[Mechanism of analgesic effect of electroacupuncture on rats with cervical spondylosis radiculopathy based on activation of astrocytes and HMGB1/TLR4/MyD88 signaling pathway]. / 基于星形胶质细胞活化与HMGB1/TLR4/MyD88ä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆå¯¹ç¥žç»æ ¹åž‹é¢ˆæ¤Žç— å¤§é¼ çš„é•‡ç—›æœºåˆ¶.

OBJECTIVES: To observe effects of electroacupuncture (EA) on the activation of astrocytes and high mobility group protein B1(HMGB1)/Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway, as well as related cytokines in rats with cervical spondylosis radiculopathy(CSR), so as to explore the analgesic mechanism of EA in treating CSR. METHODS: Twenty-four male SD rats were randomly divided into blank, sham surgery, model, and EA groups, with 6 rats in each group. CSR rat model was established by using cervical spinal cord canal puncture method. On the 7th day after successful modeling, EA was applied to rats in the EA group at bilateral "Hegu"(LI4) and "Taichong"(LR3) for 20 minutes(1.5 Hz, 1 mA), once daily for 7 consecutive days. Before and after intervention, gait impairment scores and mechanical pain thresholds were assessed. HE staining was used to observe pathological changes in spinal cord tissue. Western blot was used to detect the expression of HMGB1, TLR4, MyD88, and glial fibrillary acidic protein (GFAP) in the spinal cord. ELISA was used to measure the contents of CXC chemokine ligand 1 (CXCL1), chemokine ligand 2 (CCL2), tumor necrosis factor (TNF)-α, and interleukin (IL)-1ß in spinal cord. Immunofluorescence staining was used to observe GFAP protein positive expression in spinal cord tissue. RESULTS: There was no significant difference of all indexes between the blank group and the sham surgery group. Compared with the sham surgery group, mechanical pain threshold of rats in the model group was decreased(P<0.01), while gait impairment score, the contents of CXCL1, CCL2, TNF-α, IL-1ß, protein expressions of HMGB1, TLR4, MyD88 and GFAP, and positive expression of GFAP in spinal cord tissue were increased (P<0.01)；HE staining indicated severe overall morphological damage in the spinal cord of rats in the model group, with significant shrinkage of gray matter neurons, reduced number of Nissl bodies, and increased inflammatory cell infiltration. Compared with the model group, mechanical pain threshold in the EA group was increased (P<0.01), while gait impairment score, the contents of CXCL1, CCL2, TNF-α, IL-1ß, protein expressions of HMGB1, TLR4, MyD88 and GFAP, and positive expression of GFAP in spinal cord were reduced (P<0.01)；HE staining showed more intact neuronal cell bodies, increased number of Nissl bodies, and reduced shrinkage of gray matter neurons, inflammatory cell infiltration, and microvascular dilation in the spinal cord of rats in the EA group. CONCLUSIONS: EA can effectively alleviate pain in CSR rats, which is possibly by inhibiting astrocyte activation, HMGB1/TLR4/MyD88 signaling pathway, and reducing the release of related inflammatory cytokines, thus alleviating central sensitization in spinal segments.

Short-Term Effect of Stimulating the Pterygopalatine Ganglion Via Electroacupuncture on Choroidal Structure in Human Subjects.

Purpose: Choroidal dysfunction is implicated in various ocular pathologies. The parasympathetic pterygopalatine ganglion (PPG) innervates orbital vessels supplying the choroid. While PPG stimulation has been shown to dilate cerebral blood flow, its effects on the choroid, particularly in human subjects, require further elucidation. This study aimed to investigate the short-term influence of PPG stimulation via electroacupuncture on choroidal structure. Methods: In this crossover study, 22 healthy adults received PPG electrical stimulation and sham stimulation for one session each on two separate days in a randomized order. Measurements including choroidal thickness (ChT), choroidal vascularity index (ChVI), central subfield thickness, axial length, anterior chamber depth, and lens thickness were recorded before and at intervals (0, 15, 30, 45, and 60 minutes) postintervention. Results: The ChT on the side receiving PPG stimulation demonstrated a sustained increase, peaking at 15 minutes poststimulation (17.2 µm, P < 0.001) and persisting for up to 60 minutes. Conversely, the ChVI exhibited a more immediate response, with a peak increase immediately poststimulation (3.8%, P = 0.003), followed by a gradual return to baseline. ChT and ChVI in the contralateral eye showed a nonsignificant trend to decrease. Additionally, a notable reduction in ipsilateral axial length was observed at specific time points poststimulation. Conclusions: PPG activation via electroacupuncture elicited a short-term increase in ChT and ChVI in the ipsilateral eye compared to sham stimulation, with ChT increases trailing those of ChVI but displaying greater persistence. Translational Relevance: Electrical stimulation of the PPG can produce a short-term increase in ipsilateral ChT and ChVI.

Effects of Electroacupuncture at Varied Frequencies on Analgesia and Mechanisms in Sciatic Nerve Cuffing-Induced Neuropathic Pain Mice.

