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Soft-HGRNs:soft hierarchical graph recurrent networks for multi-agent partially observable environments

Frontiers of Information Technology & Electronic Engineering 2023年第1期24卷 117-130页

作者： Yixiang REN Zhenhui YE Yining CHEN xiaohong jiang Guanghua SONG School of Aeronautics and Astronautics Zhejiang UniversityHangzhou 310027China College of Computer Science and Technology Zhejiang UniversityHangzhou 310027China

The recent progress in multi-agent deep reinforcement learning(MADRL)makes it more practical in real-world tasks,but its relatively poor scalability and the partially observable constraint raise more challenges for its performance and deployment.Based on our intuitive observation that human society could be regarded as a large-scale partially observable environment,where everyone has the functions of communicating with neighbors and remembering his/her own experience,we propose a novel network structure called the hierarchical graph recurrent network(HGRN)for multi-agent cooperation under partial observability.Specifically,we construct the multiagent system as a graph,use a novel graph convolution structure to achieve communication between heterogeneous neighboring agents,and adopt a recurrent unit to enable agents to record historical information.To encourage exploration and improve robustness,we design a maximum-entropy learning method that can learn stochastic policies of a configurable target action entropy.Based on the above technologies,we propose a value-based MADRL algorithm called Soft-HGRN and its actor-critic variant called SAC-HGRN.Experimental results based on three homogeneous tasks and one heterogeneous environment not only show that our approach achieves clear improvements compared with four MADRL baselines,but also demonstrate the interpretability,scalability,and transferability of the proposed model.

关键词： Deep reinforcement learning Graph-based communication Maximum-entropy learning Partial observability Heterogeneous settings

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Alleviating experimental pulmonary hypertension via co-delivering FoxO1 stimulus and apoptosis activator to hyperproliferating pulmonary arteries

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药学学报:英文版 2023年第6期13卷 2369-2382页

作者： Bingbing Li Chao Teng Huiling Yu xiaohong jiang Xuyang Xing Qi jiang Chenshi Lin Zongmin Zhao Ruifeng Zhang Wei He School of Pharmacy China Pharmaceutical UniversityNanjing 211198China Department of Anesthesiology Affiliated Drum Tower of Nanjing UniversityNanjing 210008China Department of Pharmaceutical Sciences College of PharmacyUniversity of Illinois at ChicagoChicagoIL 60612USA Department of Respiratory Medicine Zhongda Hospital of Southeast UniversityNanjing 210009China Department of Anesthesiology Women's Hospital of Nanjing Medical UniversityNanjing Maternity and Child Health Care HospitalNanjing 210004China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Pulmonary hypertension(PH)is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated.The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells(PASMCs)contributes to pulmonary vascular remodeling in pulmonary hypertension,which is closely linked to the downregulation of forkhead box transcriptional factor O1(FoxO1)and apoptotic protein caspase 3(Cas-3).Here,PA-targeted co-delivery of a FoxO1 stimulus(paclitaxel,PTX)and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension.The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles,followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs.The co-loaded system(170 nm)circulates in the blood over time,accumulates in the lung,effectively targets the PAs,and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics,leading to a decrease in pulmonary arterial pressure and Fulton's index.Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis.Taken together,this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

关键词： Pulmonary hypertension Pulmonary artery smooth muscle cells Fork-head box transcriptional factor O1 Caspase 3 Co-delivery

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Dynamic value iteration networks for the planning of rapidly changing UAV swarms

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Frontiers of Information Technology & Electronic Engineering 2021年第5期22卷 687-696页

作者： Wei LI Bowei YANG Guanghua SONG xiaohong jiang School of Aeronautics and Astronautics Zhejiang UniversityHangzhou 310027China School of Computer Science and Technology Zhejiang UniversityHangzhou 310027China

In an unmanned aerial vehicle ad-hoc network(UANET),sparse and rapidly mobile unmanned aerial vehicles(UAVs)/nodes can dynamically change the UANET topology.This may lead to UANET service performance issues.In this study,for planning rapidly changing UAV swarms,we propose a dynamic value iteration network(DVIN)model trained using the episodic Q-learning method with the connection information of UANETs to generate a state value spread function,which enables UAVs/nodes to adapt to novel physical locations.We then evaluate the performance of the DVIN model and compare it with the non-dominated sorting genetic algorithm II and the exhaustive method.Simulation results demonstrate that the proposed model significantly reduces the decisionmaking time for UAV/node path planning with a high average success rate.

