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Abstract Introduction: Blood pressure (BP) assessment affects the management of arterial hypertension (AH) in chronic kidney disease (CKD). CKD patients have specific patterns of BP behavior during ambulatory blood pressure monitoring (ABPM). Objectives: The aim of the current study was to evaluate the associations between progressive stages of CKD and changes in ABPM. Methodology: This is a cross-sectional study with 851 patients treated in outpatient clinics of a university hospital who underwent ABPM examination from January 2004 to February 2012 in order to assess the presence and control of AH. The outcomes considered were the ABPM parameters. The variable of interest was CKD staging. Confounding factors included age, sex, body mass index, smoking, cause of CKD, and use of antihypertensive drugs. Results: Systolic BP (SBP) was associated with CKD stages 3b and 5, irrespective of confounding variables. Pulse pressure was only associated with stage 5. The SBP coefficient of variation was progressively associated with stages 3a, 4 and 5, while the diastolic blood pressure (DBP) coefficient of variation showed no association. SBP reduction was associated with stages 2, 4 and 5, and the decline in DBP with stages 4 and 5. Other ABPM parameters showed no association with CKD stages after adjustments. Conclusion: Advanced stages of CKD were associated with lower nocturnal dipping and greater variability in blood pressure.
Resumo Introdução: A avaliação da pressão arterial (PA) tem impacto no manejo da hipertensão arterial (HA) na doença renal crônica (DRC). O portador de DRC apresenta padrão específico de comportamento da PA ao longo da monitorização ambulatorial da pressão arterial (MAPA). Objetivos: O objetivo do corrente estudo é avaliar as associações entre os estágios progressivos da DRC e alterações da MAPA. Metodologia: Trata-se de um estudo transversal com 851 pacientes atendidos nos ambulatórios de um hospital universitário que foram submetidos ao exame de MAPA no período de janeiro de 2004 a fevereiro de 2012 para avaliar a presença e o controle da HA. Os desfechos considerados foram os parâmetros de MAPA. A variável de interesse foi o estadiamento da DRC. Foram considerados como fatores de confusão idade, sexo, índice de massa corporal, tabagismo, causa da DRC e uso de anti-hipertensivos. Resultados: A PA sistólica (PAS) se associou aos estágios 3b e 5 da DRC, independentemente das variáveis de confusão. Pressão de pulso se associou apenas ao estágio 5. O coeficiente de variação da PAS se associou progressivamente aos estágios 3a, 4 e 5, enquanto o coeficiente de variação da pressão arterial diastólica (PAD) não demonstrou associação. O descenso da PAS obteve associação com estágios 2, 4 e 5, e o descenso da PAD, com os 4 e 5. Demais parâmetros da MAPA não obtiveram associação com os estágios da DRC após os ajustes. Conclusão: Estágios mais avançados da DRC associaram-se a menor descenso noturno e a maior variabilidade da pressão arterial.
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Esse trabalho tem como objetivo investigar se o período do dia influencia no desempenho dos indivíduos numa bateria de TAF. A amostra foi composta por dez indivíduos de ambos os sexos (24,10 ± 0,96 anos), que realizaram o TAF nos três períodos do dia: manhã, tarde e noite, em três dias não consecutivos no decorrer de uma semana. O TAF foi composto por cinco testes (teste de preensão manual, teste na barra fixa, teste de flexão abdominal, teste de impulsão horizontal e Shuttle-run) para homens e quatro testes para as mulheres, que não realizaram o teste de força na barra fixa. No primeiro dia da bateria de testes, eles foram submetidos a avaliação antropométrica e de composição corporal com bioimpedância. Em cada dia de avaliação, os participantes tiveram a temperatura corporal aferida antes de iniciar os testes e responderam à percepção subjetiva de esforço (PSE) após cada teste. Para a análise estatística foi utilizado a anova one-way com post-hoc de bonferroni para comparar as diferenças de performance ao longo dos três períodos do dia. Não foram encontradas diferença significativas (P>0,05) no desempenho entre os testes realizados, nem na PSE nas comparações entre os três períodos do dia. A temperatura corporal foi significativamente (P<0,01) menor no período da manhã (36,28 ± 0,08 ºC) quando comparada ao período da tarde (36,54 ± 0,69 ºC) e da noite (36,70 ± 0,10 ºC). Assim, é possível concluir que o período do dia não influência o desempenho de adultos jovens em uma bateria de TAF.
