Modulatory effects of acupuncture on raphe nucleus-related brain circuits in patients with chronic neck pain: A randomized neuroimaging trial.

OBJECTIVE: Acupuncture has shown promise in treating neck pain. Clinical trials have shown mixed results, possibly due to heterogeneous methodologies and the lack of knowledge regarding underlying brain circuit mechanism of action. In this study, we investigated the specific contribution of the serotonergic system in treating neck pain, and the specific brain circuits involved. METHODS: A total of 99 patients with chronic neck pain (CNP) were randomized to receive true acupuncture (TA) or sham acupuncture (SA) 3 times weekly for 4 weeks. Patients with CNP in each group were assessed for primary outcomes by measuring the Visual Analog Scale (VAS) and the duration of each attack; secondary outcomes were measured using the Neck Disability Index (NDI), Northwick Park Neck Pain Questionnaire (NPQ), McGill Pain Questionnaire (MPQ), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) and the 12-item Short Form Quality Life Scale (SF-12); levels of functional circuits connectivity were assessed using resting-state functional magnetic resonance imaging in the dorsal (DR) and median (MR) raphe nucleus, before and after undergoing acupuncture. RESULTS: Patients receiving TA showed more extensive symptom improvement compared with SA. Regarding the primary outcomes, changes observed in the TA group were as follows: VAS = 16.9 mm (p < 0.001) and the duration of each attack = 4.30 h (p < 0.001); changes in the SA group: VAS = 5.41 mm (p = 0.138) and the duration of each attack = 2.06 h (p = 0.058). Regarding the secondary outcomes, changes in the TA group: NDI = 7.99 (p < 0.001), NPQ = 10.82 (p < 0.001), MPQ = 4.23 (p < 0.001), SAS = 5.82 (p < 0.001), SDS = 3.67 (p = 0.003), and SF-12 = 3.04 (p < 0.001); changes in the SA group: NDI = 2.97 (p = 0.138), NPQ = 5.24 (p = 0.035) and MPQ = 2.90 (p = 0.039), SAS = 1.48 (p = 0.433), SDS = 2.39 (p = 0.244), and SF-12 = 2.19 (p = 0.038). The modulatory effect of TA exhibited increased functional connectivity (FC) between the DR and thalamus, between the MR and parahippocampal gyrus, amygdala, and insula, with decreased FC between the DR and lingual gyrus and middle frontal gyrus, between the MR and middle frontal gyrus. Furthermore, changes in the DR-related circuit were specifically associated with the intensity and duration of pain, and the MR-related circuit was correlated with the quality of life with CNP. CONCLUSION: These results demonstrated the effectiveness of TA in treating neck pain and suggested that it regulates CNP by reconfiguring the function of the raphe nucleus-related serotonergic system.

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.].

Bibliometric Analysis of Acupuncture Therapy for Cancer Pain Over the Past 10 Years.

Purpose: Cancer pain is a common symptom of cancer patients and greatly affects quality of life. Acupuncture has certain curative effects on cancer pain. The aim of this study was to analyze and visualize the current status and research trend of acupuncture treatment for cancer pain over the last 10 years and provide directions for future development. Methods: A search of the Web of Science Core Collection from 2012-01-01 to 2022-08-20 was performed to collect studies related to acupuncture therapy for cancer pain. CiteSpace was used to conduct bibliometric analysis and visualization from the perspective of the volume of annual publications, journals, nations, institutions, authors, keywords, and references. Results: A total of 302 studies were included in the analysis. The number of publications increased steadily with some fluctuations over the past decade. Integrative Cancer Therapies was the journal with the most relevant publications, and the Journal of Clinical Oncology was the most frequently cited journal. China had the highest volume of publications, and the USA contributed most to international collaboration. The most prolific institution was Memorial Sloan Kettering Cancer Center. The most productive author was Mao JJ, and the most influential author was Lu WD. "Acupuncture" was the top keyword in frequency and centrality. The references with the highest frequency and centrality were published by HE, Y, and Ting Bao, respectively. Conclusion: A stable development trend has formed in this field. The overall collaborative network needs to be strengthened. Breast cancer and multiple myeloma, electroacupuncture and bee venom acupuncture, postoperative pain, peripheral neuropathic pain syndrome, and aromatase inhibitors-associated arthralgia syndrome are research hotspots in this field. Randomized controlled trials (RCTs), evidence-based evaluations and mechanisms (cancer-induced bone pain) are research trends and frontiers.

