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This study explored the early predictive value of volume and mean CT density of necrosis for adverse outcomes in patients with acute necrotising pancreatitis (ANP). A total of 155 patients with ANP who underwent CECT within 7 days of symptom onset were included. The necrosis volume, mean CT density, and modified CT severity index (mCTSI) were calculated. C-reactive protein (CRP) and blood urea nitrogen (BUN) levels both 48 h after symptom onset were reviewed. Adverse outcomes were recorded. The predictive value of each indicator was assessed using ROC curve analysis. There were significant associations between necrosis volume and mean CT density and organ failure (OF), persistent OF (POF), and need for intervention (p < 0.001 for all). For predicting OF, the area under the curve (AUC) was significantly higher for necrosis volume than for mCTSI and BUN (AUC: 0.84 vs 0.67, p = 0.0011; 0.84 vs 0.71, p = 0.0193, respectively). For predicting POF and need for intervention, the AUCs for necrosis volume were significantly higher than those for mCTSI (AUC: 0.79 vs 0.66, p = 0.0045; 0.77 vs 0.61, p = 0.0019, respectively), but did not significantly differ from those for CRP and BUN. For predicting OF, a significantly better predictive value was achieved with mean CT density than with mCTSI (AUC: 0.79 vs 0.67, p = 0.0163). There were no significant differences in predictive value between mean CT density, CRP, and BUN. The volume and mean CT density of necrosis based on CECT can provide early prediction of OF, POF, and need for intervention. • Compared to mCTSI, necrosis volume might be used to more accurately diagnose organ failure and persistent organ failure and might be better associated with the need for intervention. • Necrosis volume and mean CT density based on CECT are reliable quantitative predictors for organ failure, persistent organ failure, and intervention in acute pancreatitis.

Metagenomic next-generation sequencing (mNGS) exerts a vital part in accurately diagnosing pulmonary infection. However, the diagnostic value of different samples obtained by virtual bronchoscopic navigation (VBN) combined with mNGS for pathogen detection in infections located in the peripheral lung field (PLF) is still unclear.Patients infected from July 2018 to February of the following year were carefully analyzed and divided into two parts, namely, non-infectious disease group and the infectious disease group. Then bronchial expansion tests were performed for each subject, collected liquid specimens and tissue standards, and conducted regular mNGS and microbiological detection and analysis. The value of mNGS and culture in pathogen detection was compared, at the same time, the performance of tissue mNGS and bronchoalveolar lavage fluid (BALF) mNGS in the diagnosis process was compared. When discrete variables were processed, Pearson χ2 and Fisher's exact test could be used to perform categorical variables analysis. Continuous variables were analyzed and compared by Mann-Whitney U test.After mNGS diagnosis, Acinetobacter baumannii, Pseudomonas aeruginosa and Rothia mucilaginosa were the bacterial species showing the highest abundances. In addition, mNGS achieved the sensitivities in the detection of pathogens in tissues and BALF of 72.9% and 81.4%, respectively, and it is higher than conventional culture. Bacterial diagnostic sensitivity was significantly different between BALF and tissue using mNGS (95.0% vs. 62.5%, P=0.03). The sensitivity and specificity of BALF in detecting fungal infections were not significantly different from those of mNGS. A consistency test showed that these two methods had some degree of consistency (k=0.673, P=0.000).This study showed that the mNGS in BALF samples and the mNGS in tissue samples which could be used to test for pathogens in the lungs. The sensitivity will increase when mNGS is combined with culture. Also, mNGS of BALF and tissues had some degree of consistency to detect fungal infections, whereas mNGS of BALF had better sensitivity to detect bacterial infection than mNGS of tissues.

