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Raltitrexed as a synergistic hyperthermia chemotherapy drug screened in patient-derived colorectal cancer organoids

Cancer Biology & Medicine 2021年第3期18卷 750-762页

作者： Lisi Zeng Quanxing Liao Haoran Zhao Shengwei Jiang Xianzi Yang Hongsheng Tang Qingjun he Xiansheng Yang Shuxian Fang jinfu he Weiwen Cui Laiqiang Huang Shaohua Ma Shuzhong Cui Institute of Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityGuangzhou 510095China Department of Abdominal Surgery Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityGuangzhou 510095China Institute of Biopharmaceutical and health Engineering Shenzhen International Graduate SchoolTsinghua UniversityShenzhen 518055China Tsinghua-Berkeley Shenzhen Institute(TBSI) Tsinghua UniversityShenzhen 518055China Shenzhen Key Laboratory of Gene and Antibody Therapy Tsinghua UniversityShenzhen 518055China Department of Medical Oncology Affiliated Cancer Hospital and Institute of Guangzhou Medical UniversityGuangzhou 510095China Department of Bioengineering University of CaliforniaBerkeley 94720USA

Objective:Organoids have recently been used as in vitro models to screen chemotherapy drugs in combination with hyperthermia treatment in colorectal cancer.Our research aimed to establish a library of patient-derived colorectal cancer organoids to evaluate synergism between chemotherapy drugs and hyperthermia;validate an index of the hyperthermia chemotherapy sensitization enhancement ratio(HCSER)to identify the chemotherapeutics most enhanced by hyperthermia;and recommend chemotherapy drugs for hyperthermic intraperitoneal treatment.Methods:Organoids were grown from cells extracted from colorectal cancer patient samples or colorectal cancer cell lines.Cells from both sources were encapsulated in 3 D Matrigel droplets,which were formulated in microfluidics and phase-transferred into identical cell-laden Matrigel microspheres.The microspheres were seeded in 96-well plates,with each well containing a single microsphere that developed into an organoid after 7 days.The organoids were used to evaluate the efficacy of chemotherapy drugs at both 37℃ as a control and 43℃ for 90 min to examine hyperthermia synergism.Cell viability was counted with 10%CCK8.Results:We successfully established a library of colorectal cancer organoids from 22 patient parental tumors.We examined the hyperthermia synergism of 7 commonly used hyperthermic intraperitoneal chemotherapy drugs.In 11 of the 22 patient organoids,raltitrexed had significant hyperthermia synergism,which was indexed as the highest HCSER score within each patient group.Conclusions:Our results primarily demonstrated the use of patient-derived colorectal cancer organoids as in vitro models to evaluate hyperthermia synergistic chemotherapeutics.We found that hyperthermia enhanced the effect of raltitrexed the most among the common anti-colorectal cancer drugs.

关键词： Colorectal cancer organoids hyperthermia chemotherapy sensitization enhancement ratio raltitrexed

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Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

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World Journal of Emergency Medicine 2024年第2期15卷 91-97页

作者： Qing Zhao jinfu Ma Jianguo Xiao Zhe Feng Hui Liu Department of Diagnosis and Treatment of Cadres the First Medical CenterChinese PLA General HospitalBeijing 100853China Intensive Care Unit the 305th Hospital of Chinese PLABeijing 100032China Department of Critical Care Medicine the First Medical CenterChinese PLA General HospitalBeijing 100853China Nephrology Department the First Medical CenterChinese PLA General HospitalBeijing 100853China

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

关键词： Sepsis Acute kidney injury Interleukin 32 Toll-like receptor 2 Bioinformatics analysis

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Mechanical behavior and failure mechanisms of rock bolts subjected to static-dynamic loads

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International Journal of Mining Science and Technology 2024年第3期34卷 281-288页

作者： Hongpu Kang Guiyang Yuan Linpo Si Fuqiang Gao jinfu Lou Jinghe Yang Shuangyong Dong CCTEG Coal Mining Research InstituteBeijing 100013China State Key Laboratory of Intelligent Coal Mining and Strata Control Beijing 100013China