关键词： Dynamic value iteration networks Episodic Q-learning Unmanned aerial vehicle(UAV)ad-hoc network Non-dominated sorting genetic algorithm II(NSGA-II) Path planning

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Metal phenolic network-stabilized nanocrystals of andrographolide to alleviate macrophage-mediated inflammation in-vitro

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Chinese Chemical Letters 2023年第1期34卷 225-229页

作者： Kosheli Thapa Magar George Frimpong Boafo Makhloufi Zoulikha xiaohong jiang Xiaotong Li Qingqing Xiao Xuyang Xing Xiaochun Wang Lifang Fan Zhenfeng Wu Wei He School of Pharmacy China Pharmaceutical UniversityNanjing 211198China jiangsu Aosaikang Pharmaceutical Co. Ltd.Nanjing 211112China Key Laboratory of Modern Preparation of TCM Ministry of EducationJiangxi University of Chinese MedicineNanchang 330004China

Macrophages play a crucial role in initiating,maintaining,and resolving inflammation through the phenotypic shift,inducing or inhibiting the production of inflammatory cytokines.Therefore,macrophages are potential targets for treating inflammatory diseases.Andrographolide(AND)is a potent anti-inflammatory drug that can reduce pro-inflammatory cytokines and suppress NF-κB/MAPK pathway in activated macrophages.Although AND has many medicinal properties,its lower water solubility and first-pass effect in the liver have hindered its clinical application.In this context,by using a metal phenolic network as a stabilizer,we designed and prepared highly stabilized AND nanocrystals(AND-MPN Ns)with high drug loading capacity to facilitate the clinical application of AND.Our findings showed that AND-MPN Ns could be used to enhance the anti-inflammation in-vitro via macrophage polarization,reducing proinflammatory cytokines IL-6 and TNF-α,and suppressing the NF-κB signaling pathway activation.The results demonstrated the potential of AND-MPN Ns to combat inflammatory diseases effectively.

关键词： Inflammation Macrophages Andrographolide Metal phenolic network Nanocrystals

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Targeted co-delivery of daunorubicin and cytarabine based on the hyaluronic acid prodrug modified liposomes

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Chinese Chemical Letters 2022年第10期33卷 4600-4604页

作者： George Frimpong Boafo Yejiao Shi Qingqing Xiao Kosheli Thapar Magar Makhloufi Zoulikha Xuyang Xing Chao Teng Emmanuel Brobbey Xiaotong Li xiaohong jiang Xiaochun Wang Yi Yang Samuel Kesse Wei He Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityNanjing 211198China Institute of Translation Medicine Shanghai UniversityShanghai 200444China

Breast cancer is the most prevalent cancer in women,and it was hard to prevent or diagnose at an early stage.Thus,it is imperative to develop advanced therapeutics for effective treatment.Herein,a targeted daunorubicin(DNR)and cytarabine(ara-C)co-delivery system was developed by modifying the ara-C loaded liposomes(LIP-ara-C)with the hyaluronic acid-DNR(HA-DNR)prodrugs.The co-assembled hybrid nanoparticles(HA-DNR/LIP-ara-C HNPs)exhibited good serum and storage stability with an average diameter of approximately 100 nm.By specifically binding to the CD44 receptors that overexpressed on cancer cells,these HNPs could be uptake via endocytosis and accumulate intracellularly,in which an optimized DNR and ara-C combination at a molar ratio of 1:5 could generate enhanced synergistic effects with reduced dose-related toxicity on cancer cells.