Study on the Specific Expression of Infrared Radiation Temperature on the Body Surface of Acupoint in Rats with Chronic Myocardial Ischemic Injury.

BACKGROUND: Infrared thermal imaging technology was used to observe the changes in infrared radiation temperature at acupoints in rats caused by chronic myocardial ischemia injury. OBJECTIVE: This study aims to compare the difference of body surface infrared radiation temperature information of three groups of acupoints: bilateral Neiguan (PC6), bilateral Yanglingquan (GB33), and bilateral Sham Acupoints (SA) in the pathological state of myocardial ischemia injury, and to explore the relationship between acupoints and viscera state. METHODS: SPF adult Wistar male rats (n = 20) were randomly divided into a control (CTL; n = 10) and an isoproterenol group (ISO; n = 10). Chronic myocardial injury was induced in rats by subcutaneous injection of isoproterenol hydrochloride for 14 d. On the second day after the establishment of the model, the serum levels of cardiac troponin (cTnI) and creatine kinase isoenzyme (CK-MB) were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of the myocardial tissue in the two groups were observed by hematoxylin-eosin (HE) staining and their pathological scores were evaluated, which was then used to determine the myocardial ischemic injury. Two days before and after the establishment of the model, the electrocardiograms (ECG) of the two groups of rats were recorded by the (ECG) data acquisition system, and the infrared thermal imaging platform was used to detect the temperature of the six acupoints. RESULTS: 1. After subcutaneous injection of isoproterenol hydrochloride for 14 days, the ST segment of the ECG decreased in the ISO group compared with that of the CTL group; 2. Myocardial tissue injury was serious in the ISO group compared to the CTL group; 3. Serum cTn-I and CK-MB were significantly increased (P <0 01) in the ISO group, compared to that in the CTL group; 4. The infrared radiation temperature on the body surface of bilateral Neiguan (PC6) acupoints decreased significantly in the ISO group, compared to that of the CTL group. CONCLUSION: Infrared thermal imaging technology can be used to detect the changes in the energy state of acupoints. Chronic myocardial ischemic injury can cause a decrease in IR temperature on the body surface of bilateral Neiguan (PC6) acupoints, suggesting that visceral diseases can lead to changes in the energy metabolism of acupoints.

Efficacy of Moxibustion for Primary Osteoporosis: A Trial Sequential Meta-Analysis of Randomized Controlled Trials.

Background: Primary osteoporosis (PO) is a systemic metabolic skeletal disease. Previous studies have shown that moxibustion can reduce pain intensity and enhance response rate, bone mineral density (BMD), and living function of the patients with PO. However, consensus on its efficacy does not exist, and evidence of moxibustion for PO is also insufficient. Methods: We searched five English and four Chinese databases with various additional sources and published reviews through December 1, 2021, to evaluate potentially concerned randomized controlled trials (RCTs). Two independent researchers addressed selection screening, data extraction, and risk of bias assessment. The data of this meta-analysis were analyzed using the RevMan v.5.4 software. Additionally, the trial sequential analysis v.0.9.5.10 ß was used to estimate the sample size. In contrast, the quality of evidence from the RCTs was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Results: The current meta-analysis included 14 RCTs containing 898 participants. The methodological quality of the RCTs was moderate. The review demonstrated that a combination of moxibustion and conventional medicine (CM) significantly reduced pain intensity and improved the BMD compared with CM. Furthermore, it was found that moxibustion plus CM/moxibustion could improve response rates compared with CM. However, it was found that the reduction of pain intensity and improvement of BMD by moxibustion showed no significant difference compared with CM. It was also evident that the sample size of most outcomes was inadequate. Moreover, all evidence obtained in this study was ranked as low to critically low. Conclusions: In conclusion, it was demonstrated that moxibustion is a potentially effective agent for treating PO. However, high-quality studies should be implemented in the future because this study only obtained low-quality evidence. This study was registered in the PROSPERO platform (CRD42021291310).

