Plastein reaction enhanced bile-acid binding capacity of soybean protein hydrolysates and whey protein hydrolysates.

Plastein reaction is a modification reaction that can improve the functional properties of protein hydrolysate. The product of the reaction is a thixotropic aggregation of peptides. This study investigated the formation condition of soybean-whey plastein and bile acid binding capacity of plastein. Soy protein and whey protein were hydrolyzed by pepsin. The mixture (1:1, w/w) of two hydrolysates was modified by pepsin again. After the reaction, the decrease in free amino groups and the turbidity of the modified hydrolysate were measured to obtain appropriate reaction condition. Results showed that the concentration of hydrolysates 40% (w/v), enzyme ratio of 2.0 KU/g protein, pH 5.0, 37 °C, reaction time of 3.0 h respectively, were showed maximum changes in protein hydrolysates. Tricine SDS-PAGE analysis under denaturing conditions revealed that whey protein was more sensitive to pepsin and yielded different polypeptides (PPs) of molecular weight ranged from 3.5-17 kDa. However, a high molecular weight PP was completely hydrolyzed while PPs of 14.2-26 kDa were partially digested after pepsin treatment. Native page analysis further revealed the presence of a high-molecular weight PP in crude and purified plastein product. The bile acid binding capacity was improved by the plastein reaction. The amount of binding sodium deoxycholate, sodium taurocholate, and sodium cholate were 0.75, 2.0 and 1.87 µmol/100 mg respectively.

[Relationship between epidermal growth factor receptor gene expression and radiosensitivity of non-small-cell lung cancer cells].

OBJECTIVE: To explore the relationship between epidermal growth factor receptor (EGFR) gene expression and radiosensitivity of non-small-cell lung cancer (NSCLC) cells. METHODS: EGFR sequence-specific double-stranded RNA (dsRNA-EGFR) was chemically synthesized. NSCLC cell line SPC-A1 was transfected with dsRNA-EGFR formulated with Lipofectamine 2000. Western blot and real-time PCR were used to determine the EGFR mRNA and protein expression, respectively. Colony inhibition test was adopted to observe the radiosensitizing effect. To establish the nude mouse tumor models, calculate the tumor growth inhibition rate and make the tumor growth curve by measuring its size and weight. RESULTS: EGFR mRNA levels were 1.51 ± 0.22, 1.38 ± 0.15 and 0.45 ± 0.11 in the control group, dsRNA-unrelated group and dsRNA-EGFR group, respectively (F = 482.7, P < 0.01). The contents of EGFR protein were 2340.87 ± 10.99, 2231.85 ± 35.66 and 832.03 ± 39.13 in the control group, dsRNA-unrelated group and dsRNA-EGFR group, respectively (F = 263.3, P < 0.05). Compared with the control group, dsRNA-EGFR sequence specifically decreased the expressions of EGFR mRNA by 70.2% and EGFR protein by 64.5%. The colony inhibition rates of the control group, dsRNA-unrelated combined with radiotherapy group and dsRNA-EGFR combined with radiotherapy group were 9.3%, 12.5% and 65.5%, and the tumor growth inhibition rates were 21.3%, 24.4% and 64.2%, respectively. The combination of dsRNA-EGFR and radiotherapy significantly inhibited the tumor growth in vitro and in vivo. CONCLUSIONS: DsRNA-EGFR shows an apparent inhibitory effect on the expression of EGFR mRNA and protein of NSCLC cells, effectively inhibit the tumor growth in vivo, and enhance the radiosensitivity of NSCLC.

[Diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration in paratracheal mediastinal lesions].

