Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema.

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 ß-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 ß-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of ß-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-α-induced barrier dysfunction and increased α-tubulin and ß-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 ß-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.

Asthma control and severe exacerbations in patients with moderate or severe asthma in Jilin Province, China: a multicenter cross-sectional survey.

BACKGROUND: 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. METHODS: The study enrolled 1546 patients in five grade one general hospitals from January to December 2013. Asthma medication, patient self-management, asthma control test (ACT) scores and frequency of severe asthma exacerbations during the follow-up (12 months) were collected via a follow-up questionnaire. RESULTS: In the study, 889 patients provided a complete follow-up questionnaire. Severe asthma exacerbations occurred in 54.89 % of patients. ACT score ≤15, asthma medication ≤ 3 months, severe asthma, income level lower than average Per Capita Disposable Income (PCDI) and a lower educational level were risk factors of a severe exacerbation. CONCLUSIONS: Poor adherence to asthma medication, poor asthma symptom control, lower income, a low educational level might be possible reasons for the high incidence of severe asthma exacerbations and poor asthma control in Jilin Province of China.

Sirt1 restrains lung inflammasome activation in a murine model of sepsis.

Excessive inflammation is a major cause of organ damage during sepsis. The elderly are highly susceptible to sepsis-induced organ injury. Sirt1 expression is reduced during aging. In the present study, we investigated the role of Sirt1, a histone deacetylase, in controlling inflammatory responses in a murine sepsis model induced by cecal ligation and puncture (CLP). We examined lung inflammatory signaling in inducible Sirt1 knockout (Sirt1(-/-)) mice and wild-type littermates (Sirt1(+/+)) after CLP. Our results demonstrated that Sirt1 deficiency led to severe lung inflammatory injury. To further investigate molecular mechanisms of Sirt1 regulation of lung inflammatory responses in sepsis, we conducted a series of experiments to assess lung inflammasome activation after CLP. We detected increased lung inflammatory signaling including NF-κB, signal transducer and activator of transcription 3, and ERK1/2 activation in Sirt1(-/-) mice after CLP. Furthermore, inflammasome activity was increased in Sirt1(-/-) mice after CLP, as demonstrated by increased IL-1ß and caspase-7 cleavage and activation. Aggravated inflammasome activation in Sirt1(-/-) mice was associated with the increased production of lung proinflammatory mediators, including ICAM-1 and high-mobility group box 1, and further disruption of tight junctions and adherens junctions, as demonstrated by dramatic reduction of lung claudin-1 and vascular endothelial-cadherin expression, which was associated with the upregulation of matrix metallopeptidase 9 expression. In summary, our results suggest that Sirt1 suppresses acute lung inflammation during sepsis by controlling inflammasome activation pathway.

Deletion of Src family kinase Lyn aggravates endotoxin-induced lung inflammation.

Overwhelming acute inflammation often leads to tissue damage during endotoxemia. In the present study, we investigated the role of Lyn, a member of the Src family tyrosine kinases, in modulating inflammatory responses in a murine model of endotoxemia. We examined lung inflammatory signaling in Lyn knockout (Lyn(-/-)) mice and wild-type littermates (Lyn(+/+)) during endotoxemia. Our data indicate that Lyn deletion aggravates endotoxin-induced pulmonary inflammation and proinflammatory signaling. We found increased activation of proinflammatory transcription factor NF-κB in the lung tissues of Lyn(-/-) mice after endotoxin challenge. Furthermore, during endotoxemia, the lung tissues of Lyn(-/-) mice showed increased inflammasome activation indicated by augmented caspase-1 and IL-1ß cleavage and activation. The aggravated lung inflammatory signaling in Lyn(-/-) mice was associated with increased production of proinflammatory mediators and elevated matrix metallopeptidase 9 and reduced VE-cadherin levels. Our results suggest that Lyn kinase modulates inhibitory signaling to suppress endotoxin-induced lung inflammation.

