Research progress on mechanisms of acupuncture and moxibustion underlying improvement of oxidative stress. / é’ˆç¸æ”¹å–„æ°§åŒ–åº”æ¿€ä½œç”¨æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

Oxidative stress is associated with a variety of disease pathologies, it may lead to mitochondrial dysfunction, damage of impaired DNA repairment, cell damage or apoptosis. Acupuncture and moxibustion therapy has been proved to have a role in reducing oxidative stress in organisms under pathological conditions. In the present paper, we collected literatures in both English and Chinese from domestic and foreign databases on the mechanisms of acupuncture and moxibustion underlying amelioration of oxidative stress over the past 5 years, and analyzed the link between acupuncture-moxibustion intervention and redox biology from four aspects： 1) regulation of the production of reactive oxygen species (ROS), 2) affecting antioxidant enzyme-related pathways to reduce ROS, 3) repairing proteins, lipids and DNAs attacked by ROS, and 4) inhibiting downstream apoptosis or autophagy of ROS pathway. By summarizing and prospecting such antioxidant mechanisms, this paper may provide some basis and ideas for in-depth mechanism research on acupuncture and moxibustion to improve oxidative stress and related diseases.

Moxibustion attenuates liver metastasis of colorectal cancer by regulating gut microbial dysbiosis.

The liver metastasis is the primary factor attributing to the poor prognosis of colorectal cancer (CRC). Moxibustion has been used clinically against multiple malignancies. In this study, we explored the safety, efficacy, and the potential functional mechanisms of moxibustion in modulating the liver metastasis of CRC by using GFP-HCT116 cells-derived CRC liver metastasis model in Balb/c nude mice. The tumor bearing mice were randomly divided into model control and treatment groups. Moxibustion was applied to the BL18 and ST36 acupoints. CRC liver metastasis was measured by fluorescence imaging. Furthermore, feces from all mice were collected, and 16S rRNA analysis was used to assess their microbial diversity, which was analyzed for its correlation with liver metastasis. Our results indicated that the liver metastasis rate was decreased significantly by moxibustion treatment. Moxibustion treatment also caused statistically significant changes in the gut microbe population, suggesting that moxibustion reshaped the imbalanced gut microbiota in the CRC liver metastasis mice. Therefore, our findings provide new insights into the host-microbe crosstalk during CRC liver metastasis and suggest moxibustion could inhibit CRC liver metastasis by remolding the structure of destructed gut microbiota community. Moxibustion may serve as a complementary and alternative therapy for the treatment of patients with CRC liver metastasis.

Trends in Acupuncture Therapy in Cardiovascular Disease: A Bibliometric Analysis.

Purpose: Acupuncture has been used for almost half a century to treat and prevent cardiovascular (CV) problems. However, most of its effects are poorly understood, and there are few studies based on bibliometric analysis of the general trends in acupuncture therapy in cardiovascular disorders (CVD). Thus, we aimed to show the present state and trends in this sector during the last few years. Methods: Articles were obtained from the Web of Science Core Collection (WOSCC) from its inception to May 30, 2021. The acquired information from the articles was analyzed by The Online Bibliometric Analysis Platform website (https://bibliometric.com), Citespace and VOSviewer in respective form in order to assess and forecast the hottest areas and trends in this field. Results: The final analysis included a total of 384 articles and reviews. Over the years, the number of publications has gradually increased. The United States and University of California Irvine were the country and institution that contributed the most to the field. John C Longhurst was the most productive author; Li P the most cited author. Co-occurrence analysis revealed 5 branches (including acupuncture, blood pressure, electroacupuncture, stimulation, cardiovascular responses) and 12 clusters. Recent keyword bursts included "reflex," "arcuate nucleus," "electroacupuncture," "cardiovascular disease" and "hypertension." Conclusion: Yearly publications continue to increase every decade, indicating a bright future in this scientific field. Acupuncture's function in CVD is a future study priority.

The effectiveness and safety of acupuncture/electroacupuncture for chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis.

