Prophylactic Effect of Gossypin Against Percutaneously Administered Sulfur Mustard
青少年自我伤害行为影响因素与情绪管理对策-社会心理学论文-社会学论文
青少年自我伤害行为影响因素与情绪管理对策-社会心理学论文-社会学论文——文章均为WORD文档，下载后可直接编辑使用亦可打印——心理学情绪管理论文第五篇：青少年自我伤害行为影响因素与情绪管理对策摘要：自我伤害行为是应对负性情绪的常用策略, 普遍存在于冲动型、情绪管理薄弱的青少年群体中, 严重影响其身心健康和发展, 是重要的疾病负担之一, 应引起广大学者和学校卫生工作者的关注和重视。
作者对自我伤害行为的概念和界定、流行病学和危害、影响因素进行了文献研究和分析, 并提出以培养青少年情绪管理能力为重点的预防和干预策略。
关键词：情绪; 自我伤害行为; 精神卫生; 青少年;Emotional regulation and self-injury behavior among adolescentsTANG JieDepartment of Preventive Medicine, School of Public Health, Guangzhou Medical UniversityAbstract：Self-injury behavior, a common strategy for coping with negative emotions, is widespread among adolescents with impulsive and emotional dysregulation. Self-injury behavior severely impacts an adolescents mental and physical well-being, and has become one of the important disease burdens, which deserves much attention from both scholars and school health care providers. Based on literature review, the definition, epidemiology and influencing factors of self-injury,as well as proposed prevention and intervention strategies for self-injury focusing on emotional regulation, were provided.自我伤害行为(self-harm behavior, SB) 是一个宽泛的概念, 其核心内涵指个体故意伤害自己的身体组织。
尖孢镰刀菌对秀丽隐杆线虫生物学特性及表达转录组的影响
华南农业大学学报 Journal of South China Agricultural University 2024, 45(3): 381-389DOI: 10.7671/j.issn.1001-411X.202308007易杏盈, 肖月, 张东华, 等. 尖孢镰刀菌对秀丽隐杆线虫生物学特性及表达转录组的影响[J]. 华南农业大学学报, 2024, 45(3): 381-389.YI Xingying, XIAO Yue, ZHANG Donghua, et al. Effects of Fusarium oxysporum on the biological characteristics and expression transcriptome of Caenorhabditis elegans[J]. Journal of South China Agricultural University, 2024, 45(3): 381-389.尖孢镰刀菌对秀丽隐杆线虫生物学特性及表达转录组的影响易杏盈1，肖 月1，张东华1，刘 丽1，闫晓慧1，伍建榕1,2(1 西南林业大学 生物多样性保护学院/云南省高校森林灾害预警控制重点实验室, 云南 昆明 650224；2 西南林业大学 林学院/西南地区生物多样性保育国家林业局重点实验室, 云南 昆明 650224)摘要: 【目的】探讨尖孢镰刀菌Fusarium oxvsporum对秀丽隐杆线虫Caenorhabditis elegans生物学特征的影响，明确线虫响应尖孢镰刀菌侵染的关键通路。
【方法】将尖孢镰刀菌活性孢子和灭活孢子分别与秀丽隐杆线虫共培养，测定C. elegans寿命、体长、运动能力、繁殖力以及咽泵运动速率等基本生物学特征；进行全基因组测序，通过GO和KEGG分析明确线虫响应尖孢镰刀菌侵染的关键通路和生物学功能。
【结果】尖孢镰刀菌活性分生孢子与线虫共培养可导致线虫寿命下降，虫体显著缩短，线虫繁殖力显著降低；但共培养并未对线虫的咽泵运动速率及运动能力产生明显影响。
光谱法研究药物小分子与蛋白质大分子的相互作用的英文
Spectroscopic Study of the Interaction between Small Molecules and Large Proteins1. IntroductionThe study of drug-protein interactions is of great importance in drug discovery and development. Understanding how small molecules interact with proteins at the molecular level is crucial for the design of new and more effective drugs. Spectroscopic techniques have proven to be valuable tools in the investigation of these interactions, providing det本人led information about the binding affinity, mode of binding, and structural changes that occur upon binding.2. Spectroscopic Techniques2.1. Fluorescence SpectroscopyFluorescence spectroscopy is widely used in the study of drug-protein interactions due to its high sensitivity and selectivity. By monitoring the changes in the fluorescence emission of either the drug or the protein upon binding, valuable information about the binding affinity and the binding site can be obt本人ned. Additionally, fluorescence quenching studies can provide insights into the proximity and accessibility of specific amino acid residues in the protein's binding site.2.2. UV-Visible SpectroscopyUV-Visible spectroscopy is another powerful tool for the investigation of drug-protein interactions. This technique can be used to monitor changes in the absorption spectra of either the drug or the protein upon binding, providing information about the binding affinity and the stoichiometry of the interaction. Moreover, UV-Visible spectroscopy can be used to study the conformational changes that occur in the protein upon binding to the drug.2.3. Circular Dichroism SpectroscopyCircular dichroism spectroscopy is widely used to investigate the secondary structure of proteins and to monitor conformational changes upon ligand binding. By analyzing the changes in the CD spectra of the protein in the presence of the drug, valuable information about the structural changes induced by the binding can be obt本人ned.2.4. Nuclear Magnetic Resonance SpectroscopyNMR spectroscopy is a powerful technique for the investigation of drug-protein interactions at the atomic level. By analyzing the chemical shifts and the NOE signals of the protein in thepresence of the drug, det本人led information about the binding site and the mode of binding can be obt本人ned. Additionally, NMR can provide insights into the dynamics of the protein upon binding to the drug.3. Applications3.1. Drug DiscoverySpectroscopic studies of drug-protein interactions play a crucial role in drug discovery, providing valuable information about the binding affinity, selectivity, and mode of action of potential drug candidates. By understanding how small molecules interact with their target proteins, researchers can design more potent and specific drugs with fewer side effects.3.2. Protein EngineeringSpectroscopic techniques can also be used to study the effects of mutations and modifications on the binding affinity and specificity of proteins. By analyzing the binding of small molecules to wild-type and mutant proteins, valuable insights into the structure-function relationship of proteins can be obt本人ned.3.3. Biophysical StudiesSpectroscopic studies of drug-protein interactions are also valuable for the characterization of protein-ligandplexes, providing insights into the thermodynamics and kinetics of the binding process. Additionally, these studies can be used to investigate the effects of environmental factors, such as pH, temperature, and ionic strength, on the stability and binding affinity of theplexes.4. Challenges and Future DirectionsWhile spectroscopic techniques have greatly contributed to our understanding of drug-protein interactions, there are still challenges that need to be addressed. For instance, the study of membrane proteins and protein-protein interactions using spectroscopic techniques rem本人ns challenging due to theplexity and heterogeneity of these systems. Additionally, the development of new spectroscopic methods and the integration of spectroscopy with other biophysical andputational approaches will further advance our understanding of drug-protein interactions.In conclusion, spectroscopic studies of drug-protein interactions have greatly contributed to our understanding of how small molecules interact with proteins at the molecular level. Byproviding det本人led information about the binding affinity, mode of binding, and structural changes that occur upon binding, spectroscopic techniques have be valuable tools in drug discovery, protein engineering, and biophysical studies. As technology continues to advance, spectroscopy will play an increasingly important role in the study of drug-protein interactions, leading to the development of more effective and targeted therapeutics.。
《PlantPhysiology》双语教学教案
《Plant Physiology》（双语）教学教案任课教师：王晓峰教授单位：生命科学学院植物学系授课班级：生科丁颖班、农学丁颖班等Introduction计划学时：2 h一.教学目的了解植物生理学的对象、内容、产生和发展及发展趋势。
二.教学重点植物生理学的内容及发展趋势，植物生理学与分子生物学的关系。
三.教学难点植物生理学的发展趋势四.教学方法采用以多媒体教学法为主。
五.教学用具多媒体硬件支持。
六.教学过程●Introduction of my research work briefly (5 min)●Concept of plant physiology and main contents and chapters of this course (20 min) ●Tasks of plant physiology（20 min）Some examples: Photoperiod, Solution culture, Water culture, Senescence, Ethylene, Tissue culture, Plant growth substance, Photomorphogenesis, Etiolation.●Establishment and development of plant physiology（30 min）In ancient China and western countries→Experimentally/scientifically→J.von Liebig’s work→Modern plant physiology. Establishment and development of plant physiology in China.●Perspectives of plant physiology（10 min）Five problems of human beings : Food, Energy, Environment, Resources, Population ●Summary of the contents of introduction（5 min）Chapter 1 Water Metabolism教学章节：植物对水分的需要、植物细胞对水分的吸收、植物根系对水分的吸收、蒸腾作用、植物体内水分的运输、合理灌溉的生理基础计划学时：3 h一、教学目的通过本章学习，主要了解植物对水分吸收、运输及蒸腾作用的基本原理，认识维持植物水分平衡的重要性，为合理灌溉提供理论基础。
