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Background: GPC5 rs2352028 is associated with the risk of lung cancer, but its relationship with lung cancer prognosis is unclear. Materials & methods: The authors collected blood samples from 888 patients with lung cancer and used a Cox proportional hazards model to analyze the association between prognosis and GPC5 polymorphism rs2352028. Results: GPC5 rs2352028 C > T was associated with a better prognosis. Patients with CT genotype had longer overall survival than those with CC genotype. Additionally, older and early-stage patients with CT + TT genotype had a lower risk of death than those with CC genotype. Conclusion: GPC5 rs2352028 C > T may play a protective role in patients with lung cancer and GPC5 rs2352028 may be a potential genetic marker for lung cancer prognosis.

Intestinal dysbiosis is one of the major causes of the occurrence of metabolic syndromes, such as obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Polysaccharide-based microbial therapeutic strategies have excellent potential in the treatment of metabolic syndromes, but the underlying regulatory mechanisms remain elusive. Identification of the internal regulatory mechanism of the gut microbiome and the interaction mechanisms involving bacteria and the host are essential to achieve precise control of the gut microbiome and obtain valuable clinical data. Polysaccharides cannot be directly digested; the behavior in the intestinal tract is considered a "bridge" between microbiota and host communication. To provide a relatively comprehensive reference for researchers in the field, we will discuss the polysaccharide extraction and purification processes and chemical and structural characteristics, focusing on the polysaccharides in gut microbiota through the immune system, gut-liver axis, gut-brain axis, energy axis interactions, and potential applications.

The objectives of this study were (1) to prepare Armillariella tabescens mycelia polysaccharides (PAT) with remarkably growth inhibitory effect on typical food-borne pathogenic bacteria using a green and efficient polyamide method and (2) to explore the antibacterial mechanism of PAT for use as a natural antibacterial agent. The sugar and uronic acid contents of PAT were 93.41% and 12.24%, respectively. PAT could inhibit the growth of Escherichia coli, Proteus vulgaris, Bacillus subtilis, and Staphylococcus aureus cells, with minimum inhibitory concentrations of 0.5, 1.0, 4.0, and 4.0 mg/mL, respectively. Ultra-high-resolution field emission scanning electron microscopy and high-resolution transmission electron microscopy analysis revealed cell wall and membrane rupture of E. coli treated with PAT. Further, 0.5-4.0 mg/mL PAT was found to significantly (P 0.01) and concentration-dependently increase the conductivity of the broth, exudation of the intracellular protein, and alkaline phosphatase and β-galactosidase activities. Confocal laser scanning microscopy revealed morphological changes in E. coli DNA after PAT treatment and intracellular reactive oxygen species accumulation; flow cytometry revealed E. coli cell apoptosis. Our findings provide a theoretical basis and technical support for the development of PAT as a natural antibacterial product.

Efficient and accurate traveltime calculations of seismic waves have important applications in tomography, prestack migration, earthquake location, etc. Anisotropy significantly affects the traveltimes of seismic wave. For high-resolution imaging and inversion, it is necessary to consider anisotropy in the traveltime calculations. The fast sweeping method (FSM) does not need to track and store the minimum traveltime point of wavefront, which has important applications in computing the anisotropic first-arrival traveltime. The conventional method that solves a transformed traveltime quartic equation combined with FSM is suitable for general anisotropic media. However, this method involves finding the intervals of roots and solving the quartic equations using bisection algorithm at each iteration, leading to high computational cost and instability for the 3D problems. In our previous work, for the vertical transversely isotropic (VTI) case, we developed an FSM to compute the qP-wave first-arrival traveltimes by analytically solving the simplified quadratic slowness equation in a specific triangular-pyramid stencil. This method greatly improves the computational efficiency. However, for the qP and qSV waves, analytically solving the slowness equation cannot be extended to tilted transversely isotropic (TTI) media. To address this problem, we introduced the Newton method in the triangular-pyramid local solver to quickly solve the TTI slowness equation. For the qSH wave, its slowness equation is quadratic and simple to solve. The proposed method provides an efficient procedure for the traveltime calculations of qP, qSV, and qSH waves in 3D general TTI media. Numerical examples have verified the efficiency and accuracy of the proposed method.

SUMMARY Traveltime computations are an important aspect of seismic data processing applications such as traveltime tomography, migration and seismic source localization. Seismic anisotropy is a widespread feature of the Earth. Solutions to the eikonal equation that account for such anisotropy are needed for high-resolution seismic imaging and inversion. The fast sweeping method (FSM) has been widely used in computing the first-arrival traveltimes for anisotropic media because it does not need to expand the wave front from the point of the smallest traveltime. To apply FSM on strong anisotropic media, one has to solve the slowness equation derived from the Christoffel equation. All the previous developed FSM methods transform the quartic coupled slowness surface equation of quasi-P (qP) and quasi-SV (qSV) waves to the quartic equation in terms of the unknown traveltime, then numerically solve this quartic equation to compute the first-arrival traveltimes of the qP waves. However, the computational cost is significantly increased due the numerically solving the quartic equation, especially for the 3-D problems. In this study, we find a way to transform the quartic slowness equation into a quadratic one if a specific triangular-pyramid stencil around a target point is used. As the quadratic equation has the analytical solution and does not need a numerical solver, the computational efficiency of the scheme is greatly improved. We apply this methodology to develop an efficient 3-D FSM to compute the first-arrival traveltimes for qP waves in 3-D vertical transversely isotropic (VTI) media. We use both layered VTI model and complex VTI model to demonstrate the efficiency of the proposed method to obtain accurate traveltimes in 3-D VTI media involving strong anisotropy.

