Catgut embedding in acupoints combined with repetitive transcranial magnetic stimulation for the treatment of postmenopausal osteoporosis: study protocol for a randomized clinical trial.

Background: To date, the clinical modulation for bone metabolism based on the neuro-bone mass regulation theory is still not popular. The stimulation of nerve systems to explore novel treatments for Postmenopausal osteoporosis (PMOP) is urgent and significant. Preliminary research results suggested that changes brain function and structure may play a crucial role in bone metabolism with PMOP. Thus, we set up a clinical trial to investigate the effect of the combination of repetitive transcranial magnetic stimulation (rTMS) and catgut embedding in acupoints (CEA) for PMOP and to elucidate the central mechanism of this neural stimulation in regulating bone metabolism. Method: This trial is a prospective and randomized controlled trial. 96 PMOP participants will be randomized in a 1:1:1 ratio into a CEA group, an rTMS group, or a combined one. Participants will receive CEA, rTMS, or combined therapy for 3 months with 8 weeks of follow-up. The primary outcomes will be the changes in Bone Mineral Density scores, total efficiency of Chinese Medicine Symptoms before and after treatment. Secondary outcomes include the McGill Pain Questionnaire Short-Form, Osteoporosis Symptom Score, Mini-Mental State Examination, and Beck Depression Inventory-II. The leptin, leptin receptor, and norepinephrine levels of peripheral blood must be measured before and after treatment. Adverse events that occur during the trial will be recorded. Discussion: CEA achieves brain-bone mass regulation through the bottom-up way of peripheral-central while rTMS achieves it through the top-down stimulation of central-peripheral. CEA combined with rTMS can stimulate the peripheral-central at the same time and promote peripheral bone mass formation. The combination of CEA and rTMS may play a coordinating, synergistic, and side-effect-reducing role, which is of great clinical significance in exploring better treatment options for PMOP.Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300073863.

Acupoints catgut embedding recovers leptin resistance via improving autophagy progress mediated by AMPK-mTOR signaling in obese mice.

Purpose: Leptin resistance represents a primary pathological manifestation in obesity. Investigating potential treatments and associated mechanisms to restore leptin sensitivity is crucial for effective obesity management. This study aimed to explore the therapeutic potential of acupoints catgut embedding (ACE) in addressing obesity and its associated leptin resistance. Methods: A simple obesity model was established by subjecting C57 male mice to a high-fat diet (HFD) for 12 weeks, followed by ACE treatment administered to half of the obese mice for a duration of 4 weeks. The levels of leptin and its receptor-lepRb, were assessed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. Autophagy progression markers were evaluated through quantitative polymerase chain reaction (qPCR) and Western blot analysis. Also, the liver autophagosomes were photographed using electron microscopy. The role of autophagy in regulating leptin resistance was elucidated using an autophagy suppression model. Results: Comparative analyses demonstrated that ACE treatment resulted in a significant reduction in body weight and blood lipid levels compared to the HFD group. Furthermore, serum leptin levels decreased, while liver lepRb expression increased following ACE treatment. The mRNA and protein expression levels of autophagy in liver were adjusted by ACE treatment. Interestingly, the beneficial effects of ACE were attenuated upon the administration of an autophagy inhibitor. Additionally, ACE treatment led to the activation of the AMPK-mTOR signaling pathway, a crucial regulator of autophagy. Conclusion: These findings suggest that ACE therapy holds promise for recovering leptin resistance by enhancing autophagy progression, mediated via the AMPK-mTOR signaling pathway in liver.

Yingxiang Acupoint Embedding Improves Mucosal Barrier Function in Rats with Local Allergic Rhinitis.

