高血压患者血压昼夜节律消失与一氧化氮和内皮素关系的研究

目的探讨高血压昼夜节律与血浆一氧化氮(NO)和内皮素(ET)及其与左心室肥大的关系。方法选择原发性高血压患者90例,根据24 h动态血压(24ABPM)检测结果将其分为血压昼夜节律正常组50例及血压昼夜节律消失组40例;另选血压正常者30例作为对照组。采用G riess法测NO,用放射免疫法测ET;采用PH ILIPS HD I 5000型彩色多普勒仪测定三组受试者的室间隔厚度(IVS),左室舒张末期内径(LVDd)、左室后壁厚度(LVPW)、左心室重量(LVM),以>215 g为左心室肥大的诊断标准。结果血压昼夜节律消失组与血压昼夜节律正常组比较,ET、IVS、LVPW、LVDd、和LVM均显著增高,NO、ET、NO/ET明显降低(P<0.05)。夜间血压下降率与NO、NO/ET呈正相关(r=0.467,0.267,0.713,P<0.05),与ET、IVS、LVPW、LVDd和LVM呈负相关(r=-0.761~-0.264,P<0.05)。结论NO和ET水平可能参与昼夜血压节律的调节,ET升高与血压昼夜节律消失有关,并加重左心室肥大。     

Light-induced phase-shifts in the circadian expression rhythm of mammalian period genes in the mouse heart

To investigate the molecular mechanism that regulates circadian rhythms in mammalian peripheral tissues, we examined the phase shifts evoked by light exposure in the circadian mRNA expression rhythms of mammalian Period genes (mPer1, mPer2 and mPer3) and a clock-controlled gene Dbp, in the mouse heart, by Northern blot analysis. The light pulse did not induce any acute mRNA expression of mPer in the heart, but the pulse gave rise to phase shifts in the circadian mRNA rhythms. On the first day after the exposure, only mPer1 mRNA showed a phase shift, whereas obvious phase shifts were not observed in the rhythms of mPer2, mPer3 and Dbp mRNAs. On the second day, phase shifts occurred to a similar extent in the mRNA rhythms of all four genes examined. The rhythm of mPer1 mRNA shifted fastest among those of the three mPers. Therefore mPer1 seems to play an important role in phase resetting of mammalian peripheral oscillators. Immediate responses to light pulses in mRNA expression of mPers may not be required for phase shifting of peripheral circadian oscillators. Our findings suggest that mammals require more than one day to have peripheral oscillators entrained to a new daily schedule.     

老年高血压患者血压昼夜节律对左室肥厚的影响

【摘要】 目的 研究老年高血压患者的血压昼夜节律变化对左室肥厚的影响。方法 选取我院126例高血压患者,根据心脏彩超提示左室肥厚情况分为肥厚组（n=52例）和非肥厚组（n=74例）。比较两组动态血压指标及血压变异性,进行多因素分析探讨血压变异性对左室肥厚的影响。 结果 高血压肥厚组24h平均收缩压（24hSBP）、白天平均收缩压（dSBP）、夜间平均收缩压（nSBP）、24h收缩压标准差（24hSSD）、24h舒张压标准差（24hDSD）、白天收缩压标准差（dSSD）、夜间收缩压标准差（nSSD）均高于非肥厚组,差异有统计学意义（P＜005）。Logistic回归分析显示,24h SBP 与dSSD、nSSD为左室肥厚的独立危险因素（P＜005）。结论 老年高血压患者的24h SBP 与dSSD、nSSD是影响左室肥厚的独立危险因素,平稳控制血压对防止左室肥厚的发生有一定影响。     

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.     

Nicotine and smoking: Effects upon subjective changes in mood

A Mood Adjective Check List and an activation scale were used to measure subjective reports on mood changes in 24 male habitual smokers before and after smoking cigarettes with known content of nicotine, at different times of day and rates of puffing. Ratings on pleasantness were dose related. Aggression and anxiety showed effects attributable to circadian influence and slight decreases in both factors occurred after smoking the highest nicotine cigarette. The MACL scores were greatly affected by the experimental procedure. Levels of inner tension were found related to the nicotine inhaled. The heuristic value of the concept of activation in these studies is suggested.This work was supported by the Tobacco Research Council, and carried out at the Institute of Psychiatry, London.     

限时进食对恶性肿瘤的潜在防治作用

间歇性禁食是一种新的饮食干预策略,其可能改善恶性肿瘤治疗的疗效并减少并发症。限时进食是间歇性禁食的一种特殊形式,通常仅限制每天的进食时间窗而不限制热量,除了和其他间歇性禁食手段一样能够控制体重并改善代谢紊乱以外,限时进食还能调节昼夜节律并影响自噬水平,具有潜在的抗衰作用,相关研究已经表明了它预防肿瘤发生以及减缓肿瘤发展的潜力。同时,由于实施方案便利、不良反应轻微,限时进食有着不错的依从性及安全性,有可能成为一种适合肿瘤患者长期实施的辅助治疗方案乃至健康生活方式。本文从改善肥胖和代谢紊乱、调节昼夜节律和自噬水平以及目前与肿瘤相关的研究进展这三个方面阐述了限时进食对恶性肿瘤的潜在作用,旨在为将来的相关研究提供理论依据和探索方向,探讨限时进食作为一种营养干预手段对恶性肿瘤发生的潜在预防作用以及对恶性肿瘤的治疗或辅助治疗作用,以期可以完善对肿瘤患者的营养干预策略,改善患者的生活质量及预后。     

