Endothelial cell-specific anticoagulation reduces inflammation in a mouse model of acute lung injury.

Tissue factor (TF)-dependent coagulation contributes to lung inflammation and the pathogenesis of acute lung injury (ALI). In this study, we explored the roles of targeted endothelial anticoagulation in ALI using two strains of transgenic mice expressing either a membrane-tethered human tissue factor pathway inhibitor (hTFPI) or hirudin fusion protein on CD31+ cells, including vascular endothelial cells (ECs). ALI was induced by intratracheal injection of LPS, and after 24 h the expression of TF and protease-activated receptors (PARs) on EC in lungs were assessed, alongside the extent of inflammation and injury. The expression of TF and PARs on the EC in lungs was upregulated after ALI. In the two strains of transgenic mice, expression of either of hTFPI or hirudin by EC was associated with significant reduction of inflammation, as assessed by the extent of leukocyte infiltration or the levels of proinflammatory cytokines, and promoted survival after LPS-induced ALI. The beneficial outcomes were associated with inhibition of the expression of chemokine CCL2 in lung tissues. The protection observed in the CD31-TFPI-transgenic strain was abolished by injection of an anti-hTFPI antibody, but not by prior engraftment of the transgenic strains with WT bone marrow, confirming that the changes observed were a specific transgenic expression of anticoagulants by EC. These results demonstrate that the inflammation in ALI is TF and thrombin dependent, and that expression of anticoagulants by EC significantly inhibits the development of ALI via repression of leukocyte infiltration, most likely via inhibition of chemokine gradients. These data enhance our understanding of the pathology of ALI and suggest a novel therapeutic strategy for treatment.

Myocyte enhancer factor 2D provides a cross-talk between chronic inflammation and lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer. Chronic inflammation may play an important role in the lung carcinogenesis among those patients. The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases. METHODS: We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition. Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis. RESULTS: Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC). Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation. Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549. MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement. CONCLUSIONS: Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors. MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.

Association between polymorphisms of autophagy pathway and responses in non-small cell lung cancer patients treated with platinum-based chemotherapy.

Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (G>A) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (A>C) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (C>A) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (A>G) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (G>A) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (G>A) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (G>A) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (G>A) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (G>A) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (G>A) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.

Implementation of the World Health Organization Framework Convention on Tobacco Control in China: An arduous and long-term task.

China is the largest producer and consumer of tobacco in the world. Consequently, the burden of tobacco-related diseases in China is enormous. Implementation of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) may lead to a significant reduction in tobacco-related morbidity and mortality both in China and globally. In this review, the authors summarize the epidemic of tobacco use and the progress made in implementing the WHO FCTC, including the promotion of legislation for smoke-free public places; smoking-cessation assistance; labeling of tobacco packaging; enforcement of bans on tobacco advertising, promotion, and sponsorship; increased taxes on tobacco products; increased tobacco prices; improvements in public awareness of the dangers of smoking; and identifying the barriers to implementing effective tobacco-control measures in China. Since the WHO FCTC officially took effect in China on January 9, 2006, China has taken some important steps, especially in promoting legislation for smoke-free public places. Because tobacco permeates the fabric of society, business, commerce, and politics in China, commitments and actions from the government are crucial, and implementing the WHO FCTC in China will be an arduous and long-term task.

Chinese consensus on early diagnosis of primary lung cancer (2014 version).

The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment.

Prevention and management of lung cancer in China.

Lung cancer is the leading cause of cancer-related death worldwide. In China, the incidence of lung cancer has grown rapidly, resulting in a large social and economic burden. Several researchers have devoted their studies to lung cancer and have demonstrated that there are many risk factors for lung cancer in China, including tobacco use, environmental pollution, food, genetics, and chronic obstructive pulmonary disease. However, the lung cancer incidence is still growing rapidly in China, and there is an even higher incidence among the younger generation. One explanation may be the triple-neglect situation, in which medical policies that neglect prevention, diagnosis, and supportive care have increased patients' mortality and reduced their quality of life. Therefore, it is necessary to enhance the efficiency of prevention and early diagnosis not only by focusing more attention on treatment but also by drawing more attention to supportive care for patients with lung cancer.