INTRODUCTION: Epithelial barrier disruption is the initial cause of various diseases. We previously reported that acupoint catgut embedding (AE) improves tight junction proteins (TJs) in rats with allergic rhinitis. However, whether AE improves the epithelial barrier in local allergic rhinitis (LAR) remains unknown. METHODS: A total of 36 Sprague Dawley (SD) male rats aged 5-7 weeks were divided into 6 groups with 6 rats each: control group, LAR model group, false acupoint embedding + LAR group, acupoint embedding + LAR group, capsaicin + LAR group, and tunicamycin + acupoint embedding + LAR group. Behavioral observation, ELISA to detect inflammatory factors in nasal lavage fluid and serum IgE, nasal mucosal permeability test, hematoxylin-eosin staining, PCR to detect Substance P (SP), Western blot, and immunofluorescence to detect endoplasmic reticulum stress (ERS) index and TJs were used to investigate the mechanism of AE in LAR. RESULTS: AE improved the symptoms and pathological features of nasal mucosa of LAR rats, reduced the inflammatory factors (IL4, IL5, IL13) of nasal lavage fluid, and showed no significant change in serum IgE levels in all groups. In addition, AE decreased the expression of SP in nasal mucosa of LAR rats, inhibited ERS, increased the expression of tight junction protein, reduced the permeability of nasal mucosa, and improved the function of nasal mucosal barrier. CONCLUSION: This study confirms that AE can improve the nasal mucosal barrier function of LAR by reducing the expression of SP, inhibiting ERS and increasing the expression of TJs, thus enhancing the nasal mucosal barrier function.

Efficacy and Safety of Acupoint Catgut Embedding for Knee Osteoarthritis: a Protocol for Systematic review and Meta-Analysis.

Background: Knee osteoarthritis causes physical dysfunction, and its prevalence increases with age. Although clinical studies examined acupoint catgut embedding in patients with knee osteoarthritis, no systematic reviews or meta-analyses have been conducted to date. We aim to comprehensively review the effects of acupoint catgut embedding on knee osteoarthritis. Methods: Eleven databases will be searched from inception to August 1, 2023, without language limitations. Additionally, two registration platforms-ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry-will be searched for ongoing trials. The primary outcomes will be assessed using the Visual Analog Scale and the Western Ontario and McMaster Universities Osteoarthritis Index. Secondary outcomes include the total effective rate, Lysholm Score, and adverse effects. Two reviewers will independently select the studies, extract data, and evaluate the risk of bias and the quality of evidence. Discussion: This systematic review will provide evidence regarding the safety and efficacy of acupoint catgut embedding in patients with knee osteoarthritis.

Acupoint catgut embedding attenuates fibromyalgia pain through attenuation of TRPV1 signaling pathway in mouse.

Objectives: Chronic pain is considered as pain lasting for more than three months and has emerged as a global health problem affecting individuals and society. Chronic extensive pain is the main syndrome upsetting individuals with fibromyalgia (FM), accompanied by anxiety, obesity, sleep disturbances, and depression, Transient receptor potential vanilloid 1 (TRPV1) has been reported to transduce inflammatory and pain signals to the brain. Materials and Methods: Acupoint catgut embedding (ACE) is a novel acupuncture technique that provides continuous effects and convenience. ACE was performed at the bilateral ST36 acupoint. Results: We demonstrated similar pain levels among all groups at baseline. After cold stress, chronic mechanical or thermal nociception was induced (D14: mechanical: 1.85 ± 0.13 g; thermal: 4.85 ± 0.26 s) and reversed in ACE-treated mice (D14: mechanical: 3.99 ± 0.16 g; thermal: 7.42 ± 0.45 s) as well as Trpv1-/- group (Day 14, mechanical: 4.25 ± 0.2 g; thermal: 7.91 ± 0.21 s) mice. Inflammatory mediators were augmented in FM individuals and were abridged after ACE management and TRPV1 gene loss. TRPV1 and its linked mediators were increased in the thalamus (THA), somatosensory cortex (SSC), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) in FM mice. The up-regulation of these mediators was diminished in ACE and Trpv1-/- groups. Conclusion: We suggest that chronic pain can be modulated by ACE or Trpv1-/-. ACE-induced analgesia via TRPV1 signaling pathways may be beneficial targets for FM treatment.

Effect of acupoint catgut embedding on p38 MAPK pathway in the lung tissue of asthmatic rats. / 穴位埋线通过调节p38ä¸è£‚åŽŸæ´»åŒ–è›‹ç™½æ¿€é ¶é€šè·¯å¯¹å“®å–˜å¤§é¼ æ°”é“ä¸Šçš®çš„å½±å“.

