[Mechanism of melatonin-mediated antihyperglycemic effect of transcutaneous auricular vagus nerve stimulation].

OBJECTIVE: To observe the effects of transcutaneous auricular vagus nerve stimulation （taVNS） on plasma melatonin （MLT） content and insulin receptor expression in the liver, the skeletal muscles, and the pancreas of Zucker diabetic fatty （ZDF） rats, so as to explore the hypoglycemic mechanism of taVNS. METHODS: Thirty male ZDF rats were randomly divided into model group, taVNS group and sham-taVNS group, with 10 rats in each group； besides, 10 male Zucker lean rats of the same strain were collected for the blank control group. ZDF rats were fed with high-fat diet to induce type 2 diabetes mellitus （T2DM） rat model. In the taVNS group, HANS-100A electroacupuncture instrument was used to stimulate the cavum conchae of both sides. The stimulation sites of rats in the sham-taVNS were the same as the taVNS group, but without electricity delivered. The above interventions were performed 30 min each time, once daily, lasting for 6 weeks. Fasting blood glucose （FBG） was measured weekly in each group, the plasma metatonin （MLT） content was detected by ELISA, and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was determined by Western blot. RESULTS: Compared with the blank control group, the level of FBG of rats were increased （P<0.01）, the plasma MLT content was decreased （P<0.01） and the insulin receptor expression level in the pancreatic tissue was decreased （P<0.01） in the model group. In the taVNS gruop, FBG was decreased （P<0.05, P<0.01）, the plasma MLT content was increased （P<0.01）, and the insulin receptor expression level in the liver, the skeletal muscle and the pancreas was increased （P<0.05, P<0.01, P<0.001） when compared with the model group. Compared with the taVNS group, FBG was increased （P<0.05, P<0.01）, the plasma MLT content was decreased （P<0.01）, and the expression level of insulin receptors in the skeletal muscle and the pancreas was decreased （P<0.01, P<0.001） in the sham-taVNS group. CONCLUSION: The taVNS can improve the insulin resistance and ultimately obtain the antihyperglycemic effect through regulating MLT concentration.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study.

INTRODUCTION: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. METHODS: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. RESULTS: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. CONCLUSION: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Prolonged Longitudinal Transcutaneous Auricular Vagus Nerve Stimulation Effect on Striatal Functional Connectivity in Patients with Major Depressive Disorder.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective for treating major depressive disorder (MDD). We aimed to explore the modulating effect of prolonged longitudinal taVNS on the striatal subregions' functional connectivity (FC) in MDD patients. METHODS: Sixteen MDD patients were enrolled and treated with taVNS for 8 weeks. Sixteen healthy control subjects (HCs) were recruited without intervention. The resting-state FC (rsFC) based on striatal subregion seed points and the Hamilton Depression Scale (HAMD) were evaluated in the MDD patients and HCs at baseline and after 8 weeks. A two-way ANCOVA test was performed on each rsFC metric to obtain the (group-by-time) interactions. RESULTS: The rsFC values between the left ventral caudate (vCa) and right ventral prefrontal cortex (vPFC), and between the right nucleus accumbens (NAc) and right dorsal medial prefrontal cortex (dmPFC) and ventrolateral prefrontal cortex (vlPFC) are lower in the MDD patients compared to the HCs at baseline, and increase following taVNS; the rsFC values between the left vCa and right, superior occipital gyrus (SOG), and between the left dorsal caudate (dCa) and right cuneus are higher in MDD patients and decrease following taVNS. CONCLUSIONS: Prolonged longitudinal taVNS can modulate the striatum rsFC with the prefrontal cortex, occipital cortex, temporal cortex, and intra-striatum, and these changes partly underlie any symptomatic improvements. The results indicate that prolonged longitudinal taVNS may produce beneficial treatment effects by modulating the cortical striatum circuitry in patients with MDD.

Does acupuncture therapy affect peripheral inflammatory cytokines of major depressive disorder? A protocol for the systematic review and meta-analysis.

