Atomization inhalation of terbutaline and budesonide efficiently improved immunity and lung function of AECOPD patients

Chronic obstructive pulmonary disease （COPD） is a syndrome of chronic progressive airflow limitation as a result of chronic inflammation of the airways and lung parenchyma. COPD patients always have airway hyperreactivity （AHR）, so how to reduce AHR becomes the key purpose of clinical treatment. It is hypothesized that combined inhalation of corticosteroids and β2-agonists can reduce the AHR in COPD. In this study, atomization inhalation of budesonide and terbutaline plus conventional therapies was applied to treat AECOPD （acute exacerbation of chronic obstructive pulmonary disease） patients for two weeks. The results showed that additional inhalation of budesonide and terbutaline could upregulate serum IL-2 levels, the percentages of CD3^＋ T and CD4^＋ T cells, and CD4/CD8 ratio, and decrease eosinophils and serum CRP level more efficiently than conventional treatment in patients with AECOPD. And the lung function of the atomization inhalation group was improved more obviously after the treatment compared with the conventional treatment group. Thus, atomization inhalation of terbutaline and budesonide can control AECOPD effectively, and has wide clinical perspective in controlling and preventing the exacerbation of COPD. Cellular ＆ Molecular Immunology. 2008;5（4）：287-291.     

Regulation of antitumor immunity by inflammation-induced epigenetic alterations

Chronic inflammation promotes tumor development,progression,and metastatic dissemination and causes treatment resistance.The accumulation of genetic alterations and loss of normal cellular regulatory processes are not only associated with cancer growth and progression but also result in the expression of tumor-specific and tumor-associated antigens that may activate antitumor immunity.This antagonism between inflammation and immunity and the ability of cancer cells to avoid immune detection affect the course of cancer development and treatment outcomes.While inflammation,particularly acute inflammation,supports T-cell priming,activation,and infiltration into infected tissues,chronic inflammation is mostly immunosuppressive.However,the main mechanisms that dictate the outcome of the inflammation-immunity interplay are not well understood.Recent data suggest that inflammation triggers epigenetic alterations in cancer cells and components of the tumor microenvironment.These alterations can affect and modulate numerous aspects of cancer development,including tumor growth,the metabolic state,metastatic spread,immune escape,and immunosuppressive or immunosupportive leukocyte generation.In this review,we discuss the role of inflammation in initiating epigenetic alterations in immune cells,cancer-associated fibroblasts,and cancer cells and suggest how and when epigenetic interventions can be combined with immunotherapies to improve therapeutic outcomes.     

Cellular exposure to muscle relaxants and propofol could lead to genomic instabilityin vitro

Anesthesia is widely used in several medical settings and accepted as safe.However,there is some evidence that anesthetic agents can induce genomic changes leading to neural degeneration or apoptosis.Although chromosomal changes have not been observed in vivo,this is most likely due to DNA repair mechanisms,apoptosis,or cellular senescence.Potential chromosomal alterations after exposure to common anesthetic agents may be relevant in patients with genomic instability syndromes or with aggressive treatment of malignancies.In this study,the P388 murine B cells were cultured in vitro,and spectral karyotyping (SKY) was utilized to uncover genomewide changes.Clinically relevant doses of cisatracurium and propofol increased structural and numerical chromosomal instability.These results may be relevant in patients with underlying chromosomal instability syndromes or concurrently being exposed to chemotherapeutic agents.Future studies may include utilization of stimulated peripheral blood lymphocytes to further confirm the significance of these results.     

Development ofLeishmania vaccines:predicting the future from past and present experience

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. Resistance to infection is associated with a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemotherapeutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many labo-ratories. Major impediments in Leishmania vaccine development include: lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis.     