Wave‐mode separation is a critical step in anisotropic elastic‐wave imaging. To avoid high computational costs and additional corrections, we apply a separation formula in the space domain that projects Cartesian components of the elastic wavefield onto the polarization vectors in the orthogonal direction. By solving the Christoffel equation, we implement the conversion from the phase velocity direction to the polarization direction. We use similarity between the seismic wave propagation and the optical flow problem to calculate the phase angle based on the Horn–Schunck algorithm. Compared with the conventional Poynting vector, the optical flow vector is more robust, particularly for complex underground structures. We demonstrate the performance of the proposed approach for two‐dimensional transversely isotropic media with three numerical examples and discuss the potential extension to three‐dimensional media.

Elastic reverse-time migration (ERTM) is becoming increasingly feasible with the development of high-performance computing. It can provide more physical information on subsurface structures. However, the crosstalk artifacts degrade the imaging resolution of ERTM. To obtain high-resolution ERTM imaging, we have developed additional constraints through a convolutional neural network (CNN) in the dip-angle domain. This procedure can significantly improve the image quality of ERTM by recognizing the dominant reflection events and rejecting the crosstalk artifacts in the dip-angle domain. This method can be divided into the following three steps. First, we generate the dip-angle gathers of ERTM using Poynting vectors shot by shot. Then, we stack all the dip-angle gathers over all the shots. Finally, we adopt the CNN to predict the dip-angle constraint, which can suppress the crosstalk artifacts and enhance the ERTM image quality. The picking method using CNN is an end-to-end procedure that can perform automatic picking without additional human intervention once the network is well-trained. The numerical examples have verified the potential of our method.

Least-squares reverse time migration (LSRTM) is a powerful tool in seeking broadband-wavenumber reflectivity images. It produces better images over reverse-time migration (RTM) at the expense of computational cost. The Hessian effect can be measured in the image domain with the point-spread function (PSF). Here, we try to measure the Hessian effect in the data domain with the so-called trace-spread function (TSF). The difference between PSF and TSF is that the former originates from ${{\mathbf{L}}^{T}}{\mathbf{L}}$ in the image domain while the latter from ${\mathbf{L}}{{\mathbf{L}}^{T}}$ in the data domain. By comparing the TSFs with their original corresponding traces (or beams), we can design adaptive matching filters for preconditioning to alleviate the Hessian effect. However, the full TSF matrix is expensive. In this article, we propose a multiscale solution, which first has a diagonal approximation to ${\mathbf{L}}{{\mathbf{L}}^{T}}$ in beams, and then handle the full submatrix composed of the one-beam traces using the Sherman–Morrison formula. The preconditioned beams are superimposed into a “deblurred” data for remigration. Through synthetic and real data examples, we see that: 1) single-step data-domain LSRTM can yield deblurred RTM images via adaptive matching filters and 2) the beam-by-beam consideration outperforms the trace-by-trace one.

Least-squares reverse-time migration (LSRTM) distinctly improves seismic imaging quality, but at an expensive computation overhead involving tens of iterations. We herein take a computationally cheaper single-step LSRTM solution, which intrinsically performs deblurring through a data-domain Wiener deconvolution. However, the Wiener filter mainly solves the signal estimation problems for stationary signals. Subsalt imaging often suffers from strong salt-related reflections and artifacts. The former and the latter give rise to strong amplitude variance and changed source wavelets in the demigrated data, increasing its nonstationarity and hindering the data-deblurring operation in the single-step LSRTM. To alleviate the nonstationarity during the data-domain deblurring, we consider a Gabor deconvolution method. Testing on the Sigsbee data sets shows that the Gabor deconvolution method is effective, producing subsalt images of more balanced events and fewer artifacts than the raw RTM image. The Gabor deconvolution-related result also outperforms the standard single-step LSRTM result with more robust behavior and better subsalt imaging quality.