OBJECTIVE: To explore the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in diagnosing mediastinal lesions. METHODS: A total of 264 patients with mediastinal lesions on chest CT at Provincial Hospital Affiliated to Shandong University between January 2010 and April 2012 were retrospectively enrolled. Their cytopathological results were difficult to be assessed by conventional bronchoscopy. There were 222 cases whose lymph nodes long axis was >1.5 cm. Among them, 174 cases underwent TBNA alone (group A) and the other 48 cases EBUS-TBNA alone (group B). The remaining 42 cases whose lymph nodes long axis was <1.5 cm belonged to group C and underwent TBNA (group C1) and EBUS-TBNA (group C2) sequentially as a combined procedure. The associations of pathologic examinations, diagnostic positive rate and complications were analyzed. RESULTS: Among 174 cases in group A, 154 cases were diagnosed with a positive diagnostic rate of 88.5%. There were 135 malignant lesions while 19 cases were diagnosed with benign diseases and 5 cases had accidental vascular injury. Among 48 cases in group B, 45 cases were diagnosed with a positive diagnostic rate of 93.8%. There were 33 malignant lesions while 12 cases were diagnosed with benign diseases. Among 42 patients in group C1, 31 cases were diagnosed by TBNA with a positive diagnostic rate of 73.8%. There were 23 malignant lesions while 8 cases were diagnosed with benign diseases and 2 cases had accidental vascular injury. Among 42 patients in group C2, 39 cases were diagnosed with a positive diagnostic rate of 92.8%. There were 30 malignant lesions while 9 cases had benign diseases. No difference existed in diagnostic positive rate between groups A and B (χ(2) = 0.621, P = 0.431) while the diagnostic positive rate in group A was much higher than group C1 (χ(2) = 5.945, P = 0.015). The difference between groups B and C2 was insignificant (χ(2) = 0.065, P = 0.320) while there was significant difference between groups C1 and C2 (χ(2) = 5.486, P = 0.019). CONCLUSION: With a low complication rate, EBUS-TBNA can yield a higher diagnostic positive rate in diagnosing small mediastinal diseases than conventional TBNA.

[The diagnostic value of medical thoracoscopy for unexplained pleural effusion].

OBJECTIVE: To explore the endoscopic features of patients with unexplained pleural effusion, and to evaluate the diagnostic value of medical thoracoscopy. METHODS: A retrospective analysis of 2380 patients with unexplained pleural effusion (1320 males and 1060 females; age 15-94 years) in Shandong Provincial Hospital from 1992 to 2011 were performed .The diagnosis was confirmed by medical thoracoscopy. RESULTS: The endoscopic findings of malignant pleural effusion mostly showed nodules of varying sizes. The nodules could be grape-like, cauliflower-like, fused into masses, or diffused small nodules . The appearance of cancerous nodules was more diversified compared to tuberculous nodules. Tuberculous pleurisy was manifested as diffuse pleural congestion and miliary changes, multiple small gray-white nodules, fibrin deposition and adhesion in the pleural cavity, pleural thickening and loculation . The pathological diagnosis was as follows: pleural metastases in 899 (37.8%), primary pleural mesothelioma in 439 (18.4%), tuberculous pleurisy in 514 (21.6%), non-specific inflammation in 226 (9.5%), empyema in 190 (8.0%), hepatic pleural effusion in 36 (1.5%) and pleural effusion of unknown causes in 76 (3.2%) cases. The diagnostic positive rate of medical thoracoscopy was 96.8%. No serious complications were observed. CONCLUSION: Medical thoracoscopy is a relatively safe procedure and has an important application value in the diagnosis of unexplained pleural effusion.

[Effect of trichostatin A and paclitaxel on the growth and apoptosis of lung adenocarcinoma cell lines].

OBJECTIVE: To investigate the effect of trichostatin A (TSA)/paclitaxel on the growth and apoptosis in human lung adenocarcinoma cell line A549 cells. METHODS: Human lung adenocarcinoma A549 cells were cultured in DMEM in the presence of paclitaxel and the histone deacetylase inhibitor trichostatin A, and the growth curve was obtained by trypan-blue exclusion assay and cell count. Apoptosis was assessed using Hoechst 33258 staining and flow cytometry, and cell cycle was detected by flow cytometry analysis. The proteins of PARP, caspase-3, survivin and tubulin acetylation were detected by Western blotting. RESULTS: Significant growth reduction was observed in the A549 cells following treatment with paclitaxel or the histone deacetylase inhibitor TSA. The combined treatment with TSA/paclitaxel caused the highest inhibition of cell growth. The apoptosis rate of A549 cells treated with TSA or paclitaxel for 24 hours was (17.6 ± 1.8)% and (39.2 ± 3.7)%, respectively, but a significantly higher apoptosis rate was (64.2 ± 4.2)% was induced by combined treatment with TSA and paclitaxel. In contrast with the control group, the cell cycle was markedly arrested at G2/M phase in the TSA and paclitaxel group (P < 0.05). The Western blot analysis demonstrated that treatment with TSA/paclitaxel led to a synergistic increase of acetylated tubulin, PARP and caspase-3, and reduced the expression of survivin. CONCLUSION: TSA or paclitaxel alone can inhibit the cell growth and induce apoptosis, and the combination of TSA and paclitaxel exerts a synergistic effect on the growth and apoptosis in lung adenocarcinoma cells.