Role of a serum-based biomarker panel in the early diagnosis of lung cancer for a cohort of high-risk patients.

BACKGROUND: This study applied a combined cancer biomarker panel to clinically identify small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in a high-risk population. METHODS: The serum levels of 4 biomarkers (progastrin-releasing peptide [ProGRP], carcinoembryonic antigen [CEA], squamous cell carcinoma antigen [SCC], and cytokeratin 19 fragment [CYFRA21-1]) were determined in 153 patients with a high risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC, and 89 without lung cancer). Information about diagnosis delays was collected through interviews of all participants. RESULTS: Significantly higher serum levels of ProGRP (P < .0001) were found among the SCLC patients versus the rest of the population. A receiver operating characteristic curve analysis established the cutoff values of ProGRP, CEA, SCC, and CYFRA21-1 as 300 pg/mL, 7.3 ng/mL, 3 ng/mL, and 6.5 ng/mL, respectively. The sensitivity and specificity of ProGRP in diagnosing SCLC were 75% and 100%, respectively. Among the 14 lung cancer patients with a false-negative computed tomography (CT) result, the diagnostic panel detected 8 additional cancers. CONCLUSIONS: This panel increased the diagnostic specificity for high-risk subjects (those with renal failure being excluded), and auxiliary to a CT scan, it increased the sensitivity for patients with lung cancer. These results might be applied to shorten the diagnosis delay at health care institutions in China.

Prevalence of undiagnosed and undertreated chronic obstructive pulmonary disease in lung cancer population.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a risk factor and important coexisting disease for lung cancer; however, the current status of management of COPD in lung cancer patients is not fully described. This study addressed this issue in a general teaching hospital in China. METHODS: Medical records of hospitalized lung cancer patients in Zhongshan Hospital, Fudan University, between January 2006 and December 2010 were reviewed. The definition of COPD was according to the spirometric criteria of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document. The diagnostic rate (COPD recorded as a discharge diagnosis/spirometry-defined percentage) and conformity to GOLD treatment guidelines were investigated. The factors influencing diagnosis were analysed. RESULTS: During the study period, the prevalence of spirometry-defined COPD in hospitalized lung cancer patients was 21.6% (705/3263). The overall diagnostic rate of COPD was 7.1%, and the treatment conformity for stable and acute exacerbation of COPD was 27.1% and 46.8%, respectively. Respiratory physicians had a higher diagnostic rate than non-respiratory doctors (34.8% vs 2.9%, P < 0.001) and a better treatment conformity for acute exacerbation of COPD (63.6% vs 37.5%, P = 0.048). Patients with COPD as a discharge diagnosis had more chance to receive guideline-consistent treatment. The diagnostic rate of COPD was higher among patients with a history of smoking, respiratory diseases or symptoms. CONCLUSIONS: COPD is substantially underdiagnosed and undertreated in a hospitalized lung cancer population. History of smoking, respiratory diseases and symptoms promotes diagnosis. Education of COPD knowledge among patients and doctors is urgently required in this special population.

Two microRNA panels to discriminate three subtypes of lung carcinoma in bronchial brushing specimens.