Guava is a popular fruit consumed worldwide with beneficial effects in regulation of glucose and lipid metabolism. Although polysaccharides are a major phytochemical component of guava, to date, the alleviative effects of polysaccharides from the guava fruit against diet-induced obesity remain unclear. The relationship between the anti-obesity effects of guava polysaccharide (GP) and gut microbiota is unknown. In current study, seven-week-old C57BL/6 mice were fed high-fat diet (HFD) supplemented with GP (100 mg/kg) by oral gavage for 11 weeks. GP supplementation alleviated HFD-induced body weight gain and visceral obesity, and reduced serum cholesterol, triglyceride, and LDL-C levels. In addition, GP ameliorated insulin resistance and prevented hepatic lipid accumulation and meta-inflammation in both liver and adipose tissues in obese mice. Remarkably, GP treatment restored the Firmicutes/Bacteroidetes ratio, induced growth of beneficial bacteria including Clostridium XlVa, Parvibacter, and Enterorhabdus, and decreased in inflammation-related bacteria Mucispirillum in mice fecal samples, accompanied with enhanced production of colonic short chain fatty acids especially butyric acid. However, the metabolic benefits of GP diminished in antibiotics-treated HFD-fed mice. Overall, GP improved metabolic profiles in HFD-induced obese mice via the mediation of gut microbiota-dependent pathways. GP might be developed and utilized as prebiotics in nutraceutical and food industry.

In comparison with conventional reverse time migration (RTM), least-squares RTM (LSRTM) can improve imaging resolution and compensate irregular illumination caused by acquisition geometry and compl...

With the progress in computational power and seismic acquisition, elastic reverse time migration is becoming increasingly feasible and helpful in characterizing the physical properties of subsurface structures. To achieve high‐resolution seismic imaging using elastic reverse time migration, it is necessary to separate the compressional (P‐wave) and shear (S‐wave) waves for both isotropic and anisotropic media. In elastic isotropic media, the conventional method for wave‐mode separation is to use the divergence and curl operators. However, in anisotropic media, the polarization direction of P waves is not exactly parallel to the direction of wave propagation. Also, the polarization direction of S‐waves is not totally perpendicular to the direction of wave propagation. For this reason, the conventional divergence and curl operators show poor performance in anisotropic media. Moreover, conventional methods only perform well in the space domain of regular grids, and they are not suitable for elastic numerical simulation algorithms based on non‐regular grids. Besides, these methods distort the original wavefield by taking spatial derivatives. In this case, a new anisotropic wave‐mode separation scheme is developed using Poynting vectors. This scheme can be performed in the angle domain by constructing the relationship between group and polarization angles of different wave modes. Also, it is performed pointwise, independent of adjacent space points, suitable for parallel computing. Moreover, there is no need to correct the changes in phase and amplitude caused by the derivative operators. By using this scheme, the anisotropic elastic reverse time migration is more efficiently performed on the unstructured mesh. The effectiveness of our scheme is verified by several numerical examples.

We are grateful to editor Jan S. Hesthaven, and two anonymous reviewers for improving the initial manuscript. We thank D. Keyes and D. Peter's supporting for the High-Performance Computing facilities. The research reported in this publication was in part supported by funding from King Abdullah University of Science and Technology (KAUST). For computer time, this research used the resources of the Information Technology Division and Extreme Computing Research Center (ECRC) at KAUST.

Traditional least-squares reverse time migration (LSRTM) often aims to improve the quality of seismic imaging, such as removing the acquisition footprint, suppressing migration artifacts and enhancing resolution. In this paper, we find that the conventional reflectivity defined in the LSRTM is related to the normal-incident reflection coefficient and the background velocity. Compared with the defined reflectivity, our inverted result is relatively “true”. With reflected data, LSRTM is mainly sensitive to impedance perturbations. According to an approximate relationship between them, we reformulate the perturbation related system into a reflection-coefficient related one. Then, we seek the inverted image through linearized iteration. Moreover, with the assumption that the density varies more gradually than the migration velocity, only the knowledge of the latter is required, although the reflected waves are produced at impedance discontinuities. We test our method using the 2D Marmousi synthetic dataset.

Standard anticoagulant treatment alone for acute lower extremity deep vein thrombosis (DVT) is ineffective in eliminating thrombus from the deep venous system, with many patients developing postthrombotic syndrome (PTS). Because catheter-directed thrombolysis (CDT) can dissolve the clot, reducing the development of PTS in iliofemoral or femoropopliteal DVT. This meta-analysis compares CDT plus anticoagulation versus standard anticoagulation for acute iliofemoral or femoropopliteal DVT. Ten trials were included in the meta-analysis. Compared with anticoagulant alone, CDT was shown to significantly increase the percentage patency of the iliofemoral vein ( P < .00001; I2 = 44%) and reduce the risk of PTS ( P = .0002; I2 = 79%). In subgroup analysis of randomized controlled trials, CDT was not shown to prevent PTS ( P = .2; I2 = 59%). A reduced PTS risk was shown, however, in nonrandomized trials ( P < .00001; I2 = 47%). Meta-analysis showed that CDT can reduce severe PTS risk ( P = .002; I2 = 0%). However, CDT was not indicated to prevent mild PTS ( P = .91; I2 = 79%). A significant increase in bleeding events ( P < .00001; I2 = 33%) and pulmonary embolism (PE) ( P < .00001; I2 = 14%) were also demonstrated. However, for the CDT group, the duration of stay in the hospital was significantly prolonged compared to the anticoagulant group ( P < .00001; I2 = 0%). There was no significant difference in death ( P = .09; I2 = 0%) or recurrent venous thromboembolism events ( P = .52; I2 = 58%). This meta-analysis showed that CDT may improve patency of the iliofemoral vein or severe PTS compared with anticoagulation therapy alone, but measuring PTS risk remains controversial. However, CDT could increase the risk of bleeding events, PE events, and duration of hospital stay.

