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Tuning morphology and doping additional rare earth (RE) cations are potential techniques to promote the photocatalytic performance of ceria (CeO2), evaluating the collaborative effects of morphology and RE dopants is significant for producing high active ceria-based catalysts. So in this work, cubic, polyhedral and rod-like nanoceria doped with 10 mol % La (lanthanum), Y (yttrium), or Sm (samarium) were synthesized by a facile template-free hydrothermal method. Phases, morphologies, oxygen vacancies (OVs) concentration, energy band structure, photo-carriers separation/recombination, and photodegradation ratio toward methylene blue (MB) dye of as prepared ceria were studied. Results show that doped CeO2 maintains a similar morphology structure with un-doped sample and the band gap narrows slightly. Y-doped nanoceria, with an improved separation and a reduced recombination of photo-excited electrons (e−) and holes (h+), owns a higher MB photodegradation ratio than that of samples doping with La or Sm, which is measured as 79.04, 84.43, and 85.59% for Y-doped cubic, polyhedral, and rod-like CeO2. The collaborative influence of morphology tuning and RE (La, Y, and Sm) doping on photocatalytic performance of nanoceria includes the effects of doped elements and the formation of OVs. The elevation of OVs concentration as well as the separation efficiency of photo-generated e−/h+ are suggested to further enhance the photocatalytic performance of ceria. [ABSTRACT FROM AUTHOR]

Background: Rectal cancer is mainly cured by radical resection with neoadjuvant chemoradiation or adjuvant chemotherapy. Pathological T1 lesions can be managed by local treatment and radiotherapy thereafter. Lower morbidity is the key benefit of these local treatments. Since nodal metastasis is important for staging, radical resection (RR) is suggested. Rectal cancer has higher surgical morbidity than colon cancer; local treatment has been the preferred choice by patients. Methods: We retrospectively enrolled data of 244 patients with pT1 rectal adenocarcinoma. A total of 202 patients (82.8%) underwent RR, including low anterior resection (LAR) and abdomino-perineal resection (APR), and 42 patients (17.2%) underwent LT, including transanal excision and colonoscopic polypectomy. Results: In our study, seven patients (16.7%) had loco-regional recurrence and distant metastasis from the LT group while eight patients (4.0%) had distant metastasis without loco-regional recurrence from the RR group. The lymph node metastasis rate in RR group was 8.4%. Forty-seven patients (24.2%) underwent LAR with temporary stoma, and its reversal rate was 100%. In the RR group, postoperative complication rate was 10.4% with a mortality rate of 0.5%. Recurrence-free survival (RFS) was 95.7% for RR and 80.2% for LT (P = 0.001), and overall survival (OS) was 93.7% for RR and 70.0% for LT (P = 0.001). Conclusion: This study found that RFS and OS in patients of pT1 rectal adenocarcinoma that had received RR were better than receiving LT. Further adjuvant chemotherapy was possible for some RR patients. A higher recurrence rate after LT must be balanced against the morbidity and mortality associated with RR. [ABSTRACT FROM AUTHOR]

Ceria nanorods (NRs) with an average length of 23, 73, 115, 131, and 192 nm were synthesized separately by a facile hydrothermal method and then were roasted at 600 °C in air, 50% H2, and pure H2 to generate various concentrations of surface oxygen vacancies (OVs). OVs concentration in ceria lattice is firstly increasing and then trends to decrease with the rising of ceria NRs length, while the band gap of ceria NRs expands with length increasing and slightly widens with the elevation of surface OVs concentration. Separation efficiency of photo-excited electrons/holes (e−/h+) and photodegradation ratio of methylene blue (MB) with ceria NRs elevate firstly and then decrease with the length increasing, while the generated OVs promote the photocatalytic activity of ceria. The ceria NRs with an average length of 115 nm and calcined in hydrogen show a better photocatalytic activity with the MB degradation ratio of 86.32%. [ABSTRACT FROM AUTHOR]

Background: Clinically, metastatic rectal cancer has been considered a subset of left-sided colon cancer. However, heterogeneity has been proposed to exist between high and middle/low rectal cancers. We aimed to examine the efficacy of anti-epidermal growth factor receptor (EGFR) treatment for middle/low rectal and left-sided colon cancers.Methods: This study enrolled 609 patients with metastatic colorectal cancer who were treated with anti-EGFR therapy. They were divided into groups based on primary tumour locations: the right-sided colon, the left-sided colon or the middle/low rectum. The efficacy of first-line and non-first-line anti-EGFR treatment was analysed. Genomic differences in colorectal cancer data from The Cancer Genome Atlas (TCGA) were investigated and visualised with OncoPrint and a clustered heatmap.Results: On first-line anti-EGFR treatment, patients with middle/low rectal tumours had significantly lower progression-free survival, overall survival, and overall response rates (6.8 months, 27.8 months and 43%, respectively) than those with left-sided colon cancer (10.1 months, 38.3 months and 66%, respectively). Similar outcomes were also identified on non-first-line anti-EGFR treatment. In TCGA analysis, rectal tumours displayed genetic heterogeneity and shared features with both left- and right-sided colon cancer.Conclusions: Anti-EGFR treatment has lower efficacy in metastatic middle/low rectal cancer than in left-sided colon cancer. [ABSTRACT FROM AUTHOR]

