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【深呼吸测试和5分钟短期记录中的心率变异性（HRV）：在343位受试者中，耳光体积描记法与ECG测量值一致。】
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DOI：10.1007/s00421-016-3401-3
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BACKGROUND & AIMS: PURPOSE:We analyzed heart rate variability (HRV) taken by ECG and photoplethysmography (PPG) to assess their agreement. We also analyzed the sensitivity and specificity of PPG to identify subjects with low HRV as an example of its potential use for clinical applications. METHODS:The HRV parameters: mean heart rate (HR), amplitude, and ratio of heart rate oscillation (E-I difference, E/I ratio), RMSSD, SDNN, and Power LF, were measured during 1-min deep breathing tests (DBT) in 343 individuals, followed by a 5-min short-term HRV (s-HRV), where the HRV parameters: HR, SD1, SD2, SDNN, Stress Index, Power HF, Power LF, Power VLF, and Total Power, were determined as well. Parameters were compared through correlation analysis and agreement analysis by Bland-Altman plots. RESULTS:PPG derived parameters HR and SD2 in s-HRV showed better agreement than SD1, Power HF, and stress index, whereas in DBT HR, E/I ratio and SDNN were superior to Power LF and RMSSD. DBT yielded stronger agreement than s-HRV. A slight overestimation of PPG HRV over HCG HRV was found. HR, Total Power, and SD2 in the s-HRV, HR, Power LF, and SDNN in the DBT showed high sensitivity and specificity to detect individuals with poor HRV. Cutoff percentiles are given for the future development of PPG-based devices. CONCLUSION:HRV measured by PPG shows good agreement with ECG HRV when appropriate parameters are used, and PPG-based devices can be employed as an easy screening tool to detect individuals with poor HRV, especially in the 1-min DBT test.背景与目标： 目的：我们分析了心电图和光电容积描记法（PPG）测得的心率变异性（HRV），以评估其一致性。我们还分析了PPG的敏感性和特异性，以鉴定低HRV的受试者，作为其在临床应用中潜在用途的一个例子。
方法：在1分钟的深呼吸测试（DBT）中测量了HRV参数：平均心率（HR），幅度和心率振荡比（EI差，E / I比），RMSSD，SDNN和Power LF ）中的343个人，然后是5分钟的短期HRV（s-HRV），其中的HRV参数为：HR，SD1，SD2，SDNN，压力指数，功率HF，功率LF，功率VLF和总功率，也被确定。通过Bland-Altman图通过相关分析和一致性分析比较参数。
结果：s-HRV中PPG导出的参数HR和SD2显示出比SD1，Power HF和应力指数更好的一致性，而在DBT HR中，E / I比和SDNN优于Power LF和RMSSD。 DBT产生了比s-HRV更强的一致性。发现PPG HRV略高于HCG HRV。 s-HRV中的HR，总功率和SD2，DBT中的HR，功率LF和SDNN对检测HRV较差的个体显示出高灵敏度和特异性。为基于PPG的设备的未来开发提供了截止百分位数。
结论：当使用适当的参数时，PPG测量的HRV与ECG HRV显示出良好的一致性，并且基于PPG的设备可以用作检测HRV较差的个体的简便筛查工具，尤其是在1分钟DBT测试中。 -
2 An optimization study of the ultra-short period for HRV analysis at rest and post-exercise.
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【运动和运动后HRV分析的超短时间优化研究。】
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DOI：10.1016/j.jelectrocard.2020.10.002
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BACKGROUND & AIMS: BACKGROUND:Ultra-short-term heart rate variability (HRV) analysis (< 5 min) has been extensively growing in the field of exercise performance for autonomic assessment. However, the validation of ultra-short-term HRV was unclear in the recovery period of exercise. This study aimed to elucidate the agreement between ultra-short-term HRV (0-30 s, 0-1 min, 0-2 min, 0-3 min, 0-4 min) and standard short-term HRV (5 min) and to explore the optimal recording duration under rest and post-exercise conditions. METHODS:69 participants were recruited to perform physical exercise on a treadmill with an intensity of 6 km/h, 9 km/h and 12 km/h, independently. The standard deviation of RR-interval (SDNN) and root mean square of successive differences of RR-intervals (RMSSD) were calculated by using ultra-short periods and standard period at rest condition (Pre-E) and three post-exercise trials, i.e., Post-E1, Post-E2 and Post-E3, respectively. One-way ANOVA with repeated-measures and Cohen's d statistics were conducted, and Bland-Altman analysis and interclass correlation coefficients (ICC) were used to assess the levels of agreement. RESULTS:For SDNN and RMSSD, the results of agreement analysis at rest condition were different from those at post-exercise. At Pre-E, SDNN and RMSSD were reliable for ultra-short-term HRV analysis at all ultra-short periods, i.e., 0-30 s, 0-1 min, 0-2 min, 0-3 min and 0-4 min, with most ICCs greater than 0.9 and Cohen's d showing trivial differences (Cohen's d = 0.024-0.117). However, at post-exercise, SDNN0-30s, SDNN0-1min, RMSSD0-30s