The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,w...The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,we first prepared the DTX-loaded activated carbon nanoparticles(DTX-AC-NPs)by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon.We then prepared DTX-loaded nanoliposomes(DTX-LPs)by the proliposome method.The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro.The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites.The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies.DTX-AC-NPs significantly increased DTX-AUC_((0-24)) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo.This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.展开更多
Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediat...Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is unknown.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifyingβ-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs withβ-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate thatβ-glucan-modified MSN,with a particle size of∼100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.展开更多
针对基本的快速搜索随机树(rapidly-exploring random tree,RRT)算法用于路径规划时存在的树扩展无导向性、密集障碍物区域规划效率低、局部区域节点聚集等问题,提出一种新的RRT改进算法。该算法采用增强的目标偏向策略,并引入可变的权...针对基本的快速搜索随机树(rapidly-exploring random tree,RRT)算法用于路径规划时存在的树扩展无导向性、密集障碍物区域规划效率低、局部区域节点聚集等问题,提出一种新的RRT改进算法。该算法采用增强的目标偏向策略,并引入可变的权值系数,提高随机树扩展的导向性和灵活性;同时采用局部节点过滤机制,过滤局部区域内聚集的节点;最后,使用节点直连策略对初始路径进行优化处理。仿真实验的结果表明,改进的RRT算法规划路径的速度更快且生成的路径质量更高,充分证明了改进算法的有效可行性。展开更多
In hybrid wireless sensor networks composed of both static and mobile sensor nodes, the random deployment of stationary nodes may cause coverage holes in the sensing field. Hence, mobile sensor nodes are added after t...In hybrid wireless sensor networks composed of both static and mobile sensor nodes, the random deployment of stationary nodes may cause coverage holes in the sensing field. Hence, mobile sensor nodes are added after the initial deployment to overcome the coverage holes problem. To achieve optimal coverage, an efficient algorithm should be employed to find the best positions of the additional mobile nodes. This paper presents a genetic algorithm that searches for an optimal or near optimal solution to the coverage holes problem. The proposed algorithm determines the minimum number and the best locations of the mobile nodes that need to be added after the initial deployment of the stationary nodes. The performance of the genetic algorithm was evaluated using several metrics, and the simulation results demonstrated that the proposed algorithm can optimize the network coverage in terms of the overall coverage ratio and the number of additional mobile nodes.展开更多
Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV d...Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%-30%), and low-risk (<5%) groups. The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines, which were further categorized into the upper neck (retropharyngeal region and level Ⅱ), middle neck (levels Ⅲ and Va), and lower neck (levels Ⅳ and Vb and the supraclavicular fossa). The high-risk anatomic sites were adjacent to the nasopharynx, whereas those at medium- or low-risk were separated from the nasopharynx. If the high-risk anatomic sites were involved, the rates of tumor invasion into the adjacent medium-risk sites increased; if not, the rates were significantly lower (P < 0.01). Among the 1920 (81.1%) patients with positive LN, the incidence rates of LN metastasis in the upper, middle, and lower neck were 99.6% , 30.2%, and 7.2%, respectively, and skip metastasis happened in only 1.2% of patients. In the 929 patients who had unilateral upper neck involvement, the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease spreads stepwise from proximal sites to distal sites, and LN metastasis spreads from the upper neck to the lower neck. Individualized CTV delineation for NPC may be feasible.展开更多
Purpose: This work evaluates the use of target and organs at risk (OAR) dose-volume goals in 3D conformal radiotherapy (3DCRT) planning for node positive breast cancer (NPBC) patients undergoing regional nodal irradia...Purpose: This work evaluates the use of target and organs at risk (OAR) dose-volume goals in 3D conformal radiotherapy (3DCRT) planning for node positive breast cancer (NPBC) patients undergoing regional nodal irradiation after lumpectomy/mastectomy. Methods: Dosimetric data for 262 NPBC patients receiving regional nodal and whole breast/chest wall (WB/CW) irradiation from 2000-2009 were analyzed. In all cases, target & OAR volumes were delineated on treatment CT scans for field generation and dose-volume histograms (DVHs) were generated. Cases were analyzed to identify how frequently they met treatment planning institutional dose-volume goals (“institutional guidelines” & standardized in 2005) and how this would affect OAR doses. Results: The incidence of cases from 2000-2009 meeting current institutional guidelines improved over the study period. Target coverage improved from 2005-2009, when guidelines were followed as a part of the plan approval. Those cases from 2000-2004 meeting acceptable target goals were found to be significantly different from those cases from 2005-2009 (p < 0.01). However, no significant difference between cases meeting OAR goals for plans from 2000-2004 versus 2005-2009 was found. Conclusions: The use of institutional guidelines in 3DCRT for WB/CW and regional nodal irradiation for NPBC patients improved target coverage without a statistically significant increase in heart and lung doses.展开更多
Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC...Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.展开更多
基金the support of Pharmacy Laboratory Centre and Animal Centre of Shenyang Pharmaceutical Universitysupported by the State Key Laboratory(Long-acting and Targeting Drug Delivery System)the Special Construction Project(Taishan ScholarePharmacy Specially Recruited Experts).
