The regulatory mechanism of physiological sleep-wake / 中国药理学通报

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism / 环境与职业医学

Background Long-term exposure to noise during sleep may has adverse effects on metabolic system, and liver lipid metabolism is closely related to circadian clock genes. Objective To investigate the effects of long-term noise exposure during sleep on liver circadian clock and lipid metabolism in mice and its related mechanism. Methods Twenty C57BL/6J male mice were randomly divided into two groups: a noise exposure group and a control group with 10 mice in each group. The mice in the noise exposure group were exposed to white noise at 90 dB sound pressure level (SPL) for 30 consecutive days, 8 h a day, from 9:00 to 17:00. The mice in the control group were exposed to background noise ≤40 dB SPL. After noise exposure, the animals were neutralized at 14:00 (ZT6) and 2:00 (ZT18), 5 animals at each time spot, and the liver tissues were collected. Total cholesterol and triglyceride in liver were determined by cholesterol oxidase method and glycerol phosphate oxidase method respectively. The expressions of circadian clock genes (Clock, Bmal1, Rev-erbα, and Rev-erbβ) and lipid metabolism genes (Srebp1c, Hmgcr, Fasn, Lxrα, Acc1, and Chrebp) in liver were detected by quantitative real-time PCR. Results Compared with the control group, the content of total cholesterol in liver in the noise exposure group increased by 48% (P<0.05) and the content of liver triglyceride increased by 61% (P<0.05) at ZT18. The mRNA expression levels of circadian clock genes Clock and Bmal1 in the noise exposure group was significantly increased at ZT18 and decreased at ZT6 (P<0.05). The mRNA expression level of Rev-erbα decreased at both ZT6 and ZT18 (P<0.05). The mRNA expression level of Rev-erbβ had no significant change at ZT6 and ZT18. The mRNA expression levels of liver lipid metabolism related genes Srebp1c, Hmgcr, Chrebp, and Lxrα in the noise exposure group were higher than those in the control group at ZT18 (P<0.05). The mRNA expression levels of Acc1 and Fasn showed no significant change at ZT6, then an upward trend at ZT18, but no significant difference between the two time spots (P>0.05). Conclusion Long-term noise exposure during sleep can cause circadian clock and lipid metabolism disorders in mice. Among them, suppression of key circadian clock genes may be associated with Rev-erbα-mediated upregulation of the nuclear receptors Srebp1c and Chrebp for lipid synthesis and deposition in the liver, resulting in lipid metabolism disorder.

Cardiovascular rhythmicity in overweight and obese children / Ritmicidade cardiovascular em crianças com sobrepeso e obesidade

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.

population analysis of the CLOCK rs3749474T-rs4864548A haplotype and its relationship with obesity / Análisis poblacional in silico del haplotipo CLOCK rs3749474T-rs4864548A y su relación con obesidad

Se ha sugerido que el haplotipo rs3749474T/rs4864548A del gen CLOCK aumentaría el riesgo de obesidad, pero se desconoce el patrón de variabilidad poblacional de estos alelos y del haplotipo. El objetivo de este estudio es determinar el nivel de ligamiento entre los alelos de riesgo rs3749474T y rs4864548A a partir de la base de datos 1000Genomes para confirmar la existencia del haplotipo TA de los polimorfismos rs3749474-rs4864548 del gen CLOCK y su frecuencia cinco macro poblaciones. Se analizó el desequilibrio de ligamiento y las frecuencias haplotípicas para 2504 individuos, de 26 poblaciones, utilizando el estadístico r y la prueba exacta de Fisher. Existe una alta frecuencia del haplotipo TA en Latinoamérica (44,8%), un alto desequilibrio de ligamiento (r= 0,92) a nivel mundial entre esos alelos, una alta diferenciación entre macro poblaciones y una alta homogeneidad al interior de ellas. La evidencia presentada permite sugerir la realización de posteriores estudios de asociación entre este haplotipo y el nivel de riesgo de obesidad y sobrepeso en poblaciones latinoamericanas.