and RMSSD0-1min showed significant differences with SDNN5min and RMSSD5min, respectively (p < 0.01), and the ICCs was not perfect (< 0.9). HRV analysis with time duration longer than 2 min showed nearly perfect reliability in all post-exercise trials, with trivial differences (Cohen's d = -0.003-0.110) and perfect ICCs (ICCs = 0.916-0.998). Furthermore, the limits of the agreement became tighter as the period duration increased in Bland-Altman plots. CONCLUSIONS:This study demonstrated that ultra-short-term HRV analysis was a good surrogate of standard HRV time-domain measures to reflect the autonomic regulation at rest and post-exercise. Specifically, ultra-short-term HRV0-30s or HRV0-1min was recommended at rest condition, whereas longer than 2 min recording period was reliable to obtain SDNN and RMSSD for the accuracy of HRV analysis.背景与目标： 背景：超短期心率变异性（HRV）分析（<5分钟）在用于自主评估的运动表现领域已得到广泛发展。但是，在运动恢复期间，超短期HRV的有效性尚不清楚。本研究旨在阐明超短期HRV（0-30s，0-1min，0-2min，0-3min，0-4min）与标准短期HRV（5min）之间的一致性并探索在休息和运动后条件下的最佳录音时间。
方法：招募了69名参与者，分别在6km / h，9km / h和12km / h的跑步机上进行体育锻炼。 RR间隔的标准偏差（SDNN）和RR间隔的连续差的均方根（RMSSD）是通过使用超短周期和静止状态下的标准周期（Pre-E）以及三个运动后试验来计算的，即分别为Post-E1，Post-E2和Post-E3。进行了带有重复测量的单向方差分析和Cohen d统计，并使用了Bland-Altman分析和类间相关系数（ICC）来评估一致性水平。
结果：对于SDNN和RMSSD，静止状态下的协议分析结果与运动后的结果不同。在Pre-E上，SDNN和RMSSD在所有超短周期（即0-30s，0-1min，0-2min，0-3min和0-4）的超短期HRV分析中都是可靠的min，大多数ICC大于0.9，Cohen d表现出微不足道的差异（Cohen d = 0.024-0.117）。然而，运动后，SDNN0-30s，SDNN0-1min，RMSSD0-30s和RMSSD0-1min分别与SDNN5min和RMSSD5min表现出显着差异（p <0.01），而ICC并不完美（<0.9）。持续时间超过2分钟的HRV分析显示，在所有运动后试验中，可靠性几乎都是完美的，差异不大（Cohen d = -0.003-0.110）和完美的ICC（ICC = 0.916-0.998）。此外，随着Bland-Altman地块中时间段的增加，协议的限制越来越严格。
结论：这项研究表明，超短期HRV分析是标准HRV时域测量的良好替代，可反映静息和运动后的自主神经调节。具体而言，建议在静止状态下使用超短期HRV0-30s或HRV0-1min，而对于HRV分析的准确性而言，超过2分钟的记录时间对于获得SDNN和RMSSD是可靠的。 -
【在乘用车模拟驾驶过程中发生碰撞威胁时，心率变异性（HRV）和肌肉系统活动（EMG）。】
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DOI：10.2478/s13382-013-0148-5
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BACKGROUND & AIMS: OBJECTIVES:The aim of the study was to verify whether simultaneous responses from the muscular and circulatory system occur in the driver's body under simulated conditions of a crash threat. MATERIALS AND METHODS:The study was carried out in a passenger car driving simulator. The crash was included in the driving test scenario developed in an urban setting. In the group of 22 young male subjects, two physiological signals - ECG and EMG were continuously recorded. The length of the RR interval in the ECG signal was assessed. A HRV analysis was performed in the time and frequency domains for 1-minute record segments at rest (seated position), during undisturbed driving as well as during and several minutes after the crash. For the left and right side muscles: m. trapezius (TR) and m. flexor digitorum superficialis (FDS), the EMG signal amplitude was determined. The percentage of maximal voluntary contraction (MVC) was compared during driving and during the crash. RESULTS:As for the ECG signal, it was found that in most of the drivers changes occurred in the parameter values reflecting HRV in the time domain. Significant changes were noted in the mean length of RR intervals (mRR). As for the EMG signal, the changes in the amplitude concerned the signal recorded from the FDS muscle. The changes in ECG and EMG were simultaneous in half of the cases. CONCLUSION:Such parameters as mRR (ECG signal) and FDS-L amplitude (EMG signal) were the responses to accident risk. Under simulated conditions, responses from the circulatory and musculoskeletal systems are not always simultaneous. The results indicate that a more complete driver's response to a crash in road traffic is obtained based on parallel recording of two physiological signals (ECG and EMG).背景与目标： 目的：该研究的目的是验证在模拟碰撞危险条件下，驾驶员体内是否同时发生了肌肉和循环系统的同时反应。
材料与方法：该研究在乘用车驾驶模拟器中进行。该事故包括在城市环境中开发的驾驶测试方案中。在22名年轻男性受试者的组中，连续记录了两种生理信号-ECG和EMG。评估心电图信号中RR间隔的长度。在时域和频域中，在静止（坐姿），无扰动驾驶以及碰撞过程中和碰撞后的几分钟内，对时长为1分钟的记录段进行了HRV分析。对于左侧和右侧肌肉：m。斜方肌（TR）和m。浅指屈肌（FDS），确定肌电信号幅度。在驾驶过程中和碰撞期间比较了最大自愿收缩（MVC）的百分比。
结果：关于ECG信号，发现在大多数驱动程序中，时域中反映HRV的参数值发生了变化。注意到RR间隔的平均长度（mRR）有显着变化。对于EMG信号，振幅的变化与从FDS肌肉记录的信号有关。在一半的病例中，心电图和肌电图的变化是同时发生的。
结论：mRR（ECG信号）和FDS-L振幅（EMG信号）等参数是对事故风险的响应。在模拟条件下，循环系统和肌肉骨骼系统的响应并不总是同时发生的。结果表明，基于两个生理信号（ECG和EMG）的并行记录，可以获得驾驶员对道路交通事故更完整的响应。 -