ECIL3_Antifungal_prophylaxis_update_2009
Antifungal prophylaxis in leukemia patients 2009 update of the ECIL-1 and 2 guidelinesObjectivesMethods1.QuestionnaireSummer 2005Do you Use Antifungal Prophylaxis?(N= 38)908070605040302010Yes Allo Auto InductionDo you Use Antifungal Prophylaxis?(N= 38)Allo Auto Induction Fluco57.157.155 Itra caps7.19.55Itra sol21.414.320 Itra iv 3.6 4.85 Vorico 3.6 4.85 Ambisome 3.6--Nystatin10.714.315 Non-abs amphoB17.919.025 AmphoB aerosol7.1--2. Literature ReviewPopulation Dose Effect RefAllogeneic 400 mg qd Proven 18 →7%Slavin 1995, Marr 2000Autologous400 mg qdUnknown Goodman 1992 (52% auto)AML w/o SCT 400 mg qdNoneSchaffner 1995400 mg qdProven/probable 24 →7%Rotstein 1999In allogeneic SCT fluconazole 400 mg qd to reduce the incidence of IFI AI In autologous SCT fluconazole 400 mg qd to reduce the incidence of IFI CIII In AML w/o SCT fluconazole 400 mg qd to reduce the incidence od IFIAIDoes Fluconazole Prophylaxis Reduce theIncidence of IFI?Reduce Attributable Mortality?Population Dose Effect RefAllogenic400 mg qd21% →13%Slavin1995, Marr2000 Autologous400 mg qd 5.6% →0.6%Goodman 1992 (52%auto)AML w/o SCT400 mg qd None Schaffner 1995400 mg qd 4.5% →0.7%Rotstein 1999In allogeneic SCT fluconazole400 mg qd to reduce attributable mortality AI In autologous SCT fluconazole400 mg qd to reduce attributable mortality AI In AML w/o SCT fluconazole400 mg qd to reduce attributable mortality CIIIReduce Overall Mortality?Population Dose Effect RefAllogeneic400 mg qd55% →28%Slavin1995, Marr2000 Autologous400 mg qd None Goodman 1992 (52%auto)AML w/o SCT400 mg qd None Schaffner 1995400 mg qd None Rotstein 1999In allogeneic SCT fluconazole400 mg qd to reduce overall mortality AI In autologous SCT fluconazole400 mg qd to reduce overall mortality CIII In AML w/o SCT fluconazole400 mg qd to reduce overall mortality CIIIPopulation Dose EffectRefAllogeneic 400 mg qd Days until empiric antifungals 18 →21Slavin 1995, Marr 2000Autologous400 mg qdUnknownGoodman 1992 (52% auto)AML w/o SCT 400 mgqdEmpiric antifungals 33% →48%Schaffner 1995400 mg qdEmpiric antifungals 50% →57%Rotstein 1999In allogeneic SCT fluconazole 400 mg qd to reduce empiric antifungals AI (?)In autologous SCT fluconazole 400 mg qd to reduce empiric antifungals CIII In AML w/o SCT fluconazole 400 mg qd to reduce empiric antifungalsEIDoes Fluconazole Prophylaxis Reduce the Use of Empirical Antifungal Therapy?Population Dose ResultRef Allogeneic Various Relapse rate 33%univariate risk factor analysis Offner 1998Autologous???AML w/o SCT VariousRelapse rate 16%multivariate risk factor analysisCornely 2003In allogeneic SCT secondary prophylaxis to reduce BT-IFI C III In autologous SCT secondary prophylaxis to reduce BT-IFI C III In AML w/o SCT secondary prophylaxis to reduce BT-IFIC IIIDoes Secondary Prophylaxis Reduce theIncidence of Breakthrough IFI?Itraconazole: meta-analysisN Os/IV IFI IAI FI-MorGotzsche& Johansen 310.510.27-0.96--Bow530.610.38-0.890.910.44-1.180.780.38-1.60Glasmacher136/20.600.43-0.890.670.41-1.100.650.43-0.98Efficacy of itraconazole correlates closely with the dose: oral solution at 400 mg/day or iv formulation at 200 mg/day (supported by in vitro studies and animal models)Menichetti Os vs. placebo Mixed~75% AL Double-blind201/205Morgenstern Os vs. fluco Mixed~1/3 auto’sOpen218/227Harousseau Os vs. amphoB Mixed~70% AL Double-blind281/276Lass-Flörl Os vs. amphoB Mixed Open52/54 Marr Itra* vs. fluco Allogeneic Tx Open151/148 Winston Itra vs. fluco Allogeneic Tx Open71/67Invasive fungalinfections Proven deep fungalOverallmortalityAttributablemortalityEmpirictherapyToxicity24 % vs33 % (0.035) 2.5 vs4.4 % (ns)7% vs9%(ns)1 vs5(ns)ns(for AL)ns10 vs13 (ns) 6 vs1 (0.06)-7 vs0(0.024)*34 vs52Itra> flucoIA: 1.8 % vs3.3 % (ns) 2.8 % vs4.7 % (ns)6 % vs8 %(ns)1 vs5ns ns1 vs4 5.7 % vs5.5 %(ns)--ns7 % vs15 % (0.03)Mold: 5 % vs12 % (0.03)(ns) -ns Itra> fluco9 % vs25 % (0.01) IA: 4 % vs12 % (ns)45 % vs42 %(ns)9 % vs18 %(ns)-Itra> flucoItraconazole for allo BMTPosaconazoleDesign and Treatment DesignPopulationsTreatmentregimenDuration oftreatmentFollow upIncidence of Proven/Probable IFIsWhile on Treatment*2%1%8%6%7/29122/28817/2883/291P = .0038P = .00132%1%8%7%7/30425/29820/2982/304P = .0009P = .0001Incidence of Proven/Probable IFIsDuring Fixed Time Period*5%2%9%7%16/30127/29921/2997/301P = .0740P = .00595%1%11%9%14/30433/29826/2984/304P = .0031P <.0001HSCT + GVHDFluconazole(AI) vs. posaconazole(AI) inAllogeneic HSCTPrimary prophylaxis with Primary prophylaxis with voriconazole voriconazole inallogeneic hematopoietic stem cell transplant recipients recipients : Two trials analyzed1-Wingard J et al. 2 –Marks D et alStudy Overview•••––––UPDATE ECIL-3 2009WingardJ et al. 2007UPDATE ECIL-3 2009Study Endpoints•––••Primary endpoint: fungal-free survival (FFS) at 180 days –•–Wingard J et al. 2007Patient CharacteristicsFLU N=295VORI N=305Age (median)43 years43 years% 18 years or above92%91% DiseaseAML101 (34%)133 (44%) ALL64 (22%)58 (19%) CML60 (20%)43 (14%) MDS49 (17%)49 (16%) NHL21 (7%)22 (7%) Disease risk status = good263 (89%)283 (93%) Donor source = related169 (57%)168 (55%)UPDATE ECIL-3 2009Wingard J et al. 2007SafetyToxicities (Grades 3Toxicities (Grades 3--5)*FLU N = 295VORI N = 305Liver 18%15%Confusion 5%6%Photopsia 0%1%Psychosis 4%2%Renal 11%9%Hypoxia22%18%UPDATE ECIL-3 2009Wingard J et al. 2007Fungal-free SurvivalFluconazole (N=295) 75% at 180 Days Voriconazole (N=305) 78% at 180 DaysII II I I I II I I I I II I II I I III I III I I I II I I II I I I I I IIII II I II I I I I I I I I II I II I I I II I I I II I I I I I I I I p=0.72UPDATE ECIL-3 2009Wingard J et al. 2007Microbiologically Documented Proven/Probable Fungal Infections Through Day 180Fungal Genus FLU VORI •Aspergillus*16*7*•Candida33•Zygomycetes32•Other11Totals**23**13***p = 0.05** p = 0.11Wingard J et al. 2007Voriconazole(VOR) versus itraconazole(ITR) for primary prophylaxis of invasive fungal infections in allogeneic HSCT recipients Marks et al. ICAAC 2009, San Francisco, M-1249aMarks D et al. 2009UPDATE ECIL-3 2009 Antifungal prophylaxis in allogeneic SCTProposed changes onlyNeutropenia w/o GvHDFluconazole* 400 mg/d AIPosaconazole No data Voriconazole200 mg bid Provisional AI GvHD> grade IFluconazole400 mg/d CIPosaconazole200 mg tid AIVoriconazole200 mg bid Provisional AIEchinocandinsVan Burik J et al. Clin Infect Dis 2004Few patients, not exclusively high-riskpatients, few proven FIUPDATE ECIL-2 2007 Caspofungin versus itraconazole in patients with hematologic malignanciesMattiuzzi et al. AAC 2006; 50: 14355 (52%)44(51%)7 (6%) 5 (6%)40 (37%)29 (34%)Insufficient data to propose recommendationdue to design and statisticsOral and IV PolyenesLiposomal amphotericin B in BMTrecipientsFalagas& Vardakas, Am J Hematol2006Low-dose liposomal amphotericin B in prolonged neutropeniaPenack et al. Ann Oncol2006; 17: 13065 (4.6%)22 (20.2%)5/75 (6.7%)20/57 (35%)6282464210Aerosolized Aerosolized amphotericin amphotericin BSchwartz et al. Blood 1999; 93: 3654-3661Rijnders et al. Clin Infect Dis 2008; 46: 1401-8UPDATE ECIL-3 2009Liposomal AmB Placebon=139n=132Aerosolized liposomal amphotericin B plus fluconazole during prolonged neutropeniaRijnders et al. Clin Infect Dis 2008; 46: 1401-8ResultsRijnders et al. Clin Infect Dis2008; 46: 1401-8ResultsFluconazole(dose?) was given to all patientsDiscontinuation of inhalation therapy for at least one weekReasons for discontinuationRijnders et al. Clin Infect Dis2008; 46: 1401-8Aerosolized liposomal amphotericin B plus fluconazole during prolonged neutropenia•ECIL-3 recommendationPrimary antifungal Prophylaxis in Cancer Patients: Fluco v. Drug with Anti-mold Activity: Meta-analysisAnti--mould Relative Outcome