Vaporization of perfluorocarbon attenuates sea-water-drowning-induced acute lung injury by deactivating the NLRP3 inflammasomes in canines.

Seawater-drowning-induced acute lung injury (SD-ALI) is a life-threatening disorder characterized by increased alveolar-capillary permeability, an excessive inflammatory response, and refractory hypoxemia. Perfluorocarbons (PFCs) are biocompatible compounds that are chemically and biologically inert and lack toxicity as oxygen carriers, which could reduce lung injury in vitro and in vivo. The aim of our study was to explore whether the vaporization of PFCs could reduce the severity of SD-ALI in canines and investigate the underlying mechanisms. Eighteen beagle dogs were randomly divided into three groups: the seawater drowning (SW), perfluorocarbon (PFC), and control groups. The dogs in the SW group were intratracheally administered seawater to establish the animal model. The dogs in the PFC group were treated with vaporized PFCs. Probe-based confocal laser endomicroscopy (pCLE) was performed at 3 h. The blood gas, volume air index (VAI), pathological changes, and wet-to-dry (W/D) lung tissue ratios were assessed. The expression of heme oxygenase-1 (HO-1), nuclear respiratory factor-1 (NRF1), and NOD-like receptor family pyrin domain containing-3 (NLRP3) inflammasomes was determined by means of quantitative real-time polymerase chain reaction (qRT-PCR) and immunological histological chemistry. The SW group showed higher lung injury scores and W/D ratios, and lower VAI compared to the control group, and treatment with PFCs could reverse the change of lung injury score, W/D ratio and VAI. PFCs deactivated NLRP3 inflammasomes and reduced the release of caspase-1, interleukin-1ß (IL-1ß), and interleukin-18 (IL-18) by enhancing the expression of HO-1 and NRF1. Our results suggest that the vaporization of PFCs could attenuate SD-ALI by deactivating NLRP3 inflammasomes via the HO-1/NRF1 pathway.

Non-invasive detection of EGFR and TP53 mutations through the combination of plasma, urine and sputum in advanced non-small cell lung cancer.

The sensitivity and utility of liquid biopsy in clinical practice requires some improvement. The aim of the present study was to improve the detection of epidermal growth factor (EGFR) and cellular tumor antigen p53 (TP53) mutations in liquid biopsies from patients with advanced non-small cell lung cancer (NSCLC) by combining plasma, sputum and urine samples under the same sequencing platform. Plasma, sputum and urine samples, and tumor tissues were obtained from 50 patients with NSCLC and were analyzed using next-generation sequencing. The sensitivity of EGFR-sensitive mutation detection was 84% in plasma, 63% in sputum, 28% in urine, and 91% when combining the three liquid samples (P<0.001). The sensitivity of TP53 mutation detection increased from 87% in plasma to 94% when the three samples were combined (P<0.001). The sensitivity of EGFR or TP53 mutations detection was higher in patients with multiple metastatic sites compared with patients ≤1 metastatic site. In addition, the progression free survival (PFS) rates obtained following analysis of the three samples independently in patients with EGFR sensitizing mutations were similar, and were 9.0 months in the tissue sample, 7.5 months in plasma, 7.9 months in the sputum and 7.3 months in urine (P=0.721). The PFS of patients with TP53 mutations was shorter compared with patients without TP53 mutations and was as follows: Tissue, 8.2 months compared with 10.2 months (P=0.412); plasma, 8.4 months compared with 10.2 months (P=0.466); sputum, 8.3 months compared with 9.1 months (P=0.904); and when combined, 8.8 months compared with 10.3 months (P=0.599). The combination of plasma, sputum and urine increased the detection of EGFR or TP53 mutation with higher sensitivity, and may improve the predictive value of personalized treatment.

Differences in the genomic profiles of cell-free DNA between plasma, sputum, urine, and tumor tissue in advanced NSCLC.

