Modulation of visceral pain by brain nuclei and brain circuits and the role of acupuncture: a narrative review.

Visceral pain is a complex and heterogeneous pain condition that is often associated with pain-related negative emotional states, including anxiety and depression, and can exert serious effects on a patient's physical and mental health. According to modeling stimulation protocols, the current animal models of visceral pain mainly include the mechanical dilatation model, the ischemic model, and the inflammatory model. Acupuncture can exert analgesic effects by integrating and interacting input signals from acupuncture points and the sites of pain in the central nervous system. The brain nuclei involved in regulating visceral pain mainly include the nucleus of the solitary tract, parabrachial nucleus (PBN), locus coeruleus (LC), rostral ventromedial medulla (RVM), anterior cingulate cortex (ACC), paraventricular nucleus (PVN), and the amygdala. The neural circuits involved are PBN-amygdala, LC-RVM, amygdala-insula, ACC-amygdala, claustrum-ACC, bed nucleus of the stria terminalis-PVN and the PVN-ventral lateral septum circuit. Signals generated by acupuncture can modulate the central structures and interconnected neural circuits of multiple brain regions, including the medulla oblongata, cerebral cortex, thalamus, and hypothalamus. This analgesic process also involves the participation of various neurotransmitters and/or receptors, such as 5-hydroxytryptamine, glutamate, and enkephalin. In addition, acupuncture can regulate visceral pain by influencing functional connections between different brain regions and regulating glucose metabolism. However, there are still some limitations in the research efforts focusing on the specific brain mechanisms associated with the effects of acupuncture on the alleviation of visceral pain. Further animal experiments and clinical studies are now needed to improve our understanding of this area.

Corrigendum: Circulating exosomal microRNA profiles in migraine patients receiving acupuncture treatment: a placebo-controlled clinical trial.

[This corrects the article DOI: 10.3389/fnmol.2022.1098766.].

Traditional Chinese medicine in treating ischemic stroke by modulating mitochondria: A comprehensive overview of experimental studies.

Ischemic stroke has been a prominent focus of scientific investigation owing to its high prevalence, complex pathogenesis, and difficulties in treatment. Mitochondria play an important role in cellular energy homeostasis and are involved in neuronal death following ischemic stroke. Hence, maintaining mitochondrial function is critical for neuronal survival and neurological improvement in ischemic stroke, and mitochondria are key therapeutic targets in cerebral stroke research. With the benefits of high efficacy, low cost, and high safety, traditional Chinese medicine (TCM) has great advantages in preventing and treating ischemic stroke. Accumulating studies have explored the effect of TCM in preventing and treating ischemic stroke from the perspective of regulating mitochondrial structure and function. In this review, we discuss the molecular mechanisms by which mitochondria are involved in ischemic stroke. Furthermore, we summarized the current advances in TCM in preventing and treating ischemic stroke by modulating mitochondria. We aimed to provide a new perspective and enlightenment for TCM in the prevention and treatment of ischemic stroke by modulating mitochondria.

Efficacy and safety of nonpharmacological strategies for the treatment of oligoasthenospermia: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Oligoasthenospermia (OAT) is the most common cause of male infertility, and the annual incidence of the disease continues to increase due to changing lifestyle habits, increased work pressure and increased environmental pollution. A variety of nonpharmacological therapies have been reported to be effective for treating OAT; however, there is a lack of direct evidence comparing these different nonpharmacological therapies. Therefore, the optimal strategy has yet to be identified. OBJECTIVES: A network meta-analysis was performed to evaluate the efficacy and safety of nonpharmacological treatments for OAT, thus providing an evidence-based medical reference for the clinical treatment of oligoasthenospermia. METHODS: The Web of Science, Cochrane Library, Embase, PubMed, Weipu (VIP), Wan Fang Data, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature (CBM) databases were searched from inception to April 2022 to identify randomized controlled trials (RCTs) that examined nonpharmacological treatments for oligozoospermia. Grey literature was also searched. Studies that met the quality criteria were analysed using Stata 16.0 and Review Manager 5.4 software. RESULTS: A total of 4629 publications were initially retrieved; ultimately, 38 RCTs were analysed, including 8 nonpharmacological therapies and 3080 patients. Each intervention outperformed the sham intervention and no treatment approaches in terms of improved efficacy. In terms of improved total effective rate and sperm concentration, warming acupuncture may be the most effective treatment (SUCRA = 80.1% and 93.4%, respectively). Electroacupuncture perhaps resulted in the best improvement in sperm motility a% and a + b% (SUCRA = 96.6% and 82.0%, respectively). In terms of the incidence of adverse reactions, the three safest interventions probably were no treatment, warming acupuncture, and sham intervention (SUCRA = 88.0%, 68.8% and 62.9%, respectively). In terms of improving the reproductive hormones FSH, LH, and T, the best interventions perhaps were hyperbaric oxygen, 2 Hz TEAS, and electroacupuncture (SUCRA = 85.1%, 96.8% and 99.4%, respectively). CONCLUSIONS: Nonpharmacological treatments for oligoasthenospermia have good clinical efficacy. Warm acupuncture and electroacupuncture have better overall efficacy and safety. These treatment approaches can be recommended based on the actual situation. If a patient is complicated with varicoceles, they should be removed before symptomatic treatment. Due to the limitations of the quality of the included studies, the findings need to be further validated.