4 Unconstrained Estimation of HRV Indices After Removing Respiratory Influences From Heart Rate.
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【从心率中去除呼吸影响后，HRV指标的无限制估计。】
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DOI：10.1109/JBHI.2018.2884644
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BACKGROUND & AIMS: OBJECTIVE:This paper proposes an approach to better estimate the sympathovagal balance (SB) and the respiratory sinus arrhythmia (RSA) after separating respiratory influences from the heart rate (HR). METHODS:The separation is performed using orthogonal subspace projections and the approach is first tested using simulated HR and respiratory signals with different spectral properties. Then, RSA and SB are estimated during autonomic blockade and stress using the proposed approach and the classical heart rate variability (HRV) analysis. Both real- and ECG-derived respiration (EDR) are used and the reliability of the EDR is evaluated. RESULTS:Mean absolute percentage errors lower than [Formula: see text] were obtained after removing previously known respiratory signals from simulated HR. The proposed indices were able to improve the quantification of SB during autonomic withdrawal. In the stress data, differences ( ) among relaxed and stressful phases were found with the proposed approach, using both the real respiration and the EDR, but they disappeared when using the classical HRV. CONCLUSION:A better assessment of the autonomic nervous system' response to pharmacological blockade and stress can be achieved after removing respiratory influences from HR, and this can be done using either the real respiration or the EDR. SIGNIFICANCE:This work can be used to better identify vagal withdrawal and increased sympathetic activation when the classical HRV analysis fails due to the respiratory influences on HR. Furthermore, it can be computed using only the ECG, which is an advantage when developing wearable systems with limited number of sensors.背景与目标： 目的：本文提出了一种在将呼吸影响与心率（HR）分开后，更好地估计交感迷走平衡（SB）和呼吸窦性心律不齐（RSA）的方法。
方法：使用正交子空间投影进行分离，并且首先使用模拟的HR和具有不同光谱特性的呼吸信号测试该方法。然后，使用拟议的方法和经典心率变异性（HRV）分析，在自主神经阻滞和压力期间估算RSA和SB。真实呼吸和心电衍生呼吸（EDR）均被使用，并且评估了EDR的可靠性。
结果：从模拟心率中去除先前已知的呼吸信号后，获得的平均绝对百分比误差低于[公式：参见文本]。拟议的指标能够在自主停药期间改善SB的定量。在压力数据中，使用实际呼吸和EDR，通过所提出的方法发现了放松阶段和压力阶段之间的差异（），但是当使用经典HRV时，它们消失了。
结论：去除HR的呼吸影响后，可以更好地评估植物神经系统对药理学阻断和压力的反应，这可以通过实际呼吸或EDR来完成。
意义：当经典的HRV分析由于呼吸对HR的影响而失败时，这项工作可用于更好地识别迷走神经退缩和增加的交感神经激活。此外，可以仅使用ECG进行计算，这在开发传感器数量有限的可穿戴系统时是一个优势。 -
【呼吸对HRV测量的影响：对运动员的纵向随访的影响。】
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DOI：10.1080/17461391.2013.767947
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BACKGROUND & AIMS: :The purpose of the present work was to compare daily variations of heart rate variability (HRV) parameters between controlled breathing (CB) and spontaneous breathing (SB) sessions during a longitudinal follow-up of athletes. HRV measurements were performed daily on 10 healthy male runners for 21 consecutive days. The signals were recorded during two successive randomised 5-minutes sessions. One session was performed in CB and the other in SB. The results showed significant differences between the two respiration methods in the temporal, nonlinear and frequency domains. However, significant correlations were observed between CB and SB (higher than 0.70 for RMSSD and SD1), demonstrating that during a longitudinal follow-up, these markers provide the same HRV variations regardless of breathing pattern. By contrast, independent day-to-day variations were observed with HF and LF/HF frequency markers, indicating no significant relationship between SB and CB data over time. Therefore, we consider that SB and CB may be used for HRV longitudinal follow-ups only for temporal and nonlinear markers. Indeed, the same daily increases and decreases were observed whatever the breathing method employed. Conversely, frequency markers did not provide the same variations between SB and CB and we propose that these indicators are not reliable enough to be used for day-to-day HRV monitoring.背景与目标： ：本研究的目的是在运动员的纵向随访过程中比较控制呼吸（CB）和自发呼吸（SB）期间心率变异性（HRV）参数的每日变化。每天对10名健康的男性跑步者进行连续21天的HRV测量。在两个连续的随机5分钟会话中记录信号。一次会议在CB中进行，另一次在SB中进行。结果显示两种呼吸方法在时域，非线性和频域上存在显着差异。但是，在CB和SB之间观察到显着相关性（RMSSD和SD1高于0.70），表明在纵向随访期间，这些标志物提供了相同的HRV变化，而与呼吸方式无关。相比之下，使用HF和LF / HF频率标记观察到了独立的每日变化，表明SB和CB数据之间没有随时间的显着关系。因此，我们认为SB和CB仅可用于时间和非线性标记物用于HRV纵向随访。实际上，无论采用哪种呼吸方法，每天都观察到相同的每日增加和减少。相反，频率标记在SB和CB之间没有提供相同的变化，我们建议这些指标不够可靠，无法用于日常HRV监测。
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6 Effects of Walking Training with Restricted Blood Flow on HR and HRV Kinetics and HRV Recovery.