Given the unclear preference criteria for regorafenib in treating refractory metastatic colorectal cancer (mCRC), this study aimed to construct an algorithm in selecting right patients for regorafenib. This was a multicenter retrospective cohort study. Patients with pathology confirmed mCRC and administered with regorafenib for > 3 weeks were enrolled. Patients with good response were defined to have progression-free survival (PFS) of ≥ 4 months. The Kaplan–Meier plot was used to analyze survival. A Cox proportional hazards model was used to analyze univariate and multivariate prognostic factors and was visualized using forest plot. A clustering heatmap was used to classify patients according to responses. The decision tree and nomogram were used to construct the approaching algorithm. A total of 613 patients was analyzed. The median PFS and overall survival (OS) were 2.7 and 10.6 months, respectively. The partial response and stable disease rate are 2.4% and 36.4%. The interval between metastasis (M1) and regorafenib, metastatic status (number, liver, and brain), and CEA level were independent prognostics factors of PFS that classifies patients into three groups: good, bad and modest-1/modest-2 group with PFS > = 4 months rates of 51%, 20%, 39% and 30%, respectively. Results were used to develop the decision tree and nomogram for approaching patients indicated with regorafenib. The preference criteria for regorafenib in treating patients with refractory mCRC are small tumor burden (CEA), slow growth (interval between metastasis and regorafenib) and poor/scanty spread (metastatic status: number and sites of metastasis): The 3S rules. TRIAL registration ClinicalTrials.gov Identifier: NCT03829852; Date of first registration (February 11, 2019). [ABSTRACT FROM AUTHOR]

Homogeneously rare-earth (RE=La, Sm and Y) ions doped CeO2 nanoparticles (NPs) with enhanced photocatalytic performance were synthesized by a facile KOH-NaOH molten flux method. XRD, TEM, EDS mapping and XPS results demonstrate that RE cations have been successfully doped into the CeO2 lattice, which leads to the lattice expansion/shrinking, and more oxygen vacancies are generated after RE ions doping. The UV-Vis DRS and PL spectra indicate that RE-doped CeO2 samples have slightly narrower band gaps and significantly reduced photo-generated electron-hole recombination rates. 5% RE ions doped CeO2 NPs show excellent photocatalytic performances and the photodegradation ratio of methylene blue (MB) increases from 71.63% of undoped CeO2 to 76.35%, 77.51% and 77.37% for 5%-La, 5%-Sm and 5%-Y-doped CeO2 NPs, respectively. The obviously reduced recombination rate of e−/h+ pairs after RE ions doping may be the critical factor for the enhanced photocatalytic performance. [ABSTRACT FROM AUTHOR]

Molten salts synthesis (MSS) is a simple and potential technique for ceria nanoparticles (NPs) production, but the relevant effects of salt medium and cerium precursor on the synthesized ceria NPs need further attention. In the present work, we investigated the influences of frequently employed KCl–LiCl and KOH–NaOH molten flux and typical inorganic cerium precursors on the characterizations and photocatalytic property of ceria NPs. Results show that the CeO2 NPs obtained in molten KOH–NaOH flux have smaller particle/crystal sizes but more serious agglomeration than that from KCl–LiCl flux. UV–Vis DRS spectra reveal that the ceria synthesized in molten hydroxides from the cerium nitrate precursor has the narrowest band gap of 2.87 eV in studied ceria samples. The ceria NPs obtained from KCl–LiCl flux have wider band gaps of 3.15–3.29 eV and faster recombination rates of photo-generated e− and h+. It was found that the ceria NPs obtained in molten KCl–LiCl salt show better photocatalytic activities for methylene blue (MB) degradation and may be due to the uniform size distribution and well-dispersed particles. [ABSTRACT FROM AUTHOR]

Solid oxide membrane-assisted electrolytic reduction of solid Cr2O3 to Cr in molten CaCl2 was performed using a sintered porous Cr2O3 cathode paired with an yttria-stabilized zirconia (YSZ) tube anode containing carbon-saturated liquid copper alloy. Analyses of the reduction mechanism, ion migration behavior, and effects of cathode pellet porosity and particle size on the electrolysis products and reduction rate revealed that the cathode microstructure and electrolytic conditions were key factors influencing the electrolysis process. Optimal results were obtained when the cathode was characterized by high porosity and a small particle size because this combination of features contributed to ion migration. Good electrochemical activation was observed when cathode pellets prepared by 4 MPa molding followed by 2 h of sintering at 1150°C were applied. The electrode reduction process (Cr3+ → Cr2+ → Cr) was promoted by high electrode voltages, and Cr metal was efficiently formed. The proposed method appears to be well suited for electrolytic Cr production because it does not require expensive pre-electro-lysis techniques or generate harmful by-products. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the diurnal fluctuations of macular vessel density (VD) in primary open-angle glaucoma (POAG) and healthy subjects using optical coherence tomography angiography. Methods: A total of 22 POAG eyes and 15 healthy eyes were included in this study. Macular VD, intraocular pressure, and blood pressure were repeatedly measured from 8 AM to 8 PM at a 2-h interval on a single day. Main outcome measures: the macular VD measurements, their diurnal fluctuations, including the difference between their maximal and minimal value (max–min) and their coefficient of variation (CV) in superficial capillary plexus (SCP) and deep capillary plexus (DCP). The mixed-effects model was performed to compare the fluctuations between groups. Results: After adjusted age, the diurnal fluctuations of macular VD in SCP and DCP were significantly higher in POAG eyes compared with healthy subjects (max–min: 6.65 ± 3.54%, 3.92 ± 3.63%, respectively; p = 0.037 and CV: 0.06 ± 0.03, 0.04 ± 0.03, respectively; p = 0.003). The fovea VD in DCP of POAG eyes was higher than in healthy subjects (31.52 ± 4.68% and 25.71 ± 3.70%, p = 0.009). However, there was no significant difference between the fovea VD in SCP in two groups (20.97 ± 4.75% and 19.29 ± 4.35%, p = 0.670). The diurnal macular superficial VD measured in most of the participants was lower in the morning. Conclusions: Whether it is a max–min or a CV assessment method, the POAG eyes had more significant diurnal fluctuations of macular VD than healthy controls, suggesting impaired vascular autoregulation in POAG eyes. [ABSTRACT FROM AUTHOR]

