Effects of Sirt1 on proliferation,migration,and apoptosis of endothelial progenitor cells in peripheral blood of SD rats with chronic obstructive pulmonary disease

Objective:To explore the effect of Sirt1 on the function of endothelial progenitor cells(EPCs)in rats with chronic obstructive pulmonary disease(COPD).Methods:A rat COPD model was established via smoking and endotoxin administration for three months.The peripheral circulating EPCs were isolated by gradient centrifugation,and their functions,cell cycle distribution,apoptosis,and Sirt1 expression were examined.The function changes of EPCs in the presence or absence of Sirt1 agonist and inhibitor were estimated;meanwhile,the expressions of Sirt1,FOXO3a,NF-κB,and p53 were also evaluated.Results:The proliferation,adhesion,and migration of EPCs decreased while the apoptosis rate was increased in the COPD rats.The expression of Sirt1 protein in EPCs of the COPD group was significantly lower than that in the control group(P<0.01).The overexpression of the Sirt1 gene using a gene transfection technique or Sirt1 agonists(SRT1720)improved the proliferation,migration,and adhesion,and decreased the apoptosis of EPC.However,Sirt1 inhibitor(EX527)decreased EPC functions in the COPD group.The effect of Sirt1 expression on EPC function may be related to reduction of FOXO3a and increase of NF-κB and p53 activity.Conclusions:Increased expression of Sirt1 can improve the proliferation and migration of EPCs and reduce their apoptosis in COPD rats.This change may be related to FOXO3a,NF-κB,and p53 signaling pathways.

Effects of electroacupuncture at Zusanli(ST36) on inflammatory cytokines in a rat model of smokeinduced chronic obstructive pulmonary disease

OBJECTIVE： Improvement in lung function was reported after acupuncture treatment of chronic obstructive pulmonary disease （COPD）, but little is known about the underlying mechanisms. Because an immune response imbalance could be seen in COPD, we hypothesize that electroacupuncture （EA） may play a role in regulating inflammatory cytokines and contribute to lung protection in a rat model of smoke-induced COPD. METHODS： A COPD model using male Sprague-Dawley rats exposed to cigarette smoke was established. The rats were randomly divided into four groups （control, sham, COPD, and COPD plus EA）, and COPD model was evaluated by measuring pulmonary pathological changes and lung function. EA was applied to the acupuncture point Zusanli （ST36） for 30 min/d for 14 d in sham and COPD rats. Bronchoalveolar lavage fluid （BALF） was used to measure levels of tumor necrosis factor-a （TNF-a）, interleukin-113 （IL-113）, and malonaldehyde （MDA）. RESULTS： Compared with the control rats, COPD rats had significant changes in lung resistance （R,） and lung compliance （C,） （both P〈0.01）, bronchi and bronchiole airway obstruction （P〈0.01）, and levels of MDA, TNF-α, and IL-1β（P〈0.01）. There were no significant differences between the control and the sham groups. Compared with the COPD rats, the COPD plus EA rats had decreased R, and increased CL （both P〈0.05）, and reduced bronchi and bronchiole airway obstruction （P〈0.05, P〈0.01, respectively）, while levels of TNF-α, IL-1β, and MDA in BALF were lowered （P〈0.05 and P〈0.01, respectively）. However, TNF-α and IL-1β levels of the EA group rats remained higher than those of the control group （P〈0.05）. CONCLUSION： EA at ST36 can reduce lung injury in a COPD rat model, and beneficial effects may be related to down-regulation of inflammatory cytokines. The anti-inflammatory and antioxidant effects may prolong the clinical benefit of EA.

