MMP12 is a Potential Predictive and Prognostic Biomarker of Various Cancers Including Lung Adenocarcinoma.

OBJECTIVE: This study sought to explore the clinical value of matrix metalloproteinases 12 (MMP12) in multiple cancers, including lung adenocarcinoma (LUAD). METHODS: Using >10,000 samples, this retrospective study demonstrated the first pan-cancer analysis of MMP12. The expression of MMP12 between cancer groups and their control groups was analyzed using Wilcoxon rank-sum tests. The clinical significance of MMP12 expression in multiple cancers was assessed using receiver operating characteristic curves, Kaplan-Meier curves, and univariate Cox analysis. A further LUAD-related analysis based on 4565 multi-center and in-house samples was performed to verify the findings regarding MMP12 in pan-cancer analysis partly. RESULTS: MMP12 mRNA is highly expressed in 13 cancers compared to their controls, and the MMP12 protein level is elevated in some of these cancers (e.g., colon adenocarcinoma) (P < .05). MMP12 expression makes it feasible to distinguish 21 cancer tissues from normal tissues (AUC = 0.86). A high MMP12 expression is a prognosis risk factor in eight cancers, such as adrenocortical carcinoma (hazard ratio >1, P < .05). The elevated MMP12 expression is also a prognosis protective factor in breast-invasive carcinoma and colon adenocarcinoma (hazard ratio <1, P < .05). Some pan-cancer findings regarding MMP12 are verified in LUAD-MMP12 expression is upregulated in LUAD at both the mRNA and protein levels (P < .05), has the potential to distinguish LUAD with considerable accuracy (AUC = .91), and plays a risk prognosis factor for patients with the disease (P < .05). CONCLUSIONS: MMP12 is highly expressed in most cancers and may serve as a novel biomarker for the prediction and prognosis of numerous cancers.

Hsa_circ_0096157 silencing suppresses autophagy and reduces cisplatin resistance in non-small cell lung cancer by weakening the Nrf2/ARE signaling pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of cancer morbidity and mortality worldwide, and new diagnostic markers are urgently needed. We aimed to investigate the mechanism by which hsa_circ_0096157 regulates autophagy and cisplatin (DDP) resistance in NSCLC. METHODS: A549 cells were treated with DDP (0 µg/mL or 3 µg/mL). Then, the autophagy activator rapamycin (200 nm) was applied to the A549/DDP cells. Moreover, hsa_circ_0096157 and Nrf2 were knocked down, and Nrf2 was overexpressed in A549/DDP cells. The expression of Hsa_circ_0096157, the Nrf2/ARE pathway-related factors Nrf2, HO-1, and NQO1, and the autophagy-related factors LC3, Beclin-1, and p62 was evaluated by qRT‒PCR or western blotting. Autophagosomes were detected through TEM. An MTS assay was utilized to measure cell proliferation. The associated miRNA levels were also tested by qRT‒PCR. RESULTS: DDP (3 µg/mL) promoted hsa_circ_0096157, LC3 II/I, and Beclin-1 expression and decreased p62 expression. Knocking down hsa_circ_0096157 resulted in the downregulation of LC3 II/I and Beclin-1 expression, upregulation of p62 expression, and decreased proliferation. Rapamycin reversed the effect of interfering with hsa_circ_0096157. Keap1 expression was lower, and Nrf2, HO-1, and NQO1 expression was greater in the A549/DDP group than in the A549 group. HO-1 expression was repressed after Nrf2 interference. In addition, activation of the Nrf2/ARE pathway promoted autophagy in A549/DDP cells. Moreover, hsa_circ_0096157 activated the Nrf2/ARE pathway. The silencing of hsa_circ_0096157 reduced Nrf2 expression by releasing miR-142-5p or miR-548n. Finally, we found that hsa_circ_0096157 promoted A549/DDP cell autophagy by activating the Nrf2/ARE pathway. CONCLUSION: Knockdown of hsa_circ_0096157 inhibits autophagy and DDP resistance in NSCLC cells by downregulating the Nrf2/ARE signaling pathway.