RATIONALE: Effective treatment for lung cancer requires accuracy in subclassification of carcinoma subtypes. OBJECTIVES: To identify microRNAs in bronchial brushing specimens for discriminating small cell lung cancer (SCLC) from non-small cell lung cancer (NSCLC) and for further differentiating squamous cell carcinoma (SQ) from adenocarcinoma (AC). METHODS: Microarrays were used to screen 723 microRNAs in laser-captured, microdissected cancer cells from 82 snap-frozen surgical lung specimens. Quantitative reverse-transcriptase polymerase chain reaction was performed on 153 macrodissected formalin-fixed, paraffin-embedded (FFPE) surgical lung specimens to evaluate seven microRNA candidates discovered from microarrays. Two microRNA panels were constructed on the basis of a training cohort (n = 85) and validated using an independent cohort (n = 68). The microRNA panels were applied as differentiators of SCLC from NSCLC and of SQ from AC in 207 bronchial brushing specimens. MEASUREMENTS AND MAIN RESULTS: Two microRNA panels yielded high diagnostic accuracy in discriminating SCLC from NSCLC (miR-29a and miR-375; area under the curve [AUC], 0.991 and 0.982 for training and validation data set, respectively) and in differentiating SQ from AC (miR-205 and miR-34a; AUC, 0.977 and 0.982 for training and validation data set, respectively) in FFPE surgical lung specimens. Moreover, the microRNA panels accurately differentiated SCLC from NSCLC (AUC, 0.947) and SQ from AC (AUC, 0.962) in bronchial brushing specimens. CONCLUSIONS: We found two microRNA panels that accurately discriminated between the three subtypes of lung carcinoma in bronchial brushing specimens. The identified microRNA panels may have considerable clinical value in differential diagnosis and optimizing treatment strategies based on lung cancer subtypes.

High-dose N-acetylcysteine in the prevention of COPD exacerbations: rationale and design of the PANTHEON Study.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation; from a pathophysiological point of view it involves many components, including mucus hypersecretion, oxidative stress and inflammation. N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. Long-term efficacy of NAC 600mg/d in COPD is controversial; a dose-effect relationship has been demonstrated, but at present it is not known whether a higher dose provides clinical benefits. The PANTHEON Study is a prospective, ICS stratified, randomized, double-blind, placebo-controlled, parallel-group, multi-center trial designed to assess the efficacy and safety of high-dose (1200 mg/daily) NAC treatment for one year in moderate-to-severe COPD patients. The primary endpoint is the annual exacerbation rate. Secondary endpoints include recurrent exacerbations hazard ratio, time to first exacerbation, as well as quality of life and pulmonary function. The hypothesis, design and methodology are described and baseline characteristics of recruited patients are presented. 1006 COPD patients (444 treated with maintenance ICS, 562 ICS naive, aged 66.27±8.76 yrs, average post-bronchodilator FEV1 48.95±11.80 of predicted) have been randomized at 34 hospitals in China. Final results of this study will provide objective data on the effects of high-dose (1200 mg/daily) long-term NAC treatment in the prevention of COPD exacerbations and other outcome variables.

[Value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography in early diagnosis of lung cancer].

OBJECTIVE: To evaluate the application value of (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in early diagnosis of lung cancer. METHODS: Retrospective analyses were conducted for 347 cases of pulmonary space-occupying lesions at Zhongshan Hospital from June 2010 to October 2012. The diagnostic validity of PET/CT and fluorodeoxyglucose maximum standardized uptake value (SUVmax) of lesions were compared respectively. Among different morphological characteristics, pathologic types and levels of tumor markers. The diagnostic value of PET/CT was also evaluated along with serum tumor markers for lung cancer. RESULTS: SUVmax was positively correlated with lesion size (r = 0.484, P < 0.05) and negatively with tumor differentiation degree (r = -0.232, P < 0.01). It was significantly higher in tumor marker positive group than the negative group (10.6 ± 5.5 vs 7.6 ± 5.4, P < 0.05). The diagnostic specificity, sensitivity and accuracy of PET/CT were 50.0%, 96.6% and 89.3% in lung cancer. And the greater the lesion, the higher the diagnostic accuracy (P < 0.05). PET/CT plus serum tumor markers could boost the diagnostic specificity of lung cancer by 30% (P < 0.01). CONCLUSIONS: (18)F-FDG PET/CT has high diagnostic values for early stage pulmonary nodules. It can also suggest the differentiation degree of lung cancer. Combined use of serum tumor markers and (18)F-FDG PET/CT increases the early diagnostic specificity of lung cancer.