Liquid biopsy has provided an efficient way for detection of gene alterations in advanced non-small-cell lung cancer (NSCLC). However, the correlation between systematic determination of somatic genomic alterations in liquid biopsy and tumor biopsy still remained unclear, and the concordance rate between cell-free DNA (cfDNA) and matched tumor tissue DNA needs to be increased. A prospective study was performed to detect differences in genetic profiles of cfDNA in sputum, plasma, urine, and tumor tissue from 50 advanced NSCLC patients in parallel by the same next-generation sequencing (NGS) platform. Driver genes alterations were identified in cfDNA sample and matched tumor sample, with an overall concordance rate of 86% in plasma cfDNA, 74% in sputum cfDNA, 70% in urine cfDNA, and 90% in cfDNA of combination of plasma, sputum, and urine. And the concordant rate of cfDNA in sputum in patients with smoking history was higher than that in patients without history of smoking (89% vs. 66%, P = 0.033) and equal to that in plasma cfDNA of the smoking patients (89% vs. 89%). In conclusion, sputum cfDNA can be considered as an alternative medium to liquid biopsy, while the complementarity of genomic profiles in cfDNA among plasma, sputum, and urine was beneficial to detect more diver genes alterations and improve the utility of liquid biopsy in advanced NSCLC (Liquid Biopsy for Detection of Driver Mutation in NSCLC; NCT02778854).

Whole-Genome Analysis of an Extensively Drug-Resistant Acinetobacter baumannii Strain XDR-BJ83: Insights into the Mechanisms of Resistance of an ST368 Strain from a Tertiary Care Hospital in China.

Acinetobacter baumannii is an important pathogen of nosocomial infections. Nosocomial outbreaks caused by antibiotic-resistant A. baumannii remain a significant challenge. Understanding the antibiotic resistance mechanism of A. baumannii is critical for clinical treatment. The purpose of this study was to determine the whole-genome sequence (WGS) of an extensively drug-resistant (XDR) A. baumannii strain, XDR-BJ83, which was associated with a nosocomial outbreak in a tertiary care hospital of China, and to investigate the antibiotic resistance mechanism of this strain. The WGS of XDR-BJ83 was performed using single-molecule real-time sequencing. The complete genome of XDR-BJ83 consisted of a 4,011,552-bp chromosome and a 69,069-bp plasmid. The sequence type of XDR-BJ83 was ST368, which belongs to clonal complex 92 (CC92). The chromosome of XDR-BJ83 carried multiple antibiotic resistance genes, antibiotic efflux pump genes, and mobile genetic elements, including insertion sequences, transposons, integrons, and resistance islands. The plasmid of XDR-BJ83 (pBJ83) was a conjugative plasmid carrying type IV secretion system. These results indicate that the presence of multiple antibiotic resistance genes, efflux pumps, and mobile genetic elements is likely associated with resistance to various antibiotics in XDR-BJ83.

The effects of perfluorocarbon on ICAM-1 expression in LPS-induced A549 cells and the potential mechanism.

Acute lung injury (ALI)/ARDS is a critical clinical syndrome with high mortality, and the effective therapeutic methods for the treatment remain limited. Previous studies have indicated that liquid ventilation with perfluorocarbon (PFC) may be advantageous over conventional mechanical ventilation in the treatment of ALI/ARDS. Additionally, PFC inhibits the inflammatory response caused by ALI/ARDS. However, the anti-inflammatory mechanism remains to be completely elucidated. In the present study, the aim was to determine the anti­inflammatory mechanism of PFC and the association with microRNA (miR). PFC was used to modulate LPS­induced A549 cells, with the cells divided into four groups: Untreated control group; LPS group, treated with 10 µg/ml LPS; LPS+PFC group, treated with 10 µg/ml LPS and PFC; and PFC group, treated with PFC alone. The intercellular adhesion molecule­1 (ICAM­1) mRNA and protein expression levels of each group were detected by reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blotting, respectively. A549 cells were transfected with miR­17­3p mimics, miR­17­3p inhibitors or negative controls to observe the alterations in the anti­inflammatory effects of PFC. A dual luciferase reporter gene assay was used to determine whether ICAM­1 is a target gene of miR­17­3p. PFC was observed to attenuate the mRNA and protein expression levels of ICAM­1 in LPS­induced A549 cells, with no significant effect on the untreated A549 cells. miR­17­3p was demonstrated to be regulated by PFC. Transfection with miR­17­3p mimics enhanced the anti­inflammatory effects of PFC, whereas the miR­17­3p inhibitor weakened the anti­inflammatory effects of PFC at early time points. To conclude, the current study indicates that ICAM­1 was a target gene of miR­17­3p, and PFC has anti­inflammatory effects. Additionally, the present study is the first report, to the best of our knowledge, that PFC is able to attenuate ICAM-1 expression in LPS-induced A549 cells by increasing miR-17-3p expression.

