Acute exacerbation of chronic obstructive pulmonary disease （AECOPD） belongs to the pulmonary collateral disease of traditional Chinese medicine， and its pathogenesis is always lung deficiency and blood stasis， heat and toxin stagnation. Lung deficiency and blood stasis are the pathological basis of COPD， and heat and toxin stagnation lead to acute exacerbation of the disease. Currently， there are few direct studies on the intervention of traditional Chinese medicine regulating NETs in AECOPD， but based on the idea of treating similar diseases differently， exploring NETs as a biological target for "heat toxin blocking the meridians" can provide modern theoretical support for the traditional Chinese medicine treatment method of clearing heat and regulating meridians for AECOPD， and provide new ideas for the mechanism research and new drug development of AECOPD. Studies have shown that the overproduction of neutrophil extracellular traps （NETs） can mediate lung inflammation and damage lung epithelial and endothelial cells， which is intrinsically consistent with the pathogenesis of this traditional Chinese medicine. Based on the theory of collateral disease， this paper combs the relevant generation pathways of NETs and the modern scientific mechanism of NETs involved in the pathogenesis of AECOPD， analyzes the correlation between the pathogenesis of AECOPD "heat and toxin stagnation" and the biological effects of NETs， and summarizes the potential targets of traditional Chinese medicine to regulate nets in the prevention and treatment of AECOPD. NETs can damage the airway epithelium and alveolar microvascular endothelium through cytotoxic effects， activate multiple inflammatory signaling pathways to release a large number of pro-inflammatory factors， induce mucus hypersecretion and promote thrombosis， and mediate the occurrence and development of AECOPD. This pathological process corresponded to the pathogenesis of heat and poison burning the qi collaterals of the lung， consuming the blood collaterals， and brewing phlegm and blood stasis over time. Existing studies have shown that traditional Chinese medicine monomers， compounds and acupuncture and moxibustion can inhibit the Peptidylarginine deiminase 4（PAD₄）， nicotinamide adenine dinucleotide phosphate（NADPH） oxidase 2（NOX₂）， nuclear factor-κB（NF-κB）， Toll like protein（TLR） and other signaling pathways， reduce the excessive release of NETs， play a role in clearing heat and dredging collateral， detoxification and blood stasis， and reduce lung tissue damage. At present， there are few direct studies on the regulation of NETs by traditional Chinese medicine in AECOPD. However， relying on the idea of treating different diseases together， mining NETs as the biological target of "heat and toxin stagnation" can provide modern theoretical support for the treatment of AECOPD with traditional Chinese medicine to clear heat and clear collaterality， and provide new ideas for the mechanism research and new drug research and development of AECOPD.

Chronic obstructive pulmonary disease(COPD)is a common but preventable and treatable lung disease characterized by persistent airflow limitation.Comorbidities related to COPD have recently received widespread attention because of their serious effects on the quality of life and prognosis of patients,and their role in promoting the malignant development of COPD.Experimental animal models provide a key for studying the pathogenesis of COPD and its related comorbidities and for exploring effective treatment methods.This review summarizes the modeling methods and research progress into experimental animal models of COPD-related comorbidities,to provide references and guidance for future clinical research and screening of animal models of related comorbidities.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Chronic obstructive pulmonary disease(COPD)is a common but preventable and treatable lung disease characterized by persistent airflow limitation.Comorbidities related to COPD have recently received widespread attention because of their serious effects on the quality of life and prognosis of patients,and their role in promoting the malignant development of COPD.Experimental animal models provide a key for studying the pathogenesis of COPD and its related comorbidities and for exploring effective treatment methods.This review summarizes the modeling methods and research progress into experimental animal models of COPD-related comorbidities,to provide references and guidance for future clinical research and screening of animal models of related comorbidities.