Addressing the intricate challenge of chronic neuropathic pain has significant implications for the physical and psychological well-being of patients, given its enduring nature. In contrast to opioids, electroacupuncture (EA) may potentially provide a safer and more efficacious therapeutic alternative. Our objective is to investigate the distinct analgesic effects and potential mechanisms of EA at frequencies of 2 Hz, 100 Hz, and 18 kHz in order to establish more precise frequency selection criteria for clinical interventions. Analgesic efficacy was evaluated through the measurement of mice's mechanical and thermal pain thresholds. Spinal cord inflammatory cytokines and neuropeptides were quantified via Quantitative Real-time PCR (qRT-PCR), Western blot, and immunofluorescence. Additionally, RNA sequencing (RNA-Seq) was conducted on the spinal cord from mice in the 18 kHz EA group for comprehensive transcriptomic analysis. The analgesic effect of EA on neuropathic pain in mice was frequency-dependent. Stimulation at 18 kHz provided superior and prolonged relief compared to 2 Hz and 100 Hz. Our research suggests that EA at frequencies of 2 Hz, 100 Hz, and 18 kHz significantly reduce the release of inflammatory cytokines. The analgesic effects of 2 Hz and 100 Hz stimulation are due to frequency-dependent regulation of opioid release in the spinal cord. Furthermore, 18 kHz stimulation has been shown to reduce spinal neuronal excitability by modulating the serotonergic pathway and downstream receptors in the spinal cord to alleviate neuropathic pain.

Electroacupuncture Protocol for Sensory and Motor Function Recovery After Orthognathic Surgery: a Randomized Clinical Trial.

Importance: Orthognathic surgery is utilized to rectify facial deformities, but it can lead to neurosensory alterations. Electroacupuncture has been shown to enhance sensitivity and motor functions in patients post-surgery. However, its application in traumatic facial injuries remains inadequately researched. Objective: To investigate the effects of electroacupuncture on sensitivity and orofacial function in patients undergoing orthognathic surgery. Design, Setting, and Population: A randomized clinical trial involving patients undergoing bimaxillary orthognathic surgery and genioplasty who are randomly allocated to either a physiotherapy (PT) or physiotherapy plus electroacupuncture group (PTEA). Exposures: Participants will be allocated to their respective therapies for a duration of six weeks. The PT group will receive a 50-minute physical therapy session along with 30 minutes of simulated procedure. The PTEA group will receive 50 minutes of physical therapy followed by 30 minutes of electroacupuncture. Main Outcomes and Measures: Before treatment, sensitivity will be assessed using the SMILE Sensitivity Test-BAURU kit, edema will be evaluated using the MD Anderson Cancer Center Head and Neck Lymphedema protocol, range of motion will be measured using a digital caliper, and muscle pain and fatigue will be gauged using numerical scales. The chewing function will be evaluated using the Chewing Quality Assessment Questionnaire. Results: All assessments will be repeated at three and six months following the initiation of treatment. Conclusions and Relevance: This study may provide reliable and high-quality clinical evidence regarding the impact of electroacupuncture on restoring altered sensation and motor function in patients undergoing orthognathic surgery.

Electroacupuncture Relieves Neuropathic Pain via Adenosine 3 Receptor Activation in the Spinal Cord Dorsal Horn of Mice.

Neuropathic pain (NPP) is a devastating and unbearable painful condition. As prevailing treatment strategies have failed to mitigate its complications, there remains a demand for effective therapies. Electroacupuncture (EA) has proved a potent remedial strategy in NPP management in humans and mammals. However, past studies have investigated the underlying mechanism of the analgesic effects of EA on NPP, focusing primarily on adenosine receptors in peripheral tissues. Herein, we elucidate the role of the adenosine (Adora-3) signaling pathway in mediating pain relief through EA in the central nervous system, which is obscure in the literature and needs exploration. Specific pathogen-free (SPF) male adult mice (C57BL/6 J) were utilized to investigate the effect of EA on adenosine metabolism (CD73, ADA) and its receptor activation (Adora-3), as potential mechanisms to mitigate NPP in the central nervous system. NPP was induced via spared nerve injury (SNI). EA treatment was administered seven times post-SNI surgery, and lumber (L4-L6) spinal cord was collected to determine the molecular expression of mRNA and protein levels. In the spinal cord of mice, following EA application, the expression results revealed that EA upregulated (p < 0.05) Adora-3 and CD73 by inhibiting ADA expression. In addition, EA triggered the release of adenosine (ADO), which modulated the nociceptive responses and enhanced neuronal activation. Meanwhile, the interplay between ADO levels and EA-induced antinociception, using an Adora-3 agonist and antagonist, showed that the Adora-3 agonist IB-MECA significantly increased (p < 0.05) nociceptive thresholds and expression levels. In contrast, the antagonist MRS1523 exacerbated neuropathic pain. Furthermore, an upregulated effect of EA on Adora-3 expression was inferred when the Adora-3 antagonist was administered, and the EA treatment increased the fluorescent intensity of Adora-3 in the spinal cord. Taken together, EA effectively modulates NPP by regulating the Adora-3 signaling pathway under induced pain conditions. These findings enhance our understanding of NPP management and offer potential avenues for innovative therapeutic interventions.

Overview of mechanism of electroacupuncture pretreatment for prevention and treatment of cardiovascular and cerebrovascular diseases.

