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Background. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, which will eventually lead to joints deformity and functional damage. The aim of this research is to evaluate the effect of moxibustion on the serum indicators related to bone and cartilage metabolism, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 3 (MMP-3), and vascular endothelial growth factor (VEGF) in patients with RA and to explore the mechanism of moxibustion in the treatment of RA. Methods. We recruited 70 RA patients who met the inclusion criteria, and they were randomly divided into two groups, a treatment group and a control group in equal ratio. The control group took methotrexate, folate, or leflunomide orally, while the treatment group received methotrexate, folate, or leflunomide orally and moxibustion at ST36 (Zusanli), BL23 (Shen shu), and Ashi points. We compared the clinical symptoms, RA serological disease markers and serum contents of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), MMP-1, MMP-3, and VEGF of RA patients before and after treatment. Results. (1) The clinical symptoms and RA serological disease markers of the two groups improved after treatment (P P β, TNF-α, and VEGF decreased in both groups after treatment (P P P P P > 0.05, P > 0.05). Above all, the contents of IL-1β, TNF-α, MMP-1, MMP-3, and VEGF in the treatment group decreased more significantly than those in the control group (P Conclusion. The improvement effect of moxibustion on the clinical symptoms of RA patients may be related to influence on the contents of IL-1β, TNF-α, MMP-1, MMP-3, and VEGF, and moxibustion may play a potential role in bone protection.

In Traditional Chinese Medicine (TCM), moxibustion had been used for thousands of years. Many clinical case reports and scientific studies had proved that moxibustion had a good effect in treating acute gastric ulcer (AGU). Some studies had shown that the relative content and species of bacteria in the intestinal would be changed when gastric mucosal injury happened. However, there was little research on the effect of intestinal microbiome with AGU rats that were treating by moxibustion. This study is aimed at analyzing the effect of fecal microbiome in rats with AGU by the 16S rDNA sequencing technology. Male SD rats were established by orally feeding once with 70% ethanol at 4 ml/kg except the control group, then treated by moxibustion in the stomach meridian group (“Liangmen,” “Zusanli”) and the gallbladder meridian group (“Riyue,” “Yanglingquan”) for 5 days. The 16S rDNA sequencing technology analysis of feces combined with histopathological methods and molecular biological detection methods was used to evaluate the therapeutic mechanism of moxibustion on AGU. AGU brought cause changes in the number and species of intestinal bacteria. Moxibustion on stomach meridian group could reduce the area of gastric mucosal injury and regulate the relative content of GAS and EGF. Moreover, moxibustion on the stomach meridian group could increase the relative content and species of beneficial bacteria in the intestine of rats with AGU. The relative abundance of intestinal probiotics was significantly upregulated in Alphaproteobacteria, Actinomycetales, and Bacillales. In addition, moxibustion might promote the repair of gastric mucosal injury by increasing the number and species of beneficial bacteria in the intestine.

The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA) on the neuroendocrine-immune (NEI) network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund’s adjuvant (CFA) model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli) acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

The mitogen-activated protein kinases (MAPKs), especially p38MAPK, play a pivotal role in chronic pain. Electroacupuncture (EA) relieves inflammatory pain underlying the descending pathway, that is, the periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), and the spinal cord dorsal horn (SCDH). However, whether EA antagonizes inflammatory pain through regulation of p38MAPK in this descending facilitatory pathway is unclear. Complete Freund’s adjuvant (CFA) was injected into the hind paw of rats to establish inflammatory pain model. EA was administrated for 30 min at Zusanli and Kunlun acupoints at 0.5, 24.5, 48.5, and 72.5 h, respectively. The paw withdrawal threshold (PWT), paw edema, and Phosphor-p38MAPK-Immunoreactivity (p-p38MAPK-IR) cells were measured before (0 h) and at 1, 3, 5, 7, 25, and 73 h after CFA or saline injection. EA increased PWT at 1, 3, 25, and 73 h and inhibited paw edema at 25 and 73 h after CFA injection. Moreover, the increasing number of p-p38MAPK-IR cells which was induced by CFA was suppressed by EA stimulation in PAG and RVM at 3 and 5 h and in SCDH at 5, 7, 25, and 73 h. These results suggest that EA suppresses inflammation-induced hyperalgesia probably through inhibiting p38MAPK activation in the descending facilitatory pathway.