Background and objectives: Accumulating evidences suggest that chronic systemic inflammation (CSI) is independently associated with large number of major non-communicable chronic diseases (NCDs) ranging from metabolic disorders to cancers, and neutrophil-to-lymphocyte ratio (NLR) has been accepted as a novel, convenient marker for CSI response. Testosterone deficiency in men is linked to high risk of NCDs. This cross-sectional study aimed to investigate the individual and joint association of bioavailable testosterone (BIOT) and aging with NLR. Methods: A total of 132 male adults were enrolled during Jan. 2011 and Oct. 2017 in the first affiliated hospital of University of Science and Technology of China. Local weighted regression (LOESS) and multivariable generalized linear regression models were utilized to comprehensively examine the individual and joint association between BIOT and age with NLR. Results: Obvious linear relationships between NLR and BIOT or age were observed with the LOESS models. NLR was negatively correlated to BIOT after adjusting for some potential confounding factors (P = 0.034). As compared to the lowest quartile of BIOT, the adjusted decrease of NLR for the 2nd, 3rd and 4th quartiles were 0.40, 0.64 and 0.72, respectively. Meanwhile, NLR was observed to be independently correlated to elevated age (P = 0.043). Furthermore, as compared to the counterparts, men over 70 years combined with plasma BIOT less than 4.7 nmol/L had the highest NLR level, which suggested that low BIOT and aging jointly correlated to the level of NLR (P = 0.005). Conclusion: BIOT deficiency and aging were individually and jointly correlated to CSI. Men over 70 years combined with BIOT < 4.7 nmol/L were more like to have higher grade of CSI than others. [ABSTRACT FROM AUTHOR]

Dendrobium officinale is a rare and endangered perennial herb in China, which have been used in preparing Chinese tonic medicine for hundreds of years. The severe shortage of this herb and high price have caused that many similar plants were processed as an adulterant and it became difficult to distinguish genuine D. officinale by traditional authentication methods. A sensitive, convenient, and specific method for rapid identification of D. officinale is urgently needed. In the present study, 3D front-face fluorescence technique merged with Independent Component Analysis was used to get the "pure" independent fluorescence signals. The overall 3D-FFF spectra were decomposed into seven independent components (IC). To distinguish D. officinale from other species, IC1 and IC4 were chosen as fluorescence markers and the fluorescence intensity (FI) value at 340 nm/ 442 nm (excitation /emission wavelength) of IC1and 315 nm/ 468 nm of IC4 were used to build a linear model for identifying D. officinale successfully. Compared with other Dendrobium species, D. officinale showed much higher FI1 and FI4 value which is a direct criterion for identification. Meanwhile, even though the FI values of D. officinale may fluctuate due to the difference of growing conditions, the relation between FI1 and FI4 amazingly always fit the linear model constructed (FI4 = 9.9046 + 0.6119FI1, R2 = 0.9811). The linear model is an important finding and specific for D. officinale. Based on the FI value and the goodness of fit in the linear model, D. officinale can be identified quickly. [ABSTRACT FROM AUTHOR]

Single-walled carbon-nanohorns (SNH) exhibit huge application prospects. Notably, spherical SNH possess different morphology from conventional carbon nanotubes (CNT). However, there is a tremendous lack of studies on the nanotoxicity and mechanism of SNH, and their comparison with nanotubes. Here, the dissimilarity between SNH and CNT is found in many aspects including necrosis, pyroptosis, apoptosis, protein expression, hydrolases leakage, lysosome stress, membrane disturbance and the interaction with membrane proteins. The improved biocompatibility of SNH over four types of established CNT is clearly demonstrated in macrophages. Importantly, a key transmembrane protein, glycoprotein nonmetastatic melanoma protein B (GPNMB) is discovered to initiate the nanotoxicity. Compared to CNT, the weaker nano-GPNMB interaction in SNH group induces lower degree of cascade actions from nano/membrane interplay to final cell hypotoxicity. In conclusion, the geometry of single-construct unit, but not that of dispersive forms or intracellular levels of nanocarbons make the most difference. [ABSTRACT FROM AUTHOR]

Thermally stable blue nonstoichiometric nanoceria was produced by feeding nanoceria with an average size of 50 nm into a DC thermal plasma reactor. The effects of different plasma power levels and atmospheres were investigated. XRD results showed the ceria lattice parameter increased with plasma power. SEM and TEM results showed that the shape of nanoparticles changed after plasma treatment; the blue nonstoichiometric nanoceria had highly regular shapes such as triangular pyramids and polyhedral in contrast to the irregular shape of the raw nanoceria. Significant downshift was found in the Raman spectra of the plasma products, with a 7.9-cm shift compared with raw nanoceria, which was explained by the reduction of Ce. X-ray photoelectron spectroscopy results showed that the Ce fraction increased from 14% in the raw nanoceria to 38-39% for the product CeO, indicating the high reduction state on the ceria surface. It was determined that this blue nonstoichiometric nanoceria was stable up to 400 °C in air, but the color changed to pale yellow after 4 h at 500 °C in air indicating oxidation to CeO. Additionally, this novel stable nano-CeO caused a red shift in the UV-visible absorption results; a 48-nm red shift occurred for the nonstoichiometric nanoceria produced at 15 kW compared with the raw nanoceria. The band gap was calculated to be 2.5 eV while it was 3.2 eV for the raw nanoceria, indicating that this novel stable blue nonstoichiometric nanoceria should be a promising material for optical application. [ABSTRACT FROM AUTHOR]