This work aims to investigate whether the time of day influences the performance of individuals in a TAF battery. The sample consisted of ten individuals of both genders (24.10±0.96 years), who performed the FAT in three periods of the day: morning, afternoon and night, on three non-consecutive days over the course of a week. The FAT consisted of five tests (handgrip test, fixed bar test, abdominal flexion test, horizontal impulsion test and Shuttle-run) for men and four tests for women, who did not perform the strength test on the bar. fixed. On the first day of the battery of tests, they underwent an anthropometric and body composition assessment with bioimpedance. On each evaluation day, the participants had their body temperature measured before starting the tests and answered the subjective perception of exertion (RPE) after each test. For the statistical analysis, one-way anova with Bonferroni post-hoc was used to compare performance differences over the three periods of the day. No significant differences (P>0.05) were found in the performance between the tests performed, nor in the PSE in the comparisons between the three periods of the day. Body temperature was significantly (P<0.01) lower in the morning (36.28±0.08 ºC) when compared to the afternoon (36.54±0.69 ºC) and night (36.70 ±0.10 ºC). Thus, it is possible to conclude that the time of day does not influence the performance of young adults in a TAF battery.
Este trabajo tiene como objetivo investigar si la hora del día influye en el rendimiento de los individuos en una batería de pruebas de aptitud física (BAF). La muestra estuvo conformada por diez individuos de ambos sexos (24,10±0,96 años), quienes realizaron el BAF en tres momentos del día: mañana, tarde y noche, en tres días no consecutivos en el transcurso de una semana. La BAF constaba de cinco pruebas (handgrip test, test de barra fija, test de flexión abdominal, test de impulsión horizontal y Shuttle-run) para hombres y cuatro pruebas para mujeres, que no realizaron la prueba de fuerza en barra fija. El primer día de la batería de pruebas se les realizó una valoración antropométrica y de composición corporal con bioimpedancia. En cada día de evaluación, a los participantes se les tomó la temperatura corporal antes de comenzar las pruebas y respondieron la percepción subjetiva de esfuerzo (PSE) después de cada prueba. Para el análisis estadístico, se utilizó Anova unidireccional con Bonferroni post-hoc para comparar las diferencias de rendimiento en los tres períodos del día. No se encontraron diferencias significativas (P>0,05) en el rendimiento entre las pruebas realizadas, ni en el PSE en las comparaciones entre los tres períodos del día. La temperatura corporal fue significativamente (P<0,01) más baja en la mañana (36,28 ± 0,08 ºC) en comparación con la tarde (36,54 ± 0,69 ºC) y la noche (36,70 ± 0,10 ºC). Por lo tanto, es posible concluir que la hora del día no influye en el rendimiento de los adultos jóvenes en una BAF.
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The clock gene Rev-erbα, also known as nuclear receptor subfamily 1 group D member 1 (Nr1d1), is a crucial regulatory factor in organisms. It exhibits circadian rhythmic expression in metabolically active tissues such as skeletal muscles, heart, liver, and adipose tissue, responding to various environmental stimuli. Rev-erbα plays a significant role in regulating circadian rhythms, metabolic homeostasis, and other physiological processes, earning its designation as an “integrator” of the circadian system and metabolism. Rev-erbα establishes complex connections with other clock genes through the transcriptional-translational feedback loop (TTFL), which is important for the rhythmic output of biological clock system and for the relative stability of phases and cycles. Mitochondrial biogenesis is a physiological process initiated by cells to maintain energy homeostasis by using existing mitochondria as a template for self-growth and division. As the “energy factory” of organism, disruptions in mitochondrial biogenesis are closely associated with the development of various diseases. Studies have shown that not only the factors involved in mitochondrial biogenesis have circadian oscillations, but also the morphology, dynamics and energy metabolism of mitochondria themselves have cyclic fluctuations throughout the day, suggesting that mitochondrial biogenesis is regulated by the biological clock system, in which the clock gene Rev-erbα plays a key role, it drives mitochondrial biogenesis and synergistically regulates autophagy to normalize a number of physiological processes in the body. Rev-erbα is sensitive to both internal and external environmental changes, and disruptions in circadian rhythms, metabolic diseases, and aging are significant inducers of changes in Rev-erbα expression, and its concomitant inflammation and oxidative stress may be an intrinsic mechanism for inhibiting mitochondrial biogenesis. Therefore, the enhancement of mitochondrial biogenesis by regulating the Rev-erbα activity status may be an important way to improve the pathology and promote the health of organism. Exercise, as a commonly accepted non-pharmacological tool, plays an important role in enhancing mitochondrial biogenesis and promoting health. It has been found that there is a close relationship between exercise and Rev-erbα. On the one hand, exercise stimulation directly affects the expression of Rev-erbα, especially high-intensity and long-term regular exercise; on the other hand, Rev-erbα achieves indirect regulation of exercise capacity by mediating processes such as skeletal muscle mitochondrial biogenesis and autophagy, muscle mass maintenance, energy metabolism and skeletal muscle regeneration. Based on the above findings, it is hypothesized that Rev-erbα may serve as a key bridge between exercise and mitochondrial biogenesis. Exercise enhances the transcriptional response of Rev-erbα in the nucleus, upregulates the expression of Rev-erbα protein in cytoplasm, activates the AMP-activated proteinkinase (AMPK)/ silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) pathway, regulates Ca2+ flux and downstream signaling molecules; meanwhile, exercise can upregulate antioxidant gene expression and alleviate oxidative stress through Rev-erbα, which ultimately enhances the function of mitochondria, and promotes mitochondrial biogenesis. In conclusion, the clock gene Rev-erbα emerges as a crucial target for exercise-induced enhancement of mitochondrial biogenesis. In this paper, the biological characteristics ofRev-erbα, the role of Rev-erbα in regulating mitochondrial biogenesis and the factors that may influence it, the interaction between exercise and Rev-erbα, and the potential mechanism of exercise-induced mitochondrial biogenesis via Rev-erbα are sorted out and discussed, which can provide theoretical references to the mechanism of exercise-promoted mitochondrial biogenesis.
