Both clinical and preclinical evidence showed that electroacupuncture (EA) at Baihui (Governing Vessel 20, GV20) and Dazhui (GV14) could relieve sensorimotor disability after ischemic stroke (IS). However, the mechanism behind this therapeutic remains to be unraveled, and the current findings of its underlying mechanism are mainly focusing on neurons, with little evidence from astrocyte. Astrocyte plays an essential role in IS pathology, and IL-17A as a critical mediator in IS. This study aimed to investigate the relationship between the activity of astrocyte and expression of IL-17A during the regulation of sensorimotor function. The sensorimotor-related behaviors in mice were assessed by using Adhesive removal test and Rotarod test, and the expression/function of IL-17A was evaluated by ELISA, RT-PCR, and Western Blot. In vivo calcium activity of astrocyte was detected by two-photon calcium imaging. Our results revealed that EA preconditioning promoted the recovery of sensorimotor function in IS mice, and this therapeutic effect was absent when the astrocytic activity was chemogenetically inhibited. In addition, astrocytic calcium activity of IS mice could be mimicked by overexpressing IL-17A. Altogether, these results suggested the IL-17A in the astrocyte may play a key role in the functional recovery after stroke. These findings not only elucidate a critical pathway for understanding how IL-17A in astrocytic calcium activity influences the functional recovery after stroke, but also suggest a potential valuable therapeutic strategy for stroke.

To investigate the mechanism by which electroacupuncture (EA) at "Zusanli" (ST36) ameliorates the impairment of feeding behavior and gastric vagal afferent signaling induced by short-term high-fat diet (HFD) exposure. The study comprised two parts. In part 1, 42 SPF male C57BL/6J mice were randomly divided into a normal diet (ND) group (n=14) and an HFD group (n=28). After 4 weeks, HFD-fed mice were subdivided into an HFD group and an EA group (n=14 each). The EA group received EA at bilateral "Zusanli" (ST36). Stimulation parameters were:2 mA, 2 Hz/15 Hz, 20 min/session, once daily, 6 sessions/week for 2 consecutive weeks. Body weight was recorded weekly. After the intervention, 24 h food intake was measured. Liver wet weight, inguinal white adipose tissue (iWAT) wet weight, and epididymal white adipose tissue (eWAT) wet weight were recorded. Gastric emptying rate was assessed using the phenol red meal test. Serum cholecystokinin (CCK) content was measured by ELISA. Protein expressions of protein gene product 9.5 (PGP9.5) and calcitonin gene-related peptide (CGRP) in the gastric antrum were evaluated by Western blot. The co-expression density index of PGP9.5 and CGRP in the gastric antrum and c-Fos expression levels in the nodose ganglion (NG) were detected by immunofluorescence staining. In part 2, another 32 SPF male C57BL/6J mice were fed an HFD for 4 weeks and then randomly divided into 4 groups (n=8 each):sham operation group, sham + EA group, vagotomy (resection of the gastric vagal branches) group, and vagotomy + EA group. The acupoint and intervention parameters were the same as above. Body weight, 24 h food intake, liver wet weight, iWAT wet weight, eWAT wet weight, the co-expression of PGP9.5 and CGRP in the gastric antrum, and the number of c-Fos positive neurons in the NG were measured. Compared to the ND group, 4-week HFD feeding increased body weight, liver wet weight, and adipose tissue (iWAT and eWAT) wet weights, while decreased gastric emptying rate and serum CCK levels(P<0.05). The relative protein expressions of both PGP9.5 and CGRP in the gastric antrum were down-regulated(P<0.05). Meanwhile, the co-expression density index of PGP9.5 and CGRP in the gastric antrum was reduced(P<0.05). The number of c-Fos positive neurons in the NG decreased in HFD-fed mice(P<0.05). Compared to the HFD group, EA treatment reduced body weight, 24 h food intake, liver wet weight, and adipose tissue (iWAT and eWAT) wet weights(P<0.05). EA also increased gastric emptying rate and serum CCK levels(P<0.05). Moreover, EA up-regulated the relative protein expressions of PGP9.5 and CGRP as well as their co-expression density index in the gastric antrum(P<0.05). Finally, EA increased the number of c-Fos positive neurons in the NG(P<0.05). In the vagotomy experiment, compared with the sham operation group, the sham{L-End} +{L-End} EA group showed a significant decrease in body weight, food intake, liver wet weight, adipose tissue wet weight (P<0.05). After gastric branch vagotomy, however, the regulatory effects of EA on body weight, food intake, liver wet weight, and other indicators were weakened. Similarly, after surgery EA did not exert a significant modulatory effect on the co-expression level of PGP9.5 and CGRP in the gastric antrum or on the expression of c-Fos-positive neurons in the NG. Short-term HFD leads to desensitization of gastric vagal afferent signaling, manifested as impairment of local gastric vagal sensory nerves and a decrease in the number of activated neurons in the NG. EA can suppress food intake by repairing gastric vagal afferent signaling.

