Neural mechanism of gastric motility regulation by electroacupuncture at RN12 and BL21: A paraventricular hypothalamic nucleus-dorsal vagal complex-vagus nervegastric channel pathway

AIM: To study the neural mechanism by which electroacupuncture(EA) at RN12(Zhongwan) and BL21(Weishu) regulates gastric motility.METHODS: One hundred and forty-four adult Sprague Dawley rats were studied in four separate experiments. Intragastric pressure was measured using custommade rubber balloons, and extracellular neuron firing activity, which is sensitive to gastric distention in the dorsal vagal complex(DVC), was recorded by an electrophysiological technique. The expression levels of c-fos, motilin(MTL) and gastrin(GAS) in the paraventricular hypothalamic nucleus(PVN) were assayed by immunohistochemistry, and the expression levels of motilin receptor(MTL-R) and gastrin receptor(GAS-R) in both the PVN and the gastric antrum were assayed by western blotting.RESULTS: EA at RN12 + BL21(gastric Shu and Mu points), BL21(gastric Back-Shu point), RN12(gastric Front-Mu point), resulted in increased neuron-activating frequency in the DVC(2.08 ± 0.050, 1.17 ± 0.023, 1.55 ± 0.079 vs 0.75 ± 0.046, P < 0.001) compared with a model group. The expression of c-fos(36.24 ± 1.67, 29.41 ± 2.55, 31.79 ± 3.00 vs 5.73 ± 2.18, P < 0.001), MTL(22.48 ± 2.66, 20.76 ± 2.41, 19.17 ± 1.71 vs 11.68 ± 2.52, P < 0.001), GAS(24.99 ± 2.95, 21.69 ± 3.24, 23.03 ± 3.09 vs 12.53 ± 2.15, P < 0.001), MTL-R(1.39 ± 0.05, 1.22 ± 0.05, 1.17 ± 0.12 vs 0.84 ± 0.06, P < 0.001), and GAS-R(1.07 ± 0.07, 0.91 ± 0.06, 0.78 ± 0.05 vs 0.45 ± 0.04, P < 0.001) increased in the PVN after EA compared with the model group. The expression of MTL-R(1.46 ± 0.14, 1.26 ± 0.11, 0.99 ± 0.07 vs 0.65 ± 0.03, P < 0.001), and GAS-R(1.63 ± 0.11, 1.26 ± 0.16, 1.13 ± 0.02 vs 0.80 ± 0.11, P < 0.001) increased in the gastric antrum after EA compared with the model group. Damaging the PVN resulted in reduced intragastric pressure(13.67 ± 3.72 vs 4.27 ± 1.48, P < 0.001). These data demonstrate that the signals induced by EA stimulation of acupoints RN12 and BL21 are detectable in the DVC and the PVN, and increase the levels of gastrointestinal hormones and their receptors in the PVN and gastric antrum to regulate gastric motility. CONCLUSION: EA at RN12 and BL21 regulates gastric motility, which may be achieved through the PVN-DVCvagus-gastric neural pathway.

Role of vasoactive intestinal peptide and nitric oxide in the modulation of electroacupucture on gastric motility in stressed rats

AIM: To investigate the effects and mechanisms of vasoactive intestinal peptide (VIP) and nitric oxide (NO) in the modulation of electroacupucture (EA) on gastric motility in restrained-cold stressed rats. METHODS: An animal model of gastric motility disorder was established by restrained-cold stress. Gastric myoelectric activities were recorded by electrogastroent erography (EGG). VIP and NO concentrations in plasma and gastric mucosal and bulb tissues were detected by radioimmunoassay (RIA). VIP expression in the gastric walls was assayed using avidin-biotin-peroxidase complex (ABC) and image analysis. RESULTS: In cold restrained stressed rats, EGG was disordered and irregular. The frequency and amplitude of gastric motility were higher than that in control group (P < 0.01). VIP and NO contents of plasma, gastric mucosal and bulb tissues were obviously decreased (P < 0.01). Following EA at “Zusanli” (ST36), the frequency and amplitude of gastric motility were obviously lowered (P < 0.01), while the levels of VIP and NO in plasma, gastric mucosal and bulb tissues increased strikingly (P < 0.01, P < 0.05) and expression of VIP in antral smooth muscle was elevated significantly (P < 0.01) in comparison with those of model group. CONCLUSION: VIP and NO participate in the modulatory effect of EA on gastric motility. EA at “Zusanli” acupoint (ST36) can improve gastric motility of the stressed rats by increasing the levels of VIP and NO.

Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase Ⅳ protein levels in Alzheimer's disease model rats

Genistein has a neuroprotective effect in Alzheimer＇s disease, but its mechanism of action needs further clarification. Accumulating evidence suggests that excessive phosphorylation of tau protein causes production of neurofibrillary tangles, which is one of the main pathological characteristics of Alzheimer＇s disease, and tau protein can be phosphorylated by calcium/calmodulin dependent protein kinase IV （CAMK4）. After 7 days of pre-administration of genistein （90 mg/kg）, an Alzheimer＇s disease rat model was established using an intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-β peptide （25-35）. The rat was then continu- ously administered genistein （90 mg/kg） for 42 days. The Morris water maze test, western blotting and hematoxylin-eosin staining results showed that genistein significantly decreased the escape latency and increased the number of times crossing the platform, reduced p-tau, CALM, CAMKK1 and p-CAMK4 protein levels in the hippocampus, and alleviated hippocampal neuron damage. These findings indicate that genistein may play a neuroprotective role in Alzheimer＇s disease through regulating CAMK4 to modulate tau hyperphosphorylation. Key