OBJECTIVES: To observe the effect of catgut embedding at "Feishu"(BL13), "Dingchuan" (EX-B1) and "Danzhong" (CV17) on expression of phosphorylated p38 mitogen activated protein kinase (p-p38 MAPK), interleukin-4 (IL-4), interferon-γ (IFN-γ) and changes of airway epithelial cells (AEC) in the lung tissue of bronchial asthma (BA) rats, so as to explore its mechanisms underlying improvement of BA. METHODS: Forty male Wistar rats were randomly and equally divided into blank control, model, dexamethasone (DEX) and catgut embedding groups. The BA model was established by intraperitoneal injection of suspension of ovalbumin and aluminum hydroxide. Rats of the DEX group received intraperitoneal injection of DEX (1.5 mg/kg), once daily for 2 weeks, and those of the catgut embedding group received catgut embedding at BL13, EX-B1 and CV17 only one time. The rats' sneezing times per miniute in each group were recorded. H.E. staining was used to observe the histopathological changes of the lung tissue under light microscope. A transmission electron microscope (TEM) was used to observe the ultrastructural changes of AEC in the lung tissue, including the thickness of bronchial wall and bronchial smooth muscle by using an image analysis software. The protein expressions of p-p38 MAPK, IL-4 and INF-γ in the lung tissue were determined using Western blot. RESULTS: Morphological observation revealed that in the model group, light microscope showed deformed and swollen bronchial tube wall with increased folds and thickened bronchial smooth muscle；and TEM showed a large number of autophagy vesicles containing swollen and deformed organelles in the AEC, and apparent reduction of intracellular mitochondria, these situations were obviously milder in both DEX and catgut embedding groups. Compared with the blank control group, the sneezing times, thickness of bronchial wall and bronchial smooth muscle in the model group were significantly increased (P<0.01), and the expressions of p-p38 MAPK and IL-4 in lung tissue were significantly increased (P<0.01), while the expression of IFN-γ was significantly decreased (P<0.01) in the model group. In comparison with the model group, the sneezing times, thickness of bronchial wall and bronchial smooth muscle, protein expressions of p-p38 MAPK and IL-4 were significantly decreased (P<0.01), while the expression of IFN-γ was obviously increased (P<0.01) in both the DEX and catgut embedding groups. CONCLUSIONS: Acupoint catgut embedding can reduce the expression of IL-4 and increase the expression of IFN-γ by inhibiting p38 MAPK signal pathway of lung tissues in BA rats, which may contribute to its effect in alleviating the degree of airway epithelial cells damage.

Effects of electroacupuncture combined with acupoint catgut embedding on gastrointestinal motility and gastrointestinal hormones in rats with functional dyspepsia.

Electroacupuncture (EA) or acupoint catgut embedding (ACE) plays a therapeutic role in functional dyspepsia (FD). Herein, we aimed to elucidate the influences of EA combined with ACE on gastrointestinal motility and gastrointestinal hormones in rats with FD. Sprague-Dawley rats were randomized into the control group, model group, EA group, ACE group, and EA + ACE group (n = 10). Except for the control group, the rats in all groups were modeled by combining neonatal iodoacetamide gastrogavage and modified tail-clamping stimulation. The rats were treated with different treatments according to their groups. The rats were observed for changes in general behavior, body weight, food intake, and paw mechanical pain threshold. Gastric emptying rate (GER) and intestinal propulsive ratio (IPR) were measured in each group, and serum gastrointestinal hormone (motilin [MTL], leptin, gastrin [GAS], vasoactive intestinal peptide [VIP], calcitonin gene-related peptide [CGRP], and somatostatin [SS]) levels, oxidative stress factors (superoxide dismutase [SOD] and malondialdehyde [MDA]) and 5-hydroxytryptamine (5-HT) levels were also measured. Decreased mean body weight, paw mechanical pain thresholds, food intake, and GER and IPR were found in rats of the model group in comparison to the control group. Serum MTL, GAS, SS, and SOD levels were reduced, and serum leptin, VIP, CGRP, MDA, and 5-HT levels were increased in rats of the model group in comparison to the control group. Elevated mean body weight, paw mechanical pain threshold, food intake, GER and IPR, and serum MTL, GAS, SS, and SOD levels, and reduced serum leptin, VIP, CGRP, MDA, and 5-HT levels were observed in rats of the EA, ACE, and EA + ACE groups relative to the model group. EA combined with ACE treatment was more effective than the EA or ACE treatment alone. EA combined with ACE treatment improves gastrointestinal motility and gastrointestinal hormone levels, promotes food intake, and reduces visceral hypersensitivity in FD rats.