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Objective:To investigate the characteristics of the nocturnal melatonin secretion concentration and circadian rhythm in patients with wake-up stroke (WUS).Methods:Patients with acute ischemia stroke (AIS) admitted to the Department of Neurology, the Second Affiliated Hospital of Soochow University from October 2019 to August 2022 were enrolled. They were divided into WUS group and non-WUS group. Saliva samples within one week after admission were collected (at 19∶00, 20∶00, 21∶00, 22∶00, and 23∶00) and melatonin concentration was measured. Melatonin secretion curve graph was drawn, dim light melatonin onset (DLMO) was calculated, and circadian rhythms were evaluated. The differences in endogenous circadian rhythms between the WUS group and the non-WUS group were compared. The relevant factors of WUS were determined by multivariate logistic regression analysis. Results:A total of 116 patients with AIS were included, with 79 males (68.1%), aged 59.9±10.3 years; 35 patients (30.2%) were WUS. Univariate analysis showed that there was a statistically significant difference in the infarct site between the WUS group and the non-WUS group ( P=0.019). At 21:00 ( P=0.004) and the average ( P=0.038) nighttime melatonin concentration in the WUS group were significantly lower than those in the non-WUS group, and DLMO showed a significant delay compared to the non-WUS group (21:28:08 vs. 20:57:57; P=0.015). Multivariate logistic regression analysis showed a significant independent correlation between DLMO delay and WUS (odds ratio 1.792, 95% confidence interval 1.123-2.858; P=0.014). Conclusion:Patients with WUS may have endogenous circadian rhythm delay, which is an independent risk factor for WUS.
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Objective To investigate whether discontinuous sleep supplementation can reduce myocardial ischemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.Methods The rats were injected intra-peritoneal with 1％streptozotocin(STZ)30 mg/kg combined with high-fat and high-glucose diet to replicate diabetic model.Forty diabetic rats were randomly divided into four groups with 10 in each:sham surgery group(Sham group),ischemia-reperfusion group(I/R group),in which the left anterior descending coronary artery(LDA)was ligated for thirty minutes and reperfusion for 2 h,circadian rhythm disorder group(Crd group,24 h daily light and food),discontinuous sleep supplementation group(Dss group,every 3 hours of illumination and 1.5 hours break at night).We analyzed the myocardial infarct size(by 2,3,5-triphenyltetrazolium chloride stai-ning),determined serum creatine kinase-myoglobin(CK-MB)activity and cardiac troponinⅠ(cTnⅠ)concentrations;the expression level of BMAL1 and REV-ERBα was determined by Western blot.Results Compared to the sham group,the I/R group showed a significantly increased in myocardial infarct size,serum CK-MB activity and cTnⅠ concentration.The expression of the myocardial biological clock gene BMAL1 was down-regulated,while the ex-pression of REV-ERBα was up-regulated(P<0.05).Compared to the I/R group,the Crd group showed a signifi-cantly increase in myocardial infarct size,serum CK-MB activity and cTnⅠ concentration.The expression of the myocardial biological clock gene BMAL1 was down-regulated,while the expression of REV-ERBα was up-regulated(P<0.05).Compared to the Crd group,Dss group showed a significantly decrease in the myocardial infarct size,serum cTn concentration and CK-MB activity.Furthermore,there was an increased protein expression of BMAL1 and a decrease of REV-ERBα(P<0.05).Conclusions Discontinuous sleep supplementation can reduce myocardial is-chemia-reperfusion injury in diabetic rats aggravated by circadian rhythm disorder.
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Circadian rhythm is one of the biorhythms formed by organisms in the process of evolution to adapt to the rotation of the earth,which is manifested as a cyclical biorhythm of about 24 hours produced by the body under the control of the internal biological clock,coordinating sleep/wakefulness,body temperature regulation,endocrine time and other activities.Long-term circadian rhythm disorders can cause increased risk of metabolic disorders,gastrointestinal diseases,neurodegenerative diseasesand other illnesses.As a typical model animal,the aquatic organism zebrafish(Danio rerio)has been widely used in experimental studies of circadian rhythm.This paper introduces in detailthe operating mechanism of zebrafish circadian clock,the influencing factors of the input system,the genes and pathways of the circadian clock,and the physiological output,summarizes the application and advantages in circadian rhythm research,finally looks forward to future research and development,in order to provide theoretical support for circadian rhythm regulation mechanism research,related drug development and disease treatment strategies.