The Potential Mechanisms Underlying Aspirin-induced Inhibition of Ovarian Tumor Cell Growth

1 Introduction Ovarian cancer remains the most lethal disease of the gynecological cancers. Owing to the lack of an effective screening approach combined with inadequate therapeutic approach for advanced disease, fewer than 25% of ovarian cancers are identified at an early curable stage. Thus these make ovarian cancer a strong candidate for chemoprevention. In 2001, Akhmedkhanov et al. demonstrated a 2-3 folds decrease in epithelial ovarian cancer associated with Aspirin use. These epidemiological observations suggest that an improved understanding of the mechanisms by which NSAID may decrease the development of ovarian cancer could lead to improved approaches for chemoprevention of this deadly disease. In this research, we explored the potential mechanism underlying epidemiological observations that ovarian cancer occurs at a lower frequency in women exposed to Aspirin(ASP).     

细胞胀亡的研究进展

Oncosis is a special kind of non-apoptotic cell death mode. It is characterized by cellular swelling, organelle swelling, blebbingand increased membrane permeability. More and more attentions pay to the research of this field in recent years. The review discuss the recent advances of oncosis on pathological change, molecular mechanisms and detection approaches．     

The role of chemokines in acute and chronic hepatitis C infection

Hepatitis C imposes a significant burden on global healthcare. Chronic infection is associated with progressive inflammation of the liver which typically manifests in cirrhosis, organ failure and cancer. By virtue of elaborate evasion strategies, hepatitis C virus （HCV） succeeds as a persistent human virus. It has an extraordinary capacity to subvert the immune response enabling it to establish chronic infections and associated liver disease. Chemokines are low molecular weight chemotactic peptides that mediate the recruitment of inflammatory cells into tissues and back into the lymphatics and peripheral blood. Thus, they are central to the temporal and spatial distribution of effector and regulatory immune cells. The interactions between chemokines and their cognate receptors help shape the immune response and therefore, have a major influence on the outcome of infection. However, chemokines represent a target for modulation by viruses including the HCV. HCV is known to modulate chemokine expression in vitro and may therefore enable its survival by subverting the immune response in vivo through altered leukocyte chemotaxis resulting in impaired viral clearance and the establishment of chronic low-grade inflammation. In this review, the roles of chemokines in acute and chronic HCV infection are described with a particular emphasis placed on chemokine modulation as a means of immune subversion. We provide an in depth discussion of the part played by chemokines in mediating hepatic fibrosis while addressing the potential applications for these chemoattractants in prognostic medicine.     

Impaired CTLA-4 responses in COPD are associated with systemic inflammation

Systemic inflammation is a feature of chronic obstructive pulmo- nary disease （COPD）. Defects in T cell-mediated anti-inflamma- tory pathways such as cytotoxic T lymphocyte antigen-4 （CTLA- 4） may promote damaging inflammation. This study provides novel data implicating the impaired induction of an anti-inflam- matory molecule, CTLA-4 in the elevated inflammation observed in COPD patients. Low induction of CTLA-4 in COPD patients paralleled increased markers of systemic inflammation ex vivo and increased T-cell responses to a bacterial superantigen, staphylo- coccal enterotoxin-B （SEB） in vitro. This mechanism may explain the increased inflammation in COPD patients.     

Nippostrongylus brasiliensis infection leads to the development of emphysema associated with the induction of alternatively activated macrophages

Chronic obstructive pulmonary disease (COPD) is the 5(th) most prevalent disease worldwide leading to severe morbidity and mortality in developed countries. The disease is strongly associated with smoking, and can be characterized by progressive and irreversible deterioration in lung function and destruction of the lung parenchyma. We show here that infection with the hookworm Nippostrongylus brasiliensis results in deterioration in lung function, destruction of alveoli and long-term airways hyperresponsiveness, consistent with COPD and emphysema. N. brasiliensis infection leads to chronic low level hemorrhaging in the lung and the presence of hemosiderin-laden macrophages in the absence of an overt inflammatory infiltrate. Microarray analysis of gene expression in diseased lungs and quantitative RT-PCR analysis of purified macrophages revealed a state of prolonged tissue injury and the presence of alternatively activated macrophages producing MMP-12. Taken together, these data show that lung tissue damage caused by hookworm infection can result in the development of COPD and emphysema.     

