Electroacupuncture alleviates myocardial ischemia-reperfusion injury by inhibiting hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla.

Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.

Glutamatergic neurons in lateral hypothalamus play a vital role in acupuncture preconditioning to alleviate MIRI.

Myocardial ischemia-reperfusion injury (MIRI) has high morbidity and mortality worldwide. Increasing evidence has shown that electroacupuncture (EA) plays a critical role in alleviating MIRI. The aim of this study is to investigate whether glutamatergic neurons in the lateral hypothalamus (LH) have vital effect on MIRI as well as the underlying mechanism during the EA pretreatment. The MIRI model was established by ligating the left anterior descending (LAD) coronary artery for 30 min followed by reperfusion for 2 h. Chemogenetics, electrocardiogram (ECG) recording, ELISA, multichannel physiology recording, and immunofluorescence staining methods were combined to demonstrate that firing frequencies of neurons in the LH and expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the percentage of infarct size and the levels of cardiac troponin I (cTnI) and creatine kinase isoenzymes (CK-MB) were similar to inhibition of glutamatergic neurons in LH, also attenuated morphology of myocardial tissue was induced by MIRI. However, activation of glutamatergic neurons in LH weakened the above effects of EA pretreatment.NEW & NOTEWORTHY This study demonstrates that EA preconditioning can attenuate myocardial injury for MIRI, which is similar to inhibition of glutamatergic neurons in LH. However, chemical activation of glutamatergic neurons in LH attenuates the protective effect of EA pretreatment. These findings help better understand the mechanisms of EA to regulate cardiac function.

Involvement of purinergic P2Y1R in antidepressant-like effects of electroacupuncture treatment on social isolation stress mice.

Depression is a common neuropsychiatric disorder with high incidence and disability. Electroacupuncture (EA) is effective in the treatment of depression. However, the underlying mechanisms are not fully understood. Social isolation stress during post-weaning period can impair purinergic signaling in the brain of rodents and has emerged as a major risk factor for depression. The purpose of this study was to investigate the involvement of P2Y1 receptor (P2Y1R) in the antidepressant-like effects of EA. In this study, C57BL/6 mice were randomly assigned to group-housed (GH) or social isolated (SI) groups at post-natal day 21. After 6 weeks of social isolation, EA was performed on acupoints "Bai-hui" (GV20) and "Yin-tang" (GV29), or non-acupoints for 4 weeks. The SI mice received either intracerebroventricular injection of a selective P2Y1R agonist, MRS2365 (1 nmol); or a selective P2Y1R antagonist, MRS2179 (2 µmol), before and after EA. We found that SI mice exhibited depression-like behaviors accompanied with anxiety-like behaviors. The expressions of P2Y1R were well co-localized with GFAP-positive astrocytes and increased in the prefrontal cortex and hippocampus of SI mice. After treated with MRS2179, the depression-like behaviors of SI mice were attenuated, but not with MRS2365. Meanwhile, we found that EA could attenuate social isolation caused depression- and anxiety-like behaviors, and inhibited the up-regulation of P2Y1R in the prefrontal cortex and hippocampus of SI mice. Notably, the positive effects of EA on depression-like behaviors of SI mice could be reversed by MRS2365, while MRS2365 had no effect on the anxiolytic-like effects of EA. Therefore, we provide new evidence that EA could ameliorate depression- and anxiety-like behaviors in social isolation stress mice, and P2Y1R was involved in the antidepressant-like effects of EA.

Circular RNA expression profiling in the nucleus accumbens: Effects of electroacupuncture treatment on morphine-induced conditioned place preference.

Electroacupuncture (EA) has been developed on the basis of traditional Chinese acupuncture. EA can suppress craving in opioid addicts and opioid-seeking responses in rodents. However, the molecular mechanism of EA on the rewarding properties of morphine and craving responses is not known. Here, we have applied a conditioned place preference paradigm in mice to measure morphine-induced rewarding effects along with EA treatment. Circular RNAs (circRNAs) can function as micro RNA (miRNA) sponges to effectively regulate gene expression levels. CircRNA profiling within the nucleus accumbens (NAc) was performed in EA-treated and sham-treated mice. Following RNAseq, data were analyzed by gene ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) tools. We identified 112 significantly differentially expressed circRNAs, including 51 that were up-regulated and 61 that were down-regulated. Our bioinformatics analyses show that these differentially expressed circRNAs map into pathways that are mainly involved with renin secretion and the cGMP-PKG signaling. We further constructed a circRNA-miRNA network that predicts the potential roles of the differentially expressed circRNAs and the interaction of circRNAs with miRNAs. Our secondary sequencing and bioinformatics analysis in the NAc after EA treatment on morphine-induced CPP provides putative novel targets on molecular mechanisms involved in morphine reinforcement and possibly craving.

