Lung fibrosis is associated with inflammation, apoptosis and oxidative damage. The transcription factor nuclear factor erythroid 2-related factor-2 (Nrf2) prevents damage to cells from oxidative stress by regulating the expression of antioxidant proteins. Sulforaphane (SFN), an Nrf2 activator, additionally regulates excessive oxidative stress by promoting the expression of endogenous antioxidants. The present study investigated if SFN protects against lung injury induced by bleomycin (BLM). The secondary aim of the present study was to assess if this protection mechanism involves upregulation of Nrf2 and its downstream antioxidants. Pulmonary fibrosis was induced in C57/BL6 mice by intratracheal instillation of BLM. BLM and age-matched control mice were treated with or without a daily dose of 0.5 mg/kg SFN until sacrifice. On days 7 and 28, mice were assessed for induction of apoptosis, inflammation, fibrosis, oxidative damage and Nrf2 expression in the lungs. The lungs were investigated with histological techniques including haematoxylin and eosin staining, Masson's trichrome staining and terminal deoxynucleotidyl transferase UTP nick end labeling. Inflammatory, fibrotic and apoptotic processes were confirmed by western blot analysis for interleukin-1 beta, tumor necrosis factor-alpha, transforming growth factor-beta and caspase-3 protein expressions. Furthermore, protein levels of 3-nitro-tyrosine, 4-hydroxynonenal, superoxide dismutase 1 and catalase were investigated by western blot analysis. It was demonstrated that pulmonary fibrosis induced by BLM significantly increased apoptosis, inflammation, fibrosis and oxidative stress in the lungs at days 7 and 28. Notably, SFN treatment significantly attenuated the infiltration of the inflammatory cells, collagen accumulation, epithelial cell apoptosis and oxidative stress in the lungs. In addition, SFN treatment increased expression of the Nrf2 gene and its downstream targets. In conclusion, these results suggested that SFN treatment of pulmonary fibrosis mouse models may attenuate alveolitis, fibrosis, apoptosis and lung oxidative stress by increasing the expression of antioxidant enzymes, including NAPDH quinone oxidoreductase, heme oxygenase-1, superoxide dismutase and catalase, via upregulation of Nrf2 gene expression. Thus, the results from the present study may facilitate the development of therapies for BLM-toxicity and pulmonary fibrosis.

慢性阻塞性肺疾病（COPD）是以不完全可逆气流受限为特征的慢性气道疾病。NIPPV对急性期COPD患者的疗效得到肯定［1］，为探讨NIPPV对我国COPD稳定期患者的疗效，本研究采用 Meta 分析方法，系统评价我国COPD稳定期患者应用NIP-PV的RCT，为临床提供依据。

Epithelial-mesenchymal transition (EMT) has been reported to play an important role in the migration and invasion of tumor cells. Hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) has emerged as an important regulator of the development of cancer. However, the role of HPIP in lung cancer is unclear. Thus, in the present study, we investigated the role of HPIP in transforming growth factor (TGF)-β1-induced EMT in A549 lung cancer cells in vitro. Our data demonstrated that HPIP was overexpressed in the lung cancer cell lines. TGF-β1 increased the expression of HPIP in the A549 cells. In addition, HPIP silencing significantly attenuated TGF-β1-induced EMT and migration/invasion in the A549 cells. Furthermore, knockdown of HPIP greatly inhibited TGF-β1-induced phosphorylation of Smad2 in the A549 cells. In conclusion, we demonstrated that HPIP silencing suppressed TGF-β1-induced EMT in lung cancer cells by inhibiting Smad2 activation. Therefore, HPIP may be a new therapeutic target for the treatment of lung cancer.

Objective To observe the clinical curative effect and safety of human immunoglobulin for intravenous injection in treating childhood severe mycoplasm pneumonia.Methods One hundred and thirty three children with severe mycoplasm pneumonia in clinic and wards of this hospital from October 2010 to November 2011 were randomly divided into treatment group(n=56) and control group(n=57).All the patients were administered with erythromycin,azithromycin and symptomatic treatment for two weeks.The treatment group also received human immunoglobulin for intravenous injection 400 mg/(kg·d) for 3 days compared to the control group.Results The symptom-free period of fever,cough,wheeze and wet rales in the treatment group were(2.1±1.3)d,(4.2±1.2)d,(2.5±1.2)d and(3.6±1.1)d,respectively;and in the control group(3.3±1.0)d,(5.6±2.3)d,(4.3±2.5)d and(5.4±1.8)d,respectively.The difference between the two group was statistically significant(P<0.01).Conclusion Human immunoglobulin for intravenous injection has a greater efficacy and fewer side effects on children with mycoplasm pneumonia.

