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Preoperative ultrasound combined with routine blood tests in predicting the malignant risk of pancreatic cystic neoplasms

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Cancer Biology & Medicine 2022年第10期19卷 1503-1516页

作者： xiuchao wang Junjin wang Xi Wei Lihui Zhao Bo Ni Zekun Li Chuntao Gao Song Gao Tiansuo Zhao Jian wang Weidong Ma Xiao Hu Jihui Hao Department of Pancreatic Cancer Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Diagnostic and Therapeutic Ultrasonography Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Hepatobiliary and Pancreatic Surgery The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Objective:Accurate preoperative identification of benign or malignant pancreatic cystic neoplasms(PCN)may help clinicians make better intervention choices and will be essential for individualized treatment.Methods:Preoperative ultrasound and laboratory examination findings,and demographic characteristics were collected from patients.Multiple logistic regression was used to identify independent risk factors associated with malignant PCN,which were then included in the nomogram and validated with an external cohort.The Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were calculated to evaluate the improvement in the predictive power of the new model with respect to that of a combined imaging and tumor marker prediction model.Results:Malignant PCN were found in 83(40.7%)and 33(38.7%)of the model and validation cohorts,respectively.Multivariate analysis identified age,tumor location,imaging of tumor boundary,blood type,mean hemoglobin concentration,neutrophil-tolymphocyte ratio,carbohydrate antigen 19-9,and carcinoembryonic antigen as independent risk factors for malignant PCN.The calibration curve indicated that the predictions based on the nomogram were in excellent agreement with the actual observations.A nomogram score cutoff of 192.5 classified patients as having low vs.high risk of malignant PCN.The model achieved good C-statistics of 0.929(95%CI 0.890–0.968,Pwangjunjinnomogram.***.io/DynNomapp/.

关键词： Pancreatic cystic neoplasms malignancy prediction nomogram ultrasound blood routine

Dietary Lactiplantibacillus plantarum KX041 attenuates colitis-associated tumorigenesis and modulates gut microbiota

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Food Science and Human Wellness 2023年第5期12卷 1626-1636页

作者： Tao wang Panpan wang Li Yin xiuchao wang Yuanyuan Shan Yanglei Yi Yuan Zhou Bianfang Liu Xin wang Xin Lü College of Food Science and Engineering Northwest Agriculture and Forestry UniversityYangling 712100China Faculty of Food Science and Engineering Kunming University of Science and TechnologyKunming 650500China

Colorectal cancer(CRC)is one of the most common cancers and supplementation of probiotics may be a promising intervention method. The present study aimed to investigate the anti-CRC effects of Lactiplantibacillus plantarum KX041 on a CRC mouse model. The CRC mice were induced by 10 mg/kg azoxymethane and 2% dextran sulfate sodium. L. plantarum KX041 was orally administrated once daily(1 × 10^(9) CFU/mouse). Results showed that L. plantarum KX041 could significantly inhibit inflammation, tumor formation, and induce tumor cells apoptosis. Moreover, this probiotic could ameliorate the damage of intestinal barrier by recovering tight junction protein expression(like Occludin, Claudin-1, and ZO-1)and preventing goblet cell loss. Furthermore, the oxidative stress was alleviated by increasing the level of antioxidant mediators(like GSH and SOD)and reducing the level of oxidative mediators(like MDA and MPO). In addition, treatment with L. plantarum KX041 could directly regulate gut microbiota, thereby increasing the abundance of beneficial bacteria(like SCFAs-producing bacteria, Akkermansia)and decreasing the abundance of harmful bacteria(like pro-inflammatory bacteria, Parasutterella), which in turn raised SCFAs levels and lowered LPS levels. In conclusion, L. plantarum KX041 could effectively ameliorate CRC via reshaping intestinal microenvironment, alleviating inflammation, maintaining intestinal permeability, and attenuating oxidative stress.

关键词： Lactiplantibacillus plantarum KX041 Colorectal cancer Gut microbiota Inflammation Intestinal permeability

BICC1 drives pancreatic cancer progression by inducing VEGF-independent angiogenesis

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3794-3805页

作者： Chongbiao Huang Hui Li Yang Xu Chao Xu Huizhi Sun Zengxun Li Yi Ge Hongwei wang Tiansuo Zhao Song Gao xiuchao wang Shengyu Yang Peiqing Sun Zhe Liu Jing Liu Antao Chang Jihui Hao Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy300060 TianjinChina Department of Anorectal Surgery The Second Hospital of Tianjin Medical UniversityTianjinChina Department of Cellular and Molecular Physiology the Pennsylvania State University College of MedicineHersheyPAUSA Department of Cancer Biology Wake Forest Baptist Comprehensive Cancer CenterWake Forest Baptist Medical CenterWinston-SalemNCUSA Department of Immunology School of Basic Medical SciencesTianjin Medical UniversityTianjinChina