Background: Acupuncture is widely used as adjuvant therapy for major depressive disorder (MDD). There is robust evidence that inflammation is closely associated with MDD. To date, only a few numbers of studies have investigated the potential relationship between acupuncture and the change of inflammatory biomarkers in patients with MDD. Additionally, the results are inconsistent among studies. The current study aims to provide a comprehensive, systematic review of the association between acupuncture and changes in peripheral inflammation of patients with MDD, and clarify the alterations of inflammatory cytokines before and after acupuncture treatment by meta-analysis. Methods and analysis: This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible randomized controlled trials (RCTs) reporting acupuncture, with inflammatory cytokines as the outcome measured before and after intervention in patients with MDD, were searched in electronic databases, such as PubMed, Embase, Cochrane, SINOMED, Wanfang, China national knowledge infrastructure (CNKI), and Chongqing VIP (CQVIP). Primary outcomes of interest will be validated to measure the levels of inflammatory cytokines before and after acupuncture treatment in patients with MDD. Discussion: Acupuncture can drive anti-inflammatory effects, as well as symptom changes in MDD, which may represent a viable, multi-faceted treatment approach in MDD. Systematic review registration: [PROSPERO], identifier [CRD42021289207 on 04 December 2021].

The pro-inflammatory factors contribute to the EEG microstate abnormalities in patients with major depressive disorder.

Pro-inflammatory factors may be associated with abnormalities in functional brain networks, which may be a mechanism in the pathogenesis of major depressive disorder (MDD). Electroencephalogram (EEG) microstates reflect the functioning of brain networks. However, the relationship between pro-inflammatory factors and the microstate abnormalities in patients with MDD is poorly understood. 24 MDD patients and 24 age-and sex-matched healthy controls (HC) were recruited. Montgomery-Asberg Depression Rating Scale(MADRS) were assessed. Serum (interleukin- 2(IL- 2), tumor necrosis factor-α (TNF-α) and hs-C-reactive protein (CRP)and EEG data were collected. K-means clustering was performed to characterize different microstates. For each microstate, duration, occurrence and coverage were estimated. Four microstates (e.g. A, B, C, D) were characterized, MDD group showed lower duration, occurrence and coverage of microstate B and microstate D, while higher duration of microstate A and microstate C and levels of IL-2, TNF-α, hs-CRP than HC group. The duration, occurrence and coverage of microstate D were negatively correlated with levels of pro-inflammatory factors (IL-2, TNF- α and hs- CRP) (all P < 0.05). Serum pro-inflammatory induced the abnormalities of microstate D. Together, these findings add to the understanding of the pathophysiology of MDD and point to pro-inflammatory factors contribute to EEG microstate abnormalities in patients with MDD.

[Effect of transcutaneous auricular vagus nerve stimulation on nocturnal autonomic nervous function in primary insomnia patients].

OBJECTIVE: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the sleep quality and nocturnal heart rate variability (HRV) in patients with primary insomnia. METHODS: Twenty-one patients with primary insomnia were included. Using SDZ-ⅡB electric acupuncture apparatus, Xin (CO15) and Shen (CO10) were stimulated with disperse-dense wave, 4 Hz/ 20 Hz in frequency, (0.2±30%) ms of pulse width and tolerable intensity. Electric stimulation was given once every morning and evening of a day, 30 min each time, for 4 weeks totally. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), objective sleep structure (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], the percentages of non-rapid eye movement period 1, 2, 3, and the percentage of rapid eye movement period to TST [N1%, N2%, N3%, REM%] ) and nocturnal HRV (high frequency [HF], low frequency [LF], the ratio of LF to HF [LF/HF], standard deviation for the normal RR intervals [SDNN], squared root of the mean sum of squares of differences between adjacent intervals RR [RMSSD], the percentage of adjacent RR intervals with differences larger than 50 ms in the entire recording [PNN50%], the mean of sinus RR intervals [NNMean] ) were compared in the patients separately. RESULTS: After treatment, the score of each item and the total score of PSQI and SL were all reduced as compared with those before treatment (P<0.01, P<0.001); SE, N3%, LF, HF, LF/HF, SDNN, NNMean and RMSSD were all increased compared with those before treatment (P<0.001, P<0.01). CONCLUSION: The taVNS improves the sleep quality and objective sleep structure in patients with primary insomnia, which is probably related to the regulation of autonomic nervous functions.

