Mel-filter banks, featuring precision and recall values up to 98.37% and 98.22% respectively. Additionally, visualization of the learned filters reveals that they are able to better capture the more relevant features for the cough data. Overall, the learnable front-end requires a relatively few parameters, and it can be expected that incorporating more advanced neural network frameworks could potentially further boost the performance.
Drug-resistant bacterial infections have emerged as a critical global public health challenge, characterized by high mortality rates, substantial healthcare costs, and rapid transmission characteristics that pose a severe test to modern medical practice. Traditional Chinese medicine(TCM), with its comprehensive theoretical framework and extensive clinical experience, demonstrates unique advantages in infectious disease management. Particularly in addressing drug-resistant bacterial infections, TCM has achieved remarkable progress by integrating its fundamental principle of "strengthening vital Qi while eliminating pathogens" with contemporary research methodologies. This review systematically examines the current epidemiological landscape of antimicrobial resistance, elucidates the theoretical foundations of TCM intervention, and analyzes its therapeutic advantages and mechanistic actions. By synthesizing these perspectives, we aim to provide novel insights and approaches for combating drug-resistant bacterial infections.
Objective: This study aims to investigate the potential of Bu-Fei Yi-Shen Formula (BYF) in ameliorating airway epithelial barrier dysfunction in chronic obstructive pulmonary disease (COPD) and to elucidate the underlying mechanisms. Methods: By establishing both in vivo and in vitro models of COPD, this study examined lung function, lung tissue pathology, inflammatory cytokines levels, cellular apoptosis rate, oxidative stress intensity, and TEER. Concurrently, it quantified the expression levels of proteins relevant to apical junctions, apoptosis, and the Nrf2 signaling pathway. These exhaustive analyses were undertaken to decipher the intricate mechanisms by which BYF ameliorates the disruption of airway epithelial barrier integrity in COPD. Results: BYF significantly improved lung function, attenuated lung tissue pathological damage, reduced inflammatory cytokines levels, inhibited cellular apoptosis, upregulated the expression of apical junctional proteins, and alleviated oxidative stress injury in a COPD rat model. In vitro, BYF restored the CSE-induced decreases in TEER values and apical junctional protein expression in BEAS-2B cells, while reducing airway epithelial cell apoptosis apoptosis and oxidative stress injury. Furthermore, BYF counteracted the inhibitory effects of CSE on Nrf2, facilitating the expression of HO-1, a downstream protein of Nrf2. The addition of ML385 exacerbated the apoptosis, oxidative stress, and barrier dysfunction induced by CSE; however, the co-administration of ML385 and BYF reversed the inhibitory effects of ML385. Conclusion: These findings underscore that BYF ameliorates airway epithelial barrier dysfunction in COPD by activating the Nrf2/ HO-1 signaling pathway.
To evaluate the protective effect of Bufei Yishen Formula (BYF) against cigarette smoke extract (CSE)-induced injuries in human bronchial epithelial BEAS-2B cells and explore the underlying mechanism. BEAS-2B cells exposed to CSE were treated with normal rat serum, BYF-medicated rat serum at low or high doses, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), PDTC combined with high-dose BYF-medicated serum, or S-carbomethyloysteine (S-CMC, as the positive control). CCK-8 assay was used to determine the optimal concentration and treatment time of CSE, BYF-medicated serum and S-CMC. The treated cells were examined for inflammatory factor levels in the supernatant and cellular expressions of MUC5AC and MUC5B using ELISA, cell ultrastructural changes with transmission electron microscopy, and cell apoptosis rate using flow cytometry. The expression levels of TLR4/NF‑κB pathway-associated mRNAs and proteins were determined by qRT-PCR and Western blotting. CSE exposure significantly increased secretions of IL-1β, IL-6 and TNF-α, mRNA and protein expressions of MUC5AC and MUC5B, and early and total apoptosis rates in BEAS-2B cells, where the presence of apoptotic bodies was detected. CSE also significantly enhanced the mRNA and protein expressions of TLR4, I-κB, and NF-κB and reduced mRNA and protein expressions of AQP5. Treatments of the CSE-exposed cells with BYF-medicated serum, PDTC and S-CMC all significantly lowered inflammatory factor levels, MUC5AC and MUC5B expressions, and early and total cell apoptosis rates, and partly reversed the changes in cellular ultrastructure and mRNA and protein expressions of the TLR4/NF-κB pathway, and the effects were the most conspicuous following the combined treatment with high-dose BYF-medicated serum and PDTC. BYF can inhibit cell apoptosis, inflammation and mucus hypersecretion in CSE-induced BEAS-2B cells by inhibiting the TLR4/NF-κB signaling pathway.
