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利多卡因调节cGAS-STING信号通路对LPS诱导的小胶质细胞炎性损伤的影响

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卒中与神经疾病 2024年第2期31卷 192-200页

作者：尹健赵馨贾彤河北省张家口市第一医院麻醉科 075000 张家口市第五医院麻醉科河北北方学院附属第一医院麻醉科

目的探讨利多卡因(Lidocaine,Lido)通过调节环鸟苷酸-腺苷酸合成酶(Cyclic guanosine monophosphate synthase,cGAS)-干扰素基因刺激因子(Stimulator of interferon genes,STING)信号通路对脂多糖(lipopolysaccharide,LPS)诱导的小胶质细胞炎性损伤的影响及其作用机制。方法0~200μg/mL的利多卡因处理LPS诱导的BV2小胶质细胞24 h,四甲基偶氮唑蓝(Methylthiazolyl-tetrazolium,MTT)测定细胞活性,选择最佳药物水平;将BV2细胞分为对照组(Control组)、LPS诱导组(LPS组,1μg/mL LPS)、利多卡因低水平组(Lido-L组,2μg/mL Lido+1μg/mL LPS)、利多卡因中水平组(Lido-M组,20μg/mL Lido+1μg/mL LPS)、利多卡因高水平组(Lido-H组,200μg/mL Lido+1μg/mL LPS)和利多卡因高水平+STING激活剂DMXAA组(Lido-H+DMXAA组,200μg/mL Lido+1μg/mL LPS+100μg/mL DMXAA);Griess法检测NO水平;酶联免疫吸附法((Enzyme-linked immunosorbent assay,ELISA)检测单核细胞趋化蛋白-1(Monocyte ehemoattractant protein-1,MCP-1)、前列腺素E2(Prostaglandin E2,PGE2)、环氧化酶2(Cyclooxyge-nase 2,COX-2)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)、白细胞介素(Interleukin,IL)-10和IL-1β水平;Hoechst染色检测细胞凋亡;免疫荧光检测钙离子结合调节因子(Ionized calcium-binding adapter molecule 1,Iba-1)和精氨酸酶-1(Arginase-1,Arg-1)表达水平;Western blot检测环鸟苷酸-腺苷酸合成酶(Cyclic guanosine monophosphate synthase,cGAS)、干扰素基因刺激因子(Stimulator of interferon genes,STING)、核苷酸结合寡聚化结构域样受体3(Nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)蛋白水平。结果0~200μg/mL的利多卡因能增加LPS诱导的BV2细胞活力,选择2、20和200μg/mL的利多卡因进行后续实验。与Control组比较,LPS组BV2细胞出现大量细胞发生凋亡现象,TNF-α,IL-1β、一氧化氮(Nitric oxide,NO)、PGE2,MCP-1和COX-2水平、Iba-1阳性表达率及Cgas,STING和NLRP3蛋白表达水平显著增高,IL-10水平和Arg-1阳性表达率显著降低(P<0.05);与LPS组比较,Lido-L组、Lido-M组和Lido-H组BV2细胞凋亡逐渐减少,TNF-α,IL-1β,NO,PGE2,MCP-1和COX-2水平、Iba-1阳性表达率及cGAS,STING和NLRP3蛋白表达水平显著降低,IL-10水平和Arg-1阳性表达率显著增高,且呈水平依赖性(P<0.05);与Lido-H组比较,Lido-H+DMXAA组BV2细胞凋亡增加,TNF-α,IL-1β,NO,PGE2,MCP-1和COX-2水平、Iba-1阳性表达率及cGAS,STING和NLRP3蛋白表达水平显著增高,IL-10水平和Arg-1阳性表达率显著降低(P<0.05)。结论利多卡因对LPS诱导的小胶质细胞炎性损伤的保护作用机制可能与抑制cGAS-STING信号通路的激活有关。

关键词：利多卡因小胶质细胞脂多糖环鸟苷酸-腺苷酸合成酶-干扰素基因刺激因子信号通路炎性损伤

普鲁卡因调节HMGB1-RAGE信号通路对脑缺血再灌注大鼠的神经保护作用研究

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中国临床神经科学 2024年第4期32卷 373-380页

