基于心/肺经的经脉关键问题创新研究

项目来源

国家重点研发计划(NKRD)

项目主持人

方剑乔

项目受资助机构

浙江中医药大学

立项年度

2018

立项时间

未公开

项目编号

2018YFC1704600

项目级别

国家级

研究期限

未知 / 未知

受资助金额

750.00万元

学科

中医药现代化研究

学科代码

未公开

基金类别

“中医药现代化研究”重点专项

关键词

经络现象 ; 心肺经 ; 循经感传 ; 生物学特征 ; 特异性 ; 机制研究 ; Meridian phenomena ; Heart and Lung meridians ; Propagated sensation along the channels ; Biological characteristics ; Specificity ; Mechanism research

参与者

周美启;高昕妍;曾芳;乔海法;蒋永亮

参与机构

安徽中医药大学;中国中医科学院针灸研究所;成都中医药大学;陕西中医药大学

项目标书摘要:本项目围绕心、肺经研究经络学说的经脉现象、经脉循行中体表—内脏之间、体表—体表之间的联系特点、规律及其生物学基础等关键问题。在“心、肺二经循经经脉现象的生物学特征”方面,已初步揭示健康者、心肺疾病患者心肺二经的微循环特性、热传输特性、代谢特性及电学特性,呈现相对特异性;在“心、肺经经脉循经现象的生物学机制”方面,已建立微透析—高效液相色谱—电喷雾串联四级杆质谱检测方法,发现大鼠DMNV核团中的神经递质含量与肺功能相关;在“心、肺经对心、肺功能的影响”方面,发现肺经五输穴对肺部疾病有特异性的治疗作用,心经五输穴对心脏疾病有特异性的治疗作用,电针改善心肌缺血小鼠心脏功能与α、β-AR表达有关;在“心、肺疾病的体表反应与心、肺经循行的相关性及机制研究”方面,发现心肺疾病模型大鼠体表神经源性反应分布与心肺经循行或同节段有较高一致性,心肺疾病患者出现的压痛点和局部皮肤异常改变与心肺经的循行部位存在着高度重合性;在“基于经脉“体表—内脏”联系的循经针刺效应的临床评价”方面,已制定针刺干预慢性持续性哮喘和慢性稳定型心绞痛的临床研究方案,并开展临床研究;在“基于经脉“体表—体表”联系的循经针刺效应的临床评价及其机制”方面,已制定针刺干预肩前痛和颈型颈椎病的临床研究方案,并开展临床研究。

Application Abstract: This project focuses on key questions of the meridian theory,such as meridian phenomena,characteristics and rules underlying distributions and associations of meridians(meridian-viscera and site-to-site association),as well as the biological basis of meridians.Regarding biological characteristics of meridian phenomena for the heart and lung meridians,we have preliminary revealed the microcirculatory,thermal,metabolic and electrical characteristics of these two meridians in healthy adults and patients of cardiopulmonary diseases.Results indicate that meridian specificity exists.Regarding biological mechanism of meridian phenomena for these two meridians,detection methods of microdialysis sampling and high performance liquid chromatography-electrospray tandem mass spectrometry have been established.Results indicate that the content of neurotransmitter in the dorsal motor nucleus of the vagus has correlation with the lung function.Regarding effects of these two meridians on cardiopulmonary functions,results reveal five-shu acupoints of lung meridian have specific therapeutic effect on lung diseases.Five-shu acupoints of heart meridian have specific therapeutic effect on heart diseases and electroacupuncture can improve the heart function in myocardial ischemia mice by regulating expression of α and β-AR.Regarding correlations and mechanism investigations between peripheral responses of cardiopulmonary diseases and distributions of these two meridians,results indicate that distributions of neurogenic responses in rats of cardiopulmonary diseases is consistent with circulations of these two meridians or the the same segment.In patients of cardiopulmonary diseases,distributions of tender points and regional abnormal skin changes are also highly coincident with the circulation of these two meridians.Regarding clinical evaluations on the effect of acupuncture according to the meridian-viscera association theory,protocols of acupuncture on chronic persistent asthma and stable angina pectoris are built and trials are ongoing.Regarding the mechanism clinical evaluation on the effect of acupuncture based on the site-to-site association theory,protocols of acupuncture on anterior shoulder pain and cervical spondylosis are established and trials are ongoing.