Cardio-cerebrovascular disease (CCVD) is a serious threat to huma strategy to prevent the occurrence and development of disease by giving electroacupuncture intervention before the disease occurs. EAP has been shown in many preclinical studies to relieve ischemic symptoms and improve damage from ischemia-reperfusion, with no comprehensive review of its mechanisms in cardiovascular disease yet. In this paper, we first systematically discussed the meridian and acupoint selection law of EAP for CCVD and focused on the progress of the mechanism of action of EAP for the prevention and treatment of CCVD. As a result, in preclinical studies, AMI and MCAO models are commonly used to simulate ischemic injury in CCVD, while MIRI and CI/RI models are used to simulate reperfusion injury caused by blood flow recovery after focal tissue ischemia. According to the meridian matching rules of EAP for CCVD, PC6 in the pericardial meridian is the most commonly used acupoint in cardiovascular diseases, while GV20 in the Du meridian is the most commonly used acupoint in cerebrovascular diseases. In terms of intervention parameters, EAP intervention generally lasts for 30 min, with acupuncture depths mostly between 1.5 and 5 mm, stimulation intensities mostly at 1 mA, and commonly used frequencies being low frequencies. In terms of molecular mechanisms, the key pathways of EAP in preventing and treating cardiovascular and cerebrovascular diseases are partially similar. EAP can play a protective role in cardiovascular and cerebrovascular diseases by promoting autophagy, regulating Ca2+ overload, and promoting vascular regeneration through anti-inflammatory reactions, antioxidant stress, and anti-apoptosis. Of course, both pathways involved have their corresponding specificities. When using EAP to prevent and treat cardiovascular diseases, it involves the metabolic pathway of glutamate, while when using EAP to prevent and treat cerebrovascular diseases, it involves the homeostasis of the blood-brain barrier and the release of neurotransmitters and nutritional factors. I hope these data can provide experimental basis and reference for the clinical promotion and application of EAP in CCVD treatment.

Safety and efficacy of electro-thumbtack needle for acute mountain sickness patients: a protocol of a randomized, single-blinded, and placebo-controlled study.

BACKGROUND: Acute mountain sickness (AMS) is considered the most common altitude sickness. It can be detrimental to the health of tourists who rapidly ascend high mountains, and can also impair the performance of individuals who move to the plateau for work or education. Acupuncture has been shown to improve AMS as a simple, safe, and effective nonpharmacological method, in case electro-thumbtack needle (ETN) is a more convenient form of acupuncture for both doctor and patient. There are no studies validating the effectiveness of electro-thumbtack needle in improving symptoms in participants with AMS. In this study, we will conduct a randomized controlled trial to evaluate the clinical efficacy and safety of electro-thumbtack needle in participants with AMS. Our hypothesis is that electro-thumbtack needle is safe and effective in treating participants with AMS. METHODS: This study is a single-center, randomized, single-blinded, and placebo-controlled study involving at least 114 participants who were diagnosed with AMS. The participants randomly assigned in a 1:1 ratio to the electro-thumbtack needle group and the sham acupuncture group. The treatment protocol involved stimulation of seven predefined acupuncture points, including Zhong Wan (RN12), bilateral Nei Guan (PC6), bilateral He Gu (LI4), and bilateral Tai Yang (EX-HN5), for approximately one minute each, with continuous application over 48 h. The primary outcome was improvement in 2018 Lake Louise score (LLS) after 48 h of treatment. Secondary outcome indicators included the incidence of participants with moderate-to-severe AMS (AMS > 5)and AMS, the LLS, visual analogue scale of headache, clinical functioning scores, the Groningen Sleep Quality Survey, the Stanford Somnolence Scale, blood pressure, oxygen saturation, and heart rate, in addition to treatment-related adverse events were also captured. DISCUSSION: This trial aims to ascertain the therapeutic benefits of ETN in mitigating AMS symptoms, thereby contributing to the evidence base for traditional medical practices, particularly acupuncture, in high-altitude medicine. TRIAL REGISTRATION: Chinese Clinical Trials Registry: ChiCTR2300073882. Registered on 24 July 2023.

Systematic review and Meta-analysis of brain plasticity associated with electroacupuncture in experimental ischemic stroke.

OBJECTIVE: To systematically evaluate the role of electroacupuncture in maintaining brain plasticity in ischemic stroke mediated brain damage. METHODS: We searched for all relevant trials published through Oct 7, 2022 from seven databases. Metho-dological quality was assessed using the CAMARADES Risk of Bias Tool. A Meta-analysis of comparative effects was performed using Review Manager v.5.3 software. RESULTS: A total of 101 studies involving 2148 animals were included. For most studies, primary outcomes results of the Meta-analysis indicate that EA significantly improved ischemic stroke rat's postsynaptic density thickness [Standardized Mean Difference (SMD) = 1.41, 95% confidence interval (CI) (0.59, 2.23), P = 0.0008], numerical density of synapses [SMD = 1.55, 95% CI (0.48, 2.63), P = 0.005] compared with non-EA-treated. Similarly, EA could improve parts of biomarkers of synapses, neurogenesis, angiogenesis and neurotrophin activity than the control group (P < 0.05). CONCLUSION: The existing evidence suggests EA regulating ischemic stroke may be through brain plasticity. More rigorous and high quality studies should be conducted in the future.

Regulatory role of electroacupuncture on satellite glial cell activity in the colon and dorsal root ganglion of rats with irritable bowel syndrome.

OBJECTIVE: To investigate the role of satellite glial cells in irritable bowel syndrome (IBS) and the effect of electroacupuncture (EA) at the Tianshu (ST25) and Shangjuxu (ST37) combination. METHODS: A model for visceral hypersensitivity in IBS was induced through colorectal distension (CRD) stimulation. Clean-grade male Sprague-Dawley (SD) rats were randomly divided into four groups: a normal group (NG), a model group (MG), an electroacupuncture group (EA), and a glial cell inhibitor group (FCA). Bilateral EA (2/100 Hz, 1 mA, 30 min) was administered at the Tianshu (ST25) and Shangjuxu (ST37) in week 6. Abdominal withdrawal reflex (AWR) scores were used to assess the behavioral response associated with visceral hyperalgesia, while hematoxylin-eosin staining was employed to evaluate pathological changes in the colon. The protein and mRNA levels of glial fibrillary acidic protein (GFAP) in the colon and colon-related dorsal root ganglion (DRG) were analyzed using immun-ofluorescence, immun-ohistochemistry, Western blotting, real-time polymerase chain reaction. The impact of EA on electrophysiological properties of colon-related DRG neurons was observed through whole-cell patch clamp analysis. RESULTS: EA significantly reduced the visceral pain behavior scores in rats with IBS in response to graded (20, 40, 60, 80 mm Hg) CRD stimulation. Additionally, EA downregulated the protein and mRNA expression levels of GFAP in the colon and colon-related DRG of rats with IBS. EA also regulated the resting membrane potential, rheobase and action potential of colon-related DRG neurons in rats with IBS. CONCLUSIONS: EA can regulate the excitatory properties of colon-related DRG neurons by downregulating the protein and mRNA expression of GFAP in the colon and colon-related DRG, indicating a potential neurobiological mechanism by which EA relieves visceral hypersensitivity in rats with IBS.