Purpose: The use of multidisciplinary teams (MDTs), which address colorectal cancer treatment planning through weekly regular group meetings, was begun in October 2007. We analyzed and compared the outcomes of colorectal cancer patients with metastatic disease before and after the era of MDTs. Methods: From 2001 to 2010, 1075 patients who presented with stage IV disease and were treated in Taipei Veterans General Hospital were enrolled in the study. Among these patients, 439 (40.8 %) were diagnosed after MDTs had been established. The percentage of patients receiving surgical treatment for metastatic disease was calculated and compared before and after MDTs were established, and the survival rate was compared using a log-rank test, with a significance of P < 0.05. Results: A significantly improved survival rate in patients with stage IV disease was observed after establishment of MDTs, with the 3-year survival rate increasing from 25.6 to 38.2 % ( P < 0.001). Based on multivariate analysis, establishment of a MDT was an independent prognostic factor in patients with stage IV disease (hazard ratio = 0.74, 95 % confidence interval = 0.624∼0.866, P < 0.001). The percentage of liver resection in patients with liver metastasis increased from 19.6 to 35.2 % after the establishment of MDTs, whereas the percentage of lung resection in patients with lung metastasis remained stationary from 12.4 to 14.3 %. Conclusions: In the era of MDTs, intensive cooperation between different specialists has increased the referral rate for metastasectomy, resulting in significantly improved outcomes of colorectal patients in initial stage IV disease. [ABSTRACT FROM AUTHOR]

Background: Carcinoembryonic antigen (CEA) is widely used as a tumor marker in colorectal cancer (CRC). This study aimed to evaluate the role of the degree of change in CEA levels during the treatment period and found that the degree of change highly correlated with disease survival and Response Evaluation Criteria in Solid Tumors (RECIST) criteria in evaluating therapy response. Methods: A total of 447 metastatic CRC patients treated with surgery of the primary tumor followed by systemic therapy at a single center from the year 2000 through 2011 were reviewed. The degree of change in CEA levels was expressed as the CEA ratio (post-CEA/pre-CEA) and classified into four groups during the treatment period for further evaluation. The imaging change of the same population was also compared with the CEA ratio during the treatment period. Results: The CEA ratio was significantly correlated with different chemotherapy regimens ( p < 0.001), pre-treatment CEA level ( p < 0.001), lymphovascular invasion ( p = 0.006), and tumor differentiation ( p = 0.018). CEA ratio and imaging change according to RECIST criteria were both correlated with overall survival ( p < 0.001). These two methods for evaluating treatment response were highly correlated ( p < 0.001). Conclusions: CEA ratio was found to be a reliable prognostic factor in stage IV CRC, and was highly correlated with the imaging survey according to RECIST criteria. Further prospective studies are essential to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Dan-gua Fang (丹瓜方) on adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism. Methods: Forty 13-week-old diabetic Goto-Kakizaki (GK) rats were randomly divided into model, Dan-gua Fang, metformin and simvastatin groups (n=10 for each), and fed high-fat diet ad libitum. Ten Wistar rats were used as normal group and fed normal diet. After 24 weeks, liver expression of AMPKα mRNA was assessed by real-time PCR. AMPKα and phospho-AMPKα protein expression in liver was evaluated by Western blot. Liver histomorphology was carried out after hematoxylin-eosin staining, and blood glucose (BG), glycosylated hemoglobin A1c (HbA1c), food intake and body weight recorded. Results: Similar AMPKα mRNA levels were found in the Dan-gua Fang group and normal group, slightly higher than the values obtained for the remaining groups ( P<0.05). AMPKα protein expression in the Dan-gua Fang group animals was similar to other diabetic rats, whereas phospho-AMPKα (Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group ( P<0.05), respectively. However, phosphor-AMPKα/AMPKα ratios were similar in all groups. Dan-gua Fang reduced fasting blood glucose with similar strength to metformin, and was superior in reducing cholesterol, triglycerides, high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin. Dan-gua Fang decreases plasma alanine aminotransferase (ALT) significantly. Conclusion: Dan-gua Fang, while treating phlegm-stasis, could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet, and effectively protect liver histomorphology and function. This may be partly explained by increased AMPK expression in liver. Therefore, Dan-gua Fang might be an ideal drug for comprehensive intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer. Methods: Between April 2005 and March 2012, patients ( n = 158) diagnosed with metastatic colorectal cancer after at least four courses of first-line bevacizumab-based ( n = 95) or cetuximab-based triplet ( n = 63) were retrospectively analyzed. The KRAS genotypes were sequenced for all patients. The Kaplan-Meier method was used for survival analysis, and Cox proportional hazards models were used for univariate and multivariate analyses. Results: Cetuximab-based triplet was associated with a higher objective response rate (66.0 vs. 47.2 %, p = 0.037) and a higher conversion rate to resectability (39.7 vs. 20.0 %, p = 0.007) compared to bevacizumab-based triplet. Compared with bevacizumab-based triplet, cetuximab-based triplet significantly increased progression-free survival in patients with measurable metastatic colorectal cancer who achieved objective tumor response (responders) (median 13.1 vs. 10.5 months, p = 0.023), but no significant increase was observed for overall survival. After adjustment for group differences in baseline characteristics and combined chemotherapy agents, cetuximab-based triplet remained an independent determinant of progression-free survival in responders as compared with bevacizumab-based triplet. KRAS mutation was not a prognostic factor in patients with metastatic colorectal cancer. Conclusions: As compared with bevacizumab-based triplet, cetuximab-based triplet as the first-line treatment of metastatic colorectal cancer was associated with better progression-free survival in patients with measurable tumors who achieved objective tumor response to bio-chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant chemotherapy use in stage II colorectal cancer (CRC) is debated. We evaluated the prognostic significance of clinicopathological features recommended by most guidelines for identifying high-risk stage II CRC and adjuvant chemotherapeutic response. Methods: We enrolled 1,039 stage II CRC patients who underwent curative surgery at Taipei Veterans General Hospital from January 2005 to December 2010. Seventy-seven patients who received radiotherapy were excluded. The endpoint was disease-free survival. Results: Of 962 patients, 37 had stage T4 tumors; 50, lymphovascular invasion; 39, poor differentiation; 249, preoperative carcinoembryonic antigen (CEA) levels >5 ng/mL; and 53 underwent emergent operations. One hundred ninety-four patients received 5-fluorouracil-based adjuvant chemotherapy. During a median follow-up period of 60.2 months, recurrence developed in 110 patients (11.4 %). The 5-year disease-free survival (DFS) was 87.6 %. In multivariate analysis, preoperative CEA >5 ng/ml ( p = 0.001), emergent operation for obstruction/perforation ( p = 0.008), lymphovascular invasion ( p = 0.014), and T4 disease ( p = 0.030) were significantly associated with poor DFS. High-risk stage II patients ( n = 484) benefited from adjuvant chemotherapy (5-year DFS with and without adjuvant chemotherapy, 87.3 vs. 78.9 %; p = 0.028). Conclusions: Adjuvant chemotherapy improved DFS in high-risk stage II CRC patients, but not in low-risk patients. [ABSTRACT FROM AUTHOR]