Outpatient treatment of chronic obstructive pulmonary disease: comparisons with asthma

Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of expiratory airflow limitation caused by chronic inflammation of the airways and lung parenchyma. The airway inflammatory response in COPD is initiated by smoking in the overwhelming majority of cases, and chronic exposure to cigarette smoke initiates a series of events that cause damage to central airways, peripheral airways, and terminal airspaces, leading to physiologic and clinical abnormalities. The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy. The outpatient treatment of COPD differs from the approach used in asthma and can be divided into 3 subgroups: health care maintenance, drug therapy, and nondrug therapy. Smoking cessation, regular spirometry, and immunization are important components of health care maintenance. Drug therapy consists of optimal bronchodilator therapy supplemented, when necessary, with either inhaled corticosteroids or theophylline. Nondrug therapies include pulmonary rehabilitation, supplemental oxygen, and surgery.     

树突状细胞在慢性阻塞性肺疾病中的作用

树突状细胞(dendritic cells,DCs)作为机体内最重要的一种抗原提呈细胞,在慢性阻塞性疾病(chronic obstructive pulmonary disease,COPD)炎症的发生发展过程中具有重要作用.长期烟雾刺激,会导致肺部DCs亚群失衡,DCs向肺部炎症部位募集,通过与CD4+T细胞的相互作用,导致Th17/调节性T细胞免疫失衡,介导COPD细胞免疫过程.此外,COPD肺组织中肺泡弹性蛋白降解形成的具有抗原活性的弹性蛋白肽与肺部DCs的免疫作用,在COPD疾病的持续进展过程中具有十分重要的作用.     

早期慢性阻塞性肺疾病诊断与防治研究

慢性阻塞性肺疾病（COPD）是以持续气流受阻进行性发展为特征的一种可预防和治疗的疾病。COPD发病率、致残率较高,严重威胁人类健康安全。目前,早发现、早诊断、早治疗是我国COPD防治的重要手段。我国早期COPD病例数量大,不同患者症状存在明显差异性。研究早期COPD诊治情况,有望探索对患者进行个体化治疗的方法,进一步促进临床治疗策略的制定,提高慢性阻塞性肺疾的临床诊治研究水平。本文现就COPD早期的诊治研究进行综述,以期为临床诊治慢性阻塞性肺疾提供理论参考依据。     

Airway inflammation in chronic obstructive pulmonary disease: comparisons with asthma

Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of expiratory airflow limitation caused by chronic inflammation of the airways and lung parenchyma. The airway inflammatory response in COPD is initiated by smoking in the overwhelming majority of cases, and chronic exposure to cigarette smoke initiates a series of events that causes damage to central airways, peripheral airways, and terminal airspaces, leading to physiologic and clinical abnormalities. Although COPD shares some clinical features with asthma, another prevalent airway inflammatory disease, there are distinct differences in the phenotypic characteristics of airway inflammation between COPD and asthma. The eosinophil is the most prominent inflammatory cell in asthma, with mast cells, lymphocytes, and macrophages playing important but less prominent roles. In COPD the cellular composition of the airway inflammatory infiltrate differs, with neutrophils, macrophages, and lymphocytes assuming prominence and the eosinophil playing a minor role, except in the setting of exacerbations. The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy.     

Respiratory mechanics measured by forced oscillation technique in combined pulmonary fibrosis and emphysema

The coexistence of emphysema and pulmonary fibrosis is known as combined pulmonary fibrosis and emphysema (CPFE). The aim of this study was to compare the lung mechanics measured by multi-frequency forced oscillation technique (FOT) among patients with CPFE, interstitial pneumonia (IP), and chronic obstructive pulmonary disease (COPD). FOT and pulmonary function tests were performed in 41 patients with CPFE, 47 with IP, and 86 with COPD. Whole-breath resistance at 20 Hz was significantly lower in patients with CPFE than in those with IP or COPD, irrespective of the severity of airflow limitation. Within-breath analyses of resistance revealed no difference among the 3 groups; however, the difference between inspiratory and expiratory phases of reactance at 5 Hz, which reflects expiratory flow limitation, in patients with CPFE was significantly higher than in those with IP and lower than in those with COPD. In conclusion, both emphysema and fibrosis affect lung mechanics in CPFE, leading to different findings from IP or COPD alone.     