Sepsis results in high morbidity and mortality. Immunomodulation strategies could be an adjunctive therapy to treat sepsis. Acupuncture has also been used widely for many years in China to treat sepsis. However, the underlying mechanisms are not well-defined. We demonstrated here that EA preconditioning at ST36 obviously ameliorated CLP-induced intestinal injury and high permeability and reduced the mortality of CLP-induced sepsis rats. Moreover, electroacupuncture (EA) pretreatment exerted protective effects on intestinal mucosal immune barrier by increasing the concentration of sIgA and the percentage of CD3+,γ/δ, and CD4+ T cells and the ratio of CD4+/CD8+ T cells. Although EA at ST36 treatments immediately after closing the abdomen in the CLP procedure with low-frequency or high-frequency could not reduce the mortality of CLP-induced sepsis in rats, these EA treatments could also significantly improve intestinal injury index in rats with sepsis and obviously protected intestinal mucosal immune barrier. In conclusion, our findings demonstrated that EA at ST36 could improve intestinal mucosal immune barrier in sepsis induced by CLP, while the precise mechanism underlying the effects needs to be further elucidated.

As a traditional therapy applied for thousands of years, acupuncture has recently been attracting more and more investigators throughout the world. In the theory of traditional Chinese medicine, it is proposed that acupuncture can strengthen the human body to resist diseases by puncturing needles at certain points. The characteristic that acupuncture enhances resistance is closely related with the immune system, which functions in defense, homeostasis, and surveillance. More and more research has revealed that acupuncture can regulate immunity, for example, to enhance anticancer and antistress immune function and exert anti-inflammation effects. This may be the basis of acupuncture in preventing and treating later diseases. This special issue was developed to stimulate the continuing efforts in promoting the research on acupuncture and immunity. The acupuncture point ST36 (Zusanli) is widely applied in immune-related diseases. In “Electroacupuncture at Bilateral Zusanli Points (ST36) Protects Intestinal Mucosal Immune Barrier in Sepsis” M. Zhu et al. reported that EA preconditioning at ST36 obviously ameliorated CLP-induced intestinal injury and high permeability and exerted protective effects on intestinal mucosal immune barrier by increasing the concentration of sIgA and the percentage of CD3+, γ/δ, and CD4+ T cells and the ratio of CD4+/CD8+ T cells, which eventually decreased the mortality of sepsis. “Moxibustion and Acupuncture Ameliorate Crohn's Disease by Regulating the Balance between Th17 and Treg Cells in the Intestinal Mucosa” by C. Zhao et al. provided evidence from a randomized controlled clinical trial that moxibustion and acupuncture regulated the ratio of Th17 and Treg cells in the intestinal mucosa of CD patients and restored the balance between these immune cell subsets, providing the basis for clinical application of treatment for CD. “Herb-Partitioned Moxibustion Regulates the TLR2/NF-κB Signaling Pathway in a Rat Model of Ulcerative Colitis” by X. Wang et al. assessed the regulation of the TLR2/NF-κB signaling pathway by herb-partitioned moxibustion in the intestinal mucosa of rats with ulcerative colitis (UC). It was reported that herb-partitioned moxibustion modulated the excessive local immune response by inhibiting TLR2 signaling, thereby promoting the repair of damaged colonic mucosa. “Mediators, Receptors, and Signalling Pathways in the Anti-Inflammatory and Antihyperalgesic Effects of Acupuncture” by J. L. McDonald et al. reviewed both demonstrated and proposed anti-inflammatory effects of acupuncture and analyzed the complex crosstalk between receptors during inflammation to elucidate the mediators and signaling pathways activated by acupuncture. Researches with new advances which demonstrated that acupuncture activated a novel cholinergic anti-inflammatory pathway and chemokine-mediated proliferation of opioid-containing macrophages in inflamed tissues were also included. “Immunoregulation on Mice of Low Immunity and Effects on Five Kinds of Human Cancer Cells of Panax japonicus Polysaccharide” by Z. Jie et al. investigated the immunoregulative effects of Panax japonicus polysaccharide (PJPS) on mice of low immunity. The results indicated that PJPS significantly improved the immune function of mice processed by cyclophosphamide and PJPS did not work on the five kinds of human cancer cells. In summary, this issue provides different evidence presented by diverse authors covering several topics related to advances in acupuncture for inflammation or immune diseases. As inflammation is the coherent pathophysiologic progress in many kinds of diseases, immune system and response of the human body are influenced in diseases such as cancer; the anti-inflammation effect of acupuncture may be a very important underlying mechanism of acupuncture in treating diseases. Moreover, TCM focuses on the theory that prevention before the onset of the diseases or intervening in an early stage of diseases is much better than treating after the onset. Preconditioning by acupuncture which means stimulation with acupuncture before the onset of diseases has been widely applied from ancient time to present clinical practice, proposing a potential field in preventing diseases. Acupoints selection, combination of the acupoints, or different methods of stimulation of acupuncture may result in quite different effects on immune system. Further research is urgently essential to elucidate the relation between acupuncture and immune responses and what kind of stimulation might induce the best effect. Of course, the selected topics and papers are not a comprehensive representation of the area of this special issue. Nonetheless, they represent many-faceted evidence that we have the pleasure of sharing with the readers.

