Effect of Long-Term Aging on Fatigue and Thermal Cracking Performance of Polyphosphoric Acid and Styrene-Butadiene-Styrene-Modified Bio-Blend Bitumen.

Polyphosphoric acid (PPA) and styrene-butadiene-styrene (SBS) were adopted to produce PPA-SBS-modified bio-blend bitumen, which achieved excellent mechanical performance. However, its long-range performance, such as the fatigue and thermal cracking behavior under long-term thermal oxidation, is not well understood. Therefore, a pressure aging vessel (PAV) system was applied to simulate the aging behavior of the bitumen under the action of thermal oxidation. Then, a linear amplitude sweep (LAS) test combined with a viscoelastic continuum damage (VECD) model was applied to investigate the fatigue properties of the bitumen. Moreover, a bending beam rheometer (BBR) test was conducted to evaluate the thermal cracking resistance of the bitumen before and after PAV aging. Meanwhile, an atomic force microscope (AFM) was applied to observe the microscopic topography. The results show that the original compound-modified bitumen can bear more fatigue damage than that of the control bitumen at the failure point, and it also has excellent fatigue resistance at 2.5%, 5%, 7.5%, and 10% applied strain. Moreover, the VECD model can accurately predict the fatigue life of the bitumen under different applied strains. The variation ratio of stiffness modulus for the compound-modified bitumen is below that of the control bitumen after PAV aging, so it shows a better anti-aging performance. Finally, the AFM test shows that PPA and bio-bitumen decrease the heterogeneity of the bitumen, reducing the difference between phases.

LncRNA EWSAT1 Regulates the Tumorigenesis of NSCLC as a ceRNA by Modulating miR-330-5p/ITGA5 Axis.

The aim of the study is to investigate how lncRNA EWSAT1 regulates the tumorigenesis of non-small cell lung cancer (NSCLC) as a ceRNA by modulating miR-330-5p/ITGA5 axis. qRT-PCR was conducted to evaluate the expression of EWSAT1 in NSCLC tissue. Then, A549 cells were selected and divided into Blank shScramble, shEWSAT1, miR-330-5p inhibitor, shEWSAT1 + miR-330-5p inhibitor, and siITGA5 and miR-330-5p inhibitor + siITGA5 groups. Besides, a series of in-vitro experiments were carried out to determine the changes in cell proliferation, apoptosis, invasion, and migration in each group. In addition, xenograft models were also constructed on nude mice to detect the tumor volume and weight, and the expression of Ki67 and apoptosis in xenograft tumor were evaluated. In NSCLC tissue and cell, EWSAT1 was upregulated significantly, demonstrating a correlation with tumor diameter, differentiation, lymph node metastasis, and TNM stage. Dual luciferase reporter gene assay confirmed targeting relationships among miR-330-5p, EWSAT1, and ITGA5. In comparison with the Blank group, the number of cell clones in the shEWSAT1 group and siITGA5 decreased, with declined invasion and migration but increased apoptotic rate. Meanwhile, ITGA5, MMP-2, and MMP-9 were downregulated with upregulated cleaved caspase-3. However, the changes above were totally reversed in the miR-330-5p inhibitor group, and miR-330-5p inhibitor transfection abolished the effect of shEWSAT1. In addition, subcutaneous xenotransplantation showed that the tumor growth in shEWSAT1 group retarded significantly, with downregulation of Ki67 and increase apoptotic rate. Silencing EWSAT1 could inhibit the expression of ITGA5 via upregulating miR-330-5p, thus, resulting in the inhibition of NSCLC cell growth.

Conditional survival rate estimates of lobectomy, segmentectomy and wedge resection for stage IA1 non-small cell lung cancer: A population-based study.

