Introduction Neutrophil extracellular traps (NETs) contribute to chronic inflammation in chronic obstructive pulmonary disease (COPD). Jinwei Guben Formula (JWGB) is a clinically used TCM for COPD, but its mechanism regarding NETs and glucocorticoid sensitivity is unclear. This study aimed to investigate whether JWGB modulates NETs formation and glucocorticoid efficacy via HDAC2 in COPD.Methods An integrated approach combining UHPLC-MS/MS, network pharmacology, molecular docking, and human neutrophil experiments was used.Results We identified 168 compounds in JWGB. Network analysis predicted 42 active ingredients and highlighted the NETs formation pathway. Key ingredients showed strong binding to HDAC2 and MPO. Experimentally, JWGB inhibited CSE-induced NETs release and inflammation. Notably, JWGB upregulated HDAC2 expression in COPD neutrophils and synergized with methylprednisolone, allowing a low dose (100 mu M) to match the efficacy of a high dose (500 mu M).Discussion Our findings reveal that JWGB alleviates COPD by simultaneously inhibiting NET formation and restoring HDAC2 function. This dual action provides a mechanistic basis for its clinical efficacy and suggests its potential as a steroid-sparing strategy to overcome glucocorticoid resistance.Conclusion JWGB may alleviate neutrophilic inflammation in COPD by inhibiting NET formation and upregulating HDAC2. Its synergy with glucocorticoids suggests potential as a steroid-sparing therapy.

INTRODUCTION:Neutrophil extracellular traps (NETs) contribute to chronic inflammation in chronic obstructive pulmonary disease (COPD). Jinwei Guben Formula (JWGB) is a clinically used TCM for COPD, but its mechanism regarding NETs and glucocorticoid sensitivity is unclear. This study aimed to investigate whether JWGB modulates NETs formation and glucocorticoid efficacy via HDAC2 in COPD. METHODS:An integrated approach combining UHPLC-MS/MS, network pharmacology, molecular docking, and human neutrophil experiments was used. RESULTS:We identified 168 compounds in JWGB. Network analysis predicted 42 active ingredients and highlighted the NETs formation pathway. Key ingredients showed strong binding to HDAC2 and MPO. Experimentally, JWGB inhibited CSE-induced NETs release and inflammation. Notably, JWGB upregulated HDAC2 expression in COPD neutrophils and synergized with methylprednisolone, allowing a low dose (100 μM) to match the efficacy of a high dose (500 μM). DISCUSSION:Our findings reveal that JWGB alleviates COPD by simultaneously inhibiting NET formation and restoring HDAC2 function. This dual action provides a mechanistic basis for its clinical efficacy and suggests its potential as a steroid-sparing strategy to overcome glucocorticoid resistance. CONCLUSION:JWGB may alleviate neutrophilic inflammation in COPD by inhibiting NET formation and upregulating HDAC2. Its synergy with glucocorticoids suggests potential as a steroid- sparing therapy.

Chronic obstructive pulmonary disease (COPD) is a persistent, often progressive lung disease with a highly heterogeneous patient population. Its management has traditionally relied on clinical symptoms and pulmonary function tests. However, this approach has limitations due to a poor alignment between the clinical symptoms and underlying individual pathological mechanisms, as well as a heavy reliance on chest imaging, restricting its wide application in resource-limited settings. This review aimed to bridge the gap between clinical presentation and underlying mechanisms by systematically mapping cellular inflammatory phenotypes to targeted therapies. We critically examined the evolution from clinical to cellular phenotyping, highlighting the potential of mechanistic, cell-based classifications to improve COPD management. The proposed cellular phenotype classification—neutrophilic (>60% sputum neutrophils), eosinophilic (≥3% eosinophils), lymphocytic, macrophage, and mixed granulocytic—has been validated in multinational cohorts and provides a framework for precision interventions: inhibiting the CXCR1/2 pathway or neutrophil elastase for the neutrophilic phenotype, and anti-interleukin-5/interleukin-13 biologics or Th2 blockade for the eosinophilic phenotype. We propose a four-tiered diagnostic pathway comprising biomarker screening, multi-omics validation, consensus assignment, and dynamic therapy escalation. This approach shifts COPD management from symptom control to pathogenesis modification. However, substantial challenges remain in translating cellular phenotypes into routine practice, warranting further research.