To investigate the mechanism of electroacupuncture (EA) at sensitized "Sanyinjiao" (SP6) in improving primary dysmenorrhea (PDM), with a focus on the role of Piezo1 protein in EA effects. Sixty female rats were randomly divided into a blank group (n=10) and a model establishment group (n=50). Mechanical pain thresholds at the left SP6 acupoint were measured using a von Frey electronic algometer. According to the change rate of mechanical pain threshold, the model establishment group was further divided into model high-sensitization group, model low-sensitization group, EA high-sensitization group, and EA low-sensitization group (n=10 each). The PDM rat model was established by combined injection of estradiol benzoate and oxytocin. The two EA groups received EA at SP6 (50 Hz, dense wave, 20 min/d) for 5 consecutive days.Writhing responses were recorded to evaluate abdominal pain severity;uterine blood flow was observed by laser speckle imaging;uterine histopathology was examined by HE staining;mast cell degranulation rate at the SP6 region was detected by toluidine blue staining;ultrastructural changes of uterine tissue were observed by transmission electron microscopy;levels of prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α) in serum and uterine homogenate, and serum tumor necrosis factor-α (TNF-α) were measured by ELISA;protein expressions of Piezo1, calcitonin gene-related peptide (CGRP), and Tryptase in the SP6 region, as well as Piezo1 in the uterus, were detected by Western blot;immunofluorescence was used to detect CGRP and Tryptase expressions at SP6;RT-qPCR was performed to measure mRNA expressions of Piezo1 and cyclooxygenase-2 (COX-2) in the uterus. Compared with the blank group, the model high-sensitization and model low-sensitization groups showed increased writhing times, writhing scores and writhing latencies (P<0.01), decreased uterine blood perfusion (P<0.01), elevated uterine pathological scores (P<0.01), and increased mast cell degranulation rate (P<0.01). Serum and uterine PGF2α contents, serum TNF-α content and PGF2α/PGE2 ratio were significantly increased (P<0.01), while serum and uterine PGE2 contents were significantly decreased (P<0.01). Protein expressions of Piezo1, CGRP, Tryptase, and positive expressions of CGRP and Tryptase at the acupoint, mRNA and protein expressions of Piezo1, and COX-2 mRNA in the uterus were up-regulated (P<0.01), accompanied by ultrastructural damage in uterine tissue. Compared with the corresponding model groups, the writhing latencies were increased further, and the other indicators mentioned above were significantly reversed in the two EA groups (P<0.01, P<0.05). Moreover, the EA high-sensitization group exhibited more obvious improvements than the EA low-sensitization group (P<0.01). EA at SP6 with different sensitization states effectively alleviates pain in PDM rats, with a better effect in the high-sensitization state. The mechanism is dependent on acupoint sensitization, which may involve regulating Piezo1 expression at the acupoint, inhibiting mast cell degranulation and neurogenic inflammation, and down-regulating the Piezo1/COX-2/PGs pathway in the uterus to reduce inflammatory factor release, thereby producing analgesic effects.

To observe the role of tyrosine hydroxylase (TH)-positive neurons in the nucleus tractus solitarius (NTS) and locus coeruleus (LC) in electroacupuncture (EA)-mediated improvement of blood-brain barrier (BBB) damage in APP/PS1 mice, so as to explore the mechanism of the NTSTH-LC neural circuit underlying the effect of EA on prevention and treatment of Alzheimer's disease (AD). (1) Eight 4-month-old male C57BL/6 mice served as the control group, and 16 age-matched male APP/PS1 mice were randomly divided into the model and EA groups (n=8). The EA group received EA stimulation at "Neiguan" (PC6) and "Jianshi" (PC5) once every other day for 4 weeks. After intervention, Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Western blot was performed to detect the expression levels of hippocampal tight junction proteins, including Occludin, Claudin-5, and zonula occludens-1 (ZO-1). Immunofluorescence was used to assess the co-localization of TH/c-Fos in NTS and LC, as well as TH/norepinephrine (NE) co-localization in LC. (2) Five TH-cre mice received retrograde tracing virus injection into LC to observe whether TH-positive neurons in NTS project to LC. (3) Twenty-one 7-month-old APP/PS1 mice were injected with chemogenetic activation virus (AAV2/9-hSyn-DIO-hM3D-mCherry-WPRE-hGH-pA) or empty virus (AAV2/9-Ef1α - DIO-mCherry-WPRE-hGH-pA) into the NTS, and AAVretro-TH-CRE-WPRE-hGH-pA virus into the LC. After 21 d of virus expression, 6 mice injected with empty virus were taken as mCherry+CNO+EA group;3 mice from the activation virus group were randomly selected for brain slice patch-clamp to verify virus functionality. The remaining mice were randomly divided into 2 groups (n=6):hM3D+CNO+EA, and hM3D+saline+EA groups. EA was applied to PC6 and PC5 once daily for 15 d. After intervention, learning and memory abilities were evaluated by Morris water maze and novel object recognition tests. BBB permeability was detected by Evans blue (EB) staining. Immunofluorescence was used to measure TH/c-Fos and TH/NE co-localization in the LC. (1) Compared with the control group, the model group showed significantly impaired learning and memory abilities (P<0.01), decreased expressions of hippocampal Occludin, Claudin-5, and ZO-1 (P<0.01), and increased TH/c-Fos co-localization (c-Fos expression in TH-positive neurons) in NTS and LC, as well as TH/NE co-localization in LC (P<0.01). Compared with the model group, the EA group exhibited improved learning and memory abilities (P<0.05, P<0.01), increased expressions of hippocampal tight junction proteins (P<0.01), and reduced TH/c-Fos and TH/NE co-localization (P<0.01, P<0.05). (2) Retrograde tracing confirmed that TH-positive neurons in NTS project to LC. (3) Compared with the mCherry+CNO+EA group and hM3D+saline+EA group, the hM3D+CNO+EA group showed significantly impaired learning and memory (P<0.01), increased EB content in brain tissue, and elevated TH/c-Fos and TH/NE co-localization in the LC (P<0.01). EA at PC6 and PC5 can ameliorate BBB damage and learning/memory deficits in AD mice, and its mechanism may be related to inhibiting the activation of the NTSTH-LC neural circuit.