Objective:To introduce the clinical characteristics,diagnosis and treatment experience of one case of acute respiratory tract obstruction and review the relevants literature to heighten the understanding of tracheal mucosa associated lymphoid tissue lymphoma,and to provide a feasible way to reduce the acute dyspnea.Methods:Bronchoscopic examination,local tissue biopsies,and the treatment of argon plasma coagulation and cryosurgery were performed in the patient with acute dyspnea.After the treatment the patients was treated with local radiotherapy.Results:The dyspnea of patient was significantly impoved.The pathological results showed tracheal mucosa associated lymphoid tissue lymphoma which was also called non-Hodgkin's lymphoma.The tracheal has no stenosis under bronchoscope.Conclusion:The primary tracheal mucosa associated lymphoid tissue lymphoma is very rare.The local tissue biopsies under fiberoptic bronchoscope is the main diagnostic method.Bronchoscopic argon plasma coagulation and cryosurgery which is convenient and small traumatic can ease the patients with acute dyspnea,its combination with radiotherapy,chemotherapy or immunochemical therapy is suitable treatment for the tracheal mucosa associated lymphoid tissue lymphoma and other tracheal neoplasms.

Haze weather is becoming one of the biggest problems in many big cities in China. It triggers both public anxiety and official concerns. Particulate matter (PM) plays the most important role in causing the adverse health effects. Chemical composition of PM2.5 includes primary particles and secondary particles. The toxicological mechanisms of PM2.5 to the human body include the oxidative stress, inflammation and carcinogenesis. Short or long-term exposure to PM (especially PM2.5) can cause a series of symptoms including respiratory symptoms such as cough, wheezing and dyspnea as well as other symptoms. There are positive associations between PM2.5 and mortality due to a number of causes. PM2.5 is considered to contribute to the onset of asthma, the exacerbation of chronic obstructive pulmonary disease (COPD) in haze weather. Some approaches including outdoor health care, indoor health care and preventive medications can prevent the patients with chronic airway diseases from exacerbations.

No systemic evaluation of asthma control in Jilin Province has been reported. Asthma control might provide the basis for asthma management in this region. A multicenter hospital-based cross-sectional study was performed to investigate the asthma control and related factors for severe asthma exacerbations in patients with moderate or severe asthma in Jilin Province, China.

Objective:Examined the impairment of regulatory T cells in cord blood from offspring of allergic asthmatic mothers. Methods:Cord blood mononuclear cells from 62 healthy neonates(40 healthy mothers and 22 allergic asthmatic mothers) were isolated,and cultured with stimuli: lipid A(TLR4 ligands),peptidoglycan(Ppg-TLR2 ligands),mitogen(PHA,phytohemagglutinin) and Dermatophagoides pteronyssinus1.And then the amount of CD4+CD25+Foxp3+T cells was acounted with flow cytometry;cytokine concentrations were measured in supernatants by LUMINEX technology;the suppressive function of regulatory T cells were examinated by isolating and culturing of CD4+CD25+T cells and CD4+CD25-T cells in vitro. Results:Cord blood from offspring of allergic asthmatic mothers showed Ppg-induced fewer regulatory T cells(CD4+CD25+Foxp3+T,P=0.03) and lower IL-10 secretion(P=0.03).Furthermore,the suppressive capacity of regulatory T cells was impaired in PHA-induced division and proliferation of T effector cells in cord blood of offspring from allergic asthmatic mothers(P=0.05).Meanwhile,the suppressive capacity of regulatory T cells to IL-13 production by effector cells was partially impared(P=0.07). Conclusion:In offspring of allergic asthmatic mothers,regulatory T cells amount,and suppressive function were impaired at birth,which maybe potentially contribute to the the susceptibility to allergic diseases.

Cisplatin [cis-diamminedichloroplatinum II (CDDP)] is one of the most classical and effective chemotherapeutic drugs for the treatment of cancers including lung cancer. However, the presence of cisplatin resistance in cancer lowers its curative effect and limits its usage in the clinic. The aim of the present study was to investigate the underlying mechanisms of cisplatin resistance in lung cancer involving endoplasmic reticulum (ER) stress and autophagy. In the present study, we detected the effect of cisplatin on cell viability, ER stress and autophagy in lung cancer cell lines A549 and H460. We also tested the effects of ER stress and autophagy on apoptosis induced by cisplatin. The results showed that cisplatin induced apoptosis, ER stress and autophagy in lung cancer cell lines. In addition, the inhibition of ER stress by 4-phenylbutyric acid (4-PBA) or tauroursodeoxycholic acid sodium (TUDC) enhanced cisplatin-induced apoptosis in the human lung cancer cells. Meanwhile, combination treatment with the autophagic inhibitor 3-methyladenine (3-MA) or chloroquine (CQ) further increased the apoptosis induced by cisplatin in the human lung cancer cells. The present study provides a novel treatment strategy - cisplatin in combination with an autophagic inhibitor or an ER stress inhibitor leads to increased apoptosis in human lung cancer cells.