[Adult hospital acquired pneumonia: a multicenter study on microbiology and clinical characteristics of patients from 9 Chinese cities].

OBJECTIVE: To investigate the etiology and clinical characteristics of hospital-acquired pneumonia (HAP) in China and to provide evidence for appropriate therapy. METHODS: We performed a prospective multicenter study in 13 Chinese urban tertiary hospitals. All HAP cases diagnosed at respiratory general ward and respiratory intensive care unit (RICU) from August 2008 to December 2010 were studied. Epidemiological data, etiology and clinical characteristics of enrolled patients were collected. Sputum or tracheal aspirate and blood cultures, Legionella antibodies and Streptococcus pneumoniae urinary antigen tests were performed. Bacteria to antimicrobial susceptibility test was performed. RESULTS: A total of 610 cases of HAP were diagnosed during the study, with an overall incidence of 1.4% among 42 877 hospitalized patients, while the incidence was 0.9% (362/41 261) in respiratory general ward and 15.4% (248/1616) in RICU. 93.9% (573 cases) of patients had at least one underlying disease, and 91.0% (555 cases) had exposure to at least one antimicrobial agent within 90 days prior to HAP diagnosis. Pathogens were identified in 487 patients, with Acinetobacter baumannii [30.0% (183/610)], Pseudomonas aeruginosa [22.0% (134/610)], Staphylococcus aureus [13.4% (82/610)] and Klebsiella pneumonia [9.7% (59/610)] being the most common pathogens. Eighteen patients (3.0%) had infection with fastidious bacteria. A. baumannii and S. aureus were the more frequent pathogens in the ventilator-associated pneumonia (VAP) cases [50.5% (97/192) and 21.4% (41/192)] as compared to non-VAP cases [20.6% (86/418) and 9.8% (41/418), P < 0.01]. A. baumannii and S. aureus were also frequent pathogens in cases with a score of more than 20 by the acute physiology and chronic health evaluation II (APACHEII) scoring [45.7% (69/151) and 20.5% (31/151)], as compared to cases with a score of less than 20 of APACHE II [24.8% (114/459) and 11.1% (51/459), P < 0.01]. A. baumannii showed high resistance rates to carbapenems [more than 70% (109/142)], and the susceptibility to cefoperazone/sulbactam, polymyxin B and tigecycline were 40.8% (58/142), 99.3% (141/142) and 95.8% (136/142) respectively. Resistance rates of P. aeruginosa to meropenem and imipenem were 48.8% (40/82) and 70.7% (58/82) respectively. Methicillin-resistant S. aureus (MRSA) accounted for 87.8% (43/49) in all strains of S. aureus. Mortality rate of VAP cases was 34.5% (61/177), significantly more than that of HAP patients [22.3% (135/605), P < 0.05]. The average hospital stay of patients with HAP was (23.8 ± 20.5) days, significantly more than that of the average for inpatients [(13.2 ± 13.6) days, P < 0.01] during the study period. Mean costs of HAP were (108 950 ± 116 608) yuan, significantly higher than the average hospital costs of respiratory inpatients (17 999 ± 33 364) yuan. CONCLUSIONS: Among Chinese patients hospitalized in urban tertiary medical centers, HAP incidence and mortality rate were high, which increased the patients' hospital stay and the medical costs. Common pathogens were A. baumannii, P. aeruginosa, S. aureus and K. pneumonia. The common bacteria of HAP in China showed high resistance rates to antibiotics.

Angiotensin II plays a critical role in diabetic pulmonary fibrosis most likely via activation of NADPH oxidase-mediated nitrosative damage.