In some alloys such as 9%Cr heat resistant steels and magnesium alloys, the creep constitutive equation of the power-law requires a term of threshold stress due to the presence of second phase particles. It is necessary to establish an estimation method of C∗ for such alloys to predict the life of their components. In this paper, the General Electric/Electric Power Research Institute (GE/EPRI) method and the reference stress method were modified to estimate C∗ for power-law creep materials with threshold stress. The finite element method was used to verify the accuracy of the modified methods. The accuracy of the calculation equation of C∗ in the American Society for Testing Materials (ASTM) E 1457 was also assessed. The results indicated that the modified GE/EPRI method was sufficiently exact as an engineering method. h1 was slightly affected by the applied load and significantly affected by the threshold stress. The accuracy of the modified reference stress method increased with increased applied load and was within ±40%. The accuracy of the calculation equation of C∗ in ASTM E 1457 was not affected by the threshold stress and the equation could be directly used for power-law creep materials with threshold stress.

Lung cancer is by far the leading cause of cancer death in the world. Despite the improvements in diagnostic methods, the status of early detection was not achieved. So, a new diagnostic method is needed. The aim of this study is to obtain the highly specific nucleic acid aptamers with strong affinity to tumor markers in the serum of the lung cancer patients for targeting the serum. Aptamers specifically binding to tumor markers in the serum of the lung cancer patients were screened from the random single-stranded DNA library with agarose beads as supports and the serum as a target by target-substituting subtractive SELEX technique and real-time quantitative polymerase chain reaction technique. Subsequently, the secondary single-stranded DNA library obtained by 10 rounds of screening was amplified to double-stranded DNA, followed by high-throughput genome sequence analysis to screen aptamers with specific affinity to tumor markers in the serum of the lung cancer patients. Finally, six aptamers obtained by 10 rounds of screening were identified with high specific affinity to tumor markers in the serum of the lung cancer patients. Compared with other five aptamers, the aptamer 43 was identified both with the highest specificity to bind target molecule and without any obvious affinity to non-specific proteins. The screened aptamers have relatively high specificity to combine tumor markers in the serum of the lung cancer patients, which provides breakthrough points for early diagnosis and treatment of lung cancer.

A moving grid nonlinear finite element method was used in this study to simulate crack propagation. The relevant elements were split along the direction of principal stress within the element and thus automatic optimization processing of local mesh was realized. We discussed the moving grid nonlinear finite element algorithm was proposed, compiled the corresponding script files based on the dedicated finite element language of Finite Element Program Generator (FEPG), and generate finite element source code programs according to the script files. Analyses show that the proposed moving grid finite element method is effective and feasible in crack propagation simulation.

Jing Dong,1 Zhi Zhang,2 Tao Gu,3 Shu-Feng Xu,4 Li-Xin Dong,3 Xin Li,5 Bao-Hong Fu,3 Zhan-Zhao Fu3 1Basic Research for Oncology, North China University of Science and Technology, 2Department of Oncology, Workers’ Hospital of Tangshan City, Tangshan, 3Department of Oncology, 4Department of Respiratory Medicine, The First Hospital of Qinhuangdao City, Qinhuangdao, 5Department of Oncology, Chengde Medical College, Chengde, People’s Republic of China Objective: This study aimed at exploring the role of microRNA-21 (miR-21) in predicting brain metastases (BM) from non-small cell lung cancer (NSCLC). Methods: A total of 132 NSCLC patients, including 68 patients with BM and 64 patients without BM, were included in the study. NSCLC cells were collected and assigned to the inhibitor (IN) group, the mock group, and the negative control (NC) group. The quantitative real-time polymerase chain reaction assay was used to detect the miR-21 expression. Cell proliferation, migration, invasion, and apoptosis were detected by colony-forming assay, MTT assay, transwell assay, and flow cytometry, respectively. Angiogenesis was measured by endothelial cell tube formation assay. Results: The miR-21 expression was higher in NSCLC patients with BM than in those without BM. The miR-21 expression in the IN group was lower than that in the NC and mock groups. Compared with the NC and mock groups, the values of optical density (OD) and the colony-forming number decreased in the IN group. Compared with the NC and mock groups, cell invasion and migration abilities significantly reduced in the IN group. The IN group had higher apoptosis rate than the NC and mock groups. The tube length was shorter and the number of junction points was less in the IN group in comparison to the NC and mock groups. Conclusion: miR-21 might be a potential biomarker for the development of BM in NSCLC patients and could promote the proliferation, migration, invasion, and angiogenesis of NSCLC cells. Keywords: non-small cell lung cancer, microRNA-21, brain metastases, angiogenesis

