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INTRODUCTION: Abnormal alternative splicing (AS) contributes to aggressive intrahepatic invasion and metastatic spread, leading to the high lethality of hepatocellular carcinoma (HCC). OBJECTIVES: This study aims to investigate the functional implications of UPF3B-S (a truncated oncogenic splice variant) in HCC metastasis. METHODS: Basescope assay was performed to analyze the expression of UPF3B-S mRNA in tissues and cells. RNA immunoprecipitation, and in vitro and in vivo models were used to explore the role of UPF3B-S and the underlying mechanisms. RESULTS: We show that splicing factor HnRNPR binds to the pre-mRNA of UPF3B via its RRM2 domain to generate an exon 8 exclusion truncated splice variant UPF3B-S. High expression of UPF3B-S is correlated with tumor metastasis and unfavorable overall survival in patients with HCC. The knockdown of UPF3B-S markedly suppresses the invasive and migratory capacities of HCC cells in vitro and in vivo. Mechanistically, UPF3B-S protein targets the 3'-UTR of CDH1 mRNA to enhance the degradation of CDH1 mRNA, which results in the downregulation of E-cadherin and the activation of epithelial-mesenchymal transition. Overexpression of UPF3B-S enhances the dephosphorylation of LATS1 and the nuclear accumulation of YAP1 to trigger the Hippo signaling pathway. CONCLUSION: Our findings suggest that HnRNPR-induced UPF3B-S promotes HCC invasion and metastasis by exhausting CDH1 mRNA and modulating YAP1-Hippo signaling. UPF3B-S could potentially serve as a promising biomarker for the clinical management of invasive HCC.
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Selenium (Se) is an essential element for aquatic organisms as well as humans. It can be toxic to organisms depending on its concentration and chemical speciation; thus, considerable efforts have been made to unravel the biogeochemical cycling of Se in aquatic systems. Mathematical models provide an important tool to better understand the fate of Se in different environment compartments. However, a comprehensive review of modeling Se in aquatic systems with current challenges and opportunities is missing. To fill this gap, we firstly summarize the processes governing Se cycling in aquatic systems, including particle adsorption and desorption, diffusion, biological uptake, redox reactions, and volatilization. Then, we critically review the available models, identifying the compartments modelled, environmental factors considered, and the Se species and geochemical processes used in each model, providing an assessment of their advantages and limitations. Data availability for modeling studies is investigated, highlighting how to better quantify the redox reactions, estimate of Se loadings, and mass balance. For the modeling of Se cycling in aquatic systems, the ability of the models to link sources to biota concentrations under a range of hydrodynamic conditions and with mechanistic representations of transport, transformation, and uptake processes is required. The majority of the current models can conduct this task; however, to better present the uptake processes of Se in the food web, two-way coupling of the Se cycling model with a food web model is recommended.
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Selenio , Humanos , Selenio/química , Cadena Alimentaria , Modelos TeóricosRESUMEN
In order to improve the real-time performance of the trajectory tracking of autonomous vehicles, this paper applies the alternating direction multiplier method (ADMM) to the receding optimization of model predictive control (MPC), which improves the computational speed of the algorithm. Based on the vehicle dynamics model, the output equation of the autonomous vehicle trajectory tracking control system is constructed, and the auxiliary variable and the dual variable are introduced. The quadratic programming problem transformed from the MPC and the vehicle dynamics constraints are rewritten into the solution of the ADMM form, and a decreasing penalty factor is used during the solution process. The simulation verification is carried out through the joint simulation platform of Simulink and Carsim. The results show that, compared with the active set method (ASM) and the interior point method (IPM), the algorithm proposed in this paper can not only improve the accuracy of trajectory tracking, but also exhibits good real-time performance in different prediction time domains and control time domains. When the prediction time domain increases, the calculation time shows no significant difference. This verifies the effectiveness of the ADMM in improving the real-time performance of MPC.