It has been suggested that the rs3749474T/rs4864548A haplotype of the CLOCK gene increases the risk of obesity, but the population variability of these alleles and the haplotype is unknown. This research aims to determine the linkage between the rs3749474T and rs4864548A alleles from the database of 1000Genomes to confirm the existence of the TA haplotype polymorphisms of these alleles and their frequency in five macro populations. Linkage disequilibrium and haplotype frequencies for 2504 individuals from 26 populations were analyzed using the r statistic and Fisher's exact test. There is a high frequency of the TA haplotype in Latin America (44.8%), a high linkage disequilibrium (r2= 0.92) worldwide between these alleles, a high differentiation between macro populations, and a high homogeneity. The evidence warrants further studies on the association between this haplotype and the risk of obesity and overweight in Latin American populations.

Difference in ketone bodies levels between diurnal and nocturnal fasting in children: observational study

Introduction Children are susceptible to developing preoperative ketonemia, which can be affected by changes in the circadian rhythm and counter-regulatory hormones. It is unclear whether ketonemia depends on the timing of fasting. Objective To assess the effect of preoperative fasting time (diurnal vs. night) on the preoperative concentration of ketone bodies in children. Methods We conducted a prospective-observational clinical study between September 2020 and March 2021, including children under 48 months of age scheduled for elective surgery. Two groups were identified based on fasting time, as follows: diurnal fasting (group A, n = 40) and nocturnal fasting (group B, n = 52). Demographic data, duration of fasting, time of excess fasting, type of food intake, the concentration of ketone bodies and capillary blood glucose, level of anxiety, and dehydration were analyzed in both groups. Results Diurnal fasting was associated with higher incidence of ketonemia compared with nocturnal fasting (Group A: 62.5% (95% CI 48.1-82.0); group B: 38,5% (95% CI 26.5-52.5), P=0.02). Most of the patients exceeded the duration of fasting recommended by preoperative fasting guidelines (95.6%). The type of food eaten before surgery was significantly associated with the presence of ketonemia (P=0.01). Conclusions Preoperative ketonemia is relatively common in patients under 48 months of age, especially among those who undergo diurnal fasting compared to nocturnal fasting.

Introducción Los niños son susceptibles a desarrollar cetonemia preoperatoria que puede verse afectada por cambios en el ritmo circadiano y las hormonas contrarreguladoras. No está claro si la cetonemia depende de la hora del ayuno. Objetivo Evaluar el efecto del momento del ayuno preoperatorio (diurno vs. nocturno) sobre la concentración preoperatoria de los cuerpos cetónicos en niños. Métodos Llevamos a cabo un estudio clínico observacional entre septiembre de 2020 y marzo de 2021, en niños menores de 48 meses, programados para cirugía electiva. Se identificaron dos grupos basados en la hora del ayuno, como sigue: ayuno diurno (grupo A, n = 40) y ayuno nocturno (grupo B, n = 52). En ambos grupos se analizaron los datos demográficos, la duración del ayuno, el tiempo excesivo de ayuno, el tipo de ingesta de alimentos, la concentración de cuerpos cetónicos, la glicemia capilar, el nivel de ansiedad y la deshidratación. Resultados El ayuno diurno se asocio con una mayor incidencia de cenotemia en comparación con el ayuno nocturno (Grupo A: 62,5% (IC 95% 48,1-82,0); grupo B: 38,5% (95% CI 26.5-52.5), P=0.02). La mayoría de los pacientes excedieron el tiempo de ayuno recomendado según las guías de ayuno preoperatorio (95,6%). El tipo de alimentos ingeridos antes de la cirugía se asoció de manera importante con la presencia de cetonemia (P=0,01). Conclusiones La cetonemia preoperatoria es relativamente común en pacientes menores de 48 meses de edad, especialmente entre quienes se someten a ayuno diurno en comparación con ayuno nocturno.