Electroacupuncture inhibits hippocampal oxidative stress and autophagy in sleep-deprived rats through the protein kinase B and mechanistic target of rapamycin signaling pathway.

OBJECTIVE: To investigate the effects of acupuncture on learning and memory impairment, oxidative stress and autophagy induced by sleep depriv ation in rats, and to analyze the related mechanism. METHODS: Thirty Wistar rats were randomly divided into a normal group, sleep deprivation group and acupuncture group. The rat model of sleep deprivation was established by a modified multiplatform sleep deprivation method. The Baihui (GV20), Shenmen (HT7) and Sanyinjiao (SP6) acupoints of rats were located to give electroacupuncture (density wave, frequency 20 Hz, intensity 1 mA) to maintain the needle feeling, and to keep the needle for 15 min and continuous acupuncture for 7 d. The spatial learning and memory abilities of the rats were detected by the water maze test. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the brain were detected by an assay kit, and the autophagy related proteins light chain 3 alpha (LC3A), light chain 3 beta (LC3B) and Beclin 1 and the activation of the protein kinase B (PKB/AKT) and mechanistic target of rapamycin (mTOR) signaling pathway in the rat's brain were detected by Western blotting. RESULTS: Compared with the normal group, the time spent in the target quadrant (P < 0.05) and the number of times entering the target quadrant (P < 0.05) in the rats of sleep deprivation group were significantly reduced, and the content of MDA was significantly increased (P < 0.01), while the activities of SOD and GPX (P < 0.01) in the brain were significantly decreased, and LC3A Ⅱ/Ⅰ, LC3B Ⅱ/Ⅰ and Beclin 1 increased significantly (P < 0.01), while p-AKT (ser473)/AKT, p-mTOR (ser2448)/mTOR and p-p70s6K (thr389)/p70S6 decreased significantly (P < 0.01). Compared with the sleep deprivation group, the time spent in the target quadrant and the times of entering the target quadrant (P < 0.05) in the rats of acupuncture group after 7 d of treatment were significantly increased, Additionally, the content of MDA was significantly decreased (P < 0.05), while the activities of SOD and GPX (P < 0.05) in the brain were significantly increased. Moreover, the levels of LC3A Ⅱ/Ⅰ, LC3BⅡ/Ⅰ and Beclin 1 decreased significantly (P < 0.05), and that of p-AKT (ser473)/AKT, p-mTOR (ser2448)/mTOR and p-p70s6K (thr389)/p70s6k increased significantly (P < 0.05). CONCLUSION: Acupuncture can significantly improve the learning and memory damage caused by sleep deprivation and inhibit oxidative stress and autophagy, and its effect is related to the activation of AKT/mTOR signaling.