To explore the mechanism of electroacupuncture (EA) at "Zusanli" (ST36) in combination with omeprazole in treating gastrointestinal injury induced by indomethacin in mice. Thirty C57BL/6J mice were randomly divided into normal control, model, omeprazole, EA combined with omeprazole (combination), and combination + nuclear factor E2-related factor 2 (Nrf2) inhibitor (inhibitor) groups, with 6 mice in each group. The gastrointestinal injury mouse model was established by intragastric administration of indomethacin (30 mg/kg). EA was applied to bilateral ST36 for 20 min, a total of 2 times. The omeprazole (10 mg/kg) was given by gavage. Mice in the inhibitor group were intraperitoneally injected with the Nrf2 inhibitor ML385 (30 mg/kg). HE staining was used to observe the morphological changes of the gastrointestinal mucosa. The contents of glutathione (GSH), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in gastric tissue and the activities of SOD and glutathione peroxidase (GSH-Px) in colon tissue were detected by colorimetric method. The level of reactive oxygen species (ROS) in colon tissue was detected by flow cytometry. The mRNA and protein expressions of Nrf2/heme oxygenase-1 (HO-1) signaling pathway-related factors Kelch-like epichlorohydrin-related protein factor 1 (Keap1), Nrf2, HO-1 and NADPH oxidase 1 (NOX1) in colon tissue were detected by qPCR and Western blot, respectively. After modeling and compared with the normal control group, the mice of model group showed severe gastrointestinal mucosal damage, with decreased GSH content and SOD activity in gastric tissue (P<0.01), increased MDA content (P<0.01), elevated ROS levels, and increased Keap1 and NOX1 mRNA and protein expressions in colon tissue (P<0.01), reduced SOD and GSH-Px activities (P<0.01, P<0.05), decreased Nrf2 and HO-1 mRNA and protein levels in colon tissue (P<0.01). Compared with the model group, the gastric mucosal injury was improved, the content of GSH and the activity of SOD in the gastric tissue were increased (P<0.01, P<0.05), while the content of MDA was decreased (P<0.05, P<0.01) in both omeprazole and combination groups. In comparison with the model and the omeprazole groups, the combination group showed improved colonic mucosal injury, decreased ROS level (P<0.01), increased SOD and GSH-Px activities (P<0.05), up-regulated mRNA and protein expressions of Nrf2 and HO-1 (P<0.01), and down-regulated mRNA and protein expressions of Keap1 and NOX1 (P<0.01, P<0.05) in colon tissue. However, the improvement of gastrointestinal oxidative stress of combination treatment was reversed after the injection of Nrf2 inhibitor in the inhibitor group (P<0.01, P<0.05). The integration of acupuncture and medication can effectively ameliorate indomethacin-induced gastrointestinal oxidative stress injury, which may be related to its function in activating the Nrf2/HO-1 signaling pathway.