Objective:To investigate the association between estimated cumulative low-density lipoprotein cholesterol (LDL-C) exposure and the severity of coronary artery disease and long-term adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS).Methods:The subjects were from the PROMISE study. This study was a prospective cohort study led by Fuwai Hospital, Chinese Academy of Medical Sciences, with participation from eight regional tertiary hospitals as sub-centers, and enrolled 18 701 patients with confirmed coronary heart disease between January 2015 and May 2019. Among them, 8 429 patients with ACS were included in this study. The estimated cumulative LDL-C exposure was calculated by multiplying LDL-C by age. Participants were then divided into four groups based on quartiles. Baseline data and coronary angiography data were collected, and participants were followed for 2 years. The primary endpoint was MACCE, which was composed of all-cause death, cardiac death, myocardial infarction, revascularization, and stroke. Spearman correlation analysis was used to estimate the correlation between cumulative LDL-C exposure and the severity of coronary artery disease. The differences in MACCE among the four groups were compared, and multivariate Cox regression was used to divide the estimated cumulative exposure LDL-C into two groups, three groups, and four groups to analyze its relationship with MACCE.Results:The 8 429 ACS patients included in the study had an age of (60.9±11.4) years, with 1 951(23.1%) females. Spearman correlation analysis revealed that estimated cumulative LDL-C exposure was positively associated with the preoperative SYNTAX score, three-vessel lesions disease, left main disease, and the number of target lesions (correlation coefficients r=0.14, 0.10, 0.04 and 0.03, respectively, with all P<0.05). The 2-year follow-up results indicated that the incidence rates of MACCE, all-cause death, cardiac death, myocardial infarction, and stroke in ACS patients grouped by different levels of estimated cumulative LDL-C exposure were statistically significant (all P<0.05). The results of the Cox multivariate regression analysis showed that when the estimated cumulative LDL-C exposure was treated as a continuous variable and analyzed in two, three, and four groups, with the lowest group as the reference, the risk of MACCE occurrence in the high-value group increased by 21% (95% CI 1.08-1.37, P=0.002), 24% (95% CI 1.07-1.43, P=0.004), and 21% (95% CI 1.02-1.43, P=0.025) respectively. Conclusions:A positive correlation was found between estimated cumulative LDL-C exposure and severity of coronary artery disease. High estimated cumulative LDL-C exposure level is a risk factor for MACCE in ACS patients within 2 years.

Acute ST-segment elevation myocardial infarction with multivessel disease is one of the high-risk types of coronary heart disease.Early opening of infarct-related artery and reperfusion of myocardium could significantly reduce the mortality in acute phase.However,the presence of non-culprit lesions in non-infarct-related arteries is still at risk and has an important impact on the long-term prognosis of patients.It remains controversial on how to precisely evaluate the clinical significance and revascularization value of non-culprit lesions.This article aims to review the research status and progress of guidance strategies of non-culprit lesion revascularization in patients with ST-segment elevation myocardial infarction and multivessel disease.

Objectives:To investigate the impacts of American College of Cardiology/American Heart Association (ACC/AHA) coronary artery classification on the progression of coronary non-target lesions and revascularization in patients with coronary heart disease.Methods:From January 2010 to September 2014,1255 patients who underwent two consecutive coronary angiographies at Fuwai Hospital and had coronary non-target lesions were retrospectively analyzed.Lesion characteristics of all coronary non-target lesions were recorded at both procedures.All non-target lesions were divided into A,B1,B2 and C lesion group according to ACC/AHA coronary artery classification.Patients were divided into non-B2/C lesion group (noncomplex lesion group) and B2/C lesion group (complex lesion group) according to whether the non-target lesion had B2/C lesion The characteristics of all non-target coronary artery lesions and quantitative coronary angiography results were recorded.Lesion progression and revascularization were compared between different groups.Results:There were 1003 (79.9％) male patients,mean age was (58.0±9.7) years old,and 853 patients had B2/C lesions.There were 1670 non-target lesions,including 619 A/B1 lesions (214 A lesions and 405 B1 lesions) and 1051 B2/C lesions (796 B2 lesions and 255 C lesions).Follow-up time was (14.8±4.5) months.Compared with the patients in noncomplex lesion group,patients in complex lesion group were older,had lower proportion of family history of coronary heart disease and stroke (all P<0.05).The baseline levels of leukocytes,C-reactive protein,erythrocyte sedimentation rate (ESR),triglyceride and HbA1c were higher in complex lesion group than those in noncomplex lesion group.Complex lesion group had higher risk of lesion progression (21.8％ vs.13.2％,P<0.001) compared with noncomplex lesion group,similar results were observed in revascularization (16.5％ vs.11.2％,P=0.013),and there was no statistically difference in non-target lesion related myocardial infarction (P>0.05).At the lesion level,compared with A/B1 lesion,B2/C lesion was associated with a higher rate of lesion progression (17.4％ vs.11.0％,P<0.001),and a higher rate of revascularization (13.0％ vs.9.2％,P=0.018).Multivariate Cox regression analysis showed that lesion classification (B2/C) was an independent risk factor for non-target lesion progression (HR=1.732,95％CI:1.275-2.351,P<0.001) and non-target lesion revascularization (HR=1.477,95％CI:1.053-2.070,P=0.024).Conclusions:The risk of non-target lesion progression and revascularization is higher in complex groups compared with noncomplex groups according to ACC/AHA classification.So patients with complex lesions should receive more strict medical care to control related risk factors and improve their outcome.

Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.