Electroacupuncture inhibits visceral pain via adenosine receptors in mice with inflammatory bowel disease.

To investigate the involvement of peripheral adenosine receptors in the effect of electroacupuncture (EA) on visceral pain in mice with inflammatory bowel disease (IBD). 2,4,6-Trinitrobenzene sulfonic acid (TNBS) was used to induce the visceral pain model. EA (1 mA, 2 Hz, 30 min) treatment was applied to bilateral acupoints "Dachangshu" (BL25) 1 day after TNBS injection once daily for 7 consecutive days. Von Frey filaments were used to measure the mechanical pain threshold. Western blot was used to detect the protein expression levels of adenosine 1 receptor (A1R), adenosine 2a receptor (A2aR), adenosine 2b receptor (A2bR), adenosine 3 receptor (A3R), substance P (SP), and interleukin 1 beta (IL-1ß) in colon tissue. EA significantly ameliorated the disease-related indices and reduced the expression of SP and IL-1ß in the colon tissues of mice with IBD. EA increased the expression of A1R, A2aR, and A3R and decreased the expression of A2bR in the colon tissue. Furthermore, the administration of adenosine receptor antagonists influenced the effect of EA. EA can inhibit the expression of the inflammatory factors SP and IL-1ß by regulating peripheral A1, A2a, A2b, and A3 receptors, thus inhibiting visceral pain in IBD mice.

Bone marrow-derived interstitial cells of cajal are increased by electroacupuncture in the colon of diabetic mice.

BACKGROUND AND AIM: Insufficiency of interstitial cells of cajal (ICC) in the muscular plexus of colon has been proved in diabetic mice. Electroacupuncture (EA) at ST36 can accelerate ICC supplement in the colon of diabetic mice, but the source of increased ICC has not been clearly explored. Bone marrow cells possess the potential of migration and differentiation into ICC of the intestine. Our aim is to explore the effects of EA on variations of bone marrow-derived ICC in the colon of diabetic mice as well as its mechanism. METHODS: Wild C57BL/6 mice were divided into six groups with random assignment method: control group, diabetic mellitus (DM) group, bone marrow transplantation (BMT) + DM group, BMT + DM + sham EA group, BMT + DM + low-frequency EA group, and BMT + DM + high-frequency EA group. Flow cytometric method was adopted to identify the chimera model. The specific location and expression levels of c-Kit+ green fluorescent protein (GFP+) cells in colon were detected by immunofluorescence. Western blot and quantitative polymerase chain reaction were used to assess the expression level of c-Kit, GFP, membrane-band stem cell factor (mSCF), p-ERK, p-c-Jun, ETV1, stromal cell-derived factor 1 (SDF-1), CXCR4, transforming growth factor ß1 (TGF-ß1), and smad3. RESULTS: c-Kit+ GFP+ cells in the muscular plexus of colon were apparently increased in the EA groups; the protein and mRNA expression level of CXCR4, SDF-1, TGF-ß1, smad3, c-kit, mSCF, p-ERK, p-c-Jun, and ETV1 were elevated in the EA groups. CONCLUSIONS: Electroacupuncture can effectively increase bone marrow-derived ICC in the colon by SDF-1/CXCR4, TGF-ß1/Smad3, and mSCF/Kit-p-ERK/p-c-Jun-ETV1 signal pathway.

Cognitive improvement effects of electro-acupuncture for the treatment of MCI compared with Western medications: a systematic review and Meta-analysis.

BACKGROUND: Almost half of mild cognitive impairment (MCI) patients progress to dementia, which is associated with decreased quality of life and obstacles to independent living. Relevant management is expected to prevent MCI patients from progressing to dementia. In recent years, electroacupuncture (EA) has been used to treat various kinds of neurological disorders including MCI. This study evaluates the use of EA for MCI patients to increase cognitive function through a comparison with Western medications. METHODS: Randomized controlled trials (RCT) or systematical reviews (SR) of EA versus Western medications for MCI were searched using the following 10 databases: Pubmed, Cochrane Library, CINAHL, EMBASE, China National Knowledge Infrastructure (CNKI), National Digital Science Library (NDSL), Journal of Oriental Neuropsychiatry (JON), Korean Medical Database (KMBASE), KoreaMed, and OASIS, from October 2007 to August 2017, without language restriction. A methodological quality assessment of RCTs or SRs that met inclusion criteria was conducted using Cochrane Risk of bias (RoB) tool and a meta-analysis by RevMan (Review Manager) 5.3.5 version of Cochrane collaboration. RESULTS: Five RCTs with 257 patients met inclusion criteria and those were randomly divided into two groups: the EA group (n = 103) and Western medications group (n = 154). The methodological quality of the included studies showed high risk or/and unclear of risk of bias. The meta-analysis of five studies reported that the EA group was better than the Western medications group, improving the Mini Mental State Examination (MMSE) score by 0.65 [95% CI 0.28~1.01] higher mean difference, Montreal Cognitive Assessment (MoCA) score by 0.66 [95% CI 0.00~1.32] higher mean difference. Adverse effects were not reported in the selected studies. CONCLUSION: Electroacupuncture was an effective treatment for MCI patients by improving cognitive function. However, the included studies presented a low methodological quality and no adverse effects were reported. Thus, further comprehensive studies with a design in depth are needed to derive significant results.