Purpose: A dozen clinical trials examining a combination of temsirolimus and cetuximab in treating metastatic colon cancer are currently underway. We investigated the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in the synergism between temsirolimus and cetuximab in colon cancer. Methods: Five colon cancer cell lines were used for in vitro studies. Signal transduction pathways were assessed by immunoblotting. The synergism between studied drugs was analyzed with combination indexes. Gene silencing was performed using small interfering RNAs. The efficacies of temsirolimus and cetuximab were tested in nude mice with colon cancer xenografts. Transcriptional activity was assessed using a reporter assay. The inhibitors leupeptin, chloroquine, and MG132 were used to assess protein degradation. The association between CIP2A, clinicopathological parameters, and survival was examined by immunohistochemical staining using a tumor tissue microarray. Results: Temsirolimus decreased the resistance of cells to cetuximab by both inhibiting transcription of CIP2A and increasing degradation of CIP2A through the lysosomal-autophagy pathway. The mammalian target of rapamycin (mTOR) protein immunoprecipitated along with CIP2A. Temsirolimus decreased expression of phosphorylated extracellular regulated protein kinase (pErk) and phosphorylated v-akt murine thymoma viral oncogene (pAKT) and decreased the interaction of CIP2A and mTOR in cell lines without the K-ras codon 12 mutation. CIP2A was a prognostic marker only in colon cancer patients with weak expression of pErk or pAKT. Conclusions: Temsirolimus decreases cellular resistance to cetuximab by regulating CIP2A expression in colon cancer cells. Potential biomarkers for CIP2A inhibitors include pErk and pAKT. [ABSTRACT FROM AUTHOR]

Background: The prognosis for colorectal cancer (CRC) patients with unresectable metastases is dismal. This study compared outcomes of different metastatic treatments. Patients and methods: We collected 653 CRC cases with unresectable metastases including 490 cases receiving primary tumor resection then chemotherapy (surgery group) and 163 patients receiving neoadjuvant chemotherapy then did or did not receive operations (chemotherapy (C/T) group) from 2004 to 2010. The statistical endpoint was overall survival from the date of diagnosis. Results: In the C/T group, 124 (76 %) patients received an operation after 9.0 ± 6.2 months of chemotherapy, including 57 (34.9 %) patients with curative surgery. The C/T group had a higher proportion of T4 lesions (37.4 %) than the surgery group (26.9 %). Survival of the C/T group was longer than that of the surgery group (28.8 ± 8.8 vs. 24.3 ± 7.5 months; p = 0.043). Survival of 57 patients receiving curative surgery was 36.0 ± 6.3 months, which was significantly better than that of the 67 patients receiving palliative resection (25.2 ± 5.6, p < 0.001). In the surgery group, 42 (8.6 %) patients received curative metastasectomy after 8.5 ± 7.1 months of postoperative chemotherapy; survival was 30.8 ± 7.8 months, which was significantly better than that of patients who did not receive metastasectomy (22.4 ± 6.3 months). In multivariate analysis, poor differentiation, lymphovascular invasion, isolated cancer nodules, clinical risk score, and curative surgery were independent prognostic factors of overall patient survival. Conclusions: Neoadjuvant chemotherapy can improve outcome of CRC patients with unresectable metastases. [ABSTRACT FROM AUTHOR]