Clinical significance and potential pathogenesis of VCAN in adult non-cystic fibrosis bronchiectasis: a retrospective study.

BACKGROUND: The pathogenesis of adult non-cystic fibrosis (CF) bronchiectasis is complex, and the relevant molecular mechanism remains ambiguous. Versican (VCAN) is a key factor in inflammation through interactions with adhesion molecules. This study constructs a stable panoramic map of mRNA, reveals the possible pathogenesis of bronchiectasis, and provides new ideas and methods for bronchiectasis. METHODS: Peripheral blood and tissue gene expression data from patients with bronchiectasis and normal control were selected by bioinformatics analysis. The expression of VCAN in peripheral blood and bronchial tissues of bronchiectasis were obtained by transcriptome sequencing. The protein expression levels of VCAN in serums were verified by the enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of VCAN in co-culture of Pseudomonas aeruginosa and bronchial epithelial cells were verified by real-time quantitative polymerase chain reaction (RT-qPCR). In addition, the biological function of VCAN was detected by the transwell assay. RESULTS: The expression of VCAN was upregulated in the bronchiectasis group by sequencing analysis (P < 0.001). The expression of VCAN in the bronchial epithelial cell line BEAS-2B was increased in P. aeruginosa (P.a), which was co-cultured with BEAS-2B cells (P < 0.05). The concentration of VCAN protein in the serum of patients with bronchiectasis was higher than that in the normal control group (P < 0.05). Transwell experiments showed that exogenous VCAN protein induced the migration of neutrophils (P < 0.0001). CONCLUSIONS: Our findings indicate that VCAN may be involved in the development of bronchiectasis by increasing the migration of neutrophils and play an important role in bronchial pathogenesis.

CEP55: an immune-related predictive and prognostic molecular biomarker for multiple cancers.

BACKGROUND: Centrosomal protein 55 (CEP55) plays a significant role in specific cancers. However, comprehensive research on CEP55 is lacking in pan-cancer. METHODS: In-house and multi-center samples (n = 15,823) were used to analyze CEP55 in 33 cancers. The variance of CEP55 expression levels among tumor and control groups was evaluated by the Wilcoxon rank-sum test and standardized mean difference (SMD). The clinical value of CEP55 in cancers was assessed using receiver operating characteristic (ROC) curves, Cox regression analysis, and Kaplan-Meier curves. The correlations between CEP55 expression and the immune microenvironment were explored using Spearman's correlation coefficient. RESULTS: The data of clustered regularly interspaced short palindromic repeats confirmed that CEP55 was essential for the survival of cancer cells in multiple cancer types. Elevated CEP55 mRNA expression was observed in 20 cancers, including glioblastoma multiforme (p < 0.05). CEP55 mRNA expression made it feasible to distinguish 21 cancer types between cancer specimens and their control samples (AUC = 0.97), indicating the potential of CEP55 for predicting cancer status. Overexpression of CEP55 was correlated with the prognosis of cancer individuals for 18 cancer types, exhibiting its prognostic value. CEP55 expression was relevant to tumor mutation burden, microsatellite instability, neoantigen counts, and the immune microenvironment in various cancers (p < 0.05). The expression level and clinical relevance of CEP55 in cancers were verified in lung squamous cell carcinoma using in-house and multi-center samples (SMD = 4.07; AUC > 0.95; p < 0.05). CONCLUSION: CEP55 may be an immune-related predictive and prognostic marker for multiple cancers, including lung squamous cell carcinoma.

Combination effects of baicalin with linezolid against Staphylococcus aureus biofilm-related infections: in vivo animal model.