1病例摘要患者,女,46岁,因"胸痛、咳嗽、咳痰3个月"入院。该患者缘于3个月前无明显诱因出现右侧胸痛,伴有发热、咳嗽、咳痰,体温最高达39℃,无寒战,咳大量白色黏痰。2个月前于当地医院诊断为"肺炎、支气管哮喘",给予"青霉素"抗感染治疗,无明显疗效。1个半月前,咳出物中发现直径约5mm的石头样物体,后于当地医院行抗感染（诺氟沙星,具体用量不详）治疗,疗效不佳。5天前出现双侧胸痛。现患者为

Lung endothelial damage contributes to the pathogenesis of acute lung injury. New strategies against lung endothelial barrier dysfunction may provide therapeutic benefits against lung vascular injury. Cell-cell junctions and microtubule cytoskeleton are basic components in maintaining endothelial barrier integrity. HDAC6, a deacetylase primarily localized in the cytoplasm, has been reported to modulate nonnuclear protein function through deacetylation. Both α-tubulin and β-catenin are substrates for HDAC6. Here, we examined the effects of tubastatin A, a highly selective HDAC6 inhibitor, on TNF-α induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. Selective HDAC6 inhibition by tubastatin A blocked TNF-α-induced lung endothelial cell hyperpermeability, which was associated with increased α-tubulin acetylation and microtubule stability. Tubastatin A pretreatment inhibited TNF-α-induced endothelial cell contraction and actin stress fiber formation with reduced myosin light chain phosphorylation. Selective HDAC6 inhibition by tubastatin A also induced β-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of β-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-α-induced barrier dysfunction and increased α-tubulin and β-catenin acetylation in endothelial cells. Furthermore, in a mouse model of endotoxemia, tubastatin A was able to prevent endotoxin-induced deacetylation of α-tubulin and β-catenin in lung tissues, which was associated with reduced pulmonary edema. Collectively, our data indicate that selective HDAC6 inhibition by tubastatin A is a potent approach against lung endothelial barrier dysfunction.

UNLABELLED:Objection: The aim of this study is to investigate the association between promoter methylation of RASSF1A and p16 and the clinicopathological features in lung cancers. MATERIALS AND METHODS:PubMed, EBSCO, Ovid, Wiley, Web of Science, Wanfang, and VIP databases were searched using combinations of keywords related to RASSF1A, p16, methylation, and lung cancers. After screening for relevant studies, following a strict inclusion and exclusion criteria; the selected studies were incorporated into the present meta.analysis conducted using Comprehensive Meta Analysis 2.0. (CMA 2.0). RESULTS:We initially retrieved 402 studies, out which 13 studies met the inclusion and exclusion criteria for this meta.analysis, and contained a total of 1,259. patients with lung cancers. The results of this meta.analysis showed that the differences in promoter methylation ratio between the lung cancer patients in tumor, node, metastasis. (TNM) I.II and III.IV were not statistically significant. Based on histological types, patients with adenocarcinoma. (AC) and squamous cell carcinoma. (SCC) showed no significant differences in the promoter methylation ratios of RASSF1A, while the promoter methylation ratio of p16 was significantly higher in SCC patients compared to AC patients. Based on smoking status, the promoter methylation ratios of both RASSF1A and p16 was significantly higher in lung cancer patients with smoking history compared to nonsmokers. CONCLUSION:The present meta.analysis provides convincing evidence that the promoter methylation ratio of RASSF1A and p16 is associated with clinicopathological features in lung cancers, and could be used as effective biomarkers in early diagnosis in lung cancers.

Pro-inflammatory mediators such as TNF-α induce caspase activation in endothelial cells, which leads to degradation of cellular proteins, induction of apoptotic signaling, and endothelial cell dysfunction. New therapeutic agents that can inhibit caspase activation may provide protection against inflammatory injury to endothelial cells. In the present study, we examined the effects of selective histone deacetylase 6 (HDAC6) inhibition on TNF-α induced caspase 3 activation and cell-cell junction dysfunction in lung endothelial cells. We also assessed the protective effects of HDAC6 inhibition against lung inflammatory injury in a mouse model of endotoxemia. We demonstrated that selective HDAC6 inhibition or knockdown of HDAC6 expression was able to prevent caspase 3 activation in lung endothelial cells and maintain lung endothelial cell-cell junctions. Mice pre-treated with HDAC6 inhibitors exhibited decreased endotoxin-induced caspase 3 activation and reduced lung vascular injury as indicated by the retention of cell-cell junction protein VE-Cadherin level and alleviated lung edema. Collectively, our data suggest that HDAC6 inhibition is a potent therapeutic strategy against inflammatory injury to endothelial cells.

Jinyan Yu,* Zhongsen Ma,* Sreerama Shetty, Mengshi Ma, and Jian Fu The Second Hospital of Jilin University, Jilin, China; Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, Kentucky; Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, Kentucky; and Center for Biomedical Research, University of Texas Health Science Center, Tyler, Texas