Immediate and long-term results of bronchial artery embolization for hemoptysis due to benign versus malignant pulmonary diseases.

BACKGROUND: Bronchial artery embolization (BAE) is widely used for the treatment of hemoptysis. The immediate and long-term results of BAE for hemoptysis in patients with benign and malignant pulmonary diseases were inconsistent in previous studies and were thus investigated. METHODS: This was a retrospective review of the clinical records of 154 patients (108 with benign disease and 46 with malignant disease) who received BAE for hemoptysis from January 2005 to June 2011 at the Chinese People's Liberation Army General Hospital. RESULTS: Immediate cessation of hemoptysis was achieved in 98 patients with benign disease (90.7%) and 42 patients with malignancy (91.3%). The long-term control rate of hemoptysis in patients with benign disease was 74.3% (80/108) at 1 year, significantly higher than in patients with cancer (16/46, 35.5%, P < 0.01). The worst outcomes in the benign and malignant groups were observed in patients with aspergilloma and squamous cell lung cancer, respectively. The average number of abnormal vessels on bronchial arteriography was higher in the benign group than in the malignant group (3 ± 1.3 versus 2 ± 1.1, respectively, P < 0.01). Moreover, recurrent hemoptysis was independently associated with the presence of massive hemoptysis and bronchial-pulmonary artery shunt in both groups (P < 0.05). CONCLUSIONS: BAE is a relatively safe procedure for patients with hemoptysis. Immediate control of hemoptysis with BAE is achieved in most cases, but the long-term hemoptysis control rate is worse in malignant lung diseases than in benign conditions, especially among patients with squamous cell lung cancer.

Comparisons of multiple characteristics between young and old lung cancer patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Risk factors that contribute to younger patients with lung cancer are still relatively unknown. The aim of this study was to compare the clinical characteristics, histological types, stages at diagnosis, treatment modalities and survival rates between young and old patients with lung cancer.</p><p><b>METHODS</b>The study was designed as a retrospective review of all lung cancer patients admitted to the Third Affiliated Hospital of Harbin Medical University from 1998 to 2008. Survival analyses using univariate and multivariate approaches were performed to compare the survival rates between different age groups and to discover potential prognostic factors.</p><p><b>RESULTS</b>This research included 3320 patients with primary lung cancer, of whom 626 (18.8%) were 45 years old or younger at the time of diagnosis. The percentage of smokers and the male to female ratios between the young and old patient groups were 51.27% vs. 70.6% (P < 0.001) and 1.99 vs. 2.13 (P = 0.4801), respectively. The young patient group had a higher incidence of adenocarcinoma and fewer surgeries. The 1-year, 3-year and 5-year survival rates in the young patient group were generally lower than those of the old patient group, with significant differences (P = 0.0232). The clinical stage of the tumor was a prognostic factor for both non-small cell lung cancer patients (P < 0.0001) and small cell lung cancer patients (P = 0.0002). Symptoms, diagnostic method, histology, smoking, treatment modality and body mass index were shown to have significant relationships with the survival of lung cancer patients (P < 0.05).</p><p><b>CONCLUSIONS</b>Patients with lung cancer who are younger than 45 years old might have a significantly poorer prognosis than that of older patients. Symptoms, diagnosis method, histology, smoking, treatment modality and body mass index can be independent prognostic factors for lung cancer.</p>

[Gastrointestinal B-cell lymphoma: a morphologic and immunohistochemical study of 194 cases].