作者：尹健赵馨贾彤张家口市第一医院麻醉科张家口075000 张家口市第五医院麻醉科张家口075000 河北北方学院附属第一医院麻醉科张家口075000

目的探讨普鲁卡因(PCA)调节高迁移率族蛋白1-晚期糖基化终末产物受体(HMGB1-RAGE)信号通路对脑缺血/再灌注(CI/R)大鼠的神经保护作用。方法采用线栓法制备CI/R大鼠模型,缺血处理2 h,再灌注24 h。将大鼠随机分为假手术组,模型组(CI/R组)... 详细信息

目的探讨普鲁卡因(PCA)调节高迁移率族蛋白1-晚期糖基化终末产物受体(HMGB1-RAGE)信号通路对脑缺血/再灌注(CI/R)大鼠的神经保护作用。方法采用线栓法制备CI/R大鼠模型,缺血处理2 h,再灌注24 h。将大鼠随机分为假手术组,模型组(CI/R组),普鲁卡因低、中、高剂量组(PCA-L组、PCA-M组、PCA-H组),普鲁卡因高剂量+HMGB1重组蛋白组(PCA-H+HMGB1组),各组n=10。对大鼠进行神经功能评分,苏木精-伊红染色法观察大鼠脑组织海马CA1区组织病理变化,Tunel染色法检测大鼠脑组织海马CA1区神经元凋亡,酶联免疫吸附(ELISA)法检测大鼠脑组织中TNF-α、IL-1β水平;免疫组化法检测大鼠脑组织NGF表达;Western blot法检测大鼠脑组织中HMGB1、RAGE表达。结果与假手术组比较,CI/R组脑组织损伤严重,神经功能评分、神经元凋亡率、IL-1β及TNF-α水平、NGF表达、HMGB1及RAGE表达均显著升高(均P<0.05);与CI/R组比较,PCA-L组、PCA-M组、PCA-H组大鼠脑组织损伤相对减轻,神经功能评分、神经元凋亡率、IL-1β及TNF-α水平、HMGB1及RAGE表达均呈显著降低,NGF表达显著升高,呈剂量依赖效应(P<0.05);与PCA-H组比较,PCA-H+HMGB1组大鼠脑组织损伤加重,神经功能评分、神经元凋亡率、IL-1β及TNF-α水平、HMGB1及RAGE表达均显著升高,NGF表达显著降低(均P<0.05)。结论普鲁卡因对CI/R大鼠的神经具有一定的保护作用,其机制可能与抑制HMGB1-RAGE信号通路激活相关。

关键词：普鲁卡因高迁移率族蛋白1-晚期糖基化终末产物受体(HMGB1-RAGE)信号通路脑缺血再灌注神经保护

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基于多尺度特征增强的合成孔径光学图像复原

物理学报 2024年第6期73卷 209-221页

作者：张银胜童俊毅陈戈单梦姣王硕洋单慧琳无锡学院江苏省集成电路可靠性技术及检测系统工程研究中心无锡214105 南京信息工程大学电子信息工程学院南京210044

受物理孔径大小和光线散射等影响,合成孔径光学系统成像因通光面积不足和相位失真而出现降质模糊.传统合成孔径光学系统成像复原算法对噪声敏感,过于依赖退化模型,自适应性差.对此提出一种基于生成对抗网络的光学图像复原方法,采用U-Ne... 详细信息

受物理孔径大小和光线散射等影响,合成孔径光学系统成像因通光面积不足和相位失真而出现降质模糊.传统合成孔径光学系统成像复原算法对噪声敏感,过于依赖退化模型,自适应性差.对此提出一种基于生成对抗网络的光学图像复原方法,采用U-Net结构获取图像多级尺度特征,利用基于自注意力的混合域注意力提高网络在空间、通道上的特征提取能力,构造多尺度特征融合模块和特征增强模块,融合不同尺度特征间的信息,优化了编解码层的信息交互方式,增强了整体网络对原始图像真实结构的关注力,避免在复原过程中被振铃现象产生的伪影干扰.实验结果表明,与其他现有方法相比,该方法在峰值信噪比、结构相似性和感知相似度评估指标上分别提高了1.51%,4.42%和5.22%,有效解决合成孔径光学系统成像结果模糊退化的问题.