This study explores the effects of dynamic and static loading on rock bolt performance a key factor in maintaining the structural safety of coal mine roadways susceptible to coal bursts.Employing a housemade load frame to simulate various failure scenarios,pretension-impact-pull tests on rock bolts were conducted to scrutinize their dynamic responses under varied static load conditions and their failure traits under combined loads.The experimental results denote that with increased impact energy,maximum and average impact loads on rock bolts escalate significantly under pretension,initiating plastic deformation beyond a certain threshold.Despite minor reductions in the yield load due to impactinduced damage,pretension aids in constraining post-impact deformation rate and fluctuation degree of rock bolts.Moreover,impact-induced plastic deformation causes internal microstructure dislocation,fortifying the stiffness of the rock bolt support system.The magnitude of this fortification is directly related to the plastic deformation induced by the impact.These findings provide crucial guidance for designing rock bolt support in coal mine roadway excavation,emphasizing the necessity to consider both static and dynamic loads for improved safety and efficiency.

关键词： Rock bolt Pretension Static and dynamic load Impact

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Influences of Lactiplantibacillus plantarum and Saccharomyces cerevisiae fermentation on the nutritional components,flavor property and lipid-lowering effect of highland barley

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未来食品学报(英文) 2024年第3期4卷 258-266页

作者： Juan Bai Linzhao he jinfu Zhang Xiangyue Gu Beiqi Wu Anlin Wang Ying Zhu Jiayan Zhang Yansheng Zhao Jie Yuan Xiang Xiao School of Food and Biological Engineering Jiangsu UniversityZhenjiang 212013China

Highland barley is a well-known cereal in Qinghai-Tibet Plateau area with high nutritional value,which has been reported to be a health-promoting grain for the obesity and the diabetes.Fermentation by certain microbiota can improve the flavor property and nutritional characteristics.In the present study,Lactiplantibacillus plantarum and Saccharomyces cerevisiae were singly or jointly applied to ferment highland barley,and the profile of volatile substances and lipid-lowering effects of the respective extracts were analyzed.Results indicated that either L.plantarum or S.cerevisiae or co-fermentation could consume the polysaccharides of highland barley to provide energy,and dramatically increase the contents of total protein and polyphenol.Gas chromatography-mass spectrometry(GC-MS)analysis revealed that the presence of S.cerevisiae was critical for production of the pleasant flavors,especially for the ethyl ester substances including hexadecanoic acid ethyl,hexanoic acid ethyl ester and so on.Meanwhile,we found that fermented highland barley extracts by L.plantarum exhibited stronger lipid-lowering effects in Caenorhabditis elegans than that by S.cerevisiae,while the co-fermentation not only emitted pleasant odors but also exerted high hypolipidemic function.In all,co-fermentation by L.plantarum and S.cerevisiae was proposed to be a promising processing to improve the flavor and functional properties of highland barley.

关键词： Highland barley Lactiplantibacillus plantarum Saccharomyces cerevisiae Fermentation Flavor property Lipid-lowering

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Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1693-1710页

作者： Xiong Chen jinfu Qian Shiqi Liang Jianchang Qian Wu Luo Yujuan Shi Hong Zhu Xiang Hu Gaojun Wu Xiaokun Li Guang Liang Department of Endocrinology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China Chemical Biology Research Center School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China Department of Wound Repair the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China Department of Cardiology the First Affiliated HospitalWenzhou Medical UniversityWenzhou 325035China School of Pharmaceutical Sciences Hangzhou Medical CollegeHangzhou 311399China

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses via MAPKs–NFκB signaling pathway in HG-challenged cardiomyocytes, which further results in fibrosis and hypertrophy. We then generated cardiomyocyte-specific FGFR1 knockout mice and showed that a lack of FGFR1 in cardiomyocytes prevents diabetes-induced cardiac inflammation and preserves cardiac function in mice. Pharmacological inhibition of FGFR1 by a selective inhibitor, AZD4547, also prevents cardiac inflammation, fibrosis, and dysfunction in both type 1 and type 2 diabetic mice. These studies have identified FGFR1 as a new player in driving DCM and support further testing of FGFR1 inhibitors for possible cardioprotective benefits.