Fluconazole Antirisk*Robenshtok et al. J Clin Oncol2007; 25 (34)Inclusion criteria should provide a high enough incidence of IFI (> 10%?) to warrant PAC•Double-blind•Study end points–Incidence of proven and probable invasive yeast and mould infections(EORTC/MSG criteria): requires adherence to diagnostic protocol–Overall mortality and fungus-attributable mortality–(superficial and mucosal infections)–Toxicity–Colonization and resistanceIncrease of microbial shift and induction of resistance during antifungal prophylaxis!These findings may reflect, at least, partly,antifungal selection pressure caused byantifungals in high-risk patientsAzole resistant yeasts in patients receivingantifungal prophylaxisMain results ReferencesPeriod NopatientsMarr 2002 1994-1997655FLU increased colonisations with non albicans species (53%) mostly C. glabrataand C krusei, 5.3% of C. albicans were FLU resistant1988-1992474FLU-prophylaxis was directly associated with fungemia by C. krusei(OR=27.07)Abi-Said 1997and C. glabrata(5.08)1993253No increase in infections and colonisation in patients receiving FLU Winston 19931994-1995300No significant increase in breakthrough infections Slavin19951989-1990463Significant increase in C. krusei infections and colonisation by C. krusei(41%) Wingard19911989-1996234 C. krusei fungemia increased significantly (doubled from 5-to 10%) in patientsAbbas2000with FLU1994-1995274Colonisation by non C. albicans increased in both study arms, FLU and placebo Laverdiere20001991365No differences were found between the study groups Goodman 19921996-1999395Increased infection with C glabrata and C krusei were observed Martino 2002Martino 19941999-2001304No difference in the incidence of IFI during the study period (FLU 16%, vs ITRA13%)1999-2000882Breakthrough infections for MICA and FLU were 1.6% and 2.4%. C. glabrataVan Burik2004colonisation in the FLU and C. albicans in the MICA-arm increasedsignificantlyDrug monitoring of itraconazoleConclusions : Drug monitoringrecommended for oral formulationfrequency not well defined, probablyweeklyDuration of antifungal prophylaxisN (%)Drug Duration15 (50)Flu 400mg q.d.Neutrophil count ≥500/µl6 (19)Flu 100-200mg q.d.End of immunesuppression4 (12)Itra200 mg b.i.d.d 30 (1)end of immunesuppression(3)4 (12)Amph Bconv. 0,5 mg/kg q.d. (1) lipid 1-3mg/kg q.d. (3)Neutrophil count ≥500/µl => Flu till end ofimmunesuppression2 (6)No prophylaxis3. Evidence-Based RecommendationsUPDATE ECIL-3 2009: Summary slide Primary antifungal prophylaxis in leukemia patients •Induction chemotherapy of acute leukemia。
无导线起搏与传统起搏对三尖瓣反流短期影响的对比研究
㊃心脏电生理学专题㊃无导线起搏与传统起搏对三尖瓣反流短期影响的对比研究郭雨龙㊀付明鹏㊀刘晨㊀乔宇㊀郭金锐㊀刘可㊀郭涛650102昆明,云南省阜外心血管病医院心律失常中心通信作者:郭雨龙,电子信箱:kktury8859@DOI:10.3969/j.issn.1007-5410.2023.04.004㊀㊀ʌ摘要ɔ㊀目的㊀比较无导线起搏与传统起搏患者的短期三尖瓣反流变化情况,并分析三尖瓣反流的相关因素㊂㊀方法㊀回顾性纳入2020年1月至2022年11月在云南省阜外心血管病医院就诊的新植入起搏器94例患者,分为无导线起搏组(47例)和传统起搏组(47例),通过经胸超声心动图评估术前㊁术后6月内的三尖瓣反流程度及恶化情况,比较两组三尖瓣反流恶化的发生率㊂Logistic回归分析发生三尖瓣反流的相关因素㊂㊀结果㊀发生三尖瓣反流恶化者共29例(30.9%),无导线起搏组和传统起搏组的发生风险相似(14例比15例,29.8%比31.9%),差异无统计学意义(χ2=0.050,P=0.823)㊂二元logistic回归分析结果显示,单腔起搏器是发生三尖瓣中㊁大量反流的独立影响因素(χ2=10.031,P=0.010)㊂㊀结论㊀与传统起搏器相比,无导线起搏器可能并不减少术后短期发生三尖瓣反流的风险㊂ʌ关键词ɔ㊀无导线起搏;㊀心脏起搏;㊀三尖瓣反流;㊀三尖瓣瓣下复合体基金项目:云南省临床医学中心项目;云南省卫生健康委员会医学后备人才培养计划(H-2018037);云南省阜外心血管病医院院级科研基金项目(2019YFKT-04)Comparison of the short-term effects of leadless pacing and traditional pacing on tricuspidregurgitation㊀Guo Yulong,Fu Mingpeng,Liu Chen,Qiao Yu,Guo Jinrui,Liu Ke,Guo TaoDepartment of Arrhythmia,Fuwai Yunnan Cardiovascular Hospital,Kunming650102,ChinaCorresponding author:Guo Yulong,Email:kktury8859@.ʌAbstractɔ㊀Objective㊀To compare the short-term risk of tricuspid regurgitation in patients treatedwith leadless pacemaker or traditional pacemaker,and to determine its related factors.㊀Methods㊀A totalof94patients who were newly implanted leadless or traditional pacemakers in Fuwai Yunnan CardiovascularHospital from January2020to November2022were retrospectively enrolled.All were divided into theleadless pacemaker group(n=47)and the tranditional pacemaker group(n=47).The transthoracic echocardiography was used to evaluate the severity and deterioration of tricuspid regurgitation before and6months after operation.Logistic regression analyses was used to assess its related factors.㊀Results㊀A totalof29(30.9%)patients had tricuspid regurgitation deterioration.There was no significant difference in therisk of tricuspid regurgitation deterioration between the leadless and tranditional pacemaker groups(14casesvs.15cases,29.8%vs.31.9%,χ2=0.050,P=0.823).Binary logistic regression analyses resultindicated that single-chamber pacemaker was an independent factor of moderate to massive tricuspid regurgitation(χ2=10.031,P=0.010).㊀Conclusions㊀Compared with traditional pacemaker,leadless pacemaker probably cannot reduce the short-term risk of tricuspid regurgitation after operation.ʌKey wordsɔ㊀Leadless pacemaker;㊀Cardiac pacing;㊀Tricuspid regurgitation;㊀Tricuspid subvalvular apparatusFund program:Yunnan Provincial Clinical Medical Center Project;Yunnan Provincial Health Commission Medical Reserve Talent Training Plan(H-2018037);Yunnan Fuwai Cardiovascular DiseaseHospital Hospital-Level Research Fund Project(2019YFKT-04)㊀㊀心脏起搏是严重心动过缓最有效的治疗方式㊂传统心脏起搏器由脉冲发生器及相连接的电极导线构成,电极导线一般通过上腔静脉途径植入心腔内,右心室起搏电极导线跨过三尖瓣进入右室内固定㊂但是在以机械机制为主的多种机制介导下,传统心脏起搏会有加重恶化三尖瓣反流风险㊂无导线起搏是近年来最新的心脏起搏技术,与传统起搏器不同,无导线起搏器体积仅有胶囊大小,可通过特殊的输送装置,经下腔静脉途径植入右心室内,植入成功后输送装置可完全撤除,具有创伤小㊁恢复快,以及避免了囊袋并发症等特点㊂其心腔内留存的无导线起搏器仅在右心室内,不会遗留跨三尖瓣的电极导线㊂但是,无导线起搏对患者三尖瓣反流影响的临床研究数据较少,且尚无直接比较无导线起搏与传统起搏的报道㊂因此,我们通过纳入无导线起搏与匹配的传统起搏患者,在术前与术后短期通过经胸超声心动图评估三尖瓣反流情况,比较两组之间三尖瓣反流恶化的发生率,以此评估无导线起搏对三尖瓣反流的影响,希望能为无导线起搏的进一步推广应用提供有价值的临床信息㊂1㊀对象和方法1.1㊀研究对象回顾性队列研究㊂纳入2020年1月至2022年11月在云南省阜外心血管病医院新植入起搏器患者,分为无导线起搏组和传统起搏组㊂纳入标准: (1)无导线起搏组符合无导线起搏适应证,且成功完成无导线起搏器植入手术者;(2)传统起搏组按照年龄㊁性别进行1ʒ1匹配,纳入同期就诊的符合传统起搏适应证且成功完成植入者㊂排除标准: (1)因传统起搏感染㊁电极故障或电池耗竭而转用无导线起搏者;(2)仅植入心房电极单腔起搏器者;(3)原有起搏器更换或升级者㊂本研究符合医学研究伦理学要求(编号:2022-94)㊂所有患者均知情同意㊂1.2㊀方法1.2.1㊀无导线起搏器植入手术㊀采用美敦力无导线起搏器(型号Micra TM MC1VR01或Micra TM AV MC1AVR1),所有操作均在导管室血管造影机透视指导下完成㊂穿刺右股静脉,置入导引钢丝,逐级扩张;若右股静脉穿刺或置入导丝不顺则换用左股静脉,沿导引钢丝置入输送装置,应用输送装置将无导线起搏器送至右心室内;多体位投照(至少三个体位:右前斜30ʎ㊁左前斜45ʎ及正位)确认跨过三尖瓣到达右心室中下间隔部,造影确认与心肌贴靠情况满意后,施加一定压力推送输送系统,并释放无导线起搏器,稍微回退输送鞘管,通过牵拉试验证实无导线起搏器头端勾挂满意,且测试阈值㊁阻抗㊁感知等参数满意后方可剪断拉绳;若不满意,则回收后重新定位释放㊂整个手术过程中,静脉推注3000U肝素,输送鞘管持续肝素盐水冲洗,最后撤除输送装置㊁缝合伤口,最后加压包扎㊂1.2.2㊀传统起搏器植入手术㊀采用传统起搏器,所有操作均在导管室血管造影机透视指导下完成㊂穿刺左锁骨下静脉或腋静脉,置入导引钢丝,若穿刺或置入导丝不顺则改为右侧植入,沿锁骨下做4~ 5cm皮肤切口,逐层分离至深筋膜层,制作合适大小的皮下囊袋,应用可撕开鞘管置入起搏电极,右房电极定位固定至右心耳,右室电极定位固定至右室间隔部或心尖部(均使用主动固定电极),测试阈值㊁阻抗㊁感知等参数满意后,拔除可撕开鞘管,电极尾端连接脉冲发生器并埋置于囊袋内,充分止血㊁冲洗后逐层缝合,最后加压包扎㊂1.3㊀观察指标和随访所有患者在植入术前1周内及术后6个月内完成经胸超声心动图对三尖瓣反流情况进行评估㊂使用GE或飞利浦超声探头,在彩色血流多普勒下测量三尖瓣反流束面积与右心房面积比和(或)缩流颈宽度综合评估三尖瓣反流情况的变化㊂其中,面积比<10%为微量反流,10%~20%为少量或轻度反流,21%~40%为中量或中度反流,>40%为大量或重度反流;缩流颈宽度<3mm为少量或轻度反流,缩流颈宽度3~7mm为中量或中度反流,缩流颈宽度>7mm为大量或重度反流㊂此外,三尖瓣反流恶化定义为与术前相比,术后面积比增加超过5%和(或)缩流颈宽度增加超过1mm㊂1.4㊀统计学方法应用SPSS20.0软件进行统计分析㊂符合正态分布的计量资料用 xʃs表示,组间比较采用独立样本t检验;计数资料用百分构成比表示,组间比较采用χ2检验㊂Logistic回归分析影响术后新增三尖瓣中㊁大量反流的相关因素㊂P<0.05为差异有统计学意义㊂2㊀结果2.1㊀两组的基线临床资料比较如表1所示,两组的诊断差异有统计学意义,表现为无导线起搏组诊断为ȡⅡ度房室传导阻滞的比例显著低于传统起搏组,而诊断为心房颤动伴RR长间歇的比例显著高于传统起搏组(P= 0.005)㊂其余基线临床资料相似,差异均无统计学意义(均为P>0.05)㊂2.2㊀两组的起搏器植入术后即刻右室电极参数比较无导线起搏组中,38例(80.9%)使用Micra TM表1㊀两组的基线临床资料比较项目总体(94例)无导线起搏组(47例)传统起搏组(47例)t/χ2值P值年龄( xʃs,岁)78.9ʃ9.979.3ʃ9.978.4ʃ10.00.4390.688男性[例(%)]56(59.6)28(59.6)28(59.6)0.000 1.000诊断[例(%)]10.7810.005㊀窦房结功能障碍38(40.4)19(40.4)19(40.4)㊀ȡⅡ度房室传导阻滞34(36.2)11(23.4)23(48.9)㊀心房颤动伴RR长间歇22(23.4)17(36.2)5(10.6)心功能指标( xʃs)㊀左室射血分数(%)62.0ʃ7.262.7ʃ6.261.2ʃ8.10.9900.325㊀左室舒张末期内径(mm)46.6ʃ6.646.4ʃ6.846.9ʃ6.50.2950.769表2㊀两组起搏器植入术后即刻右室电极参数比较( xʃs)项目总体(94例)无导线起搏组(47例)传统起搏组(47例)t值P值右室电极阻抗(Ω)797.8ʃ214.0819.6ʃ196.8775.9ʃ230.00.9880.326右室电极阈值(V@0.4ms)0.70ʃ0.420.70ʃ0.490.71ʃ0.340.1310.896 R波感知振幅(mV)9.96ʃ4.759.28ʃ4.4010.64ʃ5.02 1.3980.166表3㊀两组术前和术后的三尖瓣反流情况比较[例(%)]项目总体(94例)无导线起搏组(47例)传统起搏组(47例)χ2值P值术前三尖瓣反流14.7960.002㊀无或微量32(34.0)10(21.3)22(46.8) 6.8230.009㊀少量/轻度43(45.7)21(44.7)22(46.8)0.0430.836㊀中量/中度11(11.7)8(17.0)3(6.4) 