As a new type of nerve regulation technology, Vagus Nerve Stimulation is currently used in the treatment of nervous system diseases. Auricular Vagus Nerve Stimulation has become one of the research hotspots in this fi...As a new type of nerve regulation technology, Vagus Nerve Stimulation is currently used in the treatment of nervous system diseases. Auricular Vagus Nerve Stimulation has become one of the research hotspots in this field, because there is no implantation risk. However, there is no unified standard for the treatment parameters of aVNS for nervous system diseases. In this paper, the research progress of the anatomical structure and parameters of the vagus nerve and its role in nervous system diseases are reviewed to provide basis for further research.展开更多
Previous studies have shown that vagus nerve stimulation can improve patients' locomotor function.The stimulation of the auricular vagus nerve,which is the only superficial branch of the vagus nerve,may have simil...Previous studies have shown that vagus nerve stimulation can improve patients' locomotor function.The stimulation of the auricular vagus nerve,which is the only superficial branch of the vagus nerve,may have similar effects to vagus nerve stimulation.However,the precise mechanisms remain poorly understood.In this study,rat models of cerebral ischemia/reperfusion injury were established by modified Longa ligation.Twenty-four hours later,7-day auricular vagus nerve stimulation was performed.The results showed that auricular vagus nerve stimulation promoted the secretion of acetylcholine,inhibited the secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α,and reduced connexin 43 phosphorylation in the ischemic penumbra and motor cortex,promoting locomotor function recovery in rats with cerebral ischemia/reperfusion injury.These findings suggested that auricular vagus nerve stimulation promotes the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury by altering the secretion of acetylcholine and inflammatory factors and the phosphorylation of connexin 43.This study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine on November 8,2019(approval No.PZSHUTCM191108014).展开更多
Preeclampsia is a serious obstetric complication.Currently,there is a lack of effective preventive approaches for this disease.Recent studies have identified transcutaneous auricular vagus nerve stimulation(taVNS)as a...Preeclampsia is a serious obstetric complication.Currently,there is a lack of effective preventive approaches for this disease.Recent studies have identified transcutaneous auricular vagus nerve stimulation(taVNS)as a potential novel non-pharmaceutical therapeutic modality for preeclampsia.In this study,we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt.Our results showed that taVNS promoted the release of acetylcholine(ACh).ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS(mtROS),presumably through M3AChR.This reduced the release of pro-apoptotic proteins(cleaved caspase-3,NF-kB-p65,and cytochrome C)and helped preserve the morphological and functional integrity of mitochondria,thus reducing the apoptosis of placental trophoblasts,improving placental function,and relieving preeclampsia.Our study unravels the potential pathophysiological mechanism of preeclampsia.In-depth characterization of the UPRmt is essential for developing more effective therapeutic strategies for preeclampsia targeting mitochondrial function.展开更多
Objective: To confirm whether self-administered AVNA treatment is effective in improving emotional distressunder the COVID-19 pandemic.Methods: A smartphone-based online, randomized, controlled trial was designed from...Objective: To confirm whether self-administered AVNA treatment is effective in improving emotional distressunder the COVID-19 pandemic.Methods: A smartphone-based online, randomized, controlled trial was designed from 26 February 2020 to 28April 2020 in four study sites, including Wuhan, Beijing, Shenyang, and Guangzhou of China. Local residentswho had considerable emotional distress with a score of the Hospital Anxiety and Depression Scale (HADS) ≥9 were recruited. Participants were randomly assigned to three times of AVNA (n = 191) per day, in morning,around noon, and in evening or usual care (UC, n = 215) once daily for 14 days. The primary outcome was theresponse rate, which was the proportion of participants whose Hospital Anxiety and Depression Scale (HADS)score reduced from baseline by ≥ 50%. The assessment was conducted at baseline, 3 days, and 14 days.Results: The AVNA group had a markedly higher response rate than the UC group at 3 days (35.6% vs. 24.9%,P = 0.02) and at 14 days (70.7% vs. 60.6%, P = 0.02). The AVNA group showed significantly greater reductionin scores of HADS at the two measurement points and BAI at 3 days (P ≤ 0.03), with average respective effectsize of 0.217 and 0.195. Participants with AVNA spent less time falling asleep and rated their sleep qualitybeing remarkably higher than those with UC at endpoint.Conclusion: During COVID-19 pandemic period, treatment with self-administrated AVNA was more effectivethan UC in reducing emotional distress of isolated populations. These findings support self-administered AVNAas a treatment option for patients with emotional distress under the COVID-19 pandemic or other emergentevents.展开更多
Implantable cervical vagus nerve stimulation(i VNS) is a representative and promising neuromodulation.However,the invasive nature restricts its application.Traditional auricular acupuncture treatment has a long histor...Implantable cervical vagus nerve stimulation(i VNS) is a representative and promising neuromodulation.However,the invasive nature restricts its application.Traditional auricular acupuncture treatment has a long history.The auricular branch of the vagus nerve(ABVN) is a branch on the surface of the ear.Some studies demonstrates that transcutaneous auricular vagus nerve stimulation(ta VNS) would achieve similar effects as i VNS.Ta VNS and i VNS share a common anatomical basis and acting mechanism.In this article,we made a comparison between i VNS and ta VNS in indications and efficacy.The recent studies have revealed similar clinical efficacy of ta VNS,ta VNS would expand the indication of i VNS.Highquality clinical evidences are needed before ta VNS become be an alternative of i VNS.展开更多