N6-methyladenosine (m6A) is a prevalent mRNA modifier, yet its role in chronic obstructive pulmonary disease (COPD) remains unexplored. We sourced expression levels of m6A methylation regulators from the GSE76925 dataset. These regulators' differential expression (DEMs) predicted COPD risk via random forest and support vector machine models. Additionally, a nomogram model using DEMs estimated COPD prevalence. We employed consistent cluster analysis of m6A methylation regulators to categorise COPD samples into distinct subtypes. Analyses of immune cell infiltration in these subtypes and differential gene expression (DEGs) across m6A methylation subtypes were conducted. A cell model validated several m6A regulators and their associated pathways. Fifteen m6A methylation regulators showed differential expression and were used in random forest and support vector machine models. Eleven were selected for a nomogram model, which decision curve analysis suggested could benefit patients. Consensus cluster analysis divided the COPD samples into two subtypes: Cluster A and Cluster B. Cluster B was associated with neutrophil and eosinophil-dominated immunity, while Cluster A was linked with monocyte-dominated immunity. Validation of some research findings was achieved through cell experiments. m6A methylation regulators appear instrumental in diagnosing and classifying subtypes of COPD.

目的 利用生物信息学的方法探究IL-8在慢性阻塞性肺疾病(COPD)中的差异表达机制及其相关基因的功能.方法 使用基因表达综合数据库(gene expression omnibus,GEO)筛选慢阻肺患者和正常对照样本的mRNA、miRNA和lncRNA的表达数据;独立样本秩和检验比较IL-8的表达差异;基因富集分析(gene set enrichment analy-sis,GSEA)与IL-8表达相关的正负相关基因;通过预测IL-8相关的差异miRNA和差异lncRNA绘制IL-8-miR-NA-lncRNA环状网络;利用String构建差异基因网络并利用MCODE筛选蛋白互作网络中的关键基因;利用R软件的clusterProfiler包对IL-8正负表达相关基因进行基因本体论(gene ontology,GO)和京都基因与基因组百科全书数据库(KEGG)富集分析.结果 IL-8在慢阻肺患者中高表达;基因富集分析发现IL-8相关的正负相关基因富集在细胞转化和一些受体信号通路上;通过IL-8-miRNA-lncRNA环状网络发现lncRNA中SNHG5、MALAT1通过SNHG5/MALAT1-miR-32-5p-IL-8轴调控IL-8与慢阻肺的疾病相关;Go和Kegg通路富集在蛋白乙酰转移酶/组蛋白脱乙酰酶、PI3K-Akt通路、TNF-α/IL-17信号通路等信号通路中.结论 IL-8可能作为治疗慢阻肺的靶点,有望通过调控IL-8及其相关通路以调节糖皮质激素抵抗、抑制炎症反应而治疗慢性阻塞性肺疾病.

Abstract BackgroundChronic obstructive pulmonary disease (COPD) has become the fourth most lethal disease in the world and is expected to rise to the third most lethal disease in the world after 2030.COPD is complex and has clinical heterogeneity. However, identifying the subgroup characteristics of chronic obstructive pulmonary disease has become a challenge.ObjectivesThe ultimate goal of studying these different subgroups is to find patients with unique treatment goals and formulate targeted treatment plans to improve the prognosis of the disease and improve the quality of life of patients.MethodsWe obtained the relevant gene chip by searching the gene expression omnibus (GEO) database. According to the gene expression profile, 151patients with chronic obstructive pulmonary disease were divided into three subgroups, which showed different expression patterns. Therefore, we used weighted gene coexpression analysis (WGCNA) to identify the differences between different subgroups and identified five subgroup specific weighted gene coexpression analysis modules.ResultsThe characteristics of WGCNA module showed that subjects in subgroup I showed airway remodeling characteristics; Subjects in subgroup II showed metabolic activity; Subjects in subgroup III showed inflammatory characteristics.ConclusionsThis study obtained the clinical subgroup classification of chronic obstructive pulmonary disease through consensus clustering, and found that patients in different subgroups may have unique gene expression patterns, which can help researchers explore new treatment strategies for COPD according to the characteristics of clinical subgroups.