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【限制血流的步行训练对HR和HRV动力学及HRV恢复的影响。】
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DOI：10.1055/a-0942-7479
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BACKGROUND & AIMS: :The aim of this study was to investigate the effects of walking training with and without blood flow restriction (BFR) on heart rate (HR) and heart rate variability (HRV) kinetics and HRV recovery. Twenty-one men (53.5±3.2 years; 82.4±13.5 kg; 168.5±7.2 cm) were randomly assigned to two training groups: walk training group with (BFR-W; n=11) and without (NOR-W; n=10) BFR. Before and after training, all subjects underwent body composition evaluation, incremental test, and one constant load test. Walking training was performed 3 times/week, during 6 weeks. Each session was composed by 5 sets of 3-min walking and 1-min rest between the sets. All parameters of HR on- and off-kinetics and RMSSD15 0 parameter of HRV on-kinetics were improved for BFR-W group after training (p<0.05), with an interaction effect for HR on-kinetics parameters and RMSSD15 0 parameter (p<0.05). Also, parameters of time and frequency domain of HRV recovery were also improved in BFR-W after training (p<0.05), with no interaction effect (p>0.05). Additionally, in BFR-W group, RMSSD60s values were improved in some moments after training (p<0.05). Therefore, this study demonstrates that a 6-week walking training with BFR improved cardiac autonomic responses on the onset and recovery of exercise.背景与目标： ：这项研究的目的是研究有无血流限制（BFR）的步行训练对心率（HR）和心率变异性（HRV）动力学及HRV恢复的影响。将21名男性（53.5±3.2岁; 82.4±13.5 kg; 168.5±7.2 cm）随机分为两个训练组：有（BFR-W; n = 11）和没有（NOR-W; n = 10）BFR。训练前后，所有受试者均接受身体成分评估，增量测试和一项恒定负荷测试。在6周内，每周进行3次步行训练。每个阶段由5组3分钟的步行和1分钟的休息时间组成。训练后BFR-W组的HR动力学和非动力学的所有参数以及HRV动力学的RMSSD15 0参数均得到改善（p <0.05），并且HR动力学参数和RMSSD15 0参数（p <0.05）。此外，训练后的BFR-W中HRV恢复的时域和频域参数也得到了改善（p <0.05），没有相互作用（p> 0.05）。此外，在BFR-W组中，训练后的某些时候RMSSD60s值有所改善（p <0.05）。因此，这项研究表明，使用BFR进行的6周步行训练可改善运动开始和恢复时的心脏自主神经反应。 -
【阵发性心房颤动的预测：一种基于机器学习的方法，结合了特征向量和HRV信号专家分类的组合。】
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DOI：10.1016/j.cmpb.2018.07.014
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BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:Paroxysmal Atrial Fibrillation (PAF) is one of the most common major cardiac arrhythmia. Unless treated timely, PAF might transform into permanent Atrial Fibrillation leading to a high rate of morbidity and mortality. Therefore, increasing attention has been directed towards prediction of PAF, to enable early detection and prevent further progression of the disease. Notwithstanding the pharmacological and electrical treatments, a validated method to predict the onset of PAF is yet to be developed. We aim to address this issue through integrating classical and modern methods. METHODS:To increase the predictivity, we have made use of a combination of features extracted through linear, time-frequency, and nonlinear analyses performed on heart rate variability. We then apply a novel approach to local feature selection using meticulous methodologies, developed in our previous works, to reduce the dimensionality of the feature space. Subsequently, the Mixture of Experts classification is employed to ensure a precise decision-making on the output of different processes. In the current study, we analyzed 106 signals from 53 pairs of ECG recordings obtained from the standard database called Atrial Fibrillation Prediction Database (AFPDB). Each pair of data contains one 30-min ECG segment that ends just before the onset of PAF event and another 30-min ECG segment at least 45 min distant from the onset. RESULTS:Combining the features that are extracted using both classical and modern analyses was found to be significantly more effective in predicting the onset of PAF, compared to using either analyses independently. Also, the Mixture of Experts classification yielded more precise class discrimination than other well-known classifiers. The performance of the proposed method was evaluated using the Atrial Fibrillation Prediction Database (AFPDB) which led to sensitivity, specificity, and accuracy of 100%, 95.55%, and 98.21% respectively. CONCLUSION:Prediction of PAF has been a matter of clinical and theoretical importance. We demonstrated that utilising an optimized combination of - as opposed to being restricted to - linear, time-frequency, and nonlinear features, along with applying the Mixture of Experts, contribute greatly to an early detection of PAF, thus, the proposed method is shown to be superior to those mentioned in similar studies in the literature.背景与目标： 背景与目的：阵发性房颤（PAF）是最常见的严重心律不齐之一。除非及时治疗，PAF可能会转变为永久性房颤，从而导致高发病率和死亡率。因此，人们越来越关注PAF的预测，以能够及早发现并预防疾病的进一步发展。尽管进行了药理学和电学治疗，但仍未开发出验证有效的预测PAF发作的方法。我们旨在通过整合古典和现代方法来解决这个问题。