关键词：图像处理合成孔径多尺度特征融合

利多卡因调节RhoA/ROCK轴对结直肠癌细胞生物学行为的影响

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中国细胞生物学学报 2024年第3期46卷 466-476页

作者：赵馨尹健贾彤张家口市第五医院麻醉科张家口075000 张家口市第一医院麻醉科张家口075000 河北北方学院附属第一医院麻醉科张家口075000

该文主要探讨利多卡因(lidocaine,Lido)通过调节Ras同源基因家族成员A(Rho A)/Rho相关的卷曲螺旋激酶(ROCK)轴对结直肠癌(CRC)细胞生物学行为的影响。该研究使用0~1250μmol/L的利多卡因处理人结直肠癌细胞LS513,CCK-8法检测细胞活力筛... 详细信息

该文主要探讨利多卡因(lidocaine,Lido)通过调节Ras同源基因家族成员A(Rho A)/Rho相关的卷曲螺旋激酶(ROCK)轴对结直肠癌(CRC)细胞生物学行为的影响。该研究使用0~1250μmol/L的利多卡因处理人结直肠癌细胞LS513,CCK-8法检测细胞活力筛选适宜药物浓度。将细胞分为对照组(Control组)、利多卡因低浓度组(Lido-L组,500μmol/L Lido)、利多卡因中浓度组(Lido-M组,750μmol/L Lido)、利多卡因高浓度组(Lido-H组,1000μmol/L Lido)和利多卡因高浓度+ROCK信号通路激活剂LPA组(Lido-H+LPA组,1000μmol/L Lido+10μmol/L LPA)。Edu检测细胞增殖;划痕愈合实验和Transwell小室实验分别检测细胞迁移和侵袭能力;流式细胞仪检测细胞凋亡情况;Westernblot检测PCNA、Bax、Bcl-2、RhoA、ROCK1、E-cadherin和N-cadherin蛋白表达情况。该研究得出与0μmol/L利多卡因相比,500μmol/L、750μmol/L、1000μmol/L和1250μmol/L利多卡因处理的LS513细胞活力显著降低(P<0.05),选择500μmol/L、750μmol/L和1000μmol/L的利多卡因进行后续实验。与Control组相比,Lido-L组、Lido-M组和Lido-H组LS513细胞Edu阳性率,划痕愈合率,细胞侵袭数及PCNA、N-cadherin、Bcl-2、RhoA和ROCK 1蛋白表达水平降低(P<0.05),细胞凋亡率以及E-cadherin和Bax蛋白表达增加(P<0.05);与Lido-H组相比,Lido-H+LPA组LS513细胞Edu阳性率,划痕愈合率,细胞侵袭数及PCNA、N-cadherin、Bcl-2、RhoA和ROCK 1蛋白表达水平显著增加(P<0.05),细胞凋亡率、E-cadherin和Bax蛋白表达水平显著降低(P<0.05)。利多卡因可能通过抑制RhoA/ROCK信号通路抑制结直肠癌细胞恶性生物学行为。

关键词：利多卡因 Ras同源基因家族成员A/Rho相关的卷曲螺旋激酶信号通路结直肠癌恶性生物学行为

松散耦合系统蒙特卡罗临界计算源收敛判定方法研究

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核动力工程 2024年第2期45卷 10-18页

作者：张寅成昱廷周琦朱庆福夏兆东宁通张振洋国家国防科技工业局核技术支持中心北京100070 中国原子能科学研究院反应堆工程技术研究所北京102413

为提高蒙特卡罗程序在松散耦合系统临界安全计算中的可靠性与准确性,需要对计算结果进行源收敛判定。本文提出了一种考虑裂变源分布及统计偏差权重因子的改进型香农熵的收敛判定方法,将裂变源迭代过程中相邻代际之间裂变源分布的相对偏... 详细信息