We observed the inhibitive effect of electroacupuncture (EA) at Zusanli on inflammatory mediators of postoperative intra-abdominal adhesions to find out the relationship between EA and the cholinergic anti-inflammatory pathway. Sixty-four rats were divided into 8 groups (A–H, each = 8): A = sham control; B = abdominal adhesions model; C = abdominal adhesions plus EA; D = sham acupoint control; E = abdominal adhesions plus vagotomy; F = abdominal adhesions plus EA after vagotomy; G = abdominal adhesions plusα-bungarotoxin (BGT); and H = abdominal adhesions plus EA afterα-BGT.α-BGT (1 μg/kg) was injected into the abdominal cavity after surgery, and the bilateral celiac vagotomy was done during the surgery. On the third day the levels of inflammatory mediators (TNF-α, nitric oxide (NO), and nitric oxide synthase (NOS)) in tissues were evaluated. The abdominal adhesion groups developed obvious edema. Compared with sham control, the abdominal adhesion resulted in a significant elevation of inflammatory mediators. EA lowered the elevated levels of inflammatory mediators significantly; EA plusα-BGT and vagotomy showed less anti-inflammatory effects. The activation of the cholinergic anti-inflammatory pathway might be one of the mechanisms of EA at Zusanli acupoints to exert the anti-inflammatory effects.

We aimed to investigate the preventive effects of acupuncture for complications after radical hysterectomy. A single-center randomized controlled single-blinded trial was performed in a western-style hospital in China. One hundred and twenty patients after radical hysterectomy were randomly allocated to two groups and started acupuncture from sixth postoperative day for five consecutive days. Sanyinjiao (SP6), Shuidao (ST28), and Epangxian III (MS4) were selected with electrical stimulation and Zusanli (ST36) without electrical stimulation for thirty minutes in treatment group. Binao (LI14) was selected as sham acupuncture point without any stimulation in control group. The main outcome measures were bladder function and prevalence of postoperative complications. Compared with control group, treatment group reported significantly improved bladder function in terms of maximal cystometric capacity, first voiding desire, maximal flow rate, residual urine, and bladder compliance, and decreased bladder sensory loss, incontinence, and urinary retention on fifteenth and thirtieth postoperative days. Treatment group showed significant advantage in reduction of urinary tract infection on thirtieth postoperative day. But no significant difference between groups was observed for lymphocyst formation. By improving postoperative bladder function, early intervention of acupuncture may provide a valuable alternative method to prevent bladder dysfunctional disorders and urinary tract infection after radical hysterectomy.