[Transcutaneous auricular vagus nerve stimulation promotes gastric motility by up-rgulating α7nAChR and suppressing NF-κB p65 expression in duodenum in rats with functional dyspepsia].

OBJECTIVE: To study the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on gastric sensitivity and motility in rats with functional dyspepsia (FD), so as to explore its underlying mechanism in improving FD. METHODS: A total of 48 young SD rats were randomly divided into control (n=10), model (n=9), taVNS (n=9), subdiaphragmatic vagus nerve stimulation (SDVNS, n=9) and sham SDVNS (n=7) groups. The FD model was established by gavage of 0.1% iodoa-cetamide+2% glucose, once daily for 6 days. Rats in the taVNS group received taVNS (0.5 mA) of optopoint "Heart" and "Stomach" for 30 min, once daily for 14 days, while rats in the SDVNS group received subdiaphragmatic vagus nerve stimulation through the implanted electrode, and those of the sham SDVNS group received only application of the same electrodes without electrical stimulation. Electromyogram (EMG) of the cervical trapezius muscle (reflecting gastric sensitivity) was recorded before and after intragastric expansion via an air ballon and the gastric emptying rate was calculated for assessing the gastric motility. The contents of acetylcholine (ACh), nicotinic acetylcholine receptor α7 subunit (α7nAChR), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in the duodenum tissue were detected by enzyme-linked immunosorbent assay (ELISA). The expression of nuclear factor kappa B (NF-κB) p65 in the duodenum tissue was determined by Western blot. RESULTS: In comparison with the control group, the EMG change rate at intragastric pressure levels of 40, 60 and 80 mm Hg, expression of NF-κB p65 protein, and contents of IL-6, IL-1ß and TNF-α were significantly increased (P<0.05,P<0.01, P<0.001), while the gastric emptying rate, ACh and α7nAChR contents considerably decreased (P<0.05, P<0.001) in the model group. After interventions, the EMG change rate, contents of IL-6, IL-1ß and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.05, P<0.01, P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.05, P<0.001) in both taVNS and SDVNS groups relevant to the model group. In comparison with the sham SDVNS group, the EMG change rate, contents of IL-6, IL-1ß and TNF-α, and expression of NF-κB p65 were notably decreased (P<0.01, P<0.05,P<0.001), and the gastric emptying rate, ACh and α7nAChR contents obviously increased (P<0.01, P<0.001) in the both SDVNS and taVNS groups. CONCLUSION: taVNS can reduce gastric sensitivity and promote gastric emptying in FD model rats, which may be closely related to its functions in up-regulating ACh and α7nAChR contents and inhibiting the activation of NF-κB p65 signaling in the duodenum.

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.

Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal α7nAchR/NF-κB signal pathway.

BACKGROUND: Stress-induced neuroinflammation was considered to play a critical role in the pathogenesis of depression. Transcutaneous auricular vagus nerve stimulation (taVNS) is a relatively non-invasive alternative treatment for patients suffering from major depressive disorder. The anti-inflammatory signal of vagus nerve is mediated by α7 nicotinic acetylcholine receptor (α7nAchR), and the hippocampus, the region with the most distribution of α7nAchR, regulates emotions. Here, we investigated the role of α7nAchR mediating hippocampal neuroinflammation in taVNS antidepressant effect though homozygous α7nAChR (-/-) gene knockout and α7nAchR antagonist (methyllycaconitine, MLA). METHODS: There were control, model, taVNS, α7nAChR(-/-) + taVNS, hippocampus (Hi) MLA + taVNS and Hi saline + taVNS groups. We used the chronic unpredicted mild stress (CUMS) method to establish depressive model rats for 42 days, excepting control group. After the successful modeling, except the control and model, the rats in the other groups were given taVNS, which was applied through an electroacupuncture apparatus at the auricular concha (2/15 Hz, 2 mA, 30 min/days) for 21 days. Behavioral tests were conducted at baseline, after modeling and after taVNS intervention, including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST). These tests are widely used to evaluate depression-like behavior in rats. The samples were taken after experiment, the expressions of α7nAchR, NF-κB p65, IL-1ß and the morphology of microglia were detected. RESULTS: Depression-like behavior and hippocampal neuroinflammation in CUMS model rats were manifested by down-regulated expression of α7nAchR, up-regulated expression of NF-κB p65 and IL-1ß, and the morphology of microglia was in amoebic-like activated state. TaVNS could significantly reverse the above-mentioned phenomena, but had rare improvement effect for α7nAChR(-/-) rats and Hi MLA rats. CONCLUSION: The antidepressant effect of taVNS is related to hippocampal α7nAchR/NF-κB signal pathway.