Objective: To study the toxicity features of high glucose on the endothelial cell cycle and the influence of Dan Gua-Fang (丹瓜方), a Chinese herbal compound prescription, on the reproductive cycle of vascular endothelial cells cultivated under a high glucose condition; to reveal the partial mechanisms of Dan Gua-Fang in the prevention and treatment of endothelial injury caused by hyperglycemia in diabetes mellitus (DM); and offer a reference for dealing with the vascular complications of DM patients with long-term high blood glucose. Methods: Based on the previous 3-(4,5)-dimethylthiahiazo (z-y1)-3-5-diphenytetrazoliumromide (MTT) experiment, under different medium concentrations of glucose and Dangua liquor, the endothelial cells of vein-304 (ECV-304) were divided into 6 groups as follows: standard culture group (Group A, 5.56 mmol/L glucose); 1/300 herb-standard group (Group B); high glucose culture group (Group C, 16.67 mmol/L glucose); 1/150 herb-high glucose group (Group D); 1/300 herb-high glucose group (Group E); and 1/600 herb-high glucose group (Group F). The cell cycle was assayed using flow cytometry after cells were cultivated for 36, 72 and 108 h, respectively. Results: (1) The percentage of cells in the G/G phase was significantly increased in Group C compared with that in Group A ( P<0.05), while the percentage of S-phase (S%) cells in Group C was significantly reduced compared with Group A ( P<0.05); the latter difference was dynamically related to the length of growing time of the endothelial cells in a high glucose environment. (2) The S% cells in Group A was decreased by 30.25% (from 40.23% to 28.06%) from 36 h to 72 h, and 12.33% (from 28.06% to 24.60%) from 72 h to 108 h; while in Group C, the corresponding decreases were 23.05% and 21.87%, respectively. The difference of S% cells between the two groups reached statistical significance at 108 h ( P<0.05). (3) The percentage difference of cells in the G/M phase between Group C and Group A was statistically significant at 72 h ( P<0.01). (4) 1/300 Dan Gua-Fang completely reversed the harmful effect caused by 16.67 mmol/L high glucose on the cell cycle; moreover it did not disturb the cell cycle when the cell was cultivated in a glucose concentration of 5.56 mmol/L. Conclusions: High glucose produces an independent impact on the cell cycle. Persistent blocking of the cell cycle and its arrest at the G/G phase are toxic effects of high glucose on the endothelial cell cycle. The corresponding variation of the arrest appears in the S phase. 1/300 Dan Gua-Fang completely eliminates the blockage of high glucose on the endothelial cell cycle. [ABSTRACT FROM AUTHOR]

Over the last two decades, automatic speaker recognition has been an interesting and challenging problem to speech researchers. It can be classified into two different categories, speaker identification and speaker verification. In this paper, a new classifier, extreme learning machine, is examined on the text-independent speaker verification task and compared with SVM classifier. Extreme learning machine (ELM) classifiers have been proposed for generalized single hidden layer feedforward networks with a wide variety of hidden nodes. They are extremely fast in learning and perform well on many artificial and real regression and classification applications. The database used to evaluate the ELM and SVM classifiers is ELSDSR corpus, and the Mel-frequency Cepstral Coefficients were extracted and used as the input to the classifiers. Empirical studies have shown that ELM classifiers and its variants could perform better than SVM classifiers on the dataset provided with less training time. [ABSTRACT FROM AUTHOR]

Purpose: We retrospectively analyzed preoperative levels of carbohydrate antigen (CA) 19-9 in colorectal cancer (CRC) patients to determine the prognostic value of CA19-9 in CRC patients with normal carcinoembryonic antigen (CEA) levels. Methods: A total of 639 patients who underwent curative surgery at Taipei Veterans General Hospital between 2002 and 2006 were enrolled. We excluded 254 patients (39.7 %) with high preoperative CEA levels and analyzed 385 patients with normal CEA levels. The measured endpoint was the postoperative disease-free survival (DFS). The prognostic value of CA19-9 was determined using log-rank test and Cox regression analysis. Results: High CA19-9 levels were significantly associated with advanced disease and were detected in 5.8 % of patients with stage I disease, 11.7 % of those with stage II disease, and 22.5 % of those with stage III disease ( P < 0.001). The 5-year DFS in patients with normal CA19-9 levels was 82.0 %, which was significantly higher than that in patients with high CA19-9 levels (68 %; P < 0.001). In a multivariate analysis, the most important independent factor affecting the 5-year DFS was tumor-node-metastasis stage (95 % CI, 1.26-2.36; HR = 1.72). After stratification by other factors, high CA19-9 level remained an independent prognostic factor for patients with normal CEA levels. Patients with high CA19-9 levels also showed a higher incidence of lung metastasis (23.1 %) than those with normal CA19-9 levels (7.2 %). Conclusions: CA19-9 may be a prognostic factor for CRC patients with normal CEA levels. An aggressive follow-up protocol for lung metastasis should be used for these patients. [ABSTRACT FROM AUTHOR]