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The depth of contaminated sediments constrains the water environment of large shallow lakes and can affect shallow lake water quality through sediment resuspension and nutrient release. Although such effects can be avoided by sediment dredging methods, we still cannot precisely quantify the depth of sediment dredging. Therefore, we used organic index method, pollution index method and potential ecological risk evaluation to evaluate the contamination status of split samples of in situ sediments layer by layer, and established a comprehensive contamination index evaluation method for layer-by-layer sediments, then combined with the contamination release characteristics of split samples to assess the contamination degree of the sediments obtained. The results show that the content of nitrogen and phosphorus in the surface layer of Lake Townsend sediments is generally higher than that in the middle and bottom sediments, and the heavy metals also satisfy this pattern, which is consistent in the sediments of both east and west regions. We also simulated the release process of nitrogen and phosphorus nutrients in the in situ sediment of Tangxun Lake in 2019, and the experimental results showed that the risk of nitrogen and phosphorus nutrient release in the sediment was mainly concentrated in the surface and middle layers, and the risk of elemental nitrogen release was significantly greater than that of phosphorus release. Finally, a comprehensive evaluation was carried out to obtain the desilting depth of the sediments in Lake Townsend, and it can be determined that the recommended desilting depth is about 20 cm for West Lake and 30 cm for East Lake. The results show that the recommended dredging depth can be determined based on this method, which provides an important scientific basis for sediment dredging in Tangxun Lake and even provides a new paradigm for sediment dredging depth estimation in similar large shallow lakes.
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Lagos , Contaminantes Químicos del Agua , Monitoreo del Ambiente , Sedimentos Geológicos , Contaminantes Químicos del Agua/análisis , China , Calidad del Agua , Fósforo/análisis , Nitrógeno/análisisRESUMEN
Although the synergistic effect of traditional therapies combined with tumor targeting or immunotherapy can significantly reduce mortality, cancer remains the leading cause of disease related death to date. Limited clinical response rate, drug resistance and off-target effects, to a large extent, impede the ceilings of clinical efficiency. To get out from the dilemmas mentioned, bacterial therapy with a history of more than 150 years regained great concern in recent years. The rise of biological engineering and chemical modification strategies are able to optimize tumor bacterial therapy in highest measure, and meanwhile avoid its inherent drawbacks toward clinical application such as bacteriotoxic effects, weak controllability, and low security. Here, we give an overview of recent studies with regard to bacteria-mediated therapies combined with chemotherapy, radiotherapy, and immunotherapy. And more than that, we review the bacterial detoxification and targeting strategies via biological reprogramming or chemical modification, their applications, and clinical transformation prospects.
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Quantifying the effect of hydraulic disturbances on sediment phosphate release is a key issue in the water quality assessment of lakes, especially for the shallow lakes which are susceptible to winds and waves. Here, we sampled the original sediment columns from 12 positions in the eastern, central, and western areas of the Chaohu Lake, a representative shallow lake in China, and observed phosphate release under three levels of hydraulic disturbances in the laboratory. When the disturbance was weak and sediment on the surface of bottom mud moved individually (the Individual Motion Mode), sediment phosphate release rate was insignificant (0.24 mg/m2/day). When the disturbance was medium and only a small percentage (< 16%) of surface sediment started to move (the Small Motion Mode), the phosphate release rate sharply increased to 4.81 mg/m2/day. When the disturbance was further strengthened and most (≥ 16%) of the surface sediment moved (the General Motion Mode), the phosphate release rate was more than doubled (10.23 mg/m2/day). With the increase in hydraulic disturbance intensity, the variation range of phosphate release also became wider. Spatial distribution showed that the release rate varies the most in the western area, followed by the eastern and the central areas. By extrapolating the experimental results to the real scale, it was found that the phosphate release fluxes would probably fall within a wide range between 203.43 to 7311.01 kg/day under different levels of hydrodynamic disturbances which considerably affects phosphate release from shallow lakes. This study also has implications for the pollutant management in other shallow lakes.