方法：为了提高可预测性，我们利用了通过对心率变异性进行线性，时频和非线性分析而提取的特征的组合。然后，我们使用在我们先前的工作中开发的细致方法，将新颖的方法应用于局部特征选择，以减少特征空间的维数。随后，采用专家混合分类，以确保对不同过程的输出做出准确的决策。在当前的研究中，我们分析了53对心电图记录中的106个信号，这些记录来自称为房颤预测数据库（AFPDB）的标准数据库。每对数据包含一个30分钟的ECG段，该段在PAF事件发作之前结束，另一个30分钟的ECG段在距发作至少45分钟的距离处结束。
结果：与单独使用任何一种分析相比，结合使用经典分析和现代分析所提取的特征，在预测PAF发作方面明显更有效。而且，专家混合分类比其他知名分类器产生了更精确的类区分。使用心房颤动预测数据库（AFPDB）对所提出方法的性能进行了评估，结果数据库的敏感性，特异性和准确性分别为100％，95.55％和98.21％。
结论：PAF的预测已成为临床和理论上的重要问题。我们证明，利用-而不是限于-线性，时频和非线性特征的优化组合，以及应用专家混合，对PAF的早期检测有很大贡献，因此，该方法被展示优于文献中类似研究中提到的那些。 -
【量化训练负荷的初步研究：HRV在训练实践中的使用。】
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DOI：10.1080/17461391.2015.1004373
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BACKGROUND & AIMS: :Recent laboratory studies have suggested that heart rate variability (HRV) may be an appropriate criterion for training load (TL) quantification. The aim of this study was to validate a novel HRV index that may be used to assess TL in field conditions. Eleven well-trained long-distance male runners performed four exercises of different duration and intensity. TL was evaluated using Foster and Banister methods. In addition, HRV measurements were performed 5 minutes before exercise and 5 and 30 minutes after exercise. We calculated HRV index (TLHRV) based on the ratio between HRV decrease during exercise and HRV increase during recovery. HRV decrease during exercise was strongly correlated with exercise intensity (R = -0.70; p < 0.01) but not with exercise duration or training volume. TLHRV index was correlated with Foster (R = 0.61; p = 0.01) and Banister (R = 0.57; p = 0.01) methods. This study confirms that HRV changes during exercise and recovery phase are affected by both intensity and physiological impact of the exercise. Since the TLHRV formula takes into account the disturbance and the return to homeostatic balance induced by exercise, this new method provides an objective and rational TL index. However, some simplification of the protocol measurement could be envisaged for field use.背景与目标： ：最近的实验室研究表明，心率变异性（HRV）可能是训练负荷（TL）量化的合适标准。这项研究的目的是验证一种新的HRV指数，该指数可用于评估田间条件下的TL。 11名训练有素的长跑男运动员进行了4次不同持续时间和强度的运动。使用Foster和Banister方法评估TL。另外，在运动前5分钟以及运动后5和30分钟进行HRV测量。我们根据运动过程中HRV下降与恢复过程中HRV上升之间的比率计算HRV指数（TLHRV）。运动期间HRV降低与运动强度密切相关（R = -0.70; p <0.01），但与运动时间或训练量无关。 TLHRV指数与Foster（R = 0.61; p = 0.01）和Banister（R = 0.57; p = 0.01）方法相关。这项研究证实，运动和恢复阶段的HRV变化受运动强度和生理影响的影响。由于TLHRV公式考虑了运动引起的干扰和稳态平衡的恢复，因此该新方法提供了客观合理的TL指数。但是，可以设想一些简化的协议测量以供现场使用。
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【2-甲氧基苯乙烯潘酮及其类似物的发现，总合成，HRV 3C蛋白酶抑制活性和构效关系。】
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DOI：10.1016/s0960-894x(01)00648-5
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BACKGROUND & AIMS: :2-Methoxystypandrone, a naphthoquinone, was isolated from a Chinese herb Polygonum cuspidatum by bioassay guided fractionation using HRV 3C-protease assay. It showed an IC(50) value of 4.6 microM and is moderately selective. A new 10-step, total synthesis of 2-methoxystypandrone was accomplished in 45% overall yield using a Diels-Alder approach. Several analogues of this compound were prepared. Isolation, synthesis and HRV 3C-protease structure-activity relationships of these compounds have been described.背景与目标： 通过使用HRV 3C蛋白酶测定法的生物测定指导分级分离，从中药虎杖中分离出2：2-甲氧基stypandrone（萘醌）。它显示的IC（50）值为4.6 microM，具有中等选择性。使用Diels-Alder方法，新的10步全合成2-甲氧基苯乙烯吡喃酮的总收率为45％。制备了该化合物的几种类似物。已经描述了这些化合物的分离，合成和HRV 3C-蛋白酶结构-活性关系。
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【筛查呼吸道样本以检测人类鼻病毒（HRV）和肠病毒：全面的VP4-VP2分型显示HRV种类C的高发生率和遗传多样性。】
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DOI：10.1128/JCM.00993-09
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BACKGROUND & AIMS: :Rhinovirus infections are the most common cause of viral illness in humans, and there is increasing evidence of their etiological role in severe acute respiratory tract infections (ARTIs). Human rhinoviruses (HRVs) are classified into two species, species A and B, which contain over 100 serotypes, and a recently discovered genetically heterogeneous third species (HRV species C). To investigate their diversity and population turnover, screening for the detection and the genetic characterization of HRV variants in diagnostic respiratory samples was performed by using nested primers for the efficient amplification of the VP4-VP2 region of HRV (and enterovirus) species and serotype identification. HRV species A, B, and C variants were detected in 14%, 1.8%, and 6.8%, respectively, of 456 diagnostic respiratory samples from 345 subjects (6 samples also contained enteroviruses), predominantly among children under age 10 years. HRV species A and B variants were remarkably heterogeneous, with 22 and 6 different serotypes, respectively, detected among 73 positive samples. Similarly, by using a pairwise distance threshold of 0.1, species C variants occurring worldwide were provisionally assigned to 47 different types, of which 15 were present among samples from Edinburgh, United Kingdom. There was a rapid turnover of variants, with only 5 of 43 serotypes detected during both sampling periods. By using divergence thresholds and phylogenetic analysis, several species A and C variants could provisionally be assigned to new types. An initial investigation of the clinical differences between rhinovirus species found HRV species C to be nearly twice as frequently associated with ARTIs than other rhinovirus species, which matches the frequencies of detection of respiratory syncytial virus. The study demonstrates the extraordinary genetic diversity of HRVs, their rapid population turnover, and their extensive involvement in childhood respiratory disease.