文摘The objective of this study is to compare the targeting ability of activated carbon nanoparticles and nanoliposomes,which are used as carriers for delivering docetaxel(DTX)to the metastatic lymph nodes.In this study,we first prepared the DTX-loaded activated carbon nanoparticles(DTX-AC-NPs)by modifying the activated carbon with nitric acid oxidation and absorbing DTX in the concentrated nitro-oxide nanocarbon.We then prepared DTX-loaded nanoliposomes(DTX-LPs)by the proliposome method.The physiochemical properties of DTX-AC-NPs and DTX-LPs were carefully evaluated in vitro.The metastatic lymph node uptake and the injection site retention were investigated by analyzing the DTX concentration in metastatic lymph nodes and injection sites.The result showed that DTX-AC-NPs and DTX-LPs with suitable and stable physicochemical properties could be used for in vivo lymph node targeting studies.DTX-AC-NPs significantly increased DTX-AUC_((0-24)) and prolonged DTX-retention in metastatic lymph nodes compared to DTX-LPs and non-modified activate carbon in vivo.This study demonstrated activated carbon nanoparticles may be potential intralymphatic drug delivery system to preferentially target regional metastatic lymph nodes.
基金supported by the Doctoral Start-up Foundation of Liaoning Province,China(Grant No.:2021-BS-127)China Medical University,China Medical University Cancer Hospital in animal experiments.
文摘Particle size and surface properties are crucial for lymphatic drainage(LN),dendritic cell(DC)uptake,DC maturation,and antigen cross-presentation induced by nanovaccine injection,which lead to an effective cell-mediated immune response.However,the manner in which the particle size and surface properties of vaccine carriers such as mesoporous silica nanoparticles(MSNs)affect this immune response is unknown.We prepared 50,100,and 200 nm of MSNs that adsorbed ovalbumin antigen(OVA)while modifyingβ-glucan to enhance immunogenicity.The results revealed that these MSNs with different particle sizes were just as efficient in vitro,and MSNs withβ-glucan modification demonstrated higher efficacy.However,the in vivo results indicated that MSNs with smaller particle sizes have stronger lymphatic targeting efficiency and a greater ability to promote the maturation of DCs.The results also indicate thatβ-glucan-modified MSN,with a particle size of∼100 nm,has a great potential as a vaccine delivery vehicle and immune adjuvant and offers a novel approach for the delivery of multiple therapeutic agents that target other lymph-mediated diseases.
文摘针对基本的快速搜索随机树(rapidly-exploring random tree,RRT)算法用于路径规划时存在的树扩展无导向性、密集障碍物区域规划效率低、局部区域节点聚集等问题,提出一种新的RRT改进算法。该算法采用增强的目标偏向策略,并引入可变的权值系数,提高随机树扩展的导向性和灵活性;同时采用局部节点过滤机制,过滤局部区域内聚集的节点;最后,使用节点直连策略对初始路径进行优化处理。仿真实验的结果表明,改进的RRT算法规划路径的速度更快且生成的路径质量更高,充分证明了改进算法的有效可行性。
文摘In hybrid wireless sensor networks composed of both static and mobile sensor nodes, the random deployment of stationary nodes may cause coverage holes in the sensing field. Hence, mobile sensor nodes are added after the initial deployment to overcome the coverage holes problem. To achieve optimal coverage, an efficient algorithm should be employed to find the best positions of the additional mobile nodes. This paper presents a genetic algorithm that searches for an optimal or near optimal solution to the coverage holes problem. The proposed algorithm determines the minimum number and the best locations of the mobile nodes that need to be added after the initial deployment of the stationary nodes. The performance of the genetic algorithm was evaluated using several metrics, and the simulation results demonstrated that the proposed algorithm can optimize the network coverage in terms of the overall coverage ratio and the number of additional mobile nodes.