VEGF inhibitors are one of the most successful antiangiogenic drugs in the treatment of many solid tumors.Nevertheless,pancreatic adenocarcinoma(PAAD)cells can reinstate tumor angiogenesis via activation of VEGF-independent pathways,thereby conferring resistance to VEGF inhibitors.Bioinformatic analysis showed that BICC1 was one of the top genes involved in the specific angiogenesis process of PAAD.The analysis of our own cohort confirmed that BICC1 was overexpressed in human PAAD tissues and was correlated to increased microvessel density and tumor growth,and worse prognosis.In cells and mice with xenograft tumors,BICC1 facilitated angiogenesis in pancreatic cancer in a VEGF-independent manner.Mechanistically,as an RNA binding protein,BICC1 bounds to the 3’UTR of Lipocalin-2(LCN2)mRNA and post-transcriptionally up-regulated LCN2 expression in PAAD cells.When its level is elevated,LCN2 binds to its receptor 24p3R,which directly phosphorylates JAK2 and activates JAK2/STAT3 signal,leading to increased production of an angiogenic factor CXCL1.Blocking of the BICC1/LCN2 signalling reduced the microvessel density and tumor volume of PAAD cell grafts in mice,and increased the tumor suppressive effect of gemcitabine.In conclusion,BICC1 plays a pivotal role in the process of VEGF-independent angiogenesis in pancreatic cancer,leading to resistance to VEGF inhibitors.BICC1/LCN2 signaling may serve as a promising anti-angiogenic therapeutic target for pancreatic cancer patients.

关键词： cancer resistance thereby

A new combined criterion to better predict malignant lesions in patients with pancreatic cystic neoplasms

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Cancer Biology & Medicine 2018年第1期15卷 70-78页

作者： Chungen Lan Xin Li xiuchao wang Jihui Hao He Ren Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Centerfor Cancer Key Laboratory of Cancer Prevention and Therapy TianjinTianjin's Clinical Research Center for CancerTianjin 300060China

Objective:Cystic lesions of the pancreas have been increasingly recognized.Some lesions exhibit benign behavior,while others have unequivocal malignant potential.Thus,accurate identification of malignancy in patients diagnosed with pancreatic cystic neoplasms(PCNs)remains a major challenge.The aim of this study was to define a combined criterion to better predict malignant lesions in patients with PCNs.Methods:We retrospectively analyzed 165 patients who underwent resection of PCNs from October 2011 to May 2017.The relationship among malignancy and serum carbohydrate antigen 19-9(CA19-9),preoperative neutrophil-to-lymphocyte ratio(NLR),and the presence of enhanced solid component on imaging was analyzed.Results:NLR before surgery in patients with malignant PCNs(2.81±2.14)was significantly higher than that in patients diagnosed with pancreatic neuroendocrine tumor(1.90±0.69,P=0.013)or healthy volunteers(1.40±0.48;P1.976 and presence of enhanced solid component were independent predictors of PCN malignancy.A combined criterion meeting any two or more of the three elements including CA19-9≥39 U/m L,NLR>1.976,and presence of enhanced solid component on computed tomography imaging is an indicator with a high positive predictive value of 80.5%and a high negative predictive value of 87.9%,and thus,represents a highly accurate test(86.1%).Conclusions:The new combined criterion is an effective predictor of tumor malignancy in patients with PCNs.

关键词：损害膀胱预言胰腺标准 PCN 切除术行为

Nuclear PLD1 combined with NPM1 induces gemcitabine resistance through tumorigenic IL7R in pancreatic adenocarcinoma

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癌症生物学与医学:英文版 2023年第8期20卷 599-626页

作者： Danqi Fu Jingrui Yan Zhaoyu Zhang Yang Liu Xiaoqing Ma Jinsheng Ding Shengyu Yang Ran Zhao Antao Chang Chuntao Gao Jing Liu Tiansuo Zhao xiuchao wang Chongbiao Huang Song Gao Ying Ma Bo Tang Yukuan Feng Hongwei wang Jihui Hao Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Centre for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of General Surgery Changzheng HospitalNaval Medical University(Second Military Medical University)Shanghai 200003China Department of Cellular and Molecular Physiology Penn State College of MedicineHersheyPennsylvania 17033USA