Study on the Mechanism of Action of Different Acupuncture Regimens on Premature Ovarian Failure Model Rats.

Objective: To study the mechanism of acupuncture on premature ovarian failure (POF) through the apoptosis pathway mediated by Bcl-2/Bax. Methods: POF rats were successfully obtained by cyclophosphamide. They were divided into five groups. After that, acupuncture was performed. The blank group and model group were not treated. The routine acupuncture group was acupuncture at Guanyuan, Sanyinjiao, Zhongji, and Guilai four points. The Neck-seven-acupuncture group was selected from Fengchi, Fengfu, Tianzhu, and Wangu four acupoints; the three-viscera simultaneous treatment group selected Guanyuan, Shenshu, Sanyinjiao, Taichong, and Baihui five points; and the data mining group selected Guanyuan and Sanyinjiao two points for 14 days of treatment. During the treatment, some rats were shed one after another due to the side effects of bone marrow suppression caused by mold-making. After treatment, serum estradiol (E2), follicle forming hormone (FSH), and luteinizing hormone (LH) were detected by radioimmunoassay, Bcl-2 and Bax proteins were analyzed by Western blot method, and Bcl-2 and Bax RNA were analyzed by PCR method. Results: Bcl-2 increased and Bax decreased in rats with premature ovarian failure treated with acupuncture. It shows that acupuncture can affect the secretion of ovarian-related hormones and the expression of apoptosis-related proteins, which is more significant in the conventional acupuncture point group. Conclusion: Acupuncture can inhibit the apoptosis of granulosa cells in ovarian tissue of rats with premature ovarian failure and improve ovarian function. The mechanism of its effect is to promote Bcl-2 gene expression and protein synthesis and inhibit Bax gene expression and protein synthesis. The conventional treatment group works best. This provides an experimental basis for the clinical use of acupuncture to intervene in the treatment of premature ovarian failure.

Systematic Review and Network Meta-analysis of Acupuncture Combined with Massage in Treating Knee Osteoarthritis.

Background: Knee osteoarthritis is a common clinical disease with frequent occurrence. More and more studies have shown that external therapies such as acupuncture and massage are beneficial to the treatment of knee osteoarthritis. Objective: The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTS) was to evaluate the efficacy and safety of acupuncture and massage combined with treatment of KOA and to provide some reference for clinical treatment of KOA. Methods: Network meta-analysis was used to evaluate the efficacy of acupuncture combined with massage in the treatment of knee osteoarthritis. PubMed, Cochrane Library, Web of Science, Embase, Chinese Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang were searched by computer for randomized controlled trials on acupuncture combined with massage in the treatment of knee osteoarthritis. All researchers independently screened the literature, extracted data, and evaluated quality, and studies that met the quality criteria were analyzed using Stata16.0 software. Results: A total of 3076 articles were retrieved, and finally, 49 studies involving 10 acupuncture combined with massage methods were included. The total sample size was 4458, including 2182 in the experimental group and 2276 in the control group. The results of network meta-analysis showed the following: in terms of effective rate, the optimal first three interventions were floating needle+massage, needle knife+massage, and silver needle+massage; in terms of reducing VAS score, the optimal first three interventions were common acupuncture+massage, needle knife+massage, and warm needle+massage; in terms of improving total Lysholm index score, the optimal first three interventions were silver needle+massage, electroacupuncture+massage, and needle knife+massage; in terms of reducing total WOMAC score, the optimal first three interventions were silver needle+massage, electrothermal needle+massage, and common acupuncture+massage; in terms of reducing WOMAC stiffness score, the optimal first three interventions were warm needle+massage, silver needle+massage, and common acupuncture+massage; and in terms of reducing WOMAC joint function score, the optimal first three interventions were silver needle+massage, warm needle+massage, and common acupuncture+massage. Conclusion: The results showed that acupuncture combined with massage could improve the clinical therapeutic effect of patients with knee osteoarthritis. Limited by the quality of the included studies, the conclusions obtained still need to be further validated.

