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XELOX(capecitabine plus oxaliplatin)plus bevacizumab(anti-VEGF-A antibody)with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer:a multicenter,open-label,randomized,controlled,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2104-2113页

作者： Qiu-Zhong Pan Jing-Jing Zhao Liang Liu Dong-Sheng Zhang Li-Ping Wang Wen-Wei Hu De-Sheng Weng Xiang Xu yi-Zhuo Li Yan Tang Wei-Hong Zhang Jie-Yao Li Xiao Zheng Qi-Jing Wang Yong-Qiang Li Tong Xiang Li Zhou Shuang-ning Yang Chen Wu Rong-Xing Huang Jia He Wei-Jiao Du Lu-Jun Chen Yue-Na Wu Bin Xu Qiong Shen yi Zhang Jing-Ting Jiang Xiu-bao Ren Jian-Chuan Xia State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Department of Biotherapy Sun Yat-Sen University Cancer CenterGuangzhouGuangdong 510060PR China Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerTianjin 300060PR China Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060PR China Department of Biotherapy/Immunology Tianjin Medical University Cancer Institute and HospitalTianjin 300060PR China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhou 510060PR China Department of Oncology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052PR China Department of Tumor Biological Treatment the Third Affiliated Hospital of Soochow UniversityChangzhouJiangsu 213003PR China Jiangsu Engineering Research Center for Tumor Immunotherapy ChangzhouJiangsu 213003PR China Institute for Cell Therapy of Soochow University ChangzhouJiangsu 213003PR China Department of Stem Cell&Regenerative Medicine State Key Laboratory of TraumaBurn and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042PR China Imaging Diagnosis and Interventional Center Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060PR China

Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer(mCRC),but the prognosis remains *** phase 3 trial(***:NCT03950154)assessed the efficacy and adverse events(AEs)of the combination of PD-1 blockade-activated DC-CIK(PD1-T)cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC.A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab(the control group,n=102)or the same regimen plus autologous PD1-T cell immunotherapy(the immunotherapy group,n=100)every 21 days for up to 6 cycles,followed by maintenance treatment with capecitabine and *** main endpoint of the trial was progression-free survival(PFS).The median follow-up was 19.5 *** PFS was 14.8 months(95%CI,11.6-18.0)for the immunotherapy group compared with 9.9 months(8.0-11.8)for the control group(hazard ratio[HR],0.60[95%CI,0.40-0.88];p=0.009).Median overall survival(OS)was not reached for the immunotherapy group and 25.6 months(95%CI,18.3-32.8)for the control group(HR,0.57[95%CI,0.33-0.98];p=0.043).Grade 3 or higher AEs occurred in 20.0%of patients in the immunotherapy group and 23.5%in the control groups,with no toxicity-associated deaths *** addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

关键词： PD1 immunotherapy bevacizumab

肠道中钙和铁相互作用对其吸收影响的研究进展

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食品科学 2024年第4期45卷 323-335页

作者：李奕程永强唐宁中国农业大学食品科学与营养工程学院北京100083

钙和铁是人体健康必需的金属元素,在骨骼形成、氧气运输等多种代谢过程中发挥重要作用。然而,钙和铁缺乏却是常见的营养问题,可能会分别导致骨质疏松和贫血。而且其相互作用可能会干扰彼此的吸收和生物利用度,因此,了解钙和铁在肠道中... 详细信息

钙和铁是人体健康必需的金属元素,在骨骼形成、氧气运输等多种代谢过程中发挥重要作用。然而,钙和铁缺乏却是常见的营养问题,可能会分别导致骨质疏松和贫血。而且其相互作用可能会干扰彼此的吸收和生物利用度,因此,了解钙和铁在肠道中的吸收机制及其相互作用对制定有效的预防或治疗营养性疾病的策略至关重要。已有大量研究表明,短期补充钙会抑制铁的吸收,而长期补充钙对总体铁稳态没有影响。这可能是由于钙摄入对铁吸收的影响是一种短暂和适应性反应,具体的分子机制可能是钙对铁相关转运蛋白的调节,但还需要更多的研究阐明这一过程。此外,关于铁如何影响钙吸收的研究较少,有研究表明高剂量的铁可能对钙的吸收和保留有负面作用,但铁对钙吸收的具体影响和机制尚不清楚。本文综述了钙和铁在肠道中的吸收机理、摄入钙和铁直至吸收过程中钙和铁所发生的相互作用,并详细阐述了钙和铁吸收过程中相互影响的内在机制,这对改善钙和铁的摄入和吸收,以及预防由营养缺乏导致的公共健康问题具有一定的指导意义。

关键词：钙铁吸收相互作用分子机制

Glycine Attenuates Myocardial Fibrosis in Myocardial Infarction in Rats Partly through Modulating Signal Transducer and Activator of Transcription 3/Nuclear Factor-κB/Transforming Growth Factor-β axis