Suppressing PKC-dependent membrane P2X3 receptor upregulation in dorsal root ganglia mediated electroacupuncture analgesia in rat painful diabetic neuropathy.

Painful diabetic neuropathy (PDN) is a common and troublesome diabetes complication. Protein kinase C (PKC)-mediated dorsal root ganglia (DRG) P2X3 receptor upregulation is one important mechanism underlying PDN. Accumulating evidence demonstrated that electroacupuncture (EA) at low frequency could effectively attenuate neuropathic pain. Our previous study showed that 2-Hz EA could relieve pain well in PDN. The study aimed to investigate whether 2-Hz EA relieves pain in PDN through suppressing PKC-mediated DRG P2X3 receptor upregulation. A 7-week feeding of high-fat and high-sugar diet plus a single injection of streptozotocin (STZ) in a dose of 35 mg/kg after a 5-week feeding of the diet successfully induced type 2 PDN in rats as revealed by the elevated body weight, fasting blood glucose, fasting insulin and insulin resistance, and the reduced paw withdrawal threshold (PWT), as well as the destructive ultrastructural change of sciatic nerve. DRG plasma membrane P2X3 receptor level and DRG PKC expression were elevated. Two-hertz EA failed to improve peripheral neuropathy; however, it reduced PWT, DRG plasma membrane P2X3 receptor level, and DRG PKC expression in PDN rats. Intraperitoneal administration of P2X3 receptor agonist αß-meATP or PKC activator phorbol 12-myristate 13-acetate (PMA) blocked 2-Hz EA analgesia. Furthermore, PMA administration increased DRG plasma membrane P2X3 receptor level in PDN rats subject to 2-Hz EA treatment. These findings together indicated that the analgesic effect of EA in PDN is mediated by suppressing PKC-dependent membrane P2X3 upregulation in DRG. EA at low frequency is a valuable approach for PDN control.

Electroacupuncture ameliorates spatial learning and memory impairment via attenuating NOX2-related oxidative stress in a rat model of Alzheimer's disease induced by Aß1-42.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by progressive deterioration of cognition and memory, in which oxidative stress has been played a crucial role in the pathology of AD. Electroacupuncture (EA) is a widely used therapy based on traditional acupuncture combined with modern electrotherapy in Asia. The present study aimed to determine the effects of EA treatment on spatial learning and memory impairment, and to elucidate the status of NOX2-related oxidative stress in a rat model of Alzheimer's disease induced by Beta-amyloid1-42 (Aß1-42). Fifty-six adult female Sprague-Dawley (SD) rats were randomly divided into four groups: sham, sham+EA, AD and AD+EA. The rats in Sham+EA and AD+EA groups were respectively administrated EA treatment at Baihui and yongquan acupoints, once a day for 30 min, lasting for 28 days. The spatial learning and memory functions were assessed by Morris water maze (MWM) test. The activities of total antioxidant capacity (T-AOC), reactive oxygen species (ROS), malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OH-dG) were evaluated. Moreover, the neuronal injury was detected by Nissl staining. Meanwhile, the NeuN expression was examined in the hippocampus, the expression levels of Nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase2(NOX2) was detected by immunofluorescence staining and western blot. The results showed that EA treatment significantly improved spatial learning and memory impairment in rats induced by Aß1-42. Concomitantly, EA treatment markedly restored T-AOC and attenuated the abnormal increase in levels of ROS, MDA and 8-OH-dG in the hippocampus of the AD rats. More notably, EA treatment also effectively ameliorated neuronal injury and counteracted the aberrant increase of NOX2 levels in the hippocampus of AD rats. Our findings suggested that EA is a potential strategy for the treatment of AD, and the possible mechanism is associated with the alleviation of neuronal injury and inhibition of NOX2-related oxidative stress.