[Effect of electroacupuncture at "Fenglong" (ST 40) on liver cholesterol metabolism in hyperlipidemia rats based on AMPK/mTOR pathway].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Fenglong" (ST 40) on the expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), and the expression of the downstream molecules related to cholesterol metabolism i.e. sterol regulatory element binding protein-2 (SREBP-2), recombinant 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), and adenosine triphosphate binding cassette transporter G5/G8(ABCG5/G8) in the rats with hyperlipidemia (HPL) so as to explore the possible mechanism of EA in the intervention of HPL. METHODS: Thirty SPF-grade male SD rats were randomly divided into a blank group, a model group, an AMPK agonist group, an EA group, and an EA+AMPK inhibitor group, 6 rats in each group. The high-fat feeding method was adopted to establish HPL model. After successfully modeled, the rats in the EA group received EA intervention at bilateral "Fenglong" (ST 40), with disperse-dense wave, in the frequency of 2 Hz/100 Hz, the intensity of 1 mA. EA was given once daily, for 30 min in one intervention. In the AMPK agonist group, the intraperitoneal injection with AMPK agonist A-769662 was administered, 30 mg/kg, twice a day. In the EA+AMPK inhibitor group, the intraperitoneal injection of AMPK inhibitor Compound C was administered, 25 mg/kg, once a day, 30 min before EA intervention. In the intervention groups, the interventions were delivered continuously for 5 days a week and lasted 4 weeks. Using automated biochemical analyzer, the blood lipid-related indexes (serum total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C] and high-density lipoprotein cholesterol [HDL-C] as well as alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) were detected in the rats. HE staining and oil red O staining were used to observe the morphology of liver tissue. Liver index was calculated by the weight. Using ELISA, the contents of TC and TG of liver tissue and the contents of of TC and bile acid in feces were detected. The protein phosphorylation levels of AMPK and mTOR in the liver tissue were detected using Western blot; and the positive expression of SREBP-2, HMGCR and ACBG5/G8 was detected using immunohistochemical staining. RESULTS: After modeling, the levels of serum TC, TG and LDL-C of rats in the model group, the AMPK agonist group, the EA group and the EA+AMPK inhibitor group were all higher than those in the blank group (P<0.01); and there was no statistically difference in the levels of serum HDL-C among groups (P>0.05). After intervention, compared with the blank group, in the model group, the levels of serum TC, TG, LDL-C, ALT and AST, the liver index, the levels of TC and TG in liver tissue, the levels of TC and the bile acid in feces were increased (P<0.01); HE and oil red O staining showed that the hepatocytes were disordered, and there were macrovesicular lipid droplets in the cells and the obvious lipid accumulation; the protein expression of phosphorylated AMPK (p-AMPK) in liver tissue and the ratio of p-AMPK and AMPK were reduced (P<0.01), the protein expression of phosphorylated mTOR (p-mTOR) and the ratio of p-mTOR and mTOR were elevated (P<0.01); and the positive expression of SREBP-2, HMGCR, ABCG5 and ABCG8 in liver tissue was increased (P<0.01, P<0.05). Compared with the model group, in the AMPK agonist group and the EA group, the levels of serum TC, TG, LDL-C, ALT and AST, liver indexes, the levels of TC and TG in liver tissue were reduced (P<0.01), while the levels of TC and bile acid in feces were increased (P<0.05, P<0.01); HE staining and oil red O staining showed that the hepatocytes were in order, and lipid accumulation; the protein expression of p-AMPK and the ratio of p-AMPK and AMPK in liver tissue increased (P<0.01), while the protein expression of p-mTOR and the ratio of p-mTOR and mTOR decreased (P<0.01); the positive expression of SREBP-2 and HMGCR in liver tissue was reduced (P<0.01), while that of ABCG5 and ABCG8 up-regulated (P<0.05, P<0.01) . Compared with the EA group, in the EA+AMPK inhibitor group, the levels of serum TC, TG, LDL-C, ALT and AST, liver index, the levels of TC and TG in liver tissue were increased (P<0.05, P<0.01), while the levels of TC and bile acid in feces were reduced (P<0.01); lipid accumulation was aggravated; the protein expression of p-AMPK and the ratio of p-AMPK and AMPK in liver tissue were reduced (P<0.01, P<0.05), while the protein expression of p-mTOR and the ratio of p-mTOR and mTOR elevated (P<0.05, P<0.01); the positive expression of SREBP-2 and HMGCR in liver tissue was increased (P<0.01), while that of ABCG5 and ABCG8 was down-regulated (P<0.01). CONCLUSION: EA at "Fenglong" (ST 40) can attenuate hyperlipidemia in HPL rats. It may be achieved by regulating the AMPK/mTOR pathway, inhibiting the expression of cholesterol synthesis related molecules, SREBP-2 and HMGCR, and up-regulating the expression of cholesterol excretion molecules, ABCG5 and ABCG8, thereby reducing liver cholesterol accumulation and increasing cholesterol excretion.

[Stable chronic obstructive pulmonary disease treated by adjunctive therapy of electrothermal acupuncture: a randomized controlled trial].

OBJECTIVE: To assess the effect and safety of electrothermal acupuncture in adjunctive treatment of stable chronic obstructive pulmonary disease (COPD) in patients. METHODS: Sixty-six stable COPD patients were randomly divided into an observation group and a control group, with 33 cases in each group. The patients in the control group were treated with bronchodilator inhalation combined with respiratory training for 4 weeks. In the observation group, on the basis of the treatment as the control group, electrothermal acupuncture was delivered at bilateral Quchi (LI 11), Zusanli (ST 36) and Sanyinjiao (SP 6), and the conventional filiform needling was operated at the supplementary acupoints selected according to the individual syndrome. The interventions in the observation group were given once every two days, 3 treatments a week, for consecutive 4 weeks. Before and after treatment completion, the lung functions (forced expiratory volume in the first second [FEV1], forced vital capacity [FVC], FEV1/FVC and the percentage of diffusing capacity of the lungs for carbon monoxide [DLCO%]), 6 min walking distance (6MWD) and the score of COPD assessment test (CAT) were compared between the two groups. The attacks of acute exacerbation were recorded in 1-year follow-up visit in the two groups and the safety of electrothermal acupuncture was evaluated. RESULTS: After treatment, FEV1, FVC, FEV1/FVC, DLCO% and 6MWD were increased (P<0.01, P<0.05), and CAT scores were decreased (P<0.01) in the two groups compared with those before treatment. FEV1, FVC, FEV1/FVC and 6MWD were higher and CAT score was lower in the observation group when compared with those of the control group (P<0.05). In the 1-year follow-up visit, the cases of acute exacerbation in the observation group were fewer than that in the control group (P<0.05). There were no treatment-related adverse reactions in the observation group. CONCLUSION: On the basis of bronchodilator inhalation and respiratory training, electrothermal acupuncture can ameliorate the lung function, strengthen motor ability, reduce the cases of acute exacerbation safely and effectively in the patients with stable COPD.