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.

[Application prospect of common viral tracers in study on brain effect of acupuncture].

The feasibility and prospect of viral tracers and mediating functional components are explored in study on brain effect of acupuncture. In the paper, proceeding with viral tracers, the viral tracers used to analyze the structure of specific neural circuits are introduced, as well as their mediated probes, optical/chemical genetics techniques, Cre-LoxP systems, etc. The viral tracers and their functional components can not only mark specifically nerve cells or neural circuits, but also interfere with the function of specific types of neurons or nuclei. They solve some disadvantage of traditional nerve tracing method that only describes the morphology of neurons of one brain region and the simple projection among brain regions, and the indirect and non-specific absorption. The viral tracers and their functional components play the important approach to decoding the mechanism on brain effect of acupuncture when introduced in experimental acupuncture so as to provide an in vivo, real-time and intuitive novel method for a further analysis of neurobiological mechanism on brain effect of acupuncture.

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.

[Effect of transcutaneous auricular vagus nerve stimulation on hyperglycemia and insulin receptors expression in impaired glucose tolerance rats].

OBJECTIVE: To explore the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on blood glucose regulation and the expression of insulin receptors (INR) of hypothalamus, liver and skeletal muscle tissues in impaired glucose tolerance (IGT) rats, so as to reveal its mechanisms underlying improvement of IGT. METHODS: Thirty-six male Wistar rats were randomly divided into control, model, transcutaneous auricular none-vagus nerve stimulation (tnVNS), and taVNS groups (n=9 in each group). The IGT model was established by feeding the rats with high-fat and high-sugar diet for 5 weeks, and subsequent intraperitoneal injection of a dose of streptozotocin (20 mg/kg). Transcutaneous electrostimulation (2 mA, 2 Hz/15 Hz) was applied to auricular concha (taVNS) or auricular margin (tnVNS), respectively. The treatment was conducted for 30 min once daily for 4 weeks. The body weight, fasting plasma glucose (FPG), 2 h plasma glucose (2 h PG) were recorded every week. The contents of plasma insulin (INS), glucagon (GC), glycosylated hemoglobin (GHbA1c) were detected by using enzyme linked immunosorbent assay (ELISA). The expression levels of INR in hypothalamus, liver and skeletal muscle tissues were detected by Western blot. RESULTS: After modeling, the rats' body weight, the contents of FPG, 2 h PG, GC and GHbA1c were significantly up-regulated (P<0.001, P<0.05, P<0.01), and the content of INS and expression of INR in hypothalamus, liver and skeletal muscle tissues were significantly down-regulated in the model group compared with the control group (P<0.001, P<0.01, P<0.05). Following the treatment, the increased FPG, 2 h PG, GC, and the decreased INS and INR expression of hypothalamus, liver and skeletal muscle tissues were apparently reversed in the taVNS group relevant to the model group (P<0.001, P<0.01, P<0.05). Compared with the tnVNS group, the FPG and 2 h PG contents were considerable decreased, and the content of INS and INR expression of hypothalamus and liver were obviously increased in the taVNS group (P<0.001, P<0.05, P<0.01). CONCLUSION: taVNS can improve the blood glucose and insulin sensitivity in IGT rats, which may contribute to its effectiveness in up-regulating the expression of INR in hypothalamus, liver and skeletal muscle tissues.