Combined Effects of Chronic Obstructive Pulmonary Disease and Depression on Spatial Memory in Old Rats

Objective To investigate the combined effects of chronic obstructive pulmonary disease(COPD)and depression on spatial memory in old rats,aiming to better understand the comorbidity of the two diseases in geriatric patients.Methods The SD rats were assigned into five groups:adult control group(n=6),elderly control group(n=6),elderly COPD group(n=6),elderly depression group(n=6)and elderly COPD with depression group(n=6).Smoking and chronic unpredictable mild stress(CUMS)with solitary support were used to induce COPD model,depression model,respectively,and the both were applied for the comorbidity model.Learning and memory deficits were assessed by Morris water maze(MWM)test.The activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in serum and hippocampus tissue were determined by Xanthinoxidase method and Thiobarbituric acid reaction(TBAR)method,respectively.Results The results of pulmonary histology,lung function,open-field test and sucrose consumption demonstrated the comorbidity models of COPD and depression in elderly rats were successfully established using smoking and CUMS with solitary support.Compared with the elderly control group,the group of COPD with depression had obviously longer time of latency and longer travel distance to reach the platform in MWM test(LSD-t=-10.116,P=0.000;LSD-t=-6.448,P=0.000).The SOD activity in serum and hippocampus decreased significantly(LSD-t=2.629,P=0.014;LSD-t=2.215,P=0.044)and the MDA content in serum and hippocampus increased significantly(LSD-t=-2.140,P=0.042;LSD-t=-2.070,P=0.049)in elderly COPD with depression group.Conclusions COPD in comorbidity of depression could induce spatial memory deficit in old rats.The mechanisms might be related to the overloaded and free radical metabolic imbalance.These results suggest a potential therapeutic target for comorbidity of COPD and depression in geriatric patients.

Regulatory Effect of Shenge Yifei Capsule on TGF-β1/Smad Signaling Pathway in Rats with Chronic Obstructive Pulmonary Disease

[Objectives]This study aimed to study the effects of Shenge Yifei capsule on the TGF-β1/Smad signaling pathway in rats with chronic obstructive pulmonary disease(COPD).[Methods]Ten rats were randomly selected as the control group,and the other 40 rats were selected for modeling by fumigation combined with Klebsiella pneumoniae infection.A total of 38 rats were successfully modeled.They were randomly divided into model group(8 rats),low-dose Shenge Yifei capsule group(10 rats),high-dose Shenge Yifei capsule group(10 rats)and theophylline group(10 rats)in accordance with the principle of half male and half female.The rats in the model and control groups were given with distilled water by gavage,and the rats in the drug administration groups were given with corresponding drugs.The TGF-β1 level in the serum,and the expression levels of TGF-β1,Smad2,Smad3 and Smad7 and TGF-β1,Smad3 and Smad7 in airway tissues were detected.[Results]After 12 weeks,the serum TGF-β1 levels of the theophylline group and high-dose Shenge Yifei capsule group were lower than that of the low-dose Shenge Yifei capsule group(P<0.05).The expression levels of TGF-β1 and Smad3 in the theophylline group and high-dose Shenge Yifei capsule group were lower than that in the low-dose Shenge Yifei capsule group(P<0.05).The expression levels of TGF-β1 and Smad3 in the high-dose Shenge Yifei capsule group were lower than those in the low-dose Shenge Yifei capsule group and theophylline group(P<0.05).The expression levels of Smad7 and the proteins in the model group were lower than those in the other groups(P<0.05).The expression levels of Smad7 in the theophylline group and high-dose Shenge Yifei capsule group were higher than that in the low-dose Shenge Yifei capsule group(P<0.05).After 18 weeks,no significant difference was found in serum TGF-β1 level among the theophylline group and low and high-dose Shenge Yifei capsule groups(P>0.05).The expression levels of Smad7 and the proteins in the model group were lower than those in the other groups.The expression level of Smad7 in the high-dose Shenge Yifei capsule group was lower than that in the theophylline group(P<0.05).[Conclusions]Shenge Yifei capsule can regulate the TGF-β1/Smads signaling pathway.They can down-regulate the expression of TGF-β1,Smad2 and Smad3 and up-regulate the expression of Smad7,reducing the degree of airway modeling,delaying the development of COPD disease.Conventional high-dose Shenge Yifei capsule is more effective in inhibiting the expression of Smad2.

Effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor of chronic obstructive pulmonary disease rat

Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.