[Brian effects of electroacupuncture on sleep quality and cognitive function in patients with insomnia related to cerebral infarction].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on sleep quality, sleep structure, and cognitive function in patients with insomnia related to cerebral infarction, and to explore the brain effect mechanism of EA on insomnia related to cerebral infarction. METHODS: Thirty-six patients with insomnia related to cerebral infarction were randomly divided into an EA group (18 cases, 1 case was eliminated and 1 case dropped out) and a sham acupuncture group (18 cases, 1 case was eliminated and 2 cases dropped out). Both groups received conventional treatment for cerebral infarction. The EA group received EA at Sishencong (EX-HN 1) with continuous waves at a frequency of 2 Hz, at an intensity tolerable to the patient. The sham acupuncture group received sham acupuncture at non-acupoints with the same EA parameters but electrical stimulation was interrupted after 30 s. Both groups were treated for 20 min each session, once daily, 5 days per week, for a total of 4 weeks. Pittsburgh sleep quality index (PSQI), Montreal cognitive assessment-basic (MoCA-B) scores, and short-term memory (STM) encoding test accuracy and average reaction time were observed before and after treatment in the two groups. Polysomnography (PSG) was used to evaluate sleep structure, and electroencephalogram (EEG) data were collected to observe the standardized power value of the Theta frequency band before and after treatment. RESULTS: Compared with before treatment, PSQI score was decreased and MoCA-B score was increased in the EA group after treatment (P<0.001); the EA group had lower PSQI score and higher MoCA-B score than those in the sham acupuncture group (P<0.001, P<0.01). Compared with before treatment, STM encoding test accuracy was increased and average reaction time was shortened in the EA group after treatment (P<0.01, P<0.001); sleep efficiency (SE) was increased (P<0.01), total sleep time (TST), REM, and N3 stages were prolonged (P<0.01, P<0.05), and sleep latency (SL) was shortened (P<0.01). The standardized power value of the Theta frequency band in EEG channels F3, C3, C4, O1 and O2 was decreased (P<0.05). After treatment, the EA group had higher STM encoding test accuracy, shorter average reaction time (P<0.05), higher SE (P<0.01), longer TST, REM and N3 stages (P<0.01), and shorter SL (P<0.01) than those in the sham acupuncture group. There was no statistically significant difference in the standardized power value of the Theta frequency band between the two groups (P>0.05). CONCLUSION: EA could regulate sleep quality and structure in patients with insomnia related to cerebral infarction, and improve cognitive function, possibly related to the reduction of slow-wave activity in EEG.

[Electroacupuncture with different frequencies for paclitaxel-induced peripheral neuropathy: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of electroacupuncture (EA) at frequencies of 2 Hz, 100 Hz, and 2 Hz/100 Hz for chemotherapy-induced peripheral neuropathy (CIPN). METHODS: One hundred and sixty female breast cancer patients with CIPN induced by paclitaxel were randomly divided into a 2 Hz EA group (40 cases, 1 case dropped out), a 100 Hz EA group (40 cases, 2 cases dropped out), a 2 Hz/100 Hz EA group (40 cases, 3 cases dropped out), and a medication group (40 cases, 2 cases dropped out). The three EA groups received acupuncture at bilateral Quchi (LI 11), Waiguan (TE 5), Hegu (LI 4), Zusanli (ST 36), and Yanglingquan (GB 34). Electrodes of the HANS-200E acupoint nerve stimulator were connected to the same side Hegu (LI 4) and Waiguan (TE 5), and Zusanli (ST 36) and Sanyinjiao (SP 6), with EA stimulation frequencies of 2 Hz, 100 Hz, and 2 Hz/100 Hz, respectively. Each session lasted 30 min, once every other day, three times a week. The medication group received oral mecobalamin tablets, 0.5 mg per dose, three times a day. All groups were treated for four weeks. The functional assessment of cancer therapy/gynaecologic oncology group-neurotoxicity (FACT/GOG-Ntx), peripheral neurotoxicity grading based on the National Cancer Institute-common terminology criteria for adverse events Version 5.0 (NCI-CTCAE V5.0), and peripheral neuropathy pain visual analogue scale (VAS) scores were observed before and after treatment, and at follow-up after 4 weeks of treatment completion, and clinical efficacy was evaluated after theatment. RESULTS: Compared before treatment, FACT/GOG-Ntx scores in all groups were decreased after treatment and during follow-up (P<0.01). The score reduction between before and after treatment in the three EA groups was greater than the medication group (P<0.01, P<0.05), with the 2 Hz and 2 Hz/100 Hz EA groups showing a greater reduction than the 100 Hz EA group (P<0.05). The reduction of FACT/GOG-Ntx score between before treatment and follow-up in the 2 Hz and 2 Hz/100 Hz EA groups was greater than the medication group (P<0.01). Peripheral neurotoxicity grading in the three EA groups were improved after treatment (P<0.01). Compared before treatment, the peripheral neurotoxicity grading in the 2 Hz and 2 Hz/100 Hz EA groups was improved at follow-up (P<0.01, P<0.05). The VAS scores for peripheral neuropathy pain in the three EA groups were decreased after treatment (P<0.01, P<0.05). At follow-up, VAS scores in the 2 Hz, 2 Hz/100 Hz, and medication groups were decreased (P<0.01, P<0.05), with a greater reduction in the 2 Hz/100 Hz EA group than the medication group after treatment and follow-up (P<0.01, P<0.05). The overall effective rates for the 2 Hz, 100 Hz, 2 Hz/100 Hz, and medication groups were 79.5% (31/39), 68.4% (26/38), 81.1% (30/37), and 47.4% (18/38), respectively, with the 2 Hz and 2 Hz/100 Hz groups showing higher effective rates than the medication group (P<0.05). CONCLUSION: EA is effective in treating paclitaxel-induced CIPN. While there is no overall difference in efficacy among the different frequencies, 2 Hz and 2 Hz/100 Hz EA showing potential advantages. For patients with concurrent peripheral neuropathy pain, 2 Hz/100 Hz electroacupuncture is recommended.

[Electroacupuncture promotes angiogenesis in MIRI rats by modulating the AMPK/KLF2 signaling pathway]. / ç”µé’ˆè°ƒæŽ§è ºè‹·é ¸æ´»åŒ–è›‹ç™½æ¿€é ¶/Kruppelæ ·å› å­2ä¿¡å·é€šè·¯ä¿ƒè¡€ç®¡æ–°ç”Ÿå‡è½»å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤å¤§é¼ å¿ƒè‚ŒæŸä¼¤.