A study on the use of acupoint catgut embedding in the treatment of pre-diabetes: a meta-analysis and data mining approach.

Objective: The efficacy of acupoint catgut embedding (ACE) for the treatment of pre-diabetes remains controversial. Therefore, this study investigated the clinical efficacy and acupoint selection in ACE for the treatment of pre-diabetes. Methods: Eight common databases were searched for relevant literature on ACE for pre-diabetes. Meta-analysis was used to evaluate its efficacy and safety, and data mining was used to explore the protocol for acupoint selection. Results: The meta-analysis revealed that compared with conventional treatment alone, conventional treatment combined with ACE reduced the levels of glycated hemoglobin A1c [mean difference (MD) -0.45, 95% confidence interval (CI) -0.67 to -0.24%, p < 0.001], fasting blood glucose (MD -0.61 mmol/L, 95% CI -0.87 to -0.36 mmol/L, p < 0.001), 2-h postprandial glucose (MD -0.77 mmol/L, 95% CI -0.98 to -0.55 mmol/L, p < 0.001), total cholesterol (MD -0.37 mmol/L, 95% CI -0.74 to 0.00 mmol/L, p = 0.049), triglyceride (MD -0.49 mmol/L, 95% CI -0.77 to -0.20 mmol/L, p < 0.001) and low-density lipoprotein cholesterol (MD -0.23 mmol/L, 95% CI -0.33 to -0.12 mmol/L, p < 0.001), and increased high-density lipoprotein cholesterol levels (MD 0.16 mmol/L, 95% CI 0.05 to 0.27 mmol/L, p = 0.004), whereas changes in the body mass index and the adverse event rates were comparable between groups. Data mining revealed that Pishu (BL20), Weiwanxiashu (EX-B3), Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Weishu (BL21), and Taixi (KI3) were the core acupoints used in ACE for pre-diabetes. Conclusion: ACE can effectively improve blood glucose and lipid levels in pre-diabetes patients and has a good safety profile. ACE consisting of Pishu (BL20), Weiwanxiashu (EX-B3), Zusanli (ST36), Shenshu (BL23), Sanyinjiao (SP6), Weishu (BL21), and Taixi (KI3), is a promising complementary strategy for the treatment of pre-diabetes.

Acupoint catgut embedding for simple obesity in animal studies: a systematic review and Meta-analysis.

OBJECTIVE: To assess the efficacy of acupoint catgut embedding (ACE) for simple obesity in preclinical animal experiments. METHODS: We searched the following 14 electronic databases: PubMed, Cochrane Library, EMBASE, Oriental Medicine Advanced Searching Integrated System, KoreaMed, Korean Studies Information Service System, Science-on, Research Information Sharing Service, Korea Citation Index, Korea Traditional Knowledge Portal, China Network Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, and Chinese Biology Medicine Database, from inception to November 2021 without language limitation. The assessment was performed according to the guidelines of Animal Research: Reporting of experiments; and Meta-analysis was performed using Reviewer Manager 5.4.1 software. RESULTS: Twenty-four studies involving 813 animals were selected. Meta-analysis showed that ACE was beneficial for weight control [ 40, = -50.63, 95% (－57.59, －43.67), 0.000 01, = 0%] and reduced the Lee index [ 40, = －18.79, 95% (－20.01, －17.57), 0.000 01, = 0%]. However, when efficacy of ACE was compared with that of manual acupuncture, electroacupuncture, or oilistat therapy, statistical difference was not observed between the two groups. CONCLUSIONS: This systematic review suggests that ACE may be efficacious in treating obesity. Moreover, the analyses highlighted the necessity to perform well-designed, higher-quality experiments.