[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.

Effect of glucocorticoid in mice of asthma induced by ovalbumin sensitisation and RSV infection.

OBJECTIVE: To investigate the inflammatory changes and the airway hyper-responsiveness in the asthma mouse model infected by respiratory syncytial virus and elucidate the relationship between the infection and the effect of glucocorticoid. METHODS: 60 BALB/c mice were randomly divided into 6 groups. One of these is the control group; the others are the OVA/sham group, the OVA/sham +Dex group, the PBS/RSV group, the OVA/RSV group and the OVA/RSV+Dex group. The airway resistance was measured using a sealed body plethysmograph. Pathological slides were stained with hematoxylin-eosin, and the peribronchial inflammation was observed microscopically. The concentrations of IL-4, IFN-gamma, TGF-beta1 in lung tissues were detected by ELISA. RESULTS: Compared with the control group, the degree of the airway inflammation and hyperresponsiveness and the concentrations of IL-4/IFN-gamma, TGF-beta1 in all four OVA groups increased significantly. And there was a statistically significant difference between the OVA/sham group and the OVA/sham+Dex group, and between the OVA/RSV group and the OVA/RSV+Dex group respectively. Compared with the OVA/RSV group, there was an obvious aggravation of airway inflammation and hyper-responsiveness in the OVA/RSV+Dex group. CONCLUSIONS: Glucocorticoid significantly reduces airway inflammation and hyper-responsiveness induced by repetitive OVA challenge in the mouse model of asthma. However, the significant decrease in Th1 and increase in Th2 inflammation and aggravation of airway hyper-responsiveness in the mice in OVA/RSV group show that they are not sensitive to glucocorticoid. The effects of infection with RSV on the mouse model of asthma could be the cause of the glucocorticoid resistance during the therapy.

[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.

Evaluation of the properties of whey protein films with modifications.

Whey protein concentrate (WPC) has been widely studied as a biodegradable bio-based packaging material in the food industry. In this study, different whey protein films were obtained through physical, chemical, enzymatic, and composite modifications. The molecular structure, micro-morphology, mechanical properties, barrier properties, and other characteristics of the films were evaluated. The results illustrated that the thickness of WPC with composite modification increased and the transmittance decreased, but the mechanical properties and barrier properties were more prominent. The WPC film prepared by physical modification combined with transglutaminase has the best film-forming effect, the tensile strength (TS) was 5.45 MPa, the elongation at break (EAB) was 25.19%, the WVP was 5.53 g·mm/m2 ·hr·kPa, and the Oxygen permeability (OP) was 1.83 meq/K, and its microstructure was and uniform. In addition, based on the the results of SDS-PAGE and Fourier transform infrared spectroscopy (FTIR), the intermolecular and intramolecular interactions of various modification methods on WPC were studied, thus contributing to analyze the properties of the film. This study provides theoretical basis and technical support for the industrial production of protein-based films.

Mechanical properties of whey protein concentrate based film improved by the coexistence of nanocrystalline cellulose and transglutaminase.

Whey Protein Concentrate (WPC) has been researched as food packaging materials in recent years. However, WPC films own the drawbacks on the barrier ability to water vapor and mechanical properties. In the presented work, Transglutaminase (TGase) and different concentrations of nanocrystalline cellulose (NCC) (0-15% wt. of WPC) were incorporated into the WPC matrix to prepare WPC-NCC composite film, their transmittance, mechanical properties, water vapor permeability and microstructures were investigated and compared with that of WPC films. Results illustrated that NCC as fillers in the protein network blended with WPC markedly improved the mechanical properties. The tensile strength of composite film increased from 1.3 to 3.15 MPa as NCC increased to 15% wt. of WPC. Moreover, TGase took a promoted effect on mechanical properties. The composite film achieved a maximal elongation value of 86.7% when TGase was added at 9 U/g of WPC. SDS-PAGE confirmed that TGase positively facilitated the formation of the protein polymers. FTIR analysis observed conformational changes caused by TGase in the films and implied the interaction between WPC and NCC. Results suggest NCC and TGase have a synergy effect on mechanical properties of WPC based film, and TGase-crosslinked WPC-NCC composite film can be applied as an alternative packaging material.