项目受资助省

浙江省

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  • 1.Coordinate-based (ALE) meta-analysis of acupuncture for musculoskeletal pain

    • 关键词:
    • musculoskeletal pain; acupuncture; functional magnetic resonanceimaging; activation likelihood estimation; meta-analysis;CENTRAL-NERVOUS-SYSTEM; BRAIN ACTIVITY; BASAL GANGLIA; FUNCTIONALCONNECTIVITY; PREVALENCE; NETWORK; NOCICEPTION; PERCEPTION; MECHANISMS;ANALGESIA

    Background: Neuroimaging studies have been widely used to investigate brain regions' alterations in musculoskeletal pain patients. However, inconsistent results have hindered our understanding of the central modulatory effects of acupuncture for musculoskeletal pain. The main objective of our investigation has been to obtain comprehensive evidence of acupuncture for musculoskeletal pain diseases. Methods: The PubMed, Web of Science, Google Scholar, Embase, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine disc Database, Clinical Trial Registration Platform, and Wanfang Database were searched for neuroimaging studies on musculoskeletal pain diseases published from inception up to November 2021. Then, the relevant literature was screened to extract the coordinates that meet the criteria. Finally, the coordinate-based meta-analysis was performed using the activation likelihood estimation algorithm. Results: A total of 15 neuroimaging studies with 183 foci of activation were included in this study. The ALE meta-analysis revealed activated clusters in multiple cortical and sub-cortical brain structures in response to acupuncture across studies, including the thalamus, insula, caudate, claustrum, and lentiform nucleus. Conclusions: The studies showed that acupuncture could modulate different brain regions, including the thalamus, insula, caudate, claustrum, and lentiform nucleus. The findings offer several insights into the potential mechanisms of acupuncture for musculoskeletal pain and provide a possible explanation for the observed clinical benefit of this therapy.

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  • 2.Diagnostic Performance o f Generative Adversarial Network-Based Deep Learning Methods for Alzheimer's Disease: A Systematic Review and Meta-Analysis

    • 关键词:
    • generative adversarial networks (GANs); Alzheimer's disease; mildcognitive impairment (MCI); diagnosis; psychoradiology; systematicreview; meta-analysis;MILD COGNITIVE IMPAIRMENT; NATIONAL INSTITUTE; ASSOCIATION WORKGROUPS;CLINICAL-DIAGNOSIS; BRAIN ATROPHY; PET; PREDICTION; AD; PROGRESSION;GUIDELINES

    Alzheimer's disease (AD) is the most common form of dementia. Currently, only symptomatic management is available, and early diagnosis and intervention are crucial for AD treatment. As a recent deep learning strategy, generative adversarial networks (GANs) are expected to benefit AD diagnosis, but their performance remains to be verified. This study provided a systematic review on the application of the GAN-based deep learning method in the diagnosis of AD and conducted a meta-analysis to evaluate its diagnostic performance. A search of the following electronic databases was performed by two researchers independently in August 2021: MEDLINE (PubMed), Cochrane Library, EMBASE, and Web of Science. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to assess the quality of the included studies. The accuracy of the model applied in the diagnosis of AD was determined by calculating odds ratios (ORs) with 95% confidence intervals (Cis). A bivariate random-effects model was used to calculate the pooled sensitivity and specificity with their 95% Cls. Fourteen studies were included, 11 of which were included in the meta-analysis. The overall quality of the included studies was high according to the QUADAS-2 assessment. For the AD vs. cognitively normal (CN) classification, the GAN-based deep learning method exhibited better performance than the non-GAN method, with significantly higher accuracy (OR 1.425, 95% CI: 1.150-1.766, P = 0.001), pooled sensitivity (0.88 vs. 0.83), pooled specificity (0.93 vs. 0.89), and area under the curve (AUC) of the summary receiver operating characteristic curve (SROC) (0.96 vs. 0.93). For the progressing MCI (pMCI) vs. stable MCI (sMCI) classification, the GAN method exhibited no significant increase in the accuracy (OR 1.149, 95% CI: 0.878-1.505, P = 0.310) or the pooled sensitivity (0.66 vs. 0.66). The pooled specificity and AUC of the SROC in the GAN group were slightly higher than those in the non-GAN group (0.81 vs. 0.78 and 0.81 vs. 0.80, respectively). The present results suggested that the GAN-based deep learning method performed well in the task of AD vs. CN classification. However, the diagnostic performance of GAN in the task of pMCI vs. sMCI classification needs to be improved.