During the stainless steel making process, Fe-Cr-Ni of lower sulfur content can be recycled from stainless steel dust (SSD) by briquettes reduction. An investigation of cooperative desulfurization efficiency for bearing carbon SSD briquettes reduction process is conducted. First, slag amount prediction model is established through corundum crucible erosion behavior in order to analyze the desulfurization efficiency. Next, the effects of carbon amount, CaF2 amount, silicon ferrous, basicity and feeding modes on the desulfurization rate and the sulfur distribution ratio are analyzed. Furthermore, sulfur distribution ratio prediction model between SSD briquettes and molten iron is originally established in the principle of thermodynamic equilibrium. Results show that basicity, CaF2, silicon ferrous and carbon amount could promote the desulfurization rate and sulfur distribution ratio. When simultaneously adding iron ingot and SSD briquettes, feeding mode has a higher desulfurization rate and better metal/slag separation than when adding iron ingot prior to SSD briquettes. During the experiment, desulfurization rate varies from 55% to 70% and the sulfur distribution ratio results range from 2 to 10. The sulfur distribution ratio prediction results greatly match with experimental results implying that the desulfurization rate analysis method through corundum crucible erosion behavior is more accurate.

Ovarian carcinoma is the leading cause of death from gynecologic malignancies. The oncogenic role of anaplastic lymphoma kinase (ALK) is well characterized in many hematopoietic and solid tumors. ALK expression in ovarian carcinoma has been reported but the exact status of ALK protein and its association with clinicopathologic features requires further investigation. ALK expression was determined by immunohistochemistry in 110 primary ovarian carcinomas, including 85 cases of serous carcinoma and 25 cases of mucinous carcinoma. Fluorescence in situ hybridization (FISH) and real-time reverse transcription polymerase chain reaction (RT-PCR) were used for evaluating ALK translocation in ALK-positive ovarian carcinomas. Among 110 ovarian carcinomas, 23 (20.9%) cases were ALK positive by immunohistochemistry. All ALK-positive cases were ovarian high-grade serous carcinoma. ALK expression was detected in 23/85 (27.1%) ovarian serous carcinoma and 0/25 (0%) in ovarian mucinous carcinoma. None of the 23 ALK IHC-positive cases harbored ALK gene translocations by FISH or RT-PCR. ALK protein expression was associated with patient age, tumor stage, and histologic type. Specifically, the probability of ALK protein expression was significantly higher in high-grade serous carcinomas in older patients (above 50 y) with advanced disease (FIGO stage III and IV) compared with the low-grade serous and mucinous carcinomas in younger patients with relatively early disease. In conclusion, aberrant ALK expression is observed in ovarian serous carcinoma but not in mucinous carcinoma, is independent of gene translocation, and might be associated with progression and prognosis.

The contribution of CXCL12/CXCR4/CXCR7 axis to cancer progression has been increasingly recognized. However, its role in thyroid cancer development remains unclear. The present study aimed to examine the expression and function of CXCL12 and its receptors in thyroid cancer. The expression of CXCL12/CXCR4/CXCR7 in human tissue specimens of papillary, follicular, medullary, and anaplastic thyroid carcinoma, follicular adenoma, Hashimoto's thyroiditis and nodular goiter were examined by immunohistochemistry using a tissue microarray. CXCR4 and CXCR7 were over-expressed in human thyroid cancer cells K1 by transduction of recombinant lentivirus. The effect of overexpression of CXCR4 and CXCR7 on K1 cell proliferation and invasion and the molecular mechanism underlying the effect were investigated. CXCL12 was exclusively expressed in papillary thyroid carcinoma tissue but absent in other types of thyroid malignancies and benign lesions. CXCR7 was widely expressed in the endothelial cells of all types of malignancy but only occasionally detected in benign lesions. CXCR4 was expressed in 62.5% of papillary thyroid carcinoma tissue specimens and in 30–40% of other types of malignancy, and it was either absent or weakly expressed in benign lesions. CXCL12 stimulated the invasion and migration of K1 cells overexpressing CXCR4, but did not affect K1 cells overexpressing CXCR7. K1 cell proliferation was not affected by overexpression of CXCR4 or CXCR7. Overexpression of CXCR4 in K1 cells significantly increased AKT and ERK phosphorylation and markedly induced the expression and activity of matrix metalloproteinase-2 (MMP-2). Thus, CXCL12 may be an effective diagnostic marker for papillary thyroid carcinoma, and CXCL12/CXCR4/CXCR7 axis may contribute to thyroid cancer development by regulating cancer cell migration and invasion via AKT and ERK signaling and MMP-2 activation.