Objectives:Reduning (RDN) injection is a traditional Chinese medicine (TCM) extract injection commonly used as an adjunct therapy for severe pneumonia (SP) in clinical practice in China; however, further validation is required. This study aims to systematically assess the efficacy and safety of RDN injection in treating SP. Methods:The study was conducted using the data from CNKI, WanFang, VIP, SinoMed, PubMed, Embase, Cochrane Library, and Web of Science databases from their inception to 6 April 2024. We collected randomized controlled trials on the treatment of SP using RDN injection, and used Review Manager (version 5.3) for meta analysis. The primary outcomes was clinical efficacy. We used the Cochrane Risk of Bias Assessment Tool 2 (RoB 2) to assess the risk of bias for each study. Results:A total of 1,897 patients with SP from 22 studies were included. The meta-analysis results showed that the combination of RDN injection and conventional treatment or antibiotic treatment for patients with SP was superior to traditional and antibiotic treatments alone in terms of clinical efficacy [risk ratio = 1.25%; 95% confidence interval (CI) (1.20, 1.30); p < 0.00001], fever reduction time [mean difference (MD) = -1.55 days; 95% CI (-1.91, -1.18); p < 0.00001], cough disappearance time [MD = -1.97 days; 95% CI (-2.63, -1.31); p < 0.00001], lung rales disappearance time [MD = -2.39 days; 95% CI (-3.09, -1.70); p < 0.00001], chest X-ray improvement time [MD = -2.73 days; 95% CI (-2.96, -2.49); p < 0.00001], and hospitalization time [MD = -3.11 days; 95% CI (-3.80, -2.41); p < 0.00001]. Moreover, no significant improvement was observed in the Acute Physiology and Chronic Health Evaluation II (APACHE II) scale compared to the control group [MD = -2.45 points; 95% CI (-6.07, 1.17); p = 0.19]. Lastly, not all studies reported any serious adverse events; however, some studies did report adverse reactions. Conclusion:The administration of RDN injection as an adjunct therapy for SP can enhance clinical efficacy, reduce fever duration, accelerate cough resolution, shorten the time for lung rales to resolve, accelerate chest X-ray improvement, and decrease hospitalization duration. Further well-designed and standardized large sample clinical studies are needed for validation. Systematic review registration:PROSPERO, identifier CRD42024540365.
Gleditsia sinensis Fructus (GSF) exhibits anti-cancer activity and is effective against lung adenocarcinoma (LUAD). However, its underlying mechanisms remain unclear. In this study, the potential chemical components, targets, and pathways of GSF in treating LUAD were investigated using UHPLC-HRMS combined with network pharmacology analysis. These findings were subsequently verified via molecular docking, molecular dynamics simulation, and in vitro cell experiments. The results showed that a total of 61 components targeting 192 LUAD-related genes were identified, and 177 candidate targets of GSF against LUAD were obtained, among which AKT1, SRC, EGFR, IL6, and TNF may be the core targets. Enrichment analysis revealed that the mechanisms were related to various cancer-related pathways, particularly the PI3K-AKT signaling pathway. Molecular docking demonstrated that the active components of GSF, particularly luteolin, exhibited excellent binding affinity to the top five core targets. Molecular dynamics simulation results showed a similar trend. Therefore, we identified luteolin as the primary active component of GSF. The cell experiments revealed that luteolin significantly inhibited cell growth and proliferation and promoted the apoptosis of A549 cells, exhibiting effects similar to those of cisplatin. In addition, luteolin significantly upregulated the expression of Bax and cleaved-caspase3 and decreased the expression of P-AKT and BCL2. Our results demonstrate that GSF can exert anti-LUAD effects through multi-components, multi-targets, and multi-pathways. Luteolin, one of the main active components of GSF, suppressed proliferation and induced apoptosis in A549 cells, possibly through inhibiting the AKT signaling pathway.