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Lagos , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Sedimentos Geológicos , Fosfatos/análisis , Fósforo/análisis , Contaminantes Químicos del Agua/análisis , Calidad del AguaRESUMEN
Based on the main components in the residual soil to meet the characteristics of ceramic grain production raw materials, and combining with the principle of anti-filter layer technology for seepage control of hydraulic buildings, a lead wire cage filled with silt grains made from lake dehydration silt can be obtained. Moreover, the same-position treatment method of bed surface is desilted by this kind of ceramic lead wire cage in a reasonable structural form to improve water environment. In order to investigate the inhibition effect of this method on sediment resuspension, the effect law on water quality and the growth of indigenous microorganisms, 25 experimental groups were constructed to simulate 5 flow patterns of eutrophic lakes in this paper. We can analyze the inhibition effect of ceramic lead wire cage on sediment resuspension by monitoring the change of suspended matter content, monitoring the concentration change of ammonia nitrogen and soluble phosphorus can show the effect of ceramic lead cage on water quality, and monitoring the dissolved oxygen content can indirectly reflect the effect of the growth of indigenous microorganisms to some extent. The results show that in a certain flow mode, the ceramic lead wire cage can effectively inhibit the resuspension of the sediments, prevent the release of nitrogen and phosphorus nutrients in the sediments, and promote the growth of microbial attachment. The research results will maximize the benefits of the utilization of silt resources, and will optimize the in situ repair methods, and have broad application prospects.
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Lagos , Contaminantes Químicos del Agua , China , Mezclas Complejas , Sedimentos Geológicos/química , Lagos/química , Nitrógeno/análisis , Nutrientes , Fósforo/análisis , Contaminantes Químicos del Agua/análisisRESUMEN
Long non-coding RNAs (lncRNAs), as competitive endogenous RNAs (ceRNAs), play a critical role in biological processes of cancer. However, the roles of specific lncRNAs in ceRNA network of lung adenocarcinoma (LUAD) remains largely unclear. Herein, we identified the roles of lncRNA ADAMTS9-AS1/AS2 (ADAMTS-AS1/AS2) in lung adenocarcinoma by bioinformatics analyses and functional verification. First, differentially expressed genes ADAMTS9-AS1, ADAMTS9-AS2 and ADAMTS9 were screened out from GSE130779. Then the expression correlation of these three genes was analyzed. The results showed that ADAMTS9-AS1, ADAMTS9-AS2 and ADAMTS9 were down-regulated in LUAD, and were positively correlated with each other. After that, miRcode was used to find miR-150 which binds to ADAMTS9-AS1/ADAMTS9-AS2/ADAMTS9. Next, co-expression analysis and functional enrichment analyses were performed to further analyze differentially expressed genes. The results showed that the differentially expressed genes were mainly enriched in Beta3 integrin cell surface interactions and epithelial-to-mesenchymal transition. Finally, the cell functions of ADAMTS9-AS1 and ADAMTS9-AS2 in A549 and NCI-H1299 cell lines were verified. In vitro cell studies confirmed that ADAMTS9-AS1 and ADAMTS9-AS2 play an inhibitory role in LUAD cells.
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Epithelioid sarcoma (ES) was first described by Enzinger in 1970. It is a rare variant of soft tissue sarcoma with a 5-year overall survival (OS) rate of 50%. Here, we reported a case of epithelioid sarcoma in the parapharyngeal space of an adult, resulting in a favorable prognosis after chemotherapy and radiation therapy. A 34-year-old female who complained of pharynx pain and discomfort was suspected of having a tumor in the right parapharyngeal space by CT scan. Excision biopsy suggested epithelioid sarcoma. Clinical and radiological studies did not reveal tumor distant metastasis in the patient. After excisional biopsy, the patient underwent chemotherapy and external beam radiation treatment. She has remained alive for 2 years and 7 months without recurrence since her last treatment. In this paper, we also provide a detailed review of the role of radiotherapy in the treatment of epithelioid sarcoma in previously reported cases.