[Value of low-dose spiral computed tomography in lung cancer screening].

OBJECTIVE: To explore the application value of low-dose spiral computed tomography (LDCT) in lung cancer screening. METHODS: A total of 2251 asymptomatic subjects undergoing chest LDCT scan at Center of Physical Examination, Affiliated Zhongshan Hospital, Fudan University between June 2011 and December 2012 were prospectively enrolled. The incidence rates of lung nodule and lung cancer were analyzed to compare the value of LDCT screening in subjects with smoking-related high, medium and low risks of lung cancer. The value of serum tumor biomarker in the reduction of false positive of LDCT was also discussed. RESULTS: Among all subjects, 9.9% (222/2251) displayed at least 1 non-calcified nodule with a diameter ≥ 4 mm. Two subjects were diagnosed with lung cancer and 1 of them received surgical resection. Other subjects with lung nodules were followed. There was no statistical difference in the incidence rates of lung nodule between the high, medium and low-risk groups of lung cancer associated with smoking (8.8%, 9.5% and 10.1%, P = 0.864). The incidence rates of lung nodule in subjects ≥ 55 years old were higher than that of those <55 years old (12.7% vs 9.1%, P = 0.034). Female gender had a high risk of ground glass opacity (GGO) or ground glass nodule (GGN) (P = 0.015). The independent or combined increase of serum tumor biomarkers of carcinoembryonic antigen (CEA), neuron specific enolase (NSE), cytokeratin fragment 21-1 (Cyfra211) and squamous cell carcinoma antigen (SCC) might not predicate the incidence of lung nodule. CONCLUSION: LDCT screening is highly valuable in lung cancer screening.

Pro-inflammatory phenotype of COPD fibroblasts not compatible with repair in COPD lung.

Chronic obstructive pulmonary disease (COPD) is characterized by loss of elastic fibres from small airways and alveolar walls, with the decrease in elastin increasing with disease severity. It is unclear why there is a lack of repair of elastic fibres. We have examined fibroblasts cultured from lung tissue from subjects with or without COPD to determine if the secretory profile explains lack of tissue repair. In this study, fibroblasts were cultured from lung parenchyma of patients with mild COPD [Global initiative for chronic Obstructive Lung Disease (GOLD) 1, n= 5], moderate to severe COPD (GOLD 2-3, n= 12) and controls (non-COPD, n= 5). Measurements were made of proliferation, senescence-associated ß-galactosidase-1, mRNA expression of IL-6, IL-8, MMP-1, tropoelastin and versican, and protein levels for IL-6, IL-8, PGE(2,) tropoelastin, insoluble elastin, and versican. GOLD 2-3 fibroblasts proliferated more slowly (P < 0.01), had higher levels of senescence-associated ß-galactosidase-1 (P < 0.001) than controls and showed significant increases in mRNA and/or protein for IL-6 (P < 0.05), IL-8 (P < 0.01), MMP-1 (P < 0.05), PGE(2) (P < 0.05), versican (P < 0.05) and tropoelastin (P < 0.05). mRNA expression and/or protein levels of tropoelastin (P < 0.01), versican (P < 0.05), IL-6 (P < 0.05) and IL-8 (P < 0.05) were negatively correlated with FEV1% of predicted. Insoluble elastin was not increased. In summary, fibroblasts from moderate to severe COPD subjects display a secretory phenotype with up-regulation of inflammatory molecules including the matrix proteoglycan versican, and increased soluble, but not insoluble, elastin. Versican inhibits assembly of tropoelastin into insoluble elastin and we conclude that the pro-inflammatory phenotype of COPD fibroblasts is not compatible with repair of elastic fibres.

FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells.