BACKGROUND:Recurrent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) impose disease deterioration and economic burden. Tan Yin Wan (TYW), a traditional Chinese medicine (TCM) formulation, has shown promise in COPD management, but robust clinical evidence is lacking. OBJECTIVE:We aimed to evaluate the efficacy and safety of TYW in delaying AECOPD onset, with subgroup analyses exploring the TCM principle of "Treating Winter Disease in Summer" (Dongbing Xiazhi, ), which advocates reinforcing physiological resilience in low-risk seasons to mitigate exacerbation and severity of disease in high-risk seasons. METHODS:In this multicenter, randomized, double-blind, placebo-controlled, phase Ⅳ clinical trial, participants with moderate-to-severe COPD and high exacerbation risk received TYW or an identical placebo, in addition to standard therapy for 52 weeks. The primary outcome was time to the first AECOPD. Secondary outcomes included the severity of the first AECOPD, annualized exacerbation rate, proportion of AECOPD cases, symptom scales (Breathlessness, Cough, and Sputum Scale (BCSS), COPD Assessment Test (CAT), and modified Medical Research Council Dyspnea Scale (mMRC)), 6-Minute Walk Distance (6MWD), pulmonary function and safety. RESULTS:A total of 342 patients were recruited from 18 centers between July 13, 2021, and June 5, 2023, with 308 patients in the full analysis set (FAS) and 297 in the per-protocol set (PPS). TYW significantly prolonged the time to the first AECOPD vs. placebo after adjustment for baseline confounding (adjusted HR = 0.55, 95% CI = 0.35 - 0.87, p = 0.01), and the restricted mean survival time difference (ΔRMST) was 30.45 days (95% CI = 4.68 - 56.23, p = 0.02). Improvements were demonstrated in BCSS, CAT, mMRC, and 6MWD at multiple timepoints (all p < 0.05), though lung function showed no significant differences. Exploratory subgroup analysis indicated a numerical trend toward a prolonged time to first exacerbation by 40.29 days in summer-enrolled participants (June - August) compared to non-summer-enrolled participants. This observation is tentatively consistent with the TCM principle of "Treating Winter Disease in Summer" as a proactive preventive strategy, though formal statistical significance was not achieved. Safety profiles were comparable between groups. CONCLUSIONS:TYW adjunct therapy might delay AECOPD onset and improve symptom burden, representing a preventive intervention that embodies TCM's "Treating Disease Before Onset" (Zhi Wei Bing, ) philosophy, potentially through "Treating Winter Disease in Summer", as a proactive seasonal strategy in long-term COPD management. TRIAL REGISTRATION:This trial was registered at the Chinese Clinical Trials Registry (ChiCTR2100048801).
Lung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for approximately 35-40% of lung cancers, and the overall survival time of patients with LUAD is still very poor. B cells are important effector cells of adaptive immunity, and B-cell infiltration increases in various tumors. The role of B cells in LUAD is still largely unknown. Therefore, it is particularly important to clarify the role of B cells in LUAD. GSE164983, GSE50081, GSE37745 and GSE30219 were obtained from the GEO database. The TCGA-LUAD dataset was obtained from the TCGA database. UMAP was used to perform clustering descending and subgroup identification on single-cell RNA-sequencing (scRNA-seq) data to obtain B-cell markers. The TCGA cohort was used to obtain differentially expressed genes (DEGs). B-cell-related differentially expressed genes (BRGs) were identified through the intersection of B-cell markers and DEGs. The LASSO method was used to identify characteristic genes of BRGs and construct a prognostic risk model. LUAD patients were divided into high-risk and low-risk groups based on risk scores, and the immune landscape of the two groups was evaluated. We also analyzed the differences in clinical characteristics, mutations, immunotherapy, and drug sensitivity between the two groups. Thirty BRGs were obtained, and 6 characteristic genes were identified. Based on the characteristic genes, a prognostic risk model was constructed. According to the prognostic risk model, LUAD patients were divided into two groups: high-risk group and low-risk group. Patients in the high-risk group had worse outcomes and shorter survival times. Low-risk patients had better survival, while patients with high TNM stage accounted for a greater proportion of patients in the high-risk group. In addition, high-risk patients had a greater probability of mutation and worse immunotherapy response. Finally, we found different susceptibility profiles between the high-risk and low-risk groups. The prognostic risk model built based on the BRGs had good predictive performance, providing a new perspective on the prognosis and immunotherapy of LUAD patients and a new reference for LUAD research.