Efficacy of catgut embedding in Baihui (GV20) and Feishu (BL13) and Pishu (BL20) on lung tissue, brain tissue and blood related indexes in rats with allergic rhinitis of lung deficiency type.

OBJECTIVE: To investigate the effects of acupoint catgut embedding for 3 weeks on lung tissue, blood immunoglobulin E (IgE) and interleutin-4 (IL-4), brain tissue microglia x-42 (OX-42) and toll-like receptor-2 (TLR-2) in rats with allergic rhinitis of lung deficiency type. METHODS: Forty-five female Sprague-Dawley rats were randomly divided for two times. The first time, they were randomly divided into model group and blank group (Group C) according to 2:1, and the second time, the model group were randomly divided into model control group (Group B) and intervention treatment group (Group A) according to 1:1. 15 in each group. For Group A and Group B, the lung deficiency model was made by "sulfur-moxa fumigation", and then the allergic rhinitis model was established by "ovalbumin (OVA) sensitization". Then catgut embedding was performed at acupoints in Group A and not in Group B. After 3 weeks, collect lung tissue samples for hematoxylin-eosin staining, then take blood to observe the concentration of IgE and IL-4, and finally take brain tissue to observe the results of OX-42 and TLR-2. RESULTS: IgE level (µg/mL) was (3.11 ± 0.20) in the Group A, (4.19 ± 0.44) in the Group B, and (2.29 ± 0.30) in the Group C (all < 0.001). IL-4 level (pg/mL) was (14.2 ± 0.7) in the Group A, (18.6 ± 2.4) in the Group B, and (11.4 ± 1.2) for the Group C (all < 0.001). The mean OD for OX-42 is (0.1728 ± 0.0016) in the Group A, (0.1810 ± 0.0046) in the Group B and (0.1674 ± 0.0025) in the Group C (all < 0.001). CONCLUSION: Although 3 weeks of acupoint catgut embedding already showed obvious efficacy on rats with allergic rhinitis, the allergic reaction in the body still continued. To achieve further treatment, prolonging the catgut embedding time is necessary.

General Morphological Characteristics of the Results of Experimental Modeling of Aseptic Peritonitis.

BACKGROUND: Aseptic peritonitis is a reaction of the local immune system aimed at rejection of a foreign body, which, having antigenic properties, does not (unlike a pathogen) counteract the immune system. The suture materials, namely catgut thread, used in intracavitary surgical operations possess xenogenic properties and can be used for antigenic stimulation of the immune system of the peritoneal cavity. Consequently, we decided to use a catgut suture for antigenic stimulation of the immune system of the peritoneal cavity and to study the morphological features of the results of experimental modeling of aseptic peritonitis in albino rats. METHOD: The study involved 15 Wistar albino male rats, weighing 286,13 ± 6,26 g. To study the dynamics of destructive changes made by the catgut implant in the peritoneal cavity of the experimental animals, the animals were assigned into three groups in accordance with the time interval of their euthanasia at 3, 7, and 14 days of the experiment. RESULTS: After modeling an aseptic peritonitis, the investigation the abdominal cavity showed that in four out of five animals of the first group, that is, on day 3 of the experiment, the catgut implant had adhered to the greater omentum. The search for the fifth implant led to an unexpected discovery: we found it conjoined with the second derivative of the visceral peritoneum, similar in structure to the greater omentum, but related to the testes. On day 7, the implant embedded into the peritoneal cavity of the animals, had adhered to the serous formations of the testes in all five cases (100%, three of them - to the left epididymal omentum, and another two - to the right one). On day 14 (n = 5) it was found that in three cases it had adhered to the serous formations of the testes (60%, one of them to the left epididymal omentum, another two - to the right one) and in two cases it had adhered to the greater omentum (40%). CONCLUSION: During the experiment on implantation of a xenogenic substrate in the form of flat bundles made from the catgut thread into the peritoneal cavity of sexually mature male rats, it was found for the first time that their acceptors were not only the greater omentum, but also two derivatives of the peritoneum, homeomorphic to it and associated with the epididymides, which we reasonably called epididymal omenta and described in details.