Objective:To explore the effect and its possible mechanism of the intervention of transcutaneous auricular vagus nerve stimulation(taVNS)for the functional dyspepsia(FD)model rats.Methods:Of the 25 male SD rats,6 rats...Objective:To explore the effect and its possible mechanism of the intervention of transcutaneous auricular vagus nerve stimulation(taVNS)for the functional dyspepsia(FD)model rats.Methods:Of the 25 male SD rats,6 rats were set as blank group,the other 19 rats were established to be the functional dyspepsia(FD)model by iodoacetamide intragastric administration,and 18 FD models were successfully established.The 18 model rats were randomly divided into a model group,a shamtaVNS group,and taVNS group,with 6 rats in each group.There was no intervention applied to the rats in the blank and model groups.Whereas,the rats in sham-taVNS group received stimulation to the rim of auricular concha of both sides,and those in taVNS group received stimulation to the cavity of auricular concha of both sides,for 30 min each time,once a day,7 days in succession.After the intervention,the gastric sensitivity of the rats in each group under different pressure conditions in the stomach,the expressions of serum brain-gut peptide motilin(MTL),cholecystokinin(CCK),glucagon-likepeptidel(GLP-1),and inflammatory factors IL-4,IL-10,and IL-1βwere detected.Results:(1)Gastric sensitivity:compared with the blank group,the gastric sensitivity of the model group was higher(P<0.05).Compared with the model group,the gastric sensitivity of the taVNS group was lower(P<0.05).Compared with the sham-taVNS group,the gastric sensitivity of the taVNS group was lower(P<0.05).(2)Expression of brain-gut peptide:compared with the blank group,MTL was lower,CCK and GLP-1 were higher in the model group(all P<0.05).Compared with the model group,MTL was higher,CCK and GLP-1 were lower in the taVNS group(all P<0.05).Compared with the shamtaVNS group,CCK and GLP-1 were lower in the taVNS group(both P<0.05).(3)Expression of inflammatory factors:compared with the blank group,IL-4 and IL-10 were lower and was higher in the model group(all P<0.05).Compared with the model group,IL-10 was higher and IL-1βwas lower in the shamtaVNS group(all P<0.05),while IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Compared with the sham-taVNS group,IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Conclusion:TaVNS can reduce the gastric sensitivity of FD model rats by peripheral anti-inflammatory action and regulating the abnormal secretion of brain-gut peptide.展开更多
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...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.展开更多
Objectives:To observe the clinical long-term therapeutic effect on functional dyspepsia(FD) in the comparative study of transcutaneous auricular vagus nerve stimulation(taVNS) with transcutaneous auricular none-vagus ...Objectives:To observe the clinical long-term therapeutic effect on functional dyspepsia(FD) in the comparative study of transcutaneous auricular vagus nerve stimulation(taVNS) with transcutaneous auricular none-vagus nerve stimulation(tnVNS).Methods:A total of 90 FD patients were randomized into a taVNS group and a tnVNS group,45 cases in each one.The patients in both the taNVS group and the tnVNS group were treated 5 times a week,30 min each time,for 4 weeks totally.Before treatment,after treatment and in follow-up visit,overall symptom points,functional dyspepsia-related quality of life questionnaire(FDQOL),Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD) and self-rating depression scale(SDS) were adopted to evaluate the severity of the symptoms and observe the clinical therapeutic effect of patients.Results:Compared with the scores before treatment,the overall symptom points,FDDQL,HAMA,HAMD and SDS at each time point after treatment were all lower in the patients of the taVNS group.The scores of FDDQL after treatment were almost all higher than that before treatment in the self-comparison of each group.All of the above differences were significant statistically(all P <0.05).Compared with the tnVNS group,the overall symptom points,FDDQL, HAMA,HAMD and SDS at each time point after treatment were all lower in the taVNS group and the score of FDDQL was higher,indicating the statistical differences(all P<0.05).Conclusion:Transcutaneous auricular vagus nerve stimulation is applicable for the treatment of functional dyspepsia.Compared with the control group,taVNS obtains a better long-term effect.展开更多
Objective:To observe the influence of transcutaneous auricular vagus nerve stimulation(taVNS) on fasting plasma glucose(FPG) and serum insulin(INS) in Zucker diabetes fatty(ZDF) rats and explore the regulatory effect ...Objective:To observe the influence of transcutaneous auricular vagus nerve stimulation(taVNS) on fasting plasma glucose(FPG) and serum insulin(INS) in Zucker diabetes fatty(ZDF) rats and explore the regulatory effect of taVNS on blood glucose in ZDF rats.Methods:A total of 20 male ZDF rats were randomized into a model group and a taVNS group,10 rats in each one.Besides,the other 10 Zucker Lean(ZL) rats were selected to be a control group.The rats in the control group were fed with common forage and those in the model group and the taVNS group were fed with high-sugar and high-fat forage.The intervention of electric stimulation was applied in the rats of taVNS group,with 2/15 Hz in frequency,disperse-dense wave and 2 mA in intensity.Each intervention lasted 30 min,once a day,consecutively for 12 weeks.No any intervention was given in the control group and the model group.The body mass and FPG level were recorded once every 2 weeks in the rats.After the experiment,the rats were sacrificed and blood sample was collected.Enzyme linked immunosorbent assay(ELISA) was adopted to determine the level of serum INS in the rats.Results:After the modeling,compared with the control group,the body mass and FPG level were all higher(P <0.05,P <0.01) and the concentration of serum INS was lower(P <0.01) in the rats of the model group.After intervention,compared with the model group,the body mass was lower in week 6 to 10(P <0.01,P <0.05),FPG level was lower in week 8 to 12(P <0.01,P <0.05) and serum INS concentration was higher(P <0.01) in the rats of the taVNS group.Conclusion:TaVNS apparently improves in hyperglycemia in ZDF rats and increases serum insulin concentration in the rats.展开更多