Malachite green (MG), a recalcitrant, carcinogenic, and mutagenic triphenylmethane dye, was decolorized and detoxified using crude manganese peroxidase (MnP) prepared from the white rot fungus Irpex lacteus F17. In this study, the key factors (pH, temperature, MG, Mn(2+), H2O2, MnP) in these processes were investigated. Under optimal conditions, 96 % of 200 mg L(-1) of MG was decolorized when 66.32 U L(-1) of MnP was added for 1 h. The K m, V max, and k cat values were 109.9 μmol L(-1), 152.8 μmol L(-1) min(-1), and 44.5 s(-1), respectively. The decolorization of MG by MnP followed first-order reaction kinetics with a kinetic rate constant of 0.0129 h(-1). UV-vis and UPLC analysis revealed degradation of MG. Furthermore, seven different intermediates formed during the MnP treatment of 0.5 h were identified by LC-TOF-MS. These degradation products were generated via two different routes by either N-demethylation of MG or the oxidative cleavage of the C-C double bond in MG. Based on ecotoxicity analyses performed on bacteria and algae, it was confirmed that MG metabolites produced by the MnP-catalyzed system were appreciably less toxic than the parent compound. These studies indicate the potential use of this enzyme system in the clean-up of aquatic and terrestrial environments.

Purpose To evaluate the clinical value of immunohistochemistry (IHC) using anti-BRAF V600E antibody (clone VE1) for specific detection of the BRAF V600E mutant protein in formalin-fixed paraffin-embedded papillary thyroid carcinoma (PTC) specimens. Methods A total of 118 PTC cases and 116 control cases processed between January 2008 and June 2010 were selected and created tissue microarrays (TMAs) for the study. BRAF V600E (VE1) IHC was performed on tissue sections from PTC cases to determine mutation status. Molecular tests (Sanger sequencing/ARMS) were used to confirm the BRAF V600E gene mutation in primary PTC. Results A uniformly cytoplasmic staining throughout the tumors was observed in IHC-positive cases. BRAF V600E was detected in 68.6% (81/118) of PTC samples by IHC and in 61.9% (73/118) by Sanger sequencing/ARMS. The overall concordance between IHC and Sanger sequencing/ARMS was 93.2% (110/118). The sensitivity and specificity of the BRAF V600E IHC was 100% (73/73) and 82.2% (37/45), respectively. Positive and negative predictive values were 90.1% (73/81) and 100% (37/37), respectively. Expression of the BRAF V600E mutant protein was detected in all of 59 cases of primary carcinoma and corresponding metastatic carcinoma in lymph nodes. The concordance between IHC staining in primary and metastatic PTC was 100% (59/59). Conclusion IHC using VE1 antibody for detection of the BRAF V600E mutant protein expression in PTC showed high sensitivity and acceptable specificity, which are critical for diagnostic purposes. IHC staining for BRAF V600E showed uniformly cytoplasmic expression in both primary tumor and metastatic nodes. Therefore, IHC has high practical value for the detection of the BRAF V600E mutation in metastatic and primary PTC.

This study was retrospectively performed to analyze correlations between clinicopathological features of colorectal cancer (CRC) and mutations in KRAS, NRAS, and BRAF in Chinese patients, and to assess the importance of detecting additional mutations in KRAS exons 3 and 4 and NRAS in patients with CRC. RAS (KRAS and NRAS) and BRAF mutations were detected in 715 and 655 patients respectively. The mutation rate of RAS (KRAS or NRAS) was 45.6% (326/715). KRAS exon 2 mutations were evaluated in 36.6% of patients (262/715). Additional mutations in RAS exons occurred in 9.0% of patients (64/715), including KRAS exons 3 and 4 in 5.6% (40/715) and NRAS exons 2, 3, or 4 in 3.4% (24/715). Among 453 patients with wild-type KRAS exon 2, 14.1% (64/453) had other mutations in RAS exons. The most frequent sites of mutations were codons 12, 13, 61, and 146 in KRAS and codons 12 and 61 in NRAS. The mutation rate of BRAF (exon 15) was 4.0% (26/655), and the most frequent mutation site was codon 600. Among 440 patients with CRC who had a primary tumor resection at our center, those with mucinous or signet ring cell CRC were more likely to harbor KRAS mutations than those with adenocarcinoma (62.7% vs. 43.6%, P=0.006 and 59.3% vs. 39.6%, P=0.004, respectively). Female patients had a higher BRAF (exon 15) mutation rate than male patients (5.1% vs. 1.1%, P=0.017). Detection of both KRAS and NRAS mutations is useful for selecting patients who will benefit from anti-EGFR monoclonal antibody therapy. KRAS mutations were more frequent in patients with mucinous adenocarcinoma/signet ring cell CRC, whereas BRAF mutations were more common in female patients with CRC.

In order to develop the application of the natural polysaccharide lentinan (LNT) and decrease the side effects of doxorubicin, we successfully synthesized a novel folate-modified maleilated lentinan-doxorubicin (FA-M.LNT-DOX) polymer and used it for tumor-targeted drug delivery. The release efficiency and cytotoxicity of the prodrugs were evaluated in vitro. Although DOX release from FA-M.LNT-DOX was quite slow in a neutral buffer, it was particularly fast in an acidic solution with a pH of 5.0. Compared with DOX, FA-M.LNT-DOX showed higher cytotoxicity in HeLa cells and significantly lower cytotoxicity in normal cells. These results suggested that FA-M.LNT-DOX could be considered as a potential drug delivery candidate for folate receptor-positive cancer therapy.