<bold>ABSTRACT</bold> Objective To explore the effects of electroacupuncture (EA) at ST36 (Zusanli) and BL60 (Kunlun) on improving hyperalgesia and lower-limb motor function of the rat model with lumbar 5 (L5) spinal nerve ligation (SNL), as well as the effects on the microglial cells, BDNF/TrkB signaling pathway activation, and GABAA receptor in model rats’ spinal cord dorsal horn. Design Animal experimental study. Setting Laboratory Animal Research Center, Zhejiang Chinese Medical University. Interventions A total of 56 Sprague–Dawley rats were randomly assigned to the sham SNL group, the SNL group, the SNL plus EA group, and the SNL plus sham EA group (each group n = 14). The lumbar 5 (L5) spinal nerve in the sham SNL group was only exposed for 2–3 min and not ligated. The SNL plus EA group received EA treatment once daily from postoperative day 7 for 7 consecutive days. Acupuncture needles were inserted superficially at the same acupoints to a depth of 0.5 mm, but no electrical stimulation was applied in the SNL plus sham EA group. Outcome Measures The motor and sensory functions of each group were assessed using the MWT (mechanical withdrawal threshold), TWL (thermal withdrawal latency), lower-limb motor function score and balance beam test. The concentration variation of Iba-1, BDNF, TrkB, and GABAA α2 in the rat spinal cord was identified using Western blot and quantitative real-time PCR. Results After 7 days of intervention, the pain threshold of the SNL plus EA group significantly increased compared with the SNL group, accompanied by lower motor dysfunction scores. Moreover, the SNL plus EA group had significantly reduced Iba-1, BDNF, and TrkB while elevated GABAA α2 protein expression versus the SNL group (P < 0.05). Likewise, the mRNA expression of Iba-1, BDNF, and TrkB was decreased while GABAA α2 mRNA expression was increased in the SNL plus EA group versus the SNL group (P < 0.05). Conclusions EA at ST36 and BL60 can improve the neuropathic pain rat model's hyperalgesia and lower-limb motor function. The analgesic effects were achieved by increasing the GABAA α2 receptor expression in the spinal cord of NP rats and promoting GABA's suppression of pain signal transmission via inhibiting the microglia activation and the BDNF/TrkB signaling pathway.

ObjectiveThis study investigated whether electroacupuncture (EA) at Neiguan (PC6) acupoint alleviates adverse myocardial remodeling in post–myocardial infarction (MI) heart failure (HF) by activating the vagus nerve–mediated cholinergic pathway and its downstream α7nAChR‐Akt‐HIF‐1α‐VEGF signaling cascade.MethodsMale Sprague Dawley (SD) rats were randomized into sham, MI model, and EA groups (n = 6 per group). MI was induced by ligation of the left anterior descending coronary artery. EA was applied at PC6 for 14 days starting 1 week after MI induction. Cardiac function and structure were evaluated using echocardiography and histological examination. The expression levels of choline acetyltransferase (ChAT), α7‐nicotinic acetylcholine receptor (α7nAChR), phosphorylated Akt (p‐Akt), hypoxia‐inducible factor‐1α (HIF‐1α), and vascular endothelial growth factor (VEGF) were analyzed by real‐time quantitative PCR, Western blotting, and immunohistochemistry.ResultsEA intervention significantly attenuated pathological myocardial remodeling and improved cardiac function. Compared with the model group, EA treatment markedly enhanced cardiac function, increased contractility, reduced ventricular dilation, restored autonomic balance, and alleviated myocardial necrosis and fibrosis. Molecular studies revealed that EA treatment increased the expression of ChAT and α7nAChR, elevated p‐Akt levels, and upregulated the expression of HIF‐1α and VEGF. These findings suggest the activation of the vagus nerve–cholinergic signaling pathway and its downstream prosurvival and pro‐angiogenic pathways.ConclusionsEA attenuated maladaptive ventricular remodeling and improved cardiac performance. These effects were associated with modulation of autonomic function and engagement of the α7nAChR/Akt/HIF‐1α/VEGF signaling axis, supporting a potential neuro‐immune‐angiogenic mechanism underlying EA‐mediated myocardial repair during the subacute post‐MI phase.

