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MTT assay was applied to evaluate the effects of ESC-3 on the proliferation of liver cancer cells and human normal liver cancer cells (L02). Flow cytometry assays were performed to explore the distribution of the cell cycle. Western blot analysis, qPCR assay and immunohistochemistry (IHC) were performed to determine the expression levels of apoptosis-related or pathway-related protein isolated from cells and tumors. Xenograft models were employed to confirm the efficient of ESC-3 on inhibiting the growth of liver tumors furtherly. Significant inhibitory effects of ESC-3 were observed in liver cancer, while there is no remarkable change in the proliferation of human normal liver cancer cells after treatment with ESC-3 compared with control group. Our findings elucidated that ESC-3 might cause S-phase cycle arrest through cyclinA1 and CDK2. In addition, we demonstrated that apoptosis induced by ESC-3 was closely contacted with Notch signaling pathway and mitochondrial membrane potential (ΔΨm) in liver cancer. Importantly, ESC-3 could markedly inhibit the growth of transplantation tumors without toxic to BALB/c nude mice in xenograft models. Our study elucidated that ESC-3 could induce apoptosis through Notch signaling pathway and mitochondrial membrane potential (ΔΨm), therefore ESC-3 could be a potential therapeutic in liver cancer. [ABSTRACT FROM AUTHOR]

Background The two-dimensional phantom dose verification (2D-PDV) using hybrid plan and planar dose measurement has been widely used for IMRT treatment QA. Due to the lack of information about the correlations between the verification results and the anatomical structure of patients, it is inadequate in clinical evaluation. A three-dimensional anatomical dose verification (3D-ADV) method was used in this study to evaluate the IMRT/VMAT treatment delivery for nasopharyngeal carcinoma and comparison with 2D-PDV was analyzed. Methods Twenty nasopharyngeal carcinoma (NPC) patients treated with IMRT/VMAT were recruited in the study. A 2D ion-chamber array was used for the 2D-PDV in both single-gantry-angle composite (SGAC) and multi-gantry-angle composite (MGAC) verifications. Differences in the gamma pass rate between the 2 verification methods were assessed. Based on measurement of irradiation dose fluence, the 3D dose distribution was reconstructed for 3DADV in the above cases. The reconstructed dose homogeneity index (HI), conformity index (CI) of the planning target volume (PTV) were calculated. Gamma pass rate and deviations in the dose-volume histogram (DHV) of each PTV and organ at risk (OAR) were analyzed. Results In 2D-PDV, the gamma pass rate (3%, 3 mm) of SGAC (99.55% ± 0.83%) was significantly higher than that of MGAC (92.41% ± 7.19%). In 3D-ADV, the gamma pass rates (3%, 3 mm) were 99.75% ± 0.21% in global, 83.82% ± 16.98% to 93.71% ± 6.22% in the PTVs and 45.12% ± 32.78% to 98.08% ± 2.29% in the OARs. The maximum HI increment in PTVnx was 19.34%, while the maximum CI decrement in PTV1 and PTV2 were -32.45% and - 6.93%, respectively. Deviations in dose volume of PTVs were all within ±5%. D2% of the brainstem, spinal cord, left/right optic nerves, and the mean doses to the left/right parotid glands maximally increased by 3.5%, 6.03%, 31.13%/26.90% and 4.78%/4.54%, respectively. Conclusion The 2D-PDV and global gamma pass rate might be insufficient to provide an accurate assessment for the complex NPC IMRT operation. In contrast, the 3D-ADV is superior in clinic-related quality assurance offering evaluation of organ specific pass rate and dosevolume deviations. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a common environmental pollutant, and urinary Cd (UCd) is generally used as a marker of exposure; however, our understanding on the related urinary metabolic changes caused by Cd exposure is still not clear. In this study, we applied a mass-spectrometry-based metabolomic approach to assess the urinary metabolic changes in human with long-term environmental Cd exposure, aimed to identify early biomarkers to assess Cd nephrotoxicity. Urine samples from 94 female never smokers aged 44–70 with UCd in the range of 0.20–68.67 μg/L were analyzed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-ToF-MS) and gas chromatography–mass spectrometry (GC–MS). It was found that metabolites related to amino acid metabolism (L-glutamine, L-cystine, L-tyrosine, N-methyl-L-histidine, L-histidinol, taurine, phenylacetylglutamine, hippurate, and pyroglutamic acid), galactose metabolism (D-galactose and myo-inositol), purine metabolism (xanthine, urea, and deoxyadenosine monophosphate), creatine pathway (creatine and creatinine), and steroid hormone biosynthesis (17-α-hydroxyprogesterone, tetrahydrocortisone, estrone, and corticosterone) were significantly higher among those with a UCd level higher than 5 μg/L. Moreover, we noticed that the level of N-methyl-L-histidine had already started to elevate among individuals with a UCd concentration of ≥2 μg/L. The overall findings illustrate that metabolomics offer a useful approach for revealing metabolic changes as a result of Cd exposure. [ABSTRACT FROM AUTHOR]