2.5740.109㊀大量/重度8(8.5)8(17.0)0(0.0)8.7440.003术后三尖瓣反流14.1480.003㊀无或微量28(29.8)7(14.9)21(44.7)9.9700.002㊀少量/轻度35(37.2)18(38.3)17(36.2)0.0460.831㊀中量/中度18(19.1)11(23.4)7(14.9) 1.0990.294㊀大量/重度13(13.8)11(23.4)2(4.3)7.2310.007MC1VR01(起搏模式VVI),9例(19.1%)使用Micra TM AV MC1AVR1(起搏模式VDD),所有无导线起搏器均位于右室中低位间隔部㊂传统起搏组中,9例(19.1%)使用单腔起搏器(模式VVI),38例(80.9%)使用双腔起搏器(模式DDD);右室电极导线在心尖部3例(6.4%),在间隔部44例(93.6%)㊂如表2所示,两组起搏器植入术后右室电极的即刻参数均相似,差异无统计学意义(均为P>0.05)㊂2.3㊀两组术前和术后的三尖瓣反流情况比较如表3所示,两组术前的三尖瓣反流情况差异有统计学意义(P=0.002),表现为无导线起搏组的无或微量三尖瓣反流率明显低于传统起搏组(P= 0.009),而大量/重度三尖瓣反流率明显高于传统起搏组(P=0.003)㊂两组术后的三尖瓣反流情况差异也有统计学意义(P=0.003),表现为无导线起搏组的无或微量三尖瓣反流率明显低于传统起搏组(P=0.002),而大量/重度三尖瓣反流率明显高于传统起搏组(P=0.007)㊂与术前比较,术后新增的有临床意义的三尖瓣中大量反流有12例,其中无导线起搏组6例(12.8%),传统起搏组6例(12.8%),组间比较差异无统计学意义(χ2=0.000,P=1.000)(图1)㊂三尖瓣反流恶化者共29例(30.9%),其中无导线起搏组14例(29.8%),传统起搏组15例(31.9%),组间比较差异无统计学意义(χ2=0.050, P=0.823)(图1)㊂图1㊀两组发生三尖瓣反流情况比较2.4㊀术前三尖瓣反流程度对术后发生三尖瓣反流恶化的影响进一步研究显示,术前三尖瓣无或微少量反流者在术后出现反流恶化的比例为29.3%(22/75),而术前三尖瓣中㊁大量反流者在术后出现反流恶化的比例为36.8%(7/19),两者之间比较差异无统计学意义(χ2=0.401,P=0.527)㊂2.5㊀Logistic回归分析结果采用二元logistic回归分析(Wald后退法),分析术后新增三尖瓣中㊁大量反流的影响因素,无导线起搏组纳入因素为年龄㊁性别㊁起搏适应证诊断㊁术前左室射血分数㊁舒张末期内径及术前三尖瓣反流情况,传统起搏器纳入因素除上述外,增加右室电极位置及起搏器类型(单腔或双腔)㊂最终在无导线起搏组中未发现影响术后新增三尖瓣中㊁大量反流的有统计学意义相关因素(均为P>0.05);而在传统起搏患者中,发现起搏器类型[Exp(B)= 35.589,P=0.01]是独立影响因素,其中单腔起搏器患者术后出现新增三尖瓣中㊁大量反流的比例远高于双腔起搏器患者[4例比2例,44.4%(4/9)比5.3%(2/38),χ2=10.031,P=0.002]㊂3 讨论本研究发现,无导线起搏器与传统起搏器相比,术后短期发生三尖瓣反流恶化及新发中㊁大量三尖瓣反流的比例无统计学差异,故无导线起搏可能并不能够减少对三尖瓣反流的负面影响㊂三尖瓣反流是右心室起搏的常见并发症㊂国外研究报道术后三尖瓣反流的发生率7%~21%,三尖瓣反流恶化或加重的比例为10%~45%[1]㊂一般认为,导致或加重三尖瓣反流的机制以机械损伤为主,机械机制主要包括植入过程中起搏电极导线直接损伤瓣叶导致穿孔或撕裂㊁导线嵌顿于瓣叶之间㊁导线与瓣叶粘连或与腱索缠绕等㊂与普通电极导线相比,更粗㊁更硬的除颤电极导线导致三尖瓣反流的概率更高;此外,长期高比例右室非生理性起搏㊁慢性右心扩大及三尖瓣环扩张也是远期三尖瓣反流发生及加重的因素㊂其中,术中电极导管对三尖瓣的直接机械损伤是短期发生三尖瓣反流的主要机制㊂使用的电极越硬㊁越粗或暴力操作等均是潜在的危险因素,而慢性电极导线粘连㊁高比例右室非生理起搏及右心扩大瓣环扩张则是远期发生三尖瓣反流的主要机制[1-3]㊂国内关于三尖瓣反流的报道的例数较少且还有争议,赵波等[4]发现长期右室心尖部起搏仅导致轻微反流,引起有临床意义的三尖瓣反流恶化的比例更低㊂邹宝明等[5]发现无论右室心尖部还是间隔部起搏都不会在短期内明显加重三尖瓣反流㊂无导线起搏是最新的心脏起搏技术,与传统右室起搏不同,无导线起搏在植入后并不会长期遗留跨三尖瓣的电极导线,因此其对三尖瓣的影响及机制可能会不同㊂目前国外关于无导线起搏对三尖瓣反流作用的研究报道有限,而国内尚无相关报道㊂2019年Beurskens等[6]报道无导线起搏术后1年三尖瓣反流加重的比例为43%㊂2022年一项关于无导线起搏器的真实世界研究,纳入植入心房感知㊁心室起搏的无导线起搏器患者,发现中度以上的三尖瓣反流发生率为48.8%(21/43)[7]㊂因此,无导线起搏器导致或加重三尖瓣反流的风险依然存在,甚至可能比传统起搏器高㊂此项研究发现,在起搏器植入术后短期内,总体三尖瓣反流恶化发生概率为30.9%,无导线起搏组为29.8%,传统起搏组为31.9%,考虑到本研究中我们为了更早地发现短期影响效果,所定义的三尖瓣反流恶化的超声心动图指标较为敏感,远比临床症状更早出现变化,因此该比例应该会高于真实世界中有临床症状的三尖瓣反流发病率㊂我们发现两组间差异无统计学意义,可认为无导线起搏并不能够减少对三尖瓣的负面影响㊂表1中两组间的入院诊断有统计学差异,无导线起搏组的心房颤动伴RR长间歇患者比例更高,这是其最早及最强的植入适应证,很可能对结果造成一定影响㊂由表3中可看出,本研究无导线起搏组术前的中㊁大量三尖瓣反流者更多,这是由于我们在开展无导线起搏器植入术初期误以为其对三尖瓣反流的影响较小,因此在病人选择上有了偏差,而后续统计分析发现术前反流程度并未影响其术后恶化情况,故这种差异并不影响本文的主要研究结论㊂而经过本研究之后,我们对无导线起搏与三尖瓣的相互作用又有了更多认识,将进一步优化及改善今后对患者的处理决策,希望能更好改善预后㊂从表面上看,由于无导线起搏器并不会长期遗留跨瓣导线,从理论上来说慢性三尖瓣粘连及腱索缠绕的发生率可能会低于传统起搏器,似乎避免了传统起搏引发三尖瓣反流的一些机制㊂但是,无导线起搏器植入须使用更粗㊁更硬的输送装置,操作中对三尖瓣的损伤可能会大于传统起搏,发生瓣膜穿孔的风险是否增加尚无报道㊂另外,国外有学者发现,无导线起搏器植入后对三尖瓣瓣下复合体的干扰较大,瓣下复合体是个解剖概念,主要指与瓣膜㊁腱索连接的乳头肌,三尖瓣下一般有三组乳头肌,前组在右室游离壁,下组及间隔组分别在下壁及右室间隔面,下组及后组乳头肌可能表现不完全而腱索就直接连接到间隔面或心室壁[8]㊂固定于间隔面的无导线起搏器虽然无跨瓣导线,但可能会显著影响间隔侧的三尖瓣瓣下复合体功能,由此加重三尖瓣反流㊂然而,目前对于无导线起搏器与三尖瓣相互作用的认识有限,还需要进一步的研究及临床实践来明确,尤其需要心脏外科及心脏结构专业与起搏电生理专业的合作㊂本研究有一些局限性㊂本研究仅为临床观察性研究,例数较少,并非严密设计的随机对照研究,而且三尖瓣反流的可能影响因素较多,本研究也未能完全排除无导线/传统起搏选择以外的其他可能干扰因素,结论的说服力有限㊂总之,与传统起搏器相比,无导线起搏器可能并不减少术后短期发生三尖瓣反流的风险㊂利益冲突:无参㊀考㊀文㊀献[1]Addetia K,Harb SC,Hahn RT,et al.Cardiac ImplantableElectronic Device Lead-Induced Tricuspid Regurgitation[J].JACC Cardiovasc Imaging,2019,12(4):622-636.DOI:10.1016/j.jcmg.2018.09.028.[2]郑晓琳,张澍,陈珂萍.心内膜导线相关的三尖瓣反流[J].中国心脏起搏与心电生理杂志,2014,28(5):443-445.DOI:10.13333/ki.cjcpe.2014.05.018.㊀Zheng XL,Zhang S,Chen KP.Tricuspid valve regurgitationassociated with Endocardium leads[J].Chin J Card PacingElectrophysiol,2014,28(5):443-445.DOI:10.1333/ki.cjcpe.2014.05.018.[3]Kim JB,Spevack DM,Tunick PA,et al.The effect oftransvenous pacemaker and implantable cardioverter defibrillatorlead placement on tricuspid valve function:an observational study[J].J Am Soc Echocardiogr,2008,21(3):284-287.DOI:10.1016/j.echo.2007.05.022.[4]赵波,宋建平,邹操.长期右室心尖部起搏对三尖瓣反流的影响[J].中国心脏起搏与心电生理杂志,2012,26(4):315-318.DOI:10.13333/ki.cjcpe.2012.04.014.㊀Zhao B,Song JP,Zou C.Effects of long-term permanent rightventricular apical pacing on tricuspid regurgitation[J].Chin JCard Pacing Electrophysiol,2012,26(4):315-318.DOI:10.13333/ki.cjcpe.2012.04.014.[5]邹宝明,王景武,孙克陆,等.围术期右室流入道间隔部起搏对三尖瓣反流的影响[J].中华全科医学,2015,13(6):896-898.DOI:10.16766/ki.issn.1674-4152.2015.06.019.㊀Zou BM,Wang JW,Sun KL,et al.Influence of right ventricularinlet septum pacing on tricuspid regurgitation during perioperativeperiod[J].Chin J Gen Pract,2015,13(6):896-898.DOI:10.16766/ki.issn.1674-4152.2015.06.019. [6]Beurskens NEG,Tjong FVY,de Bruin-Bon RHA,et al.Impactof Leadless Pacemaker Therapy on Cardiac and AtrioventricularValve Function Through12Months of Follow-Up[J].CircArrhythm Electrophysiol,2019,12(5):e007124.DOI:10.1161/CIRCEP.118.007124.[7]Kowlgi GN,Tseng AS,Tempel ND,et al.A real-worldexperience of atrioventricular synchronous pacing with leadlessventricular pacemakers[J].J Cardiovasc Electrophysiol,2022,33(5):982-993.DOI:10.1111/jce.15430.[8]Tadic M.Multimodality Evaluation of the Right Ventricle:AnUpdated Review[J].Clin Cardiol,2015,38(12):770-776.DOI:10.1002/clc.22443.(收稿日期:2023-01-31)(本文编辑:李鹏)㊃读者㊃作者㊃编者㊃GB/T7713.2 2022‘学术论文编写规则“已于2023年7月1日实施㊀㊀2022年12月30日,国家市场监督管理总局和国家标准化管理委员会联合发布了GB/T7713.2 2022‘学术论文编写规则“,并已于2023年7月1日实施㊂无论是学术论文㊁学位论文还是科技报告,其撰写和编排都需要遵循一定的规范,以利于信息系统的收集㊁存储㊁处理㊁加工㊁检索㊁利用㊁交流㊁传播㊂GB/T7713 1987‘科学技术报告㊁学位论文和学术论文的编写格式“,对学术论文㊁学位论文和科技报告的撰写要求及编排格式作了统一规定㊂鉴于三者的使用对象及使用目的不尽相同,撰写要求及编排格式差异较大,后来修订GB/T7713时,将其分为3个部分分别进行修订㊂第1部分:学位论文编写规则㊂目的在于规定了学位论文的撰写格式和要求㊂第2部分:学术论文编写规则(简称 本规则 )㊂目的在于规定了学术论文的撰写要求和编排格式㊂第3部分:科技报告编写规则㊂目的在于规定了科技报告的编写㊁组织㊁编排等要求㊂本规则描述了撰写和编排学术论文的基本要求和格式规范㊂学术论文编写的标准化和规范化,是使其格式和体例规范化,语言㊁文字和符号规范化,技术和计量单位标准化,以便于学术论文的检索和传播,促进学术成果的交流和使用㊂本规则的适用范围,包括一切反映自然㊁社会和人文等的科学体系的学术论文㊂然而,由于学科门类㊁选定课题㊁研究工作方法㊁工作进行阶段㊁观测和调查等各方面的差异,采用本规则进行学术论文编写宜采取严肃性和灵活性相结合的原则㊂本规则对GB/T7713 1987中的学术论文编写内容进行了必要的检查㊁更新,进而形成单独的学术论文编写规则,代替GB/T7713 1987中的学术论文编写格式部分㊂现可登录国家标准化管理委员会网站或通过以下网址/bzgk/gb/showGb?type=online&hcno= 0B963916637B8F34B295FCF4A51A1BE5查询本规则全文㊂。
Peters (2010) Episodic Future Thinking Reduces Reward Delay Discounting
NeuronArticleEpisodic Future Thinking ReducesReward Delay Discounting through an Enhancement of Prefrontal-Mediotemporal InteractionsJan Peters1,*and Christian Bu¨chel11NeuroimageNord,Department of Systems Neuroscience,University Medical Center Hamburg-Eppendorf,Hamburg20246,Germany*Correspondence:j.peters@uke.uni-hamburg.deDOI10.1016/j.neuron.2010.03.026SUMMARYHumans discount the value of future rewards over time.Here we show using functional magnetic reso-nance imaging(fMRI)and neural coupling analyses that episodic future thinking reduces the rate of delay discounting through a modulation of neural decision-making and episodic future thinking networks.In addition to a standard control condition,real subject-specific episodic event cues were presented during a delay discounting task.Spontaneous episodic imagery during cue processing predicted how much subjects changed their preferences toward more future-minded choice behavior.Neural valuation signals in the anterior cingulate cortex and functional coupling of this region with hippo-campus and amygdala predicted the degree to which future thinking modulated individual preference functions.A second experiment replicated the behavioral effects and ruled out alternative explana-tions such as date-based processing and temporal focus.The present data reveal a mechanism through which neural decision-making and prospection networks can interact to generate future-minded choice behavior.INTRODUCTIONThe consequences of choices are often delayed in time,and in many cases it pays off to wait.While agents normally prefer larger over smaller rewards,this situation changes when rewards are associated with costs,such as delays,uncertainties,or effort requirements.Agents integrate such costs into a value function in an individual