Objective:Pancreatic ductal adenocarcinoma(PDAC)is a highly malignant gastrointestinal cancer with a 5-year survival rate of only 9%.Of PDAC patients,15%-20%are eligible for radical surgery.Gemcitabine is an important chemotherapeutic agent for patients with PDAC;however,the efficacy of gemcitabine is limited due to resistance.Therefore,reducing gemcitabine resistance is essential for improving survival of patients with PDAC.Identifying the key target that determines gemcitabine resistance in PDAC and reversing gemcitabine resistance using target inhibitors in combination with gemcitabine are crucial steps in the quest to improve survival prognosis in patients with PDAC.Methods:We constructed a human genome-wide CRISPRa/dCas 9 overexpression library in PDAC cell lines to screen key targets of drug resistance based on sgRNA abundance and enrichment.Then,co-IP,ChIP,ChIP-seq,transcriptome sequencing,and qPCR were used to determine the specific mechanism by which phospholipase D1(PLD1)confers resistance to gemcitabine.Results:PLD1 combines with nucleophosmin 1(NPM1)and triggers NPM1 nuclear translocation,where NPM1 acts as a transcription factor to upregulate interleukin 7 receptor(IL7R)expression.Upon interleukin 7(IL-7)binding,IL7R activates the JAK1/STAT5 signaling pathway to increase the expression of the anti-apoptotic protein,BCL-2,and induce gemcitabine resistance.The PLD1 inhibitor,Vu0155069,targets PLD1 to induce apoptosis in gemcitabine-resistant PDAC cells.Conclusions:PLD1 is an enzyme that has a critical role in PDAC-associated gemcitabine resistance through a non-enzymatic interaction with NPM1,further promoting the downstream JAK1/STAT5/Bcl-2 pathway.Inhibiting any of the participants of this pathway can increase gemcitabine sensitivity.

关键词： Gemcitabine resistance pancreatic ductal adenocarcinoma phospholipase D1 nucleophosmin 1 CRISPRa library

考虑海上风电与MMC阻抗耦合的柔性直流送出系统等效阻抗建模方法

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中国电机工程学报 2024年第7期44卷 2655-2669,I0012页

作者：罗永捷黄鹏段修超李奇芬王强钢周念成输配电装备及系统安全与新技术国家重点实验室(重庆大学) 重庆市沙坪坝区400044

海上风电经柔直并网系统的阻抗模型是其稳定分析的基础。然而,现有阻抗建模方法忽略海上风电与模块化多电平换流器(modular multilevel converter,MMC)间的阻抗耦合,可能导致系统稳定性判定失准。为此,该文提出一种考虑海上风电与MMC阻... 详细信息

海上风电经柔直并网系统的阻抗模型是其稳定分析的基础。然而,现有阻抗建模方法忽略海上风电与模块化多电平换流器(modular multilevel converter,MMC)间的阻抗耦合,可能导致系统稳定性判定失准。为此,该文提出一种考虑海上风电与MMC阻抗耦合的柔性直流送出系统等效阻抗精确计算方法。首先,采用谐波状态空间理论(harmonic state-space,HSS)建立MMC与风电机组的序阻抗模型;在此基础上,分析风电机组与MMC两者交流端口电压、电流与阻抗的相互耦合机理,以获得风电机组与MMC交流等效阻抗;最后,提出风电机组与MMC阻抗耦合度指标,以量化分析不同控制环节对风电机组与MMC的耦合程度的影响。在MATLAB/Simulink搭建海上风电经柔直送出系统仿真模型验证该文所建模型的精确性及阻抗耦合度的对系统稳定性的影响,并通过RT-Lab硬件在环实验证明该文所建模型在系统稳定性分析中有效性。

关键词：海上风电场柔性直流阻抗耦合耦合机理阻抗建模

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基于匹配线索回归的侧面脊柱关键点检测

激光与光电子学进展 2024年第4期61卷 317-324页

作者：高孟豪郭立君张荣倪丽欣王强何秀超宁波大学信息科学与工程学院浙江宁波315211 宁波大学医学院浙江宁波315211 宁波市海曙区第二医院浙江宁波315099 宁波大学附属第一医院浙江宁波315000

在检测侧面脊柱关键点时,由于受到器官遮挡的影响,以往的热图回归方法难以区分不同椎骨上的关键点,容易出现关键点与对应椎骨的匹配错误。为了解决这个问题,提出了一个新的单阶段侧面脊柱关键点检测方法,该方法同时预测关键点热图和关... 详细信息

在检测侧面脊柱关键点时,由于受到器官遮挡的影响,以往的热图回归方法难以区分不同椎骨上的关键点,容易出现关键点与对应椎骨的匹配错误。为了解决这个问题,提出了一个新的单阶段侧面脊柱关键点检测方法,该方法同时预测关键点热图和关键点匹配线索(椎骨中心热图和关键点offset),利用匹配线索建立关键点与对应椎骨的匹配关系。为了提升匹配效果,提出几何感知特征增强模块,通过提取关键点特征增强椎骨中心的特征表达。此外,利用加权损失函数缓解关键点热图和椎骨中心热图中正负样本比例失衡问题。实验结果表明,所提方法的平均检测误差为8.84,相较于性能第二的方法精度提升36%。