文摘Clinical target volume (CTV) delineation is crucial for tumor control and normal tissue protection. This study aimed to define the locoregional extension patterns of nasopharyngeal carcinoma (NPC) and to improve CTV delineation. Magnetic resonance imaging scans of 2366 newly diagnosed NPC patients were reviewed. According to incidence rates of tumor invasion, the anatomic sites surrounding the nasopharynx were classified into high-risk (>30%), medium-risk (5%-30%), and low-risk (<5%) groups. The lymph node (LN) level was determined according to the Radiation Therapy Oncology Group guidelines, which were further categorized into the upper neck (retropharyngeal region and level Ⅱ), middle neck (levels Ⅲ and Va), and lower neck (levels Ⅳ and Vb and the supraclavicular fossa). The high-risk anatomic sites were adjacent to the nasopharynx, whereas those at medium- or low-risk were separated from the nasopharynx. If the high-risk anatomic sites were involved, the rates of tumor invasion into the adjacent medium-risk sites increased; if not, the rates were significantly lower (P < 0.01). Among the 1920 (81.1%) patients with positive LN, the incidence rates of LN metastasis in the upper, middle, and lower neck were 99.6% , 30.2%, and 7.2%, respectively, and skip metastasis happened in only 1.2% of patients. In the 929 patients who had unilateral upper neck involvement, the rates of contralateral middle neck and lower neck involvement were 1.8% and 0.4%, respectively. Thus, local disease spreads stepwise from proximal sites to distal sites, and LN metastasis spreads from the upper neck to the lower neck. Individualized CTV delineation for NPC may be feasible.
文摘Purpose: This work evaluates the use of target and organs at risk (OAR) dose-volume goals in 3D conformal radiotherapy (3DCRT) planning for node positive breast cancer (NPBC) patients undergoing regional nodal irradiation after lumpectomy/mastectomy. Methods: Dosimetric data for 262 NPBC patients receiving regional nodal and whole breast/chest wall (WB/CW) irradiation from 2000-2009 were analyzed. In all cases, target & OAR volumes were delineated on treatment CT scans for field generation and dose-volume histograms (DVHs) were generated. Cases were analyzed to identify how frequently they met treatment planning institutional dose-volume goals (“institutional guidelines” & standardized in 2005) and how this would affect OAR doses. Results: The incidence of cases from 2000-2009 meeting current institutional guidelines improved over the study period. Target coverage improved from 2005-2009, when guidelines were followed as a part of the plan approval. Those cases from 2000-2004 meeting acceptable target goals were found to be significantly different from those cases from 2005-2009 (p < 0.01). However, no significant difference between cases meeting OAR goals for plans from 2000-2004 versus 2005-2009 was found. Conclusions: The use of institutional guidelines in 3DCRT for WB/CW and regional nodal irradiation for NPBC patients improved target coverage without a statistically significant increase in heart and lung doses.
基金the National Natural Science Foundation of China(No.82102769)the 111 Project(No.B18035,China)the Fundamental of Research Funds for the Central Universities and Beijing Natural Science Foundation(No.L212054,China).
文摘Tumor vaccine,a promising modality of tumor immunotherapy,needs to go through the process of tumor antigen generation and loading,antigen drainage to lymph nodes(LNs),antigen internalization by dendritic cells(DCs),DC maturation,and antigen cross-presentation to activate T-cells.However,tumor vaccines are often unable to satisfy all the steps,leading to the limitation of their application and efficacy.Herein,based on a smart nanogel system,an in situ nano-vaccine(CpG@Man-P/Tra/Gel)targeting LNs was constructed to induce potent anti-tumor immune effects and inhibit the recurrence and metastasis of ovarian cancer.The CpG@Man-P/Tra/Gel exhibited MMP-2-sensitive release of trametinib(Tra)and nano-adjuvant CPG@Man-P,which generated abundant in situ depot of whole-cell tumor antigens and formed in situ nano-vaccines with CpG@Man-P.Benefiting from mannose(Man)modification,the nano-vaccines targeted to LNs,promoted the uptake of antigens by DCs,further inducing the maturation of DCs and activation of T cells.Moreover,CpG@Man-P with different particle sizes were prepared and the effective size was selected to evaluate the antitumor effect and immune response in vivo.Notably,combined with PD-1 blocking,the vaccine effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis of ovarian cancer.
