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Epigenetic regulation in major depression and other stressrelated disorders: molecular mechanisms, clinical relevance and therapeutic potential

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4214-4243页

作者： Minlan Yuan Biao Yang Gerson Rothschild J.John Mann Larry D.Sanford xiangdong tang Canhua Huang Chuang Wang Wei Zhang Mental Health Center and Psychiatric Laboratory the State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Abdominal Oncology West China HospitalSichuan UniversityChengdu 610041China Department of Microbiology and Immunology Vagelos College of Physicians and SurgeonsColumbia UniversityNew YorkNY 10032USA Department of Psychiatry Columbia UniversityNew YorkNY 10032USA Molecular Imaging and Neuropathology Division New York State Psychiatric InstituteNew YorkNY 10032USA Department of Radiology Columbia UniversityNew YorkNY 10032USA Sleep Research Laboratory Center for Integrative Neuroscience and Inflammatory DiseasesPathology and AnatomyEastern Virginia Medical SchoolNorfolkVAUSA Sleep Medicine Center Department of Respiratory and Critical Care MedicineMental Health CenterTranslational Neuroscience Centerand State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Department of Pharmacology and Provincial Key Laboratory of Pathophysiology in School of MedicineNingbo UniversityNingboZhejiang 315211China West China Biomedical Big Data Center West China HospitalSichuan UniversityChengdu 610041China Medical Big Data Center Sichuan UniversityChengdu 610041China

Major depressive disorder(MDD)is a chronic,generally episodic and debilitating disease that affects an estimated 300 million people worldwide,but its pathogenesis is poorly *** heritability estimate of MDD is 30–40%,suggesting that genetics alone do not account for most of the risk of major *** factor known to associate with MDD involves environmental stressors such as childhood adversity and recent life *** studies have emerged to show that the biological impact of environmental factors in MDD and other stress-related disorders is mediated by a variety of epigenetic *** epigenetic modification alterations contribute to abnormal neuroendocrine responses,neuroplasticity impairment,neurotransmission and neuroglia dysfunction,which are involved in the pathophysiology of ***,epigenetic marks have been associated with the diagnosis and treatment of *** evaluation of epigenetic modifications holds promise for further understanding of the heterogeneous etiology and complex phenotypes of MDD,and may identify new therapeutic ***,we review preclinical and clinical epigenetic findings,including DNA methylation,histone modification,noncoding RNA,RNA modification,and chromatin remodeling factor in *** addition,we elaborate on the contribution of these epigenetic mechanisms to the pathological trait variability in depression and discuss how such mechanisms can be exploited for therapeutic purposes.

关键词： therapeutic clinical alterations

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Test-retest reliability of Epworth Sleepiness Scale Score in Obstructive Sleep Apnea After Short Intervals

Test-retest reliability of Epworth Sleepiness Scale Score in...

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中国睡眠研究会第十五届全国学术年会

作者： Xujun Feng xiangdong tang Department of Respiratory Medicine Sleep Medicine Center West China Hospital Sichuan University

Study objectives: Obstructive sleep apnea(OSA) is a common disorder, and Epworth Sleepiness Scale(ESS) is widely used to evaluate treatment effects in OSA ***, the reliability of ESS is *** investigate the repeated measures stability of ESS over a short period and effects of follow-up methods, demographic factors, and OSA severity on ESS score ***: Patients diagnosed with OSA at Sleep Medicine Center between October 2022 and May 2023 were prospectively included in this *** first ESS assessment was performed at Sleep Medicine Center, and a second ESS score was obtained within 1 week of face-to-face or telephone *** treatment interventions were applied to the patients between the pre-and *** analyses were performed to explore the effects of age, sex, body-mass index(BMI), and OSA severity on ESS ***: In total, 382 patients with OSA(80.6% men) were included, with a mean ± standard deviation age of 43.52 ± 12.41 years, BMI 26.54 ± 4.01 kg/m2, and apnea hypopnea index 47.93 ± 25.86 events/*** intraclass correlation coefficient(ICC) estimate for the ESS test-retest reliability was 0.820(0.653-0.894).The mean difference in the test-retest ESS score was 1.68 ± *** women, the difference was 0.82 ± 2.30(versus 1.89 ± 3.03 in men), and in patients with BMI > 28 or AHI ≥ 30, the difference was 2.39 ± 3.46(versus 1.38 ± 2.62 in BMI ≤ 28) and 1.77± 3.01(versus 1.35 ± 2.58 in AHI < 30), *** percentage of people with a difference in ESS score ≥ 2, 3, 5, and 7 on consecutive measures was 67%, 49%, 18%, and 4%, ***-up modalities and age did not affect variations in retested ESS ***: We recommend averaging ESS scores after two or more measurements to accurately reflect their subjective tendency toward somnolence for patients who are male, obese, or have severe OSA.