Clinical Outcomes Of Using Nebulized Budesonide As The Initial Treatment For Acute Exacerbations Of Chronic Obstructive Pulmonary Disease: A Post-Hoc Analysis.

Purpose: The current guidelines recommend the use of systemic corticosteroids (SCS) as the optimal treatment for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this real-world study was to evaluate whether nebulized budesonide (NBS) could also be used as an initial treatment for AECOPD. Patients and methods: AECOPD patients initially treated with NBS or SCS (oral/intravenous) were enrolled. A large-scale, long-term multicenter cohort study of AECOPD patients was performed to analyze outcomes for each treatment (NCT02051166). Results: Initial NBS and SCS treatment resulted in similar outcomes in terms of improvements in FEV1, PaO2, SaO2, and PaCO2. Disease severity affected outcome similarly in both groups. When the groups were stratified according to whether the initial treatment was subsequently intensified or reduced, more intubation was seen in the groups in which initial treatment was intensified. NBS escalation and SCS reduction groups spent more days in the hospital. The NBS escalation group was associated with the highest medical expenditure and a relatively higher rate of new-onset pneumonia. The NBS maintenance/reduction group showed the lowest mortality rate between groups. Stratification according to initial PaCO2 level showed more intubation in the groups with high initial PaCO2 concentrations. Conclusion: These results indicate that NBS may be used as an initial treatment in certain AECOPD patients, and further studies are needed to better define those most likely to benefit.

[Effects of trichostatin A and paclitaxel on apoptosis and microtubule stabilization in endometrial carcinoma cells: an in vitro research].

OBJECTIVE: To investigate the effects of trichostatin A (TSA) and paclitaxel (PTX) on the apoptosis and microtubulin stabilization in human endometrial carcinoma cells and its mechanism. METHODS: Human endometrial carcinoma cells of the line Ark2, KLE and AN3 were cultured in the presence of TSA (TSA group), or PTX (PTX group), or TSA plus PTX (TSA + PTX group) respectively. The growth curve was obtained by trypan-blue exclusion assay. Apoptosis was observed by annexin V and Hoechst staining. Perturbation of mitochondrial membrane potential (MMP) was detected by flow cytometry. Western blotting was used to detect the protein expression of caspase-9, poly ADP-ribose polymerase (PARP), and acetylated microtubulin. RESULTS: The growth of the Ark2, KLE, and AN3 cells of the TSA, PTX, and TSA + PTX group, especially in the latter group, was inhibited. The Ark2 cell apoptotic rates 4 days later of the TSA, PTX, TSA + PTX, and control group were 4.25% +/- 0.25%, 12.12% +/- 0.62%, 16.56% +/- 0.74%, and 46.78% +/- 2.68% respectively by annexin V staining, and 3.39% +/- 0.12%, 6.00% +/- 0.25%, 10.05% +/- 0.53%, and 22.30% +/- 1.25% respectively by Hoechst staining. The apoptotic rates of the TSA + PTX group by both staining methods were both significantly higher than those of the other groups (all P < 0.05). Lysis of caspase-9 and PARP in the Ark2 and KLE cells increased greatly 24 hours after the TSA and PTX treatment. The disappearance rate of MMP in the Ark2 and AN3 cells of the TSA + PTX groups were 16.80% +/- 0.92% and 11.28% +/- 0.78% respectively, significantly higher than that of the PTX group (5.34% +/- 0.45% and 5.61% +/- 0.56% respectively) and TSA group (4.96% +/- 0.47% and 6.46% +/- 0.62% respectively, all P < 0.05). The expression of acetylated microtubulin was increased in the Ark2 and KLE cells of the TSA + PTX groups. CONCLUSIONS: Synergy of TSA and PTX inhibits the cell growth and induces apoptosis. The acetylation of non-histone protein induced by histone deacetylase inhibitor is one of the possible mechanisms of its anti-cancer effects.

Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis.