Dihydroartemisinin (DHA), a kind of artemisinin derivatives, its activity in anti-cancer was extensively studied in recent years. There is not yet related research about dihydroartemisinin puls cisplatinum (Cis) in treatment of a human lung adenocarcinoma cancer cell line (H1299 cells) so far. This experiment is designed to study the apoptotic effect induced by DHA and Cis to H1299 cells. MTT assays, nuclear staining with Hoechst 33258 and flow cytometry were used to evaluate the apoptosis status. The expression of apoptotic-associated proteins was assessed by Western blotting and RT-qPCR. DHA and Cis pro-apoptotic activity of alone and combined administration enhanced as drug concentration increased or elongation of time. Flow cytometry revealed that the apoptosis rate of the singnal medicine group and the combined medicine group were higher than the control group. The result of RT-qPCR reveal that drug combination of Ct value about caspase-3,-8,-9 are significantly higher than monotherapy. The combined treatment with two drugs significantly enhanced caspase-8,-9,-3,-6,-7 and PARP activation, indicating that the caspase-8 participated extrinsic apoptosis pathway and the caspase-9 participated intrinsic apoptosis pathway played improtant roles respectively in the synergistic effect. In general, this study reveals the obvious synergistic action of the combined treatment with DHA and Cis in inducing apoptosis of H1299 cells by the extrinsic and intrinsic apoptosis pathway.

Lipopolysaccharide (LPS) can activate endothelial cells and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of nuclear factor (NF)-κB. A number of studies have demonstrated the cytoprotective action of perfluorocarbon (PFC) both in vivo and in vitro, but the exact mechanisms have yet to be elucidated. In this study, we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated pulmonary vascular endothelial cells (PMVECs). Intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), and interleukin-8 (IL-8) were significantly increased in the LPS-stimulated PMVECs groups. The expression of TLR-4 mRNA and protein in LPS groups was markedly increased. Meanwhile, NF-κB was activated. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α, and IL-8; the expression of TLR-4 mRNA; and the activity of NF-κB. LPS can induce PMVEC inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect PMVECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway.

To investigate the correlation of immunologic thrombocytopenia(ITP) pathogenesis with the abnormal expression of IL-21, and to explore the association of high-dose dexamethasone (HD-DEX) treatment with the IL-21 expression.26 newly diagnosed ITP patients and 24 healthy controls were enrolled in this study. The mononuclear cells and serum were obtain from density gradient centrifugation in the newly diagnosed ITP patients before HD-DXM treatment, and the samples of healthy controls were also used for assays. The protein and mRNA expression of IL-21 on peripheral blood mononuclear cells(MNC) were determined by flow cytometry and real-time reverse-transcription polymerase chain reaction. Plasma levels of IL-21, IFN-γ and IL-4 were determined by enzyme-linked immunoabsorbent assay (ELISA).IL-21 expression on mononuclear cells was significantly higher in ITP patients (13.07%) than that in normal controls (8.2%), the ratio of IL-21/GAPDH mRNA expression on MNC was significantly higher in ITP patients (9.524±0.97) than that in normal controls (3.701±0.60, P0.01). After HD-DXM therapy, the ratio of IL-21/GAPDH mRNA decreased significantly (5.87±1.21) as compared with the level before treatment. Significantly high levels of serum IL-21, IFN-γ and lower IL-4 were found in ITP patients, as compared with healthy controls. Serum IL-21 and IFN-γ levels in ITP patients decreased significantly after HD-DXM administration (P0.01), while post-treatment levels of IL-4 were increased significantly, compared with the levels before treatment (P0.01).Therapeutic effect of DXM on ITP associates with down-regalation of IL-21 expression. The increased expression of IL-21 involves in the pathogenesis of ITP.