Staphylococcus aureus is a gram-positive bacterium that can produce biofilm, and biofilm-associated infections are difficult to control. Biofilm prevents antibiotics from penetrating and killing the bacteria. Combined use of antimicrobials is a common strategy to treat S. aureus biofilm-related infections. In this in vivo study, the clinically isolated strain of S. aureus 17546 (t037) was selected to establish a biofilm-associated infection rat model, and baicalin and linezolid were used to treat the infection. CFU counting was used to determine the bacteria within the biofilm, the biofilm structure was viewed using scanning electron microscopy (SEM), histopathology was performed, and inflammatory factors were analyzed by ELISA. Baicalin was efficient in destroying the biofilm and exerted a synergistic bactericidal effect when combined with linezolid. Based on these findings, baicalin combined with linezolid may be efficacious in controlling S. aureus biofilm-related infections.

Epidermal growth factor receptor mutation p.A864V in small cell lung cancer and lung squamous cell carcinoma: a case report and review of literature.

Mutations in the epidermal growth factor receptor ( EGFR ) have been identified in 10-20% of nonsmall cell lung cancer (NSCLC), specifically lung adenocarcinomas. However, these mutations have rarely been reported in small cell lung cancer (SCLC) and lung squamous cell carcinoma (LUSC). Treatment for SCLC and LUSC patients has not yet been established. We present a rare case of p.A864V mutation in Exon 21 of EGFR gene in a patient with both SCLC and LUSC, which is the first case of such mutation type in lung cancer in the world. The patient was a 55-year-old female nonsmoker with stage IV SCLC and LUSC, gene sequencing revealed EGFR gene mutation, she refused EGFR tyrosine kinase inhibitors (TKIs) targeted therapy and received conservative treatment, which led to disease progression. In conclusion, clinicians should be aware of the possibility of the rare EGFR mutations. Platinum-based chemotherapy can be treated for SCLC and LUSC patients.

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma.

BACKGROUND: The role of HOXA family genes in the occurrence and progression of a variety of human cancers has been scatteredly reported. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD. METHODS: In-house immunohistochemistry (IHC), multi-center microarrays, RT-qPCR and RNA-seq data were incorporated for comprehensively evaluating the expression and prognostic value of HOXA4 and HOXA5 in LUAD. The mechanism of HOXA4 and HOXA5 in the formation and development of LUAD was analyzed from multiple aspects of immune correlations, upstream transcriptional regulation, functional states of single cells and co-expressed gene network. The functional roles of HOXA4 and HOXA5 in LUAD were validated by in vitro experiments. RESULTS: As a result, in 3201 LUAD samples and 2494 non-cancer lung samples, HOXA4 and HOXA5 were significantly downexpressed (P < 0.05). The aberrant expression of HOXA5 was significantly correlated with the clinical progression of LUAD (P < 0.05). HOXA5 showed remarkable prognostic value for LUAD patients (P < 0.05). The expression of HOXA4 and HOXA5 in LUAD were negatively correlated with tumor purity and positively correlated with the infiltration of various immune cells such as B cells, T cells and macrophages. HOXA4 and HOXA5 overexpression had notable inhibitory effect on the proliferation, migration and invasion of LUAD cells. CONCLUSIONS: In conclusion, the identified downexpressed HOXA4 and HOXA5 had significant distinguishing ability for LUAD samples and affected the cellular functions of LUAD cells. The low expression of HOXA5 indicated worse overall survival of LUAD patients. Therefore, the two HOXA family genes especially HOXA5 may serve as potential biomarkers for LUAD.

Clinical significance of cyclin-dependent kinase inhibitor 2C expression in cancers: from small cell lung carcinoma to pan-cancers.