Conditional survival rate (CSR) is defined as the dynamic possibility of survival, considering the changes in the survival risk over time. The present study aimed to compare the CSR of the surgical procedures for stage IA1 non-small cell lung cancer (NSCLC). Overall, data for 2,535 patients with stage IA1 NSCLC after lobectomy, segmentectomy or wedge resection were obtained from the Surveillance, Epidemiology and End Results database, and the overall survival (OS) rates were subsequently compared. CSR estimates, the possibility of patients who had already survived × years, to survive further y years, was calculated as CSR=S(x+y)/S(x), where S is the survival rate at a particular point in time. A Cox regression model and propensity-score matching were used to adjust confounding factors. There were no statistical differences in the OS among the three surgical procedures, except that OS of patients who underwent a lobectomy was improved compared with the wedge resection. The CSR of surviving to the 5th year after operation improved gradually over time. The 3-year CSR of lobectomy or segmentectomy was higher compared with that of the wedge resection. Moreover, the 3-year CSR of segmentectomy was higher compared with that of lobectomy from the 3rd year after surgery, particularly in some specific situations, such as female sex, patients ≥66 years old, patients with squamous cell carcinoma or patients with poor tumor differentiation. The present study is the first report to compare CSR following lobectomy, segmentectomy and wedge resection for patients with stage IA1 NSCLC, to the best of our knowledge. These findings indicated that lobectomy is the most conservative surgical procedure for stage IA1 NSCLC and raises questions regarding improved long-term prognosis of segmentectomy in some subsets of patients.

Conditional survival analysis of four treatment strategies for patients with stage I non-small cell lung cancer.

Conditional survival (CS) is used to describe dynamic survival possibility, taking account of the change in the survival risk that occurs with longevity. The present study aimed to explore the CS of four treatment strategies for stage I non-small cell lung cancer (NSCLC), staged according to the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system. Using the Surveillance, Epidemiology and End Results Program cohort obtained between 2004-2014, the current study first extracted data for 27,116 patients with stage I NSCLC. The actuarial cancer-specific survival rates (ACSs) and conditional cancer-specific survival rates of four treatment strategies were then compared. ACS was assessed using the Kaplan-Meier method and a log-rank test. The 3-year conditional cancer-specific survival (CCS3) of patients who had already survived for n years was calculated as CCS3=ACS(n+3)/ACS(n). Cox regression and propensity-score matching (PSM) was applied to adjust confounding factors. The 5-year ACS of patients who underwent lobectomy, sublobar resection, radiation and observation was 80.3, 72.0, 40.8 and 19.6%, respectively. The 5-year CCS3 of patients who underwent lobectomy, sublobar resection, radiation and observation was 91.7, 86.4, 77.0 and 58.2%, respectively. CCS3 increased with an increase in survival time and patients who underwent lobectomy had the highest CCS3 estimates and flattest growth, with the smallest survival gap between CCS3 and ACS. The results were similar in the PSM analysis. In conclusion, CS estimates may provide a more accurate survival prediction for patients with stage I NSCLC, and may assist with treatment decisions and surveillance strategies. In addition, the current study provided evidence that suggests lobectomy may be the optimal treatment strategy for stage I NSCLC compared with sublobar resection.

MicroRNA-198-5p inhibits the migration and invasion of non-small lung cancer cells by targeting fucosyltransferase 8.

MicroRNA-198-5p (miR-198-5p) displays crucial roles in various cancers including non-small cell lung cancer (NSCLC), but the underlying molecular mechanisms remain unclear. Fucosyltransferase 8 (FUT8) is associated with tumour metastasis and prognosis. In this study, we explored the expression of miR-198-5p and FUT8 in NSCLC patients. Results showed that miR-198-5p was under-expressed in NSCLC tissues and was negatively correlated with tumour size, lymph node metastasis and tumour-node-metastasis stage, while FUT8 expression was highly upregulated. Next, we altered miR-198-5p expression using the mimic or inhibitor in the functional study. Results showed that miR-198-5p overexpression could inhibit the migration, invasion and epithelial-to-mesenchymal transition (EMT) of NSCLC cells; reversely, suppression of miR-198-5p enhanced cell migration, invasion and EMT. In vivo, miR-198-5p overexpression inhibited the formation of mouse lung and liver metastasis. Luciferase reporter, real-time PCR and western blot assays showed that miR-198-5p could directly target FUT8 and regulate FUT8 expression. Further, FUT8 overexpression reversed the effect of miR-198-5p overexpression on the migration, invasion and EMT of NSCLC cells. Taken together, miR-198-5p functions as a tumour suppressor by targeting FUT8 in NSCLC. MiR-198-5p may be developed as a new diagnostic biomarker and therapeutic target for lung cancer.