Background: An early differentiation of malignant from benign solitary pulmonary nodules (SPNs) is essential for management and prognosis of lung cancer.Objectives: Here we investigated whether measurement of circulating sex hormones could be useful for an early detection of malignancy among patients with SPNs.Methods: We recruited 47 patients with malignant SPNs, 45 patients with benign SPNs, and 32 healthy persons. Testosterone, estradiol, and progesterone were measured. Carcinoembryonic antigen (CEA) as well as TNF-α, IL-1 and IL-6 were also measured.Results: We found that sex hormones were decreased significantly in patients with malignant SPNs, as compared to patients with benign SPNs and healthy controls (P0.05). CEA levels were only abnormally elevated in eight patients with lung adenocarcinoma. The inflammatory cytokines were remarkably higher in both patients than in normal controls. However, there was no statistical difference in these cytokines among patients.Conclusions: The reduced sex hormones levels seemed to be uniquely associated with lung cancer. Therefore, measurement of sex hormones may have clinical potential in the diagnosis of malignancy in patients with SPNs.Keywords: solitary pulmonary nodules (SPNs), sex hormones, lung cancer, biomarkers

Lipopolysaccharide (LPS) can activate pulmonary vascular endothelial cells (PMVECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study was to investigate in an in vitro model the inflammatory responses of PMVECs induced by LPS and the probable mechanism underlying the observed inflammatory responses.The present study was performed on isolated PMVECs from Sprague-Dawley rats. After being identified, PMVECs were divided into 2 groups: a control group, and a LPS (0.01, 0.1, 1, 10 mg/L) intervention group. ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detected by real time PCR. The activation of NF-κB was detected by Western blot (proteins of I-κBα and NF-κB p65) and immunocytochemical staining (NF-κB p65).Compared with the control group, cytokines secreted from PMVECs-stimulated by LPS were increased in a dose-dependent manner. When stimulated with LPS 10 mg/L for 2, 6 and 12 h, cytokines measured were all increased. ICAM-1 and TNF-α were significantly increased and peaked after 2 h before gradually declining at 6 and 12 h. IL-8 was higher after 2 h, which continued up to 12 h. The expression of TLR-4 mRNA was significantly higher and peaked after 2 h and continued to 12 h (4.34 ± 1.42, 3.62 ± 1.45, 3.32 ± 1.36), which were all higher than that of the control group (1.00 ± 0.00, P0.05). Meanwhile, NF-κB was activated at 0.5, 2, 6 and 12 h indicated by the significant degradation of IκB-α and the significant increased release of NF-κB P65 and its subsequent translocation into the nucleus with approximately synchronized.Taken together, the results demonstrated that LPS was able to induce PMVECs inflammatory injury via activating TLR-4 and subsequently activating NF-κB.

Toll-like receptor-4 (TLR-4) is integrally involved in lipopolysaccharide (LPS) signaling and has a requisite role in the activation of nuclear factor-κB (NF-κB). The exact mechanisms that lend perfluorocarbon (PFC) liquids a cytoprotective effect have yet to be elucidated. Therefore we examined in an in vitro model the cytoprotective effect of PFC on LPS-stimulated alveolar epithelial cellls (AECs).AECs (A549 cells, human lung adenocarcinoma cell line) were divided into four groups: control, PFC, LPS and LPS + PFC (coculture group) groups. Intercellular adhesion molecule-1 (ICAM-1) was detected by ELISA, tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) were detected by radioimmunological methods. The expression of TLR-4 mRNA and protein was detected by real time PCR and Western blotting, respectively. The activation of NF-κB was detected by Western blotting (proteins of I-κBa and NF-κB p65).ICAM-1, TNF-α and IL-8 were significantly increased in LPS-stimulated AECs groups. The expression of TLR-4 mRNA and protein in LPS-stimulated groups was markedly increased. Meanwhile, NF-κB was activated as indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus. There were no significant effects of PFC alone on any of the factors studied while the coculture group showed significant downregulation of the secretion of ICAM-1, TNF-α and IL-8, the expression of TLR-4 mRNA and the activity of NF-κB.Taken together, our results demonstrate that LPS can induce AEC-related inflammatory injury via the activation of TLR-4 and subsequent activation of NF-κB. PFC is able to protect AECs from LPS-induced inflammatory injury by blocking the initiation of the LPS signaling pathway, which is indicated by the significant decrease of TLR-4 expression and NF-κB activation.