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  • 3.Evidence based Medicine Biomarkers of Neuroelectrophysiology for Mental Disorders

    • 关键词:
    • mental disorder; evidence-based medicine; meta-analysis; event-relatedpotential; quantitative EEG; biomarker

    Identifying the objective biological markers is one of the most important scientific goals in psychiatric research. Recently, neuroelectrophysiological studies incorporating evidence-based medicine has provided an important approach and achieved abundant results to achieve this goal. However, there are still many controversies among current evidences, and it is difficult to reach a consensus. This article comprehensively summarized the results of psychiatric studies on mental disorders which combined the method of evidence-based medicine represented by meta-analysis and the neuroelectrophysiological technique represented by electroencephalography (EEG). To systematically analyze and summarize the neurocognitive dysfunction of mental disorders and high-risk groups, event-related potential (ERP) components are divided into early and late components including different cognitive activities such as perception processing, cognitive control, emotional response, and social cognition. Evidence based on quantitative EEG analysis are also discussed. We found that schizophrenia has defects in most of cognitive processes including perception, emotion and sociality, which indexed by amplitude reduction in most of the early and late components including P50, MMN, P300 and LPP. Attention deficit/hyperactivity disorder (ADHD) has defects in cognitive control indexed by amplitude reduction in the early and late components including the ERN and Pe. Anxiety and obsessive-compulsive disorder have defects in early cognitive control, while autism spectrum disorder (ASD) has defects in early perceptual processing and social cognition indexed by amplitude reduction of N170 and FN. In addition, abnormal P300 reflexing the impaired cognitive processing speed and attention resource allocation were found across multiple diagnosis types, which indicate that this ERP component may reflect the general cognitive deficits of mental disorders. The neuroelectrophysiological studies on evidence-based medicine for mental disorders has discovered a series of valuable ERPs or EEG objective marker features, but these features still cannot be directly used in the diagnosis of personalized medicine, until these features have been identified as objective biomarkers with high accuracy and specificity in further research and clinical practice. Future research can use multi-center database to seek the electrophysiological objective markers for mental disorders, and the integrated research combining advanced technologies including multi-modal psychoradiology and artificial intelligence methods including machine learning can further enhance the reliability and validity of biological markers of mental disorders.

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  • 4.Acupuncture for treating chronic stable angina pectoris associated anxiety and depression: A systematic review and meta-analysis

    • 关键词:
    • Acupuncture; Anxiety; Chronic stable angina pectoris; Depression;Meta-analysis; Systematic review;HEART-RATE-VARIABILITY; DISEASE; DISORDERS; RISK; CONNECTIVITY; STRESS;MARKER

    Background and objective: Despite that acupuncture is effective in treating anxiety, depression and chronic stable angina pectoris (CSAP), it remains unclear whether acupuncture can treat CSAP, anxiety and depression simultaneously. This systematic review and meta-analysis aimed to investigate the efficacy of acupuncture on CSAP-associated anxiety and depression. Methods: Eight electronic databases were searched to identify eligible randomized controlled trials (RCTs) or controlled clinical trials (i.e. "acupuncture alone or combined with standard care" versus " sham acupuncture alone, sham acupuncture with standard care, or standard care alone") from their inception to January 2021, which included PubMed, Embase, Web of Science, the Cochrane Library, CBM, CNKI, VIP and Wanfang Database. Data were extracted and meta analyses were performed using the RevMan 5.3. Risk of bias (ROB) 2.0 was used for methodological quality assessment. GRADEprofiler 3.2.2 was used to rate the quality of evidence. Results: Seven trials involving 893 subjects were included. Meta-analysis results showed that acupuncture combined with standard care was more effective in relieving anxiety and depression, reducing angina attack frequency, and angina pain intensity than sham acupuncture with standard care and standard care alone. In addition, the effect remained until 16 weeks after acupuncture. The safety of acupuncture for CSAP-associated anxiety and depression was also high. Nonetheless, the quality of evidence ranged from low to moderate. Conclusion: Acupuncture may be used as an adjunctive therapy to treat CSAP-associated anxiety and depression. However, more high-quality RCTs are required to confirm our findings.