The lncRNA RHPN1-AS1 downregulation promotes gefitinib resistance by targeting miR-299-3p/TNFSF12 pathway in NSCLC.

Although epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has exhibited notable clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of gefitinib resistance. The present study aimed to investigate the effects of the long non-coding RNA, RHPN1-AS1 on gefitinib resistance in NSCLC and explore the underlying mechanisms. In this study, RHPN1-AS1 was observed to be downregulated in gefitinib resistant patients and NSCLC cell lines. Besides, decreased expression of RHPN1-AS1 was found to be associated with poor prognosis of NSCLC patients. RHPN1-AS1 knockdown conferred gefitinib resistance to gefitinib sensitive NSCLC cells, whereas the overexpression of RHPN1-AS1 sensitized gefitinib resistant NSCLC cells to gefitinib treatment. Mechanistically, RHPN1-AS1 was found to positively regulate the expression of TNFSF12 by directly interacting with miR-299-3p. Collectively, RHPN1-AS1 modulates gefitinib resistance through miR-299-3p/TNFSF12 pathway in NSCLC. Our findings indicate that RHPN1-AS1 may serve as not only a prognostic biomarker for gefitinib resistance but also as a promising therapeutic biomarker and target for the treatment of NSCLC patients.

The upregulation of TMPRSS4, partly ascribed to the downregulation of miR­125a­5p, promotes the growth of human lung adenocarcinoma via the NF­κB signaling pathway.

In this study, with the aid of microarray technology, transmembrane protease serine 4 (TMPRSS4), a novel member of the serine protease family, was found to be upregulated in the majority of lung adenocarcinoma (LUAD) tissues compared to normal lung tissues. Of note, the clinical significance of TMPRSS4 in LUAD has not yet been reported, at least to the best of our knowledge. Through immunohistochemistry assays, we found that TMPRSS4 was overexpressed in LUAD tissues and that the TMPRSS4 expression level was also proportionally associated with the AJCC clinical stage, T stage and pathological grade. Moreover, a high expression of TMPRSS4 was found to be associated with adverse outcomes and was a significant independent factors predicting a poor prognosis. To elucidate the possible mechanisms responsible for the overexpression of TMPRSS4, we examined at microRNAs (miRNAs or miRs), which are small non­coding RNAs commonly dysregulated in human malignancies and are known to promote carcinogenesis by interacting with other types of RNAs. By means of bioinformatics analysis, a miRNA potentially targeting TMPRSS4 mRNA, namely miR­125a­5p, was selected. Dual luciferase reporter gene assays were then performed to verify the interaction. The results of MTT assays and apoptotic assays revealed that miR­125a­5p significantly inhibited cell growth and enhanced apoptosis, and the silencing of TMPRSS4 had similar effects. Furthermore, we observed that either the overexpression of miR­125a­5p or the silencing of TMPRSS4 prevented the activation of the nuclear factor (NF)-κB signaling pathway. On the whole, our findings illustrate that TMPRSS4 may be a candidate oncogene and may thus serve as a prognostic biomarker for LUAD, and its overexpression may be partly ascribed to the downregulation of miR­125a­5p. The dysregulation of miR­125a­5p and TMPRSS4 affect the biological function of LUAD cells via the NF­κB signaling pathway. The miR­125a­5p/TMPRSS4/NF­κB axis may thus provide novel insight into the pathogenic mechanisms of LUAD and may be used in the development of novel treatment strategies for LUAD.

miR-373-3p promotes lung adenocarcinoma cell proliferation via APP.

Previous studies have indicated that lung adenocarcinoma (LUAD) is one of the common human malignancies, and its incidence keeps rising. With the help of microarray technology, downregulation of miR-373-3p was observed in LUAD tissues compared with normal lung tissues. Notably, the present study demonstrated that the expression of amyloid precursor protein (APP) mRNA in LUAD tissues was overexpressed compared with adjacent tissues. Bioinformatic analysis demonstrated that miR-373-3p may interact with the 3' untranslated region of APP mRNA, and then western blot and dual-luciferase reporter gene assays were employed to verify the interaction. Finally, CCK-8 assays were used to measure the tumor-suppressing effect of miR-373-3p on A549 and it was demonstrated that overexpression of miR-373-3p may more effectively inhibit the proliferation of A549 compared with APP si-RNA. Overall, the findings suggest that miR-373-3p downregulation partly accounts for APP overexpression and leads to a promotion of cell growth in LUAD. miR-373-3p may therefore act as a valuable target in potential anticancer strategies to treat LUAD.

miR­197­3p­induced downregulation of lysine 63 deubiquitinase promotes cell proliferation and inhibits cell apoptosis in lung adenocarcinoma cell lines.