Purpose This study was aimed to investigate long-term survivals and toxicities of early-stage nasopharyngeal carcinoma (NPC) in endemic area, evaluating the role of chemotherapy in stage II patients. Materials and Methods Totally 187 patients with newly diagnosed NPC and restaged American Joint Committee on Cancer/International Union Against Cancer 8th T1-2N0-1M0 were retrospectively recruited. All received intensity-modulated radiotherapy (IMRT)±chemotherapy (CT) from 2001 to 2010. Results With 15.7-year median follow-up, 10-year locoregional recurrence-free survival, distant metastasis-free survival (DMFS), disease-specific survival (DSS), and overall survival (OS) were 93.3%, 93.5%, 92.9% and 88.2%, respectively. Multivariable analyses showed cervical lymph nodes positive and pre-treatment prognostic nutritional index = 52.0 could independently predict DMFS (p=0.036 and p=0.011), DSS (p=0.014 and p=0.026), and OS (p=0.002 and p < 0.001); Charlson comorbidity index < 3 points could predict DSS (p=0.011); age > 45 years (p=0.002) and pre-treatment lactate dehydrogenase = 240 U/L (p < 0.001) predicted OS. No grade 4 late toxicity happened; grade 3 late toxicities included subcutaneous fibrosis (4.3%), deafness or otitis (4.8%), skin dystrophy (2.1%), and xerostomia (1.1%). No differences on survivals were shown between IMRT+CT vs. IMRT alone in stage II patients, even in T2N1M0 (p > 0.05). Unsurprising, patients in IMRT+CT had more acute gastrointestinal reaction, myelosuppression, mucositis, late ear toxicity, and cranial nerve injury (all p < 0.05) than IMRT alone group. Conclusion Superior tumor control and satisfying long-term outcomes could be achieved with IMRT in early-stage NPC with mild late toxicities. As CT would bring more toxicities, it should be carefully performed to stage II patients. [ABSTRACT FROM AUTHOR]

Purpose This study aims to investigate the feasibility of contouring target volume according to residual tumor and decreasing the dose to the tumor regression field after induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC). Materials and Methods From August 2009 to August 2013, patients with stage III-IVB NPC were treated with IC and concurrent chemoradiotherapy. Gross tumor volume of nasopharynx (GTVnx)-residual and gross tumor volume of cervical lymph node (GTVnd)-residual were contoured according to post-IC residual primary tumor and any N+ disease, respectively. The tumor regression field was included in CTVnx1/CTVnd1 and prescribed a dose of 60 Gy. Outcomes and toxicities of all patients were evaluated. Results A total of 57 patients were enrolled. At a median follow-up of 68 months, three cases displayed locoregional recurrence and one case showed both distant metastasis and locoregional recurrence. All locoregional recurrences were in the GTVnx-residual/GTVnd-residual and in-field. The 5-year overall, locoregional relapse-free, distant metastasis-free, and progression- free survival rates were 82.2%, 87.7%, 85.8% and 80.3%, respectively. Conclusion After IC, contouring of GTVnx-residual/GTVnd-residual as residual tumor volume and distribution 60 Gy of radiation dose to the tumor regression field may be feasible and need further investigation. [ABSTRACT FROM AUTHOR]

Improving N use efficiency (NUE) and reducing the negative impact of N fertilization on the environment are essential for sustaining agricultural production in many intensive farming regions around the world. The objective of this research was to investigate the effect of various fertilization regimes on yield, N uptake, and NUE by maize (Zea mays L.) in long-term (15-yr) experiments performed at four sites (Changping, Zhengzhou, Yangling, and Qiyang) in China. Eight treatments were examined: unfertilized control (CK); inorganic fertilizer (manufactured source) N, N and P, N and K, and N, P, and K; inorganic N, P, and K with manure (NPKM); 1.5′ the rate of NPKM (1.5NPKM); and N, P, and K with maize stover returned (NPKS). Compared with inorganic fertilization, mixed inorganic and manure fertilization (NPKM and 1.5NPKM) resulted in more stable and significantly higher yield and NUE as well as increases in soil nutrient storage at all sites, with the most significant improvement in the acid soil (pH = 5.7) at Qiyang. Phosphorous was identified as one of the most important limiting factors in maize NUE because the NUE at all four sites increased from about 20 to 45% by increasing the available P in the soil. Higher NUEs (up to 70%) were observed mostly from the continuous manure applications. We conclude that manure and P applications are the most important and effective nutrient management strategies for both the acid and alkaline soils in this study for maize production in China. [ABSTRACT FROM AUTHOR]

The critical value of soil Olsen-P is the point above which the probability of crop yield response to fertilizer P is small or nil. Determining this critical value is fundamental when making appropriate P fertilizer recommendations. In this study, the critical values were determined for continuous maize ( Zea mays L.)-winter wheat ( Triticum aestivum L.) cropping systems from a 15-year field experiment across three sites in China using linear-linear, linear-plateau and Mitscherlich models. The mean critical values for maize using the three models ranged from 12.1 to 17.3 mg P kg−1 (average 15.3 mg P kg−1) and for winter wheat from 12.5 to 19.0 mg P kg−1 (average 16.3 mg P kg−1) among study sites. The mean critical value for maize was approximately 7% lower than that for winter wheat across all sites based on the three models. Critical values identified by the Mitscherlich model were 1.4 to 2.1 times those from linear-linear and 1.3 to 1.9 times of those from linear-plateau and were crop and site dependent. There was a significant negative correlation ( P < 0.05) between the mean critical value from the three models and the observed P uptake by either maize or wheat. Our study shows that the critical values can vary with sites, crops and models used, and thus caution should be taken when selecting the most appropriate one when making P fertilizer recommendations for agronomic return and to minimize chances of negative environment impact from overfertilization. [ABSTRACT FROM AUTHOR]