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Background: Heart failure (HF) is characterized by functional or structural dysfunction of the heart, resulting in impaired blood ejection or ventricular filling. Conventional Western Medicine (CWM) remains the mainstay of treatment for HF; however, the occurrence of adverse events (AEs) necessitates the exploration of alternative treatments. Herbal medicine and acupuncture are adjunctive therapies for HF and have shown potential for improving heart function. This systematic review and meta-analysis aimed to assess the effectiveness and safety of acupuncture and herbal medicine in treating HF., Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Citation Information by National Institute of Informatics, KoreaMed, Research Information Sharing Service, and DBpia were searched for randomized controlled trials (RCTs) evaluating the effects of acupuncture and herbal medicine along with CWM as adjunctive treatments for HF, published from inception to May 31, 2024. Treatment effectiveness was determined by evaluating the left ventricular ejection fraction as the primary metric, along with the measurement of the total effective rate, brain natriuretic peptide level, N-terminal prohormone of brain natriuretic peptide level, left ventricular end-diastolic volume, and left ventricular end-systolic volume; the administration of the Minnesota Living with Heart Failure Questionnaire; and the conduct of a 6-minute walk test. Treatment safety was evaluated based on the incidence of AEs. The methodological quality of all included RCTs was assessed using the Cochrane risk of bias tool. A meta-analysis was performed using Review Manager, version 5.4.1., Results: Of the 133 publications identified, 8 RCTs met the inclusion criteria. The meta-analysis showed significant improvements in left ventricular ejection fraction, brain natriuretic peptide levels, N-terminal prohormone of brain natriuretic peptide levels, left ventricular end-systolic volume, left ventricular end-diastolic volume, and 6-minute walk test results. Additionally, significant differences were observed in the total effective rate and Minnesota Living with Heart Failure Questionnaire responses. No significant medication-related AEs occurred in the intervention group. Conversely, 7 control patients developed well-known AEs associated with CWM., Conclusion: Acupuncture combined with herbal medicine and CWM is more effective than CWM alone, indicating a safe treatment approach. Consequently, the proactive administration of acupuncture alongside herbal medicine to patients with HF can be undertaken without concerns regarding AEs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To investigate the efficacy of acupuncture in preventing cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) and explore its underlying mechanism. Design: A randomized, double-blinded, and placebo-controlled trial. Setting/Location: Subjects were recruited from Kyung Hee University Hospital at Gangdong, Seoul, Korea Subjects: A total of 50 patients admitted with acute SAH. Interventions: The study group received acupuncture treatments ( n  = 25), while the control group underwent mock transcutaneous electrical nerve stimulation and sham acupuncture ( n  = 25) six times/week for 2 weeks. Outcome measures: The primary outcome was the incidence of delayed ischemic neurologic deficit (DIND), and secondary measurements included angiographic vasospasm, vasospasm-related infarction, modified Rankin Scale score, and plasma nitric oxide (NO) and endothelin-1 (ET-1) levels. Results: The study group treated with acupuncture showed a lower incidence of DIND (9.1%) than the control group (20.8%); however, this difference in the incidence of DIND was not statistically significant. The study group demonstrated better clinical outcomes, especially in functional recovery. Significant alterations in plasma NO and ET-1 levels after the 2-week intervention were observed only in the study group. Conclusions: Their study shows that acupuncture treatment improved functional recovery after SAH and could potentially prevent cerebral vasospasm. These effects could be attributed to the recovery of endothelial dysfunction by acupuncture through modulating the plasma NO and ET-1 levels. The study protocol has been registered on www.clinicaltrials.gov (NCT02275949).