The number of patients with non-human immunodeficiency virus (HIV) related pneumocystis carinii pneumonia (PCP) is increasing with widespread immunosuppressive treatment. We performed a meta-analysis to describe the clinical characteristics and factors associated with outcomes of PCP in HIV-negative patients. A total of 13 studies including 867 patients with non-HIV related PCP was included. The overall mortality for non-HIV patients with PCP was 30.6%. The most common underlying disorder for the development of PCP is hematological malignancies (29.1%), followed by autoimmune disease (20.1%), organ or bone marrow transplantation (14.0%), and solid tumors (6.0%). Risk factors associated with increased mortality rate including old age, female sex, longer time from onset of symptoms to diagnosis, respiratory failure, solid tumors, high lactate dehydrogenase, low serum albumin, bacterial, and aspergillus co-infection, etc (P < 0.05). Adjunctive corticosteroid and PCP prophylaxis was not shown to improve the outcome of PCP in non-HIV patients (P > 0.05). Our findings indicate that mortality in non-HIV patients with PCP is high. Improved knowledge about the prognostic factors may guide the early treatment.

Diagnostic MicroRNA Biomarker Discovery for Non-Small-Cell Lung Cancer Adenocarcinoma by Integrative Bioinformatics Analysis.

Lung cancer is the leading cause of cancer death and its incidence is ranked high in men and women worldwide. Non-small-cell lung cancer (NSCLC) adenocarcinoma is one of the most frequent histological subtypes of lung cancer. The aberration profile and the molecular mechanism driving its progression are the key for precision therapy of lung cancer, while the screening of biomarkers is essential to the precision early diagnosis and treatment of the cancer. In this work, we applied a bioinformatics method to analyze the dysregulated interaction network of microRNA-mRNA in NSCLC, based on both the gene expression data and the microRNA-gene regulation network. Considering the properties of the substructure and their biological functions, we identified the putative diagnostic biomarker microRNAs, some of which have been reported on the PubMed citations while the rest, that is, miR-204-5p, miR-567, miR-454-3p, miR-338-3p, and miR-139-5p, were predicted as the putative novel microRNA biomarker for the diagnosis of NSCLC adenocarcinoma. They were further validated by functional enrichment analysis of their target genes. These findings deserve further experimental validations for future clinical application.

DCLK1 is correlated with MET and ERK5 expression, and associated with prognosis in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive cancer for which more effective treatments are needed. In this study, strong to moderate staining of MET and ERK5 was detected in 67.1 and 48% of the analyzed 73 human mesothelioma tumors, and significant correlation of MET and ERK5 expression was identified (P<0.05). We evaluated the doublecortin-like kinase 1 (DCLK1) expression in human mesothelioma tumors. Our results showed that 50.7% of the immunohistochemistry analyzed human mesothelioma tumors have strong to moderate staining of DCLK1, and its expression is significantly correlated with MET or ERK5 expression (P<0.05). Also, the upregulation of DCLK1 is correlated with poor prognosis in MPM patients (P=0.0235). To investigate whether DCLK1 is downstream of MET/ERK5 signaling in human mesothelioma, the effect of DCLK1 expression was analyzed after treatments with either the MET inhibitor XL184 or the ERK5 inhibitor XMD8-92 in human mesothelioma cell lines. Our results showed that the MET inhibitor XL184 reduced the expression of phospho­ERK5 and DCLK1 expression in human mesothelioma cell lines. In addition, the ERK5 inhibitor XMD8-92 reduced the expression of phospho-ERK5 and DCLK1 expression in human mesothelioma cell lines. Furthermore, XML184 and XMD8-92 treatment impaired invasion and tumor sphere formation ability of H290 mesothelioma cells. These results suggest that DCLK1 is regulated by MET/ERK5 signaling in human mesothelioma, and the MET/ERK5/DCLK1 signaling cascade could be further developed into a promising therapeutic target against mesothelioma.

Predicting Diagnostic Gene Biomarkers for Non-Small-Cell Lung Cancer.

Lung cancer is the primary reason for death due to cancer worldwide, and non-small-cell lung cancer (NSCLC) is the most common subtype of lung cancer. Most patients die from complications of NSCLC due to poor diagnosis. In this paper, we aimed to predict gene biomarkers that may be of use for diagnosis of NSCLC by integrating differential gene expression analysis with functional association network analysis. We first constructed an NSCLC-specific functional association network by combining gene expression correlation with functional association. Then, we applied a network partition algorithm to divide the network into gene modules and identify the most NSCLC-specific gene modules based on their differential expression pattern in between normal and NSCLC samples. Finally, from these modules, we identified genes that exhibited the most impact on the expression of their functionally associated genes in between normal and NSCLC samples and predicted them as NSCLC biomarkers. Literature review of the top predicted gene biomarkers suggested that most of them were already considered critical for development of NSCLC.

