Electroacupuncture-modulated extracellular ATP levels in prefrontal cortex ameliorated depressive-like behavior of maternal separation rats.

Maternal separation (MS) is a type of early-life stress that has been linked to neuropsychiatric disorders, especially depression. Increasing evidence indicates that the adenosine triphosphate (ATP) level in the prefrontal cortex (PFC) is involved in the pathophysiology of depression. To investigate the potential relationship between ATP in PFC and antidepressant effects of electroacupuncture (EA) treatment, we assessed genes involved in ATP biosynthesis as well as the extracellular ATP levels in a rat model exposed to neonatal MS. Our results demonstrated that reduced expression of ABCG2 (an ATP-binding cassette protein) and ATP levels in the PFC of depressive-like rats exposed to MS can be attenuated by EA stimulus at the Baihui (GV20) and Yintang (GV29) acupoints. Moreover, the antidepressant effect of EA treatment was blocked by administration of suramin, a broad purinergic P2 receptor antagonist. Together, these results suggested that electroacupuncture may be able to modulate extracellular ATP levels in the PFC of depressive-like MS rats, potentially contributing to its antidepressant effects.

[Current situation and outlook of acupuncture-moxibustion translational medicine under the background of multi-disciplinary intersection innovation].

The common development of multi-disciplinary intersection is a hot spot in the research of acupuncture- moxibustion translational medicine. This article analyzes the current situation and reasons for slow development of acupuncture-moxibustion translational medicine, takes acupuncture-moxibustion for depressive disorder as an example, takes acupuncture and moxibustion literature, clinical evidence-based, biological mechanism and medical equipment research and development as the main line, expounds potential strategies to promote the development of acupuncture-moxibustion translational medicine under the background of multi-disciplinary intersection innovation, and discusses the future research direction of acupuncture-moxibustion translational medicine.

Restoring the Autonomic Balance in an Atrial Fibrillation Rat Model by Electroacupuncture at the Neiguan Point.

OBJECTIVES: Autonomic nervous activity imbalance plays an important role in atrial fibrillation (AF). AF can be treated by acupuncture at the Neiguan point (PC6), but the mechanism remains elusive. Here, we investigated autonomic nervous system activity in electroacupuncture (EA) at PC6 in a rat AF model. MATERIAL AND METHODS: In this study, we established a rat AF model via tail vein injection with ACh-CaCl2 for ten consecutive days with or without EA at PC6. AF inducibility and heart rate variability (HRV) were assessed by electrocardiogram. Next, we completed in vivo recording of the activity of cervical sympathetic and vagal nerves, respectively. Finally, the activities of brain regions related to autonomic nerve regulation were assessed by c-Fos immunofluorescence and multichannel recording. RESULTS: EA at PC6 decreased AF inducibility and prevented changes in HRV caused by ACh-CaCl2 injection. Meanwhile, EA at PC6 reversed the increased sympathetic and decreased vagal nerve activity in AF rats. Furthermore, EA treatment downregulated increased c-Fos expression in brain regions, including paraventricular nucleus, rostral ventrolateral medulla, and dorsal motor nucleus of the vagus in AF, while c-Fos expression in nucleus ambiguus was upregulated with EA. CONCLUSION: The protective effect of EA at PC6 on AF is associated with balance between sympathetic and vagal nerve activities.

Investigating the efficiency and tolerability of traditional Chinese formulas combined with antiarrhythmic agents for paroxysmal atrial fibrillation: A systematic review and Bayesian network meta-analysis.

BACKGROUND: The combination of antiarrhythmic drugs with traditional Chinese formulas are used treatments for the management of paroxysmal atrial fibrillation (PAF). However, the most effective treatment for PAF has yet to be been determined. A Bayesian network meta-analysis study was thus performed for comparing the relative efficacy and tolerability of different treatment alternatives. METHODS: A comprehensive literature review of randomized controlled trials (RCTs) is performed from eight database. Maintenance rate of sinus rhythm (MRSR), p-wave dispersion (Pd), left atrium diameter (LAD), left ventricular ejection fraction (LVEF), and adverse events (AEs) were used as outcomes. We also estimated treatment rank based on the surface under the cumulative ranking curve (SUCRA). This study was performed using a Bayesian network meta-analysis with a random-effects model. FINDINGS: After screening, 59 RCTs involving 5,543 patients and 16 treatments were included. The results showed that Shensong-Yangxin capsule (SSYX) plus amiodarone (81%) was the most effective treatment for MRSR according to the value of SUCRA, followed by Wenxin-Keli granules (WXKL) plus amiodarone (73%). Meanwhile, SSYX plus amiodarone (7%) was most likely to reduce Pd, followed by SSYX plus metoprolol (23%), WXKL plus amiodarone (26%), WXKL plus bisoprolol (27%). Furthermore, SSYX plus amiodarone (4%) was more effective in improving LAD. WXKL plus amiodarone was preferred because it had the lowest toxicity. For benefit-risk ratio, amiodarone combined with WXKL or SSYX appeared to be the best option. CONCLUSION: Antiarrhythmic agents combined with traditional Chinese formulas had higher efficacy and lower toxicity than other treatment alternatives. This study might provide reference to help find the better treatment options for PAF.