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Nowadays,with the improvement of people's living standards and the acceleration of the aging process of population,cerebral small vessel disease has seriously endangered the life health and quality of life of the elderly.Hypertension has been paid more and more attention as an important risk factor of cerebral small vessel disease.However,in the management of hypertension,people generally concentrate on the influence of mean arterial pressure,ignoring the role of variability and circadian rhythm of blood pressure nowadays.By expounding the pathogenesis of cerebral small vessel disease and the recent studies on blood pressure variability and circadian rhythm of blood pressure,this review discusses a series of scientific problems such as the effects of blood pressure variability and circadian rhythm of blood pressure on the occurrence and development of cerebral small vessel disease.
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The prevalence of myopia is substantial in China,significantly impacting children's visual health.Current research indicates that extended screen time and inadequate outdoor activities are pivotal factors contributing to childhood myopia.These risk factors are closely associated with light parameters,including intensity,duration,frequency and spec-trum.Moreover,inappropriate nighttime lighting can disturb children's circadian rhythms and sleep and contribute to myo-pia development.This study reviews clinical research and epidemiological data on screen time,outdoor activities,light properties and circadian rhythms,aiming to offer recommendations and guidance for preventing myopia in children.
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Objective:To investigate the characteristics of sleep disorders in patients with Alzheimer's disease and the intervention effect of integrated traditional Chinese and Western medicine.Methods:A total of 102 patients with Alzheimer's disease who had sleep disorders and received treatment at Huzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang University of Traditional Chinese Medicine were included in the observation group. A total of 102 patients who concurrently received physical examination in the same hospital were included in the control group. Clinical consultation was performed to analyze the types and characteristics of sleep disorders in patients with Alzheimer's disease. The included patients with Alzheimer's diseae were divided into group A and group B using the random number table method, with 51 patients per group. Group A received routine western medicine intervention, while group B received traditional Chinese medicine intervention and routine western medicine intervention. The types of sleep disorders were observed in patients with Alzheimer's disease and older adult patients who undergo physical examination. The changes in traditional Chinese medicine syndrome score and sleep quality were evaluated in groups A and B.Results:The incidence rates of screaming, difficulty in falling asleep, excessive daytime sleepiness, nocturnal restlessness, obstructive sleep apnea syndrome, and fragmented sleep in the observation group were 13.73% (14/102), 58.82% (60/102), 49.02% (50/102), 49.02% (50/102), 24.51% (25/102) and 98.04% (100/102), respectively, which were significantly higher than 1.96% (2/102), 23.53% (24/102), 17.65% (18/102), 4.90% (5/102), 5.88%(6/102) and 50.98% (52/102), respectively in the control group ( χ2 = 9.76, 26.22, 22.58, 50.40, 13.73, 59.46, all P < 0.05). After intervention, the scores of insomnia, dizziness and tinnitus, mental confusion, and forgetfulness in group B were 1.0 (0.00, 1.00) point, 0.00 (0.00, 1.00) point, 0.00 (0.00, 1.00) point, and 1.00 (1.00, 1.00) point, respectively, which were significantly lower than (1.00, 2.00) points, 1.00 (1.00, 2.00) points, 1.00 (0.00, 1.00) points, and 1.00 (1.00, 2.00) points in group A ( Z = -1.86, -2.13, -2.36, -2.00, all P < 0.05). After intervention, the Pittsburgh Sleep Quality Index score and the Modified Epworth Sleepiness Scale score in Group B were (7.56 ± 1.93) points and (13.02 ± 2.06) points, respectively, which were significantly lower than (10.87 ± 2.21) points and (16.44 ± 2.87) points in group A ( t = 8.05, 6.91, both P < 0.001). Conclusion:The main characteristics of sleep disorders in patients with Alzheimer's disease include screaming, difficulty in falling asleep, excessive daytime sleepiness, nocturnal restlessness, obstructive sleep apnea syndrome, and fragmented sleep. Combined traditional Chinese and western medicine can alleviate clinical symptoms and improve sleep quality in patients with Alzheimer's disease who have sleep disorders.
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Objective:To investigate the onset time distribution and influential factors in patients with acute myocardial infarction (ACI) with different body mass index (BMI) levels.Methods:A cross-sectional study was conducted to collect clinical data from 1 000 patients with AMI who received treatment at Heilongjiang Provincial Hospital from January 2016 to November 2022. The patients were divided into groups based on different BMI levels: < 18.5 kg/m 2 group ( n = 49), 18.5-24 kg/m 2 group ( n = 369), > 24-28 kg/m 2 group ( n = 338), and > 28 kg/m 2 group ( n = 244). The incidence of AMI was analyzed among patients with different BMI levels as per diurnal variation, seasonality, and weekday. Results:A total of 1 000 patients were included in this study, including 648 men and 352 women. The mean age of these patients was 65 years (range 56-74 years). The median body mass was 70 kg (range 60-76 kg), the median height was 1.69 m (range 1.60-1.72 m), and the median BMI was 24.49 kg/m 2 (range 22.22-26.79 kg/m 2). The onset time of AMI differed significantly among patients with different BMI levels in terms of the period from 0:00 to 5:59, winter, and Wednesday ( P = 0.047, 0.029, 0.005). Among all samples, the number of patients with a BMI of 18.5-24 kg/m 2 was the highest, reaching 369 cases. Conclusion:The incidence of AMI in patients with different BMI levels exhibits a regular distribution as per diurnal variation, seasonality, and weekday.