ABSTRACTPremature ovarian insufficiency (POI) is a major cause of infertility in young women. In this study, we investigated the therapeutic effects of electroacupuncture (EA) on ovarian function and granulosa cell autophagy in a high‐fat, high‐sugar (HFHS) diet–induced POI mouse model. POI was established by HFHS feeding, and mice received EA stimulation at CV4, ST36, and SP6. Ovarian morphology was evaluated using hematoxylin and eosin (HE), Masson's trichrome, and Sirius Red staining. Estrous cycles were monitored by crystal violet staining, and serum sex hormones and inflammatory cytokines were measured by ELISA. Cholesterol accumulation, apoptosis, and FSHR expression were assessed using filipin staining, TUNEL assays, and immunofluorescence, respectively. Single‐cell RNA sequencing was performed to characterize ovarian cell subpopulations and autophagy‐related transcriptional signatures. Autophagosome formation and the expression of autophagy‐related markers (Beclin1, LC3, and P62), as well as METTL3, were analyzed by transmission electron microscopy (TEM), RT‐qPCR, Western blotting, and immunohistochemistry. m6A modification levels on Beclin1 mRNA were determined using LC–MS, colorimetric assays, and RIP‐qPCR. The results demonstrated that EA significantly improved follicular development, normalized estrous cycles, reduced granulosa cell apoptosis, and decreased inflammatory cytokine levels in POI mice. Single‐cell analysis revealed that granulosa cells exhibited the highest autophagy activity and were strongly associated with senescence‐related pathways. EA markedly reduced autophagosome formation, downregulated Beclin1 and LC3 expression, and upregulated P62, indicating suppression of excessive autophagy. Furthermore, EA decreased METTL3 expression and reduced m6A modification of Beclin1 mRNA, thereby limiting Beclin1 translation. Collectively, these findings suggest that EA ameliorates HFHS‐induced POI by inhibiting METTL3‐mediated m6A methylation of Beclin1 mRNA, suppressing excessive granulosa cell autophagy, and restoring ovarian function, thereby revealing a potential epigenetic mechanism underlying the therapeutic effects of EA in diet‐related ovarian dysfunction.

To investigate the protective effects of sera from rats receiving electroacupuncture (EA) against oxygen and glucose deprivation/reoxygenation (OGD/R) injury in HT22 neurons and explore the involvement of the PI3K/Akt signaling pathway in this protective mechanism. Bioinformatics analysis was performed using public databases to identify stroke-related pathways. A rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) were treated with EA at "Shenting" and "Baihui" to prepare EA rat serum. HT22 neurons were subjected to OGD/R and treated with MCAO rat serum, EA rat serum, LY294002, or EA rat serum combined with LY294002. The changes in cell viability, apoptosis, and neuronal morphology were assessed using CCK-8 assay, TUNEL staining, and Nissl staining. Western blotting was used to detect PI3K/Akt phosphorylation and the expressions of the downstream proteins (p-mTOR/mTOR and Bcl-2) and synaptic proteins (NMDAR1 and PSD-95); the mRNA expressions of PI3K, Akt, NMDAR1, and PSD-95 were detected using RT-qPCR. HT22 neurons with OGD/R injury treated with MCAO rat serum showed significantly decreased cell viability, increased apoptosis, and impaired neuronal morphology, which were obviously improved following treatment with EA rat serum but aggravated after LY294002 treatment. The protective effect of EA rat serum was significantly attenuated by application of LY294002. HT22 neurons treated with MCAO rat serum showed decreased p-PI3K/PI3K, p-Akt/Akt, and p-mTOR/mTOR ratios with lowered expressions of Bcl-2, NMDAR1 and PSD-95, which were obviously upregulated by EA rat serum treatment but reduced after LY294002 treatment. The cells with the combined treatment showed intermediate expression levels of these molecules at both the mRNA and protein levels. Serum from rats receiving EA at "Shenting" and "Baihui" shows a protective effect against OGD/R injury in HT22 neurons, mediated possibly by activation of the PI3K/Akt signaling pathway and its downstream effectors and upregulation of synaptic plasticity-related molecules.

Electroacupuncture at Jiaji points regulates splenic immunity and gut microbiota to ameliorate peripheral immune dysfunction after spinal cord injury.

The effect of pain catastrophizing on acupuncture treatment for chronic pain in cancer survivors.

Electroacupuncture (EA) has been documented to exert therapeutic benefits in vascular dementia (VD). This study seeks to elucidate the therapeutic efficacy and underlying molecular mechanisms of EA in VD. A VD model was induced in rats, which received EA with or without an Shh pathway inhibitor. An in vitro VD model was generated by exposing BV2 microglial cells to oxygen-glucose deprivation (OGD). A battery of tests was employed: cognitive function (novel object recognition and morris water maze), histopathology (H&E and TUNEL staining), synaptic ultrastructure (transmission electron microscope), microglial activation/polarization (immunofluorescence), inflammatory cytokine secretion (ELISA), protein expression (immunoblotting), and cellular viability (CCK-8). VD model rats exhibited attenuated Shh signaling in brain tissues, which was effectively restored by EA treatment in a duration-dependent manner. EA intervention observably improved cognitive performance, mitigated neuronal damage, enhanced synaptic plasticity, suppressed pro-inflammatory responses, and promoted microglial M2 polarization. These therapeutic effects were abolished by the Shh pathway inhibitor cyclopamine. Furthermore, Shh overexpression in microglia attenuated OGD-induced pro-inflammatory activation and reduced its detrimental impact on neuronal cells. Collectively, these data indicate that the cognitive benefits of EA in VD are critically dependent on Shh-driven reprogramming of microglial responses, which in turn resolves neuroinflammation and mitigates neuronal injury, thereby informing future therapeutic strategies.