Background: This open-label pilot study is aimed to evaluate the efficacy and tolerability of the antidepressant duloxetine, which is effective for diabetic neuropathic pain, in the treatment of chronic oxaliplatin-induced peripheral neuropathy (OIPN). Methods: We enrolled a total of 39 patients with stage III or IV colorectal cancer with chronic OIPN. They were treated with duloxetine by increasing the dose from 30 mg/day to 60 mg/day. Patients' pain intensity was rated at baseline and 12 weeks after duloxetine administration. The severity of neuropathic pain was evaluated using the visual analog scale (VAS) score and the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 3 (NCI-CTCAE v3.0). Results: Nine patients (23.1%) discontinued duloxetine before the end of treatment because of adverse events. Of the remaining 30 patients, 19 patients (63.3%) had a VAS score improvement. Among them, nine (47.4%) showed a simultaneous grade improvement, and the other 10 patients (52.6%) had a stable grade according to NCI-CTCAE v3.0. Treatment with duloxetine did not impair renal or liver function and did not interfere with chemotherapy. Conclusions: Duloxetine is feasible in treating chronic OIPN with tolerable toxicity at a daily dose of 60 mg/day. [ABSTRACT FROM AUTHOR]

Purpose: The seventh edition of the American Joint Committee on Cancer (AJCC) staging system has new substages for colon cancer. We used survival data from a single medical center to analyze this new AJCC edition. Methods: The colon cancer database of Taipei Veterans General Hospital provided 1,865 patient records covering from 1999 to 2005. Survival rates were evaluated using the Kaplan-Meier method. Results: There were 268, 607, 561, and 421 patients in stages I, II, III, and IV disease with 5-year observed survival rates of 86.3%, 79.2%, 65.4%, and 12.8%, respectively. Survival rates were not significantly different between those with T4a and T4b disease ( P = 0.806). The outcome of N1c disease was similar to N1a and N1b but worse than N0 ( P = 0.004). Survival rates for M1a and M1b disease became different after reclassifying solely peritoneal seeding as M1a ( P < 0.001). No discrepancy of outcomes between stage IIIA and stage IIB/IIC remained in the seventh edition. Conclusions: Evolution from the fifth to seventh edition of the AJCC staging system is successful in separating prognostic groups by substaging. But some issues remain unresolved, including the subdivision of T4, N1, and M1. [ABSTRACT FROM AUTHOR]

Purpose: The objectives of the study were to estimate the incidence and clarify the clinicopathologic feature of sporadic microsatellite instability (MSI)-high (MSI-H) colon cancer. Furthermore, the role of MSI in colon cancer prognosis was also investigated. Methods: Microsatellite status was identified by genotyping. The clinicopathologic differences between two groups (MSI-H vs. MSI-L/S) and the prognostic value of MSI were analyzed. Results: From 1993 to 2006, 709 sporadic colon cancer patients were enrolled. MSI-H colon cancers showed significant association with poorly differentiated (28.3% vs. 7.2%, p = 0.001), proximally located (76.7% vs. 34.5%, p = 0.001), more high mucin-containing tumor (10.0% vs. 5.1%, p = 0.001) and female predominance (56.7% vs. 30.2%, p = 0.001). In multivariate analysis, MSI-H is an independent factor for better overall survival (HR, 0.459; 95% CI, 0.241-0.872, p = 0.017). Conclusions: Based on the hospital-based study, MSI-H colon cancers demonstrated distinguished clinicopathologic features from MSI-L/S colon cancers. MSI-H is an independent favorable prognostic factor for overall survival in colon cancer. [ABSTRACT FROM AUTHOR]

Computational intelligence techniques have been used in wide applications. Out of numerous computational intelligence techniques, neural networks and support vector machines (SVMs) have been playing the dominant roles. However, it is known that both neural networks and SVMs face some challenging issues such as: (1) slow learning speed, (2) trivial human intervene, and/or (3) poor computational scalability. Extreme learning machine (ELM) as emergent technology which overcomes some challenges faced by other techniques has recently attracted the attention from more and more researchers. ELM works for generalized single-hidden layer feedforward networks (SLFNs). The essence of ELM is that the hidden layer of SLFNs need not be tuned. Compared with those traditional computational intelligence techniques, ELM provides better generalization performance at a much faster learning speed and with least human intervene. This paper gives a survey on ELM and its variants, especially on (1) batch learning mode of ELM, (2) fully complex ELM, (3) online sequential ELM, (4) incremental ELM, and (5) ensemble of ELM. [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to determine the effects of diabetes on overall survival (OS) and cancer-specific survival (CSS) in patients with newly diagnosed colon cancers, with particular focus on the impact of diabetes on survival at each stage of colon cancer. Methods: From January 1999 to January 2008, 2762 consecutive patients diagnosed with colon cancer in Taipei Veterans General Hospital were enrolled. The general characteristics as well as presence of diabetes prior to colon cancer diagnosis were identified. Cox proportional hazard analyses were used for prognostic factors determination; and survival was analyzed using the Kaplan-Meier method with log-rank test. Results: A total of 469 patients (17%) had diabetes at diagnosis of colon cancer. Patients with diabetes had baseline characteristics comparable to those without diabetes with the exception that the patients with diabetes were older (>65 years). Diabetes significantly and negatively impacted OS and CSS in multivariate analyses. After adjusting for possible confounding factors, the prognostic impact of diabetes on OS and CSS was particularly significant in patients with stage II colon cancer. Conclusions: Diabetes is a poor prognostic factor in patients with newly diagnosed colon cancer, and it may directly impact the tumor behavior of stage II disease. Further study is required to elucidate the underlying pathophysiologic mechanisms. [ABSTRACT FROM AUTHOR]