FOXP3+ associated with the pro-inflammatory regulatory T and T helper 17 effector cells in asthma patients.

Asthma is a chronic bronchial inflammation that results to reversible incidence of airway obstruction and shortness of breath. Under normal circumstances, the lung immune system is maintained in a state of controlled inflammation, where balance exists between protective immunity mediated by effector cells and tolerance mediated by cells with regulatory function. Therefore, the inflammation observed in asthma patients may be caused by an imbalance between regulatory T (Treg) cells (CD4-positive with high expression of CD25 surface markers) and forkhead box P3 (FOXP3)-positive pro-inflammatory T helper 17 (Th17) cells. The aim of the present study was to evaluate whether reduced Treg cells and increased Th17 cells could be observed in the peripheral blood samples of asthma patients. As important markers of Treg cells, the expression levels of FOXP3 and interleukin (IL)-17a were analyzed via reverse trancription-quantitative polymerase chain reaction. The results indicated that the levels of cytokines that promote Th17 cells, including IL-6, IL-23 and TGF-ß, were found to increase in the bronchoalveolar lavage fluid sample of asthma patients. However, the IL-10 level in the corresponding sample was much lower compared with that in control individuals. In conclusion, these results suggest that asthma associated with a reduced proportion of Treg and Th17 cells in the blood is characterized by the expression of pro-inflammatory cytokines that may be beneficial for the continuous generation of Th17 cells.

Umeclidinium Plus Vilanterol Versus Placebo, Umeclidinium, or Vilanterol Monotherapies for Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of umeclidinium plus vilanterol as a combination therapy for chronic obstructive pulmonary disease (COPD) has not yet been clearly defined. OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy and safety of umeclidinium plus vilanterol, in contrast to either monotherapy or placebo. METHODS: Systematic searches were conducted in Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and the Chinese Biomedical Literature Database (CBM). Randomized clinical trials pertaining to the treatment of COPD with the combination of umeclidinium and vilanterol, versus umeclidinium, vilanterol or placebo, were reviewed. Studies were pooled to mean differences (MDs), with 95 % confidence intervals (CIs). RESULTS: Six studies were included in our meta-analysis. The application of umeclidinium plus vilanterol compared with umeclidinium alone showed increases in trough forced expiratory volume in 1 s [FEV1] (MD 0.05 L, 95 % CI 0.04-0.07; p < 0.00001) and forced vital capacity [FVC] (MD 0.07 L, 95 % CI 0.04-0.10; p < 0.00001). Similarly, versus vilanterol alone, the application of umeclidinium plus vilanterol showed increases in trough FEV1 (MD 0.10, 95 % CI 0.08-0.12; p < 0.00001) and FVC (MD 0.16 L, 95 % CI 0.13-0.20; p < 0.00001). Compared with placebo, umeclidinium plus vilanterol also showed increases in trough FEV1 (MD 0.21 L, 95 % CI 0.19-0.22; p < 0.00001) and FVC (MD 0.31 L, 95 % CI 0.26-0.35; p < 0.00001). In addition, umeclidinium plus vilanterol has beneficial effects on dyspnea, albuterol use, and health-related quality of life compared with the other three groups. CONCLUSIONS: Compared with the other three groups, i.e. placebo, umeclidinium and vilanterol, umeclidinium plus vilanterol improves lung function and quality of life in patients with COPD, reduces the use of albuterol, and does not increase the incidence of adverse events and serious adverse events.

Rare case of primary pleural lymphoma presenting with pleural effusion.

Primary pleural lymphoma is rare and has been described in association with human immunodeficiency virus (HIV) infection or pyothorax. We report a rare case of primary pleural lymphoma in a 73-year-old man who presented with chest pain and no history of HIV infection or pyothorax. Chest imaging showed pleural thickening and pleural effusion. Thoracoscopic pleural biopsy was performed. Histopathological and immunohistochemical examinations conformed to that of a diffuse large B-cell lymphoma. Physicians should be aware of this rare location of primary lymphoma and implement thoracoscopy as soon as possible.