Background: It is important to manage inflammation after craniotomy. It may be prudent to reduce the excessive usage of antibiotics and to add supplementary treatments like acupuncture, which would be effective and safe. However, there are only a few studies available to date on the effects of acupuncture on anti-inflammatory response after craniotomy. The aim of this study was to explore the anti-inflammatory effects of acupuncture in patients after a craniotomy., Methods: This study was a single-center, prospective, open-label, controlled trial. Forty-four subjects who underwent craniotomy for an unruptured aneurysm, facial spasm, or brain tumor were allocated to either an acupuncture group or a control group. Both groups received postoperative routine care in the Department of Neurosurgery. The subjects in the acupuncture group also received a total of 6 acupuncture treatments sessions within 8 days after craniotomy. Acupuncture treatments included acupuncture, electroacupuncture, and intradermal acupuncture. The serum interleukin (IL)-1β and IL-6, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and erythrocyte sedimentation rate levels were assessed four times within 7 days after surgery. The presence of fever, use of additional antibiotics, presence of infection including pneumonia or urinary tract infection, and safety were also reviewed., Results: The IL-1β levels of subjects who underwent aneurysmal clipping were significantly lower in the acupuncture group (P = .02). TNF-α levels of subjects who underwent aneurysmal clipping at the seventh postoperative day were also significantly lower in the acupuncture group (P = .03). Six cases of fever of unknown origin were observed in the control group, while none were seen in the acupuncture group, revealing that the incidence of fever was significantly lower in the acupuncture group (P = .02). No adverse events occurred during the trial., Conclusion: Acupuncture showed a possibility of alleviating inflammation by attenuating the levels of proinflammatory cytokines and significantly reduced the incidence of fever of unknown origin in patients after craniotomy. Acupuncture would be suitable as an adjunctive therapy to alleviate inflammation after craniotomy.

Objectives: To determine whether acupuncture at GB34 affects cerebral blood flow (CBF) via the anterior cerebral arteries (ACAs) and middle cerebral arteries (MCAs)., Methods: This study included 10 healthy young male volunteers. CBF velocity and cerebrovascular reactivity (CVR) were measured using transcranial Doppler sonography (TCD). The changes in hyperventilation-induced carbon dioxide (CO 2 ) reactivity and modified blood flow velocity at 40 mm Hg (CV40) were observed for both ACAs and MCAs before and after GB34 acupuncture treatment. Blood pressure and heart rate were also measured before and after GB34 acupuncture treatment., Results: The CO 2 reactivity of the ipsilateral MCA significantly increased after GB34 acupuncture treatment, compared with that at baseline (P=0.007). In contrast, the CO 2 reactivity of both ACAs and the contralateral MCA remained unchanged. The CV40 of both ACAs and MCAs did not change after GB34 acupuncture treatment and neither did the mean arterial blood pressure and heart rate., Conclusions: GB34 acupuncture treatment increased CO 2 reactivity specifically in the ipsilateral MCA, but had no effect on either the ACAs or the contralateral MCA. These data suggest that GB34 acupuncture treatment improves the vasodilatory potential of the cerebral vasculature to compensate for fluctuations caused by changes in external conditions and could potentially be useful for the treatment of disorders of the ipsilateral MCA circulation.

Objective: The aim of this study was to evaluate the efficacy of acupuncture and bee venom acupuncture (BVA) for idiopathic Parkinson's disease (IPD) through a sham-controlled trial. We also investigated whether there is a sustained therapeutic effect by completing follow-up assessments after treatment completion., Design: A single center, double-blind, three-armed randomized controlled trial., Settings/location: This study was performed at a university hospital in Seoul, Republic of Korea., Subjects: Seventy-three (73) patients with IPD were the subjects. They were randomly assigned to the active treatment group, sham treatment group, or conventional treatment group., Interventions: The active treatment group received acupuncture and BVA and the sham group received sham acupuncture and normal saline injections, twice a week for 12 weeks. The conventional treatment group maintained anti-parkinsonian drugs without additional intervention., Outcome Measures: The Unified Parkinson's Disease Rating Scale (UPDRS) part II and part III score, postural instability and gait disturbance (PIGD) score, gait speed and number, Parkinson's Disease Quality of Life Questionnaire, Beck Depression Inventory, and postural stability at baseline and at 12, 16, and 20 weeks., Results: Sixty-three (63) patients provided a complete data of assessments, including a final follow-up. After 12 weeks of treatment, a significant difference was observed between the active treatment group and the conventional treatment group. After the end of the treatment, the treatment effects were maintained significantly in the active treatment group only., Conclusions: It is suggested that the combined treatment of acupuncture and BVA might be safe and useful adjunctive treatment for patients with IPD.