Background:impaired glucose tolerance(IGT)is the early stage of diabetes and it would be deteriorated to type 2 diabetes mellitus(T2 DM)easily if no intervention provided.In western medicine,drug therapy assisted with...Background:impaired glucose tolerance(IGT)is the early stage of diabetes and it would be deteriorated to type 2 diabetes mellitus(T2 DM)easily if no intervention provided.In western medicine,drug therapy assisted with the intervention of lifestyle is predominated.However,drug therapy brings serious side effect and high prices,while lifestyle intervention is difficult to be insisted on by patients.Therefore,a green and effective intervention mode is urgently needed.Transcutaneous auricular vagus nerve stimulation(taVNS)is a noninvasive and green therapeutic method based on the theory of traditional Chinese medicine(TCM),which can regulate glucose metabolism and reduce blood glucose,but the clinical effect of it has not been clarified yet at present.Hence,this randomized controlled trial(RCT)aims at exploring the effectiveness and safety of taVNS in the treatment of IGT.Methods:a total of 158 patients with IGT will be randomized into a taVNS group and a transcutaneous non-auricular vagus nerve stimulation(tnVNS)group,79 cases in each one.In the taVNS group and the tnVNS group,electric stimulation would be applied to Yidan(胰胆pancreas and gallbladder,CO11)and Pi(脾spleen,CO13)on auricular concha and Jian(肩shoulder SF4,5)on auricular rim respectively.The electric stimulation parameters would be the same in the patients of two groups,for 30 min in each treatment,twice a day,6 weeks as one course and 2 courses of treatment required totally.In week 0,6 and 12 of intervention,the effectiveness indicators would be determined,i.e.fasting plasma glucose(FPG),2 h plasma glucose(2 hPG)and glycosylated hemoglobin(HbA1c)successively.On week 0 and 12,body mass index(BMI)would be calculated,respiration,pulse and blood pressure would be recorded separately.Discussion:through observing the regulatory effect of taVNS on FPG,2 hPG,HbAlc and BMI as well as the adverse reactions,the effectiveness and safety of taVNS in treatment of IGT would be evaluated.This study will provide a safe,effective,convenient and nontoxic side effect intervention for clinical treatment of IGT and prevention from the occurrence and development of T2DM.展开更多
Objective:Transcutaneous auricular vagus nerve stimulation(taVNS) can relieve the symptoms of functional dyspepsia(FD) and improve the quality of life of patients,however,the mechanism underlying this effect remains u...Objective:Transcutaneous auricular vagus nerve stimulation(taVNS) can relieve the symptoms of functional dyspepsia(FD) and improve the quality of life of patients,however,the mechanism underlying this effect remains unclear.Therefore,this study aimed to investigate the effects of taVNS on the expression of intestinal mucosal ligandins.Methods:This study was conducted on 24 specific Spathogen-free Sprague-Dawley rats(12 males and12 females).The rat model of FD was established by tail-clip stimulation.After FD was established successfully,all rats were randomized to either the normal group(n=6),model group(n=6),taVNS group(n=6),or sham-taVNS group(n=6).After two weeks of the respective intervention,the score of their general conditions,3 h food intake,gastric emptying rate,and the histology of gastric antrum tissues were observed to evaluate modeling success,and then the effect of taVNS was evaluated.Western blotting was used to assess the expression of the tight junction ligandins-ZO-1 and occludin-and the adhesion ligandin-β-catenin-in the duodenum.The effect of taVNs on the expression of intestinal mucosal barrier ligandins-ZO-1,occludin,and β-catenin-in FD rats was preliminarily investigated.Results:When the model-induced period was finished,the manifestations of FD in the model group rats were mental exhaustion,reduced activities,decreased score of the general conditions,and decreased3 h food intake,compared to the normal group rats.In addition,minimal eosinophil infiltration,without any mucosal erosion or ulcer,was observed in the gastric antrum mucosa.At the end of the study,the mental state of the FD rats improved,and their activities and gastric emptying rate increased in the taVNS group rats.Compared to the normal rats,the duodenal mucosa had less expression of the tight junction ligandins ZO-1 and occludin,but β-catenin expression remained unchangedin the model rats.The expression of the tight junction ligandins ZO-1 and occludin were increased in the duodenal mucosa of model rats after the taVNS intervention.Conclusion:TaVNS can improve the gastric motility and mental state of rats with FD.It may play a therapeutic role by improving the expression of the tight junction ligandin ZO-1 and occludin in the duodenal mucosa,while also repairing the duodenal mucosal barrier.展开更多