Electroacupuncture at LI11 promotes jejunal motility via the parasympathetic pathway.

BACKGROUND: Gastrointestinal motility disorder has been demonstrated to be regulated by acupuncture treatment. The mechanisms underlying the effects of acupuncture stimulation of abdominal and lower limb acupoints on gastrointestinal motility have been thoroughly studied; however, the physiology underlying the effects of acupuncture on the forelimbs to mediate gastrointestinal motility requires further exploration. The aim of this study was to determine whether electroacupuncture (EA) at LI11 promotes jejunal motility, whether the parasympathetic pathway participates in this effect, and if so, which somatic afferent nerve fibres are involved. METHODS: A manometric balloon was used to observe jejunal motility. The effects and mechanisms of EA at LI11 were explored in male Sprague-Dawley rats with or without drug administration (propranolol, clenbuterol, acetylcholine, and atropine) and with or without vagotomy. Three types of male mice (ß1ß2 receptor-knockout [ß1ß2-/-] mice, M2M3 receptor-knockout [M2M3-/-] mice and wild-type [WT] mice) were also studied by using different EA intensities (1, 2, 4, 6, and 8 mA). A total of 72 rats and 56 mice were included in the study. RESULTS: EA at LI11 increased the contractile amplitude of jejunal motility in the majority of both rats and mice. However, EA at LI11 did not enhance jejunal motility in rats administered atropine, rats that underwent vagotomy, and M2M3-||/- mice (at all intensities). In WT mice, EA at LI11 significantly increased jejunal motility at all intensities except 1 mA, and a plateau was reached at intensities greater than 4 mA. CONCLUSION: Our results suggest that EA at LI11 promotes jejunal motility primarily by exciting the parasympathetic pathway, and that Aδ-fibres and C-fibres may play important roles in the process.

Spatiotemporal changes of optical signals in the somatosensory cortex of neuropathic rats after electroacupuncture stimulation.

BACKGROUND: Peripheral nerve injury causes physiological changes in primary afferent neurons. Neuropathic pain associated with peripheral nerve injuries may reflect changes in the excitability of the nervous system, including the spinothalamic tract. Current alternative medical research indicates that acupuncture stimulation has analgesic effects in various pain symptoms. However, activation changes in the somatosensory cortex of the brain by acupuncture stimulation remain poorly understood. The present study was conducted to monitor the changes in cortical excitability, using optical imaging with voltage-sensitive dye (VSD) in neuropathic rats after electroacupuncture (EA) stimulation. METHODS: Male Sprague-Dawley rats were divided into three groups: control (intact), sham injury, and neuropathic pain rats. Under pentobarbital anesthesia, rats were subjected to nerve injury with tight ligation and incision of the tibial and sural nerves in the left hind paw. For optical imaging, the rats were re-anesthetized with urethane, and followed by craniotomy. The exposed primary somatosensory cortex (S1) was stained with VSD for one hour. Optical signals were recorded from the S1 cortex, before and after EA stimulation on Zusanli (ST36) and Yinlingquan (SP9). RESULTS: After peripheral stimulation, control and sham injury rats did not show significant signal changes in the S1 cortex. However, inflamed and amplified neural activities were observed in the S1 cortex of nerve-injured rats. Furthermore, the optical signals and region of activation in the S1 cortex were reduced substantially after EA stimulation, and recovered in a time-dependent manner. The peak fluorescence intensity was significantly reduced until 90 min after EA stimulation (Pre-EA: 0.25 ± 0.04 and Post-EA 0 min: 0.01 ± 0.01), and maximum activated area was also significantly attenuated until 60 min after EA stimulation (Pre-EA: 37.2 ± 1.79 and Post-EA 0 min: 0.01 ± 0.10). CONCLUSION: Our results indicate that EA stimulation has inhibitory effects on excitatory neuronal signaling in the S1 cortex, caused by noxious stimulation in neuropathic pain. These findings suggest that EA stimulation warrants further study as a potential adjuvant modulation of neuropathic pain.

Electroacupuncture at acupoint ST 37(Shangjuxu) improves function of the enteric nervous system in a novel mouse constipation model.