OBJECTIVES: To observe the effect of electroacupuncture(EA) on adenosine 5'-monophosphate-activated protein kinase (AMPK)/Kruppel-like factor 2 (KLF2) signaling pathway in ischemic myocardial tissues of rats, so as to explore the underlying mechanism of EA in attenuating myocardial ischemia-reperfusion injury (MIRI) through mediating angiogenesis. METHODS: Male SD rats were randomly divided into sham operation group, model group and EA group, with 10 rats in each group. The MIRI model was established by ligation of the anterior descending branch of the left coronary artery. Twenty-four hours after modeling, the rats in the EA group were given EA (2 Hz/100 Hz, 2 mA) at "Neiguan" (PC6) for 20 min each time, once a day for 5 consecutive days. Echocardiography was used to detect cardiac ejection fraction (EF) to evaluate cardiac function. HE staining was used to observe the morphological changes in rat myocardial tissue. Immunohistochemistry was used to detect the density of neovascularization in rat ischemic myocardium. Western blot and ELISA were used to detect the phosphorylated(p)-AMPK, AMPK, KLF2, vascular endothelial growth factor (VEGF) protein expression levels, and VEGF receptor 2 (VEGFR2) content in rat ischemic myocardial tissue, respectively. RESULTS: After modeling, compared with the sham operation group, rats in the model group had decreased EF(P<0.01), significant myocardial fiber damage with inflammatory cell infiltration, increased neovascular density (P<0.05), increased p-AMPK, AMPK, VEGF protein expression levels and VEGFR2 content in myocardial ischemic tissues(P<0.05, P<0.01), and decreased protein expression level of KLF2 (P<0.05). After EA intervention, compared with the model group, rats in the EA group had elevated EF(P<0.01), significantly reduced myocardial fiber damage, reduced inflammatory cell infiltration, increased neovascular density(P<0.01), and elevated p-AMPK, AMPK, KLF2, and VEGF protein expression levels and VEGFR2 content in the myocardial ischemic tissue (P<0.01). CONCLUSIONS: EA may promote angiogenesis, attenuate myocardial injury, and achieve cardioprotective effects in MIRI rats by regulating the expression of AMPK/KLF2 signaling pathway in myocardial tissues.

[Review of stimulation parameters of scalp-electroacupuncture for ischemic stroke]. / ç”µå¤´é’ˆæ²»ç–—ç¼ºè¡€æ€§è„‘å’ä¸­çš„åˆºæ¿€å‚æ•°ç ”ç©¶æ¦‚å†µ.

Scalp-electroacupuncture (scalp-EA) is an effective traditional Chinese medicine characteristic therapy for ischemic stroke and frequently employed in clinical practice, but there is still lack of normative standard of stimulation parameters. After searching the relevant articles, we summed up the stimulation parameters of scalp-EA for ischemic stroke from 5 aspects： 1) stimulating frequency (Low frequency is better when continuous waveform is used, and high frequency is better when dense-sparce waveform or discontinuous waveform employed), 2) waveform (Dense-sparce or discontinuous waves are better than continuous waves), 3) intensity (A tolerable stimulation strength may result in better outcomes), 4) needle retention time (In general, the needle retention time is 30 min, but still needing being determined), treatment course (Some studies showed that once a day EA for 3 continuous days is effective, 7 days, significantly effective, 14 days, further enhanced in the therapeutic effect), and 5) intervention time window (Generally, EA intervention within 6 h was mostly effective, shown by animal study). However, these parameters do not exist independently, and they can influence and interact with each other. It is difficult to observe the interaction among parameters only with single-dimension analysis. Hence, more and larger sample size studies, with strict inclusion and exclusion criteria, more reasonable research design (such as multiple factorial design, orthogonal experimental design, etc.) and multiple levels effect analysis are warranted.

[Effects of electroacupuncture on the inflammatory response and intestinal flora in obese rats]. / ç”µé’ˆå¯¹è‚¥èƒ–å¤§é¼ å°è‚ ç‚Žæ€§ååº”åŠè‚ é“èŒç¾¤çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the expressions of high mobility group protein 1(HMGB1) and myeloid differentiation factor 88 (MyD88) in the small intestine and intestinal flora of obese rats, so as to explore the potential mechanism of EA to improve obesity in rats. METHODS: After 1 week of acclimatization, 10 rats were randomly selected from 50 Wistar male rats as the normal group, and the rest rats were fed with high-fat diet for 8 weeks to establish the obese model. The successfully modeling rats were randomly divided into model group, EA group and sham EA group, with 10 rats in each group. Rats in the EA group were given EA (2 Hz, 1 mA) at "Zhongwan"(CV12), "Guanyuan"(CV4), "Zusanli" (ST36)and "Fenglong"(ST40). Rats in the sham EA group were given shallow stabs at acupoints of the EA group about 5 mm outwardly and the electrodes were clamped without being energized. Both groups were intervened for 10 min each time, 3 times (Monday, Wednesday and Friday) a week for 8 weeks. The body weights of the rats were measured before and after 8 weeks of intervention, respectively. The contents of serum lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α were measured by ELISA, and the protein and mRNA expressions of HMGB1 and MyD88 in the small intestine were detected by Western blot and real-time quantitative PCR, respectively. 16S rRNA sequencing was performed to determine the relative abundance and diversity of the bacterial flora in the fresh feces of rats. RESULTS: Compared with the normal group, the body weight, serum LPS and TNF-α contents, small intestinal HMGB1 and MyD88 protein and mRNA expression levels of rats in the model group were significantly increased (P<0.01), while the relative abundance of Lactobacillus, Muri and Bifidobacterium was decreased (p<0.01), Collinsella, Prevotella and Ruminococcus was increased (P<0.01). Compared with model group, the body weight, serum LPS and TNF-α contents, protein and mRNA expression levels of HMGB1 and MyD88 in both EA and sham EA groups were decreased (P<0.01, P<0.05), while the relative abundance of Lactobacillus, Muri and Bifidobacterium was increased (P<0.01) and Collinsella, Prevotella and Ruminococcus decreased (P<0.01). Comparison between EA group and sham EA group showed that, the contents of LPS and TNF-α in serum of rats in sham EA group were increased (P<0.01, P<0.05), the relative abundance of Lactobacillus, Muri and Bifidobacterium was lower (P<0.05, P<0.01), and Collinsella, Prevotella and Ruminococcus was higher (P<0.01). CONCLUSIONS: EA can reduce the body weight of obese rats, which may be related to the regulation of the structure of intestinal flora and the reduction of inflammatory reactions in the small intestine.