Purpose The RET fusion gene has been recently described in a subset of non–small-cell lung cancers (NSCLCs). Because we have limited knowledge about these tumors, this study was aimed at determining the clinicopathologic characteristics of patients with NSCLC harboring the RET fusion gene. Patients and Methods We examined the RET fusion gene in 936 patients with surgically resected NSCLC using a reverse transcriptase polymerase chain reaction (PCR) plus quantitative real-time PCR strategy, with validation using immunohistochemical and fluorescent in situ hybridization assays. A subset of 633 lung adenocarcinomas was also studied for EGFR, KRAS, HER2, and BRAF mutations, as well as ALK rearrangements. Patient characteristics, including age, sex, smoking history, stage, grade, International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification of subtypes of lung adenocarcinoma, and relapse-free survival, were collected. Results Of 936 patients with NSCLC, the RET fusion gene was exclusively detected in 13 patients (11 of 633 patients with adenocarcinomas and two of 24 patients with adenosquamous cell carcinomas). Of the 13 patients, nine patients had KIF5B-RET, three patients had CCDC6-RET, and one patient had a novel NCOA4-RET fusion. Patients with lung adenocarcinomas with RET fusion gene had more poorly differentiated tumors (63.6%; P = .029 for RET v ALK, P = .007 for RET v EGFR), with a tendency to be younger (≤ 60 years; 72.7%) and never-smokers (81.8%) and to have solid subtype (63.6%) and a smaller tumor (≤ 3 cm) with N2 disease (54.4%). The median relapse-free survival was 20.9 months. Conclusion RET fusion occurs in 1.4% of NSCLCs and 1.7% of lung adenocarcinomas and has identifiable clinicopathologic characteristics, warranting further clinical consideration and targeted therapy investigation.

The rare epidermal growth factor receptor (EGFR) mutation S768I has only been reported sporadically in patients with lung adenocarcinoma (AC). This study aimed to investigate the prevalence of the S768I mutation in Chinese patients with lung AC and to retrospectively analyze the response of S768I mutants to tyrosine kinase inhibitors (TKIs). A total of 6698 tissue specimens of lung AC were collected from the Department of Pathology of Shanghai Cancer Center of Fudan University between 2013 and 2015 and screened for EGFR mutations. Previously reported cases were combined with our data to evaluate the response of the S768I mutants to TKIs. Thirty-five patients (0.52 %, 35/6698) harbored the S768I mutation, including 8 (22.9 %) with just the S768I mutation and 27 (77.1 %) with compound mutations of S768I and other EGFR mutations (including G719X and L858R). The median progression-free survival (PFS) of the 8 cases with available PFS data was 5.0 months (95 % confidential interval: 0.4–9.6 months). We combined our cases with the sporadic cases from 14 previous reports (total 49 cases) to assess the response to TKIs and found that the objective response rate was 40.0 %, 74.9 %, and 60.0 % for S768I-only mutants, S768I+G719X mutants, and S768I+L858R mutants, respectively. S786I mutation is rare in lung AC and is frequently accompanied by G719X, L858R, or other EGFR mutations. Patients harboring only the S768I mutation appear to be more sensitive to TKIs than those with the wild-type EGFR. The S768I mutation may increase the sensitivity of G719X to TKIs but not the sensitivity of L858R to TKIs.

College mathematics is the foundation of other subjects, and mathematics has shown its unique charm in technical rapid development today. Mathematics plays an important role in cultivating students' innovation ability and good characters. The theory and method of mathematics is widely applied to different fields of physics, chemistry, biology, medicine, economics and management, military et al. Higher mathematics is one of the basic courses in Colleges and Universities. However, the traditional teaching mode has restricted the students' enthusiasm and creativity, even affected the quality of talents training. First of all, today's mathematics teaching in many ways is subjected to the traditional way, and the teaching methods contradict to innovative ideas. Therefore, it is an indispensable issue about how to improve the higher mathematics teaching methods and students' learning interest. Traditional mathematics teaching method only focuses on explanation of basic concept, the proof of theorem, the derivation of formula et al. Nevertheless, traditional teaching methods ignore the application of mathematics in practice, as the results, students are often able to solve problems skillfully, but they cannot use the mathematics knowledge to solve some practical problems, students even have no ideas about the connection between mathematics and specialized courses. In view of above problems, in this paper, we introduce correlation theory and principles of multi-agent, and we combine multi-agent with the characteristics of mathematics teaching in Colleges and Universities. In the process of teaching evaluation model construction, we flexibly select evaluation model, such as analytical hierarchy process model, and regression analysis model. We also introduce intelligent recommendation system based on different algorithms in order to better evaluate teaching effects.