BACKGROUND: Cyclin-dependent kinase inhibitor 2C (CDKN2C) was identified to participate in the occurrence and development of multiple cancers; however, its roles in small cell lung carcinoma (SCLC) remain unclear. METHODS: Differential expression analysis of CDKN2C between SCLC and non-SCLC were performed based on 937 samples from multiple centers. The prognosis effects of CDKN2C in patients with SCLC were detected using both Kaplan-Meier curves and log-rank tests. Using receiver-operating characteristic curves, whether CDKN2C expression made it feasible to distinguish SCLC was determined. The potential mechanisms of CDKN2C in SCLC were investigated by gene ontology terms and signaling pathways (Kyoto Encyclopedia of Genes and Genomes). Based on 10,080 samples, a pan-cancer analysis was also performed to determine the roles of CDKN2C in multiple cancers. RESULTS: For the first time, upregulated CDKN2C expression was detected in SCLC samples at both the mRNA and protein levels (p of Wilcoxon rank-sum test < 0.05; standardized mean difference = 2.86 [95% CI 2.20-3.52]). Transcription factor FOXA1 expression may positively regulate CDKN2C expression levels in SCLC. High CDKN2C expression levels were related to the poor prognosis of patients with SCLC (hazard ratio > 1, p < 0.05) and showed pronounced effects for distinguishing SCLC from non-SCLC (sensitivity, specificity, and area under the curve ≥ 0.95). CDKN2C expression may play a role in the development of SCLC by affecting the cell cycle. Furthermore, the first pan-cancer analysis revealed the differential expression of CDKN2C in 16 cancers (breast invasive carcinoma, etc.) and its independent prognostic significance in nine cancers (e.g., adrenocortical carcinoma). CDKN2C expression was related to the immune microenvironment, suggesting its potential usefulness as a prognostic marker in immunotherapy. CONCLUSIONS: This study identified upregulated CDKN2C expression and its clinical significance in SCLC and other multiple cancers, suggesting its potential usefulness as a biomarker in treating and differentiating cancers.

The clinical significance of integrin subunit alpha V in cancers: from small cell lung carcinoma to pan-cancer.

BACKGROUND: Little is known about the relationship between integrin subunit alpha V (ITGAV) and cancers, including small cell lung cancer (SCLC). METHODS: Using large sample size from multiple sources, the clinical roles of ITGAV expression in SCLC were explored using differential expression analysis, receiver operating characteristic curves, Kaplan-Meier curves, etc. RESULTS: Decreased mRNA (SMD = - 1.05) and increased protein levels of ITGAV were detected in SCLC (n = 865). Transcription factors-ZEB2, IK2F1, and EGR2-may regulate ITGAV expression in SCLC, as they had ChIP-Seq (chromatin immunoprecipitation followed by sequencing) peaks upstream of the transcription start site of ITGAV. ITGAV expression made it feasible to distinguish SCLC from non-SCLC (AUC = 0.88, sensitivity = 0.78, specificity = 0.84), and represented a risk role in the prognosis of SCLC (p < 0.05). ITGAV may play a role in cancers by influencing several immunity-related signaling pathways and immune cells. Further, the extensive pan-cancer analysis verified the differential expression of ITGAV and its clinical significance in multiple cancers. CONCLUSION: ITGAV served as a potential marker for prognosis and identification of cancers including SCLC.

Differential Proteomic and Genomic Comparison of Resistance Mechanism of Pseudomonas aeruginosa to Cefoperazone Sodium/Sulbactam Sodium.

The aim of this study was to determine the resistance mechanism of Pseudomonas aeruginosa to cefoperazone sodium/sulbactam sodium. We retrospectively analyzed the drug resistance of P.a isolated at the First Affiliated Hospital of Guangxi Medical University. Drug-resistant P.a strains were constructed, then wild-type (WT) and drug-resistant (DR) strains were compared using protein and gene microarrays to determine differences between DR and WT strains. The resistance rates of P. aeruginosa during 2013, 2014 and 2015 were 21.2%, 21.4%, and 24.6% respectively. Among 242 protein peaks of WT and DR bacteriophage proteins, 41 were differentially expressed between the two groups. The expression of 26 and 15 proteins were respectively upregulated and downregulated in the DR compared with the WT group. Gene microarray results revealed 679 mutant loci in the DR group, of which 42 with the top 50 Q values were found in the NCBI database. The rate of P.a resistance to cefoperazone sodium/sulbactam sodium remained high between 2013 and 2015. The numbers of different proteins and genetic variations in the DR strains suggested that the resistance mechanism of P.a to cefoperazone sodium/sulbactam sodium involves multiple genes and proteins that might be key to controlling P.a resistance to cefoperazone sodium/sulbactam sodium.