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Causal relationships between obstructive sleep apnea and insomnia: A bidirectional mendelian randomization study

Causal relationships between obstructive sleep apnea and ins...

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中国睡眠研究会第十五届全国学术年会

作者： Hui Jin Ye Zhang xiangdong tang West China hospital

Objectives: To explore the bidirectional causal relationship between obstructive sleep apnea(OSA) and insomnia via two-sample Mendelian randomization(MR) ***: When exploring the causal relationship from OSA to insomnia, we selected the instrumental variables(IVs) from the genomewide association study(GWAS) summary statistics of insomnia in UK Biobank(N=386533 individuals), utilized as *** other dataset of GWAS from FinnGen consortium(N=664510 individuals) proxying OSA was used as ***, we used aforementioned GWAS to conduct a reversed MR analysis to clarify their bidirectional *** analyses were performed mainly through inverse variance weighted(IVW) *** median, MR-Egger regression, weighted mode, and simple mode were adopted as a supplement to the IMW ***: MR analysis showed that OSA as exposure did not increase the risk of insomnia(OR = 1.02, 95% CI = 0.96-1.09), while insomnia as exposure did not increase the risk of OSA(OR = 0.98, 95% CI = 0.77-1.24).Conclusions: The present study found no evidence for causal associations between OSA and insomnia in individuals of European ancestry.

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Identification of surgical patients at high risk of OSAS using the Berlin Questionnaire to detect potential high risk of adverse respiratory events in post anesthesia care unit

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Frontiers of Medicine 2018年第2期12卷 189-195页

作者： Fei Liu Li Liu Fang Zheng xiangdong tang Yongxin Bao Yunxia Zuo Department of Anesthesiology West China Hospital Sichuan University Chengdu 610041 China School of Computing Chongqing University Chongqing 400044 China School of Information Science & Engineering Lanzhou University Lanzhou 730000 China Sleep Medicine Center Mental Health Center Translational Neuroscience Center West China Hospital Sichuan University Chengdu 610041China Qingdao Women's and Children's Hospital Qingdao 266000 China

Obstructive sleep apnea syndrome （OSAS） increases the risk of post-surgery complications. This study uses Berlin Questionnaire （BQ） to identify Chinese adult surgical patients who are at a high risk of OSAS and to determine if the BQ could be used to detect potential high risk of adverse respiratory events in the post anesthesia care unit （PACU）. Results indicated that only 11.4% of the patients were considered at a high risk of OSAS. Age and body mass index are the key factors for the risk of OSAS prevalence in China and also gender specific. Furthermore, the incidence of adverse respiratory events in the PACU was higher in patients with high risk of OSAS than others （6.8% vs. 0.9%, P 〈 0.001）. They also stayed longer than others in the PACU （95 ~ 28 min vs. 62 ~ 19 min, P 〈 0.001）. Age, high risk for OSAS, and smoking were independent risk factors for the occurrence of adverse respiratory events in the PACU. The BQ may be adopted as a screening tool for anesthesiologists in China to identify patients who are at high risk of OSAS and determine the potential risk of developing postoperative respiratory complications in the PACU.

关键词： obstructive sleep apnea Berlin Questionnaire Chinese surgical patients adverse respiratory event

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Factors influencing the effectiveness of digital cognitive behavioral therapy for chronic insomnia in clinical practice

Factors influencing the effectiveness of digital cognitive b...

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中国睡眠研究会第十五届全国学术年会

作者： Yuan Shi Rong Ren Ye Zhang xiangdong tang west China hospital

Objectives: Digital cognitive behavioral therapy for chronic insomnia(D-CBT-I) has been shown as efficacious as traditional ***, not all patients achieve insomnia remission after *** explored the factors influencing the effectiveness of DCBT-I in a clinical ***: A total of 414 Asian chronic insomniacs were studied during a six-week D-CBT-I *** patients were assessed at baseline and posttreatment and were determined to be remitters or nonremitters, responders or non-responders by posttreatment criteria;Insomnia Severity Index(ISI < 8) or ISI reduction ≥ 8, to examine whether remission and response status were associated with patient baseline ***: The average baseline ISI score in all subjects was 16.29 *** posttreatment, 192(46.4%) patients achieved ISI remission and 218(52.7%) patients demonstrated ISI *** baseline early morning awakening time and ISI score were independently associated with lower odds for remission(OR, 0.995 and 0.991, respectively).Increased baseline Patients Health Questionnaire-9 score was independently associated with higher odds for response(OR, 1.114).Conclusions: Our results suggest that D-CBT-I can be recommended as the first-line treatment for chronic insomnia, particularly in insomniacs with milder insomnia symptoms and more severe depressive ***, the effectiveness of D-CBT-I was adversely affected by longer early morning awakening time and higher insomnia severity at pretreatment, which may be improved by more intense intervention and greater therapeutic support or by traditional CBT-I.