AIM: Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC), and the underlying mechanism remains unclear. FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients. In this study, we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms. METHODS: Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used. mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis. RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells, and lentiviral infection was used to overexpress FoxM1 in H292 cells. MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells. RESULTS: Treatment of SPC-A-1 cells with gefitinib (1 and 10 µmol/L) upregulated the expression of FoxM1 in time- and concentration-dependent manners, while gefitinib (1 µmol/L) downregulated in H292 cells. In SPC-A-1 cells treated with gefitinib (1 µmol/L), the expression of several downstream targets of FoxM1, including survivin, cyclin B1, SKP2, PLK1, Aurora B kinase and CDC25B, were significantly upregulated. Overexpression of FoxM1 increased the resistance in H292 cells, while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis. CONCLUSION: The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro. FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

[A survey of knowledge on common cold in outpatient clinics].

OBJECTIVE: To investigate outpatients' cognition towards common cold and their habituated medication so as to provide evidence for future public healthcare education. METHODS: Patients who attended hospital for diagnosis and treatment of common cold at least within past three months were asked to fill a questionnaire independently so as to learn their cognition towards common cold and medication habit. RESULTS: Among the patients underwent survey, 52.21% had incorrect knowledge about common cold; 12.99% didn't know about the hazards of common cold; 34.80% couldn't distinguish common cold from influenza; 30.07% considered common cold couldn't get relief without treatment; 68.24% didn't know about the proper effects of influenza vaccination; 61.14% often took oral medicine even intravenous injection when they caught a common cold; 59.77% often took medication from drugstore without prescription by doctor, and a few asked doctors to prescribe medicine on their request; 19.42% didn't know about the side effects of drug for cold treatment; and 19.72% didn't know about the active ingredients of drug for cold treatment. There were significant differences in the common cold cognition among population of different ages and education background. The older or the higher education status patients had a better cognition (P < 0.01). CONCLUSION: There exist a certain degree of wrong cognition towards common cold among patients of different literacy degree and different age. Public health education on common cold need to be further strengthened.

[A survey of knowledge on common cold and its treatment situation among physicians from various levels of hospitals in mainland China].

OBJECTIVE: To investigate the cognition of the common cold and current situation of the treatment among physicians from various levels of hospitals in Chinese mainland, so as to provide evidence for future continuing medical education and rational medication. METHODS: A questionnaire designed for this survey was used to learn about the general information, cognitive degree of the common cold and prescription habits of physician who prescribed for cold within last three months, from various levels hospitals. RESULTS: A total of 1001 physicians were interviewed. Among them, 749 physicians chose right options that the cold was the common cold and the influenza with 79.84% in resident physicians and 56.76% in chief physicians. A total of 745 physicians chose options that the course of common cold will be lasting 4 to 7 days; 895 physicians chose options that old people are the most susceptible for complication; 669 physicians thought the common cold was the most common infection in winter; 841 physicians used clinical methods to diagnose the common cold; 736 physicians thought although the cold was a kind of self-limited disease and symptomatic treatment could alleviate symptoms and improve life quality, patients should see doctor in time if it turns to severer; and 745 physicians held the opinion that treatment of the common cold should focus on relieving symptoms first. In addition, 61.60% physicians had made prescription based on clinical symptoms; 505 (54.24%) of them thought compound drugs were priority in treating the common cold. However, there were still 43 physicians prescribed antibiotics for common cold. CONCLUSIONS: There is misunderstanding and discrepancy in cognition towards common cold and treatment among physicians from various levels of hospitals in mainland China. Physicians should standardize diagnosis and treatment for the common cold according to the domestic and foreign guidelines.

[Evaluation of endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of hilar and mediastinal masses of unknown etiologies].