目的 探讨姜良铎教授治疗支气管哮喘常用药物的配伍规律.方法 以2003年3月至2019年9月姜良铎教授门诊的支气管哮喘患者为研究对象,选取治疗有效病例,对处方中常用药物进行聚类分析并探索其用药、配伍规律.结果 姜良铎教授治疗支气管哮喘使用率最高的药物分别为黄芩、白芍、麻黄、赤芍、杏仁、五味子、柴胡、贝母.按照聚类分析的方法常用药物可分为5类:宣肺定喘、补气祛风类;补脾益肾、益气养阴类;通调气机、肝肺同治类;肺胃同治类;滋阴清肺类.结论 姜良铎教授治疗支气管哮喘用药注重通调气机、祛风散邪、培补正气、肝肺胃同治等理念,在治疗中兼顾肝、胃、气机、痰瘀等因素的重要作用,并将平肝和胃、调畅三焦气机、化痰祛瘀等方法应用于哮喘的治疗中.

目的:探讨伴有/不伴有合并症的慢性阻塞性肺疾病(COPD)稳定期患者病位特征及其与肺功能的相关性.方法:收集538例COPD患者的人口统计学、身体质量指数、吸烟指数、急性加重次数、合并症、呼吸困难程度、COPD评估测试、肺功能、中医证候等资料,进行统计学分析.结果:伴有与不伴有合并症的COPD稳定期患者中,病位涉及脾,在不同肺功能分级方面有差异,其中GOLD1 (x2=5.779,P＜0.05)、GOLD2 (x2=10.733,P＜0.01)、GOLD3(x2=1.372,P＞0.05)、GOLD4(x2=0.001,P＞0.05).伴有与不伴有合并症的COPD稳定期患者中,病位涉及肾,在不同肺功能分级方面表现出类似差异.Logistic回归分析显示,在GOLD2级患者中,同时具备病位在肺肾的患者在伴有与不伴有合并症的COPD稳定期患者中有差异(OR=3.003,95％CI[1.532,5.888]).结论:合并症的存在对COPD稳定期患者的病位产生影响,伴有合并症的COPD稳定期患者在早期即可出现肺肾同病,随着气流受限的增加,病位在肺肾的比例逐渐上升.

Background: The development of chronic obstructive pulmonary disease (COPD) is related to the T lymphocyte mediated inflammatory immune response and immune imbalance. The purpose of this systematic review was to evaluate the clinical efficacy and safety of acupoint application on T lymphocyte subsets in patients with COPD. Methods: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, the Cochrane Library, and EMBASE for studies published as of Oct. 31, 2019. All randomized controlled trials of acupoint application on COPD patients that met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan5.3 software was used for meta-analysis. Results: Eight studies (combined n = 524) qualified based on the inclusion criteria. Compared with routine treatment alone, acupoint application combined with routine treatment can significantly increase the T lymphocyte CD4(+)/CD8(+)ratio (MD 0.12, 95% CI 0.03-0.21,P < .01,I-2 = 49%), reduce CD8(+)T-cells (MD-0.99, 95% CI-1.70-0.28,P < .001,I-2 = 37%), reduce the times of acute exacerbations (MD-0.28, 95% CI-0.35-0.21,P < .001,I-2 = 0), and improve the clinical efficacy (MD 1.30, 95% CI 1.14-1.48,P < .001,I-2 = 39%). Conclusion: Acupoint application can improve the CD4(+)/CD8(+)ratio and CD8(+)T-cells in patients with COPD and has an auxiliary effect in reducing the times of acute exacerbations and improving clinical efficacy.

姜良铎教授以辨状态论治为指导,应用角药治疗外感发热,疗效显著.本研究通过关联规则分析姜良铎教授治疗外感发热用药规律,探讨角药在外感发热中的应用.姜良铎教授在治疗外感发热时常采用荆芥、白芷、麻黄,柴胡、黄芩、石膏,石膏、知母、连翘,党参、黄芩、紫苏叶,藿香、佩兰、青蒿/黄芩等角药组合.

定喘汤证为肺失宣肃,或脾失健运,或肾失蒸化,或三焦气化不利,致痰浊内生,感受寒邪,风寒外袭,肺气闭郁,痰浊化热,而形成风寒外束、痰热内蕴之证.定喘汤宣肺降气、清热化痰,可广泛用于哮病之风寒外束、痰热内蕴证.慢性阻塞性肺疾病无论急性加重期或稳定期,但见咳嗽气喘、痰多而黄,或微恶风寒,甚或呼吸困难等符合定喘汤证者,皆可以定喘汤加减应用,以痰热内蕴兼有表寒证者最宜.