Antibacterial synergy between linezolid and baicalein against methicillin-resistant Staphylococcus aureus biofilm in vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) can form biofilms, which prevents the penetration of antibiotics, decreasing their efficacy. This study investigated whether baicalein has synergistic antibacterial effects with linezolid in vivo. We cultivated MRSA 17546 biofilms on silicone implants and inserted them into the air pouches of rat models. The rats were treated with linezolid, baicalein, or a combination therapy for three consecutive days. All treatments reduced the number of colony-forming units (CFU) in the biofilms compared to the control (p < 0.05). However, by day two, the CFU counts were significantly lower in the combination group than in the individual treatment groups (p < 0.05). Histological analysis of the air pouches showed that the severity of the inflammatory cell infiltration was severe in the combination therapy group. In the combination group, the biofilm structure on the implant's surface was sparse and more free colonies could be seen by scanning electron microscopy (SEM); by day three, no obvious biofilm was observed. The serum levels of Staphylococcus enterotoxin A (SEA), C-reactive protein (CRP), and procalcitonin (PCT) were the lowest in the group where rats were treated with the combination of baicalein and linezolid (p < 0.05) compared to other groups. The results suggest that baicalein may inhibit the accessory gene regulator system, reducing the expression of SEA, thus lowering CRP and PCT levels. Furthermore, the inhibitory effect was more pronounced when baicalein was combined with linezolid. These results provide an important basis for the development of a new combination regimen to treat patients with biofilm-associated MRSA infections.

Circular RNA hsa_circ_0096157 contributes to cisplatin resistance by proliferation, cell cycle progression, and suppressing apoptosis of non-small-cell lung carcinoma cells.

Circular RNAs (circRNAs) play a major role in cancer development and chemotherapy resistance. This study aimed to characterize circRNA profiles associated with Cisplatin (diamminedichloroplatinum, DDP) resistance of non-small-cell lung carcinoma (NSCLC) cells. The half-maximal inhibitory concentration (IC50) of A549 and A549/DDP cells was determined using CCK-8 assay. Further, circRNA profiles and differentially expressed genes in A549 and A549/DDP cells were characterized by deep sequencing and cell proliferation was measured using MTS assay. Cell cycle progression was analyzed using flow cytometry. Apoptosis experiment was performed by TUNEL assay and flow cytometry. Cell migration and invasion were assessed using the Transwell system. Finally, signalling protein levels related to cell cycle progression and migration were measured by western blot. CCK-8 assay showed that A549/DDP cells obtained strong DDP resistance. Further deep sequencing results showed that 689 circRNAs and 87 circRNAs were significantly upregulated and downregulated in A549/DDP cells compared to A549 cells, respectively. Moreover, the circRNA hsa_circ_0096157 with the highest expression level in A549/DPP cells was further analyzed for its potential mechanism of DDP resistance in A549/DDP. With or without DDP treatment, hsa_circ_0096157 knockdown inhibited proliferation, migration, invasion and cell cycle progression but promoted apoptosis of A549/DDP cells. In addition, the western blot results also showed that hsa_circ_0096157 knockdown in A549/DDP cells increased P21 and E-cadherin but decreased CDK4, Cyclin D1, Bcl-2, N-cadherin, and Vimentin protein expression levels, indicating that cell cycle progression might be inhibited by increased P21 protein level to inhibit the expression of CDK4-cyclin D1 complex and decreased Bcl-2 protein level; and migration and invasion were suppressed by the increased E-cadherin and decreased N-cadherin and Vimentin expression levels. In contrast, hsa_circ_0096157 overexpression in A549 cells caused the opposite cellular and molecular alterations. DDP resistance in NSCLC cells was associated with significant circRNA profile alterations. Moreover, increased hsa_circ_0096157 expression contributed to DDP resistance in NSCLC cells by promoting cell proliferation, migration, invasion and cell cycle progression and inhibiting apoptosis.

The miRNA-149-5p/MyD88 axis is responsible for ursolic acid-mediated attenuation of the stemness and chemoresistance of non-small cell lung cancer cells.