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BACKGROUND: Radiotherapy is one of the most important treatments for esophageal squamous cell carcinoma (ESCC). Previously, we found that EphA5 expression was increased in ESCC cells and tumor tissues. Studies from other groups reported that EphA5 is abnormally expressed in numerous malignant tumors and may be involved in the radiosensitivity of lung cancer. However, the role of EphA5 in radiotherapy for ESCC remains unclear. METHODS: The siRNA sequences against human EPHA5 were transfected to the ESCC cells (KYSE150 and KYSE450). After ionizing radiation (IR), cell viability and colony formation assays were used to test the changes of cell proliferation in EphA5-silenced cells. Flow cytometry analysis was performed to investigate the cell apoptosis and cycle in the irradiated cells interfered by siRNA. The key molecules involved in cell cycle checkpoints and DNA damage repair were evaluated by Western blot and immunofluorescence. RESULTS: CCK8 assay and clonogenic assay showed that the proliferation of EphA5-silenced ESCC cells was inhibited after IR. At 24 h post-IR treatment, we found that the G1/S checkpoint triggered by DNA damage in EphA5-silenced cells was defective. γ-H2AX foci in the irradiated EphA5-silenced cells were impaired at 0.5 h post-IR treatment as well as ATM activation. The defective activation of ATM resulted in a decrease of p-Chk2, p-p53 and p21 expression. CONCLUSION: In conclusion, these results indicate that EphA5 silencing increases radiosensitivity in ESCC cells through ATM-dependent pathway, which provides a potential target for the radiotherapy in ESCC.
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BACKGROUND: For patients with locally advanced rectal cancer (LARC), it is unclear whether neoadjuvant chemoradiotherapy-induced pathologic complete response (pCR) individuals would further benefit from adjuvant chemotherapy (ACT). METHODS: The pCR individuals who received different ACT cycles were paired by propensity score matching. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier and log-rank test. RESULTS: In total, 1041 pCR individuals were identified from 5567 LARC cases. Specifically, 303 pCR cases had no ACT treatment, and 738 pCR patients received fluoropyrimidine-based ACT (median, 4 cycles) treatment. After 1:3 propensity score matching, 297 cases without ACT treatment were matched to 712 cases who received ACT treatment. Kaplan-Meier analysis showed that pCR individuals treated with or without ACT had the similar 3-year outcome (OS, DFS, LRFS and DMFS) (all P > 0.05). Moreover, the pCR patients received different ACT cycle(s) (0 vs. 1-4 cycles, 0 vs. ≥5 cycles) had comparable 3-year OS, DFS, LRFS and DMFS (all P > 0.05). In stratified analysis, ACT treatment did not improve 3-year survival (OS, DFS, LRFS and DMFS) for the baseline high-risk (cT3-4/cN1-2) subgroup patients (all P > 0.05). CONCLUSION: ACT, which did not improve survival, is unnecessary to neoadjuvant treatment-induced pCR LARC patients. TRIAL REGISTRATION: 2019ZSLYEC-136 (24-6-2019).
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Quimioradioterapia , Neoplasias del Recto/terapia , Adulto , Anciano , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Neoplasias del Recto/mortalidadRESUMEN
Radiotherapy and chemotherapy are two major treatment options for esophageal carcinoma, and heterogeneous treatment effects are observed in the clinical setting to provide an overall 5year survival rate of ~20%. Hence, defining the molecular mechanisms that affect the chemoradiotherapy response is vital to achieve an optimal outcome. The present study revealed that miR1555p may be involved in esophageal squamous cell carcinoma (ESCC). By means of reverse transcriptionPCR, the present study defined its differential expression pattern in six ESCC cell lines that were associated with resistance to radiation. Ectopic expression of miR1555p promoted DNA damage repair and induced resistance against radiation by nonhomologous end joining repair. It also enhanced chemoresistance, proliferation, and migration and invasion of ESCC cells. By further screening its potential target genes, the present study identified MAP3K10 as the direct target gene to exert its antichemoradiation functions. The results also demonstrated that its differential expression pattern was negatively regulated by the methylation status of the upstream CpG island. Overall, the results of the present study demonstrated that miR1555p is a key molecule for understanding the heterogeneous responses of ESCC to chemoradiotherapy, and may be used in personalized treatment plans for this high mortality tumor in the future.