Mineralogical phases of steelmaking slags have significant influences on the carbonation of the slags. In this paper, the effects of temperature and reaction time on the conversion of calcium-related phases and the carbonation degree of a slag sample were studied. The experimental conditions were a liquid-to-solid ratio of 20 mL/g, a carbon dioxide flow rate of 1 L/min and a slag particle size of 38–75 μm. The results show that the optimum carbonation temperature and reaction time are 60 °C and 90 min, respectively, and calcite phase content is about 26.78% while the conversion rates of Ca3Al2O6, CaSiO3, Ca2SiO4 and free CaO are about 40%, 42.46%, 51% and 100%, respectively, and the carbon dioxide sequestration efficiency is about 170 g/kg slag.

// Kai Xue 1, 4, * , Xun Ye 2, 5, * , Fang Liu 2 , Qunlin Zhang 1, 4 , Qifeng Wang 3, 4 , Shan Huang 6 , Jiachen Wang 1, 4 , YongMing Lu 3, 4 , Ye Guo 1, 4 , Xia Meng 2, 5 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China 2 Fudan University Shanghai Cancer Center, Institut Merieux Lab, Fudan University Shanghai Cancer Center, Shanghai, China 3 Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China 4 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 5 Medical Device Development Department (MD3), bioMerieux Co., Ltd., Shanghai, China 6 Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, China * These authors have contributed equally to this work Correspondence to: Ye Guo, email: pattrickguo@gmail.com Xia Meng, email: xmeng00@hotmail.com Keywords: sweyjawbu , ALK rearrangements, lymphoma Received: February 24, 2016 Accepted: November 02, 2016 Published: December 10, 2016 ABSTRACT In recent years molecular subtyping has become an important tool for accurate diagnosis of many cancers; for example, the detection of ALK rearrangements in lymphoma and lung cancer helps clinicians provide more precise diagnosis and treatment. Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are two routine approaches used to detect ALK rearrangements. However, difficulties with acquisition of biopsy samples, high costs, and long waiting time for results negatively impact the application of these methods. A rapid and inexpensive alternative would be a useful complement to current ALK rearrangement detection. We identified a novel gene, sweyjawbu , from Affymetrix microarray studies. Its expression correlated strongly with ALK in an analysis of 1037 cancer cell lines (correlation coefficient = 0.92). By comparing sweyjawbu transcript levels, it was possible to discriminate 12 ALK rearrangement-positive lymphoma samples from 64 ALK rearrangement-negative lymphomas. Moreover, combining measurements of sweyjawbu expression and the ratio of the 5’ and 3’ portions of the ALK transcript provided even more accurate identification of ALK rearrangement-positive lymphomas. This novel approach is an excellent complement or alternative to existing FISH and IHC methodologies.

HER2/neu alteration detection in breast cancer is important for decision making of the HER2-targeted therapy. We retrospectively analyzed the HER2/neu status by fluorescence in situ hybridization and HER2 protein expression by immunohistochemistry in a cohort of 481 patients with invasive breast cancer. Fluorescence in situ hybridization showed that 57.4% of cases exhibited HER2 amplification but 41.4% did not, and 1.2% exhibited an equivocal status. Immunohistochemistry showed that 10.4%, 16.8%, 38.3%, and 34.5% of cases had scores of 0, 1+, 2+, and 3+, respectively. The HER2 status showed a moderate agreement with HER2 expression with a score of 0, 1+, and 3+ (κ = 0.576, P.05), and the concordance rate was 90%, 61.7%, and 83.1%, respectively. The HER2 amplification occurred more likely in cases with higher immunohistochemistry scores (P.001), and polysomy 17 was observed in 28.3% of cases, but more frequently in the HER2 amplification subgroup (33.3%) than in the HER2 nonamplification subgroup (20.1%) (P.05). There was no significant correlation between the frequency of polysomy 17 and immunohistochemistry scores (P.05). In the immunohistochemistry 2+ group, 56.5% cases showed HER2/neu amplification, and polysomy 17 occurred more likely in the HER2 amplification subgroup (34.6%) than in the HER2 nonamplification group (13.0%) (P.001). We concluded that the HER2 status was correlated with HER2 protein expression levels, and it is necessary to determine the HER2 status for cases with immunohistochemistry 2+. The frequency of polysomy 17 was correlated with the HER2 copy number and partially contributed to HER2/neu amplification but not HER2 protein expression.

Systemic anaplastic large cell lymphoma (ALCL) can be divided into two subgroups, anaplastic lymphoma kinase (ALK)-positive and ALK-negative, based on the expression of ALK protein. Expression of this protein is due to genetic alterations of ALK at 2p23. Overall, observations on ALK protein, ALK mRNA, ALK-associated genetic alterations and their relationships, to one another are not often reported in the literature. In this study, we investigated the expression of ALK protein, mRNA and fusion transcripts involving ALK and their relationships in ALCL and analyzed formalin-fixed, paraffin-embedded tissues. Forty-five human cases were analyzed with immunohistochemistry for the ALK protein and RT-PCR for ALK mRNA and seven kinds of ALK involved fusion transcripts. Our results showed that the expression of ALK protein, ALK mRNA and ALK fusion transcripts were significantly related to one another (P0.01). Consistent with the expression of ALK protein, patients presenting with ALK mRNA or ALK involved fusion transcripts were significantly younger than those lacking ALK gene alteration (P0.01). This study demonstrates expression of both ALK protein and ALK mRNA are positively correlated with expression of ALK-associated fusion transcripts. Combined detection of ALK protein, ALK mRNA and ALK fusion transcripts can complement each other to aid in the diagnosis of ALCL.