How Plants Adapt to the Photoperiod

Plants are extremely sensitive to changes in their environment, particularly variations in photoperiod or day length. Photoperiodism refers to a plant's capacity to detect variations in day length and make use of this knowledge to control key developmental processes including flowering, growth, and dormancy. Through a process known as photoperiodism, plants can detect and react to variations in the number of daylight hours, or photoperiod. The physiological response of plants to the length of day or night is known as photoperiodism. The plant uses this physiological response to time-critical developmental events like flowering. In this essay, I will cover the current understanding of how plants respond to photoperiod and the molecular mechanisms underpinning this response. Three groups of plants' photoperiodic responses can be distinguished: short-day plants (SDPs), long-day plants (LDPs), and day-neutral plants (DNPs). Whereas LDPs bloom when the length of the day exceeds the crucial threshold, SDPs do so only when it is shorter than the critical threshold. Conversely, DNPs do not have a crucial day duration and can bloom at any day length. Many genes and biochemical processes control how a plant responds to the photoperiod. The creation and movement of the hormone florigen, which starts blooming in response to photoperiodic signals, is a crucial regulating mechanism. On the other hand, a class of photoreceptors known as phytochromes is involved in the biochemical mechanisms driving photoperiodic responses in plants. The perception of light's duration, quality, and amount is caused by phytochromes. The red-light-absorbing Pr form and the far-red-light-absorbing Pfr form are the two interconvertible states in which they can exist. The ratio of Pr to Pfr is altered by the duration of light exposure and is utilizes by plants to assess day length. Exposure to light in SDPs causes the expression of the CONSTANS (CO) gene, and the CO protein causes the expression of the FLOWERING LOCUS T (FT), a gene that encourages flowering. By exposing LDPs to light, a different gene called GI (GIGANTEA) is induced rather than CO, which is normally expressed. The FT gene's expression is encouraged by GI's interaction with the protein ZEITLUPE (ZTL), which also encourages flowering. In addition to these essential elements, several proteins and signalling pathways are also involved in photoperiodic responses in plants. For instance, to optimise the response to variations in day length, the photoperiodic pathway interacts with the circadian clock, which controls numerous physiological processes in plants. In some species, the hormone gibberellin (GA) also aids in the promotion of flowering. One essential adaptation that enables plants to synchronize their developmental processes with seasonal changes is their capacity to react to variations in day length. Phytochromes play a key role in how plants perceive the day in the complex network of proteins and signalling channels that make up the molecular mechanisms behind photoperiodic responses in plants. There is still much to learn about the diversity and complexity of the photoperiodic response across several plant groupings, even if much is known about it in particular species.

Sleep in the human aging process and circadian sleep rhythm disruptions / Sono no processo de envelhecimento humano e interrupções do ritmo circadiano do sono

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.

Morningness/eveningness in gestational diabetes mellitus: clinical characteristics and maternal-neonatal outcomes

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.

Progress of Research on Relationship of Circadian Rhythm Disorder and Gut Microbiota Involved in Neurodegenerative Diseases / 胃肠病学

With the increase in global life expectancy, the incidence of neurodegenerative diseases is increasing year by year. Studies have confirmed that patients with different types of neurodegenerative diseases have circadian rhythm disorder and gut microbiota dysregulation. The occurrence of neurodegenerative diseases and circadian rhythm disorder are mutually causal, and in this causal relationship, gut microbiota may play an important role. Gut microbiota affects the communication between gut and brain through "microbiota ⁃ gut ⁃ brain axis", and can affect neural development. Gut microbiota dysregulation can increase the risk of neurodegenerative diseases. At the same time, the diurnal fluctuation of gut microbiota themselves is also regulated by the host biological clock. This article reviewed the progress of research on relationship of circadian rhythm disorder and gut microbiota involved in neurodegenerative diseases.

Targeting the blood-brain barrier to delay aging-accompanied neurological diseases by modulating gut microbiota, circadian rhythms, and their interplays

The blood-brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population. Importantly, circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines, resulting in disruption of BBB integrity. Collectively, this provides a new perspective for exploring the relationship among circadian rhythms, gut microbes, and the BBB in aging-accompanied neurological diseases. In this review, we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis, and their potential roles in the BBB disruption that occurs in AAND. Based on existing literature, we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota, which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

The Circadian System Is Essential for the Crosstalk of VEGF-Notch-mediated Endothelial Angiogenesis in Ischemic Stroke / 神经科学通报·英文版