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Metilación de ADN , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Quinasas Quinasa Quinasa PAM/genética , MicroARNs/genética , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Islas de CpG , Reparación del ADN por Unión de Extremidades , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Epigénesis Genética , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Regulación Neoplásica de la Expresión Génica , Humanos , Tolerancia a Radiación , Análisis de SupervivenciaRESUMEN
Chlorophyll-a (CHLA) is a key indicator to represent eutrophication status in lakes. In this study, CHLA, total phosphorus (TP), total nitrogen (TN), turbidity (TB), and Secchi depth (SD) collected by the United States Environmental Protection Agency for the National Lakes Assessment in the continental USA were analyzed. Statistical analysis showed that water quality variables in natural lakes have strong patterns of autocorrelations than man-made lakes, indicating the perturbation of anthropogenic stresses on man-made lake ecosystems. Meanwhile, adaptive neuro-fuzzy inference systems (ANFIS) with fuzzy c-mean-clustering algorithm (ANFIS_FC), ANFIS with grid partition method (ANFIS_GP), and ANFIS with subtractive clustering method (ANFIS_SC) were implemented to model CHLA in lakes, and modeling results were compared with the multilayer perceptron neural network models (MLPNN). Results showed that ANFIS_FC models outperformed other models for natural lakes, while for man-made lakes, MLPNN models performed the best. ANFIS_GP models have the lowest accuracies in general. The results indicated that ANFIS models can be screening tools for an overall estimation of CHLA levels of lakes in large scales, especially for natural lakes.
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Inteligencia Artificial , Clorofila A/análisis , Monitoreo del Ambiente/métodos , Lagos/análisis , Algoritmos , Clorofila/análisis , Análisis por Conglomerados , Ecosistema , Eutrofización , Lagos/química , Nitrógeno/análisis , Fósforo/análisis , Estados Unidos , United States Environmental Protection Agency , Calidad del AguaRESUMEN
Background: Radiotherapy is one of the most common treatments for esophageal squamous cell carcinoma (ESCC). Radioresistance is a major obstacle that limits the efficacy of radiotherapy. H19 has been considered as a factor affecting radioresistance, whereas the specific mechanism of H19 in ESCC radioresistance remains to be further elucidated. Purpose: The objective of this study was to identify the relationship between H19 and radioresistance. The findings are expected to provide new insights into the treatment of radioresistant ESCC. Methods: The expression levels of H19 in ESCC was analyzed using the online database starBase. The Oncomine database was used to further verify the association between H19 expression and patient age, gender, and tumor stage. The overall survival rates of ESCC patients were analyzed using the KM plotter database. Clonogenic survival was conducted to identify the value of survival fraction. The optical density values were obtained via MTS assays. Cells migration and stemness were observed through Transwell and sphere formation assays. The expression levels of H19, miR-22-3p and WNT1 were analyzed using qPCR. Results: In our study, we firstly screened the H19 according to the online database starBase, and then the Oncomine database and KM plotter database showed that H19 expression was significantly upregulated in the ESCC tissues and associated with poor prognosis. Secondly, an ESCC radioresistant cell line, KYSE150R was established. Clonogenic survival showed that radiation decreased the value of survival fraction. MTS assays suggested that optical density values in KYSE150R cells were significantly higher than that in KYSE150 cells. Transwell and sphere formation assays showed radiation enhanced cell migration and stemness in ESCC cells. In addition, qPCR showed that H19 was upregulated in KYSE150R cells, and survival fraction assays showed that knockdown of H19 decreased the survival fraction values. MTS assays, migration and invasion assays suggested that H19 inhibited cells proliferation, migration and stemness in radioresistant KYSE150 cells. Moreover, qPCR assay showed that miR-22-3p expression levels was downregulated, but WNT1 was upregulated in KYSE150R cells as well as protein levels. Luciferase activity assay further showed that miR-22-3p inhibits the WNT1 expression. Conclusion: Our results demonstrate that H19 knockdown downregulates the WNT1 via upregulating miR-22-3p expression, which leads to the inhibition of cells proliferation, migration and stemness in the radioresistant ESCC cells.