Lung adenocarcinoma (LUAD) is a common cause of cancer-associated mortality. The dysregulation of microRNA (miR) expression has been reported to induce lung carcinogenesis. In the present study, miR­197­3p upregulation was detected within LUAD tissues compared with in adjacent noncancerous tissues. The suppression of miR­197­3p expression was confirmed to inhibit proliferative ability and induce apoptosis of LUAD cell lines; miR­197­3p overexpression within the HBE cell line exhibited opposing effects. Via in silico modeling, western blot analyses and dual­luciferase assays, it was confirmed that miR­197­3p directly targets the lysine 63 deubiquitinase (CYLD) gene. In the present study, the expression of miR­197­3p was negatively associated with CYLD mRNA expression within LUAD cell lines. In conclusion, the findings of the present study have provided novel insight into the association of miR­197­3p with LUAD proliferation and apoptotic regulation; the miR­197­3p/CYLD axis may serve as a novel potential therapeutic target for the treatment of LUAD.

miR-198-induced upregulation of Livin may be associated with the prognosis and contribute to the oncogenesis of lung adenocarcinoma.

Livin, a member of the inhibitor of apoptosis protein (IAP) family, is expressed at a high level in lung adenocarcinoma and influences the progression of cancer, and its response to chemotherapy and radiotherapy. Aberrant microRNA (miRNA) expression has also been associated with cancer initiation and development. However, the clinical significance of Livin and its relationship with miRNAs in lung adenocarcinoma are still unclear. In the present study, the expression level of Livin in 90 pairs of lung adenocarcinoma and their adjacent tissues were detected by immunohistochemistry staining. Spearman correlation and Kaplan-Meier, univariate and multivariate analyses were applied to evaluate the correlation between the expression of Livin and clinical characteristics. With the integration of bioinformatics analysis and dual-luciferase reporter gene assays, we identified the miRNA that can target Livin mRNA. The functional effects of miRNA-mediated Livin knockdown were assessed by Cell Counting Kit-8 (CCK-8) and apoptosis assays, and cell cycle analysis. The present study revealed that Livin was upregulated in lung adenocarcinoma tissues and may be associated with the poor prognosis in lung adenocarcinoma patients. The overexpression of Livin is partly caused by the downregulation of miR-198. Further exploration revealed that miRNA-198-mediated silencing of Livin significantly inhibited cell growth and enhanced apoptosis of A549 cells, accompanied by marked upregulation of caspase-3. Finally, we observed that the miR-198 overexpression and Livin neutralization had similar effects on improving cisplatin chemosensitivity in A549 cells. Overall, these findings suggest that Livin has the potential to become a biomarker for predicting the prognosis of lung adenocarcinoma and may provide a promising strategy for assisting chemotherapy of lung adenocarcinoma through the miR-198/Livin/caspase-3 regulatory network.

Idiopathic pulmonary fibrosis in East Asian.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease with a prognosis that can be worse than that of many cancers. Recent studies have improved our understanding of IPF and new treatment options have become available. However, most studies are conducted predominantly in Western countries while few are conducted in East Asian countries. The distribution, effectiveness of treatment, and prognosis for IPF differ among Westerners and East Asians, but whether the heterogeneity of IPF in East Asians is the result of ethnic differences and geographic variability is unclear. This study highlights the current prevalence of IPF and its characteristics in the East Asian population and it provides valuable information to understand the current clinical status of patients with IPF in light of recent advances in its diagnosis and treatment.

The Long Non-Coding RNA XIST Controls Non-Small Cell Lung Cancer Proliferation and Invasion by Modulating miR-186-5p.