Effects of traditional Chinese exercises on blood glucose and hemoglobin A1c levels in patients with prediabetes: A systematic review and meta-analysis

Background:Traditional Chinese exercises(TCEs)have a positive effect on glycemic control and hemoglobin A1 c(HbA1 c),but there is no consensus on the benefits of TCEs for patients with prediabetes.Objective:The objective of this study was to systematically investigate the effects of TCEs on blood glucose control in patients with prediabetes.Search strategy:Comprehensive retrieval of randomized controlled trials(RCTs)was carried out using PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,VIP Database for Chinese Technical Periodicals,Wanfang Data Knowledge Service Platform,China Biology Medicine disc,Google Scholar and Baidu academic databases.The retrieval window ranged from the establishment of the database to December 2018,and references related to the included trials were searched without language restrictions.Inclusion criteria:The study included RCTs with a clinical diagnosis of prediabetes that was also treated with TCEs.Data extraction and analysis:Literature screening,data extraction and literature quality assessment were performed independently by two researchers.In the case of disagreement,a third party was invited to negotiate and make a decision.Standardized mean difference(SMD)was used to estimate the therapeutic effect.Meta-analysis was performed using Review Manager 5.3.5 and Stata 15.0.Heterogeneity was assessed using Q test and I2,and the source of heterogeneity was determined using Galbraith diagram and sensitivity analysis.A Q test resulting in P<0.1 and I2>50%indicated significant difference and random effect model analysis was performed.Otherwise,a fixed effect model was applied.Begg’s and Egger’s tests were used to assess publication bias.Results:Nine RCTs involving 485 participants were included in this study.The results showed that TCEs could reduce fasting blood glucose(FBG),2 h blood glucose(2 hPBG)and HbA1 c in patients with prediabetes.The treatment subgroup showed that an intervention of 6 months had better results,while the Gongfa subgroup showed that the TCE Baduanjin yielded better results.(1)FBG:SMD=à0.73,95%confidence interval(CI)[à0.97,à0.50],P<0.00001;Baduanjin:SMD=à0.83,95%CI[à1.13,à0.53],P<0.00001;6-month treatment:SMD=à0.73,95%CI[à1.20,à0.26],P=0.002.(2)2 hPBG:SMD=à0.75,95%CI[à0.94,à0.57],P<0.00001;Baduanjin:SMD=à0.62,95%CI[à0.91,à0.32],P<0.00001;6-month treatment:SMD=à0.91,95%CI[à1.39,à0.44],P=0.0002.(3)HbA1 c:SMD=à0.56,95%CI[à0.89,à0.23],P=0.00008;Baduanjin:SMD=à0.46,95%CI[à0.83,à0.08],P=0.02;6-month treatment:SMD=à0.77,95%CI[à1.24,à0.29],P=0.002.Conclusion:TCEs had positive effects in improving blood glucose levels in patients with prediabetes.Hence,TCEs may be of potential therapeutic value for patients with prediabetes,as an adjuvant therapy along with other treatments.Although the evidence suggests that the intervention is effective for6 months,the mechanism of TCEs on glycemic control,the minimum exercise dose and their safety remain to be further studied.

Brain functional connectivity network studies of acupuncture： a systematic review on resting-state fMRI

Background： Functional magnetic resonance imaging （fMRI） is a novel method for studying the changes of brain networks due to acupuncture treatment. In recent years, more and more studies have focused on the brain functional connectivity network of acupuncture stimulation. Objective： To offer an overview of the different influences of acupuncture on the brain functional connec- tivity network from studies using resting-state fMRI. Search strategy： The authors performed a systematic search according to PRISMA guidelines, The database PubMed was searched from January 1, 2006 to December 31, 2016 with restriction to human studies in English language. Inclusion criteria： Electronic searches were conducted in PubMed using the keywords ＂acupuncture＂ and ＂neuroimaging＂ or ＂resting-state fMRI＂ or ＂functional connectivity＂, Data extraction and analysis： Selection of included articles, data extraction and methodological quality assessments were respectively conducted by two review authors. Results： Forty-four resting-state fMRI studies were included in this systematic review according to inclu- sion criteria. Thirteen studies applied manual acupuncture vs. sham, four studies applied electro- acupuncture vs. sham, two studies also compared transcutaneous electrical acupoint stimulation vs. sham, and nine applied sham acupoint as control. Nineteen studies with a total number of 574 healthy subjects selected to perform fMRI only considered healthy adult volunteers. The brain functional connec- tivity of the patients had varying degrees of change. Compared with sham acupuncture, verum acupunc- ture could increase default mode network and sensorimotor network connectivity with pain-, affective- and memory-related brain areas. It has significantly greater connectivity of genuine acupuncture between the periaqueductal gray, anterior cingulate cortex, left posterior cingulate cortex, right anterior insula, limbic/paralimbic and precuneus compared with sham acupuncture. Some research had also shown that acupuncture could adjust the limbic-paralimbic-neocortical network, brainstem, cerebellum, subcortical and hippocampus brain areas. Conclusion： It can be presumed that the functional connectivity network is closely related to the mech- anism of acupuncture, and central integration plays a critical role in the acupuncture mechanism.