关键词： Breast cancer Daunorubicin Cytarabine Co-delivery Liposomes

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Epicardial adipose tissue around the superior vena cava: A single center study of factors related to atrial fibrillation

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The Journal of Biomedical Research 2022年第6期36卷 401-408页

作者： Xingxing Sun Jun Wang Qing Yan Weizhu Ju Fengxiang Zhang Gang Yang Kai Gu Hailei Liu Zidun wang xiaohong jiang Mingfang Li Di Xu Yi Xu Hongwu Chen Minglong Chen Department of Cardiology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

The superior vena cava(SVC)is the main component of non-pulmonary vein(PV)ectopy in patients with atrial fibrillation(AF).Researchers have found that epicardial adipose tissue(EAT)volume is related to the AF substrate,which can be defined by the low voltage area(LVA).This study aimed to investigate the relationship between SVC-EAT and SVC-AF.Twenty-six patients with SVC-AF triggers were identified as the SVC-AF group.Other three groups were defined and included as the LVA-AF group(LVA>5%),non-LVA-AF group(LVA<5%),and physical examination(PE)group.EAT around left atrium(LA-EAT)and SVC-EAT volumes were obtained using a cardiac risk assessment module.According to the SVC/LA-EAT ratio,there are significant differences between the SVC-AF group and the three control groups(the SVC-AF group 0.092±0.041 vs.the LVA-AF group 0.054±0.026,the non-LVA-AF group 0.052±0.022,and the PE group 0.052±0.019,all P<0.001).Receiver operating characteristic curve analysis suggests the optimal cut-off point of SVC/LA-EAT ratio is 6.8%for detecting SVC-AF patients,with 81.1%sensitivity,73.1%specificity,and an area under the curve of 0.83(95%confidence interval,0.75-0.91).Those with SVC-AF have a higher SVC/LA-EAT ratio and empirical SVC isolation could be considered if the SVC/LA-EAT ratio was over 6.8%.

关键词： atrial fibrillation superior vena cava epicardial adipose tissue low voltage area

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大型主题乐园投资成本与收益分析

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市场周刊 2024年第4期37卷 126-130页

作者：姜小红上海金山资本管理集团有限公司上海201500

随着人民群众对文化旅游、休闲娱乐的美好生活需要不断增长,特色鲜明、丰富多样的大型主题乐园在我国兴起,既满足了群众精神层面的需求,又助力了国内旅游经济高质量发展。然而,投资大型主题乐园不仅需要面临前期的巨额建设资金、开园期... 详细信息

随着人民群众对文化旅游、休闲娱乐的美好生活需要不断增长,特色鲜明、丰富多样的大型主题乐园在我国兴起,既满足了群众精神层面的需求,又助力了国内旅游经济高质量发展。然而,投资大型主题乐园不仅需要面临前期的巨额建设资金、开园期的高额运营成本,还需要应对投资环境的变化带来的经营风险。文章针对国内大型主题乐园当下的发展机遇与风险挑战,从投资和财务管理的层面提出相关管理建议,以帮助主题乐园提高经营效益。

关键词：主题乐园投资成本收益

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In vitro Biological Effects of Ti2448 Alloy Modified by Micro-arc Oxidation and Alkali Heatment

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Journal of Materials Science & Technology 2011年第4期27卷 317-324页

作者： Xue Han Hongchen Liu Dongsheng Wang Shujun Li Rui Yang Xiaojie Tao xiaohong jiang Dental Institute General Hospital of the Chinese People's Liberation Army Beijing 100853 China Department of Stomatology General Hospital of Shenyang Military Region Shenyang 110015 China Shenyang National Laboratory for Materials Science Institute of Metal Research Chinese Academy of Sciences Shenyang 110016 China Department of Orthodontics Shenyang Hospital of Stomatology Shenyang 110002 China

The purpose of this study was to test the hypothesis that the combination of micro-arc oxidation and alkali heatment （MAH） would improve the cytocompatibility of a newly designed Ti-24Nb-4Zr-8Sn alloy. In this study, commercially pure titanium （cp Ti） and Ti-24Nb-4Zr-8Sn were used. Surface modification of Ti-24Nb- 4Zr-8Sn by a two-step treatment of micro-arc oxidation （MAO） and alkali heatment was reported. Surface characterizations were performed by scanning electron microscopy （SEM）, thin film X-ray diffraction （TF-XRD） and X-ray photoelectron spectroscopy （XPS）. The MAH layer consisted of finer crystals and possessed a higher degree of crystallity and stability than the MAO layer. A biocompatibility study on treated and untreated Ti- 24Nb-4Zr-8Sn in comparison with cp Ti was carried out to investigate the effect of the different surfaces on the bone integration property in vitro. The cellular assays revealed that the MAO and MAH layer favored the initial adhesion of MC3T3-E1 cells and that the growth rate of MC3T3-E1 cells on MAH layer was significantly higher than that on the conventional MAO-treated layer after 3-day and 5-day incubation, demonstrating the greater potential of the hybrid treatment of micro-arc oxidation followed with alkali heatment as a novel surface modification method for implanting materials.