BACKGROUND/AIMS: Long non-coding RNAs (lncRNAs) are key players in the development and progression of human cancers. The lncRNA XIST (X-inactive specific transcript) has been shown to be upregulated in human non-small cell lung cancer (NSCLC); however, its role and molecular mechanisms in NSCLC cell progression remain unclear. METHODS: qRT-PCR was conducted to assess the expression of XIST and miR-186. Cell proliferation was detected using MTT assay. Cell invasion and migration were evaluated using transwell assay. Cell cycle distribution and apoptosis rates were analyzed by flow cytometry. Luciferase reporter assay was used to identify the direct regulation of XIST and miR-186. A RNA immunoprecipitation was used to analyze whether XIST was associated with the RNA-induced silencing complex (RISC). RESULTS: We confirmed that XIST was upregulated in NSCLC cell lines and tissues. Functionally, XIST knockdown inhibited cancer cell proliferation and invasion, and induced apoptosis in vitro, and suppressed subcutaneous tumor growth in vivo. Mechanistic investigations revealed a reciprocal repressive interaction between XIST and miR-186-5p. Furthermore, we showed that miR-186-5p has a binding site for XIST. Our data also indicated that XIST and miR-186-5p are likely in the same RNA induced silencing complex. CONCLUSION: Together, our data revealed that XIST knockdown confers suppressive function in NSCLC and XIST may be a novel therapeutic marker in this disease.

Benign esophageal schwannoma compressing the trachea requiring esophagectomy: a case report.

We report a case of esophageal schwannoma in a 62-year-old woman with a 10-month history of dysphagia and dyspnea. Chest computed tomography showed a giant mediastinal mass with a maximum diameter of 9 cm, extrinsically compressing the trachea and esophagus. With a large esophageal mucosal defect and poor blood supply after removal of the tumor, we had to perform partial esophagectomy and esophagogastrostomy in the right thorax (Ivor-Lewis procedure). Pathologic and immunohistochemical examinations revealed a benign esophageal schwannoma.

Brachial plexus palsy, a rare delayed complication of the Nuss procedure for pectus excavatum: a case report.

We report a rare complication after the Nuss procedure for the correction of pectus excavatum in a 15-year-old adolescent boy. He began to have delayed right brachial plexus injury on the 15th postoperative day. Careful physical check-up revealed a painful and enlarged subaxillary lymph node. He was successfully treated using anti-inflammatory medications and physical therapy.

[Surgical treatment of primary tracheal tumors in 63 cases].

OBJECTIVE: To summarize the experience in diagnosis and treatment of primary tracheal tumors, and to improve the life quality of patients. METHODS: Sixty-three patients with primary tracheal tumors treated in the First Affiliated Hospital of China Medical University during the past 40 years were included in this study, among them, there were 42 cases of malignant tumors and 21 cases of benign tumors. The 61 patients underwent surgery including tracheal sleeve resection (22), carinal resection and reconstruction (6), semi-carinal resection and reconstruction (6), tracheal resection for tracheal tumors (17); tracheostomy (4), tracheal resection, partial resection of the thyroid (goiter) and esophagomyotomy (1), tracheal tumor resection and vertical hemilaryngectomy with reconstruction of laryngeal ventricle and trachea by sternocleidomastoid flap (2), cervical trachea and laryngeal resection (1), and carinal scrape (2). RESULTS: Fifty-five patients had an uneventful recovery. Eight patients suffered from postoperative complications, among them 3 patients died postoperatively. CONCLUSIONS: Primary tracheal tumors often present atypical symptoms, are easily misdiagnosed and with poor prognosis. The main aim of treatment remains to remove the airway obstruction.

[Detection of Chemerin and It's Clinical Significance in Peripheral Blood of Patients with Lung Cancer.].