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Objective @#To evaluate the effect of melatonin on nocturnal exacerbation of neuropathic pain and to ex plore its mechanism through the specific silencing information regulator 1 ( SIRT1)-brain and muscle ARNT-like protein 1 ( BMAL1 ) pathway .@*Methods @# 96 SPF grade male C57/B6 mice were randomly divided into three groups : the sham operation (S) group , the neuropathic pain model (NP) group and the NP model + melatonin treatment (10 mg/kg) ( NP + M) group; preoperative experimental mice were placed in the environment of the specified light pattern; the environment of alternating 12 h light and 12 h darkness was used for at least two weeks , and natural time was converted into the time of the award (ZT) , and the starting point of the light was ZT0; only the sciatic nerve was isolated in the S group , and the mouse NP model was prepared using chronic constriction injury (CCI) of the sciatic nerve in the NP group and the NP + M group , and the NP + M group was inj ected with me latonin after the operation; the expression levels of SIRT1, BMAL1, and glutathione peroxidase 1 (Gpx1) were de tected in the spinal cord at each time point at 14 d postoperatively by Western blot. Postoperative co-staining of SIRT1 in the dorsal horn of the spinal cord with the spinal cord neuronal marker neuron specific nuclear protein (NeuN) , the microglial cell activation marker ion calcium binding adapter molecule 1 (iba-1) , and the astrocyte marker glial fibrillary acidic protein ( GFAP) was carried out by immunofluorescence and iba-1 was detected at each time point to determine the activation status of microglia.@*Results @#SIRT1 , BMAL1 and Gpx1 decreased in NP group mice at 14 d ZT22 postoperatively compared to ZT10 time point in NP group ( P < 0.05) ; SIRT1 and BMAL1 were elevated in NP + M group at ZT14 time point compared to ZT14 time point in NP group (P < 0.05) , whereas Gpx1 was elevated at ZT18 time point (P < 0.05) . SIRT1 was co expressed in the dorsal horn of the spinal cord and in microglia. C ompared with ZT10 time point , microglia expression decreased in NP group mice at ZT22 time point 14 d after surgery (P < 0.05) ; compared with ZT10 time point , there was no statistically significant difference in microglia expression in NP + M group mice at ZT22 time point 14 d after surgery .@*Conclusion@#Melatonin attenuates nocturnal exacerbation of neuropathic pain by a mechanism that may be related to activation of microglia SIRT1-BMAL1 pathway protein expression .
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BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear. OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise. METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR. RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee's index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P＜0.01),and significantly increased high-density lipoprotein cholesterol level(P＜0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liver tissue and promoting the browning of parepididymal adipose tissue compared with normoxic sedentary group,hypoxic sedentary group,and normoxic exercise group.RNA-seq results showed that hypoxic exercise significantly upregulated the expression of clock genes Dbp,Nr1d1,Sik1 and adipose tissue browning gene Ppargc1a(PGC-1α)and downregulated the expression of Arntl(Bmal1),accompanied by the enhanced expression of genes related to substance metabolism.qRT-PCR indicated that hypoxic exercise significantly increased the mRNA expression levels of PGC-1α and Perilipin1(P＜0.01).Therefore,these findings indicate that clock genes play an important role in promoting adipose tissue browning during hypoxic exercise.
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ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan （AMD） developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor （OX1R）/phosphatidylinositol-specific phospholipase Cβ-1 （PLCβ-1）/protein kinase Cα （PKCα）/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway. MethodSixty SPF-grade SD rats were randomized into blank， model， suvorexant （30 mg·kg-1·d-1）， and low-， medium-， and high-dose （4.55， 9.09， 18.09 g·kg-1·d-1， respectively） AMD groups， with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine （PCPA） and administrated with corresponding drugs by gavage， and the blank group received an equal volume of normal saline. The general condition， body mass， and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin（HE）staining and Masson staining. The expression of gamma-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， epinephrine （EPI）， norepinephrine （NE）， and acetylcholine （ACh） in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate （Glu） expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1， Per2， Cry1， Cry2， Bmal1， and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR， respectively. ResultCompared with the blank group， the modeling decreased the body mass （P<0.05， P<0.01） and caused mania and disturbed resting rhythms （P<0.01）， hepatic muscle fiber fracture， and edema with inflammatory cell infiltration. In addition， the modeling decreased the GABA， 5-HT， EPI， NE， and ACh content， increased Glu content （P<0.01）， down-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.01）， up-regulated the mRNA levels of Bmal1 and Bmal2 （P<0.01）， and promoted the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both protein and mRNA levels （P<0.01）. Compared with the model group， suvorexant and AMD increased the body mass （P<0.05， P<0.01）， alleviated the mania， and increased the resting time and frequency （P<0.05， P<0.01）. Moreover， the medications elevated the levels of GABA， 5-HT， EPI， NE， and ACh， lowered the Glu level， up-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.05， P<0.01）， down-regulated the mRNA levels of Bmal1 and Bmal2， and inhibited the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both mRNA and protein levels （P<0.05， P<0.01）. ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway， and high-dose AMD demonstrated the strongest effect.
