TaVNS reduces inflammatory responses in a L-NAME-induced rat model of pre-eclampsia

Pre-eclampsia is characterized by an excessive maternal inflammatory response.The cholinergic antiinflammatory pathway(CAP)has been shown as the efferent arm of a vagal reflex with the potential to limit inflammatory responses.Therefore,in this study,the CAP regulation through the nervous vagal stimulation(VNS)reduced the severity of NG-nitro-L-arginine methyl ester(L-NAME)-induced pre-eclampsia was determined in a rat model.Rats were given 125 mg/kg/day of L-NAME via subcutaneous injection on gestational day(GD)10–16.In addition,the rats were treated by active or sham electrical stimulation once a day during GD 13–19.Systolic blood pressure(SBP),urinary albumin,and pregnancy outcomes were documented for each rat.The average fetal weights and crown-rump length(CRL)as well as the placental weights of rats in both control and experimental groups were recorded onthe 13th day,16th day and 20th day of gestation.Subsequently,placentas were collected from the rats on GD20 to measure the level of cytokines.In addition,qRT-PCR and Western blot analysis were used to detect the mRNA and protein expression ofα7 nicotinic acetylcholine receptor(α7nAChR)and nuclear factor-κB(NF-κB),respectively.Immunohistochemistry assays were also carried out to determine the location and level ofα7nAChR and NF-κB in placentas.CAP regulation through the transcutaneous auricular nerve stimulation alleviated the clinical symptoms in the rats after L-NAME induction,including hypertension,proteinuria,fetal growth retardation and fetal death.In addition,TaVNS also increasedα7nAChR expression,reduced NF-κB p65 expression,and reversed LNAME-induced proinflammatory cytokines in the placenta tissues,including tumor necrosis factor-alpha(TNF-α),high mobility group box 1(HMGB-1)and interleukin-6(IL-6).The findings of this study showed that TaVNS might be used as a promising tool to attenuate pre-eclampsia-like symptoms.In addition,the protective effect of TaVNS was associated with the improvement ofα7nAChR expression and the inhibition of inflammatory reactions at the maternal-fetal interface through activating cholinergic anti-inflammation pathway.

基于局部一致性分析经皮耳穴迷走神经刺激治疗超重/肥胖患者的临床疗效及中枢效应机制

【目的】探讨经皮耳穴迷走神经刺激(taVNS)对超重/肥胖患者的治疗效果,并分析其中枢效应机制。【方法】将26例超重/肥胖患者随机分为经皮耳穴迷走神经刺激试验组(简称taVNS组)12例和生活方式干预对照组(简称对照组)14例,对照组患者采用基于能量限制饮食模式(CRD)的线上生活方式干预,taVNS组患者在对照组的基础上采用taVNS治疗,每次治疗单侧耳朵(选择穴位包括脾点、内分泌点),每天早晚2次,每周治疗5 d,共治疗4周。观察2组患者治疗前后的体质量、体质量指数(BMI)、腰围等肥胖指标的变化情况,同时采集患者治疗后的脑部静息态磁共振功能成像(fMRI)数据,通过局部一致性(ReHo)的分析方法,观察taVNS对患者脑区ReHo的调节作用。【结果】(1)脱落情况方面:研究过程中,2组各脱落1例,最终共有24例患者(包括对照组13例和taVNS组11例)纳入观察指标的统计分析。(2)肥胖指标改善方面:治疗后,taVNS组患者的体质量、BMI、腰围均较治疗前下降(P<0.05),而对照组患者的体质量、BMI、腰围均较治疗前有下降趋势,但差异均无统计学意义(P>0.05);taVNS组对体质量、BMI、腰围等肥胖指标的改善作用均明显优于对照组,组间治疗后和治疗前后差值比较,差异均有统计学意义(P<0.05或P<0.01)。(3)fMRI结果方面:治疗后,taVNS组ReHo值大于对照组的脑区有左侧前额叶、额内侧回,对照组ReHo值大于taVNS组的脑区有右侧顶叶。提示与对照组比较,taVNS组左侧前额叶、额内侧回的ReHo增高,右侧顶叶的ReHo降低(P_(voxel)<0.001,P_(cluster)<0.05,FWE水平校正)。【结论】taVNS作为一种无创治疗手段,对超重/肥胖患者有一定的疗效,taVNS对左侧前额叶、额内侧回、右侧顶叶等相关区域功能的调节可能是其治疗肥胖的中枢效应机制。