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BACKGROUND: MicroRNA-145 (miR-145) is commonly down-regulated and has been identified as a tumor-suppressive miRNA in multiple types of cancers, as well as in esophageal squamous cell carcinoma (ESCC). In the present study, the clinical significance and prognostic value were investigated in ESCC. METHODS: A total of 126 patients with ESCC who underwent surgery were included in the present study. miR-145 expression was determined using quantitative real-time polymerase chain reaction assay (qRT-PCR) and was further correlated with patients' clinicopathological parameters. Overall survival was estimated by using Kaplan-Meier method, and univariate analysis was conducted by log-rank test. The Cox proportional hazards model was used in the multivariate analysis. RESULTS: miR-145 expression levels in ESCC tissues were significantly decreased compared with the adjacent normal zones (P < 0.001). We observed that the expression level of miR-145 was positively correlated with the tumor differentiation (P = 0.015), lymph node status (P = 0.007), distant metastasis (P = 0.008), and TNM stage (P = 0.033). ESCC patients with low miR-145 expression level had shorter overall survival than those with high miR-145 expression level (log-rank test, P = 0.032). Furthermore, multivariate Cox regression analysis showed that miR-145 expression level was independent factor in predicting the overall survival of ESCC patients (HR = 1.993, 95% CI: 1.277-8.283, P = 0.023). CONCLUSIONS: Our findings indicated that miR-145 expression may be a useful prognostic marker that could be used for predicting overall survival of patients with ESCC.
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Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , MicroARNs/biosíntesis , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/genética , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
In order to investigate the clinical value of different chemotherapies, the efficacy of intensity-modulated radiation therapy with concurrent chemotherapy following D2 radical surgery for gastric carcinoma was evaluated in this study. A total of 102 patients who underwent D2 radical surgery for gastric carcinoma followed by concurrent chemoradiotherapy (CRT) between January, 2008 and March, 2012, were selected. The 5/7 field intensity-modulated radiation therapy was used, with a planning target volume dose of 45 Gy in 25 fractions over 5 weeks. Among these patients, 45 were administered 400 mg/m2/day fluorouracil and 20 mg/m2/day tetrahydrofurfuryl alcohol through intravenous infusion 4 days before and 3 days after the radiotherapy (F-CRT group), while 57 patients received 825 mg/m2 capecitabine orally twice a day (C-CRT group). The 3-year overall and the disease-free survival rates were 75.5 and 70.5%, respectively. The overall 3-year survival rates of the F-CRT and C-CRT groups were 72.2 and 78.5% (P>0.05), respectively, and the 3-year disease-free survival rates were 67.7 and 72.8% (P>0.05), respectively. No significant differences were observed between the two groups. However, during the concurrent CRT, significant differences were found in the incidence of grade 1-2 haematological toxicity between the F-CRT and C-CRT groups (73.3 vs. 50.9%, respectively; χ2 =5.320, P=0.021). Significant differences were also found in the incidence of grade 1-2 gastrointestinal reactions between the two groups (77.8 vs. 57.9%, respectively; χ2=4.474, P=0.034). Therefore, intensity-modulated radiation therapy combined with concurrent chemotherapy following D2 radical surgery for gastric cancer was found to be safe and effective. In addition, radiotherapy was better tolerated and more likely to be completed using C-CRT rather than F-CRT.
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This paper presents an analysis of the relationship of particle velocity and convergence of the particle swarm optimization. Its premature convergence is due to the decrease of particle velocity in search space that leads to a total implosion and ultimately fitness stagnation of the swarm. An improved algorithm which introduces a velocity differential evolution (DE) strategy for the hierarchical particle swarm optimization (H-PSO) is proposed to improve its performance. The DE is employed to regulate the particle velocity rather than the traditional particle position in case that the optimal result has not improved after several iterations. The benchmark functions will be illustrated to demonstrate the effectiveness of the proposed method.