OBJECTIVE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse effect of anticancer agents with virtually no effective treatment. Safe and effective therapies are needed urgently. Acupuncture shows therapeutic possibilities in this regard but needs to be further evaluated. METHODS: A systematic search was conducted in seven databases from their inception to April 2020. Randomized controlled trials (RCTs) focused on acupuncture/electroacupuncture (EA) for the treatment of CIPN were included. Revman 5.3 software was used for meta-analysis if there was no significant heterogeneity. Otherwise, qualitative analysis was utilized. RESULTS: Nine studies involving 582 patients were included in this review. Most of the studies exhibited unclear risk of bias because some details were not mentioned. As the clinical heterogeneity was significant, qualitative analysis was performed to describe nerve conduction velocity, effective rate for motor neuropathy, pain scores, quality of life and adverse events. Meta-analysis was performed on four studies to analyze the effective rate for sensory neuropathy due to inconspicuous heterogeneity. The results indicated that acupuncture may generate a better effect on sensory neuropathy than vitamin B (risk ratio = 1.60, 95% confidence interval = 1.31-1.95, I2 = 0%, p < 0.00001). The efficacy of EA plus glutathione (GSH) appeared to be better than that of GSH alone in alleviating sensory neurotoxicity and in improving nerve conduction velocity. Acupuncture plus methylcobalamin showed more favorable effects than methylcobalamin alone in relieving neuralgia, restoring nerve conduction velocity and improving quality of life. In terms of pain relief and improved CIPN-specific quality of life, acupuncture plus standard care was better than standard care alone. In terms of pain relief, EA was more effective than usual care. CONCLUSION: Acupuncture may be effective and safe in the treatment of CIPN according to the analyzed studies. However, more studies with higher methodological quality are warranted in order to be able to draw firmer conclusions. Future rigorous RCTs will be necessary to confirm the effectiveness and safety of acupuncture for CIPN.

Acupuncture-Neuroimaging Research Trends over Past Two Decades: A Bibliometric Analysis.

OBJECTIVE: To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades. METHODS: This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references. RESULTS: A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords "acupuncture" (475) and "electroacupuncture" (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76). CONCLUSION: The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were "nerve regeneration", "functional connectivity", "neural regeneration", "brain network", "fMRI" and "manual acupuncture".

[Professor SUN Jian-hua's experience of acupuncture and moxibustion for functional gastrointestinal disorders based on "psychosomatic medicine"].

Professor SUN Jian-hua proposes that the disease location of functional gastrointestinal disorders is brain, spleen and intestines; the liver-depression and spleen-deficiency is the basis of pathogenesis; the core pathogenesis is the dysfunction of qi and disability of conducting; the key to pathogenesis is the imbalance of heart, brain and mind. The "regulating-mind and strengthening-spleen" acupuncture therapy could treat functional gastrointestinal disorders. The first essence of treatment is regulating the mind, and the treatment principles are soothing the liver and strengthening the spleen, improving the mind and regulating the intestines. In addition, the moxibustion therapy and auricular points therapy are suggested to use together. Moreover, psychological counseling and health education are important, especially attention should be paid to the treatment of the mind and body, so as to synergize the treatment effect.

[Effect of acupuncture on hypothalamic functional connectivity in patients with premature ova-rian insufficiency based on resting-state functional magnetic resonance imaging].

OBJECTIVE: To compare the differences in functional connectivity(FC) between the hypothalamus and whole brain regions in patients with premature ovarian insufficiency (POI) and healthy volunteers based on resting-state functional magnetic resonance imaging (rs-fMRI) and investigate the mechanism of acupuncture on treatment of POI. METHODS: Twelve POI patients were recruited to the acupuncture group and 12 healthy volunteers to the control group. Patients in the acupuncture group received acupuncture at two groups of acupoints alternatively, including Baihui (GV20), Zhongwan (CV12), Shenting (GV24), Shenshu (BL23), Ciliao（BL32） and so on, 30 min once time, 3 times per week for 12 weeks. The state of patients was evaluated by modified Kupperman Index (KI) and self-rating anxiety scale (SAS). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-mullerian hormone (AMH) were tested by microparticle-based chemiluminescence. B ultrasonography was used to detect the antral follicle count (AFC). Meanwhile, POI patients and healthy volunteers underwent the rs-fMRI examination before and after acupuncture treatment and after enrollment, respectively. With hypothalamus as the region of interest, the differences in FC between the hypothalamus and other brain regions in POI patients and healthy volunteers and the changes of FC between the hypothalamus and whole brain regions in POI patients before and after acupuncture were observed. RESULTS: The SAS and KI scores of pre-treatment POI patients were higher than those in the control group （P<0.01）.In compa-rison with those pre-treatment, FSH, LH, and SAS and KI scores of POI patients decreased after treatment, while AFC increased (P<0.05). Compared with the control group, the FC of the left hypothalamus with left central sulcus, right middle occipital gyrus, and left paracentral lobule increased, but decreased with left globus pallidus of the lenticular nucleus in POI patients. Furthermore, the FC of the right hypothalamus with the left hippocampus, the left para-central lobule, and the right central sulcus increased, while the FC between the right hypothalamus and the right superior frontal gyrus decreased (P<0.05). For the acupuncture group, compared with the conditions before treatment, the FC of the right hypothalamus with the left inferior frontal gyrus, the left insula, and right inferior frontal gyrus was strengthened, but weakened with the left gyrus rectus (P<0.05). CONCLUSION: The abnormal FC between the hypothalamus and whole brain regions may be one of the central pathological factors of POI. Acupuncture can improve the ovarian function and clinical symptoms of patients with POI, which may be related to its effect in regulating the FC between the hypothalamus and multiple brain regions.

Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1-Piezo2 Axis.

Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.

[Application of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients].

To analyze the application feasibility of Tiaoshen Jianpi acupuncture and moxibustion in hospice care for terminal cancer patients. Tiaoshen Jianpi acupuncture and moxibustion adjusts the spirit to regulate emotions and fortifies the spleen to supplement and boost foundation of acquired (postnatal) constitution. And it could relieve adverse reactions after radiotherapy and chemotherapy, alleviate pain and regulate emotions in hospice care for terminal cancer patients, so as to promote the progress of hospice care for terminal cancer patients.

[Short-term curative effect and safety on female abdominal obesity and defecation function treated with acupoint embedding therapy at different layers under B ultrasound].

OBJECTIVE: To investigate the short-term effect and safety on female abdominal obesity and defecation function in treatment with acupoint embedding therapy at different abdominal layers under B ultrasound. METHODS: A total of 102 female patients with abdominal obesity were randomly divided into 3 groups, i.e. a deep embedding group (34 cases, 1 case dropped out), a shallow embedding group (34 cases, 3 cases dropped out) and a sham-embedding group (34 cases, 6 cases dropped out). Finally, 92 cases were included in the three groups. Under B ultrasound, in the deep embedding group, the absor-bable surgical suture were embedded in subcutaneous fat layer and muscle layer. In the shallow embedding group, the absorbable surgical suture was embedded in the fat layer and in the sham-embedding group, no suture was embedded. The acupoints for embedding therapy included Zhongwan (CV12), Guanyuan (CV4), bilateral Guanmen (ST22), bilateral Tianshu (ST25), bilateral Daimai (GB26) and bilateral Shuidao (ST28). The acupoint embedding therapy was exerted once every two weeks, for 4 times totally. Before and after treatment, the changes in abdominal obesity indicators (waist circumference ï¼»WCï¼½, body fat rate ï¼»BFRï¼½, body mass index ï¼»BMIï¼½, abdominal subcutaneous fat thickness ï¼»ASFTï¼½) and defecation function indicators (spontaneous bowel movement times ï¼»SBMsï¼½ and Bristol stool scale ï¼»BSSï¼½) were observed and the safety indicators were assessed. RESULTS: After treatment, WC, BFR, BMI and ASFT were lower than those before treatment in both the deep embedding group and the shallow embedding group (P<0.05), those values in the deep embedding group were reduced more obviously as compared with the shallow embedding group (P<0.05). SBMs and BSS after treatment were increased as compared with those before treatment in both the deep embedding group and the shallow embedding group (P<0.05) and the increase in the deep embedding group was more obvious than in the shallow embedding group (P<0.05). The abdominal obesity indicators and defecation function indicators after treatment were not different statistically as compared with those before treatment in the sham-embedding group (P>0.05). The pain score of acupuncture in either the deep embedding group or the shallow embedding group was higher than in the sham-embedding group (P<0.05). The acceptance was more than 2 points in all of the three groups and there was no statistical significance among groups (P>0.05). CONCLUSION: Acupoint embedding therapy in both the deep and the shallow subcutaneous layers under B ultrasound may regulate the indicators of female abdominal obesity safely. The acupoint embedding therapy in the deep layer is more effective on abdominal obesity and defecation improvement as compared with that exerted in the shallow layer.