OBJECTIVE: To explore the diagnostic values of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the patients with hilar and mediastinal masses. METHODS: A total of 91 patients with mediastinal/hilar masses undergoing EBUS-TBNA in Zhongshan Hospital between September 2009 and March 2011 were retrospectively enrolled. Their unknown etiologies were difficult to be assessed by a traditional biopsy. The association of pathologic examinations and clinical data were analyzed. RESULTS: Among them, 61 patients had malignant lesions while 30 patients were diagnosed with benign diseases. In the cases with malignant lesions, the diagnostic sensitivity, specificity and accordance rate were 91.67%, 100% and 91.80% respectively. The diagnostic accordance rate of benign lesions was 60%. And 36.9% (24/65) of the samples were small-sized so as to improve the diagnostic accuracy. The combination of cytology and histology significantly increased the diagnostic accordance versus cytology alone in all cases (P < 0.01). But there was no statistically significant difference in the malignant lesion subgroup with a better tendency (P > 0.05). No severe complication occurred. CONCLUSION: With a high diagnostic accuracy and a low complication rate for the patients with hilar and mediastinal masses of unknown etiologies, EBUS-TBNA has different values for diagnosing malignant and benign lesions.

Tobacco smoking in China: prevalence, disease burden, challenges and future strategies.

About one-third of the world's tobacco is produced and consumed in China. Despite existing tobacco control policies and activities, the prevalence of smoking in China remains high with 350 million smokers and 740 million passive smokers. Furthermore, smoking rates in the young population and in females are increasing. The number of deaths attributed to tobacco use has reached 1.2 million per year, whereas the death toll is expected to rise to 2 million annually by 2025. Sociocultural factors favouring smoking initiation, lack of awareness among the public about the hazards of smoking, weak support from the government and strong resistance from the tobacco industry are major reasons for the lack of effectiveness of current tobacco control measures. Effective intervention efforts are urgently required. Commitments from the government are crucial in tobacco control. Firm action should be taken on tobacco control issues at multiple levels including a reduction in tobacco supply, increased tobacco taxation, increased education, tobacco advertising limitations, decreased second-hand smoke exposure and smoking cessation support. The health-care community should also play a leading role in anti-tobacco campaigns and take a more active role in smoking cessation programmes.

Deletion of aquaporin 5 aggravates acute lung injury induced by Pseudomonas aeruginosa.

BACKGROUND: Aquaporin (AQP) is a membrane protein that facilitates osmotic water transport. Aquaporin 5 (AQP5) expresses at type I alveolar epithelia of apical membrane that confers high osmotic water permeability. Osmosis or stretch challenge in alveoli significantly up-regulates AQP5 expression, which suggests that AQP5 may play a role in the maintenance of epithelia barrier function. Pseudomonas aeruginosa (PA), a leading gram-negative bacterial frequently isolated from ventilation-associated pneumonia patients, disrupts alveolar and airway epithelial cells and subsequently leads to blood dissemination. In this study, we hypothesized that AQP5 might be protective in acute lung injury induced by PA, and deletion of AQP5 might lead to aggravated lung injury. METHODS: Lung injury model was induced by intratracheal instillation of PA (1 × 10(6) colony-forming unit) in wild-type and AQP5 knockout mice, 2 hours and 6 hours later, blood and lung lysate were cultured to detect blood dissemination, bronchoalveolar lavage fluid and lung tissue were collected for histology analysis. Lung injury assessment, wet/dry weight ratio, protein leakage, and Evan's blue dye extravasation were evaluated for pulmonary barrier function. RESULTS: AQP5 deficiency led to increased bacterial blood dissemination and aggravated lung injury during PA infection, and AQP5 deletion also reduced mucin production in lung. Moreover, AQP5 deficiency showed declined activation of mitogen-activated protein kinase and nuclear factor-kappa B pathways in lungs before and after PA infection. CONCLUSION: Our data demonstrated that AQP5 plays a protective role in the maintenance of pulmonary barrier function against PA infection.

[A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].

OBJECTIVE: To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death. RESULTS: The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P > 0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P > 0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P > 0.05). CONCLUSIONS: Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.