The application of electroacupuncture (EA) to specific acupoints can induce a hypoglycemic effect in streptozotocin-induced rats, normal rats, and rats with steroid-induced insulin resistance. EA combined with the oral insulin sensitizer rosiglitazone improved insulin sensitivity in rats and humans with type II diabetes mellitus (DM). There are different hypoglycemic mechanisms between Zhongwan and Zusanli acupoints by EA stimulation. On low-frequency (2 Hz) stimulation at bilateral Zusanli acupoints, serotonin was involved in the hypoglycemic effect in normal rats. Moreover, after 15 Hz EA stimulation at the bilateral Zusanli acupoints, although enhanced insulin activity mainly acts on the insulin-sensitive target organs, the muscles must be considered. In addition, 15 Hz EA stimulation at the bilateral Zusanli acupoints has the combined effect of enhancing cholinergic nerve activity and increasing nitric oxide synthase (NOS) activity to enhance insulin activity. Despite the well-documented effect of pain control by EA in many systemic diseases, there are few high-quality long-term clinical trials on the hypoglycemic effect of EA in DM. Combination treatment with EA and other medications seems to be an alternative treatment to achieve better therapeutic goals that merit future investigation.

Tongue acupuncture (TA) is a method which is not used in western medicine and even in China it is applied very rarely in clinical practice. This study aimed at investigating whether additional TA can improve the efficacy of body acupuncture (BA) in patients with depression. Twenty patients with a mean age of ± SD of years were randomly divided into two groups ( patients each), one group receiving BA (Zusanli, Sanyinjiao, Neiguan, Shenting, Yintang, and Baihui) and the other receiving BA and TA (Liver, Heart, and Brain). The quantitative and qualitative outcome measures were heart rate (HR), heart rate variability (HRV), and different clinical scores. We found that in both groups all scores and HR improved significantly, whereas HRV increased partly significantly. It seems that TA can enhance acute and treatment effects of BA in patients with depression. The investigation of de qi sensation in TA needs further attention.

The aim of this study was to investigate the longitudinal effects of electroacupuncture (EA) on Zusanli (ST36) and Ashi acupoints in promoting skeletal muscle regeneration and inhibiting excessive fibrosis after contusion in rabbits. Sixty rabbits were randomly divided into four groups: normal, contusion, EA, and recombinant human insulin-like growth factor-I (rhIGF-I). An acute skeletal muscle contusion was produced on the right gastrocnemius (GM) by an instrument-based drop-mass technique. EA was performed for 15 minutes every two days with 0.4 mA (2 Hz), and GM injections were executed with rhIGF-I (0.25 mL once a week). Rabbits treated with EA had a higher T-SOD and T-AOC serum activities and lower MDA serum level, the blood perfusion of which was also significantly higher. In the EA group, the diameter of the myofibril was uniform and the arrangement was regular, contrary to the contusion group. The number and diameter of regenerative myofibers and MHC expression were increased in the EA group. EA treatment significantly decreased fibrosis formation and reduced both GDF-8 and p-Smad2/3 expressions in injured muscle. Our data indicate that EA may promote myofiber regeneration and reduce excessive fibrosis by improving blood flow and antioxidant capacities. Additionally, EA may regulate signaling factor expression after contusion.