Objective: This study aimed to examine the effectiveness and safety of acupuncture in the treatment of Parkinson's disease (PD)., Methods: English, Chinese, and Korean electronic databases were searched up to June 2016. Randomized controlled trials (RCTs) were eligible. The methodological quality was assessed using Cochrane's risk of bias tool. Meta-analysis was performed using RevMan 5.3., Results: In total, 42 studies involving 2625 participants were systematically reviewed. Participants treated using combined acupuncture and conventional medication (CM) showed significant improvements in total Unified PD Rating Scale (UPDRS), UPDRS I, UPDRS II, UPDRS III, and the Webster scale compared to those treated using CM alone. The combination of electroacupuncture and CM was significantly superior to CM alone in total UPDRS, UPDRS I, UPDRS II, and UPDRS IV. Similarly, the combination of scalp electroacupuncture, acupuncture, and CM was significantly more effective than CM alone in total UPDRS. However, our meta-analysis showed that the combination of electroacupuncture and CM was not significantly more effective than CM alone in UPDRS III, the Webster, and the Tension Assessment Scale. The results also failed to show that acupuncture was significantly more effective than placebo acupuncture in total UPDRS. Overall, the methodological quality of the RCTs was low. No serious adverse events were reported., Conclusions: We found that acupuncture might be a safe and useful adjunctive treatment for patients with PD. However, because of methodological flaws in the included studies, conclusive evidence is still lacking. More rigorous and well-designed placebo-controlled trials should be conducted., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Despite recent advances in the medical and surgical fields, complications such as infection, pneumonia, or brain swelling may occur after a craniotomy. In some patients, perioperative antibiotic prophylaxis causes adverse effects such as itching, rash, or digestive conditions. Certain patients still develop infections severe enough to require a repeat operation despite antibiotic prophylaxis. Acupuncture has been used to treat inflammatory conditions, and many basic and clinical studies have provided evidence of its anti-inflammatory and immune regulatory effects. The aim of this study is to explore the effects of acupuncture on inflammation and immune function after craniotomy., Methods: This trial will be a single-center, parallel-group clinical trial. Forty patients who underwent craniotomy for an unruptured aneurysm, facial spasm, or a brain tumor will be allocated to either the study or the control group. The study group will receive conventional management as well as acupuncture, electroacupuncture, and intradermal acupuncture, which will start within 48 h of the craniotomy. The patients will receive a total of six sessions within 8 days. The control group will only receive conventional management. The primary outcome measure will be the C-reactive protein levels, while the secondary outcomes will be the serum erythrocyte sedimentation rate and the tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 levels measured at four different time points: within 48 h prior to the craniotomy and on days 2, 4, and 7 after surgery. The presence of fever and infection, the use of additional antibiotics, the presence of infection, including pneumonia or urinary tract infection, and safety will also be investigated., Discussion: In this trial, we will observe whether acupuncture has anti-inflammatory and immune regulatory effects after a craniotomy. If our study yields positive results and a placebo-controlled study also finds favorable results following our study, acupuncture could be recommended as an adjunctive therapy after a craniotomy., Trial Registration: ClinicalTrials.gov: NCT02761096 . Registered on 27 April 2016.

Objectives: The purpose of this study was to examine the effectiveness and safety of combined treatment using acupuncture and bee venom acupuncture (BVA) as an adjunctive treatment for idiopathic Parkinson's disease (PD)., Methods: Eleven patients (7 men and 4 women) with idiopathic PD who had been receiving a stable dose of anti-parkinsonian medication for at least 4 weeks. Participants received conventional treatment for 12 weeks. Subsequently, they received additional treatment with acupuncture and BVA twice weekly for 12 weeks while still maintaining conventional treatment. All participants were assessed at baseline, 12 weeks, and 24 weeks by using the Unified Parkinson's Disease Rating Scale (UPDRS), the Parkinson's Disease Quality of Life Questionnaire (PDQL), the speed and number of steps required to walk 20 m, and the Beck Depression Inventory (BDI). Maximum excursion and directional control, measured by computerized dynamic posturography (Balance Master(®) System, NeuroCom, San Carlos, CA), were used to assess postural stability., Results: Patients who underwent 12 weeks of twice-weekly combined treatment with acupuncture and BVA showed significant improvements in gait speed, PDQL score, activities of daily living (UPDRS part II), motor symptoms (UPDRS part III), and combined UPDRS part II+III scores compared with assessments after conventional treatment., Conclusions: Combined treatment with acupuncture and BVA showed promising results as a safe adjunctive therapy for PD.