The application of acupuncture in cardiopathy: A bibliometric analysis based on Web of Science across ten recent years.

Background: With high morbidity and mortality, cardiopathy is a major component of cardiovascular disease, causing a huge burden of disease to public health worldwide. In recent years, research on acupuncture treatment of cardiopathies has been increasing. However, no bibliometric analysis has been conducted to systematically describe the research progress and hotspots in this field. Therefore, this study aimed to conduct a bibliometric analysis of the relevant literature to explore the current status and future development of acupuncture for cardiopathies. Methods: The Web of Science (WoS) Core Collection Database was searched for literature related to acupuncture therapies for cardiopathies from 2011 to 2021. Using CiteSpace 5.8 R3, cooperation network diagrams of authors, institutions, countries and journals, keyword co-occurrences, and clustering were performed and analyzed. Results: A total of 321 studies were included. Overall, the number of annual publications increased yearly. These publications came from 31 countries or regions, of which China and the United States made the greatest contributions. In total, 333 authors from 258 institutions participated in this field, and Beijing University of Chinese Medicine and Professor Fanrong Liang were the most published institution and author, respectively. Evidence-based Complementary and Alternative Medicine published the largest number of articles, and CIRCULATION was the most commonly cited journal. Based on co-occurrences and cluster analysis of 257 keywords, three research frontiers and hotspots were identified: acupuncture for blood pressure regulation, acupuncture for coronary heart disease, and acupuncture for regulation of heart rate. In these three research frontiers, the rostral ventrolateral medulla (RVLM) and autonomic nervous system (ANS) are the most popular mechanisms. Conclusion: A stable development trend has formed in this field. Further research should focus on the role of acupuncture therapies in the treatment of hypertension or hypertensive heart disease, coronary heart disease, and arrhythmia based on the mechanisms related to the RVLM and ANS.

Current status of neuroimaging research on the effects of acupuncture: a bibliometric and visual analyses.

OBJECTIVE: To conduct an inductive analysis of neuroimaging studies following the global popularity surrounding the effects of acupuncture. METHODS: The relevant works of literature on acupuncture effects-related neuroimaging studies were retrieved from the web of science core collection database from the date of its establishment to 2022. Bibexcel software was used to extract information, such as article numbers, countries, journals, agencies, funding sources and keywords. The VOSviewer software's co-occurrence and clustering module was used for the co-occurrence and cluster analysis of collaborative networks and high frequency keywords, such as authors, institutions and countries. RESULTS: Neuroimaging research on the effects of acupuncture began in the 1960 s and has since received the extensive attention of scholars. China, The United States and South Korea conduct more neuroimaging research on the effects of acupuncture than other countries. Academic journals such as Evidence-Based Complementary and Alternative Medicine, Journal of Alternative and Complementary Medicine, Neural Regeneration Research and Acupuncture in Medicine have published the highest number of acupuncture-related neuroimaging articles. Moreover, cluster analysis differentiates high-frequency keywords into six clusters. Furthermore, the use of the keyword 'density atlas' reveals that neuroimaging research on the effects of acupuncture surrounding pain and neurofunctional rehabilitation is currently the research focus. CONCLUSIONS: This bibliometric study identifies six important research hot spots: Static brain functional connectivity analysis of acupuncture analgesic effects, key theories on the scientific problems of acupuncture, acupuncture analgesic effect of the placebo effect, the neuroimaging of acupoint ST-36, the value of acupuncture in regulating the autonomic nerves and acupuncture therapy as complementary medicine.

Effectiveness and safety of acupuncture for angina pectoris: An overview of systematic reviews.