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  • 5.Roles of central orexinergic system on cardiovascular function and acupuncture on intervention of cardiovascular risk: Orexinergic system mediate the role of acupuncture

    • 关键词:
    • Central orexinergic system; Cardiovascular activity; Hypertension;Stress induced cardiovascular reactivity; Acupuncture;ROSTRAL VENTROLATERAL MEDULLA; SPONTANEOUSLY HYPERTENSIVE-RATS;TRACTUS-SOLITARIUS NEURONS; RECEPTOR MESSENGER-RNA; HYPOTHALAMIC OREXIN;HYPOCRETIN OREXIN; BLOOD-PRESSURE; DIFFERENTIAL DISTRIBUTION; PROTEINDISTRIBUTION; SYMPATHETIC OUTFLOW

    Central orexinergic system contributes to the regulation of cardiovascular function. Orexinergic neurons receiving projections of nerve fibers from multiple structures of brain which involved in control and regulation of cardiovascular function locate in hypothalamus, and their axon terminals widely project to various central structures where orexins receptors are expressed. Here, we summarize the present knowledge that describes the influence of central orexinergic system on cardiovascular activity, the relevance of dysfunction in central orexinergic system with hypertension and psychological stress induced cardiovascular reactivity which are serious risk factors for cardiovascular disease and cardiovascular death. We propose that central orexinergic system may be potentially important targets for the prevention of cardiovascular disease and cardiovascular death, and different orexinergic system involved neuronal circuits may be involved in distinct cardiovascular functions. Acupuncture having bidirectional regulatory ability and a much lower incidence of side effects can prevent disease. We review the improvement of acupuncture on hypertension and psychological stress induced cardiovascular reactivity. We think that acupuncture intervenes hypertension and psychological stress induced cardiovascular reactivity to prevent cardiovascular disease and cardiovascular death. We also summarize relation between acupuncture and central orexinergic system. We propose a hypothesis that acupuncture improve hypertension and psychological stress induced cardiovascular reactivity through regulating central orexinergic system. The knowledge is beneficial for the development of potential therapeutic targets and methods to prevent cardiovascular disease and cardiovascular death.

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  • 6.Acupuncture for chronic persistent asthma based on the theory of Meridian-viscera Association: study protocol for a multi-center randomized controlled trial in China.

    • 关键词:
    • ;

    BACKGROUND: Acupuncture is effective in symptom and quality of life improvement of chronic asthma, but the efficacy differences between different acupoints are uncertain. In terms of the theory of Meridian-viscera Association, the study aims to investigate the different effectiveness between acupoints in Lung meridian and the acupoints in Heart meridian, so as to provide the evidence to develop a better prescription of the acupuncture treatment of chronic persistent asthma.; METHODS: This study is a multicentral randomized controlled trial. A total of 68 chronic persistent asthma patients will be randomly allocated into two groups: the Lung meridian group and the Heart meridian group. This trial will include a 2-week baseline period, a 4-week treatment period with 12 sessions' acupuncture, and an 8-week follow-up period. The primary outcome is the Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes are the Asthma Control Test (ACT), Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1s (FEV1). The AQLQ and ACT will be collected at baseline, week 4, week 8, and week 12 after randomization. PEF, FEV1, the Self-rating Anxiety Scale (SAS), and the Self-rating Depression Scale (SDS) will be assessed at baseline and week 4.; DISCUSSION: The results will provide evidence for acupuncture prescription selection and the clinical efficacy improvement. The results of this trial will also be used to determine whether or not a full definitive trial will go ahead, which will further confirm the theory of Meridian-viscera Association.; TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showproj.aspx?proj=43803 ) ChiCTR1900027284. Registered on 7 November 2019.

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  • 7.Role of Cofilin in Alzheimer's Disease

    • 关键词:
    • Alzheimer's disease; A beta; structure; function; regulation of cofilin;ACTIN-DEPOLYMERIZING FACTOR; AMYLOID PRECURSOR PROTEIN; LONG-TERMPOTENTIATION; CANCER-CELL MIGRATION; DENDRITIC SPINES; LIM-KINASE;SYNAPTIC PLASTICITY; HIRANO BODIES; TAU-PROTEIN; PHOSPHATASE SLINGSHOT

    Alzheimer's disease (AD) is a degenerative neurological disease and has an inconspicuous onset and progressive development. Clinically, it is characterized by severe dementia manifestations, including memory impairment, aphasia, apraxia, loss of recognition, impairment of visual-spatial skills, executive dysfunction, and changes in personality and behavior. Its etiology is unknown to date. However, several cellular biological signatures of AD have been identified such as synaptic dysfunction, beta-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies which are related to the actin cytoskeleton. Cofilin is one of the most affluent and common actin-binding proteins and plays a role in cell motility, migration, shape, and metabolism. They also play an important role in severing actin filament, nucleating, depolymerizing, and bundling activities. In this review, we summarize the structure of cofilins and their functional and regulating roles, focusing on the synaptic dysfunction, beta-amyloid plaques, hyperphosphorylated tau, cofilin-actin rods, and Hirano bodies of AD.