Background: Subarachnoid hemorrhage (SAH) is a neurological disease with a high mortality rate. Several serious complications frequently arise after successful surgery for this condition. Cerebral vasospasm, one such complication, occurs in 50 to 70% of SAH patients. These patients suffer neurological symptoms known as delayed ischemic neurological deficit (DIND); however, the effect of treatment of vasospasm is limited. The major pathogenesis of cerebral vasospasm is the reduction of nitric oxide (NO) and activation of vasoconstrictors. Acupuncture is known to increase the production and activity of vascular endothelial cell-derived NO and improve endothelium-dependent vasodilatation. A preliminary retrospective case study to investigate the ability of acupuncture to prevent the occurrence of cerebral vasospasm has been conducted. However, no randomized, controlled clinical trials have been carried out to evaluate the efficacy of acupuncture for cerebral vasospasm., Methods/design: This trial will be a single-center, randomized, placebo-controlled, parallel group, patient-assessor-blinded clinical trial. A total of 80 patients with SAH will be randomized into two groups: a study group given acupuncture, electroacupuncture, and intradermal acupuncture, and a control group given mock transcutaneous electrical nerve stimulation and sham intradermal acupuncture. Intervention will start within 96 h after SAH, and a total of 12 sessions will be performed during a 2-week period. The primary outcome measure will be the occurrence of DIND, and the secondary outcomes will be vasospasm as measured by cerebral angiography, transcranial Doppler, clinical symptoms, vasospasm-related infarcts, NO and endothelin-1 plasma levels, mortality, and modified Rankin Scale scores., Discussion: This trial will examine the efficacy and safety of acupuncture for cerebral vasospasm after SAH. The placebo effect will be excluded and the mechanism of action of the treatments will be evaluated through blood testing., Trial Registration: ClinicalTrials.gov NCT02275949 , Registration date: 26 October 2014.

Objectives: The acupoint GB20 is known to affect vertebrobasilar blood flow regulation. However, no previous study has used transcranial Doppler imaging to examine whether acupuncture at GB20 has a selective effect on blood flow in various cerebral arteries, such as the basilar artery (BA) and the middle cerebral arteries (MCAs). Therefore, this study sought to determine the specific effects of GB20 acupuncture on cerebral blood flow (CBF)., Materials and Methods: Blood flow velocity and CO(2) reactivity were measured by transcranial Doppler imaging with a 2-MHz pulsed Doppler probe observed through both temporal windows for the MCAs and through the suboccipital window for the BA before and after GB20 acupuncture treatment in 15 healthy young male volunteers. The changes in hyperventilation-induced CO(2) reactivity and corrected blood flow velocities at 40 mmHg (CV40) were assessed for the BA and both MCAs. Blood pressure and heart rate were measured before and after the acupuncture treatment., Results: CO(2) reactivity in the BA increased significantly after GB20 acupuncture treatment compared with baseline (p=0.041). In contrast, CO(2) reactivity in both MCAs remained unchanged. The CV40 in the BA and the MCAs showed no change after the GB20 acupuncture treatment. The mean heart rate decreased significantly after the GB20 acupuncture, whereas the mean blood pressure showed no change., Conclusions: This study demonstrated that acupuncture treatment on GB20 increases CO(2) reactivity specifically in the BA, with no effect in the MCAs. These results clinically support the use of GB20 to treat disorders of posterior cerebral circulation and support the idea that particular acupoints affect specific brain regions and cerebral arteries.