关键词： Diabetic cardiomyopathy Protein tyrosine kinases FGFR1 Cardiomyocytes Inflammatory responses Toll-like receptor4 c-Src NFkB

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Effect of repeated melting of the mother ingot on the thermal stability of a Zr6oAl15Ni25 bulk glassy alloy

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Rare Metals 2003年第3期22卷 206-209页

作者： YAN Zhijie , LI jinfu WANG Honghua he Shunrong and ZhOU Yaohe1) State Key Lab. of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200030, China2) Taiyuan heavy Machinery Institute, Taiyuan 030024, China Shanghai Jiao Tong University State Key Lab. of Metal Matrix Composites 上海 200030

The effect of repeated melting of the mother ingot on the thermal stabilityof a Zr_(60)Al_+(15)Ni_(25) glassy alloy was investigated by differential scanning calorimetry(DSC). Experimental results indicate that after the repeated melting of the ingots at 1300 and 1580K, the glass transition temperature T_g increases from 686.4 to 690.7 and 696.8 K and the onsettemperature of crystallization T_x from 757.9 to 758.6 and 763.4 K, respectively, indicating thatthe thermal stability becomes higher after the repeated arc melting of the mother ingot and that itis more effective at higher temperature. Within the framework of structure heredity, the origin ofthe improvement of the thermal stability of Zr_(60)Al_+(15)Ni_(25) bulk glassy alloy is discussed.

关键词： bulk glassy alloy thermal stability differential scanning calorimetry structure heredity ZrAlNi alloy

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机器人单孔+1腹腔镜与单孔腹腔镜肾盂成形术治疗肾盂输尿管连接部梗阻患儿的疗效比较

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中华医学杂志 2024年第5期104卷 371-376页

作者：李鋆陈荆艺贾金富何少华徐迪福建医科大学省立临床医学院福建省立医院小儿外科福州350001

目的比较机器人单孔+1腹腔镜肾盂成形术(R-SILP+1)与单孔腹腔镜肾盂成形术(SILP)治疗肾盂输尿管连接部梗阻患儿(UPJO)的疗效。方法回顾性分析2020年10月至2022年9月福建省立医院小儿外科接受手术治疗的47例UPJO患儿的临床资料,根据家长... 详细信息

目的比较机器人单孔+1腹腔镜肾盂成形术(R-SILP+1)与单孔腹腔镜肾盂成形术(SILP)治疗肾盂输尿管连接部梗阻患儿(UPJO)的疗效。方法回顾性分析2020年10月至2022年9月福建省立医院小儿外科接受手术治疗的47例UPJO患儿的临床资料,根据家长选择的手术方式,将患儿分为R-SILP+1组和SILP组。比较两组患儿基线资料、手术时间、术中吻合时间、术中出血量、术后住院时间、并发症、总费用、手术前后肾实质厚度(PT)、肾盂前后径(APD)、患侧分肾功能(DRF)等,评价两种术式的临床疗效。结果47例UPJO患儿中,R-SILP+1组27例,男16例,女11例,年龄(6.6±3.5)岁;SILP组20例,男12例,女8例,年龄(6.5±3.5)岁。两组患儿手术均获得成功,无中转开放手术。两组患儿基线资料、术中出血量、并发症、术后6个月APD、PT及术后12个月APD、PT、DRF差异均无统计学意义(均P>0.05)。与SILP组相比,R-SILP+1组患儿的手术时间[(153.0±14.4)比(189.9±32.6)min,P<0.001]、术中吻合时间[(68.8±16.8)比(97.5±12.0)min,P<0.001]及术后住院时间均较短[(6.0±1.3)比(9.0±1.3)d,P<0.001],但总费用较高[(57390±7664)比(30183±4219)元,P<0.001]。结论与SILP相比,R-SILP+1治疗小儿UPJO能够取得相当的疗效,在缩短手术时间、术中吻合时间、术后住院天数方面具有一定优势,但费用较高。

关键词：输尿管梗阻肾盂输尿管连接部梗阻腹腔镜肾盂成形术机器人单孔+1 单孔腹腔镜技术

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不同工况和应用场景下CAES-CFP三联产系统特性分析

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Engineering 2024年第3期34卷 233-245页

作者： Jiajia Li Peigang Yan Guowen Zhou Xingshuo Li Qiang Li jinfu Liu Daren Yu School of Energy Science and Engineering Harbin Institute of TechnologyHarbin 150001China