Although the inhibitory roles of ursolic acid (UA) have been established in various tumors, its effects on the stemness of non-small cell lung cancer (NSCLC) cells are still unclear. Here, we constructed NSCLC cells with paclitaxel resistance (A549-PR) and showed that A549-PR exhibited a remarkably stronger stemness than the parental A549 cells, which is evident by the increase of spheroid formation capacity, stemness marker expression, and ALDH1 activity. Additionally, UA significantly reduced the stemness and paclitaxel resistance of A549-PR cells. Mechanistic investigations revealed that UA inhibited the miR-149-5p/MyD88 signaling, which is responsible for UA-mediated effects on the stemness of A549-PR cells. Notably, miR-149-5p/MyD88 axis promoted the stemness of A549 cells, while inhibition of this axis attenuated the stemness of A549-PR cells. Therefore, these results suggest that UA could attenuate the stemness and chemoresistance of NSCLC cells through targeting miR-149-5p/MyD88 axis.

Septic pulmonary embolism in China: clinical features and analysis of prognostic factors for mortality in 98 cases.

BACKGROUND: To investigate the clinical features of septic pulmonary embolism (SPE) cases and prognostic factors for in-hospital mortality in China. METHODS: A retrospective analysis was conducted of SPE patients hospitalized between January 2007 and June 2018 in the Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University. RESULTS: A total of 98 patients with SPE were identified. All patients had bilateral multiple peripheral nodules on chest computed tomography. The most common pathogen found in blood culture was Staphylococcus aureus (10/33, 30.3%). Transthoracic echocardiography was performed in 39 patients and 20 showed vegetations. Bronchoscopy was performed in 24 patients. Bronchoalveolar lavage fluid (BALF) was obtained from 15 patients (62.5%) and showed predominantly polymorphonuclear cell infiltration (52%, range of 48%~ 63%). Four patients received transbronchial lung biopsy, and histopathological examinations revealed suppurative pneumonia and organizing pneumonia. The in-hospital mortality rate was 19.4%. Age (odds ratio [OR] 1.100; 95% confidence interval [CI] 1.035-1.169), hypotension (OR 7.260; 95% CI 1.126-46.804) and ineffective or delay of empirical antimicrobial therapy (OR 7.341; 95% CI 1.145-47.045) were found to be independent risk factors for in-hospital mortality, whereas drainage treatment was found to be a protective factor (OR 0.33; 95% CI 0.002-0.677). CONCLUSIONS: SPE cases presented with nonspecific clinical manifestations and radiologic features. Blood cultures and bronchoscopy are important measures for early diagnosis and differential diagnosis. There is relationship between primary infection sites and the type of pathogen. Maintaining normal blood pressure and providing timely and appropriate initial antimicrobial therapy for effective control of the infection could improve prognosis.

A Preliminary Study of Microbiota Diversity in Saliva and Bronchoalveolar Lavage Fluid from Patients with Primary Bronchogenic Carcinoma.

BACKGROUND The present study aimed to evaluate the difference in microbiota diversity in the oral cavity and fluid bronchoalveolar lavage (BALF) of patients with lung cancer. MATERIAL AND METHODS Buccal (saliva) and lower respiratory tract BALF samples were collected from 51 patients with primary bronchogenic carcinoma and 15 healthy controls, and bacterial genomic DNA was extracted. High-throughput 16S rDNA amplicon sequencing was performed, and microbial diversity, composition, and functions of microbiota were analyzed by bioinformatics methods. RESULTS Patients with lung cancer have lower microbial diversity than healthy controls in both saliva and BALF samples. Significant segregation was observed between the different pathological types of lung cancer groups and the control group regardless of the sampling site. Treponema and Filifactor were identified as potential bacterial biomarkers in BALF samples, while Filifactor was ideal to distinguish healthy controls from lung cancer patients. Moreover, the predictive variation analysis of the KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic pathway showed that the metabolic differences in microbiota varied by sampling site. CONCLUSIONS Lung cancer patients carry a different and less diverse microorganism community than healthy controls. Certain bacterial taxa might be associated with lung cancer, but the exact species depends on the sampling site and the pathological type. This study provides basic data on the microbiota diversity in BALF and saliva samples from lung cancer patients. Further investigation with a larger sample size should help validate the enriched species in different pathological types of lung cancers.