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ABSTRACT Objective: To determine whether enteral melatonin decreases the incidence of delirium in critically ill adults. Methods: In this randomized controlled trial, adults were admitted to the intensive care unit and received either usual standard care alone (Control Group) or in combination with 3mg of enteral melatonin once a day at 9 PM (Melatonin Group). Concealment of allocation was done by serially numbered opaque sealed envelopes. The intensivist assessing delirium and the investigator performing the data analysis were blinded to the group allocation. The primary outcome was the incidence of delirium within 24 hours of the intensive care unit stay. The secondary outcomes were the incidence of delirium on Days 3 and 7, intensive care unit mortality, length of intensive care unit stay, duration of mechanical ventilation and Glasgow outcome score (at discharge). Results: We included 108 patients in the final analysis, with 54 patients in each group. At 24 hours of intensive care unit stay, there was no difference in the incidence of delirium between Melatonin and Control Groups (29.6 versus 46.2%; RR = 0.6; 95%CI 0.38 - 1.05; p = 0.11). No secondary outcome showed a statistically significant difference. Conclusion: Enteral melatonin 3mg is not more effective at decreasing the incidence of delirium than standard care is in critically ill adults.
RESUMO Objetivo: Determinar se a melatonina enteral diminui a incidência de delirium em adultos em estado grave. Métodos: Neste estudo controlado e randomizado, os adultos foram admitidos à unidade de terapia intensiva e/ou receberam apenas o padrão de cuidado habitual (Grupo Controle) ou o tratamento combinado com 3mg de melatonina enteral uma vez ao dia às 21h (Grupo Melatonina). A ocultação da alocação foi feita por meio de envelopes selados opacos e numerados sequencialmente. O intensivista que avaliou o delirium e o pesquisador que realizou a análise dos dados foram cegados quanto à alocação do grupo. O desfecho primário foi a incidência de delirium dentro de 24 horas de internação na unidade de terapia intensiva. Os desfechos secundários foram a incidência de delirium nos dias 3 e 7, a mortalidade na unidade de terapia intensiva, a duração da internação na unidade de terapia intensiva, a duração da ventilação mecânica e o escore da escala de desfecho de Glasgow (na alta). Resultados: Foram incluídos 108 pacientes na análise final, com 54 sujeitos em cada grupo. Em 24 horas de internação na unidade de terapia intensiva, a incidência de delirium não foi diferente entre os Grupos Melatonina e Controle (29,6% versus 46,2%; RR = 0,6; IC95% 0,38 - 1,05; p = 0,11). Nenhum desfecho secundário apresentou diferenças estatisticamente significativas. Conclusão: Em adultos em estado grave, 3mg de melatonina enteral não foi mais eficaz que os cuidados padrão na redução da incidência de delirium.
الملخص
Abstract Introduction: Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. Methods: We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Results: Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. Discussion: The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.
Resumo Introdução: Acredita-se que a obesidade desempenhe um papel na desregulação da ritmicidade cardíaca em crianças obesas, mas esse é um campo de investigação ainda pouco explorado. O objetivo deste trabalho foi avaliar o impacto do sobrepeso e da obesidade na ritmicidade cardiovascular circadiana e ultradiana de crianças pré-púberes, em comparação com crianças com peso normal. Métodos: Realizamos um estudo transversal com 316 crianças, acompanhadas na coorte de nascimentos Geração XXI (Portugal). Foram medidos dados antropométricos e a pressão arterial ambulatorial de 24 horas, e os perfis foram examinados com uma análise de Fourier para ritmos circadianos e ultradianos de pressão arterial (PA) e frequência cardíaca (FC). Resultados: Crianças com sobrepeso/obesidade apresentaram mais frequentemente um padrão de PA não-dipper em comparação com crianças com peso normal (31,5% vs. 21,6%; p = 0,047). A prevalência da pressão arterial média (PAM) de 24 horas e da ritmicidade da FC de 8 horas foi significativamente menor em crianças obesas (79,3% vs. 88,0%; p = 0,038 e 33,3% vs. 45,2%; p = 0,031, respectivamente). A prevalência das restantes ritmicidades da PAM e da FC foi semelhante em ambos os grupos. Não foram encontradas diferenças nos valores medianos das amplitudes e acrofases dos ritmos de PAM e FC. Discussão: As alterações encontradas na ritmicidade sugerem que a análise da ritmicidade circadiana e ultradiana pode ser sensível na detecção de desregulações cardiovasculares precoces, mas são necessários novos estudos para reforçar nossos achados e entender melhor suas implicações a longo prazo.