BACKGROUND: Electroacupuncture (EA) at acupoint ST 37 (Shangjuxu) has been used to alleviate gastrointestinal symptoms and improve gastrointestinal motility. However, the mechanisms by which EA affects the enteric nervous system (ENS) have scarcely been investigated. In this study, we investigated whether EA could improve ENS function. METHODS: A constipation model was established by gastric instillation of ice-cold saline daily for 14 days. The constipated mice were divided into two groups: the model group, which was not treated, and the EA group, which received EA at ST 37 at a frequency of 2-15 HZ and an amplitude of 1 mA for 15 min a day for 3 days. A further six mice were included as a non-constipated control group. After EA treatment, intestinal propulsion and defecation time were measured. Additionally, in jejunum, ileum and proximal colon myenteric plexus, the expressions of PGP9.5 and nNOS were measured by immunohistochemistry. RESULTS: The EA group demonstrated significant improvements in carbon propulsion rates and defecation time compared to model group (P < 0.05). In addition, after EA, the PGP9.5 and nNOS expression in jejunum, ileum and proximal colonic myenteric plexus was back to normal levels. CONCLUSION: This study suggests that EA stimulation at ST 37 is capable of ameliorating intestinal motility dysfunction, and can partly restore enteric neuron function. The ENS can participate in changes in intestinal motility by affecting inhibitory neurons.

Electroacupuncture combined with continuous adductor canal block for postoperative analgesia in patients undergoing total knee arthroplasty. / ç”µé’ˆç–—æ³•è”åˆè¿žç»­æ”¶è‚Œç®¡é˜»æ»žåœ¨å ¨è†å ³èŠ‚ç½®æ¢æœ¯æ‚£è€ æœ¯åŽé•‡ç—›ä¸­çš„åº”ç”¨.

OBJECTIVES: To observe the efficacy of electroacupuncture (EA)combined with continuous adductor canal block (CACB)for postoperative analgesia in patients undergoing total knee arthroplasty (TKA), and to explore its effect on pain factor levels. METHODS: Eighty-two patients with knee osteoarthritis undergoing unilateral TKA were randomly divided into an observation group and a control group, with 41 patients in each group. The patients in the control group were treated with CACB under ultrasound guidance on the affected side after removal of the endotracheal tube. In the observation group, electroacupuncture therapy was added on day 1-7 after operation; the acupoints included Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), Taixi (KI 3), Yinlingquan (SP 9)and Yanglingquan (GB 34), with disperse-dense wave, in frequency of 1 Hz/30 Hz, 30 min each session, once a day. The knee joint range of motion was compared between the two groups before operation and on postoperative day 1, 3, 7, and 14. The pain visual analog scale (VAS)scores were compared 6, 12, 24, and 48 h after operation. The number of times that the pain pump was pressed within 48 h after operation and the number of remedial analgesia were also compared. Serum levels of prostaglandin E2 (PGE2)and ß-endorphin (ß-EP)were measured preoperatively and at 6, 12, 24, and 48 h after operation. Adverse reaction rates within 48 h after operation were documented. RESULTS: On postoperative day 1, 3, and 7, the observation group exhibited greater knee joint range of motion than that in the control group (P<0.05). At 6, 12, 24, and 48 h after operation, VAS scores at rest and during activity in the observation group were lower than those in the control group (P<0.05). The observation group had lower numbers of pain pump use and remedial analgesia within 48 h after operation than those in the control group (P<0.05). Serum PGE2 levels were lower in the observation group at 6, 12, and 24 h after operation (P<0.05), while serum ß-EP levels were higher (P<0.05) than those in the control group. There was no statistical difference in the incidence of adverse reactions within 48 h after operation between the two groups (P>0.05). CONCLUSIONS: EA therapy could enhance the analgesic effect of CACB in TKA patients, possibly by decrease the content of PGE2 and increase the content of ß-EP, with a high level of safety.

Chuna Manual Therapy or Electroacupuncture with Pregabalin for Chemotherapy-Induced Peripheral Neuropathy: A Randomized Controlled Pilot Study.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common side effects of chemotherapy, and effective treatments for CIPN are still lacking. For this reason, there is a growing interest in complementary and alternative medicine as a potential source of nonsurgical treatments for CIPN symptoms alongside pregabalin. One such option being explored is Chuna manual therapy (CMT), a traditional Korean manual therapy. Methods: This study compares the effectiveness and safety of using only pregabalin (PG) as a conventional method of treating breast and colorectal cancer patients with CIPN symptoms with a combination of both PG and electroacupuncture (EA) or CMT, while also assessing the feasibility of future large-scale clinical studies. Due to the COVID-19 pandemic, only 74 CIPN patients were recruited to this study. Twenty-five were assigned to the PG group, 26 to the PG + EA group, and 22 to the PG + CMT group for a five-week treatment and a four-week follow-up study. Results: For the primary outcome, we evaluated the mean differences in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) compared to the baseline at week 5 (visit 4). Although we found that the PG + CMT group showed the biggest difference (-16.64 [95% CI: -25.16, -8.11]) compared to the PG group (-8.60 [95% CI: -14.93, -2.27]) and the PG + EA group (-6.73 [95% CI: -12.34, -1.13]), this finding lacked statistical significance (p = 0.2075). In terms of safety, two patients in the PG + CMT group reported side effects: one bruise and one headache. Conclusions: The low attrition and high adherence rates of all the groups, and the similar rates of side effects among them, support the feasibility of larger-scale follow-up studies.