目的 研究支气管哮喘急性发作期治疗中中医药常用药物的组方规律.方法 以1991年1月1日至2018年12月31日CNKI、CHKD、万方数据库、中国生物医学文献数据库收录的国内期刊发表的文献、硕博士毕业论文,以中药复方单用/联合西医常规治疗为主治疗支气管哮喘急性发作,且临床观察治疗有效的中药复方为研究对象,采用关联规则分析的方法对常用药物进行分析,探讨支气管哮喘急性发作期中医药常用药物的组方规律.结果 支气管哮喘急性发作期常用药物的关联规则分析发现,置信度高的中药药对组合为炙麻黄、射干;三药组合为炙麻黄、款冬花、法半夏;四药组合为炙麻黄、紫苏子、法半夏、杏仁;五药组合为炙麻黄、紫苏子、法半夏、杏仁、甘草;六药组合为炙麻黄、款冬花、紫苏子、法半夏、杏仁、甘草.结论 在支气管哮喘急性发作期,中医药治疗以祛邪为法,表里同治,或以宣肺、温肺化饮为主,或以宣肺、清热化痰为主,并辅以虫类药物以熄风解痉平喘.

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目的 分析风温肺热病临床路径变异与退出的原因和影响因素,为进一步完善临床路径的管理提供理论依据.方法 纳入北京中医药大学第三附属医院进入风温肺热病临床路径病例143例,对病历资料进行回顾性分析,填写变异调查表,分析临床路径变异结果及变异的影响因素.结果 入选的143例中,发生变异66例,总体变异发生率为46.2％.在临床路径变异者中,因患者与疾病的变异发生56次(84.85％),因医务人员的变异发生6次(9.09％),因医院系统的变异发生4次(6.06％).多因素Logistic回归分析显示,CT病变范围、中医辨证分型、医疗费用支付方式是变异的影响因素(P<0.05).结论 风温肺热临床路径的变异是由多因素共同影响,明确路径变异原因,采取针对措施,能够更好地保障临床路径顺利实施.

目的:探讨姜良铎教授治疗慢性阻塞性肺疾病(COPD)的常用药物组方规律.方法:以2003年3月至2015年8月姜良铎教授门诊、病房、会诊的COPD患者为研究对象,采用关联规则对其治疗COPD的常用药物进行分析并探索其组方规律.结果:将关联规则分析出的药物组合与临床验证,发现治疗COPD组方中置信度较高的对药有贝母、知母,苏子、苏梗等,三药组合有贝母、知母、丹参,黄芩、紫河车、杏仁等.结论:姜良铎教授治疗COPD的用药是以祛邪扶正为主,祛邪以清肺泻热、清热化痰、通腑泄热、活血化瘀为主,扶正以补益肺、脾、肾气阴虚为主,对其组方规律的探讨有助于发现既往来发现的药物组合,进一步指导临床诊疗,提高临床疗效.

Abstract To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype. We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis. Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] −9.05, 95% confidence interval [CI] [−12.00, −6.10], P < .001, I 2 = 66%), forced expiratory volume in 1 second (FEV1) (MD −407.18, 95% CI [−438.63, −375.72], P < .001, I 2 = 33%), forced expiratory volume in 1 second percent predicted (MD −9.71, 95% CI [−12.79, −6.63], P < .001, I 2 = 87%), FEV1/forced vital capacity (MD −5.4, 95% CI [−6.49, −4.30], P < .001, I 2 = 0%), and body mass index (BMI) (MD −0.81, 95% CI [−1.18, −0.45], P < .001, I 2 = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I 2 = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I 2 = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I 2 = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I 2 = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I 2 = 86%) as compared to the ACO phenotype. Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx. This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.