Effect of Maxingganshi decoction on the expression of STAT4 and STAT6 in lung tissues of rats with chronic obstructive pulmonary disease

Objective:To investigate the effect of Maxingganshi decoction on the expression of STAT4 and STAT6 in lung tissues of rats with chronic obstructive pulmonary disease (COPD).Methods:A total of 30 COPD Wistar rat models with phlegm-heat depression and lung depression were established, with half male and half female. The 30 model rats were fed in different cages, weighed and labeled. They were randomly divided into three groups: Maxingganshi decoction group, roxithromycin tablets control group, model control group. At the same time, 10 normal rats were selected as a blank control group. The white blood cell count and other cell count levels in the alveolar lavage fluid of the rats in the four groups, as well as the STAT4 and STAT6 protein levels in the lung tissues, were observed and compared.Results: After treatment, the white cell counts in Maxingganshi decoction group were significantly higher than that of the model control group (P<0.05);lymph, neutral particles and eosinophil levels were significantly lower than those of the model control group (P<0.05). Compared with roxithromycin tablets control group, white blood cell count and other classification level of cell count in Maxingganshi decoction group were not significantly different (P>0.05). After treatment, STAT4 protein levels in roxithromycin tablets control group and Maxingganshi decoction group were lower than that in the model control group (P<0.05), and STAT6 protein levels in roxithromycin tablets control group and Maxingganshi decoction group were higher than that of the model control group (P<0.05), suggesting the two means of intervention in this study could inhabit the STAT4 protein expression in lung tissue of COPD rats and promote effect on STAT6 protein. In addition, the level of STAT4 and STAT6 in the Maxingganshi decoction group was not significantly different from that in the roxithromycin tablets control group (P>0.05), suggesting that the effect of Maxingganshi decoction was similar to that of roxithromycin tablets.Conclusions: The action mechanism of Maxingganshi decoction group treating COPD may be through the STAT4 and STAT6 protein expression level to impose an effect, and thus interfere with IL-12 / STAT4 and IL-4 / STAT6 these two signaling pathways of Th1 cells and Th2 cells in the body of the gene expression, inhibiting the Th1 polarization and adjusting the imbalance of Thl/Th2 cells, so as to lower inflammatory response mediated by T cells and various kinds of pathological damage.

Effect of ipratropium bromide on airway and pulmonary muscarinic receptors in a rat model of chronic obstructive pulmonary disease

OBJECTIVE: To observe the level of muscarinic receptors in airway and lung tissues, and the effect of inhaled ipratropium bromide on these receptors in a rat model of chronic obstructive pulmonary disease (COPD). METHODS: This model was developed by exposure of rats to 250 ppm SO2 gas, 5 h/d, 5 d/wk, for a period of 7 wk. The COPD rats inhaled 0.025% aerosolized iratropium bromide for 20 min, 2 times daily, in an airtight chamber. Muscarinic receptors in airway and lung tissues of normal rats, ipratropium bromide-treated COPD rats and the recovering COPD rats were measured by the radio-ligand binding assay. RESULTS: Airway/lung pathology and pulmonary function tests showed that chronic SO2 exposure caused pathophysiologic changes similar to those observed in human COPD. The density (0.038 +/- 0.011, pmol/mg protein) and affinity (Kd, 23 +/- 11 pmol/L) of muscarinic receptors in airway and lung tissues of COPD rats were not changed compared with those of normal control rats (0.030 +/- 0.008 and 29 +/- 19, respectively, P > 0.05). Densities of the muscarinic receptors were not changed after inhalation of ipratropium bromide for 5 days, but increased significantly after inhalation for 30 days, as compared with those of the untreated COPD rats. The muscarinic receptors returned the normal levels at day 6 after cessation of ipratropium bromide treatment. There were no differences among different groups of rats in equilibrium dissociation constants (Kd). CONCLUSION: A rat model of COPD with pathophysiologic changes similar to the human counterpart was developed using chronic SO2 exposure. There was no significant change in the number and function of muscarinic receptors in airway and lung tissues of the COPD rats, but upregulation of the muscarinic receptors was observed after long-term inhalation of ipratropium bromide.