This study investigated the protective effect and mechanism of electroacupuncture at ST36 points on the intestinal barrier dysfunction and remote organ injury after intestinal ischemia and reperfusion injury in rats. Rats were subjected to gut ischemia for 30 min, and then received electroacupuncture for 30 min with or without abdominal vagotomy or intraperitoneal administration of cholinergicα7 nicotinic acetylcholine receptor (α7nAChR) inhibitor. Then we compared its effects with electroacupuncture at nonchannel points, vagal nerve stimulation, or intraperitoneal administration of cholinergic agonist. Cytokine levels in plasma and tissue of intestine, lung, and liver were assessed 60 min after reperfusion. Intestinal barrier injury was detected by histology, gut injury score, the permeability to 4 kDa FITC-dextran, and changes in tight junction protein ZO-1 using immunofluorescence and Western blot. Electroacupuncture significantly lowered the levels of tumor necrosis factor-αand interleukin-8 in plasma and organ tissues, decreased intestinal permeability to FITC-dextran, and prevented changes in ZO-1 protein expression and localization. However, abdominal vagotomy or intraperitoneal administration of cholinergicα7nAChR inhibitor reversed these effects of electroacupuncture. These findings suggest that electroacupuncture attenuates the systemic inflammatory response through protection of intestinal barrier integrity after intestinal ischemia injury in the presence of an intact vagus nerve.

Oxaliplatin, a chemotherapy drug, often leads to neuropathic cold allodynia after a single administration. Bee venom acupuncture (BVA) has been used in Korea to relieve various pain symptoms and is shown to have a potent antiallodynic effect in nerve-injured rats. We examined whether BVA relieves oxaliplatin-induced cold allodynia and which endogenous analgesic system is implicated. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat’s tail into cold water (4°C) and measuring the withdrawal latency. BVA (1.0 mg/kg, s.c.) at Yaoyangguan (GV3), Quchi (LI11), or Zusanli (ST36) acupoints significantly reduced cold allodynia with the longest effect being shown in the GV3 group. Conversely, a high dose of BVA (2.5 mg/kg) at GV3 did not show a significant antiallodynic effect. Phentolamine (α-adrenergic antagonist, 2 mg/kg, i.p.) partially blocked the relieving effect of BVA on allodynia, whereas naloxone (opioid antagonist, 2 mg/kg, i.p.) did not. We further confirmed that an intrathecal administration of idazoxan (α2-adrenergic antagonist, 50 μg) blocked the BVA-induced anti-allodynic effect. These results indicate that BVA alleviates oxaliplatin-induced cold allodynia in rats, at least partly, through activation of the noradrenergic system. Thus, BVA might be a potential therapeutic option in oxaliplatin-induced neuropathy.

This study was performed to observe the influence of sham and different verum acupuncture manipulations on skin temperature of the stimulated acupoint in healthy volunteers. Thirty-seven healthy volunteers with a mean age of 25.4 ± 2.2 years were enrolled in the study. All volunteers had experienced acupuncture before. They received sham acupuncture and two different kinds of verum acupuncture stimulation (lifting-thrusting and twisting-rotating) on Zusanli (ST36). The skin temperature of ST36 was measured before acupuncture, after needle insertion, after needle manipulation, immediately after removal of the needle, and as further control 5 minutes after removal of the needle using a FLIR i7 infrared thermal camera. During the measurement, the needling sensations of volunteers were enquired and recorded. During the sham acupuncture stimulation, the skin temperature of ST36 decreased in the first 5 minutes, when the point was exposed, and then increased gradually. During verum acupuncture stimulations, the skin temperature increased continually and then decreased in the last phase. The increase in temperature caused by lifting-thrusting stimulation was significantly higher than that of twisting-rotating manipulation, which may be related to the stimulation intensity.

Background. In traditional Chinese medicine acupuncture manipulation is one of the key factors that affect the curative results of acupuncture and more and more researches focus on how the different acupuncture manipulation techniques influence microcirculation nowadays. In this paper we demonstrate the different influences of lift-thrust reinforcing and reducing on blood perfusion.Method. The acupuncture manipulations of lift-thrust reinforcing and reducing were, respectively, applied to the 15 healthy subjects at the Zusanli acupoint and the changes of blood perfusion were monitored by Pericam Perfusion Speckle Imager (PSI).Conclusion. Both of the manipulations of lift-thrust reinforcing and reducing increase blood perfusion at Zusanli acupoint while the increasing amount of blood perfusion in the reinforcing group is significantly higher than in the reducing group.

