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.
Objective To systematically review the health economic evaluations of using long-term rhythm-control antiarrhythmic drugs (AAD) for patients with paroxysmal or persistent atrial fibrillation (AF). Methods Databases including PubMed, EMbase, Scopus, CNKI, SinoMed, WanFang Data, and official websites of well-established health technology assessment (HTA) institutions were electronically searched to present the economic evaluations of AAD and the recommendations of HTA institutions based on drug economy from inception to April 23rd, 2022. Two reviewers independently screened the literature, extracted data and systematic review was then performed. Results A total of 19 studies were included, including 11 cost-effectiveness or cost-utility analysis studies and 8 official documents from HTA institutions. Only 5 (45.5%) economic evaluations were of relatively high quality, and English language studies were of higher quality than Chinese language studies ones. The included studies lacked elements that CHEERS 2022 concerns, such as health economics analysis plans, equity and distributional effects, engagement with patients and other stakeholders and the impact on the study. Dronedarone and amiodarone were the main focus of the evaluation, and the study results showed that dronedarone was cost-effective compared with other drugs in different study designs and national settings. However, there were differences between the recommendations of HTA agencies and the results of economic evaluation studies. Conclusion The completeness of health economics evaluations needs to be improved, along with the quality of clinical evidence in the field of AF-AAD for Chinese patients. Additionally, the informational value of drugs should be thoroughly investigated through budget impact analysis and distributional cost-effectiveness analysis to provide evidence of high-quality studies for decision-makers in China.
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。
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.
The traditional paradigm of motor-imagery-based brain-computer interface (BCI) is abstract, which cannot effectively guide users to modulate brain activity, thus limiting the activation degree of the sensorimotor cortex. It was found that the motor imagery task of Chinese characters writing was better accepted by users and helped guide them to modulate their sensorimotor rhythms. However, different Chinese characters have different writing complexity (number of strokes), and the effect of motor imagery tasks of Chinese characters with different writing complexity on the performance of motor-imagery-based BCI is still unclear. In this paper, a total of 12 healthy subjects were recruited for studying the effects of motor imagery tasks of Chinese characters with two different writing complexity (5 and 10 strokes) on the performance of motor-imagery-based BCI. The experimental results showed that, compared with Chinese characters with 5 strokes, motor imagery task of Chinese characters writing with 10 strokes obtained stronger sensorimotor rhythm and better recognition performance (P < 0.05). This study indicated that, appropriately increasing the complexity of the motor imagery task of Chinese characters writing can obtain stronger motor imagery potential and improve the recognition accuracy of motor-imagery-based BCI, which provides a reference for the design of the motor-imagery-based BCI paradigm in the future.
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 regression, least absolute shrinkage and selection operator 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. 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 poorer 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. The scRNA-seq analysis showed that 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.
On account of the mechanical disturbance of external chest pressing to electrocardiogram (ECG) signal, the ECG rhythm cannot be identified reliably during the cardio-pulmonary resuscitation period. Whereas the possibility of successful resuscitation will be lowered due to interrupted external chest pressing, a new filtering algorithm, enhanced leastmean-square (eLMS) algorithm, was proposed and developed in our laboratory. The algorithm can filter the disturbance of external chest pressing without the support of hardware reference signal and correctly identify ventricular fibrillation (VF) rhythm and normal sinus rhythm in case of uninterrupted external chest pressing. Without other reference signals, this algorithm realizes filtering only through the interrupted electrocardiograma (cECG) signal. It was verified with ECG signal and disturbance signal under different signal to noise ratios and contrasted with other mature algorithms. The verification results showed that the identification effect of eLMS was superior to those of others under different signal to noise ratios. Furthermore, ECG rhythm can be correctly identified only through cECG signal. This algorithm not only reduces the research and development(R & D)costs of automated external defibrillator but also raises the identification accuracy of ECG rhythm and the possibility of successful resuscitation.
Depression, a mental health disorder, has emerged as one of the significant challenges in the global public health domain. Investigating the pathogenesis of depression and accurately assessing the symptomatic changes are fundamental to formulating effective clinical diagnosis and treatment strategies. Utilizing non-invasive brain imaging technologies such as functional magnetic resonance imaging and scalp electroencephalography, existing studies have confirmed that the onset of depression is closely associated with abnormal neural activities and altered functional connectivity in multiple brain regions. Magnetoencephalography, unaffected by tissue conductivity and skull thickness, boasts high spatial resolution and signal-to-noise ratio, offering unique advantages and significant value in revealing the abnormal brain mechanisms and neural characteristics of depression. This review, starting from the rhythmic characteristics, nonlinear dynamic features, and connectivity characteristics of magnetoencephalography in depression patients, revisits the research progress on magnetoencephalography features related to depression, discusses current issues and future development trends, and provides insights for the study of pathophysiological mechanisms, as well as for clinical diagnosis and treatment of depression.