Short term effect of Salvia miltiorrhiza in treating rat acetic acid chronic gastric ulcer and long term effect in preventing recurrence

AIM To study the short term effect of Danshen ( Salvia miltiorrhiza ) on acetic acid induced chronic gastric ulcer in rats and its long term effect in preventing recurrence. METHODS Rats with acetic acid induced gastric ulcer were treated with Danshen and cimetidine for 30 days. Traditional gastric mucosal auto radiography and 3H TdR incorporation into gastric mucosa in vitro were employed to study the effects of Danshen in rat acetic acid induced chronic gastric ulcer, including ulcer index (UI), ulcer inhibitory rate (IR) and label rate (LR). RESULTS On the day 5, 30 and 126 of ulcer making, the UI in the Danshen group was obviously lower than that in the cimetidine group and the control group (42 3±3 9, 3 6±1 2, 4 4±2 3; 49 1±3 6, 5 9±1 4, 9 2±1 3; 61 0±3 8, 8 9±2 5, 12 4±2 4, respectively, P <0 01), the IR (%) in the Danshen group was obviously higher than that in the cimetidine group (31, 59, 64 8; 19, 33, 26, respectively), and the LR in the Danshen group was obviously higher than that in the cimetidine group and the control group (10 0±0 5, 16 2±0 8, 15 0±0 6; 9 0±0 5, 13 9±0 6, 10 8±0 7; 6 5±0 7, 10 1±0 5, 8 0±0 7, respectively, P <0 01). There was no obvious difference in UI in the Danshen group on day 30 as compared with that on day 126. CONCLUSION Danshen is effective in promoting ulcer healing and preventing recurrence. The mechanism of action is to strengthen the gastric mucosal barrier and to promote the gastric mucosal cell proliferation along the edge of the ulcer.

Electroacupuncture at Feishu(BL13) and Zusanli(ST36) down-regulates the expression of orexins and their receptors in rats with chronic obstructive pulmonary disease

Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease （COPD）. Acupuncture can improve lung function in patients with COPD, but the underlying mechanisms are not well understood. Orexins （OXs）, which are found in peripheral plasma, are neuropeptides that regulate respiration and their levels are related to COPD. Therefore, we hypothesized that acupuncture might alter OXs, reduce lung inflammation and improve lung function in COPD. METHODS： COPD was induced in rats by exposure to cigarette smoke for 8 weeks and injecting with lipopolysaccharide twice. Electroacupuncture （EA） was performed at Feishu （BL13） and Zusanli （ST36） for 30 min/d for 2 weeks. Rat lung function and morphology were assessed after EA. The levels of tumor necrosis factor-α （TNF-a） and intedeukin-1β （IL-16） in bronchoalveolar lavage fluid （BALF） and orexin A and B levels in the lung tissue were detected by enzyme-linked immunosorbent assay. OX receptor mRNA levels and immunopositive cells were assessed with real-time polymerase chain reaction and immunohistochemical methods, respectively. The relationships among lung function, cell factors, and OX levels were analyzed by Pearson correlation analyses. RESULTS： Compared with the control group, lung function was significantly decreased in the rats with COPD （P〈0.05）. There were obvious increases in TNF-α and IL-1β levels in BALF （P〈0.05 and P〈0.01, respectively）, orexin A level in lung tissue （P〈0.01; but not orexin B） and mRNA expressions of OX 1 type receptor （OXR1） and OX 2 type receptor （OXR2） in lung tissue （P〈0.05 and P〈0.01, respectively）; the integrative optical densities （IODs） of both receptors were greater in the COPD group （P〈0.05）. For rats with COPD subjected to EA, lung function was improved （P〈0.05）. There were notable decreases in TNF-a and IL-1β levels （P〈0.05 and 〈0.01, respectively） in BALF. Orexin A, but not orexin B, levels in lung tissue also decreased （P〈0.01）, as did mRNA expression of OXlR and OX2R in lung tissue （P〈0.05 and P〈0.01, respectively）. Receptor IODs were also reduced after EA treatment （P〈0.05）. Furthermore, orexin A levels and ratio of forced expiratory volume in 0.3 s to forced vital capacity were strongly negatively correlated （P〈0.01）, and orexin A was positively correlated with TNF-α and IL-1β （P〈0.001 and P〈0.05, respectively）.CONCLUSION： EA at Zusanli and Feishu improved lung function of rats with COPD and had an anti-inflammatory effect, which may be related to down-regulation of OXA and its receptors.