背景与目标： 鼻病毒感染是人类最常见的病毒性疾病，越来越多的证据表明它们在严重的急性呼吸道感染（ARTIs）中起病因作用。人类鼻病毒（HRV）分为两种，分别为A和B，包含100多种血清型，以及最近发现的遗传上异源的第三种（HRV物种C）。为了研究它们的多样性和种群更新，使用嵌套引物对HRV（和肠病毒）物种的VP4-VP2区进行有效扩增和血清型鉴定，以筛查诊断性呼吸道样本中HRV变异的检测和遗传特征。在345个受试者的456个诊断性呼吸道样本中检出了HRV的A，B和C变种，分别为14％，1.8％和6.8％（6个样本还包含肠病毒），主要发生在10岁以下的儿童中。 HRV物种A和B变异非常异质，在73个阳性样本中分别检测到22和6种不同的血清型。同样，通过使用成对距离阈值0.1，全球范围内发生的C类变种被临时分配给47种不同类型，其中15种存在于英国爱丁堡的样本中。变异的快速转换，在两个采样期间仅检测到43种血清型中的5种。通过使用差异阈值和系统发育分析，可以将几种物种A和C变体临时分配给新类型。对鼻病毒种类之间临床差异的初步调查发现，HRV种类C与ARTIs的关联频率几乎是其他鼻病毒种类的两倍，这与检测呼吸道合胞病毒的频率相符。这项研究证明了HRV的非同寻常的遗传多样性，其快速的人口流动以及它们广泛参与了儿童呼吸道疾病。
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【假定的新型人类鼻病毒（HRV）物种C和B的完整编码序列表征和比较分析。】
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DOI：10.1186/1743-422X-8-5
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BACKGROUND & AIMS: BACKGROUND:Human Rhinoviruses (HRVs) are well recognized viral pathogens associated with acute respiratory tract illnesses (RTIs) abundant worldwide. Although recent studies have phylogenetically identified the new HRV species (HRV-C), data on molecular epidemiology, genetic diversity, and clinical manifestation have been limited. RESULT:To gain new insight into HRV genetic diversity, we determined the complete coding sequences of putative new members of HRV species C (HRV-CU072 with 1% prevalence) and HRV-B (HRV-CU211) identified from clinical specimens collected from pediatric patients diagnosed with a symptom of acute lower RTI. Complete coding sequence and phylogenetic analysis revealed that the HRV-CU072 strain shared a recent common ancestor with most closely related Chinese strain (N4). Comparative analysis at the protein level showed that HRV-CU072 might accumulate substitutional mutations in structural proteins, as well as nonstructural proteins 3C and 3 D. Comparative analysis of all available HRVs and HEVs indicated that HRV-C contains a relatively high G+C content and is more closely related to HEV-D. This might be correlated to their replication and capability to adapt to the high temperature environment of the human lower respiratory tract. We herein report an infrequently occurring intra-species recombination event in HRV-B species (HRV-CU211) with a crossing over having taken place at the boundary of VP2 and VP3 genes. Moreover, we observed phylogenetic compatibility in all HRV species and suggest that dynamic mechanisms for HRV evolution seem to be related to recombination events. These findings indicated that the elementary units shaping the genetic diversity of HRV-C could be found in the nonstructural 2A and 3D genes. CONCLUSION:This study provides information for understanding HRV genetic diversity and insight into the role of selection pressure and recombination mechanisms influencing HRV evolution.背景与目标： 背景：人类鼻病毒（HRV）是公认的与世界范围内大量急性呼吸道疾病（RTI）相关的病毒病原体。尽管最近的研究在系统发育上鉴定出了新的HRV种类（HRV-C），但有关分子流行病学，遗传多样性和临床表现的数据仍然有限。
结果：为了获得对HRV遗传多样性的新见解，我们确定了从儿科临床标本中鉴定出的HRV C类推定新成员（HRV-CU072，患病率1％）和HRV-B（HRV-CU211）的完整编码序列。被诊断患有急性下肢RTI症状的患者。完整的编码序列和系统发育分析表明，HRV-CU072菌株与最接近的中国菌株（N4）具有最近的共同祖先。在蛋白质水平上的比较分析表明，HRV-CU072可能会在结构蛋白以及非结构蛋白3C和3D中积累取代突变。对所有可用HRV和HEV的比较分析表明，HRV-C包含相对较高的GC含量，且与HEV-D密切相关。这可能与其复制和适应人类下呼吸道高温环境的能力有关。我们在此报告了在HRV-B物种（HRV-CU211）中很少发生的种内重组事件，并在VP2和VP3基因的边界发生了杂交。此外，我们观察到了所有HRV物种的系统发育相容性，并表明HRV进化的动力学机制似乎与重组事件有关。这些发现表明，可在非结构性2A和3D基因中找到影响HRV-C遗传多样性的基本单位。
结论：本研究为了解HRV遗传多样性提供信息，并深入了解选择压力和重组机制对HRV进化的影响。 -
【单管嵌套式定量PCR：一种用于检测逆转录病毒DNA的合理而灵敏的技术。应用于RERV-H / HRV-5并确认其兔来源。】
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DOI：10.1016/s0166-0934(03)00127-7
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BACKGROUND & AIMS: :It was reported earlier that a few patients suffering from non-Hodgkin's lymphoma had low amounts of DNA from the so-called fifth human exogenous retrovirus, HRV-5. A sensitive and rational method for large-scale screening for HRV-5 DNA was therefore developed. It is a single-tube nested quantitative PCR (stnQPCR), which uses two functionally isolated primer pairs and one probe target distinct from related endogenous retroviral sequences, yet encompassing known HRV-5 variation, allowing optimal use of sequence conservation. DNA from lymphoma, myeloma, and follicular dendritic cell lines was tested for HRV-5 positivity, as was DNA from whole blood of blood