Objectives: To suggest and discuss an integrative medicine model for stroke patients, we introduce our experience in Korea, describe treatment modalities used for stroke in Korean medicine, and present safety data on integrative care., Summary: For inpatients, integrative management is applied at the request of the primary physician with the consent of patients or their families. In the acute stage, neurologists or neurosurgeons take charge as the primary physicians. Korean medicine doctors cooperate as secondary physicians to the neurologists and neurosurgeons. After the acute stage, responsibilities are exchanged. The rehabilitation program is conducted under the supervision of rehabilitation medicine doctors. The most frequently used complementary and alternative medicine modalities are acupuncture (including manual acupuncture, electroacupuncture and intradermal acupuncture), moxibustion, herbal prescriptions, and acupuncture point injection., Conclusion: Based on our field experiences, we believe it is worthwhile to continue efforts to integrate complementary and alternative medicine and Western medicine., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: We investigated apipuncture, or acupuncture point injection with diluted bee venom, as a promising new treatment for central post stroke pain (CPSP)., Methods: Bee venom, diluted to 0.005% in normal saline, was administered to the treatment group, and normal saline given to control group as twice-weekly injections for three weeks. The points were LI15, GB21, LI11, GB31, ST36 and GB39 of the affected side and the amount of injection was 0.05 ml at each point., Results: Eight patients in each group were included in the analysis. After three weeks there were significant decreases in visual analogue pain scores compared with baseline in both groups and the treatment group improved more significantly than the control group (p = 0.009)., Conclusion: Apipuncture significantly improved CPSP in this pilot trial. Further studies of its mechanisms and a larger and long-term follow-up trial will be needed to determine more definitely the efficacy of apipuncture and to elucidate duration of improvement., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To examine the possibility of acupuncture as a new promising treatment to prevent delayed cerebral vasospasm, retrospective comparison was done of patient outcomes in patients with subarachnoid hemorrhage (SAH) treated with and without acupuncture., Materials and Methods: Twenty (20) patients with SAH were treated after their ruptured aneurysms had been secured. Acupuncture treatments were applied to the bilateral Zusanli (ST36) and Neiguan (PC6) once a day for 2 weeks, starting within 3 days of the aneurysm rupture. The incidence of angiographic vasospasm and delayed ischemic neurological deficit (DIND), the patient's functional status at discharge, and mortality rate were analyzed. Patient outcomes were compared with those of an age- and severity-matched comparison group composed of patients treated in the hospital without acupuncture., Results: None of the patients who received acupuncture died. Angiographic vasospasms occurred in 5 patients (25.0%) and DIND in 2 (10%). In terms of functional impairment, the modified Rankin score at discharge was ≤2 in 7 patients (35%). In the control group, angiographic vasospasms occurred in 10 patients (55.6%) and DIND in 7 (38.9%), similar to the reported incidence in conventionally treated patients., Conclusions: Patients with SAH who received acupuncture had a significantly lower incidence of DIND and significantly improved function at discharge, suggesting that acupuncture is effective in preventing cerebral vasospasm. In light of these promising results, a randomized controlled trial is warranted to determine the efficacy of acupuncture in a clinical setting.

Objective: To investigate brain activity patterns during acupuncture in stroke patients, and to compare the result with normal subjects using functional magnetic resonance imaging (fMRI)., Methods: A total of 11 stroke patients with motor weakness and 10 healthy subjects were studied. fMRI was performed during acupuncture on the left side at points Quchi (LI11) and Zusanli (ST36). Data were analyzed using statistical parametric maps of brain activation induced by acupuncture stimulation., Results: The results showed that stimulation of both LI11 and ST36 produced significantly different brain activation patterns between the two groups. The normal group showed a greater overall activation than the stroke group. In the normal group, parts of the frontal lobe, parietal lobe, sub-lobar, cerebellum and midbrain regions were activated by acupuncture at the left LI11. On the other hand, only the right side of the inferior parietal lobule region was activated in the stroke patients. When the left ST36 was stimulated in the normal group, both sides of the frontal lobe, parietal lobe, temporal lobe, and sub-lobar, and the left side of occipital lobe, and the right side of cerebellum and midbrain regions were activated. For the same stimulation in the stroke group, only both sides of the inferior parietal lobule and cerebellum regions were activated (P<0.05, cluster level). Deactivation pattern was not noted during any acupuncture stimulation in both groups., Conclusion: Brain signal activations during the same acupuncture were different between the healthy and the stroke patients, and the effects showed a correlation of different acupuncture points.