Generation of Methicillin-Resistant Staphylococcus Aureus Biofilm Infection in an Immunosuppressed Rat Model.

BACKGROUND Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen responsible for many related infections, and immunosuppressed individuals are more susceptible. Its pathogenicity is associated with its virulence factors, resistance to antibiotics, and ability to form biofilm (BF). MRSA-BF infections in immunosuppressed patients pose great difficulties to clinical treatment. MATERIAL AND METHODS The study aimed to establish a model of MRSA-BF infection in rats with cyclophosphamide (CTX)-induced immunosuppression. For this, rats were administered CTX on days 1 and 4. White blood cells (WBC) were counted, then rats were inoculated with a clinical MRSA 17546 (t037) on day 5. Rats were sacrificed on days 6-10 and tissue samples were examined by scanning electron microscopy. RESULTS Using the dose of CTX: 150 (mg/kg) + 100 (mg/kg) is better than the other 2 programs as the survival rates of the immunocompromised rats were higher than in the other 2 immunosuppressive groups. The survival rate was not different between rats in the clean environment and in the SPF environment. However, the survival rate was affected by the sample acquisitions. Importantly, WBC counts started to decline on day 4, and then started to rise on day 9. Moreover, MRSA-BFs were formed earlier in immunosuppressed rats compared to the normal rats, as shown by scanning electron microscopy. CONCLUSIONS The study successfully established an immunosuppressed rat model of MRSA-BF infection, which provides methodological and data support for establishment of such animal models and is useful reference for related research. Our results may help further investigation of MRSA-BF infection.

Lack of efficacy of nebulized magnesium sulfate in treating adult asthma: A meta-analysis of randomized controlled trials.

BACKGROUND: Nebulized magnesium sulfate (MgSO4) has been used to treat asthma, but the efficacy remains controversial. We aimed to comprehensively review the efficacy of nebulized MgSO4 in treating adult patients with asthma. METHODS: PubMed, Embase, and Cochrane Library were searched for relevant studies published up to July 18, 2016. Randomized controlled trials (RCTs) were included if adult patients with acute or stable asthma had been treated with nebulized MgSO4 compared with placebo or another bronchodilator. Standardized mean differences (SMDs), relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Outcomes included pulmonary function, hospital admission and adverse events. RESULTS: A total of 1386 patients from sixteen trials (1240 acute asthma patients and 146 stable asthma patients) were subjected to meta-analysis. Compared to placebo as normal saline, whether using in acute or stable adult asthma, nebulized MgSO4 did not significantly improve the respiratory function: SMD 0.39 (95% CI -0.03-0.82, P = 0.07), and 1.48 (95% CI -0.14-3.11, P = 0.07), respectively. Furthermore, nebulized MgSO4 did not reduce hospital admission in adult patients with acute asthma (RR, 0.72; 95% CI, 0.52-1.00; P = 0.05), although it was not associated with increased adverse events (RR 1.15; 95% CI, 0.88-1.52; P = 0.31). CONCLUSIONS: Evidence to date suggests that nebulized MgSO4 has no role in the management of adult patients with acute or stable asthma.

Pathogenic Effects of Biofilm on Pseudomonas Aeruginosa Pulmonary Infection and Its Relationship to Cytokines.