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自然对流工况下堆顶三维温度场及流场数值模拟研究

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核动力工程 2023年第S2期44卷 44-49页

作者：唐向东李维中国核动力研究设计院反应堆系统设计技术重点实验室成都610213

压水堆核电厂堆顶设备较多,温度场和流场复杂。为评估采用自然对流对控制棒驱动机构(CRDM)进行冷却的可行性。基于FLUENT软件,对自然对流工况下堆顶结构开展数值模拟研究,得到4种工况下的流场、温度场分布及线圈最高温升。模拟结果表明... 详细信息

压水堆核电厂堆顶设备较多,温度场和流场复杂。为评估采用自然对流对控制棒驱动机构(CRDM)进行冷却的可行性。基于FLUENT软件,对自然对流工况下堆顶结构开展数值模拟研究,得到4种工况下的流场、温度场分布及线圈最高温升。模拟结果表明,不同运行工况下,采用自然对流的方式均能将CRDM运行产生的热量完全带出堆坑,不存在堆坑窝热情况,CRDM线圈温度均不会超过其工作温度限值。为采用自然对流对CRDM进行冷却提供了重要依据。

关键词：压水堆驱动机构温度场自然对流

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Sleep Perception Moderates Treatment Response to Cognitive Behavior Therapy for Insomnia(CBT-I) in Patients with Chronic Insomnia

Sleep Perception Moderates Treatment Response to Cognitive B...

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中国睡眠研究会第十四届全国学术年会

作者： Qimeng Sun Yanyuan Dai Baixin Chen xiangdong tang Yun Li Shantou University Mental Health Center 四川大学华西医院

Study Objectives: To examine treatment response to cognitive behavior therapy for insomnia(CBT-I) in patients with insomnia with and without sleep *** : We studied 41 patients with chronic insomnia who had received 5-week CBT-I. Self-reported and objective sleep were assessed with sleep diary and actigraphy, respectively. Sleep perception was calculated as(self-reported total sleep time [TST]/objective TST). Underestimation of sleep duration(USD) was defined as less than median of sleep perception(85%) of the overall sample, while normal sleep perception(NSP) was defined as sleep perception ≥ 85%. Insomnia Severity Index(ISI) was used to assess the severity of ***: The total scores of ISI decreased significantly after CBT-I in both groups. Compared to pre-treatment, self-reported sleep efficiency(SE) increased and total wake time(TWT) decreased after CBT-I, while the magnitude of changes in SE(d=1.40 vs. d=0.81, interaction-p=0.016) and TWT(d=-1.82 vs. d=-0.85, interaction-p<0.001) were larger in the USD group. Furthermore, self-reported sleep onset latency(interaction-p=0.712) and wake after sleep onset(interaction-p=0.030) decreased in the USD group(all p<0.05), but not in the NSP group. Linear regressions showed that lower sleep perception at baseline predicted greater increase in self-reported SE(β=-0.99, p<0.001) and TST(β=-0.51, p=0.006), and greater decrease in self-reported TWT(β=1.22, p=0.023) after CBT-I after adjusting for ***: Sleep perception moderates the self-reported CBT-I effects on chronic insomnia: the phenotype of USD is associated with a better response to CBT-I especially in self-reported sleep parameters, whereas those with NSP may respond better to biological therapy.

关键词： Insomnia Sleep perception Underestimation of sleep duration(USD) Cognitive behavior therapy for insomnia(CBT-I)

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High stability of EEG spectral power across polysomnography and multiple sleep latency tests in good sleepers and chronic insomniacs

High stability of EEG spectral power across polysomnography ...

