The efficacy and safety of transcutaneous auricular vagus nerve stimulation in patients with mild cognitive impairment: A double blinded randomized clinical trial.

BACKGROUND: There are 9.9 million new cases of dementia in the world every year. Short-term conversion rate from mild cognitive impairment (MCI) to dementia is between 20% and 40%, but long-term in 5-10 years ranges from 60% to 100%. It is particularly important to prevent or prolong the development of MCI into dementia. Both auriculotherapy and vagus nerve stimulation are effective on improving cognitive functions. However, there is no double blinded randomized clinical trial to support the effectiveness of transcutaneous electrical stimulation of auricular acupoints in patients with MCI. METHODS: This randomized controlled trial involved patients with MCI, aged from 55 to 75 years old. Patients were randomly allocated to transcutaneous auricular vagus nerve stimulation (taVNS) group or sham taVNS group. In the taVNS group, two auricular acupoints were stimulated, including heart (concha, CO15) and kidney (CO10), which are in the distribution of vagus nerve. While in the sham taVNS group, two other auricular acupoints were stimulated, including elbow (scaphoid fossa, SF3) and shoulder (SF4,5), which are out of the distribution of vagus nerve. The primary outcome was the Montreal cognitive assessment-basic, MOCA-B. The secondary outcomes included auditory verbal learning test-HuaShan version (AVLT-H), shape trails test A&B (STT-A&B), animal fluence test (AFT), Boston naming test (BNT), Pittsburgh sleep quality index (PSQI), rapid eye movement sleep behavior disorder screening questionnaire (RBDSQ), Epworth sleepiness scale (ESS) and functional activities questionnaire (FAQ). These outcome measures were taken at baseline, 24 weeks later. RESULTS: After 24 weeks of intervention, the data of 52 patients were intended for analysis. After intervention, there was significant difference in the overall scores of MoCA-B between taVNS group and sham taVNS group (p = 0.033 < 0.05). In taVNS group, compared with before intervention, the overall scores of MOCA-B increased significantly after intervention (p < 0.001). As for N5 and N7, the two sub-indicators of AVLT-H, in taVNS group, compared with before intervention, both N5 and N7 increased significantly after intervention (both ps < 0.001). As for STTB, in taVNS group, compared with before intervention, STTB was significantly reduced after intervention (p = 0.016). For BNT, in taVNS group, compared with before intervention, BNT increased significantly after intervention (p < 0.001). In taVNS group, compared with before intervention, PSQI, RBDSQ, ESS and FAQ decreased significantly after intervention (p = 0.002, 0.025, <0.001, 0.006 respectively). 1 patient with a history of tympanic membrane perforation in taVNS group was reported with mild adverse reactions which disappeared a week after termination of taVNS. The intervention of taVNS is effective on increasing the overall scores of MoCA-B, N5 and N7. CONCLUSION: The clinical trial demonstrated that taVNS can improve cognitive performance in patients with MCI. This inexpensive, effective and innovative method can be recommended as a therapy for more patients with MCI in the prevention or prolonging of its development into dementia, but it is still required to be further investigated. TRIAL REGISTRATION: http://www.chictr.org.cn. (ID: ChiCTR2000038868).

Synergistic and Attenuating Effect of Electroacupuncture on Aconitine in Improving Heart Failure and Its Calcium Regulation Mechanism.

Objective: The objective is to observe the synergistic and attenuating effect of electroacupuncture (EA) on aconitine (ACO) in improving heart failure (HF) and to explore its underlying mechanism for calcium regulation. Methods: Twenty-four male Sprague-Dawley rats were randomly divided into four groups: normal control (NC) (n = 6), HF(n = 6), ACO (n = 6), and ACO + EA (n = 6). The maximum rates of left ventricular pressure rising and declining (±dp/dtmax), arrhythmia, the left ventricular systolic pressure (LVSP), ejection fraction (LVEF), and fractional shortening (LVFS) were measured by physiological recorder and ultrasound, respectively. Protein expressions of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2a), phospholamban (PLB), and Na+-Ca2+ exchange (NCX1) in the left ventricle tissue were detected by fluorescence immunoblotting. Results: Compared with the NC group, LVSP, ±dp/dtmax, LVEF, and LVFS were decreased in the HF group; compared with the HF group, LVSP, ±dp/dtmax, LVEF, and LVFS were significantly increased in the ACO + EA group. Compared with the ACO group, the incidence and the degree of arrhythmia were significantly reduced in the ACO + EA group. Compared with the NC group, the activity of SERCA2a was decreased, and the expression of PLB and NCX1 was enhanced in the HF group; compared with the HF group and ACO group, the activity of SERCA2a was increased, and the expression of PLB and NCX1 was significantly attenuated in the ACO + EA group. Conclusions: EA plays a synergistic and attenuated role in ACO improving HF, and the mechanism may be related to the enhancement of the SERCA2a activity and the decrease of the expression of PLB and NCX1 in cardiomyocytes.