Effects of electroacupuncture on chronic urinary retention after pelvic or lumbosacral tumor resection surgeries: a retrospective cohort study.

Background: Chronic urinary retention (CUR) resulting from lower motor neuron lesions (LMNL) is a medical condition secondary to pelvic or lumbosacral tumor resection surgeries. Electroacupuncture (EA) is proved to be effective and safe in treating certain lower urinary tract disorders. However, the clinical benefit and optimal duration of EA treatment for CUR following LMNL remain unknown. Methods: Using a retrospective cohort design, 20 eligible patients diagnosed with CUR resulting from LMNL secondary to pelvic or lumbosacral tumor resection surgeries were included from March 1, 2017, to June 30, 2020. The patients were treated by EA three times a week for 2 to 12 weeks and followed up for 24 weeks after treatment. The electric stimulators with a 5-Hz continuous wave (5-10 mA intensity) were separately connected to bilateral Ciliao (BL32), bilateral Zhongliao (BL33), and bilateral Huiyang (BL35), and stimulators with a 10-Hz continuous wave (1-2 mA intensity) were connected to bilateral Sanyinjiao (SP6). Current intensity was adjusted according to the patients' individual tolerance. The median follow-up was 32 weeks (range, 26-36 weeks). Responders were defined as patients whose post-void residuals (PVR) reduced by 50% or more from baseline. Adverse event was recorded. Results: Totally 20 patients [mean (standard deviation) age, 48.1 (15.5) years; 9 men (45.0%); 11 women (55.0%)] were included. Of the 20 patients, 14 (70.0%) had responded to EA treatment and stopped catheterization for achieving satisfactory spontaneous urination (PVR <100 mL without complications), 7 (35.0%) had complete resolution (90-100% reduction in PVR from baseline), and 13 (65.0%) scored 1 (much better) or 2 (moderately better) in the Patient Global Impression of Improvement (PGI-I) assessment. Moreover, 6 (30.0%) patients had responded within 4 weeks of EA treatment. According to Kaplan-Meier survival curve, we found that more than 50% patients could respond to EA treatment within 8 weeks or longer. None of the responders had ever experienced relapse in 24 weeks after EA treatment ended. None of the patients manifested urinary tract infection (UTI), newly diagnosed hydroureter or hydronephrosis. One patient diagnosed with hydronephrosis at baseline recovered after 12-week EA treatment. Two patients with UTI at baseline were prescribed antibiotics and did not present UTI again during the follow-up. Conclusions: EA could be a promising treatment option for CUR caused by LMNL following pelvic or lumbosacral tumor resection surgeries, with long-term effects and a good safety profile. The optimal duration of EA should be of 8 weeks at least. But this was a retrospective cohort study of a small sample size, so future studies are needed to investigate EA in larger populations in randomized controlled trials.

Effects of electroacupuncture on repairing neurological damage following ischemic stroke based on miR-381-mediated SDF-1/CXCR4 signaling pathway. / 基于miR-381调控SDF-1/CXCR4信号通路探讨电针对缺血性脑卒中后神经损伤修复的影响.