Network Modeling of Inammatory Dynamics Induced by Biomass Smoke Leading to Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease(COPD) is a chronic inflammatory disorder characterized by airflow obstruction and progressive damage of lung tissues. As currently more than 3 billion people use biomass fuel for cooking and heating worldwide, exposure to biomass smoke(BS) is recognized as a significant risk factor for COPD. Recent clinical data have shown that BS-COPD patients have a Th2-type inflammatory profile significantly different from that in COPD induced by cigarette smoke. As COPD is essentially proinflammatory,however, the mechanism underlying this Th2-type anti-inflammatory profile remains elusive.In this work, a network model is applied to study BS-induced inflammatory dynamics. The network model involves several positive feedback loops, activations of which are responsible for different mechanisms by which clinical phenotypes of COPD are produced. Our modeling study in this work has identified a subset of BS-COPD patients with a mixed M1-and Th2-type inflammatory profile. The model’s prediction is in good agreement with clinical experiments and our in silico knockout simulations have demonstrated several important network components that play an important role in the disease. Our modeling study provides novel insight into BS-COPD progression, offering a rationale for targeted therapy and personalized medicine for treatment of the disease in future.

Proteomic analysis of a chronic obstructive pulmonary disease mouse model to determine the efficacy of treatment using Guben Zhike decoction

Background:Guben Zhike decoction(GBZKD)is derived from the experience of Professor Enxiang Chao,an esteemed master of Chinese medicine,while treating chronic obstructive pulmonary disease(COPD).GBZKD reinforces the healthy qi and consolidates defensive qi.This study explored the efficacy and potential mechanism of action of GBZKD in a COPD mouse model using proteomics.Methods:A COPD mouse model was established through cigarette smoke exposure and intranasal lipopolysaccharide administration.The model was verified through lung function test and lung histopathological observation.Label-free quantitative proteomics was used to detect the lung tissue proteins of mice from the GBZKD,COPD,and control groups.Results:GBZKD markedly improved the lung function and associated pathological conditions in the COPD mouse model.Proteomic analysis identified 4316 proteins,of which 3696 were quantitative proteins.We highlighted 287 and 184 proteins with significant regulatory roles in the lung tissues of COPD mice and GBZKD-treated mice,respectively.These proteins participated in multiple functions,including complement/coagulation cascade,immune response,and metabolic pathways.Conclusion:GBZKD exhibits multitarget and multipathway therapeutic effects in a COPD mouse model.

Outcomes and Cost Effectiveness of a Respiratory Coordinated Care Program in Patients with Severe or Very Severe COPD

Multidisciplinary community coordinated care programs are widely adopted to optimise care of chronic disease patients, but there is a need for further evaluation in the setting of COPD. This observational study evaluated 147 patients with severe or very severe COPD who were enrolled in a multidisciplinary community respiratory coordinated care program (RCCP) from 2007 to 2012. Comparison was made of hospitalisation rates and length of stay for 12 months prior to joining the program, and the first 12 months after joining the program. This data was used to inform a cost analysis. Enrolment into RCCP halved the annual hospital admission rate from 1.18 to 0.57 admissions per year (relative risk reduction 51.4%, p < 0.001), and annual total length of stay was reduced from 8.06 to 3.59 days per patient per year (p < 0.001). Hospital admissions were reduced from 5.05 days to 2.00 days (p < 0.001). Accounting for the program’s costs, these changes resulted in a $US 906.94 ($AUD 972.80) cost saving per patient per year. A RCCP program can reduce patient hospitalisation and overall costs in the COPD setting.