V含量对TaVN复合膜微结构、力学性能和摩擦性能的影响

采用磁控溅射仪制备了一系列不同V含量的TaVN复合膜,利用X射线衍射仪研究复合膜以及磨痕的相组成,利用纳米压痕仪表征复合膜的硬度,采用高温摩擦磨损实验机研究了复合膜的室温和高温摩擦性能。结果表明:TaVN复合膜的微结构为面心立方结构,随着V含量的增加,衍射峰择优取向由(200)转变为(111);TaVN薄膜的显微硬度随着V含量增加,先增加后降低,在V含量为18.25at%时,显微硬度达到最大值,为32.3 GPa;在常温下,TaVN复合膜的摩擦系数随着V含量的增加而降低;当温度从室温升高到800℃,薄膜的摩擦系数先升高后降低。采用晶体化学理论讨论了TaVN复合膜和TaN单层膜在高温下的摩擦机理。

V含量对TaVN薄膜微观结构与摩擦学性能的影响

为探讨V元素改善TaN薄膜摩擦学性能的机制,利用磁控溅射仪在304不锈钢基体上和单晶Si片制备不同V含量的TaVN薄膜。使用X射线衍射仪、扫描电镜、显微硬度计、表面综合性能测试仪表征和分析薄膜的结构及性能。结果表明:TaVN薄膜为面心立方结构,不同V含量的TaVN薄膜均在(111)晶面呈现择优取向;随着V含量的增加,TaVN薄膜(111)晶面出现向大角度偏移的现象;不同V含量的TaVN薄膜在扫描电子显微镜下的表面光滑平整无孔隙,膜层与基体间界面清晰,截面呈明显的柱状晶结构;随着V含量的增加,TaVN薄膜硬度先升高后降低,当TaV靶材中V原子分数为15%时,硬度最高;随着V含量的增加,摩擦因数降低,其原因是在摩擦的过程中,薄膜中的V元素氧化形成具有自润滑效果的Magnéli相氧化物V_(2)O_(5);随着V含量的增加,TaVN薄膜磨损机制由磨粒磨损、黏着磨损和氧化磨损转变为磨粒磨损和氧化磨损。

不同调制周期的TiSiN/TaVN纳米多层膜的结构及性能

为了探究调制周期对TiSiN/TaVN纳米多层膜性能的影响,使用磁控溅射仪在304不锈钢和硅片上沉积TiSiN/TaVN纳米多层膜,采用X射线衍射仪、扫描电镜、纳米压痕仪、划痕仪、表面性能综合测试仪等分析和探索不同调制周期的TiSiN/TaVN纳米多层膜的微观结构、力学性能和摩擦学性能。结果表明:TiSiN/TaVN纳米多层膜均为面心立方结构,在(111)晶面和(200)晶面呈现择优取向。随着调制周期的增大,TiSiN/TaVN纳米多层膜的硬度、弹性模量、膜基结合力等先增大后减小,摩擦系数先减小后增大。当调制周期为8 nm时,TiSiN/TaVN纳米多层膜具有优异的力学性能和摩擦学性能,硬度最高为28.79 GPa,弹性模量最大为301 GPa,膜基结合力最高为29.2 N。薄膜硬度强化的主要原因是固溶强化和交变应力场。当调制周期为8 nm时,TiSiN/TaVN纳米多层膜的摩擦系数最小值为0.14,磨损机理主要为磨粒磨损和氧化磨损。TiSiN/TaVN纳米多层膜摩擦学性能改善的主要原因之一是摩擦过程中V元素与氧气反应形成了具有自润滑性能的Magnéli相氧化物V_(2)O_(5)。

Effect and mechanism study on transcutaneous auricular vagus nerve stimulation for functional dyspepsia model 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.

Transcutaneous auricular vagus nerve stimulation for functional dyspepsia:A randomized controlled trial

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.

Effects of transcutaneous auricular vagus nerve stimulation on intestinal ligandins in a rat model of functional dyspepsia

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.

Efficacy and brain mechanism of transcutaneous auricular vagus nerve stimulation for adolescents with mild to moderate depression:Study protocol for a randomized controlled trial

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.