Triple quadrupole (QQQ) MS based pseudotargeted lipidomics combines high coverage and quantitative accuracy, is commonly established by selecting the most responsive lipid ion pairs identified from high-resolution mass spectrometry (HRMS), then sending them to QQQ MS for quantification by multiple reaction monitoring. Due to the low resolution of QQQ MS, it may result in faulty peak identification in integration and method transition from HRMS to QQQ MS, thus, directly establish pseudotargeted lipidomics on HRMS is needed to improve the accuracy of present methods. We propose a method for rapidly screening high-resolution ion pairs for constructing multiplex-HRMS-based pseudotargeted lipidomics (MHPL). Firstly, high-resolution precursor and product ions for lipid quantification were obtained by HRMS. To solve the problem of lower acquisition speed in HRMS, we used the multiplex mode to simultaneously fragment co-eluting lipid precursor ions within one isolation window, scan the MS/MS mass spectra, and quantify the unique product ions (UPI) of co-eluting lipid (defined as Quan-PIs). Meanwhile, we provide a group of scripts for searching for lipid Quan-PIs in multiplex mode. The proposed MHPL strategy could ensure accurate quantification of 460 lipids within 5 injections, and was applied in serum differential lipid discovery for chronic obstructive pulmonary disease (COPD) patients. As a result, 47 differential lipids were found to comprise a potential biomarker panel for COPD diagnosis. The lipid identification and quantification in this work were conducted in the same instrument, and faulty peak identification was considerably reduced in integration and when transitioning methods from HRMS to QQQ MS.
BACKGROUND:COPD-OSA overlap syndrome is an important and prevalent condition. Patients with the overlap syndrome experience more severe respiratory symptoms and worse quality of life, and the relative risk of exacerbations is higher than in either condition alone. Because prevalence estimates of COPD-OSA overlap syndrome vary substantially across studies, there is still no consensus on its exact global prevalence. This review specifically aims to offer a comprehensive overview of the global prevalence of the COPD-OSA overlap syndrome. METHODS:Embase, PubMed, Web of Science, Cochrane and Ovid Medline databases were systematically searched for studies reporting the prevalence of COPD-OSA overlap syndrome published from database inception until February 24, 2025. Random effects meta-analysis was performed using R software. Heterogeneity among the studies was evaluated using the I2 index. Sensitivity analysis, subgroup analysis and meta-regression was conducted to evaluate the heterogeneity source of the results. Begg test was used to assess publication bias. RESULTS:A total of 41 studies involving 1,871,071 participants were included in this analysis. The global prevalence of COPD-OSA overlap syndrome was 28.3 % (95 % CI: 20.8-36.4 %). Subgroup analysis revealed that the prevalence was higher in cross-sectional studies (30.66 %, 95 % CI: 21.66 %-40.47 %) compared with cohort studies (21.24 %, 95 % CI: 9.74 %-35.69 %). Among continents, Asia exhibited the highest prevalence at 37.87 % (95 % CI: 24.46 %-52.29 %). The prevalence of overlap syndrome when OSA was assessed by home sleep apnea test (HSAT) was comparable to that assessed by polysomnography (PSG), and a higher proportion of COPD-OSA overlap syndrome was observed when using an apnea-hypopnea index (AHI) threshold of ≥5 compared with an AHI threshold of ≥10. Meta-regression analysis highlighted that those differences in study period, study population, sample size, and age were pivotal factors influencing these epidemiological patterns. CONCLUSION:Pooled analysis estimated that approximately one-third of patients exhibit COPD-OSA overlap syndrome, with this proportion increasing over time. Significant epidemiological differences were observed across populations, time periods, sample sizes, and age groups. To mitigate the adverse impact of COPD-OSA overlap syndrome on health outcomes, regular screening for individuals with COPD or OSA is recommended, along with the implementation of effective preventive and treatment strategies.