Background Depression is a common mental illness in childhood and adolescence,with an incidence of 4%–5%;it can lead to impairments in learning and social functioning.Transcutaneous auricular vagus nerve stimulation(...Background Depression is a common mental illness in childhood and adolescence,with an incidence of 4%–5%;it can lead to impairments in learning and social functioning.Transcutaneous auricular vagus nerve stimulation(taVNS)is a commonly used method of auricular acupuncture point stimulation,which is regarded as an effective treatment for adults with depression.The aim of this study was to investigate the efficacy and mechanism of taVNS for adolescents with mild to moderate depression.Methods This randomized controlled clinical trial will include 120 patients aged 12–16 years,all of whom are diagnosed with mild to moderate depression.Patients will be randomly assigned to a taVNS group and a drug control group(sertraline hydrochloride)at a ratio of 1:1.Patients will be evaluated using the 17‐item Hamilton Depression Scale,Hamilton Anxiety Rating Scale,Self‐Rating Depression Scale,Self‐Rating Anxiety Scale,and Pittsburgh Sleep Quality Index scores at baseline,as well as at the 2nd,4th,6th,8th,and 12th weeks.To investigate the underlying neural mechanisms of taVNS treatment from the perspective of the default mode network,multimodal magnetic resonance imaging(MRI;i.e.,structural MRI[sMRI],resting state MRI[rsMRI],and pseudocontinuous arterial spin‐labeled[pcASL]MRI)will be used to compare cerebral images among groups.MRI data will also be collected from 40 healthy volunteers to assess whether the participants exhibit normal development of structural and functional components.Discussion Depression is the most common mental disorder in adolescence.Drug treatment can improve depression symptoms;however,the side effects of drug treatments are often severe.This study proposes a simple physiotherapy that aims to treat adolescents with mild to moderate depression.The mechanism of taVNS in the treatment of depression will also be investigated.The results of this study will provide evidence to guide the application of taVNS in adolescents with depression.展开更多
OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic reso...OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic resonance imaging(f MRI).METHODS:Twenty-five patients with recurrent depression were enrolled in a single-arm trial of ta VNS treatment for eight weeks.Clinical results were assessed by 17-item Hamilton Depression Rating Scale(HAMD-17),Hamilton Anxiety Scale(HAMA),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS),and Ruminative Response Scale(RRS)scales.Resting-state f MRI was conducted to explore the brain effects before and after treatment.For the functional connectivity(FC)analysis,the bilateral nucleus accumbens,globus pallidus,caudate,and putamen were selected as seeds.Finally,the correlations between FC and the clinical scale scores were calculated.RESULTS:After treatment,the patients’scores of HAMD-17,HAMA,SDS,SAS,and RRS were significantly decreased(P<0.05).FC was considerably decreased between the following areas:the left globus pallidus and the right postcentral gyrus,inferior parietal gyrus,the right globus pallidus and the left superior marginal gyrus,postcentral gyrus,superior parietal gyrus,inferior parietal gyrus,precuneus,right postcentral gyrus,superior marginal gyrus,and inferior parietal gyrus,between the right caudate and the right lingual gyrus,calcarine gyrus,and cerebellum.Changes in FC between the right globus pallidus and the left inferior parietal gyrus,between the left globus pallidus and the right postcentral gyrus were negatively correlated with HAMD-17 scores change before and after treatment(before,P=0.003,r=-0.6;after,P=0.009,r=-0.54).The change of FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SDS(P=0.026,r=-0.474).The difference in FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SAS(P=0.016,r=-0.513).CONCLUSIONS:Recurrent depression could be effectively treated with ta VNS.The changes in brain FC involving the basal ganglia,default mode,and sensorimotor networks provide insight into the effects of ta VNS treatment on recurrent depression.展开更多
Objective:The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats.Methods:Healthy adul...Objective:The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats.Methods:Healthy adult male Sprague-Dawley rats were anesthetized with an intraperitoneal injection of 10% urethane.Seizures were evoked by intraperitoneal injection of pentylenetetrazol(PTZ,60 mg/kg).Femoral vein catheterization was performed for injection of sympathetic agonist and antagonists.Bipolar globe silver electrodes were utilized for epidural EEG recording.Three needles were inserted separately in subcutaneous muscles of left anterior limb,right anterior limb,and left hind limb to record ECG signals.ta-VNS was performed at auricular concha.Results:In comparison with preictal state,the mean heart rate(HR) increased slightly during epileptic seizures(P<0.05).In comparison with ictal state,the mean HR decreased a little at postictal state(P<0.05).When continuous epileptic seizures in EEG traces occurred(in ictal state),vein injection of propranolol hydrochloride(sympathetic antagonist) suppressed the epileptic seizures.When epileptic seizures occurred rarely(in postictal state),vein injection of adrenaline hydrochloride(sympathetic agonist) exacerbated the epileptic seizures.In comparison with prestimulation,the integral of EEG traces after ta-VNS decreased(P<0.05),the mean HR decreased(P<0.05),and the high power(HF) of HRV increased(P<0.05) after ta-VNS.Conclusion:The results showed that autonomic dysfunction occurred in epileptic rats characterized by enhanced sympathetic nerve activity.Epileptic seizures in EEG traces decreased,HR decreased and HF increased after ta-VNS,which indicated that ta-VNS may suppress epileptic seizures via balancing the autonomic dysfunction.展开更多
文摘As a new type of nerve regulation technology, Vagus Nerve Stimulation is currently used in the treatment of nervous system diseases. Auricular Vagus Nerve Stimulation has become one of the research hotspots in this field, because there is no implantation risk. However, there is no unified standard for the treatment parameters of aVNS for nervous system diseases. In this paper, the research progress of the anatomical structure and parameters of the vagus nerve and its role in nervous system diseases are reviewed to provide basis for further research.