Diabetic patients have a high risk of pulmonary disorders that are usually associated with restrictive impairment of lung function, suggesting a fibrotic process (van den Borst B, Gosker HR, Zeegers MP, Schols AM. Chest 138: 393-406, 2010; Ehrlich SF, Quesenberry CP Jr, Van Den Eeden SK, Shan J, Ferrara A. Diabetes Care 33: 55-60, 2010). The present study was undertaken to define whether and how diabetes causes lung fibrosis. Lung samples from streptozotocin-induced type 1 diabetic mice, spontaneously developed type 1 diabetic OVE26 mice, and their age-matched controls were investigated with histopathological and biochemical analysis. Signaling mechanism was investigated with cultured normal human lung fibroblasts in vitro. In both diabetes models, histological examination with Sirius red and hemotoxylin and eosin stains showed fibrosis along with massive inflammatory cell infiltration. The fibrotic and inflammatory processes were confirmed by real-time PCR and Western blotting assays for the increased fibronectin, CTGF, PAI-1, and TNFα mRNA and protein expressions. Diabetes also significantly increased NADPH oxidase (NOX) expression and protein nitration along with upregulation of angiotensin II (Ang II) and its receptor expression. In cell culture, exposure of lung fibroblasts to Ang II increased CTGF expression in a dose- and time-dependent manner, which could be abolished by inhibition of superoxide, NO, and peroxynitrite accumulation. Furthermore, chronic infusion of Ang II to normal mice at a subpressor dose induced diabetes-like lung fibrosis, and Ang II receptor AT1 blocker (losartan) abolished the lung fibrotic and inflammatory responses in diabetic mice. These results suggest that Ang II plays a critical role in diabetic lung fibrosis, which is most likely caused by NOX activation-mediated nitrosative damage.

[A multicentre retrospective study of pulmonary mycosis clinically proven from 1998 to 2007].

OBJECTIVE: To investigate the pathogens, clinical manifestations, prognosis of and the risk factors for pulmonary mycosis in China. METHODS: All cases of pulmonary mycosis from 16 centers in 10 cities from Jan. 1998 to Dec. 2007 that met the diagnostic criteria were included for clinical, microbiological and radiological analysis. RESULTS: Totally 474 cases of pulmonary mycosis were retrieved. The top 5 pulmonary mycosis was pulmonary aspergillosis (180 cases, 37.9%), pulmonary candidiasis (162 cases, 34.2%), pulmonary cryptococcosis (74 cases, 15.6%), pneumocystis carinii pneumonia (23 cases, 4.8%) and pulmonary mucormycosis (10 cases, 2.1%). The constituent ratio in the last 3 years was similar to that in the former 7 years. The main pathogens of pulmonary candidiasis were Candida albicans (308/474, 65.0%) and Candida tropicalis (57/474, 12.0%), which were sensitive to common azoles. Compared with bacterial pneumonia, pulmonary mycosis showed more symptoms of hemoptysis (147/474, 31.0%) and pleural effusion (95/474, 20.0%), and less radiological specificity. Classical halo sign (4/474, 0.8%) and crescentic sign (17/474, 3.6%) were only shown in several cases of pulmonary mycosis. The most common underlying diseases were tumor (including solid tumor and malignant hematological diseases) (94/474, 19.8%), chronic obstructive pulmonary disease (52/474, 11.0%), pulmonary tuberculosis (50/474, 10.5%) and diabetes (48/474, 10.1%). Compared with the other common pulmonary mycosis, pulmonary cryptococcosis affected younger patients, and more cases were community-acquired, but fewer cases with underlining diseases or compromised immune function, and had a better prognosis. CONCLUSION: The ahead five species of pulmonary mycosis in China were orderly pulmonary aspergillosis, pulmonary candidosis, pulmonary cryptococcosis, pneumocystis carinii pneumonia and pulmonary mucormycosis. The main pathogens of pulmonary candidosis were Candida albicans and Candida tropicalis, which were sensitive to common azoles. Compared with the other common pulmonary mycosis, pulmonary cryptococcosis catch younger patients, had more community-acquired cases, and had better prognosis.

[Detection of SLC34A2 in patients with pulmonary alveolar microlithiasis and the effect of SLC34A2 on transportation of calcium and phosphate in human alveolar epithelial cells].