关键词：医用光学关键点检测卷积网络可变形卷积脊柱侧弯

PD-L1 is a direct target of cancer-FOXP3 in pancreatic ductal adenocarcinoma(PDAC),and combined immunotherapy with antibodies against PD-L1 and CCL5 is effective in the treatment of PDAC

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Signal Transduction and Targeted Therapy 2020年第1期5卷 2043-2054页

作者： xiuchao wang Xin Li Xunbin Wei Haiping Jiang Chungen Lan Shengyu Yang Han wang Yanhui Yang Caijuan Tian Zanmei Xu Jiangyan Zhang Jihui Hao He Ren Department of Gastroenterology Center of Tumor Immunology and CytotherapyThe Affiliated Hospital of Qingdao University266003 QingdaoChina Department of Cellular and Molecular Physiology Penn State College of MedicineHersheyPA 17033USA Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and Hospital300060 TianjinChina Department of Geriatric Dentistry Beijing Laboratory of Biomedical MaterialsPeking University School and Hospital of Stomatologyand Biomedical Engineering DepartmentPeking University100081 BeijingChina Department of Applied Statistics College of ScienceHebei University of Technology300401 TianjinChina NHC Key Laboratory of Hormones and Development(Tianjin Medical University) Tianjin Key Laboratory of Metabolic DiseasesTianjin Medical University Chu Hsien-I Memorial Hospital&Tianjin Institute of Endocrinology300134 TianjinChina Tianjin Marvel Medical Laboratory Tianjin Marvelbio Technology Co.Ltd300381 TianjinChina

High expression of PD-L1 marks the poor prognosis of pancreatic ductal adenocarcinomas(PDAC).However,the regulatory mechanism of PD-L1 remains elusive.We recently reported that cancer Forkhead box protein 3(Cancer-FOXP3 or C-FOXP3)promoted immune evasion of PDAC by recruiting Treg cells into PDAC via upregulation of CCL5.In this study,we confirmed that PD-L1 was overexpressed in PDAC samples from two independent cohorts of patients with radical resection.Moreover,C-FOXP3 was colocalized and correlated with the expression of PD-L1 in tumor cells at the mRNA and protein levels,and this finding was confirmed by the The Cancer Genome Atlas(TCGA)database.Chromatin immunoprecipitation(ChIP)revealed that C-FOXP3 directly bound to the promoter region of PD-L1 in pancreatic cancer cells.Furthermore,overexpression of C-FOXP3 activated the luciferase reporter gene under the control of the PD-L1 promoter.However,mutation of the binding motif-a completely reversed the luciferase activity.In addition,C-FOXP3-induced upregulation of PD-L1 effectively inhibited the activity of CD8+T cells.Based on our recent finding that the CCL-5 antibody achieved a better response to PDAC models with high C-FOXP3 levels,we further demonstrated that the PD-L1 antibody strengthened the antitumor effect of CCL-5 blockade in xenograft and orthotopic mouse models with high C-FOXP3 levels.In conclusion,C-FOXP3 directly activates PD-L1 and represents a core transcription factor that mediates the immune escape of PDAC.Combined blockade of PD-L1 and CCL-5 may provide an effective therapy for patients with PDAC that have high C-FOXP3 levels.

关键词： CCL5 FOXP3 adenocarcinoma

基于阻抗灵敏度的MMC稳定性主导影响因素分析

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电力系统及其自动化学报 2024年第4期36卷 102-112页

作者：吴晓鸣沈玉明王绪利张辉段修超池源国网安徽省电力有限公司经济技术研究院合肥230000 重庆大学电气工程学院重庆400044

针对模块化多电平换流器的宽频谐振日益突出且涉及影响因素众多,通过参与因子分析难以宽频段定量寻找主导谐振因素的问题,提出模块化多电平换流器阻抗绝对灵敏度及标幺灵敏度的分析方法,来实现宽频谐振主导因素的定量研究,并降低模块化... 详细信息

针对模块化多电平换流器的宽频谐振日益突出且涉及影响因素众多,通过参与因子分析难以宽频段定量寻找主导谐振因素的问题,提出模块化多电平换流器阻抗绝对灵敏度及标幺灵敏度的分析方法,来实现宽频谐振主导因素的定量研究,并降低模块化多电平换流器的谐振风险。首先,建立模块化多电平换流器宽频阻抗模型,对延时环节和电流控制参数开展绝对灵敏度分析,来反映参数变化对系统稳定性的影响趋势;然后,对灵敏度比重标幺化消除各因素间量纲的影响,得到模块化多电平换流器互联系统在各频段稳定性的主导因素;最后,通过Matlab/Simulink模型验证了理论分析的正确性。

关键词：模块化多电平换流器宽频谐振主导因素阻抗模型灵敏度分析