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 263-270页

作者： ning Li Yong Wang Chun Li Xu Chen Xue-Feng Zhang Nan Nan Tan yi-Qin Hong Ming-Yan Shao Bing-Hua Tang Dong-Qing Guo School of Life Science Beijing University of Chinese MedicineBeijingChina College of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijingChina Modern Research Center of Traditional Chinese Medicine School of Traditional Chinese Material MedicaBeijing University of Chinese MedicineBeijingChina

Objective: Inflammation and fibrosis are strongly associated with each other. Glycine is present in various traditional Chinese medicines and exhibits anti-inflammatory activity. However, the effects of glycine on myocardial fibrosis(MF) in rats with myocardial infarction(MI) have not been reported. The purpose of this study is to investigate the effects of glycine therapy on MF and comprehend its underlying mechanisms. Materials and Methods: Left anterior descending artery ligation-induced MI in Sprague Dawley rats was leveraged to assess the therapeutic effects of Glycine. Rats received either normal saline or glycine(0.5 mg/g bodyweight) for 7 days. Results: Glycine upregulated cardiac ejection fraction and fractional shortening to improve cardiac function, as evaluated by echocardiography. Histological and immunohistochemical analyses demonstrated that glycine could decrease inflammatory cell infiltration and alleviate collagen deposition. Western blotting revealed that nuclear factor-κB(NF-κB)-mediated inflammatory signaling was also downregulated by glycine treatment. The expression of signal transducer and activator of transcription 3(STAT3), tumor necrosis factor-α, and transforming growth factor-β(TGF-β) was decreased significantly in the glycine-treated group compared to the model group. Thus, glycine plays a protective role against myocardial ischemia and subsequent MF. Conclusion: The protective effects of glycine were achieved partly through STAT3/NF-κB/TGF-β signaling pathway.

关键词： Glycine myocardial fibrosis signal transducer and activator of transcription 3/nuclear factor-κB/transforming growth factor-β

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机械应力对巨噬细胞的功能调节作用及机制

生物化学与生物物理进展 2024年第5期51卷 1010-1022页

作者：张亚宁张艺扉天津大学医学工程与转化医学研究院天津300072

巨噬细胞作为先天免疫系统识别外界环境刺激的先锋,能够响应环境细微变化对自身功能实现适应性调节,在维持体内稳态和抵抗感染方面起关键作用。生理或病理组织微环境存在多种机械应力刺激,对巨噬细胞的免疫功能具有重要影响。本文围绕... 详细信息

巨噬细胞作为先天免疫系统识别外界环境刺激的先锋,能够响应环境细微变化对自身功能实现适应性调节,在维持体内稳态和抵抗感染方面起关键作用。生理或病理组织微环境存在多种机械应力刺激,对巨噬细胞的免疫功能具有重要影响。本文围绕机械应力对巨噬细胞的功能调节,从影响细胞行为和极化的角度综述,总结巨噬细胞机械应力感知及转导的分子机制,展望巨噬细胞力学生物学研究在组织工程、再生医学以及肿瘤免疫治疗领域的应用前景,为深入理解巨噬细胞功能可塑性提供有力支持。

关键词：力学生物学巨噬细胞机械力感知与转导

基于Curvelet域的注意力机制卷积网络地震数据去噪

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煤田地质与勘探 2024年第8期52卷 165-176页

作者：包乾宗周梅邱怡长安大学地质工程与测绘学院陕西西安710054 自然资源部矿山地质灾害成灾机理与防控重点实验室陕西西安710054 海洋油气勘探国家工程研究中心北京100028 中国电建集团西北勘测设计研究院有限公司陕西西安710065

【目的】地震资料中的噪声严重影响着对地下地层信息的准确解释。基于地震资料中横向相关性较强的有效信号在Curvelet域分布在特定系数上,而随机噪声在Curvelet域通常会均匀分布于所有系数,可对信号进行更有效的分离。【方法】基于注意... 详细信息