Chinese Herb Injections in the Adjuvant Treatment for Ulcerative Colitis: A Network Meta-Analysis of Randomized Controlled Trials.

Ulcerative colitis refers to an inflammatory disease lasting for a long time, which affects the colon. In China, injections of traditional Chinese herbs have been generally combined with traditional Western medicines such as mesalazine and sulfasalazine to treat ulcerative colitis. Nevertheless, the safety and efficacy exhibited by different CHIs for treating UC remains controversial. Therefore, a network meta-analysis method was employed in this study for the assessment of the effect and safety exhibited by CHI for treating UC. Seven English and Chinese databases were searched for relevant randomized controlled trials (RCTs) from the time of database creation to December 30, 2021. An assessment was conducted for the included RCTs' quality with the use of the Cochrane risk offset assessment device, and this study processed the data with the use of Review Manager 5.3 or Stata16.0 software. On the whole, 42 literature with data on 3668 patients were included. The overall response rate, inflammatory factors, recurrence rate, and adverse reactions were evaluated. In comparison with traditional Western medicines-based treatment, CHI integrated with traditional Western medicines presented an overall response rate (P < 0.05) and could better reduce the TNF-α (P < 0.05), IL-6(P < 0.05), and IL-8 level rate (P < 0.05) while better increasing the IL-10 level rate (P < 0.05). Besides, adverse reactions of CHI integrated with traditional Western medicine had a lower incidence (P < 0.05), and no significant distinction was identified in recurrence rate levels between the two interventions. CHI has some efficacy for treating UC. Xiangdan injection, Shenmai injection, Shengmai injection, and Danshen injection may be the most effective CHI. Nevertheless, more multicenter randomized controlled double-blind trials with great quality and large samples are required for research confirmation. Trial Registration: the registration was made for the protocol of this network meta-analysis in PROSPERO with ID CRD42021251429.

Circulating exosomal microRNA profiles in migraine patients receiving acupuncture treatment: A placebo-controlled clinical trial.

Background: Acupuncture has a long history of being used in Chinese medicine for the treatment of migraine. However, molecular biomarkers for diagnosis and prognosis of migraine and its treatment are lacking. This study aimed to explore whether acupuncture could regulate differentially expressed exosomal miRNAs between patients with migraine without aura (MWoA) and healthy controls (HCs) and to identify diagnostic biomarkers that helped differentiate MWoA patients from HCs and identify prognostic biomarkers that helped to predict the effect of acupuncture. Methods: Here, we isolated serum exosomes from patients with MWoA and HCs before and after true and sham acupuncture treatment. Then, small RNA sequencing and bioinformatics analysis were performed to screen out key miRNAs specifically responding to acupuncture treatment. Pearson's correlation analysis was used to evaluate the correlation between miRNAs and clinical phenotypes. Finally, we applied a machine learning method to identify diagnostic biomarkers of MWoA patients and identify prognostic biomarkers that helped to predict the effect of acupuncture. Results: Small RNA sequencing identified 68 upregulated and 104 downregulated miRNAs in MWoA patients compared to those in HCs. Further, we identified eight upregulated and four downregulated miRNAs in migraine patients after true acupuncture treatment (trAMWoA), but not in the sham acupuncture treatment (shAMWoA) or HC group. Among them, has-miR-378a-5p was positively correlated with time unable to work, study, or do housework due to migraine (p < 0.05), whereas has-miR-605-3p was negatively correlated with the restrictive subscale of the migraine-specific quality of life questionnaire (MSQ) (p < 0.05). We then evaluated the diagnostic and prognostic potential of these 12 miRNAs in patients with MWoA. The combination of serum levels of exosomal has-miR-369-5p, has-miR-145-5p, and has-miR-5,010-3p could serve as diagnostic and prognostic biomarkers for MWoA patients following acupuncture treatment. Conclusion: This is the first study on the serum exosomal miRNA profiles of migraineurs before and after acupuncture treatment. Our results improve our understanding of the molecular functions of miRNAs in MWoA. More importantly, they expand our view of evaluating the clinical outcomes of migraine patients treated with acupuncture, using exosomal RNA markers. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000034417, July 2020.