OBJECTIVE: To study the morphologic and immunohistochemical features of gastrointestinal B-cell lymphomas. METHODS: One hundred and ninety-four cases of gastrointestinal B-cell lymphoma were retrieved from the archival file. The clinical features and pathologic findings were reviewed. Immunohistochemical study for B-cell markers, T-cell markers, bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67 was carried out. RESULTS: The male-to-female ratio was 1.4:1. The age of patients ranged from 8 to 85 years. Amongst the 194 cases studied, 128 (66.0%) were diagnosed as diffuse large B-cell lymphoma, including 16 cases of large cell lymphoma associated with mucosa-associated lymphoid tissue (MALT) lymphoma component. There were also 40 cases (20.6%) of MALT lymphoma, 8 cases (4.1%) of follicular lymphoma, 5 cases of (2.6%) of lymphoplasmacytic lymphoma, 3 cases (1.6%) of mantle cell lymphoma, 1 case of (0.5%) of B-lymphoblastic lymphoma and 9 cases (4.6%) of indefinite type (including 5 biopsy cases). The site of involvement included stomach (100 cases, 51.5%), small intestine (43 cases, 22.2%), ileocecal junction (26 cases, 13.4%), appendix (1 case, 0.5%), colon (21 cases, 10.8%) and rectum (3 cases, 1.6%). Amongst the 163 cases which had undergone surgical resection, 20 cases (12.3%) cases had invasion down to the mucosa, 20 cases (12.3%) down to the superficial muscular layer, 19 cases (11.6%) down to the deep muscular layer and 104 cases (63.8%) with full-thickness involvement. Histologic examination showed lymphoepithelial lesions in 52 cases, residual lymphoid follicles in 29 cases, coagulative necrosis in 66 cases and nodular growth pattern in 30 cases. The lymphoma cells in all cases were immunoreactive for B-cell marker CD20. There was also various degrees of positivity for bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67. CONCLUSIONS: Gastrointestinal B-cell lymphomas can be subdivided into two main groups: large B-cell lymphomas and small B-cell lymphomas. The latter group often poses diagnostic pitfalls. Accurate pathologic typing requires correlation with histologic and immunohistochemical findings.

Enhancement of HER-2 degradation by carbamazepine in breast cancer SKBR-3 cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the anti-tumor effect and the mechanism of down-regulation of HER - 2 by cabamazepine in SKBR - 3 cells , a breast cancer cell line with HER - 2 over - expression.</p><p><b>METHODS</b>Western blotting was performed to evaluate the Her-2 expression level. The mRNA level of HER-2 was detected by RT-PCR. Immunoprecipitation was applied to detect the chaperon function and acetylation level of HSP90. The viability of cells was tested by MTT assay.</p><p><b>RESULTS</b>Cabamazepine treatment down-regulated HER-2 expression. Only HER-2 protein level decrease was observed with 10 micromol/L cabamazepine treatment, but both protein and mRNA expressions were inhibited by 100 micromol/L cabamazepine. Cabamazepine treatment could induce a higher acetylation level of HSP90 and destroy its chaperon function. Cabamazepine exerted synergism with Herceptin in promoting HER-2 protein degradation and synergism or potentiation with Herceptin or 17-AAG in inhibition of proliferation.</p><p><b>CONCLUSION</b>Cabamazepine can reduce the expression of HER-2 and show a synergistic effect with Herceptin or 17-AAG. There may be potential benefits of carbamazepine for cancer therapy in future. HER-2;</p>