Background: The number of systematic reviews meta-analyses (SRs/MAs) on the effectiveness of acupuncture for angina pectoris (AP) is increasing. Due to the inconsistent conclusions and unknown quality of these SRs/MAs, this overview aimed to systematically evaluate and synthesize the existing SRs/MAs, attempting to provide more reliable evidence for the effectiveness and safety of acupuncture in the treatment of AP. Methods: SRs/MAs were searched via eight databases from inception to March 14, 2022. The risk of bias was evaluated using the Risk of Bias in Systematic reviews (ROBIS) tool. The quality of the methodology, reporting, and evidence were assessed by the Assess Systematic Reviews 2 (AMSTAR-2), the Preferred Reporting Item for Systematic Review and Meta-analysis for Acupuncture (PRISMA-A), and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, respectively. Results: Sixteen SRs/MAs were included and fifteen SRs/MAs were considered being of critically low quality according to AMSTAR-2. Only three SRs/MAs were rated at low risk of bias. No study reported all the items listed in the PRISMA-A checklist. No high-quality evidence with GRADE assessment was found. With the low-quality evidence, acupuncture combined with other interventions was superior to monotherapy (medications or Chinese medicine) in the angina symptom and electrocardiogram recovery. No adverse effects owing to acupuncture were reported. Conclusions: Owing to the lack of high-quality evidence provided by the current SRs/MAs, the effectiveness of acupuncture for AP still warrants further proof. Further researches with more critical design and methodology are needed for providing more convincing evidence. Registration: This review was registered at PROSPERO (www.crd.york.ac.uk/prospero/): CRD42021219367.

Downregulation of lncRNA Miat contributes to the protective effect of electroacupuncture against myocardial fibrosis.

BACKGROUND: Myocardial fibrosis changes the structure of myocardium, leads to cardiac dysfunction and induces arrhythmia and cardiac ischemia, threatening patients' lives. Electroacupuncture at PC6 (Neiguan) was previously found to inhibit myocardial fibrosis. Long non-coding RNAs (lncRNAs) play a variety of regulatory functions in myocardial fibrosis, but whether electroacupuncture can inhibit myocardial fibrosis by regulating lncRNA has rarely been reported. METHODS: In this study, we constructed myocardial fibrosis rat models using isoproterenol (ISO) and treated rats with electroacupuncture at PC6 point and non-point as control. Hematoxylin-eosin, Masson and Sirius Red staining were performed to assess the pathological changes and collagen deposition. The expression of fibrosis-related markers in rat myocardial tissue were detected by RT-qPCR and Western blot. Miat, an important long non-coding RNA, was selected to study the regulation of myocardial fibrosis by electroacupuncture at the transcriptional and post-transcriptional levels. In post-transcriptional level, we explored the myocardial fibrosis regulation effect of Miat on the sponge effect of miR-133a-3p. At the transcriptional level, we studied the formation of heterodimer PPARG-RXRA complex and promotion of the TGF-ß1 transcription. RESULTS: Miat was overexpressed by ISO injection in rats. We found that Miat can play a dual regulatory role in myocardial fibrosis. Miat can sponge miR-133a-3p in an Ago2-dependent manner, reduce the binding of miR-133a-3p target to the 3'UTR region of CTGF mRNA and improve the protein expression level of CTGF. In addition, it can also directly bind with PPARG protein, inhibit the formation of heterodimer PPARG-RXRA complex and then promote the transcription of TGF-ß1. Electroacupuncture at PC6 point, but not at non-points, can reduce the expression of Miat, thus inhibiting the expression of CTGF and TGF-ß1 and inhibiting myocardial fibrosis. CONCLUSION: We revealed that electroacupuncture at PC6 point can inhibit the process of myocardial fibrosis by reducing the expression of lncRNA Miat, which is a potential therapeutic method for myocardial fibrosis.

Electroacupuncture at PC6 (Neiguan) Attenuates Angina Pectoris in Rats with Myocardial Ischemia-Reperfusion Injury Through Regulating the Alternative Splicing of the Major Inhibitory Neurotransmitter Receptor GABRG2.

Angina pectoris is the most common manifestation of coronary heart disease, causing suffering in patients. Electroacupuncture at PC6 can effectively alleviate angina by regulating the expression of genes, whether the alternative splicing (AS) of genes is affected by acupuncture is still unknown. We established a rat model of myocardial ischemia-reperfusion by coronary artery ligation and confirmed electroacupuncture alleviated the abnormal discharge caused by angina pectoris measured in EMG electromyograms. Analysis of the GSE61840 dataset established that AS events were altered after I/R and regulated by electroacupuncture. I/R decreased the expression of splicing factor Nova1 while electroacupuncture rescued it. Further experiments in dorsal root ganglion cells showed Nova1 regulated the AS of the GABRG2, specifically on its exon 9 where an important phosphorylation site is present. In vivo, results also showed that electroacupuncture can restore AS of GABRG2. Our results proved that electroacupuncture alleviates angina results by regulating alternative splicing.