Regulation of serum microRNA expression by acupuncture in patients with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: To screen for differentially expressed serum microRNAs (miRNAs) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) compared with healthy participants and explore the mechanism of acupuncture in the treatment of IBS-D based on miRNAs. METHODS: IBS-D patients that met the Rome III diagnostic criteria and age- and sex-matched healthy participants were enrolled between April 2017 and December 2017. Serum miRNA levels were initially determined using a TaqMan low-density array (TLDA) in pooled samples. Markedly altered miRNAs in IBS-D patients were subsequently validated using quantitative real-time polymerase chain reaction (qRT-PCR) on individual samples. All IBS-D patients accepted the acupuncture therapy for 6 weeks. The disease severity was assessed using the IBS symptom severity scale (IBS-SSS) questionnaire before and after treatment. After acupuncture, the patients' serum was re-analyzed for altered expression of the miRNAs by qRT-PCR. RESULTS: TLDA and qRT-PCR analysis revealed six upregulated miRNAs (miR-1305, miR-575, miR-149-5p, miR-190a-5p, miR-135a-5p, and miR-148a-3p; P < 0.05) and two downregulated miRNAs (miR-194-5p, miR-127-5p; P < 0.05) in IBS-D patients compared with healthy controls. Post acupuncture treatment, total IBS-SSS scores, severity of abdominal pain, duration of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits and disruption in quality of life decreased significantly (P < 0.001). Furthermore, the upregulated miR-148a-3p levels in IBS-D patients also decreased significantly after acupuncture (P < 0.05). CONCLUSIONS: The over-expression or reduced expression of several miRNAs may contribute to IBS-D pathogenesis. Acupuncture might downregulate miR-148a-3p through multiple pathways to alleviate or relieve IBS-D symptoms. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17010860 (Chinese Clinical Trials Registry).

Networks Are Associated With Acupuncture Treatment in Patients With Diarrhea-Predominant Irritable Bowel Syndrome: A Resting-State Imaging Study.

Background: Irritable Bowel Syndrome (IBS), as a functional gastrointestinal disorder, is characterized by abdominal pain and distension. Recent studies have shown that acupuncture treatment improves symptoms of diarrhea-predominant irritable bowel syndrome (IBS-D) by altering networks in certain brain regions. However, few studies have used resting-state functional magnetic resonance imaging (fMRI) to compare altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment. Objective: To analyze altered resting-state inter-network functional connectivity in IBS-D patients before and after acupuncture treatment. Methods: A total of 74 patients with IBS-D and 31 healthy controls (HCs) were recruited for this study. fMRI examination was performed in patients with IBS-D before and after acupuncture treatment, but only at baseline in HCs. Data on the left frontoparietal network (LFPN), default mode network (DMN), salience network (SN), ventral attention network (VAN), auditory network (AN), visual network (VN), sensorimotor network (SMN), dorsal attention network (DAN), and right frontoparietal network (RFPN) were subjected to independent component analysis (ICA). The functional connectivity values of inter-network were explored. Results: Acupuncture decreased irritable bowel syndrome symptom severity score (IBS-SSS) and Hamilton Anxiety Scale (HAMA). It also ameliorated symptoms related to IBS-D. Notably, functional connectivity between AN and VAN, SMN and DMN, RFPN and VAN in IBS-D patients after acupuncture treatment was different from that in HCs. Furthermore, there were differences in functional connectivity between DMN and DAN, DAN and LFPN, DMN and VAN before and after acupuncture treatment. The inter-network changes in DMN-VAN were positively correlated with changes in HAMA, life influence degree, and IBS-SSS in IBS-D. Conclusion: Altered inter-network functional connectivity is involved in several important hubs in large-scale networks. These networks are altered by acupuncture stimulation in patients with IBS-D.

[Bidirectional regulation of acupuncture: a subgroup analysis of multicenter randomized controlled trial of acupuncture with Tiaoshen Jianpi for irritable bowel syndrome].