[Bibliometric analysis on clinical trials of auricular acupuncture treatment of obesity].

OBJECTIVE: To review the current situation of researches on auricular acupuncture treatment for obesity by using bibliometric analysis, so as to provide a reference for clinical application and experimental research in the future. METHODS: Articles written in both Chinese and English and published from the time of establishment of the following databases were collected from databases of CNKI, Wanfang, PubMed and Web of Science by using key words of "otopoint sticking" "otopoint seed-pres-sing" "auriculotherapy" "ear/auricular acupuncture" "auricular pressure" "auricular-plaster therapy" "acupuncture and auricular pressure" "auriculopressure" "transcutaneous vagus nerve stimulation (taVNS)" "obesity" "adiposity" "adiposis" and "fatty". The articles met our inclusive criteria were analyzed for summarizing their publication years, involved journals, research organizations and selected acupoints. RESULTS: A total of 61 qualified Chinese and 44 English articles were retrieved and published in 45 and 25 journals, respectively. The commonly-used acupoints are "Endocrine" "Stomach" "Spleen" "Shenmen" "Hunger point" "Sanjiao" "Lung" and "Subcortex". The employed auricular acupoint therapy mainly includes auricular acupressure, ear acupuncture, auricular vagus nerve stimulation, and auricular laser radiation. CONCLUSION: Current clinical literature on auricular acupuncture treatment of obesity is relatively lower in quality. Thus, strict research protocols and randomized controlled clinical trials with multiple centers and larger samples are definitely necessary for providing reliable evidence for clinical treatment of obesity by using auricular acupuncture therapy.

[Instant adjustive effect of auricular electroacupuncture on brain default model network of patients with primary insomnia].

OBJECTIVE: To investigate the immediate brain effect of auricular electroacupuncture (EA) in the treatment of primary insomnia (PI). METHODS: In this study, 15 subjects with PI who were diagnosed according to Pitsburgh Sleep Quality Index (PSQI), and other 15 age- and gender-matched subjects without insomnia were recruited in the present study. The PI patients received EA (4 Hz/20 Hz, a tolerable electrical current strength) of auricular concha for 30 min, and their resting state functional magnetic resonance imaging (fMRI) data before and after treatment were collected. The healthy subjects received no any treatment and their resting state fMRI data were collected. The diffe-rence of default mode network functional connectivity between the patients and healthy subjects, and changes of the patient's brain functional connectivity after EA treatment were estimated by using seed-point-based analysis (SPBA). RESULTS: Analysis by taking the posterior cingulate gyrus as the seed-point showed that compared with the healthy participants before treatment, the patient's brain functional connectivity between the posterior cingulate gyrus and the right insula, or the inferior frontal gyrus of the right opercularis region, or the right rolandic operculum was increased. After 30 minutes' EA treatment, the functional connectivity between the posterior cingulate gyrus and the precuneus, the left angular gyrus, the left frontal superior gyrus, the left frontal middle cortex, the right temporalis inferior gyrus, the right temporalis middle gyrus or the left medial orbitofrontal cortex was decreased, while the functional connectivity between the posterior cingulate gyrus and the right lingual gyrus, or the cortex surrounding the right calcarine fissure was increased. CONCLUSION: EA of auricular concha has an instant effect in modulating the brain default mode network in PI patients, which may be its brain mechanism underlying improvement of PI.

[A modified device for transcutaneous electrical auricular concha stimulation in rats].

In the present paper, we introduce a newly modified device named "transcutaneous electrical auricular concha stimulator (TEACS)" for rats. It concludes a main unit (power and control buttons) with newly designed specific output electrodes. Each of the output electrode is made up of two pieces of iron sheet containing magnet and can be firmly attached to the auricular concha and the corresponding site of dorsal auricle, respectively. The two iron sheets are separately connected to each of the output terminal of the main unit via two pieces of wire. This newly modified output electrode replaces the original wire clip, and solves the problems of easy loosening and easy injury of the original spring clip due to repeated usage, being simple, flexible and convenient in application.

