基于网络药理学探讨清金化浊方治疗慢阻肺的作用机制＊

目的 利用网络药理学方法探讨清金化浊方治疗慢阻肺的作用机制。方法 在中药系统药理学数据库和分析平台（Traditional Chinese Medicine Systems Pharmacology，TCMSP）平台检索组方君臣药物的主要化学成分及作用靶点，通过TTD、CTD、DisGeNET、GeneCards数据库获得慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease，COPD）相关靶点，筛选药物与疾病的交集靶点及有效活性成分。利用Cytoscape3.7.2构建药物-化合物-靶点-疾病网络，利用STRING数据库构建蛋白质-蛋白质相互作用关系（Protein-Protein Interaction，PPI）网络 拓扑分析图，并分析核心靶点。利用DAVID数据库进行基因功能（Gene Ontology，GO）和基于京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）富集分析，并绘制通路-靶点网络图。基于网络分析结果，纳入2020年1月-2021年1月我科收治的AECOPD患者，采用区组随机法按1：1分为对照组（西医治疗组）、研究组（清金化浊方联合西医治疗组），比较两组患者的IL-6、TNF-α水平。结果 筛选得到164个中药成分靶点，3051个COPD靶点，映射得出药物-疾病交集靶点112个。分析得出清金化浊方治疗COPD主要有槲皮素、β-谷甾醇、山奈酚、豆甾醇、木犀草素等有效活性成分，涉及IL-6、TNF、MAPK3、VEGFA、TP53、PTGS2、MAPK1、PIK3CG等关键靶点。富集于药物反应、一氧化氮生物合成过程的正调控、缺氧反应等生物过程及83条信号通路，其中TNF、HIF-1和PI3K-Akt信号通路在COPD的治疗中最为重要。临床研究显示，两组治疗7天后IL-6、TNF-α均较治疗前下降；治疗后组间比较，研究组低于对照组（P<0.05）。结论 清金化浊方主要以抗炎为核心，兼有调节氧平衡、降低气道黏液高分泌、改善气道重塑、调节免疫功能及血液高凝状态等多方面的作用，为其临床应用提供一定指导价值，亦为进一步开展后续课题研究提供科学依据。     

Dynamic obstruction induced by systolic anterior motion of the mitral valve in a volume-depleted left ventricle: an unexpected cause of acute heart failure in a patient with chronic obstructive pulmonary disease

Systolic anterior motion (SAM) of the mitral valve (MV) and left ventricular outflow tract (LVOT) dynamic obstruction (DO) typically occur in hypertrophic cardiomyopathy; however, they can appear in an apparently normal heart in association with changes in cardiac loading conditions and/or hyperdynamic left ventricular (LV) performance. Meanwhile, chronic obstructive pulmonary disease (COPD) can impair LV filling by elevating pulmonary vascular resistance. The authors report a case of transient acute heart failure caused by LVOT DO resulting from SAM of the MV in a severely volume-depleted LV in a patient with acute COPD exacerbation.     

以社区医疗为核心的多学科合作综合COPD管理模式探究

目的探讨以社区医疗为核心的多学科合作综合COPD管理模式对COPD稳定期患者依从性、临床症状控制及急性发作频率的管理效果。方法抽取2017年1-6月期间签约家庭医生的COPD稳定期患者60例,随机分为综合管理组和常规管理组,每组各30例。综合管理组实施以全科医生为核心的COPD慢病管理模式,并选择同时期未实施慢病管理模式的COPD患者30例为常规管理组。不同管理模式实施24个月后,对患者及其家属依从性、BODE指数和急性发作等情况进行调查。结果干预2年后,综合管理组30例完成随访,常规管理组3例失访;综合管理组戒烟、合理用药、合理运动依从性、6 MWT和FEV1%pre均高于常规管理组,差异有统计学意义(P<0.05);两组BODE指数分别为(2.87±1.25)和(3.37±1.88),综合管理组低于常规管理组,差异有统计学意义(P<0.05);干预第2年,综合管理组人均急性发作次数和住院天数分别为(2.14±0.22)次和(6.51±2.62)天,均低于常规管理组,差异有统计学意义(P<0.05)。结论以社区医疗为核心的多学科合作综合COPD管理模式可行,值得进一步推广。     

Mortality Related to Chronic Obstructive Pulmonary Disease and Co-morbidities in the United States,A Multiple Causes of Death Analysis

ABSTRACT

Chronic obstructive pulmonary disease (COPD) mortality based on the underlying cause of death (UCOD) underestimates disease burden. We aimed to determine the current COPD mortality rate, trends and the distribution of co-morbidities using United States (US) multiple-cause of death (MCOD) records.

All 38,905,575 death certificates of decedents aged ≥45 years in the United States were analyzed for 1999–2015. COPD was defined by ICD–10 codes J40–J44 and J47 based either on the UCOD or up to 20 contributing causes coded. Annual age–standardized COPD death rates were computed by age, gender and race/ethnicity for those with any mention of COPD.

In 2015, COPD was mentioned in 11.59% (292,572 deaths) in MCOD, compared to 11.13% (243,617 deaths) in 1999, a 4% increase. However, it was reported as the UCOD for only 5.56% and 4.97% in 2015 and 1999 respectively, an 11% increase. The most common UCOD in subjects with any mention of COPD was respiratory disorders in 49% of males and 55% of females. The relative change in death rates differed between MCOD and UCOD. For example, among non-Hispanic white females aged 65–74 years the UCOD rate per 100,000 (95% CI) decreased from 163 (160–166) to 147 (145–150), average annual percent decrease (AAPD) –0.26, while the MCOD rate decreased from 308 (304–311) to 263 (260–267), AAPD –0.87.

Statistics based on UCOD understated the burden of COPD in the United States. MCOD rates were twice as high as UCOD rates. The relative change in death percent or rates differed between MCOD and UCOD. MCOD analysis should be repeated periodically to help evaluate the burden of COPD-related mortality.     

Management of COPD in End-of-Life Care by Spanish Pulmonologists

ABSTRACT

Chronic obstructive pulmonary disease is progressive and in its advanced stage is associated with major disability. Previous studies suggest that patients with this disease receive little palliative care, even in very advanced stages. Given this, our objectives were to describe the clinical practice of Spanish pulmonologists in the care of patients with end-stage chronic obstructive pulmonary disease, to identify potential barriers to implementing palliative care in these patients and to correlate these responses with doctor's years of experience. A link to an online survey was sent to pulmonologists on (a) symptom management, (b) structure of their department and collaboration with other services, (c) specialized medical training in palliative care, (d) communication with patients and their families, and (e) limiting barriers identified in the management of these patients. A total of 387 responses were received. The majority used opioids to treat dyspnea (52.9%) or pain (54.2%) and many treated anxiety/depression (41%). Around half of the respondents had no established routines in their departments to offer palliative care to patients with chronic obstructive pulmonary disease. There was little communication with end-of-life patients and their families on disease course, mainly associated with a lack of medical training (83% of cases) and changes in patient wishes regarding care through the disease course (81%). In our setting, communication with end-of-life patients with chronic obstructive pulmonary disease is poor. The key challenges identified are insufficient medical training and changing desires of patients. No substantial differences in attitude were found as a function of experience.