OBJECTIVE: To explore the bidirectional regulation of acupuncture based on a subgroup analysis of multicenter randomized controlled trial of acupuncture with Tiaoshen Jianpi for irritable bowel syndrome (IBS). METHODS: A total of 519 patients were included in the analysis, including 137 patients with constipation type irritable bowel syndrome (IBS-C) (92 cases in the acupuncture group and 45 cases in the polyethylene glycol [PEG] group), and 382 patients with diarrhea type irritable bowel syndrome (IBS-D) (252 cases in the acupuncture group and 130 cases in the pinaverium group). The patients in the acupuncture group were given acupuncture at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) once every other day, 3 times a week. The patients in the PEG group received polyethylene glycol 4000 powder orally, and the pinaverium group received pinaverium bromide tablets orally. All were treated for 6 weeks. The IBS symptom severity score (IBS-SSS) was assessed at baseline, treatment period (2, 4, 6 weeks of treatment) and 12 weeks of follow-up, and the IBS quality of life (IBS-QOL) score was evaluated at the baseline period, 6 weeks of treatment and 12 weeks of follow-up. RESULTS: The total IBS-SSS scores of the two groups of IBS-C patients at 2, 4, 6 weeks of treatment and follow-up of 12 weeks were lower than those in the baseline period (P<0.01). The total IBS-SSS score in the IBS-C acupuncture group was lower than that in the PEG group at 12 weeks of follow-up (P<0.05). The total IBS-SSS scores of the two groups of IBS-D patients at 2, 4, 6 weeks of treatment and 12 weeks of follow-up were lower than those in the baseline period (P<0.01). The total IBS-SSS scores in the IBS-D acupuncture group were lower than those in the pinaverium group at 2, 4, 6 weeks of treatment and 12 weeks of follow-up (P<0.05). The total IBS-QOL scores at 6 weeks of treatment and 12 weeks of follow-up were higher than those in the baseline period in both groups of patients with IBS-C (P<0.01). The total IBS-QOL scores at 6 weeks of treatment and 12 weeks of follow-up were higher than those in the baseline period in both groups in patients with IBS-D (P<0.01). The total IBS-QOL score in the IBS-D acupuncture group was higher than that in the pinaverium group at 18 weeks of follow-up (P<0.05). CONCLUSION: Acupuncture with Tiaoshen Jianpi can improve the clinical symptoms and quality of life of patients with IBS-C and IBS-D, which can regulate different functional states (constipation and diarrhea) of the same disease (irritable bowel syndrome), reflecting the bidirectional regulation of acupuncture.

Ruyiping formula inhibits metastasis via the microRNA-134-SLUG axis in breast cancer.

BACKGROUND: Metastasis is the leading cause of death among breast cancer patients. MicroRNA-134 has been reported to have a tumor-suppressive role in breast cancer. Ruyiping (RYP), a traditional Chinese formula, has been shown with the ability to reduce breast cancer metastasis in pre-clinical studies. This present study was designed to examine whether miR-134 was involved in RYP-inhibited breast cancer metastasis. METHODS: The expression of SLUG, E-Cadherin, N-Cadherin and miR-134 in MDA-MB-231 and 4 T1 cells treated with RYP or vehicle control were determined by quantitative realtime-PCR and western blot. Invasiveness determined by transwell assay as well as SLUG gene expression determined by qPCR were detected in cells transfected with chemically synthesized miR-134 mimics or inhibitors. BALB/c mice were injected with 4 T1 cells orthotopically and fed with RYP through gavage. Breast tumor growth, metastasis and tumor expression of EMT markers were detected. RESULTS: Compared with the control, Ruyiping formula significantly inhibited SLUG-regulated breast cancer cells invasion. MiR-134 was induced by RYP in vitro and in vivo and was able to suppress SLUG by targeting its 3'UTR. RYP suppressed SLUG expression and cell invasion through miR-134. In 4 T1 tumor-bearing mice, RYP significantly inhibited 4 T1 tumor growth and lung metastasis, increased the levels of miR-134 and epithelial marker while decreased the levels of SLUG and mesenchymal marker. CONCLUSION: Our data uncovered that Ruyiping formula exerts an anti-metastatic activity against breast cancer cells by regulating SLUG through miR-134. MiR-134-SLUG axis might be a promising strategy in breast cancer therapy.

Analgesic Effect of Electroacupuncture on Postherpetic Neuralgia: A Trial Protocol for a Multicenter Randomized Controlled Trial.