donors, non-Hodgkin's lymphoma and systemic lupus erythematosus patients, as well as DNA from lymph node biopsies of rheumatoid arthritis patients with lymphoma. One blood donor, one systemic lupus erythematosus patient, two previously known positive non-Hodgkin's lymphoma patients, and one rheumatoid arthritis lymphoma patient, came out positive. They had 24, 2, 148, 480 and 30 proviral copies per microg of DNA from PBMC or lymphoma tissue, respectively. During the completion of this work it was reported that HRV-5 is a rabbit endogenous retrovirus (RERV-H), and that HRV-5 positivity was due to presence of rabbit DNA. DNA from six RERV-H/HRV-5 positive samples was therefore retested. Three also contained rabbit mitochondrial DNA. A search for HRV-5 antibodies using synthetic peptides was negative in sera from three RERV-H/HRV-5 positive individuals, as well as in 144 other sera, according with a noninfectious origin of the RERV-H/HRV-5 DNA in human samples. A search for possible sources of rabbit DNA contamination was negative. Methods for prevention of PCR contamination were strictly adhered to. Three samples from RERV-H/HRV-5 positive individuals positive at the Uppsala laboratory were retested at one or two other laboratories, and all three were positive. Two other samples, which were positive in the Riga laboratory, were tested also in London and also found positive. One non-Hodgkin's lymphoma patient was RERV-H/HRV-5 positive in four consecutive samples, showing that positivity was a property of that patient. It is concluded that the stnQPCR developed to detect and quantify minute amounts of RERV-H/HRV-5 DNA is a principle which can be applied widely and HRV-5 is a RERV-H. Its presence in a few human blood samples could not be explained.背景与目标： ：早先有报道称，少数患有非霍奇金淋巴瘤的患者的所谓第五人类外源性逆转录病毒HRV-5 DNA含量低。因此，开发了一种用于大规模筛选HRV-5 DNA的灵敏而合理的方法。它是一种单管嵌套式定量PCR（stnQPCR），使用两个功能分离的引物对和一个与相关内源逆转录病毒序列不同的探针靶标，但包含已知的HRV-5变异，可以最佳地利用序列保守性。测试了来自淋巴瘤，骨髓瘤和滤泡树突状细胞系的DNA的HRV-5阳性，以及来自献血者，非霍奇金淋巴瘤和系统性红斑狼疮患者的全血的DNA，以及来自类风湿性关节炎的淋巴结活检的DNA淋巴瘤患者。一名献血者，一名系统性红斑狼疮患者，两名先前已知的阳性非霍奇金淋巴瘤患者和一名类风湿关节炎淋巴瘤患者呈阳性。每微克来自PBMC或淋巴瘤组织的DNA分别具有24、2、148、480和30个原病毒拷贝。在完成这项工作的过程中，据报道HRV-5是兔内源性逆转录病毒（RERV-H），并且HRV-5阳性是由于兔DNA的存在。因此，对来自六个RERV-H / HRV-5阳性样品的DNA进行了重新测试。三个还包含兔子线粒体DNA。使用合成肽搜索的HRV-5抗体在来自三个RERV-H / HRV-5阳性个体的血清中以及在144个其他血清中均呈阴性，根据RERV-H / HRV-5 DNA的非感染源。人类样本。寻找兔子DNA污染的可能来源是阴性的。严格遵守防止PCR污染的方法。从Uppsala实验室呈阳性的RERV-H / HRV-5阳性个体的三份样品在另外一两个实验室进行了重新测试，所有三份均为阳性。在里加实验室中呈阳性的其他两个样品也在伦敦进行了测试，并且也呈阳性。一名非霍奇金淋巴瘤患者在四个连续样本中均为RERV-H / HRV-5阳性，表明阳性是该患者的财产。结论是开发用于检测和定量微量RERV-H / HRV-5 DNA的stnQPCR是可以广泛应用的原理，HRV-5是RERV-H。无法解释它在一些人类血液样本中的存在。
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【小波分析可早期识别具有遗传易感性的阿曼高血压的后代HRV变化。】
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DOI：10.3233/THC-202469
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BACKGROUND & AIMS: BACKGROUND:Offspring with a genetic predisposition to hypertension may have higher blood pressure (BP) at rest compared with those without a genetic predisposition to hypertension. They are also expected to have a higher sympathetic component in the heart rate variability (HRV) which could be computed with signal processing algorithms.
OBJECTIVE:The purpose of this study is to design a wavelet-based system to estimate the heart rate variability that can be used to detect early cardiovascular changes in offspring with a genetic predisposition to hypertension. Early detection will help in the treatment of those young people. In this work, the relation between the hypertension and the changes in HRV is investigated.
METHODS:The frequency domain and time domain analysis of heart rate variability (HRV) are studied to understand their relationship to the autonomic nervous system in offspring with and without a genetic predisposition to hypertension in Oman at resting state. The wavelet-based soft-decision algorithm is used as the spectral analysis tool to obtain different features from the HRV signal and to select the best performing features for detection of hypertension. The main task is to classify between three categories of subjects: 36 subjects with both normotensive parents (ONT), 22 subjects with single hypertensive parent (OHT1), and 11 subjects with both hypertensive parents (OHT2).
RESULTS:The summation of the power of bands B4 and B5 of the 32 bands HRV wavelet-based spectrum, which is equivalent to the frequency range (0.046875 Hz-0.078125 Hz), is used as a classification factor among OHT2, OHT1, and ONT groups. The efficiency of classification between ONT and OHT2 is 85.10%, and between OHT1 and OHT2 is 81.81%. The result of classifying between (ONT and OHT1 as one group) and OHT2 is 85.50%.
CONCLUSIONS:The work proves that the wavelet-based spectral analysis technique is a successful tool for classifying the three groups of subjects (ONT, OHT1, and OHT2) with different susceptibility for development of hypertension.