为提高蒙特卡罗程序在松散耦合系统临界安全计算中的可靠性与准确性,需要对计算结果进行源收敛判定。本文提出了一种考虑裂变源分布及统计偏差权重因子的改进型香农熵的收敛判定方法,将裂变源迭代过程中相邻代际之间裂变源分布的相对偏差、源迭代过程中裂变源分布的蒙特卡罗统计标准差作为裂变源分布的权重,建立了改进型的香农熵收敛指标,弥补了传统香农熵对于局部裂变源收敛细节考虑的不足。将改进型的香农熵收敛指标应用在经合组织核能机构发布的乏燃料棒栅元和松散耦合铀溶液平板基准问题上。结果表明,对比传统香农熵源收敛判定指标,改进型的香农熵对裂变源迭代收敛过程更为敏感,能够更加直观和准确地判定裂变源分布伴随源迭代的收敛性。对于收敛速度慢的典型算例,应用传统香农熵判定收敛性时给出了伪收敛的结论,而改进型香农熵能准确地判定源迭代达到收敛时的迭代次数。

关键词：临界安全蒙特卡罗松散耦合系统源收敛判定香农熵

Structure,ligands,and roles of GPR126/ADGRG6 in the development and diseases

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Genes & Diseases 2024年第1期11卷 294-305页

作者： Qi Li Anran Huo Mengqi Li Jiali Wang Qiao yin Lumiao Chen Xin Chu Yuan Qin Yuwan Qi Yang Li Hengxiang Cui Qifei Cong Institute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow UniversitySuzhouJiangsu215123China Department of Neurology and Clinical Research Center of Neurological Disease The Second Affliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Department of Nephrology The Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China Department of Emergency Center The Second Affiliated Hospital of Nantong UniversityNantongJiangsu226001China Department of Neurology Huzhou Central HospitalThe Affiliated Huzhou HospitalZhejiang University School of MedicineHuzhouZhejiang 313000China Institute of Neuroscience State Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China

Adhesion G protein-coupled receptors(aGPCRs)are the second largest diverse group within the GPCR superfamily,which play critical roles in many physiological and patho-logical processes through cell-cell and cell-extracellular matrix *** adhesion GPCR Adgrg6,also known as GPR126,is one of the better-characterized ***126 was previously found to have critical developmental roles in Schwann cell maturation and its mediated myelination in the peripheral nervous system in both zebrafish and *** studies have extended our understanding of GPR126-mediated roles during develop-ment and in human *** this review,we highlighted these recent advances in GPR126 in expression profile,molecular structure,ligand-receptor interactions,and associated physiological and pathological functions in development and diseases.

关键词： Adhesion G protein-coupled receptor Function GPR126/Adgrg6 Ligand Structure

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浅薄层特超稠油油藏冷热交替开采技术研究

油气地质与采收率 2024年第1期31卷 103-110页

作者：张兆祥张仲平郑万刚殷方好佟彤中国石化胜利油田分公司石油工程技术研究院山东东营257000 山东省稠油开采技术重点实验室山东东营257000

针对浅薄层特超稠油油藏蒸汽吞吐开发初期面临的油层厚度薄、原油黏度高、蒸汽热损失大、吞吐有效期短等问题,提出了冷热交替大周期吞吐开发模式,有效改善开发效果。为此开展了浅薄层特超稠油油藏冷热交替开采三维物理模拟研究,结果表明... 详细信息

针对浅薄层特超稠油油藏蒸汽吞吐开发初期面临的油层厚度薄、原油黏度高、蒸汽热损失大、吞吐有效期短等问题,提出了冷热交替大周期吞吐开发模式,有效改善开发效果。为此开展了浅薄层特超稠油油藏冷热交替开采三维物理模拟研究,结果表明:受顶底盖层热损失影响,蒸汽吞吐温度下降迅速,峰值产量较高,但单周期生产时间较短,约100 min;降黏吞吐可以降低吞吐井附近含油饱和度,提高产油速度,降低含水率,延长吞吐周期50 min以上;提高温度可以增强降黏剂的降黏效果,第二周期开始冷热交替改善效果优于第一周期,其生产时间延长60 min,含水率降低45%,周期采出程度提高1.7%。利用数值模拟方法优化了冷热交替的注入参数,建立了该技术的政策界限:最佳转冷热交替的时机为2~3周期,注入强度为0.02 t/m;适用的油层厚度小于8 m,原油黏度小于200000 mPa•s,含油饱和度大于0.6,渗透率大于1000 mD。

关键词：冷热交替浅薄层特超稠油物理模拟生产时间

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Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection:a randomized controlled trial

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World Journal of Pediatrics 2024年第5期20卷 461-469页