Lipopolysaccharide (LPS) can activate alveolar epithelial cells (AECs) and induce inflammatory injury. Toll-like receptor-4 (TLR-4) is integrally involved in LPS signaling and has a requisite role in the activation of NF-κB. NF-κB is a key intercellular signaling event that mediates cell inflammatory responses. The aim of the study is to investigate in an in vitro model the inflammatory responses of AECs induced by LPS and the probable mechanism underlined the observed inflammatory responses. So cytokines of ICAM-1, TNF-α and IL-8 secreted by LPS-activated AECs were observed. And the initial signal molecule (the expression of TLR-4 mRNA) and the key intracellular steps (the activation of NF-κB) were studied in detail.The study was performed on A549 cells (Human lung adenocarcinoma cell line). A549 cells were divided into two groups: control, and LPS interference group. Proinflammatory cytokines ICAM-1, TNF-α and IL-8 were detected by ELISA or radioimmunological methods. The expression of TLR-4 mRNA was detected by real time PCR. The activation of NF-κB was detected by Western blot (proteins of I-κBα and NF-κB p65).Compared with control group, ICAM-1 and TNF-α of LPS-stimulated group were significantly higher and peaked after 2h before gradually declining at 6 and 12 h; IL-8 was higher after 2 h, which continued up to 12 h. The expression of TLR-4 mRNA of LPS group was significantly higher and peaked after 2 h and gradually declining at 6 and 12 h. Meanwhile, NF-κB was activated after 0.5, 2, 6 and 12 h indicated by the significant degradation of IκB-α and the significant release of NF-κB P65 and its subsequent translocation into the nucleus approximately synchronized.Taken together, the results demonstrate that LPS can induce AECs inflammatory injury via activating TLR-4 and subsequently activating NF-κB.

Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is an effective treatment for epithelial tumors, including non-small cell lung cancer (NSCLC), and is generally well tolerated. However, some clinical trials revealed that gefitinib exposure caused lung fibrosis, a severe adverse reaction. This study investigated the effect of gefitinib on lung fibrosis in mice.We generated a mouse model of lung fibrosis induced by bleomycin to investigate the fibrotic effect of gefitinib. C57BL/6 mice were injected intratracheally with bleomycin or saline, with intragastric administration of gefitinib or saline. Lung tissues were harvested on day 14 or 21 for histology and genetic analysis.The histological results showed that bleomycin successfully induced lung fibrosis in mice, and gefitinib prevented lung fibrosis and suppressed the proliferation of S100A4-positive fibroblast cells. In addition, Western blotting analysis revealed that gefitinib decreased the expression of phosphorylated EGFR (p-EGFR). Furthermore, quantitative real-time PCR (qRT-PCR) demonstrated that gefitinib inhibited the accumulation of collagens I and III.These results reveal that gefitinib reduces pulmonary fibrosis induced by bleomycin in mice and suggest that administration of small molecule EGFR tyrosine kinase inhibitors has the potential to prevent pulmonary fibrosis by inhibiting the proliferation of mesenchymal cells, and that targeting tyrosine kinase receptors might be useful for the treatment of pulmonary fibrosis in humans.