Identification of risk factors and construction of a nomogram predictive model for post-stroke infection in patients with acute ischemic stroke

BACKGROUND Post-stroke infection is the most common complication of stroke and poses a huge threat to patients.In addition to prolonging the hospitalization time and increasing the medical burden,post-stroke infection also significantly increases the risk of disease and death.Clarifying the risk factors for post-stroke infection in patients with acute ischemic stroke(AIS)is of great significance.It can guide clinical practice to perform corresponding prevention and control work early,minimizing the risk of stroke-related infections and ensuring favorable disease outcomes.AIM To explore the risk factors for post-stroke infection in patients with AIS and to construct a nomogram predictive model.METHODS The clinical data of 206 patients with AIS admitted to our hospital between April 2020 and April 2023 were retrospectively collected.Baseline data and post-stroke infection status of all study subjects were assessed,and the risk factors for poststroke infection in patients with AIS were analyzed.RESULTS Totally,48 patients with AIS developed stroke,with an infection rate of 23.3%.Age,diabetes,disturbance of consciousness,high National Institutes of Health Stroke Scale(NIHSS)score at admission,invasive operation,and chronic obstructive pulmonary disease(COPD)were risk factors for post-stroke infection in patients with AIS(P<0.05).A nomogram prediction model was constructed with a C-index of 0.891,reflecting the good potential clinical efficacy of the nomogram prediction model.The calibration curve also showed good consistency between the actual observations and nomogram predictions.The area under the receiver operating characteristic curve was 0.891(95%confidence interval:0.839–0.942),showing predictive value for post-stroke infection.When the optimal cutoff value was selected,the sensitivity and specificity were 87.5%and 79.7%,respectively.CONCLUSION Age,diabetes,disturbance of consciousness,NIHSS score at admission,invasive surgery,and COPD are risk factors for post-stroke infection following AIS.The nomogram prediction model established based on these factors exhibits high discrimination and accuracy.

Development of a prediction model to identify undiagnosed chronic obstructive pulmonary disease patients in primary care settings in China

Background:At present,a large number of chronic obstructive pulmonary disease(COPD)patients are undiagnosed in China.Thus,this study aimed to develop a simple prediction model as a screening tool to identify patients at risk for COPD.Methods:The study was based on the data of 22,943 subjects aged 30 to 79 years and enrolled in the second resurvey of China Kadoorie Biobank during 2012 and 2013 in China.We stepwisely selected the predictors using logistic regression model.Then we tested the model validity through P-P graph,area under the receiver operating characteristic curve(AUROC),ten-fold cross validation and an external validation in a sample of 3492 individuals from the Enjoying Breathing Program in China.Results:The final prediction model involved 14 independent variables,including age,sex,location(urban/rural),region,educational background,smoking status,smoking amount(pack-years),years of exposure to air pollution by cooking fuel,family history of COPD,history of tuberculosis,body mass index,shortness of breath,sputum and wheeze.The model showed an area under curve(AUC)of 0.72(95%confidence interval[CI]:0.72-0.73)for detecting undiagnosed COPD patients,with the cutoff of predicted probability of COPD=0.22,presenting a sensitivity of 70.13%and a specificity of 62.25%.The AUROC value for screening undiagnosed patients with clinically significant COPD was 0.68(95%CI:0.66-0.69).Moreover,the ten-fold cross validation reported an AUC of 0.72(95%CI:0.71-0.73),and the external validation presented an AUC of 0.69(95%CI:0.68-0.71).Conclusion:This prediction model can serve as a first-stage screening tool for undiagnosed COPD patients in primary care settings.

Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease(COPD).However,the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet.Inflammation is central to the development of COPD.In this review,we elucidate the effects and underlying mechanisms of acupuncture from an antiinflammatory perspective based on animal studies.Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD.Electroacupuncture can be an effective intervention to improve inflammation in COPD,and Feishu(BL13)and Zusanli(ST36)can be used as basic acupoints in COPD animal models.Different acupuncture types can regulate different types of inflammatory cytokines;meanwhile,different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines.In particular,acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells,inflammasomes and inflammatory cytokines.The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways:nuclear factor-κB(NF-κB)(e.g.,myeloid differentiation primary response 88/NF-κB,toll-like receptor-4/NF-κB,silent information regulator transcript-1/NF-κB),mitogen-activated protein kinase signalling pathways(extracellular signal-regulated kinase 1/2,p38 and c-Jun NH2-terminal kinase),cholinergic anti-inflammatory pathway,and dopamine D2 receptor pathway.The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation.

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.