基金supported by the National Natural Science Foundation of China,Nos.81704163 (to JJZ),81874035 (to CLS)the National Key R&D Program of China,No.2018YFC2001600 (to CLS)+1 种基金the Shanghai Health Commission Accelerated the Development of Traditional Chinese Medicine ThreeYear Action Plan Project of China,No.ZY(2018-2020)-CCCX-2001-06/2004-05 (to CLS)the Program of Shanghai Academic Research Leader of China,No.19XD1403600 (to CLS)。
文摘Previous studies have shown that vagus nerve stimulation can improve patients' locomotor function.The stimulation of the auricular vagus nerve,which is the only superficial branch of the vagus nerve,may have similar effects to vagus nerve stimulation.However,the precise mechanisms remain poorly understood.In this study,rat models of cerebral ischemia/reperfusion injury were established by modified Longa ligation.Twenty-four hours later,7-day auricular vagus nerve stimulation was performed.The results showed that auricular vagus nerve stimulation promoted the secretion of acetylcholine,inhibited the secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α,and reduced connexin 43 phosphorylation in the ischemic penumbra and motor cortex,promoting locomotor function recovery in rats with cerebral ischemia/reperfusion injury.These findings suggested that auricular vagus nerve stimulation promotes the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury by altering the secretion of acetylcholine and inflammatory factors and the phosphorylation of connexin 43.This study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine on November 8,2019(approval No.PZSHUTCM191108014).
基金supported by the National Natural Science Foundation of China (82105016)the Natural Science Foundation of Shaanxi Province (2022SF-318)+1 种基金the Scientific Research Fund Project of Shaanxi Province Department of Education (21JSO12)the National Training Program of Innovation and Entrepreneurship for Students of China (202210716017).
文摘Preeclampsia is a serious obstetric complication.Currently,there is a lack of effective preventive approaches for this disease.Recent studies have identified transcutaneous auricular vagus nerve stimulation(taVNS)as a potential novel non-pharmaceutical therapeutic modality for preeclampsia.In this study,we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt.Our results showed that taVNS promoted the release of acetylcholine(ACh).ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS(mtROS),presumably through M3AChR.This reduced the release of pro-apoptotic proteins(cleaved caspase-3,NF-kB-p65,and cytochrome C)and helped preserve the morphological and functional integrity of mitochondria,thus reducing the apoptosis of placental trophoblasts,improving placental function,and relieving preeclampsia.Our study unravels the potential pathophysiological mechanism of preeclampsia.In-depth characterization of the UPRmt is essential for developing more effective therapeutic strategies for preeclampsia targeting mitochondrial function.
基金the National Key R&D Program of China(No.2018YFC1705800 and No.2018YFC1705801)the Fundamental Research Funds for the Central public welfare research institutes(No.ZZ202017009)General Research Fund(GRF)of Research Grant Council of HKSAR(No.17115017).
文摘Objective: To confirm whether self-administered AVNA treatment is effective in improving emotional distressunder the COVID-19 pandemic.Methods: A smartphone-based online, randomized, controlled trial was designed from 26 February 2020 to 28April 2020 in four study sites, including Wuhan, Beijing, Shenyang, and Guangzhou of China. Local residentswho had considerable emotional distress with a score of the Hospital Anxiety and Depression Scale (HADS) ≥9 were recruited. Participants were randomly assigned to three times of AVNA (n = 191) per day, in morning,around noon, and in evening or usual care (UC, n = 215) once daily for 14 days. The primary outcome was theresponse rate, which was the proportion of participants whose Hospital Anxiety and Depression Scale (HADS)score reduced from baseline by ≥ 50%. The assessment was conducted at baseline, 3 days, and 14 days.Results: The AVNA group had a markedly higher response rate than the UC group at 3 days (35.6% vs. 24.9%,P = 0.02) and at 14 days (70.7% vs. 60.6%, P = 0.02). The AVNA group showed significantly greater reductionin scores of HADS at the two measurement points and BAI at 3 days (P ≤ 0.03), with average respective effectsize of 0.217 and 0.195. Participants with AVNA spent less time falling asleep and rated their sleep qualitybeing remarkably higher than those with UC at endpoint.Conclusion: During COVID-19 pandemic period, treatment with self-administrated AVNA was more effectivethan UC in reducing emotional distress of isolated populations. These findings support self-administered AVNAas a treatment option for patients with emotional distress under the COVID-19 pandemic or other emergentevents.
基金Supported by the China Academy of Chinese Medical Sciences Innovation Fund:Brain Effects and Multimodal Imaging Mechanism of Transcutaneous Auricular Vagus Nerve Stimulation in Patients with Disorder of Consciousness(CI2021A03305)the National Key Research and Development Program:Optimization and Effect Mechanism of Transcutaneous Electrical Cranial-auricular Acupoint Stimulation(TECAS) on Depression(No.2018YFC1705800)。
文摘Implantable cervical vagus nerve stimulation(i VNS) is a representative and promising neuromodulation.However,the invasive nature restricts its application.Traditional auricular acupuncture treatment has a long history.The auricular branch of the vagus nerve(ABVN) is a branch on the surface of the ear.Some studies demonstrates that transcutaneous auricular vagus nerve stimulation(ta VNS) would achieve similar effects as i VNS.Ta VNS and i VNS share a common anatomical basis and acting mechanism.In this article,we made a comparison between i VNS and ta VNS in indications and efficacy.The recent studies have revealed similar clinical efficacy of ta VNS,ta VNS would expand the indication of i VNS.Highquality clinical evidences are needed before ta VNS become be an alternative of i VNS.
基金Supported by International Cooperation and Exchange of the National Natural Science Foundation of China:NO.8182010803381473780The Fundamental Research Funds for the Central public welfare research institutes:NO.ZZ201915009.