OBJECTIVES: To investigate the effects of electroacupuncture (EA) on the miR-381, leucine-rich repeat C4 protein (LRRC4), and downstream stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) signaling pathway in rat model of ischemic stroke, and to explore the mechanism by which EA improves neurological damage following ischemic stroke. METHODS: Among 50 SPF male SD rats, 10 rats were randomly selected into a sham surgery group, and the remaining rats were used to establish the middle cerebral artery occlusion (MCAO) model. The 30 successfully modeled rats were randomly divided into a model group, an EA group, and an agonist group, with 10 rats in each group. The rats in the EA group received EA at "Baihui" (GV 20) and "Dazhui" (GV 14), with disperse-dense wave, a frequency of 2 Hz/10 Hz, and a current intensity of 1 mA, 30 min per session, once daily for a total of 14 days. The rats in the agonist group received miR-381 agonist injections into the lateral ventricle, with 10 µL per injection, every 7 days for a total of 2 injections. After intervention, ZeaLonga neurobehavioral deficit score was observed in each group. HE staining was performed to observe the morphological changes in the ischemic brain tissue of rats in each group. ELISA was used to measure the levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and nerve growth factor (NGF) in serum. Western blot was employed to detect the protein expression of LRRC4, SDF-1, CXCR4, and extracellular regulated protein kinase 1 (ERK1) in the ischemic brain tissue. Real-time PCR was utilized to assess the expression of miR-381 and LRRC4, SDF-1, CXCR4, ERK1 mRNA in the ischemic brain tissue. RESULTS: After intervention, the brain tissue showed disordered cell arrangement, reduced quantity, and significant interstitial edema, with numerous vacuoles in the model group. The pathological changes mentioned above were alleviated in the brain tissue of rats in the EA group and the agonist group. Compared with the sham surgery group, the rats in the model group exhibited increased ZeaLonga neurobehavioral deficit scores, elevated levels of serum TNF-α and IL-6 (P<0.01), and decreased serum NGF level (P<0.01)；the protein expression of SDF-1, CXCR4 and ERK1 in ischemic brain tissue was reduced (P<0.01), while LRRC4 protein expression was increased (P<0.01)；the expression of miR-381, as well as SDF-1, CXCR4 and ERK1 mRNA in ischemic brain tissue was decreased (P<0.01), while LRRC4 mRNA expression was increased (P<0.01). Compared with the model group, the rats in the EA group and the agonist group showed decreased ZeaLonga neurobehavioral deficit scores and reduced levels of serum TNF-α and IL-6 (P<0.05, P<0.01), and increased serum NGF levels (P<0.05, P<0.01); the protein expression of SDF-1, CXCR4 and ERK1 in ischemic brain tissue was increased (P<0.01), while LRRC4 protein expression was decreased (P<0.01)；the expression of miR-381, as well as SDF-1, CXCR4 and ERK1 mRNA in ischemic brain tissue was increased (P<0.05, P<0.01), while LRRC4 mRNA expression was decreased (P<0.01). CONCLUSIONS: EA at "Baihui" (GV 20) and "Dazhui" (GV 14) may promote the repair of neurological damage following ischemic stroke by up-regulating miR-381 to selectively inhibit LRRC4 expression, thereby activating the SDF-1/CXCR4 signaling pathway.

[Effects of electroacupuncture on learning-memory function and synaptic plasticity in rats with cerebral ischemia-reperfusion injury based on the BDNF/TrkB pathway].

OBJECTIVE: To observe the effects of electroacupuncture (EA) at "Baihui" (GV 20) and "Sishencong" (EX-HN 1) on the expression of brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) pathway, synaptophysin (SYN), and the levels of interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) in the hippocampus of the ischemic side in rats with cerebral ischemia-reperfusion injury (CIRI), and to explore the effects and action mechanism of EA on post-CIRI learning-memory function. METHODS: Forty-eight SPF-grade male SD rats were randomly divided into a sham operation group, a model group, an EA group, and a non-acupoint group, with 12 rats in each group. The CIRI model was established in the model group, the EA group, and the non-acupoint group using the modified ZeaLonga suture method. The rats in the EA group were treated with EA at "Sishencong" (EX-HN 1) and "Baihui" (GV 20), with disperse-dense wave at frequency of 2 Hz/10 Hz and intensity of 1 mA. The rats in the non-acupoint group were treated with EA at non-meridian and non-acupoint points under the ribs bilaterally with the same parameters as the EA group. EA were conducted for 30 min each session, once daily, for 7 days. During the intervention, body weight was measured daily at a fixed time, and neurological deficits were assessed on the 1st, 3rd, and 7th days into intervention. Brain infarct volume was measured using small animal magnetic resonance imaging before and after the intervention. After the intervention, learning-memory function were evaluated using the Morris water maze. Hippocampal morphology was observed with HE staining. The positive expression of SYN in the hippocampus of the ischemic side was detected by immunohistochemistry. BDNF, TrkB, and SYN protein expressions in the hippocampus of the ischemic side were detected by Western blot. IL-1ß and IL-18 levels in the hippocampus of the ischemic side were measured by ELISA. RESULTS: From the 2nd to the 7th day into intervention, compared with the sham operation group, the body weight of rats in the model group was decreased (P<0.01); compared with the model group and the non-acupoint group, the body weight of rats in the EA group was increased (P<0.01). On the 1st day into intervention, compared with the sham operation group, neurological function scores of rats in the model group, the EA group, and the non-acupoint group were increased (P<0.01); on the 3rd and 7th days into intervention, neurological function scores of rats in the model group were higher than those in the sham operation group (P<0.01); on the 7th day, neurological function scores of rats in the EA group were lower than those in the model group and the non-acupoint group (P<0.05). Compared with the sham operation group, escape latency was prolonged (P<0.05), and the number of platform crossings was decreased (P<0.01) in the model group; compared with the model group and the non-acupoint group, escape latency was shortened (P<0.05), and the number of platform crossings was increased (P<0.01) in the EA group. Before intervention, the high signal infarcts were observed in the left ventricles of rats in the model group, the EA group, and the non-acupoint group; after intervention compared with the model group and the non-acupoint group, infarct volume in the EA group was decreased (P<0.01). Neuronal cells in the model group and the non-acupoint group were sparsely and disorderedly arranged, with deep-stained cytoplasm and shrunken nuclei; the number and arrangement of neuronal cells in the EA group were similar to the sham operation group, with less deep-stained cytoplasm and shrunken nuclei compared to the model group. Compared with the sham operation group, the positive expression of SYN, and BDNF TrkB, and SYN protein expressions in the hippocampus of the ischemic side were decreased (P<0.01, P<0.05), while levels of IL-1ß and IL-18 were increased (P<0.01) in the model group; compared with the model group and the non-acupoint group, the positive expression of SYN, and BDNF, TrkB and SYN protein expressions in the hippocampus of the ischemic side were increased (P<0.01, P<0.05), while levels of IL-1ß and IL-18 were decreased (P<0.01) in the EA group. CONCLUSION: EA at "Baihui" (GV 20) and "Sishencong" (EX-HN 1) may improve learning-memory function in rats with CIRI by activating the BDNF/TrkB signaling pathway, reducing neuroinflammatory response, and promoting the recovery of synaptic plasticity.