Objectives:To investigate the impacts of American College of Cardiology/American Heart Association (ACC/AHA) coronary artery classification on the progression of coronary non-target lesions and revascularization in patients with coronary heart disease.Methods:From January 2010 to September 2014,1255 patients who underwent two consecutive coronary angiographies at Fuwai Hospital and had coronary non-target lesions were retrospectively analyzed.Lesion characteristics of all coronary non-target lesions were recorded at both procedures.All non-target lesions were divided into A,B1,B2 and C lesion group according to ACC/AHA coronary artery classification.Patients were divided into non-B2/C lesion group (noncomplex lesion group) and B2/C lesion group (complex lesion group) according to whether the non-target lesion had B2/C lesion The characteristics of all non-target coronary artery lesions and quantitative coronary angiography results were recorded.Lesion progression and revascularization were compared between different groups.Results:There were 1003 (79.9％) male patients,mean age was (58.0±9.7) years old,and 853 patients had B2/C lesions.There were 1670 non-target lesions,including 619 A/B1 lesions (214 A lesions and 405 B1 lesions) and 1051 B2/C lesions (796 B2 lesions and 255 C lesions).Follow-up time was (14.8±4.5) months.Compared with the patients in noncomplex lesion group,patients in complex lesion group were older,had lower proportion of family history of coronary heart disease and stroke (all P<0.05).The baseline levels of leukocytes,C-reactive protein,erythrocyte sedimentation rate (ESR),triglyceride and HbA1c were higher in complex lesion group than those in noncomplex lesion group.Complex lesion group had higher risk of lesion progression (21.8％ vs.13.2％,P<0.001) compared with noncomplex lesion group,similar results were observed in revascularization (16.5％ vs.11.2％,P=0.013),and there was no statistically difference in non-target lesion related myocardial infarction (P>0.05).At the lesion level,compared with A/B1 lesion,B2/C lesion was associated with a higher rate of lesion progression (17.4％ vs.11.0％,P<0.001),and a higher rate of revascularization (13.0％ vs.9.2％,P=0.018).Multivariate Cox regression analysis showed that lesion classification (B2/C) was an independent risk factor for non-target lesion progression (HR=1.732,95％CI:1.275-2.351,P<0.001) and non-target lesion revascularization (HR=1.477,95％CI:1.053-2.070,P=0.024).Conclusions:The risk of non-target lesion progression and revascularization is higher in complex groups compared with noncomplex groups according to ACC/AHA classification.So patients with complex lesions should receive more strict medical care to control related risk factors and improve their outcome.

OBJECTIVE：To investigate the effects of Aconitum injection on cartilage oligomeric matrix protein （COMP）， encoded protein by tumor suppressor gene p53（p53 protein）and bone morphogenetic protein 2（BMP-2）in knee osteoarthritis （KOA）model rabbit ，so as to explore the mechanism of the injection in the treatment of KOA. METHODS ：Totally 24 rabbits were randomly divided into blank group ，model group ，Sodium hyaluronate group and Aconitum injection group ，with 6 rabbits in each group. KOA model was established by injecting 2％ papain-0.03 mol/L L-cysteine solution into the articular cavity of rabbits in model group ，sodium hyaluronate group and Aconitum injection group at the 1st，4th and 7th day ，respectively，except the blank group. At the 1st，4th and 7th day after modeling succeeded ，0.1 mL/kg of normal saline ，Sodium hyaluronate injection and Aconitum injection were injected into the articular cavity of rabbits ，respectively. The cartilage tissue of knee joint was taken from above 4 groups，and the contents of COMP and p 53 protein were detected by ELISA. The cartilage morphology of rabbit knee joint was observed by naked eye. The cartilage of the knee joint was collected and stained by HE staining ，and then the histomorphology changes were observed by light microscope ；Mankin scoring was conducted. The two-step method of PV was used to make the immunohistochemical specimens of knee joint cartilage ，and the relative expression of BMP- 2 was detected. RESULTS ：Compared with blank group ，the edge of cartilage was damaged and the cartilage surface was damaged in the model group. The results of histomorphology observation showed that the joint tissue structure was obviously irregular ，the distribution of chondrocytes was disordered with morphological changes ，and the Mankin score was significantly increased （P＜0.05）；the contents of COMP and cancer cells by indirect inhibition of RAD 51-mediated re - . Suppression of ERCC 1 and RAD51 expression through ERK 1/2 inactivation is essen - tial in emodin-mediated cytotoxicity in human non-small 。E-mail： cell lung cancer cells. p53 protein in knee joint fluid were increased significantly ，while the relative expression of BMP- 2 in knee joint tissue decreased significantly （P＜0.05）. Compared with model group ，the appearance ，histomorphology changes of knee joint cartilage in administration groups were improved，Mankin scores were significantly decreased （P＜0.05）；the contents of COMP and p 53 protein in the knee joint fluid were decreased significantly ，and the relative expression of BMP- 2 in the knee joint tissue were increased significantly （P＜0.05），but there was no significant difference between Aconitum group and Sodium hyaluronate group （P＞0.05）. CONCLUSIONS ：Aconitum injection can improve synovitis inflammation ，delay articular cartilage degeneration ， promote cartilage repair and protect joints of KOA model rabbits. The mechanism may be related to inhibiting COMP secretion ， decreasing p 53 protein expression and promoting BMP- 2 release.