文摘Objective:To explore the effect and its possible mechanism of the intervention of transcutaneous auricular vagus nerve stimulation(taVNS)for the functional dyspepsia(FD)model rats.Methods:Of the 25 male SD rats,6 rats were set as blank group,the other 19 rats were established to be the functional dyspepsia(FD)model by iodoacetamide intragastric administration,and 18 FD models were successfully established.The 18 model rats were randomly divided into a model group,a shamtaVNS group,and taVNS group,with 6 rats in each group.There was no intervention applied to the rats in the blank and model groups.Whereas,the rats in sham-taVNS group received stimulation to the rim of auricular concha of both sides,and those in taVNS group received stimulation to the cavity of auricular concha of both sides,for 30 min each time,once a day,7 days in succession.After the intervention,the gastric sensitivity of the rats in each group under different pressure conditions in the stomach,the expressions of serum brain-gut peptide motilin(MTL),cholecystokinin(CCK),glucagon-likepeptidel(GLP-1),and inflammatory factors IL-4,IL-10,and IL-1βwere detected.Results:(1)Gastric sensitivity:compared with the blank group,the gastric sensitivity of the model group was higher(P<0.05).Compared with the model group,the gastric sensitivity of the taVNS group was lower(P<0.05).Compared with the sham-taVNS group,the gastric sensitivity of the taVNS group was lower(P<0.05).(2)Expression of brain-gut peptide:compared with the blank group,MTL was lower,CCK and GLP-1 were higher in the model group(all P<0.05).Compared with the model group,MTL was higher,CCK and GLP-1 were lower in the taVNS group(all P<0.05).Compared with the shamtaVNS group,CCK and GLP-1 were lower in the taVNS group(both P<0.05).(3)Expression of inflammatory factors:compared with the blank group,IL-4 and IL-10 were lower and was higher in the model group(all P<0.05).Compared with the model group,IL-10 was higher and IL-1βwas lower in the shamtaVNS group(all P<0.05),while IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Compared with the sham-taVNS group,IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Conclusion:TaVNS can reduce the gastric sensitivity of FD model rats by peripheral anti-inflammatory action and regulating the abnormal secretion of brain-gut peptide.
基金This review was supported by the National Key R&D Program of China(2018YFC1705800)the National Natural Science Foundation of China(81803872,81674072)+1 种基金the Joint Sino-German Research Project(GZ1236)the Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ201813006).
文摘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.
基金Supported by National Natural Science Foundation:81674072Beijing Municipal Administration of Hospitals Incubating Program:PZ2021001。
文摘Objectives:To observe the clinical long-term therapeutic effect on functional dyspepsia(FD) in the comparative study of transcutaneous auricular vagus nerve stimulation(taVNS) with transcutaneous auricular none-vagus nerve stimulation(tnVNS).Methods:A total of 90 FD patients were randomized into a taVNS group and a tnVNS group,45 cases in each one.The patients in both the taNVS group and the tnVNS group were treated 5 times a week,30 min each time,for 4 weeks totally.Before treatment,after treatment and in follow-up visit,overall symptom points,functional dyspepsia-related quality of life questionnaire(FDQOL),Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD) and self-rating depression scale(SDS) were adopted to evaluate the severity of the symptoms and observe the clinical therapeutic effect of patients.Results:Compared with the scores before treatment,the overall symptom points,FDDQL,HAMA,HAMD and SDS at each time point after treatment were all lower in the patients of the taVNS group.The scores of FDDQL after treatment were almost all higher than that before treatment in the self-comparison of each group.All of the above differences were significant statistically(all P <0.05).Compared with the tnVNS group,the overall symptom points,FDDQL, HAMA,HAMD and SDS at each time point after treatment were all lower in the taVNS group and the score of FDDQL was higher,indicating the statistical differences(all P<0.05).Conclusion:Transcutaneous auricular vagus nerve stimulation is applicable for the treatment of functional dyspepsia.Compared with the control group,taVNS obtains a better long-term effect.
基金Supported by National Natural Science Foundation of China:81674072Sino-German Cooperative Research Project of National Natural Science Foundation of China:GZ1236National Natural Science Foundation of China Youth Project:82004181。
文摘Objective:To observe the influence of transcutaneous auricular vagus nerve stimulation(taVNS) on fasting plasma glucose(FPG) and serum insulin(INS) in Zucker diabetes fatty(ZDF) rats and explore the regulatory effect of taVNS on blood glucose in ZDF rats.Methods:A total of 20 male ZDF rats were randomized into a model group and a taVNS group,10 rats in each one.Besides,the other 10 Zucker Lean(ZL) rats were selected to be a control group.The rats in the control group were fed with common forage and those in the model group and the taVNS group were fed with high-sugar and high-fat forage.The intervention of electric stimulation was applied in the rats of taVNS group,with 2/15 Hz in frequency,disperse-dense wave and 2 mA in intensity.Each intervention lasted 30 min,once a day,consecutively for 12 weeks.No any intervention was given in the control group and the model group.The body mass and FPG level were recorded once every 2 weeks in the rats.After the experiment,the rats were sacrificed and blood sample was collected.Enzyme linked immunosorbent assay(ELISA) was adopted to determine the level of serum INS in the rats.Results:After the modeling,compared with the control group,the body mass and FPG level were all higher(P <0.05,P <0.01) and the concentration of serum INS was lower(P <0.01) in the rats of the model group.After intervention,compared with the model group,the body mass was lower in week 6 to 10(P <0.01,P <0.05),FPG level was lower in week 8 to 12(P <0.01,P <0.05) and serum INS concentration was higher(P <0.01) in the rats of the taVNS group.Conclusion:TaVNS apparently improves in hyperglycemia in ZDF rats and increases serum insulin concentration in the rats.