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  • 8.Effectiveness and safety of tenosynovitis of the long head of the biceps brachii with acupuncture: a protocol for a systematic review and meta-analysis

    • 关键词:
    • Acupuncture; Tenosynovitis; LHB; Brachii; Meta-analysis;SURGICAL-TREATMENT; TENDINOPATHY; TENOTOMY; TENDON; OSTEOARTHRITIS;TENDINITIS; TENODESIS; DIAGNOSIS

    Background: Tenosynovitis of the long head of the biceps (LHB) brachii is a common disease in patients over 40 years old. It can always result in chronic anterior shoulder pain and limited function. Acupuncture is one of most popular conservative treatment methods, and increasing studies indicate that it has remarkable therapeutic effects on the tenosynovitis of LHB brachii. However, the effectiveness and safety of acupuncture for treating tenosynovitis of LHB brachii remain largely uncertain. In our study, we will perform the first systematic review and meta-analysis to explore the effectiveness and safety of acupuncture on the tenosynovitis of LHB brachii.Methods: We will search the randomized controlled trial (RCT) literatures involving acupuncture for treating tenosynovitis of LHB brachii in eight electric databases, including PubMed, Web of Science, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang Database, and Technology Periodical Database (VIP). We will define the visual analog scale (VAS), the Melle score of shoulder joint functional activity, and the ability assessment of daily living activities (ADL) as the primary outcomes. Besides quality of life, adverse events caused by acupuncture will be regarded as the secondary outcomes. Quality assessment of the included studies will be independently performed according to the Cochrane Risk of Bias tool. Meanwhile, the level of evidence for results will be assessed by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. All analyses will be conducted by using the RevMan software V5.3.Results: From the study, we will ascertain the effectiveness and safety of acupuncture treatment on tenosynovitis of LHB brachii.Conclusion: The conclusion of this study will confirm the effectiveness and safety of acupuncture in the treatment of tenosynovitis of LHB brachii, which can provide new evidence to guide appropriate interventions on tenosynovitis of LHB brachii with acupuncture in the future.Ethics and dissemination: Ethical approval is not required because no individual patient data are collected. This review will be published in a peer-reviewed journal and presented at an international academic conference for dissemination.

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  • 9.Acupuncture for treating chronic stable angina pectoris-associated anxiety and depression A protocol for systematic review and meta-analysis

    • 关键词:
    • acupuncture; anxiety; chronic stable angina pectoris; depression;meta-analysis;MYOCARDIAL-ISCHEMIA; CORONARY; MANAGEMENT; PROGNOSIS; DISEASE

    Background: There are numerous studies worldwide on the use of acupuncture as complementary therapy for chronic stable angina pectoris (CSAP). However, the high morbidity of CSAP-associated anxiety and depression is often overlooked. This protocol of systematic review and meta-analysis aims to assess whether acupuncture is effective as a complementary therapy for anxiety and depression in patients with CSAP. Methods: The following 8 databases will be searched from inception to February 2020 with no language restrictions: PubMed, Excerpt Medical Database, Web of Science, the Cochrane Library, Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database. Eligible randomized controlled trials and controlled clinical trials will be included. Study selection, data extraction, and risk of bias assessment will be performed independently by 2 reviewers, differences will be resolved by the third reviewer. The primary outcomes include the level of anxiety or depression measured by qualified scales, angina attack frequency, and angina pain intensity. Revman 5.3 software will be used to perform the assessment of the risk of bias and data synthesis. The review will grade the quality of the evidence based on the Grading of Recommendation, Assessment, Development, and Evaluation system. Results: This systematic review and meta-analysis will provide reliable evidence about the effect and safety of acupuncture as a complementary therapy for CSAP-associated anxiety and depression. Conclusion: The conclusion of this study will be published in a peer-reviewed journal. Ethics and dissemination: This review will not involve private information of participants, so the ethical approval will not be required. The results will be disseminated in a peer-reviewed journal or conference presentation. Important protocol modifications will be updated on PROSPERO. PROSPERO registration number: CRD42020165492.

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