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中国睡眠研究会第十五届全国学术年会

作者： Yuan Shi Rong Ren Ye Zhang Haipeng Zhang Xujun Feng xiangdong tang west china hospital

Study Objectives: To assess the stability of electroencephalographic(EEG) spectral features across overnight polysomnography(PSG) and daytime multiple sleep latency tests(MSLTs) in chronic insomniacs(CIs) and normal controls(NCs).Methods: A total of 20 NCs and 22 CIs underwent standard PSG and *** analyses were performed on EEG data from PSG and MSLTs and absolute and relative power in central, frontal and occipital channels were obtained for wake(W) and non-rapid eye movement sleep stage 1 and 2(N1, N2).Intraclass correlation coefficients(ICCs) were used to assess the stability of EEG spectral power across PSG and MSLTs for W, N1 and ***: The absolute power of all frequency bands except delta exhibited high stability across PSG and MSLTs in both NCs and *** delta absolute power was stable in NCs during N1 and N2 stages, it tended to be less stable in CIs during W and sleep *** also observed lower stability of relative power compared to absolute power though the majority of relative power outcomes maintained high stability in both ***: EEG spectral features are stable across PSG and MSLTs in W, N1 and N2 suggesting that EEG spectral power characteristics may be genetically ***, EEG signals from either an overnight PSG or a daytime MSLT may be useful for reliably exploring EEG spectral features during wakefulness or sleep.

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多导睡眠图在常见神经变性疾病中的应用研究

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四川大学学报:医学版 2023年第5期54卷 1058-1064页

作者：陈璋玥李桃美唐向东四川大学华西医院睡眠医学中心成都610041

目前大多数神经变性疾病的病因、发病机制尚不明确,为该类疾病的预防、诊断及治疗带来难题。睡眠障碍是神经变性疾病常见主诉之一,两种共病后,加重了病情的严重程度,患者生活质量进一步下降,同时加大了治疗的难度。已有大量研究对神经... 详细信息

目前大多数神经变性疾病的病因、发病机制尚不明确,为该类疾病的预防、诊断及治疗带来难题。睡眠障碍是神经变性疾病常见主诉之一,两种共病后,加重了病情的严重程度,患者生活质量进一步下降,同时加大了治疗的难度。已有大量研究对神经变性疾病患者进行睡眠监测,发现其与健康对照人群相比多导睡眠图(polysomnography,PSG)存在明显的变化,且不同的神经变性疾病之间也存在明显的差异,并与疾病的发生发展密切相关。本文将探讨帕金森病、阿尔茨海默病、亨廷顿病以及路易体痴呆患者睡眠结构的特点,对其睡眠障碍及PSG特征进行简要综述。有助于加深对神经变性疾病发病机制和病理改变的理解,明确睡眠障碍与这些疾病之间的关系,提高临床医生对疾病的进一步认识,为未来的研究提供基础。

关键词：神经变性疾病多导睡眠图睡眠障碍

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Insomnia with Objective Short Sleep Duration is Associated with Hypertension

Insomnia with Objective Short Sleep Duration is Associated w...

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中国睡眠研究会第十五届全国学术年会

作者： Yanyuan Dai Baixin Chen Le Chen Alexandros N Vgontzas Julio Fernandez-Mendoza Maria Karataraki xiangdong tang Yun Li Shantou University Mental Health Center Shantou University Medical College Department of Psychiatry and Behavioral Health Pennsylvania State University Department of Psychiatry and Behavioral Sciences University of Crete West China Hospital Sichuan University

Insomnia with objective short sleep duration(ISSD) has been proposed as the most biologically severe phenotype of the disorder associated with cardiometabolic morbidity in population-based *** this study, we investigated the association between ISSD and hypertension in a large clinical *** studied 348 patients diagnosed with chronic insomnia disorder(CID) based on International Classification of Sleep Disorders(ICSD-3) criteria and 150 normal *** short sleep duration was defined by the median total sleep time(TST) of the sample(<7 hours) measured with 1-night *** was defined based on blood pressure(BP) levels, antihypertensive medication use and/or a physician *** adjusting for potential confounders, patients with CID who slept < 7 hours were associated with 2.8-fold increased odds of hypertension compared to normal sleepers who slept ≥7 hours(odds ratio [OR]=2.81, 95% confidence interval [95%CI]=1.068–7.411) or < 7 hours(OR=2.75, 95%CI=1.005-7.542), whereas patients with CID who slept ≥ 7 hours(OR=1.52, 95%CI=0.537-4.285) or normal sleepers who slept < 7 hours(OR=1.07, 95%CI=0.294-3.904) were not significantly associated with increased odds of hypertension compared to normal sleepers who slept ≥ 7 *** regression analyses showed that, for every hour decrease in TST, systolic and diastolic blood pressure increased by 1.014 mmHg(p=0.045) and 0.923 mmHg(p=0.015), respectively, in patients with CID but not in normal *** findings further support that ISSD is a risk factor for hypertension and objective short sleep duration may be a useful marker of the biological severity of CID in clinical practice.

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