ETHNOPHARMACOLOGICAL RELEVANCE:Yiqi Huoxue Huatan granule is an empirical traditional Chinese medicine formula that has been widely used for the treatment of respiratory diseases. However, whether Yiqi Huoxue Huatan granule has a therapeutic effect on patients with stable COPD complicated with chronic respiratory failure remain unclear. AIM OF THE STUDY:To evaluate the efficacy and safety of Yiqi Huoxue Huatan granule in treating this population. MATERIAL AND METHODS:This is a double-blind randomized clinical trial, conducted at 15 health centers in China from October 2019 to December 2021. 372 participants aged 40-80, were enrolled. All had been diagnosed with stable COPD and exhibited PaO2<60 mmHg and PaCO2>50 mmHg during quiet breathing at sea level according to arterial blood gas analysis results. Eligible patients were randomly assigned to the treatment group (Yiqi Huoxue Huatan granule combined with western medicine), or the control group (a placebo together with western medicine). The treatment phase lasted 52 weeks, followed by a 52-week follow-up. The primary outcomes were mortality and the frequency of acute exacerbations of COPD. RESULTS:186 patients in the treatment group and 186 in the control group were for intention-to-treat analysis. Among them, a total of 317 patients were included in the per protocol set. Yiqi Huoxue Huatan granule combined with western medicine was found to reduce all-cause mortality by 5.62 %. Specifically, there were 11 deaths (6.96 %, 95 % CI -2.95 %-10.97 %) in the treatment group compared to 20 (12.58 %, 95 % CI -7.37 %-17.79 %) in the control group, P = 0.131. Moreover, the frequency of acute exacerbations was significantly reduced in the follow-up period (1.04 ± 1.25 [95 % CI -0.84 to 1.24] in the treatment group vs 1.24 ± 1.40 [95 % CI -1.02 to 1.46] in the control group, P = 0.183 during treatment period, while 0.71 ± 1.01 [95 % CI -0.54 to 0.87] in the treatment group vs 1.03 ± 1.22 [95 % CI -0.83 to 1.23] in the control group, P = 0.016 during follow-up period). For safety analysis, six of 186 patients in the treatment group and three of 186 patients in the control group suffer adverse events. CONCLUSIONS AND RELEVANCE:Yiqi Huoxue Huatan granule is proved to be able to reduce the mortality and the frequency of acute exacerbations of COPD. Thus, it can serve as a reasonable therapeutic option for patients with stable COPD complicated by chronic respiratory failure. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT04208581.
BACKGROUND AND OBJECTIVE:Bailing Capsules (BLC) and Yong Chong Cao Capsules (YChCC) share similar medicinal components, but Yong Chong Cao benefit from more advanced cultivation and large-scale production. This study systematically compared their therapeutic effects in patients with mild-to-severe Chronic Obstructive Pulmonary Disease (COPD). PATIENTS AND METHOD:This study was designed as a multi-center, randomized, active-controlled trial. 240 COPD patients were randomized 1:1 to receive YChCC or BLC for 24 weeks, followed by a 24‑week follow‑up. The primary endpoints were number of acute exacerbations. Secondary outcomes included, time to first exacerbation, and exacerbation duration, forced expiratory volume in 1 s (FEV1), FEV1%, forced vital capacity (FVC), FVC%, FEV1/FVC%, modified Medical Research Council dyspnea scale (mMRC), Chronic Obstructive Pulmonary Disease Assessment Test (CAT), and Chronic Obstructive Pulmonary Disease Clinical Questionnaire (CCQ). RESULTS:A total of 208 patients completed the trial (full analysis set, FAS), and 178 comprised the per‑protocol set (PPS). Compared with BLC, YChCC significantly reduced the number of acute exacerbations (FAS: p = 0.002; PPS: p = 0.003) and prolonged time to first exacerbation. No significant between‑group differences were observed in lung function parameters or mMRC, CAT, and CCQ scores. CONCLUSION:YChCC represent a promising adjuvant therapy for patients with stable COPD, ranging from mild to severe. They significantly prolong the time to the first acute exacerbation and reduce the frequency of acute exacerbations, thereby offering potential benefits in managing COPD. TRIAL REGISTRATION:This trial has been registered at ClinicalTrials.gov under the registration number NCT03745261. TRIAL REGISTRATION NUMBER (IF CLINICAL TRIAL):NCT0374526.