INTRODUCTION: The chronic neuropathic pain associated with postherpetic neuralgia (PHN) can last for several months or even many years, seriously affecting the affected person's work, sleep, mood, and daily life activities. In generaly, current treatments for PHN are at best limited and unsatisfactory, and adverse reactions are common, especially in elderly patients. Electroacupuncture (EA) is widely used clinically to manage painful diseases, but there remains a lack of evidence to support the effectiveness of EA on PHN. This study is designed to assess the efficacy and safety of EA on PHN, and to provide evidence-based medical evidence for EA treatment of PHN. METHODS: This multicenter, prospective, randomized controlled trial will recruit 448 patients with PHN at seven clinical centers. Multicenter stratified variable block randomization will be used, and the eligible patients will be randomly allocated in a ratio of 1:1 to the EA group or sham EA group. The EA group will receive 4 weeks of EA treatment, given as 30-min treatment sessions, once daily, 5 times per week, for a total of 20 treatments; the sham EA group will receive sham EA treatment under the same conditions. PLANNED OUTCOMES: The primary outcome measure is the 11-point Numeric Rating Scale pain score at week 4. The secondary outcome measures, including mechanical pain threshold, pain area of PHN, average number of pain episodes, the short-form McGill Pain Questionnaire 2, Zoster Brief Pain Inventory, the Depression, Anxiety, and Positive Outlook Scale, Patient Global Impression of Change, safety of EA, and use of concomitant medications, among others. The primary analysis of the outcomes will be the mixed-effect model with repeated measurement between groups on an intent-to-treat population. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04560361. Registered 23 September 2020 ( https://clinicaltrials.gov/ct2/show/NCT04560361?term=NCT04560361&draw=2&rank=1 ).

A Bibliometric Analysis of Research Trends of Acupuncture Therapy in the Treatment of Migraine from 2000 to 2020.

BACKGROUND: Migraine is the second-leading cause of disability worldwide. It is often characterized by attacks of severe, mostly unilateral, pulsating headache associated with symptoms such as photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia. Acupuncture therapy has been used worldwide for the treatment of migraine. However, no visual bibliometric analysis has been conducted on the effects of acupuncture on migraine over the past 20 years. Therefore, this study aimed to explore the current status and trends on the use of acupuncture in the treatment of migraine from 2000 to 2020. PURPOSE: The objective of this study is to identify the current status and emerging trends of the global use of acupuncture on migraine from 2000 to 2020 using CiteSpace and VOSviewer. METHODS: Web of Science databases were searched for publications related to acupuncture therapy for treating migraine between 2000 and 2020. CiteSpace and VOSviewer were used to analyze the number of publications per year, countries, institutions, authors, journals, references, and keywords. RESULTS: A total of 572 publications were included in the final analysis. The total number of publications has continued to increase with some fluctuations over the past 20 years. The most productive country and institution in this field were the USA, and Chengdu University of Traditional Chinese Medicine, respectively. The most active and cited authors were Liang FR and Linde K, respectively. Cephalalgia was the most productive, cited, and co-cited journal. The Linde K (2005) had the highest co-citation, citation number and centrality. The keywords "migraine" ranked first in frequency. The common type of migraine (tension-type headache), research method (randomized controlled trial, multicenter, double-blind), acupuncture's role (prophylactic, quality of life, pain), and evaluation (meta-analysis, systematic review) were the hotspots and frontier trends of acupuncture therapy on migraine between 2000 and 2020. CONCLUSION: The present study examined the research-related trend in acupuncture therapy on migraine using bibliometric methods and identified the statement and research frontiers over the past two decades. This may help researchers to identify potential hotspots and new directions for future research in this field.

[Mind-regulating and spleen-strengthening needling technique improves abdominal hypersensitivity and emotion by enhancing functional connectivity between hippocampus and brain regions in diarrhea-predominant irritable bowel syndrome patients].

