目的:观察氨氯地平片治疗非杓型老年高血压患者对血压昼夜节律异常及对动态动脉硬化指数(AASI)的影响。方法:80例患者每日晨8时顿服氨氯地平5～10mg/d,服药前及治疗8周后行24h动态血压监测。结果:80例完成治疗的患者中,60例血压昼夜节律异常逆转,同时改善AASI。而20例血压昼夜节律无逆转,AASI与治疗前比较无差异。结论:经氨氯地平片治疗后,75%的非杓型高血压患者,可改善血压昼夜节律异常及AASI。
The use of actigraphy, which can be used to estimate sleep-wake patterns from activity levels, has become common in sleep research. Actigraphy is a simple, cost-effective and non-invasive method for healthcare providers and researchers to assess patients sleep quality and screen for potential sleep disorders in recent years. But, there is no wide recognition and application of actigraphy in China up till now. This review summarized the application of actigraphy in evaluation of sleep and diagnosis of sleep disorders.
Huntington’s disease (HD) is characterized by chorea, cognitive impairment, and psychiatric symptoms. Sleep and circadian rhythm disturbances are one of the important symptoms of HD that have been gradually recognized in recent years, and have a serious impact on the quality of life of patients and their caregivers. The clinical manifestations of sleep and circadian rhythm disturbances in HD are different from those of other neurodegenerative diseases. The exact pathological mechanisms of these disturbances remain unclear and there is no specific treatment. This article reviews the current progress in the study of sleep and circadian rhythm disturbances in HD, including its pathological mechanisms, clinical manifestations, assessment methods, correlation with cognitive impairment and psychiatric symptoms, treatment and management.
Difference of chronotypes makes influence to cognitive performance of individuals in routine duties. In this paper, 55 subjects with different chronotypes were subjected to continuous sleep deprivation for 30 h by using the constant routine protocol, during which core body temperature was measured continuously, and subjective sleepiness self-rating and the performance of selective attention were measured hourly. The results showed that the phase difference of core body temperature has no significant difference, yet the amplitude and term difference among the three chronotypes are significant. There was an advance in phase between subjective sleepiness self-rating and core body temperature, and the self-rating sleepiness of evening type came the latest, and the self-rating sleepiness of morning type dissipated the fastest. The response time of selective attention showed a 2 h phase delay with subjective sleepiness self-rating. And the analysis of core body temperature showed that the later the chronotype was, the greater the phase delay was. The correct rate of selective attention of different chronotypes were inconsistent with delay of subjective sleepiness self-rating and core body temperature. We provide reference for industry, aviation, military, medical and other fields to make a more scientific scheduling/ shifting based on cognitive performance characteristics of different chronotypes.
Circadian rhythm is a physiological regulation mechanism evolved by the body to adapt to the 24-hour fluctuations in the internal and external environment. It plays an important role in many physiological and pathological processes including the immune system. Neutrophils are the most important immune cells in the human circulation, and their numbers and phenotypes also show obvious circadian fluctuations. A growing number of studies have shown that the cellular and molecular mechanisms of neutrophil circadian rhythms are disease-related. Combining the latest research on neutrophil circadian rhythm, this article briefly introduces the recruitment of neutrophils in the bone marrow, the aging of neutrophils and their infiltration into various tissues of the body, and discusses the interventions. It also discusses the therapeutic prospects based on neutrophil circadian rhythm-related mechanisms from the perspectives of intervening neutrophil aging-related chemokines and chronotherapy.
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.
ObjectiveTo explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). MethodsThe Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. GO, KEGG, and GSEA enrichment analyses were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox analysis, LASSO regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients' 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Finally, single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. ResultsDifferentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poored prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. Through scRNA-seq analysis, RORA and KLF10 were mainly expressed in natural killer cells. ConclusionThe prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.
Objective To investigate the effect of circadian rhythm disorder on rat knee cartilage and the mechanism of basic helix-loop-helix ARNT like 1 (Bmal1) on the regulation of cell cycle-related genes. Methods Forty rats were randomly divided into normal group, circadian rhythm disorder group (disorder group), Bmal1 overexpression lentivirus infection circadian rhythm disorder group (Bmal1 up-regulated group) and Bmal1 overexpression lentivirus negative infection circadian rhythm disorder group (Bmal1 negative infection group), with 10 rats in each group. Saffron fast green staining, TdT-mediated dUTP nick-end labeling staining, immunohistochemical staining, reverse transcription polymerase chain reaction and Western blotting were used to compare the pathological changes of cartilage tissue, the apoptosis of chondrocytes, and the relative mRNA expression levels of Bmal1, WEE1 G2 checkpoint kinase (Wee1), cyclin-dependent kinase 1 (Cdk1), cyclin B1 (Ccnb1), BCL2-associated X protein (Bax), apoptosis regulator 2 (Bcl2), interleukin 1 (Il1), interleukin 6 (Il6), tumor necrosis factor (Tnf) and matrix metallopeptidase 13 (Mmp13) among different groups. The relative expression levels of BMAL1, WEE1, CDK1, CCNB1, BAX and BCL2 proteins were detected, and correlation analysis was performed according to the relative expression of mRNA. Results Safranine fast green staining showed that the thickness of cartilage matrix in the normal group was normal and uniform red. The cartilage matrix in the disorder group and the Bmal1 negative infection group was destroyed, and the proteoglycan was lost obviously, showing uneven red. The thickness of cartilage matrix in the Bmal1 up-regulated group was basically normal, and the proteoglycan was not lost obviously, and the red was slightly less uniform. Compared with those of the normal group, the positive rates of apoptotic cells in articular cartilage of the disorder group and the Bmal1 negative infection group increased significantly, the mRNA and protein expression levels of Bmal1, Wee1, and Bcl2 were down-regulated, the mRNA and protein expression levels of Cdk1, Ccnb1, and Bax were up-regulated, the mRNA expression levels of Il1, Il6, Tnf and Mmp13 were up-regulated, the differences were statistically significant (P<0.05); there was no significant change in the positive rate of apoptotic cells in the articular cartilage of the Bmal1 up-regulated group, and there was no significant difference in the mRNA or protein expression of Bmal1, Wee1, Bcl2, Cdk1, Ccnb1 or Bax, nor the mRNA expression of Il1, Il6, Tnf or Mmp13 (P>0.05). Correlation analysis showed that Bmal1 was positively correlated with Wee1 and Bcl2 (r=0.84, 0.44; P<0.01), and negatively correlated with Cdk1, Ccnb1 and Bax (r=–0.55, –0.72, –0.41; P<0.01). Conclusion Chronic circadian rhythm disorder can cause the increase of chondrocyte apoptosis and osteoarthritis-like changes of articular cartilage through the expression changes of circadian clock gene Bmal1 and cell cycle-related genes and proteins.