Ischemic stroke is a major public health problem worldwide. Although the circadian clock is involved in the process of ischemic stroke, the exact mechanism of the circadian clock in regulating angiogenesis after cerebral infarction remains unclear. In the present study, we determined that environmental circadian disruption (ECD) increased the stroke severity and impaired angiogenesis in the rat middle cerebral artery occlusion model, by measuring the infarct volume, neurological tests, and angiogenesis-related protein. We further report that Bmal1 plays an irreplaceable role in angiogenesis. Overexpression of Bmal1 promoted tube-forming, migration, and wound healing, and upregulated the vascular endothelial growth factor (VEGF) and Notch pathway protein levels. This promoting effect was reversed by the Notch pathway inhibitor DAPT, according to the results of angiogenesis capacity and VEGF pathway protein level. In conclusion, our study reveals the intervention of ECD in angiogenesis in ischemic stroke and further identifies the exact mechanism by which Bmal1 regulates angiogenesis through the VEGF-Notch1 pathway.

Research progress on the association and mechanism between dietary rhythm, circadian rhythm and cardiovascular health in children and adolescents / 中国学校卫生

Abstract@#Hypertension in children can have adverse health effects such as vascular damage, cardiac metabolic risk, and organ damage during childhood, and can also increase the risk of hypertension in adulthood. Obesity has been recognized as an important cause of elevated blood pressure in children. By reviewing and summarizing relevant literature at home and abroad, the study analyzes the relationship between dietary and circadian rhythm and explores the role and mechanism of circadian rhythm in terms of the metabolic health of youth, thereby providing a scientific basis for the prevention and treatment of cardiovascular diseases in this population and to identify directions for future research.

Research progress on the biological clock genes and diabetic retinopathy / 中华眼底病杂志

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.

Research progress of genes related to insomnia disorder / 中华神经科杂志

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.

A pilot study on the clinical characteristics of blood pressure circadian rhythm disorder and its impact on orthostatic hypotension in Parkinson′s disease / 中华神经科杂志

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.

Research progress on adverse events during morning or afternoon surgery and perioperative period / 中国医师杂志

The occurrence of perioperative adverse events (PAEs) significantly affects postoperative recovery of patients. In recent years, more and more studies have found that the start time of surgery is closely related to the occurrence of PAE, especially in terms of hospital stay and cost, intraoperative and postoperative complications, and postoperative mortality. This review aims to summarize the impact of different types of surgeries on PAE starting in the morning or afternoon, and to elucidate the possible mechanisms by which morning or afternoon surgeries affect PAE occurrence from the perspectives of circadian rhythms, human factors, and infrastructure, in order to provide reference for reducing patient PAE and accelerating patient recovery.

Efficacy of Sishen pill compound combined with mesalazine in the treatment of mild to moderate ulcerative colitis and its effect on the circadian rhythm of symptoms / 中国基层医药

Objective:To investigate the efficacy of Sishen pill compound combined with mesalazine in the treatment of mild to moderate ulcerative colitis and its effect on the circadian rhythm of symptoms. Methods:A total of 136 patients with mild to moderate ulcerative colitis who received treatment in Hospital of Chengdu University of Traditional Chinese Medicine from January 2018 to December 2020 were included in this prospective randomized controlled trial. These patients were divided into a treatment group ( n = 68) and a control group ( n = 68). The treatment group was treated with Sishen pill compound combined with mesalazine. The control group was treated with mesalazine alone. All patients were treated for 12 weeks. Clinical efficacy, as well as morning abdominal pain grade, morning diarrhea score, fecal trait score, Mayo score, hemoglobin, and hypersensitive C-reactive protein pre- and post-treatment, were compared between the two groups. Results:Total response rate in the treatment group was significantly higher than that in the control group [91.18% (62/68) vs. 72.06% (49/68), χ2 = 8.28, P < 0.05]. After treatment, morning diarrhea score, morning abdominal pain score, fecal trait score, Mayo score, hemoglobin, and hypersensitive C-reactive protein in the treatment group were (0.47 ± 0.56) points, (0.53 ± 0.56) points, (3.01 ± 0.72) points, (7.13 ± 1.38) points, (108.04 ± 12.21) g/L, (4.00 ± 2.19) mg/L, respectively, and they were (0.84 ± 0.56) points, (1.12 ± 0.56) points, (4.40 ± 0.76) points, (3.25 ± 1.44) points, (102.15 ± 12.61) g/L, and (6.07 ± 3.66) mg/L respectively in the control group. There were significant differences in these indexes between the treatment and control groups ( t = 3.59, 5.95, 10.06, 9.62, 2.78, 3.99, all P < 0.05). Conclusion:Sishen pill compound combined with mesalazine can effectively reduce clinical symptoms of active ulcerative colitis, increase hemoglobin level, decrease C-reactive protein level, improve the efficiency of treatment, reduce symptoms and the number of diarrhea rhythms, and improve stool symptoms of mild to moderate ulcerative colitis patients.