OBJECTIVE: To compare the difference of brain functional connectivity between diarrhea-predominant irritable bowel syndrome (IBS-D) patients and healthy volunteers and changes after acupuncture intervention, so as to investigate the underlying mechanism of acupuncture in regulating functional activities of IBS-D patients by using seed point correlation analysis. METHODS: A total of 25 IBS-D patients and 25 healthy volunteers were recruited in the present study and respectively attributed to acupuncture group and control group. The IBS-D patients received manual acupuncture stimulation of Baihui (GV20), Yintang (EX-HN3), and bilateral Tianshu (ST25), Zusanli (ST36), Shangjuxu (ST37), Sanyinjiao (SP6) and Taichong (LR3) with mind-regulating and spleen-strengthening technique for 30 min, once a day, 3 days a week for 6 weeks. Before and after the intervention, the IBS symptom severity scale (IBS-SSS) was used to assess the patients' state of abdominal pain, distention and defecation, and Hamilton Anxiety Rating Scale (HAMA) employed to evaluate the patients' anxiety severity. The resting state functional magnetic resonance imaging (rs-fMRI) data were acquired and preprocessed by using SPM8 and DPARSE soft-wares. Seeds (bilate-ral hippocampus regions) to whole-brain analysis was performed to obtain the mean time series of the left and right seed regions, followed by making Pearson correlation analysis to obtain the correlation coefficient (time series from each seed region with the rest of the voxels in the brain), and making a multivariate comparative correction to get data of functional connectivity (FC) of bilateral hippocampus regions and to find the related difference in the brain regions. Then, the differences of the FC of brain regions between IBS-D patients and healthy volunteers were compared. RESULTS: Following acupuncture treatment, both the HAMA and IBS-SSS scores were significantly reduced in the acupuncture group compared with its pre-treatment (P<0.01). Compared with the healthy volunteers, there were a reduction in the functional connectivity between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus and left superior gyrus, and between the right hippocampus region and the right fusiform gyrus, left inferior temporal gyrus, left inferior occipital gyrus, left rectus gyrus, left insula, left precuneus, right angular gyrus, left middle occipital gyrus, right precuneus, and the left superior temporal gyrus, and an increase in the FC between the left hippocampus and left superior temporal gyrus was increased in ISB-D patients. Self-comparison showed that after the treatment, the FC was increased between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus, bilateral lingual gyrus, left amygdala, right inferior occipital gyrus, right insula, right middle frontal gyrus, left middle frontal gyrus and the left middle occipital gyrus; and between the right hippocampus seed region and the posterior inferior cerebellar lobe, left inferior temporal gyrus, left suboccipital gyrus, right fusiform gyrus, left insula, right inferior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right middle frontal gyrus, left supplementary motor area and right supplementary motor area, and decreased between the left hippocampus region and the left anterior cingulate, paracingulate gyrus and the right posterior central gyrus in IBS-D patients. CONCLUSION: Mind-regulating and spleen-strengthening acupuncture intervention may improve the abdominal pain and distension and emotional state in IBS-D patients, which is possibly associated with its effect in enhancing FC between the hippocampus and brain regions.

[Correlation between curative effect and 5-HTTLPR polymorphism in treatment of diarrhea-predominant irritable bowel syndrome with acupuncture for regulating shen and strengthening spleen].

OBJECTIVE: To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating shen and strengthening spleen and pinaverium bromide, and explore the relevant mechanism of curative effect of acupuncture in view of polymorphism of 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR). METHODS: A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating shen and strengthening spleen, i.e. Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37) and Zusanli (ST 36), etc. The treatment was given once every 2 days, 3 times a week. In the western medication group, pinaverium bromide was prescribed for oral administration, 50 mg each time, 3 times daily. The duration of treatment was 6 weeks in each group. Separately, before treatment, after treatment and in 3-month follow-up, the IBS symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) scores were adopted in assessment. After treatment, the curative effect and safety were compared between the two groups. Before treatment, 5-HTTLPR genotypes were determined in the patients. RESULTS: After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (P<0.01) and the scores in the acupuncture group were lower than those in the western medication group (P<0.01). After treatment and in follow-up, the total scores of IBS-QOL in the two groups were all increased as compared with those before treatment (P<0.01) and the score in the acupuncture group was higher than the western medication group in follow-up (P<0.01). The total effective rate was 79.2% (122/154) in the acupuncture group, higher than 58.4% (45/77) in the western medication group (P<0.01). There was no severe adverse reaction found in the two groups. The difference in the total score of IBS-SSS before and after treatment in the patients with LS and SS genotypes was greater than that in the patients with LL in the acupuncture group (P<0.01). The difference in the total score of ISB-SSS before and after treatment in the patients with SS genotype was greater than that in the patients with LL in the western medication group (P<0.01). The difference in the total score of IBS-SSS before and after treatment in the patients with LS and SS genotypes in the acupuncture group was greater than that in the patients with the same genotypes in the western medication group (P<0.01). CONCLUSION: Acupuncture for regulating shen and strengthening spleen achieves the more curative effect on IBS-D as compared with pinaverium bromide. The acupuncture regimen effectively relieves the clinical symptoms and improves the quality of life in patients as well as presents a satisfactory long-term effect and safety. The clinical curative effect of acupuncture is correlated with 5-HTTLPR polymorphism, in which, the curative effect of acupuncture may be more effective in the patients with LS and SS genotypes.