作者： Ji-Lei Lin Fen Zhang Yan-Bo Li Shu-Hua Yuan Jin-Hong Wu Jing Zhang Lei Zhang Yi He Jie Chen Yong yin Department of Respiratory Medicine Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina University of British Columbia VancouverCanada Information Technology Department Shanghai Children’s Medical Center National Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina Department of Otorhinolaryngology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong University1678 Dongfang RoadPudong DistrictShanghaiChina Department of Respiratory Medicine Sanya Women and Children’s Hospital Affiliated to Hainan Medical CollegeHainan Branch of Shanghai Children’s Medical CenterSanyaChina Department of Respiratory Medicine Linyi Maternal and Child Healthcare HospitalLinyiChina Shanghai Children’s Medical Center Pediatric Medical Complex(Pudong) ShanghaiChina Pediatric AI Clinical Application and Research Center Shanghai Children’s Medical CenterShanghaiChina

Background Saline nasal irrigation is an effective therapy for relieving common cold *** study aimed to investigate and explore the efficacy of physiological seawater nasal irrigation(PSNI)on children with mild and asymptomatic infection with *** This randomized controlled trial was conducted in Shanghai,China,and 403 children with mild and asymptomatic infection with Omicron were *** children were allocated into the PSNI group and the control *** primary outcome was the duration of viral shedding(DVS),and the secondary outcome was the change in clinical *** The median age of all participants was 5.59(6.26)years *** DVS was significantly shorter in the PSNI group[2.40(1.13)]than in the control group[3.09(2.14)](P=0.014).The multivariable Cox regression model also showed that patients in the PSNI group had an increased probability of shorter DVS compared with patients in the control group[hazard ratio(HR),1.27;95%confidence interval(CI),1.04–1.55;P=0.017].Subgroup analysis suggested that the DVS of patients without full vaccination was significantly reduced in the PSNI *** proportions of runny nose and stuffy nose were apparently reduced in the first three days in the PSNI group or the control group,but there was no evidence showing that PSNI contributes to the benefit compared with the control *** PSNI can reduce the DVS of patients with mild and asymptomatic infection with SARS-CoV-2 Omicron BA.2 variant.

关键词： Children Duration of viral shedding Omicron Physiological seawater nasal irrigation

Antibody-platinum(IV)prodrugs conjugates for targeted treatment of cutaneous squamous cell carcinoma

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Journal of Pharmaceutical Analysis 2024年第3期14卷 389-400页

作者： Xiangye yin yingjie Zhuang Haiqin Song Yujian Xu Fan Zhang Jianxin Cui Lei Zhao yingjie Yu Qixu Zhang Jun Ye Youbai Chen Yan Han Department of Plastic and Reconstructive Surgery The First Medical CenterChinese PLA General HospitalBeijing100853China Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai200023China State Key Laboratory of Organic-Inorganic Composites Beijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing100029China Department of Plastic Surgery University of Texas MD Anderson Cancer CenterHoustonTX77030USA State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China

Antibody-drug conjugates(ADCs)are a new type of targeting antibodies that conjugate with highly toxic anticancer drugs via chemical linkers to exert high specificity and efficient killing of tumor cells,thereby attracting considerable attention in precise oncology ***(Cet)is a typical antibody that offers the benefits of good targeting and safety for individuals with advanced and inoperable cutaneous squamous cell carcinoma(cSCC);however,its anti-tumor activity is limited to a single ***(CisPt)shows good curative effects;however,its adverse effects and non-tumor-targeting ability are major *** this study,we designed and developed a new ADC based on a new cytotoxic platinum(IV)prodrug(C8Pt(IV))and *** so-called antibody-platinum(IV)prodrugs conjugates,named Cet-C8Pt(IV),showed excellent tumor targeting in ***,it accurately delivered C8Pt(IV)into tumor cells to exert the combined anti-tumor effect of Cet and ***,metabolomic analysis showed that Cet-C8Pt(IV)promoted cellular apoptosis and increased DNA damage in cSCC cells by affecting the vitamin B6 metabolic pathway in tumor cells,thereby further enhancing the tumor-killing ability and providing a new strategy for clinical cancer treatment using antibody-platinum(IV)prodrugs conjugates.

关键词： Antibody drug conjugate Cutaneous squamous cell carcinoma DNA damage Platinum drug Targeted therapy