OBJECTIVE: To detect the mutation of SLC34A2 in patients with pulmonary alveolar microlithiasis and to study the effect of SLC34A2 on transportation of calcium and phosphate in human alveolar epithelial cell (A549) cells. METHODS: The gene SLC34A2 was detected by segmentation-PCR and gene sequencing. RNA was obtained by Trizol from fresh lung tissues and the target gene was acquired by RT-PCR. Eukaryotic expression of recombinant pcDNA3.1(+)-SLC34A2 was constructed and SLC34A2 was transfected to A549 cells by liposome. The expression of SLC34A2 mRNA was detected by RT-PCR, and the content of calcium and phosphate of the extracellular fluid was measured by commercial kits. The cell experiments consisted of 3 groups including a control group (5 x 10(5)/well, one well), a blank group (5 x 10(5)/well, one well), a transfection group (5 x 10(5)/well, four wells). Every experiment was repeated 6 times. RESULTS: No mutation was found in patients with pulmonary alveolar microlithiasis. SLC34A2 cDNA was successfully amplified and the eukaryotic expression recombinant pcDNA3.1(+)-SLC34A2 was successfully constructed. The amount of SLC34A2 mRNA of the transfected cells was significantly higher (2.48 +/- 0.45), compared to the control cells (0.55 +/- 0.07) and the blank cells (0.60 +/- 0.06), q = 16.25, 15.78, all P < 0.01. The content of calcium and phosphate in the supernatant of the transfected cells was lower [(0.110 +/- 0.016) mmol/L, (3.8 +/- 0.4) mmol/L], compared with the control [(0.254 +/- 0.047) mmol/L, (7.3 +/- 0.8) mmol/L] and the blank (0.262 +/- 0.041) mmol/L, (7.1 +/- 0.4) mmol/L], q = 8.657 - 13.892, all P < 0.01. CONCLUSIONS: In human lung alveolar epithelial cells, the content of calcium and phosphate in cell supernatant decreased with increased amount of SLC34A2 mRNA. Mutation of SLC34A2 may not be at the DNA level.

[Three cases of pulmonary alveolar microlithiasis in a family and clinical analysis].

OBJECTIVE: To describe the characteristics of 3 cases of pulmonary alveolar microlithiasis in a family, and therefore to improve the understanding of the disease. METHODS: To analyze the clinical, laboratory and radiological data of three patients with pulmonary alveolar microlithiasis in a family and the relevant literatures were reviewed. RESULTS: There was a typical manifestation in these three cases of pulmonary alveolar microlithiasis: progressive dyspnoea, cough, family history. Chest X-ray and computed tomography demonstrate: the pulmones was full of high density reflection of intra-alveolar microliths especially in middle-lower lobe and posterior lobe. The etiology of these three cases is still unknown, consanguineous marriage of parents is possible reason. There was not effective therapies to them. CONCLUSION: Pulmonary alveolar microlithiasis is a disease without clear known etiology and effective therapy. For a patient with radiological features of high density intra-alveolar microliths and a positive family history, the diagnosis should be highly suspected.

HPIP silencing inhibits TGF-ß1-induced EMT in lung cancer cells.

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)-ß1-induced EMT in A549 lung cancer cells in vitro. Our data demonstrated that HPIP was overexpressed in the lung cancer cell lines. TGF-ß1 increased the expression of HPIP in the A549 cells. In addition, HPIP silencing significantly attenuated TGF-ß1-induced EMT and migration/invasion in the A549 cells. Furthermore, knockdown of HPIP greatly inhibited TGF-ß1-induced phosphorylation of Smad2 in the A549 cells. In conclusion, we demonstrated that HPIP silencing suppressed TGF-ß1-induced EMT in lung cancer cells by inhibiting Smad2 activation. Therefore, HPIP may be a new therapeutic target for the treatment of lung cancer.

Acidic Zeolite†L as a Highly Efficient Catalyst for Dehydration of Fructose to 5-Hydroxymethylfurfural in Ionic Liquid.