烟草烟雾与机动车尾气暴露建立的大鼠慢性阻塞性肺疾病模型比较

目的对比烟草烟雾(CS)暴露和机动车尾气(MVE)暴露两种方法构建的大鼠慢性阻塞性肺疾病(COPD)模型的模拟程度。方法将24只雄性SD大鼠按随机数字表分为对照组、CS组与MVE组,每组8只。CS组与MVE组大鼠分别采用CS或MVE暴露建立COPD模型。建模结束后,检测各组大鼠的肺功能;收集大鼠支气管肺泡灌洗液(BALF),检测其中炎性细胞数、炎性因子白细胞介素(IL)-6和肿瘤坏死因子(TNF)-α及黏蛋白5AC(MUC5AC)含量;HE染色观察肺组织和气道病理变化;PAS染色检测气道杯状细胞增生情况。结果与对照组比较,CS组和MVE组大鼠的肺功能参数吸气阻力(RI)、肺总量(TLC)、肺静态顺应性(Cchord)均明显增高(P<0.05),而呼气流速参数FEV50/FVC明显降低(P<0.05);与MVE组相比,CS组大鼠的RI、TLC、Cchord均明显增高(P<0.05),FEV50/FVC降低(P<0.05)。肺组织HE染色结果显示,CS组和MVE组大鼠平均肺泡截距(MLI)均高于对照组(P<0.05),CS组MLI高于MVE组(P<0.05)。CS组和MVE组大鼠BALF中白细胞、中性粒细胞、巨噬细胞和淋巴细胞数,以及IL-6、TNF-α含量均高于对照组(P<0.05);且CS组中炎性细胞数、IL-6及TNF-α含量均高于MVE组(P<0.05)。肺组织PAS染色结果显示,CS组和MVE组大鼠大气道杯状细胞较对照组均明显增多(P<0.05),且CS组杯状细胞数高于MVE组(P<0.05);CS组和MVE组BALF中MUC5AC含量均高于对照组(P<0.05),且CS组大鼠BALF中MUC5AC含量高于MVE组(P<0.05)。结论应用CS或MVE暴露均可建立大鼠COPD模型,但CS暴露比MVE暴露能更好地模拟COPD急性加重期特征。

滋金补水膏对慢性阻塞性肺疾病模型大鼠的治疗作用及对lncRNAPVT1、miR-30b-5p表达的影响

【目的】探讨滋金补水膏对慢性阻塞性肺疾病(COPD)模型大鼠的治疗作用及机制。【方法】将96只大鼠随机分为正常组,模型组,滋金补水膏低、中、高剂量组,盐酸氨溴索组、滋金补水膏高剂量+pcDNA组,滋金补水膏高剂量+pcDNA-人浆细胞瘤转化迁移基因1(PVT1)组,每组12只。除正常组外,其他各组大鼠采用气道滴注脂多糖(LPS)联合烟雾暴露法构建COPD模型。建模成功后,进行给药干预。给药结束后,采用酶联免疫吸附分析(ELISA)检测大鼠血清中白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平;流式细胞术检测大鼠外周血中辅助性T细胞17/调节性T细胞(Th17/Treg)水平,苏木素-伊红(HE)染色法观察肺组织病理变化,实时定量聚合酶链反应(qRT-PCR)法检测血清和肺组织中长链非编码RNA(lncRNA)PVT1、miR-30b-5p表达,Western Blot法检测肺组织中维甲酸相关孤核受体γt(RORγt)、叉头框蛋白P3(Foxp3)蛋白表达,双荧光素酶报告基因实验验证lncRNA PVT1与miR-30b-5p的关系。【结果】与正常组比较,模型组肺泡间隔变大,支气管周围有大量炎症细胞浸润,Treg细胞比例、miR-30b-5p表达水平、Foxp3蛋白表达水平降低,IL-6、TNF-α水平,Th17细胞比例、Th17/Treg比值,lncRNA PVT1表达水平,RORγt蛋白表达水平升高(均P<0.05);与模型组比较,滋金补水膏低、中、高剂量组及盐酸氨溴索组大鼠肺组织病理损伤减轻、Treg细胞比例、miR-30b-5p表达水平、Foxp3蛋白表达水平升高,IL-6、TNF-α水平,Th17细胞比例,Th17/Treg比值,lncRNA PVT1表达水平,RORγt蛋白表达水平降低(均P<0.05)。lncRNA PVT1靶向调控miR-30b-5p表达。【结论】滋金补水膏可能通过调节lncRNA PVT1/miR-30b-5p轴促进Th17/Treg细胞平衡来抑制COPD大鼠炎症反应。