[Auricular electroacupuncture improves depression possibly by promoting hippocampal Raf/ERK/RSK/CREB signaling in chronic unpredictable mild stress induced depression rats].

OBJECTIVE: To observe the effect of auricular electroacupuncture (EA) on intracellular Raf/ extracellular signal-regulated kinase (ERK)/ ribosomal S6 kinase (RSK)/ cAMP response element-binding protein (CREB) signal pathway in the hippocampus of depression model rats, so as to explore its anti-depressive mechanism. METHODS: A total of 60 male SD rats were randomly divided into control, model, auricular EA, PD98059(ERK inhibitor), DMSO (Dimethylsulfoxide), PD98059+EA groups (n=10 in each group). The rats in the control group were fed with normal diet without any treatment. The depression model was induced by chronic unpredictable mild stress (CUMS) for consecutive 21 days. EA (20 Hz, 2 mA) was applied to bilateral auricular "Xin"(Heart) and "Shenmen" for 30 min, once daily for 28 days. Rats of the PD98059, DMSO and PD98059+EA groups received intracerebroventricular injection of PD98059(100 µmol/L), DMSO and PD98059 (dissolved by DMSO) solutions (5 µL/d), respectively, once daily for 28 days. Sucrose preference test (sucrose consumption) was conducted at the baseline, before and after the intervention. The expression of hippocampal Raf, phosphorylated (p)-Raf, ERK, p-ERK, RSK, CREB and p-CREB proteins were detected by Western blot after EA intervention. RESULTS: Following modeling, the sucrose consumption volume, and the expression levels of hippocampal Raf, p-Raf, ERK, p-ERK, RSK, CREB, p-CREB proteins were significantly lower in the model group than those in the control group (P<0.01). Following the treatment, the sucrose consumption and the expression levels of Raf, p-Raf, ERK, p-ERK, RSK, CREB, p-CREB in the auricular EA group and those of p-Raf, ERK and CREB in the PD98059+EA group were obviously increased in comparison with the model group (P<0.05, P<0.01), the expression level of p-ERK in the PD98059 group was obviously decreased in comparison with the model group (P<0.05), suggesting an improvement of depression after auricular EA. Compared with auricular EA group, the expression level of p-ERK, p-CREB and RSK in the PD98059+EA group were significantly decreased (P<0.05). CONCLUSION: EA of auricular "Xin" and "Shenmen" is able to improve depression in depression rats, which is probably related to its effect in promoting activities of hippocampal Raf/ERK/RSK/CREB signaling.

Comparison of Body, Auricular, and Abdominal Acupuncture Treatments for Insomnia Differentiated as Internal Harassment of Phlegm-Heat Syndrome: An Orthogonal Design.

Objective. To identify the optimum treatment protocol for insomnia among auricular, body, and abdominal needling methods. Methods. A three-factor (3 needling protocols) and three-level experimental scheme was designed based on orthogonal method. 54 patients of insomnia differentiated as internal harassment of phlegm-heat syndrome were given two courses of acupuncture treatment (each with 20 times of acupuncture). The therapeutic effects were evaluated by comparing the Pittsburgh sleep quality index (PSQI), Hamilton Depression Scale (HAMD) scores, and Hamilton Anxiety Scale (HAMA) scores of patients before treatment, after one course of treatment, and after two courses of treatment as well as one month after treatment. Results. Body, auricular, and abdominal acupuncture treatments all alleviated symptoms of insomnia, depression, and anxiety, but body and auricular acupuncture had stronger therapeutic effects. Conclusions. Body acupuncture at basic points shall be given priority in protocol selection for insomnia. The second-best choice is auricular acupuncture with basic points combined with points based on Traditional Chinese Medicine (TCM) theories. Abdominal needling with very quick effect can be an alternative protocol with basic points combined with syndrome differentiation points.