Pathogenesis of chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) could develop following long-term exposure of individuals to cigarette smoke, toxic gases, and particulate matter, resulting in airway flow limitation, pulmonary failure, multiple systemic effects, and, eventually, death. The disease is associated with pulmonary inflammation with its own specific characteristics, and could be exacerbated by multiple factors such as microbial infection. COPD is chronic and progressive in nature, and multiple pulmonary inflammatory cells are detected at different stages of the disease, with a possible network of interactions with parenchymal cells. The pathological changes in the lung of COPD patients are characterized by an excess of extracellular matrix deposition, yet, loss of extracellular matrix in alveoli, increased thickness of airway walls, mucus hypersecretions, and destruction of alveolar septae, resulting in narrowing of airway diameters, reduced functional lung parenchyma, and decreased elastic tethering forces to maintain airway patency. Multiple factors, such as inflammatory cytokines, proteolytic proteinases, and oxidative stress molecules are suspected to be responsible, each at some degree, for these structural changes leading to airway obstruction. Because not everyone exposed to cigarette smoke will develop the disease, it is reasonable to think that multiple risk factors are involved and that COPD could be developed along a variety of pathways. Our current understanding of pulmonary changes associated with COPD, its similarity and differences with asthma, the nature of inflammatory cells associated with the disease, and the capacity of different molecules to induce a variety of these structural alterations are discussed to advance a cellular and molecular look at the pathogenesis of COPD.     

食管癌患者放射性肺损伤预测因素分析及其与 COPD的相关性研究

目的 分析食管癌患者放射性肺损伤（RILI）预测因素,以及其与慢性阻塞性肺疾病（COPD）的相关性。方法 选取2014年1月~2017年12月我院收治的食管癌患者265例为研究对象,均行立体定向放射治疗（SBRT）治疗,治疗前均行肺功能检查,治疗后均行HRCT检查随访RILI的发生情况,回顾性分析RILI的预测因素及其与COPD是否存在相关性。结果 0、1、2、3、4、5级RP发生率分别为38.49%、38.11%、17.74%、5.28%、0.38%、0,其中12例患有间质性肺疾病的患者,9例（75.00%）发生例3级以上的RILI;发生RILI≥1级的相关因素有年龄、总剂量、V20、GOLD分级;重度及极重度COPD组患者的0级RILI的发生率为54.17%,高于轻中度COPD组（42.31%）及无COPD组（30.22%）。结论 年龄、总剂量、V20、GOLD分级与1级以上（有影像学变化）的RILI有相关性,重度COPD的RILI较正常或轻度COPD患者相对较轻,患有间质性肺疾病的患者多发生3级以上的RILI。     

Pathobiology of cigarette smoke-induced chronic obstructive pulmonary disease

Chronic obstructive pulmonary diseases (COPD), comprised of pulmonary emphysema, chronic bronchitis, and structural and inflammatory changes of small airways, is a leading cause of morbidity and mortality in the world. A better understanding of the pathobiology of COPD is critical for the developing of novel therapies, as the majority of patients with the disease have little therapeutic options at the present time. The pathobiology of COPD encompasses multiple injurious processes including inflammation (excessive or inappropriate innate and adaptive immunity), cellular apoptosis, altered cellular and molecular alveolar maintenance program, abnormal cell repair, extracellular matrix destruction (protease and anti-protease imbalance), and oxidative stress (oxidant and antioxidant imbalance). These processes are triggered by urban and rural air pollutants and active and/or passive cigarette smoke and modified by cellular senescence and infection. A series of receptor-mediated signal transduction pathways are activated by reactive oxygen species and tobacco components, resulting in impairment of a variety of cell signaling and cytokine networks, subsequently leading to chronic airway responses with mucus production, airway remodeling, and alveolar destruction. The authors provide an updated insight into the molecular and cellular pathobiology of COPD based on human and/or animal data.     

老年慢性阻塞性肺疾病患者血浆N-端脑钠肽前体与肺动脉高压的关系

目的:探讨老年慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者中血浆N-端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)与肺动脉高压的关系.方法:将99例老年COPD患者,根据心脏彩超分为单纯...