Background: For patients with cecal and ascending colonic cancers, the significance of regional lymph node (LN) metastasis at the terminal ileum has not been elucidated. We analyzed its metastatic patterns and significance. Methods: The records of patients with cecal and ascending colonic cancers receiving standard radical right hemicolectomy with D3 LN dissection between 2000 and 2010 were collected. The regional LNs were grouped according to the Japanese Classification of Colorectal Carcinoma. The regional LNs supplied by ileocolic vessels were further divided into 201-A (terminal ileal side) and 201-B (colonic side). The clinicopathologic characteristics of all cases showing positive for metastasis in 201-A LN were analyzed. Results: Forty-seven cases of cecal and 56 cases of ascending colonic cancer were included. Seven cases had 201-A-positive LNs: five (10.6%) in cecal cancers and two (3.6%) in ascending colonic cancers. They all had distant metastases ( P < 0.001), and the incidences were significantly correlated with the numbers of metastatic LNs ( P < 0.05). There was no 201-A-positive LN noted among patients with stage I to III disease. Poor prognosis was noted for patients with a 201-A-positive LN. Conclusions: Both cecal and ascending colonic cancers have a potential for LN metastasis at the terminal ileum. These cases are exclusively stage IV and have poor prognosis. [ABSTRACT FROM AUTHOR]

Our present study provided new evidence for diterbium transferrin (Tb2Tf) as a potential multi-photon-excited microscopy probe. It indicated that the Tb2Tf complex can be transported into human leukemia K562 cells via a process mediated by transferrin (Tf) receptors as an intact entity and with no obvious cellular toxicity. The supporting evidence includes the following. First, the transport kinetic behavior of Tb was compared with that of the Tf moiety. The Tb was determined by inductively coupled plasma mass spectrometry and Tf was determined by fluorescence activated cell sorting analysis. The kinetic synchronization of internalization of both Tb and Tf into human leukemia K562 cells demonstrated the Tb2Tf complex was transported into cells as a whole. Second, using confocal laser scanning microscopy, we observed the localization of Tb2Tf in the cell. This showed that the internalized Tb2Tf was mostly situated in the same perinuclear region as diferric transferrin (Fe2Tf). In addition, pretreatment with pronase largely abolished the transport process of Tb2Tf. The relative fluorescence intensities representing the uptake of Tf into the cells decreased to about 16% and the cytosolic Tb content decreased to almost the same percentage as for Tf. Furthermore, the addition of Fe2Tf can effectively inhibit transport of Tb2Tf into K562 cells. Third, no significant decrease of cell viability was observed in the presence of Tb2Tf even for 24 or 48 h by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Moreover, prospects for the use of Tb2Tf as a multi-photon-excited microscopy probe in a living system are discussed. [ABSTRACT FROM AUTHOR]

A looper is an uplifted device, which is always installed between adjacent stands in a hot strip finishing mill. A virtual looper system incorporating powerful computation capability of digital computers becomes an efficient and cost-effective tool for controller design and system analysis of this complicated and gigantic system. Accurate simulation of the looper system can not only restore the actual looper’s dynamic behavior, but can also analyze the factors that affect the looper response and provide useful information for further improvement of the control system. In this paper, a looper simulation system based on a conventional hot strip mill is established. Sensitivity analysis indicates that the reduction ratio is the most important parameter for the looper dynamics. Therefore, an auto-tuning technique for a variable reduction ratio is developed. Simulation results, compared with actual loopers behavior, demonstrate significant improvement in terms of accuracy. [ABSTRACT FROM AUTHOR]

Purpose. The aim of this study was to investigate the mechanism of permeation and cytotoxicity of vanadium compounds, [VO(acac)2], [VO(ma)2], and vanadate.Methods. Absorptive transport were carried out in Caco-2 monolayers grown on transwell inserts. Vanadium was quantified using inductively coupled plasma atomic emission spectrometry (ICP-AES). The change of Caco-2 cells in the microvilli morphology and F-actin structure was visualized by transmission electron microscopy and confocal laser scanning microscopy.Results. The three vanadium compounds were taken up by Caco-2 cells via simple passive diffusion. [VO(acac)2] were mainly transcellularly transported and exhibited the highest apparent permeabilty coefficients (8.2 × 10-6 cm). The cell accumulation of [VO(acac)2] was found to be greater than that of [VO(ma)2], and vanadate caused much less accumulation than the other two compounds. Vanadium compounds induced intracellular reactive oxygen species, reduced the transepithelial electric resistance, caused morphological change in microvilli, and led to different perturbation of F-actin structure.Conclusions. The three compounds exhibited different permeability due to different diffusion process and cellular uptake. The toxicity of vanadium complexes on Caco-2 monolayer involved F-actin-related change of tight junction and impairment of microvilli. The toxicity was also related to elevated intracellular reactive oxygen species (ROS) and their cellular accumulation. [ABSTRACT FROM AUTHOR]

The formation and growth of CeOCl crystals from a Ce3+ precursor in a molten KCl-LiCl flux was investigated. The formation of CeOCl occurred through the reaction Ce3+ + Cl− + [O2−] = CeOCl, where Ce3+ came from both CeO2−x (0 < x < 0.5) and Ce2O3, and the [O2−] was the lattice oxygen. CeOCl started to form in the powder together with ceria at 400 °C under hydrogen atmosphere, and the CeOCl content was 91.3% then decreased with increasing synthesis temperature. The growth of CeOCl crystals observed by SEM images revealed that cubic CeOCl particles were formed from polyhedral flakes. Photo-Luminescence (PL) spectra showed that the violet-blue light can be emitted from synthesized powder, which suggests CeOCl can be a potential luminescence material.Graphical abstract: [ABSTRACT FROM AUTHOR]