COPD患者吸入制剂用药不依从风险预测模型构建

目的 构建慢性阻塞性肺疾病患者吸入制剂用药不依从风险预测模型。方法 回顾性分析秦皇岛市第一医院咳喘药学服务门诊2021年10月-2023年10月收治的365例慢性阻塞性肺疾病患者信息,将2021年10月-2023年6月收治的患者作为模型组(n=303),2023年7-10月收治的患者作为验证组(n=62),模型组分为依从亚组(n=126)和不依从亚组(n=177),通过单因素分析结合多因素Logistic回归分析患者使用吸入制剂不依从的危险因素。根据回归分析结果建立风险预测模型,并以验证组患者为对象,评价所建模型预测的准确性。结果 多因素Logistic回归分析显示,同时使用2个吸入制剂(OR=3.730,95%CI为1.996~6.971,P<0.001)、一年内急性加重次数≥2次(OR=2.509,95%CI为1.509~4.173,P<0.001)、吸烟(OR=2.167,95%CI为1.309~3.588,P=0.003)、合并焦虑/抑郁(OR=2.112,95%CI为1.257~3.499,P=0.004)、改良版英国医学研究委员会呼吸困难问卷评级≥2级(OR=1.701,95%CI为1.014~2.853,P=0.044)是患者使用吸入制剂不依从的危险因素。基于此建立风险预测模型,绘制受试者工作特征曲线,可得模型组、验证组的曲线下面积分别为0.836、0.928,模型预测的总体准确率为88.71%。结论 基于同时使用2个吸入制剂、一年内急性加重次数≥2次、吸烟、合并焦虑/抑郁、mMRC评级≥2级建立的风险预测模型对COPD患者使用吸入制剂不依从风险具有一定的预测价值。

PERMA模式在老年慢阻肺患者肺功能与生活质量改善中的应用研究

目的本研究通过分析PERMA模式下激励干预对老年COPD患者心理健康和生活质量的影响,以期为临床积极心理学的干预应用提供更多试验依据。方法回顾性分析2020年12月—2022年12月在首都医科大学附属北京朝阳医院接受治疗的90例老年COPD患者的临床资料,依据不同的干预方式将患者分为观察组(45例)和对照组(45例)。对照组患者行常规干预,观察组在与对照组相同干预基础上加用PERMA模式下激励干预,2组患者均持续干预2周。干预前后对2组应用简明心境问卷(POMS-SF)评估心理健康,采用健康状况问卷量表(SF-36)评估生活质量,记录2组肺功能指标值,并对上述检测值进行比较和统计学分析。结果干预前,观察组和对照组患者POMS-SF各分量表评分差异均无统计学意义(P>0.05)。干预后,观察组和对照组患者精力-活力评分均较同组干预前升高,迷惑-混乱、紧张—焦虑、疲乏—迟钝、抑郁—沮丧和愤怒—敌意评分均较同组干预前降低,且观察组精力—活力评分高于对照组,迷惑—混乱、紧张—焦虑、疲乏—迟钝、抑郁—沮丧和愤怒—敌意评分均低于对照组,差异均有统计学意义(P<0.05)。干预前,观察组和对照组患者SF-36量表评分差异均无统计学意义(P>0.05)。干预后,观察组和对照组患者总体健康、生理功能、活力、生理职能、情感职能、社会功能、精神健康和躯体疼痛评分均较同组干预前升高(P<0.05),且观察组SF-36量表各项评分均高于对照组(P<0.05)。干预前,观察组和对照组患者FVC、FEV1、FEV1/FVC值差异均无统计学意义(P>0.05);干预后,观察组和对照组患者FVC、FEV1/FVC值均较同组干预前升高,且观察组FVC、FEV1/FVC值高于对照组(均P<0.05)。结论PERMA模式下激励干预可能改善老年慢阻肺患者心理健康与生活质量,提高患者的肺功能水平,改善患者的预后。