The spinoparabrachial tract is a major ascending pathway that transmits nociceptive signals from the spinal cord to the brain, but whether electroacupuncture (EA) relieves pain-anxiety comorbidity by modulating this pathway remains unclear. Here, we investigated the effects of EA on mechanical allodynia and anxiety-like behaviors in Complete Freund's adjuvant (CFA)-induced inflammatory pain mice using von Frey testing, the open field test, and the elevated plus maze, combined with chemogenetic manipulation of glutamatergic projections from the spinal dorsal horn (SDH) to the lateral parabrachial nucleus (LPBN). EA attenuated CFA-induced mechanical allodynia and anxiety-like behaviors and reduced c-Fos expression in both the SDH and LPBN. Chemogenetic inhibition of LPBN glutamatergic neurons mimicked the analgesic and anxiolytic effects of EA, whereas their activation abolished these effects. Activation of either ipsilateral or contralateral SDH→LPBN glutamatergic projections induced pain- and anxiety-like phenotypes that depended on intact LPBN glutamatergic output. Moreover, selective activation of spinoparabrachial glutamatergic terminals was sufficient to block the therapeutic efficacy of EA. These findings indicate that EA alleviates CFA-induced pain-anxiety comorbidity by inhibiting the SDH-LPBN glutamatergic circuit, identifying a key ascending pathway through which peripheral EA signals modulate central pain and affective processing.

To investigate the mechanism of electroacupuncture (EA) for attenuating visceral hypersensitivity in rats with post-inflammatory irritable bowel syndrome (PI-IBS) using transcriptome sequencing technology. Of 40 SPF grade male Wistar rats, 12 rats were randomly selected as the control group. Enema of 2,4,6-trinitrobenzenesulfonic acid solution (TNBS) was adopted to prepare PI-IBS models among the remaining 28 rats. The successfully-modeled 24 rats were randomized into a model group and an EA group, 12 rats in each one. In the EA group, EA was delivered at bilateral"Tianshu" (ST25) and "Dachangshu" (BL25), with disperse-dense wave, at a frequency of 2 Hz/100 Hz and an electric current of 1 mA, for 20 min, once daily, and EA intervention was composed of 10 days. Visceral sensitivity was detected by the abdominal withdrawal reflex (AWR) method, and the area under the curve (AUC) of rectus abdominis electromyography(EMG) was measured under different pressures of colonic dilation. HE staining was used to observe colonic mucosal morphology and pathological score was calculated; transcriptome sequencing was applied to detect differentially expressed genes (DEGs) in the colon; and real-time fluorescent quantitative PCR was used to detect the mRNA expression of DEGs. Compared with the control group, AWR scores and AUC under each pressure increased in the model group (P<0.001, P<0.01). Compared with the model group, EA group showed the decrease in AWR scores and AUC under each pressure (P<0.001, P<0.01). The model group exhibited the damaged colonic mucosal integrity, accompanied by mild congestion, edema, and a small amount of inflammatory cell infiltration, while the EA group showed the alleviation in colonic mucosal lesions. Regarding DEGs, there were 141 reversed genes in the EA group. When compared with the control group,DEGs in the model group were mainly enriched in cytokine-cytokine receptor interaction, chemokine signaling pathway and P53 signaling pathway, etc. DEGs in the EA group were mainly enriched in peroxisome proliferator-activated receptor signaling pathway, biosynthesis of amino acid, and P53 signaling pathway in comparison with the model group. The top 5 core DEGs reversed by EA were CXC chemokine ligand 10 (CXCL10), chemokine ligand 20 (CCL20), CXC chemokine receptor 4(CXCR4), chemokine ligand 21 (CCL21), and CXC chemokine receptor 5 (CXCR5). Compared with the control group, the mRNA expression of CXCL10 and CCL20 of the colon was elevated (P<0.001 ), and that of CXCR4 reduced (P<0.01) in the model group. When compared with the model group, EA group showed the decrease in the mRNA expression of CXCL10 and CCL20 of the colon (P<0.01, P<0.001), and the increase in that of CXCR4 (P<0.001). Electroacupuncture at "Tianshu" (ST25) and "Dachangshu" (BL25) can attenuate visceral hypersensitivity in PI-IBS rats, probably by regulating the expression of genes such as CXCL10, CCL20, CXCR4.