OBJECTIVES:To evaluate the protective effect of Bufei Yishen Formula (BYF) against cigarette smoke extract (CSE)-induced injuries in human bronchial epithelial BEAS-2B cells and explore the underlying mechanism. METHODS:BEAS-2B cells exposed to CSE were treated with normal rat serum, BYF-medicated rat serum at low or high doses, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), PDTC combined with high-dose BYF-medicated serum, or S-carbomethyloysteine (S-CMC, as the positive control). CCK-8 assay was used to determine the optimal concentration and treatment time of CSE, BYF-medicated serum and S-CMC. The treated cells were examined for inflammatory factor levels in the supernatant and cellular expressions of MUC5AC and MUC5B using ELISA, cell ultrastructural changes with transmission electron microscopy, and cell apoptosis rate using flow cytometry. The expression levels of TLR4/NF‑κB pathway-associated mRNAs and proteins were determined by qRT-PCR and Western blotting. RESULTS:CSE exposure significantly increased secretions of IL-1β, IL-6 and TNF-α, mRNA and protein expressions of MUC5AC and MUC5B, and early and total apoptosis rates in BEAS-2B cells, where the presence of apoptotic bodies was detected. CSE also significantly enhanced the mRNA and protein expressions of TLR4, I-κB, and NF-κB and reduced mRNA and protein expressions of AQP5. Treatments of the CSE-exposed cells with BYF-medicated serum, PDTC and S-CMC all significantly lowered inflammatory factor levels, MUC5AC and MUC5B expressions, and early and total cell apoptosis rates, and partly reversed the changes in cellular ultrastructure and mRNA and protein expressions of the TLR4/NF-κB pathway, and the effects were the most conspicuous following the combined treatment with high-dose BYF-medicated serum and PDTC. CONCLUSIONS:BYF can inhibit cell apoptosis, inflammation and mucus hypersecretion in CSE-induced BEAS-2B cells by inhibiting the TLR4/NF-κB signaling pathway.
Traditional Chinese medicine (TCM) is widely used in the management of chronic obstructive pulmonary disease (COPD). This study aimed to evaluate the clinical efficacy of comprehensive therapy based on TCM patterns for patients with stable, severe to very severe COPD. A multicenter, randomised, double-blind, placebo-controlled trial was conducted. Eligible patients were randomly allocated in equal proportions to two groups: the trial group, which received TCM-based therapy with Bu-Fei Jian-Pi, and Bu-Fei Yi-Shen, and Yi-Qi Zi-Shen granules tailored to TCM syndromes, and the control group, which received a placebo resembling Chinese medicine. Both groups also received conventional Western medicine as part of their treatment. Acute exacerbations (AEs), lung function, dyspnea scores, the 6-min walking test (6MWT), and the COPD assessment test (CAT) were assessed over 12 months of treatment, with an additional 12 months of follow-up. A total of 467 patients were included in the analysis with 228 in the experimental group and 239 in the control group. The Chinese herbal granules group significantly reduced AEs (0.63 vs. 1.03 events, P = 0.002), improved mMRC scores (−0.17 points, 95 https://clinicaltrials.gov/study/NCT02270424?id=NCT02270424 rank=1 .
Combined allergic rhinitis and asthma syndrome (CARAS) involves complex interactions between inflammation and lipid metabolism. This study recruited 90 CARAS patients admitted to the First Affiliated Hospital of Henan University of Chinese Medicine from August 2023 to August 2024 (30 cases each for CARASa, CARASb and CARASc), along with 30 healthy controls (HC). We systematically profiled serum lipidomes across different CARAS stages and examined associations with inflammatory cytokines and mucins. Baseline characteristics were comparable among healthy controls (HC) and CARAS subgroups. CARAS patients in the acute phase (CARASa) exhibited elevated serum-specific IgE and fractional exhaled nitric oxide, indicating heightened allergic sensitization, while pulmonary function remained preserved. Lipidomic analysis revealed a pronounced shift from fatty acids to glycerolipids in CARASa, with upregulation of triglycerides, digalactosyldiacylglycerol, phosphatidylserines, phosphatidylethanolamines, and ceramides. CARASb (chronic persistence) showed persistent dysregulation of sphingomyelins, lysophosphatidylcholines, and membrane lipids, whereas CARASc (clinical remission) exhibited partial recovery with residual alterations in specific lipid classes. Correlation analysis indicated that fatty acid depletion strongly associated with glycerolipid accumulation. Pathway enrichment highlighted stage-dependent disturbances in fatty acid transport, GLP-1/incretin turnover, sphingolipid biosynthesis, and retinoid metabolism, reflecting metabolic-immune crosstalk. Notably, differential lipids (Digalactosyldiacylglycerol, phosphatidylethanolamines and phosphatidylserine) positively correlated with pro-inflammatory cytokines (TNF-α, IL-6) and mucins (MUC1, MUC5AC) in CARASa and CARASb groups. In the CARASc group, these differential lipids showed a negative correlation with pro-inflammatory factors and mucins. These findings define a trajectory of stage-specific lipid metabolic remodeling in CARAS, linking energy metabolism and membrane lipid changes to inflammatory activation and mucin expression, providing potential metabolic biomarkers and therapeutic targets.