Efficacy Analysis of the Reinforcing and Circulation-Promoting Protocol of Acupuncture and Moxibustion in Treatment of Twenty-Four Patients with Refractory Chronic Low Back Pain.

Objectives: The purpose of this study was to observe the clinical efficacy of the reinforcing and circulation-promoting protocol of acupuncture and moxibustion in treatment of refractory chronic low back pain, analyze therapeutic principles to obtain treatment efficacy, and develop new therapeutic principles to treat chronic low back pain. Methods: Twenty-four patients from the registry of patients suffering from refractory chronic low back pain were invited to our self-controlled case series, which was conducted in "real-world" settings. We implemented the reinforcing and circulation-promoting protocol of acupuncture and moxibustion to treat these patients and used the Visual Analogue Scale (VAS) and the Oswestry Disability Index (ODI) as the observation indices. Results: All 24 patients completed the treatment of acupuncture and moxibustion. The VAS of low back pain was 6.83 ± 2.18 before treatment and 2.13 ± 1.45 after treatment. The difference before and after treatment was significant (P < 0.001). The ODI was 28.21 ± 13.06 before treatment and 16.63 ± 7.20 after treatment. Their difference before and after treatment was significant (P < 0.001). Conclusion: The reinforcing and circulation-promoting protocol of acupuncture and moxibustion is effective in treating refractory chronic low back pain mainly because low back pain can be significantly relieved and motor function can be promoted. This trial was registered with AMCTR-OOO-17000045 (3 December 2016).

Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session.

Objectives: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear. Methods: Total twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes. Results: The scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment. Conclusions: It manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

Targets preliminary screening for the fresh natural drug molecule based on Cosine-correlation and similarity-comparison of local network.

BACKGROUND: Chinese herbal medicine is made up of hundreds of natural drug molecules and has played a major role in traditional Chinese medicine (TCM) for several thousand years. Therefore, it is of great significance to study the target of natural drug molecules for exploring the mechanism of treating diseases with TCM. However, it is very difficult to determine the targets of a fresh natural drug molecule due to the complexity of the interaction between drug molecules and targets. Compared with traditional biological experiments, the computational method has the advantages of less time and low cost for targets screening, but it remains many great challenges, especially for the molecules without social ties. METHODS: This study proposed a novel method based on the Cosine-correlation and Similarity-comparison of Local Network (CSLN) to perform the preliminary screening of targets for the fresh natural drug molecules and assign weights to them through a trained parameter. RESULTS: The performance of CSLN is superior to the popular drug-target-interaction (DTI) prediction model GRGMF on the gold standard data in the condition that is drug molecules are the objects for training and testing. Moreover, CSLN showed excellent ability in checking the targets screening performance for a fresh-natural-drug-molecule (scenario simulation) on the TCMSP (13 positive samples in top20), meanwhile, Western-Blot also further verified the accuracy of CSLN. CONCLUSIONS: In summary, the results suggest that CSLN can be used as an alternative strategy for screening targets of fresh natural drug molecules.

Auricular Vagus Nerve Stimulation Ameliorates Functional Dyspepsia with Depressive-Like Behavior and Inhibits the Hypothalamus-Pituitary-Adrenal Axis in a Rat Model.

BACKGROUND: The hypothalamus-pituitary-adrenal axis is the most important endocrine system to control irritability response. Functional dyspepsia (FD) is closely related to irritability. This study aimed to preliminarily explore the corticotropin-releasing factor (CRF) mechanism of auricular vagus nerve stimulation (aVNS) for FD model rats. METHODS: Sprague-Dawley adult male rats were randomly divided into normal group, model group, aVNS group, and sham-aVNS group. Except for the normal rats, all other rats were induced into the FD model through tail-clamping stimulation for 3 weeks. Once the rat model was developed successfully, rats in the aVNS group and sham-aVNS group were intervened with aVNS or sham-aVNS for 2 weeks. No intervention was given to rats in the normal and model groups. The effect of aVNS was assessed. The expressions of hippocampal corticotropin-releasing hormone receptor 1 (CRHR1), hypothalamus CRF, adrenocorticotropic hormone (ACTH), and corticosterone in serum were assessed. RESULTS: 1. Compared with normal rats, model-developing rats showed FD-like behavior. 2. Compared with model rats, rats in the aVNS group showed an improved general condition score and gastric motility, and increased horizontal and vertical motion scores. 3. The release of corticosterone, ACTH in serum, and CRF in the hypothalamus all increased in model rats but decreased with aVNS instead of sham-aVNS. 4. The expression of hippocampus CRHR1 was lower in model rats but higher in the aVNS group. CONCLUSION: aVNS ameliorates gastric motility and improves the mental state in the FD-like rat, probably via inhibiting the CRF pathway.