الملخص
The aging process is often related to sleeping difficulties, often due to changes in circadian rhythms. The circadian timing system is centered in the suprachiasmatic nucleus - the master biological clock - which synchronizes the rhythm of oscillators throughout the body, including the sleep-wake cycle. This affects the time, duration and quality of sleep according to the development and aging process, under external and internal influences. This review addresses the human circadian timing system, including endogenous and exogenous influences on circadian rhythms, their age-related particularities, as well as the repercussions of circadian misalignment in neurodegenerative diseases. Circadian rhythms naturally weaken with aging, but there are particularities according to age. Throughout life, sleep and circadian rhythm disorders are strongly bidirectionally related to the pathophysiology of some psychiatric and neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. This knowledge could potentially create valuable opportunities to improve the health of the world's population that is under circadian misalignment and aging.
O processo de envelhecimento está frequentemente relacionado a dificuldades de dormir, muitas vezes decorrentes de alterações nos ritmos circadianos. O sistema de ronometragem circadiana está centrada no núcleo supraquiasmático - o relógio biológico mestre - o qual sincroniza o ritmo dos osciladores em todo o corpo, incluindo o ciclo sono-vigília. Isso afeta o tempo, a duração e a qualidade do sono de acordo com o processo de desenvolvimento e envelhecimento, sob influências externas e internas. Esta revisão aborda o sistema de temporização circadiana humana, incluindo as influências endógenas e exógenas nos ritmos circadianos, suas particularidades relacionadas à idade, bem como as repercussões do desalinhamento circadiano nas doenças neurodegenerativas. Os ritmos circadianos enfraquecem naturalmente com o envelhecimento, mas há particularidades de acordo com a idade. Ao longo da vida, os transtornos do sono e do ritmo circadiano estão fortemente relacionados bidirecionalmente à fisiopatologia de algumas doenças psiquiátricas e neurodegenerativas, como as doenças de Alzheimer e Parkinson. Esse conhecimento pode potencialmente criar oportunidades valiosas para melhorar a saúde da população mundial que está sob desalinhamento circadiano e envelhecimento.
الملخص
ABSTRACT Objective: This study aims to evaluate the impact of morning-evening preference in pregnancy outcomes in gestational diabetes mellitus (GDM). Materials and methods: This is a prospective cohort study of 2nd-3rd trimester GDM outpatient care in Fortaleza, Brazil (2018-2020). Eveningness was defined by the Horne-Östberg Morningness-Eveningness-Questionnaire (MEQ ≤ 41). Furthermore, we obtained a 7-day actigraphic register. Subjective sleep quality, daytime somnolence, insomnia, fatigue and depressive symptoms were also evaluated. Associations with pregnancy outcomes were investigated. Results: Among 305 patients with GDM, evening preference was found in 21 (6.9%). Patients with evening preference had worse sleep quality (p < 0.01), greater severity of insomnia (p < 0.005), fatigue (p < 0.005) and depressive symptoms (<0.009). Evening chronotype was associated with preeclampsia [p = 0.01; OR = 0.27; CI 0.09-0.79] and a greater need for admission to a neonatal intensive care unit (NICU) [p = 0.02; OR = 0.23; CI .0.06-0.80]. A lower MEQ score confirmed an association with preeclampsia [p = 0.002; OR = 0.94; CI 0.90-0.97] and this was maintained after controlling for age, arterial hypertension, sleep quality, fatigue and depressive symptoms [p < 005; OR = 0.91; CI 0.87-0.95]. Conclusion: In GDM, patients with evening preference had worse sleep quality, more insomnia, fatigue, and depressive symptoms. Furthermore, eveningness was independently associated with preeclampsia. These results indicate the important role of eveningness in adverse pregnancy outcomes.