BACKGROUND An animal (Sprague-Dawley rat) model of Pseudomonas aeruginosa biofilm associated with chronic pulmonary infection in vivo was established and the effects of the biofilm on P. aeruginosa and its relationship to cytokines were investigated. MATERIAL AND METHODS Biofilm of P. aeruginosa in alginate beads and planktonic PA0725 were purified by anion-exchange chromatograph. Sprague-Dawley (SD) rats were immunized with the biofilm and then inhaled the same strain of P. aeruginosa. Anti-biofilm antibody titer was detected using the enzyme linked immunosorbent assay (ELISA) method. The cell count and differential count in the bronchoalveolar lavage fluid (BALF) were measured. The levels of cytokines (IL-17, IL-1ß, MIP-2, and G-CSF) and tumor necrosis factor (TNF)-α in sera were also measured using an ELISA kit. RESULTS The sera anti-biofilm IgG antibody titer of immunized SD rats was increased significantly on the 5th and 8th days after inhalation. The IL-17 concentration was significantly higher on the 8th day after inhalation. The results indicated that when biofilm-pre-immunized rats were challenged with inhalation of PA0725 of P. aeruginosa, the biofilm acted as an antigen substance and mediated the antibody reaction of the antigen, which might cause serious airway inflammatory response and lung tissue injury. This effect may be related to IL-17. CONCLUSIONS P. aeruginosa biofilm protected the bacterium from antibiotics and might induce host immune damage in lung tissue and facilitate bacterium evading the host barrier.

HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2.

The proinflammatory factor high mobility group box protein 1 (HMGB1) has been implicated as an important mediator of many chronic inflammatory diseases, including asthma. Human bronchial epithelial cells (HBECs) play a central role in the pathogenesis of asthma. However, the effects of HMGB1 on HBECs and the underlying mechanisms remain unknown. Here, we investigated receptor expression and proinflammatory cytokine production by primary cultures of HBECs stimulated by HMGB1. We then examined the effects of specific receptor blockade and inhibition of p38 MAPK, ERK1/2, or PI3-K on HMGB1-induced expression of proinflammatory cytokines. HMGB1 increased the expression and secretion of TNF-α, TSLP, MMP-9, and VEGF in a dose- and time-dependent manner. HMGB1 also induced elevated expression of RAGE protein. Secretion of TNF-α, VEGF, MMP-9, and TSLP was significantly decreased by RAGE blockade and p38 MAPK pathway inhibition, while a less pronounced effect was mediated by ERK1/2 inhibition. These observations suggest that HMGB1 binds RAGE and promotes activities of p38 MAPK and ERK1/2 pathways in HBECs. This then enhances the expression of TNF-α, VEGF, MMP-9, and TSLP, which are the important inflammatory factors in asthma. These results demonstrate that HMGB1 enhances the inflammatory responses of HBECs, which are involved in the modulation of inflammatory processes in asthma.

[A clinical analysis of twenty-five cases of eosinophilic lung disease].

OBJECTIVE: To improve the diagnosis and treatment of eosinophilic lung disease. METHODS: Patients who were diagnosed with eosinophilic lung disease and hospitalized in the First Affiliated Hospital of Guangxi Medical University Hospital were retrospectively analyzed from January 2004 to August 2012. Data of etiology, clinical manifestation, imaging and pathological features, diagnosis and treatment were recorded. RESULTS: A total of 25 patients were diagnosed with eosinophilic lung disease including 9 chronic eosinophilic pneumonia, 6 churg-strauss syndrome, and 10 cases of parasitic infection of which two patients were the simple pulmonary eosinophilia (Löffler syndrome). Eosinophil counts in peripheral blood and bronchoalveolar lavage fluid (BALF) were increased. Arterial gas analysis showed varying degree of hypoxemia, which pulmonary function tests showed restrictive, obstructive, mixed ventilatory dysfunction. Chest CT showed bilateral flaky, streak or flake diffuse ground-glass infiltrates and reticular opacities. Results of pulmonary biopsy or skin biopsy identified diffuse eosinophil infiltration. Corticoidsteroid therapy alone or combined with immunosuppressive agents were both effective. CONCLUSION: (1) Liver fluke and other food-borne parasites are the most common causes in eosinophilic lung disease; followed by unexplained chronic acidophilic granulocyte pneumonia; (2) In addition to histopathological evidence, the diagnosis of eosinophilic lung disease was made comprehensively based on clinical features, laboratory test, the BALF analysis, and imaging data.