原发性高血压患者213例动态血压监测分析

目的 分析原发性高血压患者24 h动态血压监测（ABPM）变化规律及临床意义。方法 2011年1月至2013年9月对213例原发性高血压患者进行24 h ABPM,观察其24 h平均收缩压（24 h MSP）、24 h平均舒张压（24 h MDP）、白昼平均收缩压（dMSP）、白昼平均舒张压（dMDP）、夜间平均收缩压（nMSP）、夜间平均舒张压（nMDP）、夜间血压下降率。结果 213例原发性高血压患者中100例为杓型血压,78例为非杓型血压,35例为反杓型血压。随年龄增长反杓型血压发生率明显升高,其中老年组（≥60岁）患者反杓型血压发生率较中青年组（＜60岁）高,而老年组患者杓型血压发生率较中青年组患者低,差异均有统计学意义（P＜0.05）。不同年龄段女性患者反杓型血压发生率较男性高,但二者比较,差异均无统计学意义（P＞0.05）。结论 原发性高血压患者平时血压波动情况通过24 h ABPM能更加真实地反映出来。随着年龄的增长,原发性高血压患者24 h动态血压昼夜节律异常发生率不断增高,提示增龄可明确影响到原发性高血压患者的血压节律变化,应尽早进行干预治疗。     

正常人和急性心肌梗死患者心率震荡斜率的昼夜变化及与心率的相关性

目的观察正常人和急性心肌梗死（AMI）患者心率震荡（HRT）的昼夜变化规律,探讨不同人群心率与震荡斜率（TS）的相关性。方法选择100例AMI患者,平均年龄（60.87±13.72）岁,男66例,女34例;82例正常对照者,平均年龄（59.23±13.31）岁,男54例,女28例。两组均进行24h动态心电图检查,定量测定一昼夜中每小时的平均心率（HR）与TS的均值,采用圆形分布统计分析方法,计算两组TS值在昼夜分布中的高峰时点及集中时段。结果（1）正常对照组TS值在24h分布上有明显的集中趋势,高峰时点为04：34（P〈0.05）,集中时段为21：25～11：41;AMI组TS值在24h分布上无明显集中趋势（P〉0.05）。（2）正常对照组HR与TS呈负相关关系（r=-0.771,P〈0.01）;AMI组HR与TS不存在直线相关关系（r=-0.312,P〉0.05）。结论正常人TS值有昼夜节律性,明显受HR的影响。作为心脏的一个基本生物节律,其主要受自主神经的调控。而AMI患者的这种生物节律性消失,可能与自主神经功能紊乱有关。     

Racial and Ethnic Differences in Eating Duration and Meal Timing: Findings from NHANES 2011–2018

Background: In addition to quantity and quality, meal timing and eating duration are additional dietary characteristics that impact cardiometabolic health. Given that cardiometabolic health disparities exist among racial and ethnic groups, we examined whether meal timing and eating duration are additional diet-related differences among racial and ethnic groups. Methods: Participants (n = 13,084) were adults (≥20 years) from the National Health and Nutrition Examination (NHANES, 2011–2018) Survey. Times of first and last meal and the interval between them (eating duration) were derived from two 24-h dietary recalls. Multiple linear regression analyses compared these variables among race and ethnicity after adjusting for potential confounders. Results: Compared to non-Hispanic White adults, the first mealtime was significantly later for Mexican American (23 min), Non-Hispanic Asian (15 min), Non-Hispanic Black (46 min), and Other Hispanic (20 min) and Other Racial (14 min) adults (all p < 0.05). Mexican American and Non-Hispanic Asian adults had a significantly different last mealtime by 13 min earlier and 25 min later, respectively, compared to Non-Hispanic White adults. Compared to Non-Hispanic White adults, the mean eating duration was shorter for other Hispanic (20 min), Mexican American (36 min), and Non-Hispanic Black (49 min) adults. Conclusions: Meal timing and eating duration are additional dietary characteristics that vary significantly among racial and ethnic groups.     

Abnormal circadian rhythm in patients with GRIN1-related developmental epileptic encephalopathy

GRIN1 encodes the obligate subunit (GluN1) of glutamate N-methyl-d-aspartate receptor (NMDAr). Pathogenic variants in GRIN1 are a well-known cause of infantile encephalopathy characterized by profound developmental delay (DD), variable epileptic phenotypes, and distinctive behavioral abnormalities. Recently, GRIN1 has also been implicated in the pathogenesis of polymicrogyria (PMG).We investigated two patients presenting with severe intellectual disability (ID), epilepsy, stereotyped movements, and abnormal ocular movements. They showed distinctive circadian rhythm alterations and sleep-wake patterns anomalies characterized by recurrent cyclic crying or laughing spells. Genetic analysis led to the identification of two distinct de novo variants in GRIN1 affecting the same amino acid residue of an important functional protein domain.Recent advances in circadian rhythm and sleep regulation suggest that abnormal GluN1 function might play a relevant pathogenetic role for the peculiar behavioral abnormalities observed in GRIN1 patients. Our cases highlight the relevance of circadian rhythm abnormalities in epileptic children as a clue toward GRIN1 encephalopathy and expand the complex phenotypic spectrum of this severe genetic disorder.