manner.In the hyperbolic model of delay dis-counting(also referred to as intertemporal choice),for example, a subject-specific discount parameter accurately describes how individuals discount delayed rewards in value(Green and Myer-son,2004;Mazur,1987).Although the degree of delay discount-ing varies considerably between individuals,humans in general have a particularly pronounced ability to delay gratification, and many of our choices only pay off after months or even years. It has been speculated that the capacity for episodic future thought(also referred to as mental time travel or prospective thinking)(Bar,2009;Schacter et al.,2007;Szpunar et al.,2007) may underlie the human ability to make choices with high long-term benefits(Boyer,2008),yielding higher evolutionaryfitness of our species.At the neural level,a number of models have been proposed for intertemporal decision-making in humans.In the so-called b-d model(McClure et al.,2004,2007),a limbic system(b)is thought to place special weight on immediate rewards,whereas a more cognitive,prefrontal-cortex-based system(d)is more involved in patient choices.In an alternative model,the values of both immediate and delayed rewards are thought to be repre-sented in a unitary system encompassing medial prefrontal cortex(mPFC),posterior cingulate cortex(PCC),and ventral striatum(VS)(Kable and Glimcher,2007;Kable and Glimcher, 2010;Peters and Bu¨chel,2009).Finally,in the self-control model, values are assumed to be represented in structures such as the ventromedial prefrontal cortex(vmPFC)but are subject to top-down modulation by prefrontal control regions such as the lateral PFC(Figner et al.,2010;Hare et al.,2009).Both the b-d model and the self-control model predict that reduced impulsivity in in-tertemporal choice,induced for example by episodic future thought,would involve prefrontal cortex regions implicated in cognitive control,such as the lateral PFC or the anterior cingulate cortex(ACC).Lesion studies,on the other hand,also implicated medial temporal lobe regions in decision-making and delay discounting. In rodents,damage to the basolateral amygdala(BLA)increases delay discounting(Winstanley et al.,2004),effort discounting (Floresco and Ghods-Sharifi,2007;Ghods-Sharifiet al.,2009), and probability discounting(Ghods-Sharifiet al.,2009).Interac-tions between the ACC and the BLA in particular have been proposed to regulate behavior in order to allow organisms to overcome a variety of different decision costs,including delays (Floresco and Ghods-Sharifi,2007).In line with thesefindings, impairments in decision-making are also observed in humans with damage to the ACC or amygdala(Bechara et al.,1994, 1999;Manes et al.,2002;Naccache et al.,2005).Along similar lines,hippocampal damage affects decision-making.Disadvantageous choice behavior has recently been documented in patients suffering from amnesia due to hippo-campal lesions(Gupta et al.,2009),and rats with hippocampal damage show increased delay discounting(Cheung and Cardinal,2005;Mariano et al.,2009;Rawlins et al.,1985).These observations are of particular interest given that hippocampal138Neuron66,138–148,April15,2010ª2010Elsevier Inc.damage impairs the ability to imagine novel experiences (Hassa-bis et al.,2007).Based on this and a range of other studies,it has recently been proposed that hippocampus and parahippocam-pal cortex play a crucial role in the formation of vivid event repre-sentations,regardless of whether they lie in the past,present,or future (Schacter and Addis,2009).The hippocampus may thus contribute to decision-making through its role in self-projection into the future (Bar,2009;Schacter et al.,2007),allowing an organism to evaluate future payoffs through mental simulation (Johnson and Redish,2007;Johnson et al.,2007).Future thinking may thus affect intertemporal choice through hippo-campal involvement.Here we used model-based fMRI,analyses of functional coupling,and extensive behavioral procedures to investigate how episodic future thinking affects delay discounting.In Exper-iment 1,subjects performed a classical delay discounting task(Kable and Glimcher,2007;Peters and Bu¨chel,2009)that involved a series of choices between smaller immediate and larger delayed rewards,while brain activity was measured using fMRI.Critically,we introduced a novel episodic condition that involved the presentation of episodic cue words (tags )obtained during an extensive prescan interview,referring to real,subject-specific future events planned for the respective day of reward delivery.This design allowed us to assess individual discount rates separately for the two experimental conditions,allowing us to investigate neural mechanisms mediating changes in delay discounting associated with episodic thinking.In a second behavioral study,we replicated the behavioral effects of Exper-iment 1and addressed a number of alternative explanations for the observed effects of episodic tags on discount rates.RESULTSExperiment 1:Prescan InterviewOn day 1,healthy young volunteers (n =30,mean age =25,15male)completed a computer-based delay discounting proce-dure to estimate their individual discount rate (Peters and Bu ¨-chel,2009).This discount rate was used solely for the purpose of constructing subject-specific trials for the fMRI session (see Experimental Procedures ).Furthermore,participants compiled a list of events that they had planned in the next 7months (e.g.,vacations,weddings,parties,courses,and so forth)andrated them on scales from 1to 6with respect to personal rele-vance,arousal,and valence.For each participant,seven subject-specific events were selected such that the spacing between events increased with increasing delay to the episode,and that events were roughly matched based on personal rele-vance,arousal,and valence.Multiple regression analysis of these ratings across the different delays showed no linear effects (relevance:p =0.867,arousal:p =0.120,valence:p =0.977,see Figure S1available online).For each subject,a separate set of seven delays was computed that was later used as delays in the control condition.Median and range for the delays used in each condition are listed in Table S1(available online).For each event,a label was selected that would serve as a verbal tag for the fMRI session.Experiment 1:fMRI Behavioral ResultsOn day 2,volunteers performed two sessions of a delay dis-counting procedure while fMRI was measured using a 3T Siemens Scanner with a 32-channel head-coil.In each session,subjects made a total of 118choices between 20V available immediately and larger but delayed amounts.Subjects were told that one of their choices would be randomly selected and paid out following scanning,with the respective delay.Critically,in half the trials,an additional subject-specific episodic tag (see above,e.g.,‘‘vacation paris’’or ‘‘birthday john’’)was displayed based on the prescan interview (see Figure 1)indicating which event they had planned on the particular day (episodic condi-tion),whereas in the remaining trials,no episodic tag was pre-sented (control condition).Amount and waiting time were thus displayed in both conditions,but only the episodic condition involved the presentation of an additional subject-specific event tag.Importantly,nonoverlapping sets of delays were used in the two conditions.Following scanning,subjects rated for each episodic tag how often it evoked episodic associations during scanning (frequency of associations:1,never;to 6,always)and how vivid these associations were (vividness of associa-tions:1,not vivid at all;to 6,highly vivid;see Figure S1).Addition-ally,written reports were obtained (see Supplemental Informa-tion ).Multiple regression revealed no significant linear effects of delay on postscan ratings (frequency:p =0.224,vividness:p =0.770).We averaged the postscan