Clinical value of circadian clock related biomarkers for the diagnosis of chronic pancreatitis with pancreatic exocrine insufficiency / 中华胰腺病杂志

Objective:To examine the expression of core clock genes in the peripheral blood mononuclear cells (PBMCs) and the level of circadian disturbance-related proteins in the serum of chronic pancreatitis (CP) patients with pancreatic exocrine insufficiency (PEI), and explore their potential diagnostic value in clinical practice.Methods:The peripheral blood samples and related clinical data from 68 patients diagnosed with CP in Shanghai General Hospital from Jan 2015 to Jan 2022 were collected. Peripheral blood samples from 30 healthy individuals were used for control. The M-ANNHEIM classification system was used to stratify the clinical stages of patients with CP. The mRNA expression of the core clock genes, including Clock, Bmal1, Per1/2/3 and Cry1/2 in PBMCs was analyzed using realtime qPCR, and the expression of circadian disturbance-related proteins like TrkB, CD 36 and Rbp in serum was measured with ELISA. The receiver operating characteristic curve(ROC) and the area under curve (AUC) was used to test the efficiency for diagnozing PEI. Results:The mRNA expression of Per1 in CP patients was significantly decreased (0.76 vs 1, P<0.05), and the AUC for diagnozing PEI was 0.744 (95% CI 0.628-0.860), with a cut-off value of 0.72; and the sensitivity and specificity was 84.8% and 57.1%, respectively. The protein abundance of serum CD 36 was significantly increased in CP patients (33.85±19.74ng/ml vs 24.71±11.53 ng/ml, P<0.05); the AUC for diagnozing PEI was 0.834 (95% CI 0.735-0.932), with a cut-off value of 29.75 pg/ml; and the sensitivity and specificity was 74.3% and 84.8%, respectively. The expression of CD 36 was increased with the increase of CP clinical stage, and there were statistically significant differences between either two stages (all P value <0.05). The mRNA expression of Per1 in patients with CP in Stage Ⅰ was significantly higher than that in patients with CP in Stage Ⅱ or Ⅲ, and the differences were statistically significant ( P<0.05), but no statistical difference was found between Stage Ⅱ and Stage Ⅲ. Conclusions:The decreased expression of Per1 mRNA in PBMCs and increased level of CD 36 in serum are significantly related to the occurrence of PEI in CP, suggesting that they may have potential value for diagnozing PEI and guiding the clinical practice.

Biological clock rhythm disorder and hypertension / 国际脑血管病杂志

Biological clock proteins are involved in the regulation of many important physiological processes, including blood pressure. The deletion or mutation of core circadian clock genes may cause elevated blood pressure levels and disrupted blood pressure rhythms, exacerbating vascular function damage, and ultimately leading to the occurrence, development and poor outcome of ischemic stroke. This article reviews the molecular mechanism of biological clock rhythm, the relationship between biological clock gene and blood pressure regulation mechanism, the mechanism of circadian rhythm disorder in the occurrence and development of hypertension, and the relationship between blood pressure rhythm disorder and stroke.

Research progress of circadian rhythm and circadian clock gene regulation in the development of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

With the development of society, the incidence of myopia and the population of myopia has increased year by year, which has become a major public health problem. Therefore, the research on the pathogenesis and prevention and control measures of myopia is imminent. In recent years, the role of the biological clock in the development of myopia has gradually attracted scholars interest. Now the author starts from the impact of the biological clock on the axial length, retina and choroid in the development of myopia. In order to provide new ideas for the study of prevention and control measures and the pathogenesis of myopia, a brief review is made from the perspective of contemporary society and disrupted body clock.