基金Mechanisms Underlying the Regulation of Impaired Glucose Tolerance by Auricular Concha Electro-acupuncture:81,674,072。
文摘Background:impaired glucose tolerance(IGT)is the early stage of diabetes and it would be deteriorated to type 2 diabetes mellitus(T2 DM)easily if no intervention provided.In western medicine,drug therapy assisted with the intervention of lifestyle is predominated.However,drug therapy brings serious side effect and high prices,while lifestyle intervention is difficult to be insisted on by patients.Therefore,a green and effective intervention mode is urgently needed.Transcutaneous auricular vagus nerve stimulation(taVNS)is a noninvasive and green therapeutic method based on the theory of traditional Chinese medicine(TCM),which can regulate glucose metabolism and reduce blood glucose,but the clinical effect of it has not been clarified yet at present.Hence,this randomized controlled trial(RCT)aims at exploring the effectiveness and safety of taVNS in the treatment of IGT.Methods:a total of 158 patients with IGT will be randomized into a taVNS group and a transcutaneous non-auricular vagus nerve stimulation(tnVNS)group,79 cases in each one.In the taVNS group and the tnVNS group,electric stimulation would be applied to Yidan(胰胆pancreas and gallbladder,CO11)and Pi(脾spleen,CO13)on auricular concha and Jian(肩shoulder SF4,5)on auricular rim respectively.The electric stimulation parameters would be the same in the patients of two groups,for 30 min in each treatment,twice a day,6 weeks as one course and 2 courses of treatment required totally.In week 0,6 and 12 of intervention,the effectiveness indicators would be determined,i.e.fasting plasma glucose(FPG),2 h plasma glucose(2 hPG)and glycosylated hemoglobin(HbA1c)successively.On week 0 and 12,body mass index(BMI)would be calculated,respiration,pulse and blood pressure would be recorded separately.Discussion:through observing the regulatory effect of taVNS on FPG,2 hPG,HbAlc and BMI as well as the adverse reactions,the effectiveness and safety of taVNS in treatment of IGT would be evaluated.This study will provide a safe,effective,convenient and nontoxic side effect intervention for clinical treatment of IGT and prevention from the occurrence and development of T2DM.
基金Supported by the National Natural Science Foundation of China:81,674,072China Academy of Chinese Medical Sciences,2019"One Belt and One Road"International Cooperation Program of Traditional Chinese Medicine:GH201912the Fundamental Research Funds for Central Public Welfare Research Institutes:ZZ20191603,ZZ201915009,ZZ201915012.
文摘Objective:Transcutaneous auricular vagus nerve stimulation(taVNS) can relieve the symptoms of functional dyspepsia(FD) and improve the quality of life of patients,however,the mechanism underlying this effect remains unclear.Therefore,this study aimed to investigate the effects of taVNS on the expression of intestinal mucosal ligandins.Methods:This study was conducted on 24 specific Spathogen-free Sprague-Dawley rats(12 males and12 females).The rat model of FD was established by tail-clip stimulation.After FD was established successfully,all rats were randomized to either the normal group(n=6),model group(n=6),taVNS group(n=6),or sham-taVNS group(n=6).After two weeks of the respective intervention,the score of their general conditions,3 h food intake,gastric emptying rate,and the histology of gastric antrum tissues were observed to evaluate modeling success,and then the effect of taVNS was evaluated.Western blotting was used to assess the expression of the tight junction ligandins-ZO-1 and occludin-and the adhesion ligandin-β-catenin-in the duodenum.The effect of taVNs on the expression of intestinal mucosal barrier ligandins-ZO-1,occludin,and β-catenin-in FD rats was preliminarily investigated.Results:When the model-induced period was finished,the manifestations of FD in the model group rats were mental exhaustion,reduced activities,decreased score of the general conditions,and decreased3 h food intake,compared to the normal group rats.In addition,minimal eosinophil infiltration,without any mucosal erosion or ulcer,was observed in the gastric antrum mucosa.At the end of the study,the mental state of the FD rats improved,and their activities and gastric emptying rate increased in the taVNS group rats.Compared to the normal rats,the duodenal mucosa had less expression of the tight junction ligandins ZO-1 and occludin,but β-catenin expression remained unchangedin the model rats.The expression of the tight junction ligandins ZO-1 and occludin were increased in the duodenal mucosa of model rats after the taVNS intervention.Conclusion:TaVNS can improve the gastric motility and mental state of rats with FD.It may play a therapeutic role by improving the expression of the tight junction ligandin ZO-1 and occludin in the duodenal mucosa,while also repairing the duodenal mucosal barrier.