ratings acrosseventsFigure 1.Behavioral TaskDuring fMRI,subjects made repeated choices between a fixed immediate reward of 20V and larger but delayed amounts.In the control condi-tion,amounts were paired with a waiting time only,whereas in the episodic condition,amounts were paired with a waiting time and a subject-specific verbal episodic tag indicating to the subjects which event they had planned at the respective day of reward delivery.Events were real and collected in a separate testing session prior to the day of scanning.NeuronEpisodic Modulation of Delay DiscountingNeuron 66,138–148,April 15,2010ª2010Elsevier Inc.139and the frequency/vividness dimensions,yielding an‘‘imagery score’’for each subject.Individual participants’choice data from the fMRI session were then analyzed byfitting hyperbolic discount functions to subject-specific indifference points to obtain discount rates (k-parameters),separately for the episodic and control condi-tions(see Experimental Procedures).Subjective preferences were well-characterized by hyperbolic functions(median R2 episodic condition=0.81,control condition=0.85).Discount functions of four exemplary subjects are shown in Figure2A. For both conditions,considerable variability in the discount rate was observed(median[range]of discount rates:control condition=0.014[0.003–0.19],episodic condition=0.013 [0.002–0.18]).To account for the skewed distribution of discount rates,all further analyses were conducted on the log-trans-formed k-parameters.Across subjects,log-transformed discount rates were significantly lower in the episodic condition compared with the control condition(t(29)=2.27,p=0.016),indi-cating that participants’choice behavior was less impulsive in the episodic condition.The difference in log-discount rates between conditions is henceforth referred to as the episodic tag effect.Fitting hyperbolic functions to the median indifference points across subjects also showed reduced discounting in the episodic condition(discount rate control condition=0.0099, episodic condition=0.0077).The size of the tag effect was not related to the discount rate in the control condition(p=0.56). We next hypothesized that the tag effect would be positively correlated with postscan ratings of episodic thought(imagery scores,see above).Robust regression revealed an increase in the size of the tag effect with increasing imagery scores (t=2.08,p=0.023,see Figure2B),suggesting that the effect of the tags on preferences was stronger the more vividly subjects imagined the episodes.Examples of written postscan reports are provided in the Supplemental Results for participants from the entire range of imagination ratings.We also correlated the tag effect with standard neuropsychological measures,the Sensation Seeking Scale(SSS)V(Beauducel et al.,2003;Zuck-erman,1996)and the Behavioral Inhibition Scale/Behavioral Approach Scale(BIS/BAS)(Carver and White,1994).The tag effect was positively correlated with the experience-seeking subscale of the SSS(p=0.026)and inversely correlated with the reward-responsiveness subscale of the BIS/BAS scales (p<0.005).Repeated-measures ANOVA of reaction times(RTs)as a func-tion of option value(lower,similar,or higher relative to the refer-ence option;see Experimental Procedures and Figure2C)did not show a main effect of condition(p=0.712)or a condition 3value interaction(p=0.220),but revealed a main effect of value(F(1.8,53.9)=16.740,p<0.001).Post hoc comparisons revealed faster RTs for higher-valued options relative to similarly (p=0.002)or lower valued options(p<0.001)but no difference between lower and similarly valued options(p=0.081).FMRI DataFMRI data were modeled using the general linear model(GLM) as implemented in SPM5.Subjective value of each decision option was calculated by multiplying the objective amount of each delayed reward with the discount fraction estimated behaviorally based on the choices during scanning,and included as a parametric regressor in the GLM.Note that discount rates were estimated separately for the control and episodic conditions(see above and Figure2),and we thus used condition-specific k-parameters for calculation of the subjective value regressor.Additional parametric regressors for inverse delay-to-reward and absolute reward magnitude, orthogonalized with respect to subjective value,were included in theGLM.Figure2.Behavioral Data from Experiment1Shown are experimentally derived discount func-tions from the fMRI session for four exemplaryparticipants(A),correlation with imagery scores(B),and reaction times(RTs)(C).(A)Hyperbolicfunctions werefit to the indifference points sepa-rately for the control(dashed lines)and episodic(solid lines,filled circles)conditions,and thebest-fitting k-parameters(discount rates)and R2values are shown for each subject.The log-trans-formed difference between discount rates wastaken as a measure of the effect of the episodictags on choice preferences.(B)Robust regressionrevealed an association between log-differences indiscount rates and imagery scores obtained frompostscan ratings(see text).(C)RTs were signifi-cantly modulated by option value(main effectvalue p<0.001)with faster responses in trialswith a value of the delayed reward higher thanthe20V reference amount.Note that althoughseven delays were used for each condition,somedata points are missing,e.g.,onlyfive delay indif-ference points for the episodic condition areplotted for sub20.This indicates that,for the twolongest delays,this subject never chose the de-layed reward.***p<0.005.Error bars=SEM.Neuron Episodic Modulation of Delay Discounting140Neuron66,138–148,April15,2010ª2010Elsevier Inc.Episodic Tags Activate the Future Thinking NetworkWe first analyzed differences in the condition regressors without parametric pared to those of the control condi-tion,BOLD responses to the presentation of the delayed reward in the episodic condition yielded highly significant activations (corrected for whole-brain volume)in an extensive network of brain regions previously implicated in episodic future thinking (Addis et al.,2007;Schacter et al.,2007;Szpunar et al.,2007)(see Figure 3and Table S2),including retrosplenial cortex (RSC)/PCC (peak MNI coordinates:À6,À54,14,peak z value =6.26),left lateral parietal cortex (LPC,À44,À66,32,z value =5.35),and vmPFC (À8,34,À12,z value =5.50).Distributed Neural Coding of Subjective ValueWe then replicated previous findings (Kable and Glimcher,2007;Kable and Glimcher,2010;Peters and Bu¨chel,2009)using a conjunction analysis (Nichols et al.,2005)searching for regions showing a positive correlation between the height of the BOLD response and subjective value in the control and episodic condi-tions in a parametric analysis (Figure 4A and Table S3).Note that this is a conservative analysis that requires that a given voxel exceed the statistical threshold in both contrasts separately.This analysis revealed clusters in the lateral orbitofrontal cortex (OFC,À36,50,À10,z value =4.50)and central OFC (À18,12,À14,z value =4.05),bilateral VS (right:10,8,0,z value =4.22;left:À10,8,À6,z value =3.51),mPFC (6,26,16,z value =3.72),and PCC (À2,À28,24,z value =4.09),representing subjective (discounted)value in both conditions.We next analyzed the neural tag effect,i.e.,regions in which the subjective value correlation was greater for the episodic condi-tion as compared with the control condition (Figure 4B and Table S4).This analysis revealed clusters in the left LPC (À66,À42,32,z value =4.96,),ACC (À2,16,36,z value =4.76),left dorsolateral prefrontal cortex (DLPFC,À38,36,36,z value =4.81),and right amygdala (24,2,À24,z value =3.75).Finally,we performed a triple-conjunction analysis,testing for regions that were correlated with subjective value in both conditions,but in which the value correlation increased in the episodic condition.Only