Microbial Profiles of Patients With Antipsychotic-Related Constipation Treated With Electroacupuncture.

Antipsychotic-related constipation (APRC) is one of the most common side effects of taking antipsychotic medication. APRC can seriously impact patient quality of life and is potentially fatal, though the efficacy of current APRC treatments is low for most patients. In this study, we conducted a controlled, pilot randomized, sham-electroacupuncture (SEA) study to assess the efficacy of electroacupuncture (EA) in patients with APRC. We used 16S rRNA gene sequencing to assess the microbial profiles of these patients and analyze how EA treatments affected their bacteria. Methods: We treated 133 APRC patients with randomly assigned EA treatments or SEA treatments for 4 consecutive weeks, fully evaluating the patients 8 weeks after treatment. The participants, outcome assessors, and statistics were all blind to the EA and SEA treatments. Outcomes assessed included changes in spontaneous bowel movements (SBMs) and the frequency of rescue measures. We detected assessed the microbial diversity of stool specimens both before and after EA treatment using 16S rRNA gene sequencing. Results: Both EA and SEA treatments reduced the need for constipation rescue measures and did not have serious side effects. EA treatments were better than SEA treatments at increasing SBMs and reducing rescue measures. The diversity of gut microbiota changed after EA treatment. LEfSe analysis indicated changes in the genus (belonging to phylum Proteobacteria) of gut microbiota in patients following EA treatment. Conclusions: This study found that EA treatment is effective and safe for patients with APRC, and could be associated with changes in their microbial profiles. Further study, with larger sample sizes, is needed to explore the efficacy of EA intervention as a clinical treatment for APRC. Trial Registration: ChiCTR, ChiCTR-ONC-17010842, http://www.chictr.org.cn/showproj.aspx?proj=18420.

Comparative Efficacy of Multiple Therapies for the Treatment of Patients With Subthreshold Depression: A Systematic Review and Network Meta-Analysis.

Background: Subthreshold depression (SD) is considered to be the precursor stage of major depression, which is correlated with functional impairment and increased suicide rate. Although there are multiple therapies for the treatment of SD, the comparison and efficacy of various methods has yet to be evaluated. This study aimed to evaluate the efficacy of different therapies by performing a Bayesian network meta-analysis. Methods: We searched eight databases on April 3, 2021. Center for Epidemiologic Studies Depression Scale (CES-D), Beck Depression Inventory scale (BDI), the Patient Health Questionnaire-9 (PHQ-9), and the Kessler Screening Scale for Psychological Distress (K-6) were used as efficacy outcomes. This Bayesian network meta-analysis used a fixed-effects model. Findings: Twenty-one randomized controlled trials involving 5,048 participants were included in this study. The results suggested that electroacupuncture (MD -12.00, 95% CrI -15.00, -10.00), conventional acupuncture plus wheat-grain moxibustion (MD -9.70, 95% CrI -14.00, -5.30), and the Chinese traditional peripateticism pill plus group counseling (MD -9.00, 95% CrI -11.00, -6.70) had better efficacy than the control group (CG) in improving CES-D. For BDI outcome, bright light therapy (MD -9.70, 95% CrI -13.00, -6.00), behavioral activation program (MD -5.70, 95% CrI -6.10, -5.40), and dim light therapy (MD -6.30, 95% CrI -10.00, -2.20) were better than the CG. Tai chi (MD -3.00, 95% CrI -4.00, -2.00) was better than CG for PHQ-9 outcomes. Telephone-based cognitive behavioral treatment (MD -2.50 95% CrI -2.70, -2.30) was better than the CG for K-6 scores. Conclusion: Our results suggest that electroacupuncture or bright light therapy appear to be the better choices in the treatment of SD. This study provide new insights into clinical treatment selection and may aid the development of guidelines for the management of SD.