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.

Research Progress of Ferroptosis: A Bibliometrics and Visual Analysis Study.

Background: Ferroptosis is a type of cell death with major topic of debate under current research and plays an important role in disease regulation. Objective: In this study, the literature management software Bibexcel and knowledge graph tool VOSviewer were used to summarize and analyze the international research trends and hotspots about ferroptosis in recent years, which highlight the disease mechanism, diagnosis, and treatment related to ferroptosis. Material/Methods. The core collection database of Web of Science was used for retrieving ferroptosis research literature. The information such as the amount of text, the country, the period, the institution, the fund, and the keywords was extracted by the bibliometric tool Bibexcel. The cooccurrence and clustering function of VOSviewer were used to analyze the high-frequency keywords and the cooperative network of the author, institution, and country. Results: The research of ferroptosis started late and was formally proposed in 2012. It has developed rapidly and presented an "exponential" growth trend. China, the United States, Germany, Japan, and France are the main national forces of ferroptosis research development. The United States and China have a relatively high degree of support and attention to ferroptosis. Exploring oxidative stress, inducers/inhibitors, synergistic antitumor effect, relationships with other cell death types, GSH/GPX4 and iron metabolism imbalance related mechanisms of ferroptosis, and ferroptosis in the nervous system disease, ischemia-reperfusion injury, tumor, inflammation, and age-related diseases are the hot research directions. Conclusion: Ferroptosis has been a research hotspot in the field of biomedicine in recent years and has attracted the attention of scholars all over the world. The occurrence mechanism of ferroptosis and its application in neurological diseases, ischemia and reperfusion injury, tumors, inflammation, and aging are the hot directions of current research. In the future, ferroptosis can be appropriately considered for strengthening new approaches, new diseases, new inductors, new inhibitors, clinical transformation, and traditional medicine research.

Acupuncture Treatment for Cough-Variant Asthma: A Meta-Analysis.

BACKGROUND: In recent years, there have been many clinical reports on acupuncture treatment of cough-variant asthma, but no researcher has objectively analysed and evaluated the efficacy and safety of acupuncture treatment of cough-variant asthma from the perspective of evidence-based medicine. OBJECTIVE: To systematically evaluate the clinical efficacy and safety of acupuncture in treating cough-variant asthma and to provide reference values for clinical decision-making. METHODS: The comprehensive computer retrieval Chinese journal full-text database (CNKI), Chinese science and technology periodical database (VIP), ten thousand data knowledge service platform (WanFang Data), PubMed, Embase, and the Cochrane Library were used to collect literature for relevant randomized controlled trials (RCT) of acupuncture treatment of cough-variant asthma, as well as to retrieve papers and add reference retrieval after literature review, in accordance with the standard of literature filtering, data extraction, and quality evaluation. The data were meta-analysed using ReviewManager5.3 software recommended by Cochrane. RESULTS: A total of 11 randomized controlled clinical studies were screened and included, comprising 929 patients. The results of the meta-analysis showed that, compared with the control group, acupuncture intervention on CVA could enhance the total clinical effectiveness rate, reduce the relapse rate of drug withdrawal, relieve symptoms of cough, phlegm, and diaphragmatic congestion, and improve lung function-related indicators and immune inflammation indicators. There were statistically significant differences in all efficacy evaluation criteria. CONCLUSION: The clinical curative effect of acupuncture treatment for cough-variant asthma is precise and has certain advantages in relieving symptoms and reducing the recurrence rate. However, the low quality of the evaluation in the RCT research literature is a problem, and more high-quality clinical randomized controlled trials are needed to further verify the comprehensive clinical efficacy and safety of this treatment. Registration number: PROSPERO (no. CRD42020155244) (https://www.crd.york.ac.uk/prospero/).