Objectives: The objective of the study was to investigate the effect of acupuncture on the circadian rhythm of blood pressure (BP) in patients with hypertension., Design: The study was designed as a randomized, double-blind, controlled trial. Subjects were randomly divided into an active acupuncture group and a sham acupuncture group. Each patient received real or sham acupuncture treatment twice a week for 8 weeks. Acupuncture needles were inserted at bilateral ST 36 plus PC 6; placebo points., Subjects: Thirty-three (33) patients with essential hypertension were the subjects., Outcome Measures: Twenty-four (24)-hour ambulatory BP was assessed before and after treatment., Results: After the treatment period, there was a significant increase in nocturnal diastolic BP dipping compared to that at baseline (10.20±7.56 mm Hg versus 5.21±10.19 mm Hg, p=0.038) in the active acupuncture group but not in the sham acupuncture group. The nocturnal diastolic BP dipping response to active acupuncture treatment was significantly different from the response seen with the sham acupuncture treatment (p=0.041). The number of dippers also increased from 4 to 8 in the active acupuncture group. Average systolic and diastolic BP was not changed significantly except for nighttime diastolic BP (90.32±11.47 mm Hg to 87.83±9.16 mm Hg, p=0.041)., Conclusions: It is suggested that acupuncture treatment could be useful for improving the circadian rhythm of BP in patients with hypertension.

This study aimed to explore the effectiveness of both acupuncture and bee venom acupuncture as adjuvant therapies for idiopathic Parkinson's disease. We recruited 43 adults with idiopathic Parkinson's disease who had been on a stable dose of antiparkinsonian medication for at least 1 month. They were randomly assigned to 1 of 3 groups: acupuncture, bee venom acupuncture, or control. All participants were assessed using the Unified Parkinson's Disease Rating Scale, the Parkinson's Disease Quality of Life Questionnaire, the Beck Depression Inventory, the Berg Balance Scale, and the time and number of steps required to walk 30 m. Treatment groups underwent stimulation of 10 acupuncture points using acupuncture or bee venom acupuncture twice a week for 8 weeks. The initial assessment was repeated at the completion of treatment. The control group did not receive any treatment. Participants in the bee venom acupuncture group showed significant improvement on the Unified Parkinson's Disease Rating Scale (total score, as well as parts II and III individually), the Berg Balance Scale, and the 30 m walking time. When compared to the control group, the bee venom acupuncture group experienced significantly greater improvement on the Unified Parkinson's Disease Rating Scale. In the acupuncture group, the Unified Parkinson's Disease Rating Scale (part III and total scores) and the Beck Depression Inventory showed significant improvement. The control group showed no significant changes in any outcome after 8 weeks. In this pilot study, both acupuncture and bee venom acupuncture showed promising results as adjuvant therapies for Parkinson's disease., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: The objective of this study was to assess differences in brain responses between pressure and acupuncture stimulation at the same acupoint using functional magnetic resonance imaging (fMRI)., Subjects: A total of 10 healthy right-handed volunteers were studied., Design: fMRI was performed with two different paradigms; namely, pressure and acupuncture stimulation at acupuncture points LI11 and ST36 on the left. fMRI data were analyzed using SPM2., Results: In comparison with the left LI11 pressure stimulation, both sides of the parahippocampal gyrus, cerebellum, left side of thalamus, and right side of posterior cingulate regions were more activated by the left LI11 acupuncture stimulation. In comparison with the left ST36 pressure stimulation, the secondary motor cortex, limbic system (cingulate gyrus, posterior cingulate), primary visual cortex, pons, and medulla regions were more activated by left ST36 acupuncture stimulation. In comparison with the left ST36 pressure stimulation, both side of BA 4 and BA 6 were more activated by the LI11 pressure stimulation. In comparison with the left LI11 acupuncture stimulation, left BA 6, BA 8, and anterior cingulate cortex (ACC) were more activated by the left ST36 acupuncture stimulation., Conclusions: In conclusion, brain signal activation patterns according to the stimulation methods and acupoints were observed to differ. Acupuncture stimulation activated more regions than pressure at the same acupoint. In particular, acupuncture stimulation activated the limbic system, such as the parahippocampal gyrus and ACC.