Acupuncture improves neuroendocrine defects in a preclinical rat model of reproductive aging.

AIMS: Clinical data supports electroacupuncture (EA) as an effective treatment for female reproductive disorders especially gonadotropin abnormalities. This study aims to detect the mechanism of EA that improves the neuroendocrine defects particularly the luteinizing hormone (LH) surge failure in early reproductive aging females. MATERIALS AND METHODS: Middle-aged ovariectomized rats primed with hormone were treated by EA at acupoints CV4 and SP6 and undergone LH assay. Morphological experiments detected the activation of Kiss1 cells in the anteroventral periventricular nucleus (AVPV). Using targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) and RNA-sequencing, we determined the concentrations of neurotransmitter metabolites and transcriptomics in AVPV. KEY FINDINGS: EA significantly increased c-Fos and c-Fos-positive Kiss1 cells in the middle-aged AVPV as well as the total and peak LH release. Targeted LC-MS/MS and RNA-sequencing of AVPV identified differential neurotransmitters in the middle-aged females including Acetylcholine chloride, 5-Hydroxyindole-3-aceticacid, Kynurenine, Histamine, L-Histidine and L-Glycine, while EA decreased the concentration of Acetylcholine chloride. Totally 1255 differentially expressed genes modulated by EA were strongly implicated in neurotransmitter transport and KEGG pathways involved neuroactive ligand-receptor interaction, glutamatergic and gamma-aminobutyric acid-mediated synapse. Specifically, the mRNAs associated with the LH surge such as hormone receptor Pgr, adrenoceptor Adra1a, neurotransmitter transporters Slc17a6 and Slc32a1, glutamate decarboxylase Gad2 and Kiss1 were markedly altered by EA. SIGNIFICANCE: These findings showed that the age-related reduction of LH surge occurred via differential neurotransmitter metabolisms and altered transcriptions in AVPV, which proposed EA-based therapy for improving responsiveness of the hypothalamus to hormone in women with advanced age.

Postoperative Electroacupuncture Boosts Cognitive Function Recovery after Laparotomy in Mice.

Postoperative cognitive dysfunction (POCD) is a common complication that affects memory, executive function, and processing speed postoperatively. The pathogenesis of POCD is linked to excessive neuroinflammation and pre-existing Alzheimer's disease (AD) pathology. Previous studies have shown that acupuncture improves cognition in the early phase of POCD. However, POCD can last for longer periods (up to weeks and years). The long-term effects of acupuncture are unknown. In this study, we hypothesized that electroacupuncture (EA) could reduce inflammation and cognitive dysfunction induced by laparotomy over a longer period. We characterized the effects of postoperative EA on cognitive changes and investigated the underlying molecular mechanisms in mice. Laparotomy was performed in 3-month-old mice followed by daily EA treatment for 2 weeks. Our data indicated that laparotomy induced prolonged impairment in memory and executive functions, which were mitigated by postoperative EA. EA also reduced tau phosphorylation and suppressed the activation of tau-related kinases and glia, with effects comparable to ibuprofen. These findings demonstrate the beneficial effects of EA in a mouse model of POCD, suggesting that EA's ability to suppress neuroinflammation may contribute to its protective effects. In conclusion, EA may be a viable non-pharmacological intervention for managing POCD in different phases of the medical condition.

Electroacupuncture Reduces Heart Rate and Perceived Exertion During a Bike Test: A Preliminary Analysis.

BACKGROUND: Preliminary research suggests that acupuncture can improve cardiovascular function. The purpose of our study was to determine if electroacupuncture can improve performance and post-exercise recovery. METHODS: Thirty-two healthy people participated in this study (14 men and 18 women, aged 23.6 ± 3.5 years). The first visit included baseline measurements. Then, the participants received daily electroacupuncture at acupuncture point PC6 for a week, followed by a second visit. Heart rate, perceived exertion, and systolic and diastolic blood pressure were measured before, during, and after a YMCA submaximal bike test. RESULTS: The heart rate was significantly reduced during the final stage of the YMCA test (151.3 ± 7.0 to 146.7 ± 11.8; p = 0.013) on the second visit. The rate of perceived exertion was significantly lower during all stages in Visit 2 (average RPE Visit 2 = 10.71 ± 2.02; average RPE Visit 1 = 11.45 ± 1.98; p = 0.004). Systolic blood pressure significantly decreased during the 5 min post-test recovery (SBP Visit 2 = 116.9 ± 12.0; SBP Visit 1 = 145.7 ± 14.6, p < 0.05). CONCLUSIONS: A week of electroacupuncture at PC6 led to reduced heart rate and perceived exertion during exercise, making the workload feel less strenuous. Electroacupuncture at PC6 shows potential for increasing participation in physical activities by making them feel easier to accomplish.