背景与目标： 背景：具有遗传易患高血压的后代在静止时的血压（BP）可能高于没有遗传易患高血压的后代。人们还期望它们在心率变异性（HRV）中具有较高的交感成分，可以通过信号处理算法进行计算。
目的：本研究的目的是设计一种基于小波的系统，用于估计心率变异性，可用于检测具有遗传易感性高血压的后代的早期心血管变化。早期发现将有助于治疗这些年轻人。在这项工作中，研究了高血压与HRV变化之间的关系。
方法：研究了心率变异性（HRV）的频域和时域分析，以了解它们与有或没有遗传易感性的阿曼高血压后代的自主神经系统的关系。基于小波的软决策算法用作频谱分析工具，可从HRV信号中获得不同的特征，并选择性能最佳的特征来检测高血压。主要任务是对三类受试者进行分类：36名具有正常血压父母（ONT）的受试者，22名具有单一高血压父母（OHT1）的受试者和11名同时具有高血压父母（OHT2）的受试者。 strong>结果：将32个波段的HRV小波频谱的波段B4和B5的功率总和，等效于频率范围（0.046875 Hz-0.078125 Hz），用作其中的分类因子OHT2，OHT1和ONT组。 ONT和OHT2之间的分类效率为85.10％，OHT1和OHT2之间的分类效率为81.81％。 （ONT和OHT1作为一组）和OHT2的分类结果为85.50％。
结论：这项工作证明基于小波的频谱分析技术是一种成功的分析工具将高血压易感性不同的三类受试者（ONT，OHT1和OHT2）分类。
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【直升机操作期间HEMS中急诊医师的HRV比较：作为操作次数和工作量的函数的差异分析。】
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DOI：10.1007/s10484-020-09480-1
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BACKGROUND & AIMS: :Chronic stress can lead to physiological illness. Emergency physicians in danger of developing such illnesses due to their demanding working environment. The aim of this study was to investigate the physiological stress level of emergency physicians (EPs) of the Helicopter Emergency Medical Service (HEMS) between emergency operations in one shift. Furthermore, the phases of the operations were compared with respect to the activity of the autonomic nervous system. The physiological and self-perceived stress levels of 20 EPs were recorded on a HEMS air-rescue-day (age: M = 44.95, SD = 4.80). The measurement of the heart rate variability (HRV) was performed during a complete air-ambulance day and examined using analyses of variance. The heart rate rises significantly at the beginning of the emergency operation to its highest value after landing at the operation site. The HRV parameter standard deviation of all NN intervals shows a significant decrease between the alarm phase and the end of the operation. Furthermore, high values were reached regarding chronic stress. On the Symptom Checklist-90 the EPs show lower values than the norm sample. In conclusion, over the course of three emergency operations, no physiological fatigue indicators were found. In contrast, the subjective stress load was assessed as high among EPs and on average higher than the norm sample. Compared to standard values, the EPs showed lower HRV values, which indicates a strong activation of the autonomic nervous system. These lower HRV findings might be caused by a high psychological stress load.背景与目标： ：慢性应激会导致生理疾病。急诊医师因其苛刻的工作环境而处于患此类疾病的危险中。这项研究的目的是调查一次紧急操作之间的直升机紧急医疗服务（HEMS）的急诊医师（EPs）的生理压力水平。此外，相对于自主神经系统的活动，比较了手术的各个阶段。在HEMS空中救援日记录了20个EP的生理和自我感觉压力水平（年龄：M = 44.95，SD = 4.80）。心率变异性（HRV）的测量是在整个空中救护车期间进行的，并使用变异分析进行了检查。在紧急手术开始时，心率会显着上升，降落到手术部位后会达到最高值。所有NN间隔的HRV参数标准差表明，在警报阶段和操作结束之间，显着减小了。此外，在慢性压力方面达到了很高的价值。在症状清单-90中，EP的值比正常样本的值低。总之，在三个紧急手术过程中，没有发现生理疲劳指标。相反，在EP中，主观压力负荷被评估为高，平均水平高于正常样本。与标准值相比，EP显示较低的HRV值，表明自主神经系统的强烈激活。这些较低的HRV发现可能是由于较高的心理压力负荷引起的。
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【EDTA铁钠与维生素C，叶酸，葡萄糖酸铜，葡萄糖酸锌和硒代蛋氨酸联合治疗的“体弱”患者继发性贫血的初步研究：HRV非线性分析探讨了治疗的安全性可预测】
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DOI：10.26355/eurrev_202007_22280
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BACKGROUND & AIMS: OBJECTIVE:Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. PATIENTS AND METHODS:In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. RESULTS:Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. CONCLUSIONS:Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.背景与目标： 目的：心脏病患者缺铁性贫血（IDA）与运动能力下降和健康相关的生活质量下降相关，并预测心血管疾病的恶化，尤其是对于老年患者。 IDA可使心脏功能恶化，可通过心率变异性（HRV）分析进行监测，从而提供有关心脏健康的重要信息。在最近的研究中，我们探讨了EDTA铁钠与维生素C，叶酸，葡萄糖酸铜，葡萄糖酸锌和硒代蛋氨酸（FerachelForte®）联用对继发性贫血和低肾脏的“脆弱”患者的治疗效果和耐受性通过分析HRV频域来确定故障。本研究的目的是通过分析HRV的非线性域，进一步确认已经评估过的干预措施的安全性。
患者与方法：在这项前瞻性研究中，我们招募了52名“脆弱”的老年患者，这些患者最近被诊断为铁缺乏引起的继发性贫血，并伴有II级纽约心脏协会（NYHA）高血压心脏病，低肾功能衰竭和动脉粥样硬化。将患者分为2组：A组（N = 23名患者）接受口服EDTA铁钠联合维生素C，叶酸，葡萄糖酸铜，葡萄糖酸锌和硒代蛋氨酸（FerachelForte®）2片/天，含60 mg的Fe3，持续24天； B组（N = 29例患者）在住院期间（15±5天）接受了静脉滴注63 mg /天的葡萄糖酸葡萄糖酸亚铁静脉注射。我们评估了血红蛋白和血铁蛋白水平的实验室值。此外，我们使用非线性分析技术测量了治疗前后的ECG信号。
结果：本研究评估的静脉和口服治疗均有效且安全，这是由于非线性HRV分析导致的“虚弱”老年患者的心血管风险。疗效结果显示，治疗后血红蛋白和铁血含量显着增加。 HRV非线性分析表明，除A组中的SD1值外，所有评估的参数均不受治疗的影响，从而证实了该治疗方法无心血管风险。
结论：非线性HRV评估证实，口服EDTA铁钠与维生素C，叶酸，葡萄糖酸铜，葡萄糖酸锌和硒代蛋氨酸（Ferachelforte®）联合使用不会影响心血管疾病的风险，而不会引起通常报道的不良事件以及其他口服和静脉补铁疗法。
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