To observe the effects of electroacupuncture (EA) on sleep quality, cognitive function, sleep process and structure, as well as cerebral hemodynamics in elderly patients with maintenance hemodialysis (MHD). Sixty elderly MHD patients were randomized into an EA group (30 cases) and a sham acupuncture group (30 cases). EA was applied at Sishencong (EX-HN1) in the EA group, with continuous wave, in frequency of 2 Hz and in current of 1 mA. Sham acupuncture was applied at distal non-meridian and non-acupoint points in the sham acupuncture group, same EA parameters were given, and the electrical stimulation was stopped after 30 seconds. Both groups were intervened for 30 min per session, once daily, 5 days per week, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), insomnia severity index (ISI), Montreal cognitive assessment-basic (MoCA-B), mini-mental state examination (MMSE) were observed, and the incidence of sleep disorders was calculated based on PSQI score; the indexes of sleep process (sleep onset latency [SOL], total sleep time [TST], sleep efficiency [SE]) and sleep structure (percentages of stage 1 sleep [N1], stage 2 sleep [N2], stage 3 sleep [N3] and rapid eye movement sleep [REM] in TST) were observed by polysomnography system; and the cerebral hemodynamic indexes (mean blood flow velocity [Vm] of middle artery, regional cerebral blood flow [rCBF] and regional cerebral blood volume [rCBV]) were detected by transcranial Doppler ultrasound in the two groups. After treatment, the PSQI score, incidence of sleep disorders and ISI score in the EA group were decreased (P<0.05), while the scores of MoCA-B and MMSE were increased compared with those before treatment (P<0.05); in the EA group, the PSQI score, incidence of sleep disorders and ISI score were lower, while the scores of MoCA-B and MMSE were higher than those in the sham acupuncture group (P<0.001). Compared before treatment, SOL was shortened, TST was prolonged, the percentage of N1 in TST was decreased, the percentages of N2, N3 and REM in TST were increased, and SE was improved in the EA group after treatment (P<0.05); after treatment, all indexes of sleep process and structure in the EA group were superior to those in the sham acupuncture group (P<0.001, P<0.01). After treatment, the Vm of middle artery, rCBF and rCBV in the EA group were increased compared with those before treatment (P<0.05); the Vm of middle artery, rCBF and rCBV in the EA group were higher than those in the sham acupuncture group (P<0.001). EA can regulate sleep process and structure, and improve sleep quality and cognitive function in elderly MHD patients, which may be related to the improvement of cerebral hemodynamics.

To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on amyotrophic lateral sclerosis (ALS) in mouse models based on myeloid cell trigger receptor 2 (TREM2)-mediated microglial activation. Thirty-six SPF-grade male human mutant superoxide dismutase 1 (SOD1-G93A) transgenic mice were divided into a model group, an EA group, and a drug group, 12 mice in each group. Besides, 12 wide-type littermates were collected as a control group. In the EA group, EA was performed at the "Zusanli" (ST36), with an intermittent wave, at the frequency of 15 Hz, and for 10 min each intervention; once every other day, 3 interventions a week and for 4 continuous weeks. In the drug group, the intragastric administration of riluzole solution was given at 8 mg/kg, once daily, for 4 continuous weeks. After intervention completion, behavioral assessment of mice was conducted using rotarod test and wire hang test. With HE and Nissl staining adopted, morphology of motor neurons in the anterior horn of the spinal cord was observed. Immunofluorescence was used to detect the fluorescence intensity of TREM2 in the anterior horn of spinal cord. Western blot analysis was performed to measure the protein expression of interleukin (IL)-1β, γ interferon (IFN-γ), IL-4 and IL-10 in spinal cord tissue. Flow cytometry was used to analyze the proportion of CD86+ and CD206+ in spinal cord monocyte suspension. Compared with the control group, in the model group, motor neurons in the anterior horn of the spinal cord exhibited disordered arrangement; accompanied by nuclear pyknosis and cytoplasmic shrinkage; the latency to fall in the rotarod test and the cut-off time in the wire hang test were shortened, fluorescence intensity of TREM2 in the spinal anterior horn, the protein expression of IL-1β, IFN-γ, IL-4, and IL-10, and the proportion of CD86+ and CD206+ in spinal cord tissue increased(P<0.01). When compared with the model group, in the EA and drug groups, motor neurons in the anterior horn of the spinal cord were arranged regularly; nuclear pyknosis and chromatolysis were attenuated, and the structural integrity of neurons was improved; the latency to fall and the the cut-off time were prolonged, fluorescence intensity of TREM2 in the spinal anterior horn was reduced, the protein expression of IL-1β and IFN-γ decreased, and that of IL-4, and IL-10 increased in the spinal cord tissue; the proportion of CD86+ in spinal cord tissue was reduced and that of CD206+ elevated(P<0.01, P<0.05). Compared with the drug group, the EA group showed the increase of protein expression of IL-1β,and the decrease of IL-4, IL-10 in the spinal cord tissue and the proportion of CD206+ (P<0.05). Electroacupuncture at "Zusanli" (ST36) exhibits a certain improvements in motor function of SOD1-G93A transgenic mice. The underlying mechanism may be related to attenuating neuroinflammation via the modulation of microglial activation mediated by TREM2.