To analyze the MR imaging findins of acinic cell carcinoma(ACC) in parotid gland and develop the diagnosis of this disease.The MR imaging fearures of 11 patients with pathologically proved ACC were retrospectively analyzed. MR imagings were analyzed in relation to the follow:amount, location, size, shape, margin, pseudocapsule, MR signal intensity and enhanced pattern and the cervical lymphadenopathy. The clinical analysis on patients included age, sex, and follow-up.There were 11 patients, 7 lesions was located in the right parotid gland and 4 lesions was located in the left parotid gland; the average maximum diameter was (2.66±0.99)cm; 7 lesions showed lobulated,and 4 lesions showed round; 8 lesions had no pseudocapsules and 3 lesions had incomplete pseudocapsule. All lesions showed homogeneous or heterogeneous isointense and slight hyperintense on T1 WI and T2WI. On post contrast images, the tumor parenchyma ingredients showed remarkable enhancement in all lesions.The MR imaging of ACC in the parotid gland don't have specific features, but when the tumor of the parotid gland showed no pseudocapsule (or showed incomplete pseudocapsule), lobulate, small cysitc and remarkable enhancement, it may indicate ACC, and the correct diagnosis depends on clinical pathology.

Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC), which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP) can make subclassification difficult. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping these clinical entities. In our study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin 20 (CK20) and cyclinD1 were assessed. Molecular genetic alterations such as the gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed for their usefulness in differentiating these conditions. Based on our analysis, Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor types. Fluorescence in situ hybridization (FISH) can also provide important data in cases in which the malignant nature of an inverted urothelial neoplasm is unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67 and CK20 can be positively detected using FISH.

This paper analyzed hybrid DHCR production of continuous casting-hot rolling (CC-HR) and the production model of reheating furnaces. The scheduling model of reheating furnaces based on hybrid DHCR production was established. On the basis of meeting the requirements of the reheating furnaces process, the model considered the waiting time before slabs entering the reheating furnaces and the idle time of the hot rolling mill. Then, the model was solved by tabu Search. Finally, two slab groups which were few varieties and large quantities and many varieties and small quantities were simulated in the 2250mm hot rolling line for special reheating furnaces mode and non-special reheating furnaces mode. The simulation results showed that it can significantly improve thermal efficiency of reheating furnaces in the specific reheating furnaces mode.

Approximately 3–7% of non-small cell lung cancers harbor an anaplastic lymphoma kinase (ALK) gene fusion, constituting a new molecular subtype of lung cancer that responds to crizotinib, an ALK inhibitor. Although previous studies have evaluated ALK-rearranged lung cancers, the comprehensive analysis of lung cancer in Chinese has not well assessed. Herein, we identified 44 cases of ALK-rearranged samples by fluorescent in-situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcription polymerase chain reaction (RT-PCR) in a large number of surgically resected lung cancers. All 44 ALK-rearranged lung cancers were adenocarcinomas, with 2 cases having additional focal squamous components. The goal was to analyse the clinicopathological features of ALK-rearranged lung adenocarcinomas. Our data showed that a cribriform structure, prominent extracellular mucus and any type of mucous cell pattern may be either sensitive or specific to predict an ALK rearrangement. We used FISH as the standard detection method. We compared the ALK rearrangement accuracy of FISH, RT-PCR and IHC. RT-PCR could define both the ALK fusion partner and the fusion variant, but seemed unable to detect all translocations involving the ALK gene. It is noteworthy that IHC using the D5F3 antibody (Cell Signaling Technology) showed higher sensitivity and specificity than the ALK1 antibody (Dako). Therefore, we conclude that IHC remains a cost-effective and efficient technique for diagnosing ALK rearrangements and that D5F3 can be the optimal screening antibody in clinical practice.

Saccharomyces cerevisiae yeast was entrapped in alginate for the recovery of copper ions from aqueous solution, in which both yeast and alginate could take metal ions. The Freundlich isotherm had been shown to be successful in describing biosorption and a linear biosorption was assumed when the equilibrium copper ion concentration in the fluid was lower than 1 mg/l. The biosorption isotherm was found to be independent of the immobilized yeast densities ranging from 6 to 17 percent. A mathematical model describing the mass transport along with the biosorption was developed with the main assumptions that the inner diffusion with constant diffusivity was the rate limiting step of the biosorption process and the pore solution locally equilibrated with the adjacent biosorbent (both yeast and alginate). This model has theoretical advantages over the formerly proposed Shrinkage Core Model and Linear Adsorption Model. Effective diffusion coefficients of copper ion in immobilized yeast beads using the model developed were found to be independent of the immobilized yeast densities ranging from 6 to 17 percent. The average result was 2.22×10−5 cm2/s.