Electroacupuncture for ulcerative colitis patients: A meta-analysis and acupoints selection study.

Objective: To evaluate the efficacy and safety of electroacupuncture (EA) on ulcerative colitis (UC) and explore the influence of EA parameters and acupoint compatibility to optimize the clinical treatment plan. Methods: After searching eight databases, data were extracted and analyzed to determine the quality and bias of the study's methodological design, and randomized controlled trial (RCT) datas were meta-analyzed. Results: Twelve studies that meet the criteria were included. The results of meta-analysis indicated that, compared with the control group, experimental group had better clinical efficacy [RR = 1.27, 95%CI = (1.19, 1.36), P < 0.01], Other indicators such as cure rate [RR = 1.73, 95%CI = (1.43, 2.09), P < 0.01], effective rate of mucosal lesions under enteroscopy [RR = 1.24, 95%CI = (1.11, 1.38), P < 0.01], serum inflammatory factor TNF-α [MD = -41.11, 95%CI = (-46.01, 36.22), P < 0.01] were significantly better than those in the control group. Sixteen acupoints on the Ren, Bladder, Stomach, Spleen, and Liver meridians were used 74 times. RN4-ST25 is the most compatible acupoints. Conclusion: The clinical efficacy of EA in treating UC is superior than the control group's, and it has curative effects in terms of cure rate, efficacy of mucosal lesions under colonoscopy, serum inflammatory factors, and Traditional Chinese Medicine (TCM) syndrome scores. Combining acupoints of the Bladder, Stomach, and Ren meridians and using dense wave for 30 min each time for more than 6 weeks may be optimal for UC patients.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Electroacupuncture activates angiogenesis by regulating the PI3K/Pten/Thbs1 signaling pathway to promote the browning of adipose tissue in HFD-induced obese mice.

This study investigated the effect of electroacupuncture (EA) on the browning of white adipose tissue (WAT) via angiogenesis and its potential mechanism in obese mice. Four-week-old male C56BL/6 mice were randomly divided into a high-fat diet (HFD) and a normal chow diet (ND) group. After 12 weeks, HFD mice were randomly divided into two groups to receive or not receive EA for 3 weeks. After EA treatment, body weight, adipocyte size, serum glucose (GLU), triacylglycerol (TG), cholesterol (CHO), leptin (Lep), monocyte chemoattractant protein-1 (MCP-1), WAT browning-related genes, angiogenesis-related genes, and the PI3K/Pten/Thbs1 signaling pathway were evaluated. The results indicated that EA significantly reduced body weight, adipocyte size, and serum concentrations of GLU, TG, CHO, Lep and MCP-1 and promoted WAT browning. Angiogenesis and the PI3K/Pten/Thbs1 signaling pathway were all activated by EA intervention. The expression levels were consistent with the results of RNA-seq and confirmed via qRTPCR and WB. Our study showed that EA may activate angiogenesis via the PI3K/Pten/Thbs1 signaling pathway in WAT, thereby promoting the browning and thermogenesis of adipose tissue.