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices.

INTRODUCTION: As an emerging neuromodulation therapy, transcutaneous auricular vagus nerve stimulation (taVNS) has been proven to be safe and effective for epilepsy, major depressive disorders, insomnia, glucose metabolic disorders, pain, stroke, post stroke rehabilitation, anxiety, fear, cognitive impairment, cardiovascular disorders, tinnitus, Prader-Willi Syndrome, and COVID-19. AREAS COVERED: Although the history of taVNS is only two decades, the devices carrying taVNS technique have been constantly updated. Especially in recent years, the development of taVNS devices has presented a new trend. To conclude, the development of taVNS devices has entered a new era, thus the update speed and quality of taVNS devices will be considerably improved in the future. This article reviewed the history and classification of taVNS devices. EXPERT OPINION: The correlation between the effectiveness and stimulation parameters from taVNS devices still remains unclear. There is a lack of standard or harmonization among different taVNS devices. Strategies, including further comparative research and establishment of standard, have been recommended in this article to promote the future development of taVNS devices.

Efficacy and safety of acupuncture in the treatment of depression: A systematic review of clinical research.

As a common mental disorder, depression is one of the leading causes of disability around the world. Clinical studies have shown that acupuncture is an effective therapy without obvious side effects compared to limited efficacy and adverse reactions of drug therapy, cognitive behavioral therapy, and neuromodulation technology in treating depression. The objective of this review is to systematically evaluate whether acupuncture therapies for depression are safe and effective in order to provide a high-quality reference for clinical trials of acupuncture. A systematic search of the literature was carried out through bibliographic search engine PubMed. Subsequently, the study design, intervention methods, control group, results, and safety of acupuncture were analyzed. The results showed that acupuncture as an adjunct to antidepressants or as a single treatment can exert a positive impact on patients' depressive symptoms. Compared with antidepressants, acupuncture has the advantages of fast onset and long-term efficacy in the treatment of depression, and can enhance the efficacy of antidepressants. Moreover, the efficacy and safety of acupuncture in the treatment of depression maybe related to the qualification of the acupuncturist, the selection of acupoints, and intervention measures.

Effects of transcutaneous auricular vagus nerve stimulation on brain functional connectivity of medial prefrontal cortex in patients with primary insomnia.

As a representative of acupuncture and nonpharmaceutical therapy, auricular acupuncture has been widely for the treatment of insomnia. Transcutaneous auricular vagus nerve stimulation (taVNS) is a combination of auricular point stimulation and vagus nerve stimulation. It can not only treat primary insomnia effectively, but also is noninvasive, painless, portable and economical. The medial prefrontal cortex (mPFC) is a core region of default mode network (DMN), which is important for maintenance of sleep. However, the mechanism of taVNS in alleviating primary insomnia (PI) remains to be clarified. In this study, we found that taVNS could not only effectively reduce the score of Pittsburgh Sleep Quality Index, but also decreased functional connection (FC) between the left mPFC and bilateral dorsal anterior cingulate gyrus as well as FC between the right mPFC and the occipital cortex in patients with PI. Furthermore, the decrease in FC was positively correlated with the decline of sleep index score. Therefore, we proposed that treatment with taVNS can improve sleep quality and prolong sleep duration in patients with PI by reducing FC within DMN, FC between DMN and salience network, as well as FC between DMN and the occipital cortex. This may be one of mechanisms of taVNS in treating PI.

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application.

Whether in the West or the East, the connection between the ear and the rest of the body has been explored for a long time. Especially in the past century or more, the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy, and finally the concept of transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed. The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear. In the past two decades, taVNS has been a topic of basic, clinical, and transformation research. It has been applied as an alternative to drug treatment for a variety of diseases. Based on the rapid understanding of the application of taVNS to human health and disease, some limitations in the development of this field have also been gradually exposed. Here, we comprehensively review the origin and research status of the field.

Hot and Cold Theory: A Personalized Medicine Approach.

The hot and cold theory is an important part of Traditional Medicines (TMs) which can be used in health care, disease prevention, diagnosis, and treatment purposes. However, little has been said about the material basis of the theory and how the hot and cold theory can be integrated with the conventional medicine. This article will summarize how the Hot and Cold Theory may help health care providers to personalize their treatment, as well as the material basis of the theory and its future prospects.

Corrigendum to "Effect of Transcutaneous Vagus Nerve Stimulation at Auricular Concha for Insomnia: A Randomized Clinical Trial".