ABSTRACTAimsThis study aimed to elucidate the potential mechanism, especially neural circuit mechanisms, through which electroacupuncture (EA) mitigates cognitive decline in a rat model of vascular cognitive impairment (VCI).MethodsUsing a rat two‐vessel occlusion (2VO) model, we assessed the therapeutic impact of EA on spatial and non‐spatial memory. We integrated in vivo fiber photometry and immunofluorescence to monitor neuronal activities in the dentate gyrus (DG) and supramammillary nucleus (SuM), while Golgi staining was employed to evaluate hippocampal synaptic plasticity. Viral tracing and chemogenetic manipulations were utilized to characterize the functional necessity of the SuMGlu‐DG circuit.ResultsEA at ST36 significantly restored learning and memory function. This functional recovery was accompanied by improved synaptic plasticity and heightened neuronal activity in the DG. Fiber photometry revealed that EA specifically activated glutamatergic neurons in the SuM, a key upstream regulator of the DG. Notably, targeted chemogenetic inhibition of the SuMGlu‐DG circuit abolished the cognitive improvements typically induced by EA.ConclusionOur findings demonstrate that EA ameliorates learning and memory deficits in VCI through regulating the SuMGlu‐DG circuit.

ABSTRACTBackgroundImbalances between excitatory and inhibitory signals have been implicated in the pathophysiology of schizophrenia. Electroacupuncture (EA) is commonly used in clinical practice to address neuropsychiatric conditions. However, the exact therapeutic mechanisms underlying EA's effects on schizophrenia remain poorly understood.MethodsWe employed Erbb4‐nNos−/− mice, which model the genetic deficits observed in schizophrenia, as a model system for our study. The locomotor activity, social behavior, sensorimotor gating ability, working memory, spatial learning and memory, and motor skills and coordination of mice were assessed using the open‐field test, three‐chamber social interaction test, prepulse inhibition (PPI) test, Y‐maze, Morris water maze, and rotarod tests. Whole‐cell patch‐clamp recordings were performed to detect excitatory and inhibitory synaptic transmission and the intrinsic excitability of pyramidal neurons.ResultsEA alleviated behavioral deficits associated with schizophrenia in these mice. Notably, EA also enhanced GABAergic transmission and decreased the excitability of pyramidal neurons. Simultaneously, the selective nNOS inhibitor L‐NPA blocked the therapeutic effects of EA on behavioral deficits and synaptic transmission.ConclusionsEA improved schizophrenia‐like behavioral impairments and restored the balance between excitatory and inhibitory signaling, possibly through the upregulation of presynaptic GABA release. Furthermore, nitric oxide (NO) signaling may play a critical role in the observed benefits. These findings underscore the significance of excitatory–inhibitory (E/I) balance in mediating the therapeutic effects of EA, highlighting its potential as an intervention strategy for schizophrenia.

Myocardial ischemia (MI) remains a major clinical challenge, and the therapeutic potential of electroacupuncture (EA) is constrained in practice by repeated needle insertion, poor repeatability of acupoint localization, and limited long-term patient compliance. To overcome these barriers, we developed a minimally invasive implantable electroacupuncture (IEA) system based on carbon nanotube fiber (CNTF) electrodes via a minimally invasive, ultrasound-guided procedure to establish a "single-implantation, long-term stimulation" strategy, delivering both sustained mild stimulation and conventional electroacupuncture at the Neiguan (PC6) acupoint. Results demonstrated that CNTFs with a diameter of 20-30 μm, a conductivity of (2.64 ± 0.95) × 10⁵ S/m, a charge storage capacity of 13.09 ± 2.79 mC/cm², and an impedance of 133.48 ± 69.88 Ω at 1 kHz represented the balanced trade-off for performance. Within the 14-day observation period, CNTF implantation at PC6 did not induce obvious local inflammatory infiltration or pathological tissue alterations. In a rat model of isoproterenol-induced MI, the IEA system markedly improved cardiac electrophysiology attenuated cardiac remodeling and reduced serum cTnT levels demonstrating superior therapeutic effects compared with conventional EA. Kinetic analysis of electrophysiological data revealed that daily IEA facilitated faster effect accumulation and consolidation, favoring acute- or subacute-phase management, whereas alternate-day IEA achieved a higher therapeutic ceiling, suggesting its superiority for maximizing long-term functional recovery. These results provided a rationale for session-frequency-personalized therapy. Furthermore, the cardioprotective effect was mediated through the downregulation of the FXR/SHP apoptotic pathway, validated by pharmacological inhibition. This work established a safe, effective, and stable platform that merged advanced bioelectronic materials with traditional acupuncture theory, providing a promising translational solution for the chronic, home-based rehabilitation of heart disease or other diseases, particular for elderly, paralyzed, or those with limited mobility and access to clinical care.

Electroacupuncture alleviates spinal cord injury by regulating M2-like polarization of myeloid cells through CMPK2/NLRP3 inflammasome inhibition.