[Effect of Tiaoshen Jianpi acupuncture therapy on gut microbiota and fecal short-chain fatty acids in patients with diarrhea type irritable bowel syndrome].

OBJECTIVE: To observe the clinical therapeutic effect of Tiaoshen Jianpi acupuncture therapy (acupuncture for regulating the mind and strengthening the spleen) on the gut microbiota and the content of fecal short-chain fatty acids (SCFAs) in patients with diarrhea type irritable bowel syndrome (IBS-D). METHODS: A total of 20 patients with IBS-D and 20 healthy subjects were included. The patients with IBS-D were treated with Tiaoshen Jianpi acupuncture therapy at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). The treatment was given once every two days, 3 times weekly, consecutively for 6 weeks. No intervention was provided for the healthy subjects. Before and after treatment, the IBS symptom severity score (IBS-SSS) was observed in the patients. The fecal samples were collected before and after treatment separately in the patients and in the healthy subjects. Using 16S rRNA sequencing technique, the structure and diversity of gut microbiota were analyzed. Using high-performance liquid chromatography, the content of SCFAs was detected. RESULTS: After treatment, the abdominal pain severity score, the abdominal pain days score, the satisfaction in bowel movement score, the life interference score and the total IBS-SSS score were all lower than those before treatment in the patients with IBS-D (P<0.05). Compared with the healthy subjects, Firmicutes was increased (P<0.05), Bacteroidetes and Proteobacteria were decreased (P<0.05), and Shannon index was reduced (P<0.05) and Simpson index was increased in patients with IBS-D before treatment (P<0.05). Compared before treatment, Firmicutes was decreased (P<0.05), Bacteroidetes and Proteobacteria were increased (P<0.05), and Shannon index was increased (P<0.05) and Simpson index was reduced in the patients with IBS-D after treatment (P<0.05). Besides, the content of SCFAs was reduced after treatment (P<0.05). CONCLUSION: Tiaoshen Jianpi acupuncture therapy relieves abdominal pain and diarrhea, which may be related to regulating the structure and diversity of gut microbiota and reducing the content of fecal SCFAs in the patients with IBS-D.

Polysaccharide-rich extract from Polygonatum sibiricum protects hematopoiesis in bone marrow suppressed by triple negative breast cancer.

Polysaccharide is one of main components in Polygonatum sibiricum (PS), which is an herbal medicine widely used in East Asia. Polysaccharides from Polygonatum sibiricum has been shown to exhibit multiple biological activities, such as anti-diabetes, anti-inflammation, antioxidant, immunity modulation, and anticancer. Since hematopoietic system is one of determinant factors in cancer control, we here explored the effect of polysaccharide-rich extract from Polygonatum sibiricum (PREPS) on hematopoiesis in the mice bearing triple negative breast cancer (TNBC). We found that the 4T1 TNBC tumor significantly increased myeloid cells in peripheral blood, bone marrow and spleen, while decreasing bone marrow hematopoietic stem and progenitor cells (HSPCs), indicative of an inhibition of medullary hematopoiesis. When 4T1 TNBC tumor-bearing mice were treated with PREPS, the percentage of myeloid cells within tumor-infiltrating immune cells was reduced. In addition, PREPS also inhibited hematopoietic cell expansion in the spleen, which was induced by TNBC tumors. Importantly, PREPS markedly increased HSPCs and common lymphoid progenitors in the bone marrow that had been suppressed by TNBC tumors. These findings suggest that PREPS protect hematopoiesis inhibited by TNBC tumors in the bone marrow. Although PREPS alone did not achieve statistical significance in the suppression of TNBC tumor growth, it may have a long-lasting anti-tumor effect to assist TNBC therapies by sustaining hematopoiesis and lymphoid regeneration in bone marrow.