[This corrects the article DOI: 10.1155/2020/6049891.].

Effect of Transcutaneous Vagus Nerve Stimulation at Auricular Concha for Insomnia: A Randomized Clinical Trial.

Insomnia inflicts mental burden and decreases physical productivity and affects life quality. Transcutaneous vagus nerve stimulation (ta-VNS) may be an effective treatment option for insomnia. This study aims to evaluate the effect and safety of ta-VNS and compare it with transcutaneous nonvagus nerve stimulation (tn-VNS). A multicenter, randomized, clinical trial was conducted at 3 hospitals in China enrolling 72 insomnia participants from May 2016 to June 2017. Participants were randomly assigned (1 : 1) to receive 40 sessions of ta-VNS or tn-VNS treatment. 63 participants completed the trial. ta-VNS treatment significantly decreased the Pittsburgh Sleep Quality Index score, Epworth Sleepiness Scale score, Flinders Fatigue Scale score, Hamilton Depression Scale score, and Hamilton Anxiety Scale score over 4 weeks compared with those of the baseline. Moreover, it also significantly increased the 36-item Short-Form Health Survey Questionnaire scores compared with that of the baseline. However, it did not show significant differences compared with tn-VNS in changes of primary and secondary outcomes. The incidence of adverse events was low. ta-VNS significantly relieved insomnia over 4 weeks. Moreover, it also alleviated fatigue and improved participants' quality of life as well as other concomitant symptoms such as depression and anxiety. This trial is registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn) with the registration number: ChiCTR-TRC-13003519.

[Horn and cupping].

Cupping, with an ancient name of horn method, possessed other different names and operational approaches through the history. There was wrong information about cupping which was passed on due to unawareness of predecessors. Through probing into the literature and history, this article summarizes and studies warming cupping, cupping over needles, water boiled cupping and fire cupping.

[Present situation and development of acupuncture and moxibustion in Turkey].

The development and status of acupuncture-moxibustion in Turkey in the fields of education, legal establishment, treatment, etc. are introduced. There are four distinguished features of acupuncture-moxibustion development in Turkey: (1) The geographical position of the country as the link of Europe and Asia, has resulted in the special feature of acupuncture-moxibustion transmission and development. It combines both the traditional theories from the East and the modified and modern techniques from the West. (2) The combination of theories and clinical practice started when acupuncture-moxibustion was first introduced. (3) The application of acupuncture-moxibustion has gone through a process from spontaneous transmission among the people to legalization by the government, from disorderly to orderly, and from market behavior to government-lead regulation, which has powerfully promoted healthy development of the medicine. (4) Acupuncture-moxibustion education provided by registered universities has guaranteed the quality of the education itself and the competency of the professionals. It has raised the scientific and normative character of application and increased the credibility of the people, and also has ensured the sustainability of acupuncture-moxibustion development by providing qualified professionals.

Capillary blood flow in patients with dysmenorrhea treated with acupuncture.

OBJECTIVE: To observe capillary blood flow at acupoints during acupuncture treatment of primary dysmenorrhea and gain new insights into its analgesic mechanism. METHODS: Patients with primary dysmenorrhea were enrolled and randomly assigned to a treatment or control group. Subjects' symptoms were differentiated into various Traditional Chinese Medicine (TCM) syndromes and treated for 10 sessions with puncturing acupuncture or self-pressing right-hand Hegu (LI 4), adding other acupoints based on syndrome. Laser speckle was used to compare the change in the vasomotor amplitude and perfusion of the capillaries in Hegu (LI 4) before and during the treatment. Each subject was required to finish the period pain symptoms observation form, verbal rating scales, numerical rating scale, pain rating index, face rating scale, Zung self-rating depression scale, Zung self-rating anxiety scale, and numerical rating scale before and after treatments. RESULTS: After 10 sessions, the symptom scores, pain index (PI), and visual analog scale (VAS) decreased significantly in treatment group. The volume of blood flow in Hegu (LI 4) declined slightly. No significant evidence supported that needling caused capillary contraction, but the capillary vasomotor amplitude at Hegu (LI 4) increased remarkably. CONCLUSION: Acupuncture can increase the capillary blood flow, thus promoting the flow of Qi and blood in terms ofTCM theory, which facilitates pain relief.

Heated moxibustion and bloodletting in Tibetan medical literature of Dunhuang Heritage.

The paper introduces the heated moxibustion and bloodletting in Tibetan medical literature of Dunhuang Heritage. It proves that the external therapies in Tibetan medicine such as heated moxibustion and bloodletting are of very high level since the 8th century, which inspires current clinical practice. It also shows that the extensive exchange between Tibetan medicine and various kinds of medicine such as Chinese medicine promoted the development of Tibetan medicine.