Objective: To explore the clinical efficacy and safety of Qigong in reducing the self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores of patients with chronic obstructive pulmonary disease (COPD). Methods: We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE for studies published as of Dec 31, 2018. All randomized controlled trials of Qigong in COPD patients, which met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan 5.3 software was used for meta-analysis. Results: Six studies (combined n=415 patients) met the inclusion criteria. Compared with conventional therapy alone, Qigong in combination with conventional therapy significantly improved the following outcome measures: SDS score [mean difference (MD) -3.99, 95% CI (-6.17, -1.82), P<.001, I-2=69%]; SAS score[MD -4.57, 95% CI (-5.67, -3.48), P<.001, I-2=15%]; forced expiratory volume in one second/prediction (FEV1% pred) [MD 3.77, 95% CI (0.97,6.58), P<.01, I-2=0]; forced expiratory volume in one second (FEV1) [MD 0.21, 95% CI (0.13, 0.30), P<.001, I-2=0%]; forced vital capacity (FVC) [MD 0.28, 95% CI (0.16, 0.40), P<.001, I-2=0]; 6-minute walk test (6 MWT) distance [MD 39.31, 95% CI (18.27, 60.34), P<.001, I-2=32%]; and St. George's Respiratory Questionnaire (SGRQ) total score [MD -11.42, 95% CI (-21.80, -1.03), P<.05, I-2=72%]. Conclusion: Qigong can improve the SDS and SAS scores of COPD patients, and has auxiliary effects on improving lung function, 6 MWT distance, and SGRQ score.

角药是姜良铎教授临证辨状态论治的药物体现形式.所谓角药,即是3味中药的配伍组合.角药是建立在辨状态论治的思维上,临证时通过全面掌握整体状态,根据宏观与微观、大系统与子系统的动态病理变化,针对不同层次的状态采用多个由3个药物组成的组合进行诊疗的组方规则.在慢性阻塞性肺疾病稳定期治疗中,姜良铎教授常使用;黄精、白芥子、丹参;黄芪、赤芍、橘红;半夏、白术、桃仁;黄芩、栝楼、牛蒡子;麻黄、射干、五味子等角药组合,以补益肺肾、活血化痰,疗效卓著.

目的:评价消鼾利气颗粒治疗阻塞性睡眠呼吸暂停低通气综合征(OSAHS)的临床疗效.方法:将60例轻/中度OSAHS患者按照随机对照试验(RCT)原则分为治疗组与对照组各30例,治疗组采用口服消鼾利气颗粒加基础干预措施,对照组采用单纯基础干预措施,疗程1个月.观察两组治疗前后痰湿体质积分、中医证候积分、睡眠呼吸暂停低通气指数(AHI)、Epworth嗜睡量表(ESS)、夜间最低末梢血氧饱和度(LSP02)及SPO2＜90％占总睡眠时间比例(％)等的变化.结果:治疗后治疗组痰湿体质积分、中医证候积分、AHI、ESS、SPO2＜90％占总睡眠时间比例较本组治疗前下降,LSPO2升高,且与对照组同期比较均有极显著性差异(P＜0.01).相关性分析显示痰湿体质积分与中医证侯积分、AHI、ESS及SpO2＜ 90％占总睡眠时间比例均成正相关;与LSPO2成负相关.结论:消鼾利气颗粒通过调理OSAHS患者痰湿体质,从而减轻其临床症状,改善通气功能,提高患者生活质量.

Objective:To investigate the clinical efficacy and safety of traditional Qigong therapy on depression and anxiety score in patients with chronic obstructive pulmonary disease(COPD).Methods:Data in China National Knowledge Infrastructure(CNKI, 1979-2017),Wanfang database(Wanfang Data,1998-2017),Chongqing VIP Chinese scientific journal database(VIP,1979-2017),Chinese biomedical literature database(Sino Med,1978-2017),PubMed(1966-2017),and Cochrane Library before March 31,2017 were searched.Randomized controlled trials(RCTs)by taking Qigong as the main treatment for depression and anxiety score in patients with COPD were collected.Two researchers independently screened the literature and extract data.The included literature was assessed by Cochrane bias risk and analyzed by RevMan 5.3.Results:A total of 7 RCTs involving 485 patients were included.Meta-analysis showed that,compared with conventional treatment alone or no treatment,qigong combined with routine treatment could significantly improve depression score of patients(SMD -0.79,95%CI -1.09 to -0.49,P<0.001,I2=60%),the score of anxiety(SMD -0.73,95%CI -0.97 to -0.49,P<0.001,I2=39%),six minutes'walk test distance(MD 24.3,95% CI from 13.83 to 34.77,P=0.006,I2=66%),daily life score(MD -2.23,95% CI -2.90 to -1.56,P=0.26,I2=25%).Conclusion:Qigong may have certain benefits for anxiety and depression score of patients with COPD.At the same time, it may have auxiliary effects on improving the quality of daily life of patients.