BACKGROUND: Chemerin was recently found a chemoattractant just like a chemotatic factor. It can induce immune chemotaxis to dendritic cells and macrophages by binding to its receptor ChemR23. It has been known that the activation of Chemerin could enhance the phagocytosis and antigen presentation of APC. Along with this observation, the contribution of Chemerin in the genesis and development of a tumor attracts more attention. We explored the relation between Chemerin and lung cancer through detecting the expression of Chemerin in peripheral blood of patients. METHODS: The experiment selected samples of lung cancer patients and normal people. The concentration of Chemerin in peripheral blood was detected by ELISA method. T test was used to compare the statistic difference. We compared the concentration of Chemerin in peripheral blood with age, sex, pathological type, degree of differentiation, metastasis of lymphonode, UICC staging and other clinicopathological index, and analyzed by t test and one-way ANOVA. RESULTS: The concentration of Chemerin in peripheral blood of 42 patients with lung cancer (1 965.81 pg/mL+/-374.03 pg/mL) were significantly higher than the concentration of 31 healthy examination (1 111.44 pg/mL+/-250.72 pg/mL)(P<0.001). The concentration of Chemerin in peripheral blood of patients with lung cancer had no relationship with clinicopathological factors. CONCLUSIONS: Chemerin has the potential to lung cancer diagnosis as a marker.

[Prokaryotic expression and bioactivity of human platelet-derived growth factor B chain mature peptide].

OBJECTIVE: To express human platelet-derived growth factor (hPDGF) B chain mature peptide gene in a prokaryotic expression system and detect the bioactivity of the expressed protein. METHODS: hPDGF B chain mature peptide gene was amplified and expressed in E. coli, and the recombinant protein, rhPDGF-BB, was purified and renatured in GSSG/GSS system. The bioactivity of rhPDGF-BB in vitro was evaluated with SD rat osteoblasts. RESULTS: The full-length PDGF-B mature peptide gene was obtained and verified, and successfully expressed in E. coli. Bioactivity detection results showed that the expressed rhPDGF-BB obviously promoted the proliferation and DNA replication of SD rat osteoblasts in vitro (P<0.01). CONCLUSION: he PDGF-B chain mature peptide cDNA has been successfully cloned and the PDGF-B precursor highly expressed in E. coli, and renatured rhPDGF-BB displays high bioactivity as shown by MTT assay and flow cytometry. This success provides the basis for production of functional PDGF-BB and facilitates further studies of its role in fracture healing and trauma reconstruction.

[Effects of soluble matrix of nacre on bone morphogenetic protein-2 and Cbfa1 gene expressions in rabbit marrow mesenchymal stem cells].

OBJECTIVE: To provide insights into the mechanisms and pathways of osteogensis by observing the effects of water-soluble matrix of nacre (WSM) on bone morphogenetic protein-2 (BMP-2) and Cbfa1 gene expressions in rabbit marrow mesenchymal stem cells (BMSCs). METHODS: New Zealand rabbit BMSCs cultured in vitro were stimulated with different concentrations of WSM extracted at low temperature, and the activity of AKP in the cells was evaluated with the dose-effect curve generated. BMP-2 and Cbfa1 gene expressions in rabbit BMSCs exposed to WSM were assayed with one-step RT-PCR. RESULTS: The activity of AKP in rabbit BMSCs increased after stimulation with different concentrations of WSM, and the effects were the most obvious with the WSM concentration ranging from 150 to 200 microg/ml. BMP-2 gene expression in the BMSCs increased after WSM exposure, but which did not result in obvious changes in Cbfa1 gene expression. CONCLUSION: WSM induces differentiation of rabbit BMSCs towards osteoblasts by increasing BMP-2 gene expression, in which process Cbfa1 gene does not seem to play a significant role.

Single and joint effects of pesticides and mercury on soil urease.

The influence of two pesticides including chlorimuron-ethyl and furadan and mercury (Hg) on urease activity in 4 soils (meadow burozem and phaeozem) was investigated. The soils were exposed to various concentrations of the two pesticides and Hg individually and simultaneously. Results showed that there was a close relationship between urease activity and organic matter content in soil. Chlorimuron-ethyl and furadan could both activate urease in the 4 soils. The maximum increment of urease activity by chlorimuronethyl was up to 14%-18%. There was almost an equal increase (up to 13%-21%) in the urease activity by furadan. On the contrary, Hg markedly inhibited soil urease activity. A logarithmic equation was used to describe the relationship (P<0.05) between the concentration of Hg and the activity of soil urease in the 4 tested soils. Semi-effect dose (ED50) values by the stress of Hg based on the inhibition of soil urease in the 4 soils were 88, 5.5, 24 and 20 mg/kg, respectively, according to the calculation of the corresponding equations. The interactive effect of chlorimuron-ethyl or furadan with metal Hg on soil urease was mainly synergic at the highest tested concentrations.