The aim of this study was to determine the effect of violet laser stimulation on three acupuncture points in anesthetized rats and to test the hypothesis that violet laser light can modulate neurovegetative parameters like heart rate (HR), heart rate variability (HRV), and mean arterial blood pressure (MAP). Recordings were performed in 10 male anesthetized rats under three conditions in Beijing, and monitored with equipment from Graz, where also data analysis was performed. For stimulation a violet laser (emitted wavelength 405 nm, laser output 1 mW, continuous mode) was used. The electrocardiograms were recorded by an HRV Medilog AR12 system during laser acupuncture stimulation of the head, ear, and body (Baihui, “heart” ear acupoint, Zusanli). HR changed significantly only during (P=0.013) and after (P=0.038) stimulation at Baihui. Total HRV and the low frequency/high frequency ratio showed insignificant changes. There was an insignificant decrease in MAP after stimulation of Baihui acupoint. Violet laser stimulation offers a method to induce acute effects in HR and HRV in rats. Although the precise mechanism of this effect remains to be determined, alterations are significant. Violet laser stimulation on the Baihui acupoint could readily be translated to clinical studies.

This study examined the influence of the N-methyl-D-aspartate receptor (NMDAR) on the modulation of related spinal signaling after electroacupuncture (EA) treatment in normal rats. Bilateral 2 Hz EA stimulations (1-2-3.0 mA) were delivered at acupoints corresponding to Zusanli (ST36) and Sanyinjiao (SP6) in men for 30 min. Thermal sensitization was strongly inhibited by EA, but this analgesia was reduced by preintrathecal injection of the NMDAR antagonist, MK801. Phosphorylation of the NMDAR NR2B subunit, cAMP response element-binding protein (CREB), and especially phosphatidylinositol 3-kinase (PI3K) were significantly induced by EA. However, these marked phosphorylations were not observed in MK801-pretreated rats. EA analgesia was reduced by preintrathecal injection with the calcium chelators Quin2 and TMB8, similar to the results evident using MK801. Phosphorylation of PI3K and CREB induced by EA was also inhibited by TMB8. Calcium influx by NMDAR activation may play an important role in EA analgesia of normal rats through the modulation of the phosphorylation of spinal PI3K and CREB.

Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA). However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36), Xuanzhong (GB39); and Shenshu (BL23) markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP), a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r=−0.483,P=.0026). In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression.

Animal studies have shown that electroacupuncture (EA) at Zusanli (ST-36) and Zhongwan (CV-12) acupoints reduces plasma glucose concentrations in rats with type II diabetes. However, whether EA reduces plasma glucose levels in type I diabetes is still unknown. In this study, we explore the various non-insulin-dependent pathways involved in EA-induced lowering of plasma glucose. Streptozotocin (STZ) (60 mg kg−1, i.v.) was administered via the femoral vein to induce insulin-dependent diabetes in non-adrenalectomized and in adrenalectomomized rats. EA (15 Hz) was applied for 30 min to bilateral ST-36 acupoints after administration of Atropine (0.1 mg kg−1i.p.), Eserine (0.01 mg kg−1i.p.), or Hemicholinium-3 (5 μg kg−1i.p.) in non-adrenalectomized rats. Rats administered acetylcholine (0.01 mg kg−1i.v.) did not undergo EA. Adrenalectomized rats underwent EA at bilateral ST-36 acupoints without further treatment. Blood samples were drawn from all rats before and after EA to measure changes in plasma glucose levels. Expression of insulin signaling proteins (IRS1, AKT2) in atropine-exposed rats before and after EA was measured by western blot. Atropine and hemicholinium-3 completely blocked the plasma glucose lowering effects of EA, whereas eserine led to a significant hypoglycemic response. In addition, plasma glucose levels after administration of acetylcholine were significantly lower than the fasting glucose levels. In STZ-adrenalectomized rats, EA did not induce a hypoglycemic response. EA stimulated the expression of IRS1 and AKT2 and atropine treatment blocked the EA-induced expression of those insulin signaling proteins. Taken together, EA at the ST-36 acupoint reduces plasma glucose concentrations by stimulating the cholinergic nerves.