To meet the goal of worldwide decarbonization,the transformation process toward clean and green energy structures has accelerated.In this context,coal-fired power plant(CFPP)and large-scale energy storage represented by compressed air energy storage(CAES)technology,are tasked with increasing renewable resource accommodation and maintaining the power system security.To achieve this,this paper proposes the concept of a CFPP-CAES combined cycle and a trigenerative system based on that.Considering the working conditions of the CFPP,thermal characteristics of three typical operation modes were studied and some general regularities were identified.The results of various potential integration schemes discussion indicated that extracting water from low-temperature points in the feedwater system to cool pressurized air and simultaneously increase the backwater temperature is beneficial for improving performance.In addition,preheating the pressurized air before the air expanders via lowgrade water in the feedwater system as much as possible and reducing extracted steam contribute to increasing the efficiency.With the optimal integration scheme,2.85 tonnes of coal can be saved per cycle and the round-trip efficiency can be increased by 2.24%.Through the cogeneration of heat and power,the system efficiency can reach 77.5%.In addition,the contribution degree of the three compression heat utilization methods to the performance improvement ranked from high to low,is preheating the feedwater before the boiler,supplying heat,and flowing into the CFPP feedwater system.In the cooling energy generation mode,the system efficiency can be increased to over 69%.Regardless of the operation mode,the benefit produced by integration is further enhanced when the CFPP operates at higher operating conditions because the coupling points parameters are changed.In addition,the dynamic payback period can be shortened by 11.33 years and the internal rate of return increases by 5.20%under a typical application scenario.Regarding the effect of differ

关键词： Compressed air energy storage CFPP-CAES combined cycle Thermodynamic performance Technical economics

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基于双目视觉的吊卡识别及其方位检测方法

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石油机械 2024年第4期52卷 11-17页

作者：李进付中石化胜利石油工程有限公司钻井工艺研究院

针对钻井自动化中的吊卡方位需要人工参与,存在识别定位缓慢和准确性差等问题,建立了基于双目视觉的吊卡自动识别和方位检测系统。通过搭建双目相机视觉检测系统,对获取的吊卡图像进行标定、立体校正和立体匹配,进而获取吊卡图像的深度... 详细信息

针对钻井自动化中的吊卡方位需要人工参与,存在识别定位缓慢和准确性差等问题,建立了基于双目视觉的吊卡自动识别和方位检测系统。通过搭建双目相机视觉检测系统,对获取的吊卡图像进行标定、立体校正和立体匹配,进而获取吊卡图像的深度图。在原YOLOv5s目标检测算法的主干网络中引入卷积注意力机制模块,将要识别的目标即吊卡图像进行增强,进一步提高吊卡的识别准确率,结合深度图计算出吊卡中心位置相对机械手的距离和偏转角度,从而实现自动送管。通过在钻井平台的试验,验证了吊卡识别和检测方法的有效性。所得结论可为钻井平台自动化程度的进一步提高提供技术借鉴。

关键词：吊卡识别方位检测双目相机 YOLOv5s算法卷积注意力机制模块试验验证

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基于随机噪声和自适应步长的快速对抗训练方法

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计算机应用 2024年第6期44卷 1807-1815页

作者：吴锦富柳毅广东工业大学计算机学院广州510006

当前对抗训练(AT)及其变体被证明是防御对抗攻击的最有效方法,但生成对抗样本的过程需要庞大的计算资源,导致模型训练效率低、可行性不强;快速AT(Fast-AT)使用单步对抗攻击代替多步对抗攻击加速训练过程,但模型鲁棒性远低于多步AT方法... 详细信息

当前对抗训练(AT)及其变体被证明是防御对抗攻击的最有效方法,但生成对抗样本的过程需要庞大的计算资源,导致模型训练效率低、可行性不强;快速AT(Fast-AT)使用单步对抗攻击代替多步对抗攻击加速训练过程,但模型鲁棒性远低于多步AT方法且容易发生灾难性过拟合(CO)。针对这些问题,提出一种基于随机噪声和自适应步长的Fast-AT方法。首先,在生成对抗样本的每次迭代中,通过对原始输入图像添加随机噪声增强数据;其次,累积训练过程中每个对抗样本的梯度,并根据梯度信息自适应地调整对抗样本的扰动步长;最后,根据步长和梯度进行对抗攻击,生成对抗样本用于模型训练。在CIFAR-10、CIFAR-100数据集上进行多种对抗攻击,相较于N-FGSM(Noise Fast Gradient Sign Method),所提方法在鲁棒准确率上取得了至少0.35个百分点的提升。实验结果表明,所提方法能避免Fast-AT中的CO问题,提高深度学习模型的鲁棒性。

关键词：深度学习对抗样本对抗训练随机噪声自适应攻击步长

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