الملخص
Objective:To investigate the clinical characteristics of circadian rhythm disorder of blood pressure and its impact on orthostatic hypotension (OH) in Parkinson′s disease (PD).Methods:A total of 165 PD patients from Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from August 2019 to October 2021 were consecutively enrolled. Medical history and scores of motor and non-motor symptoms of patients were collected. Twenty-four-hour ambulatory blood pressure and OH data were collected, and the OH questionnaire was completed. The incidence of each type of circadian rhythm disorder of blood pressure was investigated. The t test, chi-square test and Mann-Whitney U test were used to determine between-group differences of circadian rhythm disorder of blood pressure. The linear trends in clinical characteristics were tested by linear regression analysis. Logistic regression analysis was used to analyze the relationship between different circadian rhythm disorders of blood pressure and OH as well as symptomatic OH (SOH). Results:In 165 PD patients, the incidence of reverse dipping pattern was 39.39% (65/165), nocturnal hypertension was 43.64% (72/165), and awakening hypotension was 31.52% (52/165). Compared with patients without reverse dipping pattern, patients with reverse dipping pattern were older [(71.72±7.81) years vs (65.29±9.68) years, t=-4.491, P<0.001], had later onset age [(66.67±9.10) years vs (62.16±10.66) years, t=-2.809, P=0.006], longer duration [36.00(20.50, 95.50) months vs 24.00(12.00, 41.75) months, Z=-3.393, P<0.001], higher dose of levodopa (LD) [(426.15±267.38) mg/d vs (284.00±235.58) mg/d, t=-3.590, P<0.001], higher levodopa equivalent dose (LED) [(514.80±360.03) mg/d vs (341.44±284.57) mg/d, t=-3.440, P=0.001], higher Unified Parkinson′s Disease Rating Scale (UPDRS)-Ⅱ scores (12.92±6.38 vs 9.54±5.59, t=-3.434, P=0.001), higher UPDRS-Ⅲ scores (28.34±11.60 vs 21.41±12.18, t=-3.508, P=0.001) and higher percentages of hallucinations [18.46% (12/65) vs 7.00% (7/100), χ2 =5.079, P=0.024]. Compared with patients without awakening hypotension, patients with awakening hypotension were older [(70.83±7.09) years vs (66.44±10.16) years, t=-2.811, P=0.006]. Compared with patients without nocturnal hypertension, patients with nocturnal hypertension had longer duration [39.50(15.00, 96.00) months vs 24.00 (12.00, 36.00) months, Z=-2.944, P=0.003], higher LD [(398.61±251.19) mg/d vs (294.62±254.25) mg/d, t=-2.619, P=0.010], higher LED [(493.28±344.02) mg/d vs (345.05±298.59) mg/d, t=-2.959, P=0.004], higher percentages of hallucinations [19.44% (14/72) vs 5.38% (5/93), χ2 =7.882, P=0.005], higher UPDRS-Ⅱ scores (12.08±6.33 vs 10.00±5.86, t=-2.086, P=0.039), higher UPDRS-Ⅲ scores (26.50±11.72 vs 22.42±12.66, t=-2.034, P=0.044), and greater blood pressure variability (BPV) (20.66±5.47 vs 17.44±5.36, t=-3.798, P<0.001). Trend analysis showed that the variety of circadian rhythm was positively correlated with age and duration, use of levodopa and monoamine oxidase B inhibitors and amantidine, morning and daily LD and LED, UPDRS-Ⅱ, UPDRS-Ⅲ and Hamilton Anxiety Scale scores, hallucinations, OH and SOH, and BPV in PD ( P<0.05). Multivariate Logistic regression analysis showed that awakening hypotension ( OR=3.35, 95% CI 1.55-7.22, P=0.002) and nocturnal hypertension ( OR=2.44, 95% CI 1.20-4.97, P=0.014) were risk factors for OH, and LED ( OR=1.21, 95% CI 1.01-1.43, P=0.035), UPDRS-Ⅲ scores ( OR=1.09, 95% CI 1.02-1.16, P=0.009) and w-BPV ( OR=1.14, 95% CI 1.01-1.29, P=0.029) were independent risk factors for SOH. Conclusions:Circadian rhythm disorder of blood pressure was correlated with age, duration, severity of motor symptoms. Awakening hypotension and nocturnal hypertension are independent risk factors for OH in PD.
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Insomnia is the second most common psychiatric disorder in clinical practice, and more than one-third of adults may experience different forms of insomnia during their lifetime, but the root causes behind insomnia need further clarification. Early evidences from twins and family studies had shown that insomnia can be attributed to genetics. In recent years, with the rapid development of gene sequencing technology, Nature Genetics had published several consecutive articles focusing on insomnia and genes, confirming that genetic factors played an important role in the occurrence and development of insomnia. Therefore, the recent research progresses on insomnia and circadian rhythm, cytokines, neurotransmitters, and other related genes were summarized in this review, which could help to understand the pathogenesis of insomnia and develop precise treatment strategies.
الملخص
Diabetic retinopathy (DR) is one of the most common and serious complication of diabetes mellitus, which is the main cause of vision loss in adults. Biological clock genes produce circadian rhythms and control its operation, while the disorder of the expression causes the occurrence and development of a series of diseases. It has been demonstrated that biological clock genes might take effects in the development and progression of DR. On the one hand, circadian rhythm disorder-related behavior disrupts the circadian oscillation of clock genes, and the change in its expression level is prone to unbalanced regulation of glucose metabolism, ultimately increasing the risk of type 2 diabetes mellitus and DR pathogenesis. On the other hand, DR patients exhibit symptoms of circadian rhythm disorders, and it has been suggested that the clock genes may control the development and progression of DR by affecting a variety of retinal pathophysiological processes. Therefore, maintaining normal circadian rhythm can be used as a disease prevention strategy, and studying the molecular mechanism of clock genes in DR can provide new ideas for more comprehensive elaboration of the pathogenesis of DR and search for new therapeutic targets.