Neuregulin1-ErbB4 Signaling in Spinal Cord Participates in Electroacupuncture Analgesia in Inflammatory Pain.

Chronic inflammatory pain is a severe clinical symptom that aggravates the life quality of patients and places a huge economic burden on individuals and society. As one complementary and alternative therapy, electroacupuncture (EA) is widely used in clinical practice to treat chronic inflammatory pain based on its safety and efficacy. Previous studies have revealed the potential role of adenosine, neuropeptides, and inflammatory factors in EA analgesia in various pain models, but the identity of some of the signaling pathways involved remain unknown. In the present study, we explored whether neuregulin1 (NRG1)-ErbB4 signaling is involved in EA analgesia in inflammatory pain. Repeated EA treatment at the acupoints Zusanli (ST36) and Sanyinjiao (SP6) for 3 consecutive days remarkably attenuated mechanical allodynia and thermal hyperalgesia in complete Freund's adjuvant (CFA)-treated mice, with an increased expression of NRG1 in spinal cord (SC). We found that ErbB4 kinase participated in both the EA and NRG1 mediated analgesic effects on inflammatory pain by pharmacological inhibition or genetic ablation ErbB4 in vivo. Intriguingly, the mice with conditional knockout of ErbB4 from PV+ interneurons in SC showed abnormal basal mechanical threshold. Meanwhile, NRG1 treatment could not relieve tactile allodynia in PV-Erbb4-/- mice or AAV-PV-Erbb4-/- mice after CFA injection. These experimental results suggest that regulating NRG1-ErbB4 signaling in SC could reduce pain hypersensitivity and contribute to EA analgesia in inflammatory pain.

HuangqiGuizhiWuwu Decoction Prevents Vascular Dysfunction in Diabetes via Inhibition of Endothelial Arginase 1.

Hyperglycemia induces vascular endothelial dysfunction, which contributes to the development of vascular complication of diabetes. A classic prescription of traditional medicine, HuangqiGuizhiWuwu Decoction (HGWWD) has been used for the treatment of various cardiovascular and cerebrovascular diseases, which all are related with vascular pathology. The present study investigated the effect of HGWWD treatment in streptozocin (STZ)-induced vascular dysfunction in mouse models. In vivo studies were performed using wild type mice as well as arginase 1 knockout specific in endothelial cells (EC-A1-/-) of control mice, diabetes mice and diabetes mice treated with HGWWD (60 g crude drugs/kg/d) for 2 weeks. For in vitro studies, aortic tissues were treated with mice serum containing HGWWD with or without adenoviral arginase 1 (Ad-A1) transduction in high glucose (HG) medium. We found that HGWWD treatment restored STZ-induced impaired mean velocity and pulsatility index of mouse left femoral arteries, aortic pulse wave velocity and vascular endothelial relaxation accompanied by elevated NO production in the aorta and plasma, as well as reduced endothelial arginase activity and aortic arginase 1 expression. The protective effect of HGWWD is reversed by an inhibitor of nitric oxide synthesis. Meanwhile, the preventive effect of serum containing HGWWD in endothelial vascular dysfunction is completely blocked by Ad-A1 transduction in HG incubated aortas. HGWWD treatment further improved endothelial vascular dysfunction in STZ induced EC-A1-/- mice. This study demonstrates that HGWWD improved STZ-induced vascular dysfunction through arginase 1 - NO signaling, specifically targeting endothelial arginase 1.

Transcriptome Analysis on Maternal Separation Rats With Depression-Related Manifestations Ameliorated by Electroacupuncture.

Maternal separation (MS), a stressful event in early life, has been linked to neuropsychiatric disorders later in life, especially depression. In this study we investigated whether treatment with electroacupuncture (EA) could ameliorate depression-related manifestations in adult animals that had adverse early life experiences. We demonstrated depression-like behavior deficiencies in a sucrose preference test and a forced swimming test in a rat model with neonatal MS. Repeated EA treatment at the acupoints Baihui (GV20) and Yintang (GV29) during adulthood was shown to be remarkably attenuated above behavioral deficits. Using unbiased genome-wide RNA sequencing to investigate alterations in the transcriptome of the prefrontal cortex (PFC), we explored the altered gene sets involved in circadian rhythm and neurotransmitter transporter activity in MS rats, and their expression tended to be reversed after EA treatment. In addition, we analyzed the interaction network of differentiated lncRNA- or circRNA-miRNA-mRNA by using the principle of competitive endogenous RNA (ceRNA). These results suggest that EA at GV20 and GV29 ameliorates depression-related manifestations by regulating the expression of multiple genes.