Zeolite L was synthesized by the hydrothermal method and post-treated by NH4 exchange to adjust its acidity. The samples were systematic characterized by various techniques including XRD, X-ray fluorescence spectroscopy, N2 adsorption-desorption, scanning electron microscopy, pyridine IR spectroscopy, and NH3 temperature-programmed desorption. The results demonstrated that the NH4 -exchange post-treatment increased the surface area, micropore volume, and acidity of zeolite L. The catalytic performance of the samples was tested in the dehydration of fructose to 5-hydroxymethylfurfural (HMF) in ionic liquid (1-butyl-3-methylimidazolium bromide, [bmim]Br). 99.1 % yield of HMF was obtained when the KL-80 °C-1 h sample (KL zeolite treated with 1 m NH4 NO3 solution at 80 °C for 1 h) was used. The high efficiency could be attributed to the appropriate acid properties of the catalyst. The zeolite catalyst could be reused four times without significant decrease in activity.

Sulforaphane prevents bleomycin­induced pulmonary fibrosis in mice by inhibiting oxidative stress via nuclear factor erythroid 2­related factor­2 activation.

Lung fibrosis is associated with inflammation, apoptosis and oxidative damage. The transcription factor nuclear factor erythroid 2­related factor­2 (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 age­matched 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 interleukin­1ß, tumor necrosis factor­α, transforming growth factor­ß and caspase­3 protein expressions. Furthermore, protein levels of 3­nitro­tyrosine, 4­hydroxynonenal, 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 oxygenase­1, superoxide dismutase and catalase, via upregulation of Nrf2 gene expression. Thus, the results from the present study may facilitate the development of therapies for BLM­toxicity and pulmonary fibrosis.

HDAC6 inhibition prevents TNF-α-induced caspase 3 activation in lung endothelial cell and maintains cell-cell junctions.

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.

Approaches to prevent the patients with chronic airway diseases from exacerbation in the haze weather.

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.

ER stress and autophagy are involved in the apoptosis induced by cisplatin in human lung cancer cells.

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.

Promoter methylations of RASSF1A and p16 is associated with clinicopathological features in lung cancers.

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.

Randomized, Multicenter Clinical Study of Tratinterol Hydrochloride Tablets for the Treatment of Bronchial Asthma.

PURPOSE: The aim of this study was to determine the efficacy and safety profile of tratinterol hydrochloride tablets in the treatment of bronchial asthma. METHODS: This multicenter, randomized, double-blind clinical research study was completed at 6 centers in the People's Republic of China from March 2009 to June 2010, and a randomized trial of procaterol hydrochloride tablets produced by Otsuka Pharmaceutical Co Ltd was conducted. The study was approved by the Medical Ethics Committee of the First Hospital of China Medical University. The clinical trial registration number is 2007L04263. FINDINGS: A total of 223 patients were selected for this study, with 112 patients in the treatment group and 111 in the control group. The lung function of the 2 groups after treatment significantly increased in all (P < 0.05); however, there was no significant difference in the changes between the 2 groups (P > 0.05). The occurrence of related adverse events at varying degrees in the control group was higher than in the treatment group. IMPLICATIONS: It is safe and effective to use tratinterol hydrochloride tablets to treat bronchial asthma.

Multi-organ involvement of Sweet's syndrome: a case report and literature review.

The hallmark of Sweet's syndrome (SS) is the infiltration of mature neutrophils in the upper dermis. We herein report a case of SS with multi-organ involvement. A 32-year-old man presented with fever, anemia and dyspnea. He was given antibiotics, without any improvements. Later, a number of erythematous lesions appeared, accompanied by deteriorating respiratory and cardiovascular functions. A diagnosis of SS was confirmed on a skin biopsy, and the patient was given corticosteroids, the dose of which was reduced after one month. The organ function subsequently deteriorated, and he ultimately died of multi-organ failure. Early recognition of SS with multi-organ involvement is important in patients with SS.