关键词： Titanium alloy Micro-arc oxidation Alkali heatment MC3T3-E1 cells In vitrocell response

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贝那鲁肽每日2次注射治疗中国肥胖症患者的前瞻性多中心临床研究

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中华糖尿病杂志 2024年第6期16卷 663-668页

作者：方晨许岚刘煜蒋晓红李莉黄韵陈小红郭鹤鸣张弘弘胡吉苏州大学附属第二医院内分泌科苏州215004 无锡市人民医院内分泌科无锡214023 南京医科大学附属逸夫医院内分泌科南京211112 常州市第一人民医院内分泌科常州213004 太仓市第一人民医院内分泌科太仓215413

目的探讨贝那鲁肽每日2次注射治疗中国肥胖症患者的疗效及安全性。方法为前瞻性多中心前后对照开放性非随机对照研究。选取2017年10月至2018年10月苏州大学附属第二医院内分泌科、南京医科大学附属逸夫医院内分泌科、常州市第一人民医... 详细信息

目的探讨贝那鲁肽每日2次注射治疗中国肥胖症患者的疗效及安全性。方法为前瞻性多中心前后对照开放性非随机对照研究。选取2017年10月至2018年10月苏州大学附属第二医院内分泌科、南京医科大学附属逸夫医院内分泌科、常州市第一人民医院内分泌科、无锡市人民医院内分泌科、太仓市第一人民医院内分泌科的肥胖患者为研究对象。患者入组后先接受为期28 d的饮食控制和运动指导,继而以贝那鲁肽0.2 mg每日2次皮下注射治疗12周,监测患者体重及相关代谢指标。主要观察终点是贝那鲁肽治疗前后的体重变化,次要终点是贝那鲁肽治疗前后的代谢或心血管相关风险因素(血压、腰围、臀围)的变化,同时收集糖耐量异常患者恢复到正常的比例。采用配对t检验比较治疗前后患者相关指标的差异。结果共91例肥胖症患者纳入研究,其中最后有70.3%(64/91)的患者完成试验。与治疗前相比,应用贝那鲁肽每日2次注射治疗12周后64例患者体重下降[分别为(93.15±15.39)kg和(89.30±14.52)kg,t=-9.03,P<0.001]。有31.9%(29/91)的患者体重下降≥5%,6.6%(6/91)的患者体重下降≥10%。与治疗前相比,治疗12周后,患者腰围[分别为(104.22±11.20)cm和(99.80±9.66)cm,t=-7.12,P<0.001]、臀围[分别为(110.80±8.43)cm和(107.10±7.89)cm,t=-6.39,P<0.001]、收缩压[分别为(129.66±14.89)mmHg和(125.60±11.39)mmHg,t=-2.96,P=0.004]均下降。入组时有36.3%(33/91)的患者存在糖耐量异常,干预治疗12周后有24.2%(8/33)的患者恢复正常。在此次研究中不良反应主要为恶心、呕吐和食欲减退,未发现严重不良事件。结论每日2次给予贝那鲁肽皮下注射联合饮食和运动干预对中国肥胖患者进行综合治疗,有减重及改善代谢或心血管相关风险因素的疗效,且安全性和耐受性良好。

关键词：肥胖症糖尿病前期贝那鲁肽安全性有效性

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Pathogenesis and drug response of iPSC-derived cardiomyocytes from two Brugada syndrome patients with different Nav1.5-subunit mutations

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The Journal of Biomedical Research 2021年第5期35卷 395-407,I0004-I0007页

作者： Yue Zhu Linlin Wang Chang Cui Huiyuan Qin Hongwu Chen Shaojie Chen Yongping Lin Hongyi Cheng xiaohong jiang Minglong Chen Department of Cardiology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Cardiology the Affiliated Brain Hospital of Nanjing Medical UniversityNanjing Chest HospitalNanjingJiangsu 210029China

Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.

关键词： human iPSCs Brugada syndrome disease modeling quinidine SCN5A SCN1B

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