left LPC showed this pattern (À66,À42,30,z value =3.55,see Figure 4C and Table S5),the same region that we previously identified as delay-specific in valuation (Petersand Bu¨chel,2009).There were no regions in which the subjective value correlation was greater in the control condition when compared with the episodic condition at p <0.001uncorrected.ACC Valuation Signals and Functional Connectivity Predict Interindividual Differences in Discount Function ShiftsWe next correlated differences in the neural tag effect with inter-individual differences in the size of the behavioral tag effect.To this end,we performed a simple regression analysis in SPM5on the single-subject contrast images of the neural tag effect (i.e.,subjective value correlation episodic >control)using the behavioral tag effect [log(k control )–log(k episodic )]as an explana-tory variable.This analysis revealed clusters in the bilateral ACC (right:18,34,18,z value =3.95,p =0.021corrected,left:À20,34,20,z value =3.52,Figure 5,see Table S6for a complete list).Coronal sections (Figure 5C)clearly show that both ACC clusters are located in gray matter of the cingulate sulcus.Because ACC-limbic interactions have previously been impli-cated in the control of choice behavior (Floresco and Ghods-Sharifi,2007;Roiser et al.,2009),we next analyzed functional coupling with the right ACC from the above regression contrast (coordinates 18,34,18,see Figure 6A)using a psychophysiolog-ical interaction analysis (PPI)(Friston et al.,1997).Note that this analysis was conducted on a separate first-level GLM in which control and episodic trials were modeled as 10s miniblocks (see Experimental Procedures for details).We first identified regions in which coupling with the ACC changed in the episodic condition compared with the control condition (see Table S7)and then performed a simple regression analysis on these coupling parameters using the behavioral tag effect as an explanatory variable.The tag effect was associated with increased coupling between ACC and hippocampus (À32,À18,À16,z value =3.18,p =0.031corrected,Figure 6B)and ACC and left amygdala (À26,À4,À26,z value =2.95,p =0.051corrected,Figure 6B,see Table S8for a complete list of activa-tions).The same regression analysis in a second PPI with the seed voxel placed in the contralateral ACC region from the same regression contrast (À20,34,22,see above)yielded qual-itatively similar,though subthreshold,results in these same structures (hippocampus:À28,À32,À6,z value =1.96,amyg-dala:À28,À6,À16,z value =1.97).Experiment 2We conducted an additional behavioral experiment to address a number of alternative explanations for the observed effects of tags on choice behavior.First,it could be argued thatepisodicFigure 3.Categorical Effect of Episodic Tags on Brain ActivityGreater activity in lateral parietal cortex (left)and posterior cingulate/retrosplenial and ventro-medial prefrontal cortex (right)was observed in the episodic condition compared with the control condition.p <0.05,FWE-corrected for whole-brain volume.NeuronEpisodic Modulation of Delay DiscountingNeuron 66,138–148,April 15,2010ª2010Elsevier Inc.141tags increase subjective certainty that a reward would be forth-coming.In Experiment 2,we therefore collected postscan ratings of reward confidence.Second,it could be argued that events,always being associated with a particular date,may have shifted temporal focus from delay-based to more date-based processing.This would represent a potential confound,because date-associated rewards are discounted less than delay-associated rewards (Read et al.,2005).We therefore now collected postscan ratings of temporal focus (date-based versus delay-based).Finally,Experiment 1left open the question of whether the tag effect depends on the temporal specificity of the episodic cues.We therefore introduced an additional exper-imental condition that involved the presentation of subject-specific temporally unspecific future event cues.These tags (henceforth referred to as unspecific tags)were obtained by asking subjects to imagine events that could realistically happen to them in the next couple of months,but that were not directly tied to a particular point in time (see Experimental Procedures ).Episodic Imagery,Not Temporal Specificity,Reward Confidence,or Temporal Focus,Predicts the Size of the Tag EffectIn total,data from 16participants (9female)are included.Anal-ysis of pretest ratings confirmed that temporally unspecific and specific tags were matched in terms of personal relevance,arousal,valence,and preexisting associations (all p >0.15).Choice preferences were again well described by hyperbolic functions (median R 2control =0.84,unspecific =0.81,specific =0.80).We replicated the parametric tag effect (i.e.,increasing effect of tags on discount rates with increasing posttest imagery scores)in this independent sample for both temporally specific (p =0.047,Figure 7A)and temporally unspecific (p =0.022,Figure 7A)tags,showing that the effect depends on future thinking,rather than being specifically tied to the temporal spec-ificity of the event cues.Following testing,subjects rated how certain they were that a particular reward would actually be forth-coming.Overall,confidence in the payment procedure washighFigure 4.Neural Representation of Subjective Value (Parametric Analysis)(A)Regions in which the correlation with subjective value (parametric analysis)was significant in both the control and the episodic conditions (conjunction analysis)included central and lateral orbitofrontal cortex (OFC),bilateral ventral striatum (VS),medial prefrontal cortex (mPFC),and posterior cingulate cortex(PCC),replicating previous studies (Kable and Glimcher,2007;Peters and Bu¨chel,2009).(B)Regions in which the subjective value correlation was greater for the episodic compared with the control condition included lateral parietal cortex (LPC),ante-rior cingulate cortex (ACC),dorsolateral prefrontal cortex (DLPFC),and the right amygdala (Amy).(C)A conjunction analysis revealed that only LPC activity was positively correlated with subjective value in both conditions,but showed a greater regression slope in the episodic condition.No regions showed a better correlation with subjective value in the control condition.Error bars =SEM.All peaks are significant at p <0.001,uncorrected;(A)and (B)are thresholded at p <0.001uncorrected and (C)is thresholded at p <0.005,uncorrected for display purposes.NeuronEpisodic Modulation of Delay Discounting142Neuron 66,138–148,April 15,2010ª2010Elsevier Inc.(Figure 7B),and neither unspecific nor specific tags altered these subjective certainty estimates (one-way ANOVA:F (2,45)=0.113,p =0.894).Subjects also rated their temporal focus as either delay-based or date-based (see Experimental Procedures ),i.e.,whether they based their decisions on the delay-to-reward that was actually displayed,or whether they attempted to convert delays into the corresponding dates and then made their choices based on these dates.There was no overall significant effect of condition on temporal focus (one-way ANOVA:F (2,45)=1.485,p =0.237,Figure 7C),but a direct comparison between the control and the temporally specific condition showed a significant difference (t (15)=3.18,p =0.006).We there-fore correlated the differences in temporal focus ratings between conditions (control:unspecific and control:specific)with the respective tag effects (Figure 7D).There were no correlations (unspecific:p =0.71,specific:p =0.94),suggesting that the observed differences in discounting cannot be attributed to differences in temporal focus.High-Imagery,but Not Low-Imagery,Subjects Adjust Their Discount Function in an Episodic ContextFor a final analysis,we pooled the samples of Experiments 1and 2(n =46subjects in total),using only the temporally specific