文摘Background Depression is a common mental illness in childhood and adolescence,with an incidence of 4%–5%;it can lead to impairments in learning and social functioning.Transcutaneous auricular vagus nerve stimulation(taVNS)is a commonly used method of auricular acupuncture point stimulation,which is regarded as an effective treatment for adults with depression.The aim of this study was to investigate the efficacy and mechanism of taVNS for adolescents with mild to moderate depression.Methods This randomized controlled clinical trial will include 120 patients aged 12–16 years,all of whom are diagnosed with mild to moderate depression.Patients will be randomly assigned to a taVNS group and a drug control group(sertraline hydrochloride)at a ratio of 1:1.Patients will be evaluated using the 17‐item Hamilton Depression Scale,Hamilton Anxiety Rating Scale,Self‐Rating Depression Scale,Self‐Rating Anxiety Scale,and Pittsburgh Sleep Quality Index scores at baseline,as well as at the 2nd,4th,6th,8th,and 12th weeks.To investigate the underlying neural mechanisms of taVNS treatment from the perspective of the default mode network,multimodal magnetic resonance imaging(MRI;i.e.,structural MRI[sMRI],resting state MRI[rsMRI],and pseudocontinuous arterial spin‐labeled[pcASL]MRI)will be used to compare cerebral images among groups.MRI data will also be collected from 40 healthy volunteers to assess whether the participants exhibit normal development of structural and functional components.Discussion Depression is the most common mental disorder in adolescence.Drug treatment can improve depression symptoms;however,the side effects of drug treatments are often severe.This study proposes a simple physiotherapy that aims to treat adolescents with mild to moderate depression.The mechanism of taVNS in the treatment of depression will also be investigated.The results of this study will provide evidence to guide the application of taVNS in adolescents with depression.
基金Supported by the National Natural Science Foundation of China:Neuroimaging Study of Transcutaneous Auricular Vagus Nerve Stimulation in Treatment of Refractory Depression Based on Emotion Cognition Circuit(No.81774433)Prediction of Curative Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Depression based on MRI and Machine Learning Technology(No.82174282)Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences:Study on the Mechanism and Efficacy Prediction of Transcutaneous Auricular Vagus Nerve Stimulation in the Treatment of Depression based on MRI Brain Imaging and Intestinal Flora(No.CI2021A03316)。
文摘OBJECTIVE:To examine the brain effects of transcutaneous auricular vagus nerve stimulation(ta VNS)treatment of recurrent depression based on the functional brain network by using resting-state functional magnetic resonance imaging(f MRI).METHODS:Twenty-five patients with recurrent depression were enrolled in a single-arm trial of ta VNS treatment for eight weeks.Clinical results were assessed by 17-item Hamilton Depression Rating Scale(HAMD-17),Hamilton Anxiety Scale(HAMA),Self-Rating Depression Scale(SDS),Self-Rating Anxiety Scale(SAS),and Ruminative Response Scale(RRS)scales.Resting-state f MRI was conducted to explore the brain effects before and after treatment.For the functional connectivity(FC)analysis,the bilateral nucleus accumbens,globus pallidus,caudate,and putamen were selected as seeds.Finally,the correlations between FC and the clinical scale scores were calculated.RESULTS:After treatment,the patients’scores of HAMD-17,HAMA,SDS,SAS,and RRS were significantly decreased(P<0.05).FC was considerably decreased between the following areas:the left globus pallidus and the right postcentral gyrus,inferior parietal gyrus,the right globus pallidus and the left superior marginal gyrus,postcentral gyrus,superior parietal gyrus,inferior parietal gyrus,precuneus,right postcentral gyrus,superior marginal gyrus,and inferior parietal gyrus,between the right caudate and the right lingual gyrus,calcarine gyrus,and cerebellum.Changes in FC between the right globus pallidus and the left inferior parietal gyrus,between the left globus pallidus and the right postcentral gyrus were negatively correlated with HAMD-17 scores change before and after treatment(before,P=0.003,r=-0.6;after,P=0.009,r=-0.54).The change of FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SDS(P=0.026,r=-0.474).The difference in FC between the right globus pallidus and the right postcentral gyrus was negatively correlated with the change in SAS(P=0.016,r=-0.513).CONCLUSIONS:Recurrent depression could be effectively treated with ta VNS.The changes in brain FC involving the basal ganglia,default mode,and sensorimotor networks provide insight into the effects of ta VNS treatment on recurrent depression.
基金supported by National Natural Science Foundation of China(No.81273829,Beijing,China)the Fundamental Research Funds for the Central public welfare research institutes(ZZKF08004,Beijing,China)
文摘Objective:The present study aims to investigate whether the anticonvulsant effect of transcutaneous auricular vagus nerve stimulation is associated with balancing the autonomic dysfunction in rats.Methods:Healthy adult male Sprague-Dawley rats were anesthetized with an intraperitoneal injection of 10% urethane.Seizures were evoked by intraperitoneal injection of pentylenetetrazol(PTZ,60 mg/kg).Femoral vein catheterization was performed for injection of sympathetic agonist and antagonists.Bipolar globe silver electrodes were utilized for epidural EEG recording.Three needles were inserted separately in subcutaneous muscles of left anterior limb,right anterior limb,and left hind limb to record ECG signals.ta-VNS was performed at auricular concha.Results:In comparison with preictal state,the mean heart rate(HR) increased slightly during epileptic seizures(P<0.05).In comparison with ictal state,the mean HR decreased a little at postictal state(P<0.05).When continuous epileptic seizures in EEG traces occurred(in ictal state),vein injection of propranolol hydrochloride(sympathetic antagonist) suppressed the epileptic seizures.When epileptic seizures occurred rarely(in postictal state),vein injection of adrenaline hydrochloride(sympathetic agonist) exacerbated the epileptic seizures.In comparison with prestimulation,the integral of EEG traces after ta-VNS decreased(P<0.05),the mean HR decreased(P<0.05),and the high power(HF) of HRV increased(P<0.05) after ta-VNS.Conclusion:The results showed that autonomic dysfunction occurred in epileptic rats characterized by enhanced sympathetic nerve activity.Epileptic seizures in EEG traces decreased,HR decreased and HF increased after ta-VNS,which indicated that ta-VNS may suppress epileptic seizures via balancing the autonomic dysfunction.