【目的】地震资料中的噪声严重影响着对地下地层信息的准确解释。基于地震资料中横向相关性较强的有效信号在Curvelet域分布在特定系数上,而随机噪声在Curvelet域通常会均匀分布于所有系数,可对信号进行更有效的分离。【方法】基于注意力机制卷积神经网络能够聚焦图像的重要特征,自适应提取关键信息的特点,提出一种基于Curvelet变换和注意力机制卷积神经网络(Curvelet-AU-Net)的地震数据噪声衰减方法。首先,将含噪声的地震数据通过Curvelet变换得到Curvelet变换系数,分析有效信号和噪声在Curvelet域的分布情况。其次,使用加入CBAM(Convolutional block attention module)注意力机制的U-Net网络,以含噪地震数据的Curvelet变换系数制作训练集作为输入数据,用无噪地震数据的Curvelet变换系数作为标签,通过比较实际输出与标签的损失函数值,并逐层反向传播梯度来更新网络参数,当损失函数值达到最小时,网络训练完成。最后,将测试数据输入训练好的网络模型中,再对网络输出数据进行Curvelet反变换即可得到地震数据去噪结果。【结果和结论】模拟数据与实际数据处理结果表明,与传统方法和普通卷积网络相比,该方法在不同噪声水平和尺度条件下对常见噪声(如随机噪声等)的衰减效果更优,获得的地震信号信噪比和保真度更高。由于该方法融合了Curvelet变换的稀疏表示优势和深度学习模型的自适应性,将为地震数据噪声衰减提供一种新的解决途径。

关键词：地震数据去噪深度学习 U-net网络 Curvelet变换注意力机制

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Exceptional points and quantum dynamics in a non-Hermitian two-qubit system

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Chinese Physics B 2024年第6期33卷 212-218页

作者：张益玺张振涛杨震山魏晓志梁宝龙 School of Physics Science and Information Technology Shandong Key Laboratory of Optical Communication Science and TechnologyLiaocheng UniversityLiaocheng 252059China

We study the exceptional-point(EP) structure and the associated quantum dynamics in a system consisting of a non-Hermitian qubit and a Hermitian qubit. We find that the system possesses two sets of EPs, which divide the systemparameter space into PT-symmetry unbroken, partially broken and fully broken regimes, each with distinct quantumdynamics characteristics. Particularly, in the partially broken regime, while the PT-symmetry is generally broken in the whole four-dimensional Hilbert space, it is preserved in a two-dimensional subspace such that the quantum dynamics in the subspace are similar to those in the PT-symmetry unbroken regime. In addition, we reveal that the competition between the inter-qubit coupling and the intra-qubit driving gives rise to a complex pattern in the EP variation with system parameters.

关键词： non-Hermitian system exceptional point PT-symmetry

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang yi-Yan Liu Shuang-Shuang He Dai-Qin bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng Jia-Tao Zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu State Key Laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin *** Pericytes are protective a

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

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World Journal of Clinical Cases 2024年第18期12卷 3385-3394页

作者： Yuan Liu Xiao-ning Lu Hui-Ming Guo Chan bao Juan Zhang Yu-Ni Jin Department of Gynaecology The First Affiliated Hospital of Kunming Medical UniversityKunming 650032Yunnan ProvinceChina

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse *** studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with *** To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC *** We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and *** factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification *** Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after *** nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical ***,using the nomogram,the patients were successfully classified into three risk *** The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 *** model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

关键词： Circulating tumor DNA Endometrial cancer Short-term recurrence Predictive model Prospective validation

Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 608-615页

作者： WEI Ya-ru HOU Yun-long yiN Yu-jie LI Zhen LIU yi HAN ning-xin WANG Zi-xuan LIU Lu WANG Xiao-qi HAO Yuan-jie MA Kun GU Jiao-jiao JIA Zhen-hua Graduate School Hebei University of Chinese MedicineShijiazhuang050090China Shijiazhuang yiling Pharmaceutical New Drug Evaluation Center Shijiazhuang050035China Hebei Institute of Integrated Traditional and Western Medicine Shijiazhuang050035China National Key Laboratory for Innovation and Transformation of Luobing Theory Shijiazhuang050035China Department of Cardiology Hebei Yiling HospitalShijiazhuang050091China Graduate School Hebei Medical UniversityShijiazhuang050017China

Objective To investigate the potential role of Tongxinluo(TXL)in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI)in *** A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 *** to a random number table,66 mice were randomly divided into 6 groups(n=11 per group):the sham group,the model group,the LY-294002 group,the TXL group,the TXL+LY-294002 group and the benazepril(BNPL)*** day after modeling,TXL and BNPL were administered by *** injection of LY-294002 was performed twice a week for 4 consecutive *** was used to measure cardiac function in *** staining was used to evaluate the degree of myocardial fibrosis in *** and quantitative analysis of endothelial mesenchymal transition(EndMT)after MIRI was performed by immunohistochemistry,immunofluorescence staining and flow cytometry,*** protein expressions of platelet endothelial cell adhesion molecule-1(CD31),α-smoth muscle actin(α-SMA),phosphatidylinositol-3-kinase(PI3K)and phospho protein kinase B(p-AKT)were assessed using Western *** TXL improved cardiac function in MIRI mice,reduced the degree of myocardial fibrosis,increased the expression of CD31 and inhibited the expression ofα-SMA,thus inhibited the occurrence of EndMT(P0.05).In addition,the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention,eliminated the protective effect of TXL,further supporting the protective effect of *** TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关键词： myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)pathway