tag data from Experiment 2.We performed a median split into low-and high-imagery participants according to posttest imagery scores (low-imagery subjects:n =23[15/8Exp1/Exp2],imagery range =1.5–3.4,high-imagery subjects:n =23[15/8Exp1/Exp2],imagery range =3.5–5).The tag effect was significantly greater than 0in the high-imagery group (t (22)=2.6,p =0.0085,see Figure 7D),where subjects reduced their discount rate by onaverage 16%in the presence of episodic tags.In the low-imagery group,on the other hand,the tag effect was not different from zero (t (22)=0.573,p =0.286),yielding a significant group difference (t (44)=2.40,p =0.011).DISCUSSIONWe investigated the interactions between episodic future thought and intertemporal decision-making using behavioral testing and fMRI.Experiment 1shows that reward delay dis-counting is modulated by episodic future event cues,and the extent of this modulation is predicted by the degree of sponta-neous episodic imagery during decision-making,an effect that we replicated in Experiment 2(episodic tag effect).The neuroi-maging data (Experiment 1)highlight two mechanisms that support this effect:(1)valuation signals in the lateral ACC and (2)neural coupling between ACC and hippocampus/amygdala,both predicting the size of the tag effect.The size of the tag effect was directly related to posttest imagery scores,strongly suggesting that future thinking signifi-cantly contributed to this effect.Pooling subjects across both experiments revealed that high-imagery subjects reduced their discount rate by on average 16%in the episodic condition,whereas low-imagery subjects did not.Experiment 2addressed a number of alternative accounts for this effect.First,reward confidence was comparable for all conditions,arguing against the possibility that the tags may have somehow altered subjec-tive certainty that a reward would be forthcoming.Second,differences in temporal focus between conditions(date-basedFigure 5.Correlation between the Neural and Behavioral Tag Effect(A)Glass brain and (B and C)anatomical projection of the correlation between the neural tag effect (subjective value correlation episodic >control)and the behav-ioral tag effect (log difference between discount rates)in the bilateral ACC (p =0.021,FWE-corrected across an anatomical mask of bilateral ACC).(C)Coronal sections of the same contrast at a liberal threshold of p <0.01show that both left and right ACC clusters encompass gray matter of the cingulate gyrus.(D)Scatter-plot depicting the linear relationship between the neural and the behavioral tag effect in the right ACC.(A)and (B)are thresholded at p <0.001with 10contiguous voxels,whereas (C)is thresholded at p <0.01with 10contiguousvoxels.Figure 6.Results of the Psychophysiolog-ical Interaction Analysis(A)The seed for the psychophysiological interac-tion (PPI)analysis was placed in the right ACC (18,34,18).(B)The tag effect was associated with increased ACC-hippocampal coupling (p =0.031,corrected across bilateral hippocampus)and ACC-amyg-dala coupling (p =0.051,corrected across bilateral amygdala).Maps are thresholded at p <0.005,uncorrected for display purposes and projected onto the mean structural scan of all participants;HC,hippocampus;Amy,Amygdala;rACC,right anterior cingulate cortex.NeuronEpisodic Modulation of Delay DiscountingNeuron 66,138–148,April 15,2010ª2010Elsevier Inc.143。
法布里珀罗基模共振英文
法布里珀罗基模共振英文The Fabryperot ResonanceOptics, the study of light and its properties, has been a subject of fascination for scientists and researchers for centuries. One of the fundamental phenomena in optics is the Fabry-Perot resonance, named after the French physicists Charles Fabry and Alfred Perot, who first described it in the late 19th century. This resonance effect has numerous applications in various fields, ranging from telecommunications to quantum physics, and its understanding is crucial in the development of advanced optical technologies.The Fabry-Perot resonance occurs when light is reflected multiple times between two parallel, partially reflective surfaces, known as mirrors. This creates a standing wave pattern within the cavity formed by the mirrors, where the light waves interfere constructively and destructively to produce a series of sharp peaks and valleys in the transmitted and reflected light intensity. The specific wavelengths at which the constructive interference occurs are known as the resonant wavelengths of the Fabry-Perot cavity.The resonant wavelengths of a Fabry-Perot cavity are determined bythe distance between the mirrors, the refractive index of the material within the cavity, and the wavelength of the incident light. When the optical path length, which is the product of the refractive index and the physical distance between the mirrors, is an integer multiple of the wavelength of the incident light, the light waves interfere constructively, resulting in a high-intensity transmission through the cavity. Conversely, when the optical path length is not an integer multiple of the wavelength, the light waves interfere destructively, leading to a low-intensity transmission.The sharpness of the resonant peaks in a Fabry-Perot cavity is determined by the reflectivity of the mirrors. Highly reflective mirrors result in a higher finesse, which is a measure of the ratio of the spacing between the resonant peaks to their width. This high finesse allows for the creation of narrow-linewidth, high-resolution optical filters and laser cavities, which are essential components in various optical systems.One of the key applications of the Fabry-Perot resonance is in the field of optical telecommunications. Fiber-optic communication systems often utilize Fabry-Perot filters to select specific wavelength channels for data transmission, enabling the efficient use of the available bandwidth in fiber-optic networks. These filters can be tuned by adjusting the mirror separation or the refractive index of the cavity, allowing for dynamic wavelength selection andreconfiguration of the communication system.Another important application of the Fabry-Perot resonance is in the field of laser technology. Fabry-Perot cavities are commonly used as the optical resonator in various types of lasers, providing the necessary feedback to sustain the lasing process. The high finesse of the Fabry-Perot cavity allows for the generation of highly monochromatic and coherent light, which is crucial for applications such as spectroscopy, interferometry, and precision metrology.In the realm of quantum physics, the Fabry-Perot resonance plays a crucial role in the study of cavity quantum electrodynamics (cQED). In cQED, atoms or other quantum systems are placed inside a Fabry-Perot cavity, where the strong interaction between the atoms and the confined electromagnetic field can lead to the observation of fascinating quantum phenomena, such as the Purcell effect, vacuum Rabi oscillations, and the generation of nonclassical states of light.Furthermore, the Fabry-Perot resonance has found applications in the field of optical sensing, where it is used to detect small changes in physical parameters, such as displacement, pressure, or temperature. The high sensitivity and stability of Fabry-Perot interferometers make them valuable tools in various sensing and measurement applications, ranging from seismic monitoring to the detection of gravitational waves.The Fabry-Perot resonance is a fundamental concept in optics that has enabled the development of numerous advanced optical technologies. Its versatility and importance in various fields of science and engineering have made it a subject of continuous research and innovation. As the field of optics continues to advance, the Fabry-Perot resonance will undoubtedly play an increasingly crucial role in shaping the future of optical systems and applications.。