[Effects of catgut embedding and PGLA embedding at "Zusanli" (ST 36) on skin mast cells, substance P and histamine in healthy rats].

OBJECTIVE: To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding. METHODS: One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells. RESULTS: There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05). CONCLUSION: Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.

The Effect of Catgut Embedding at Acupoints Versus Nonacupoints in Abdominal Obesity: Protocol for a Multicenter, Double-Blind, 16-Week Randomized Controlled Trial.

BACKGROUND: Obesity is an increasing problem worldwide. The effective treatments for obesity mainly include diet, physical activity, behavioral intervention, pharmacotherapy, and bariatric surgery, which all have certain limitations. As a specific type of acupuncture therapy, acupoint catgut embedding (ACE) has gained substantial attention in the management of obesity in recent years. Previous studies suggested that ACE may be an effective obesity treatment. However, the evidence for the efficacy of ACE in abdominal obesity (AO) remains inadequate due to the paucity of high-quality studies. OBJECTIVE: This study aims to investigate the difference in the effectiveness of catgut embedding at acupoints and catgut embedding at nonacupoints in patients with AO and to further validate the efficacy and safety of ACE for AO. METHODS: This is a multicenter, double-blind, 16-week randomized controlled trial. A total of 92 eligible participants with AO will be randomly divided into 2 groups (1:1 allocation ratio). The ACE group will receive catgut embedding at acupoints and the control group will receive catgut embedding at nonacupoints. The intervention will be performed every 2 weeks for a total of 6 sessions. Follow-up will be performed every 2 weeks for a total of 2 visits. The primary outcome is waist circumference. Secondary outcomes include body weight, BMI, hip circumference, and the visual analog scale of appetite. Upon the completion of the trial, we will evaluate the effect of catgut embedding at acupoints or nonacupoints on obesity indicators in patients with AO. For treatment outcomes, an intention-to-treat analysis will be performed. RESULTS: The start of recruitment began in August 2019 and is expected to end in September 2023. CONCLUSIONS: Although studies have been conducted to demonstrate the effectiveness of ACE in the treatment of obesity, the evidence for the efficacy of ACE in AO remains insufficient due to the quality of the studies. This rigorous normative randomized controlled trial will verify the effect of catgut embedding at acupoints or nonacupoints in patients with AO. The findings will provide credible evidence as to whether ACE is an effective and safe treatment for AO. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800016947; https://tinyurl.com/2p82257p. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46863.

[Acupoint catgut embedding relieves colonic inflammatory injury by down-regulating NLRP3/Caspase-1 signaling pathway in rats with ulcerative colitis].

OBJECTIVE: To observe the effect of acupoint catgut embedding (CE) on Nod-like receptor protein 3 (NLRP3)/Caspase-1 signaling pathway in "deficiency-stasis" syndrome type ulcerative colitis (UC) rats, so as to explore its mechanisms underlying improvement of UC. METHODS: A total of 58 male SD rats were randomly divided into control group (10 rats) and model group (48 rats). The "deficiency-stasis" type UC model was established by gavage of adenine and folium sennae solution for 4 weeks, followed by clycter of mixture solution of 5% trinitro-benzene-sulfonic acid and 50% ethanol. A total of 44 UC rats were randomized into model, salicylazosulfapyridine (SASP), non-acupoint CE, and acupoint CE groups (11 rats in each group). The catgut embedment was applied to bilateral "Zusanli"(ST36), "Shenshu"(BL23), "Pishu"(BL20), "Dachangshu"(BL25), "Geshu" (BL17) and "Tianshu"(ST25), or non-acupoints (the fat muscles of the buttocks), separately, once every two weeks, 3 times altogether. Rats of the SASP group received gavage of SASP solution, and those of the other groups received gavage of same amount of normal saline, once daily for 42 days. The rat's general conditions and the colon length were recorded, the disease activity index (DAI, 0 to 4 points) and colonic mucosal damage index (CMDI, 0 to 5 points) were calculated. Histopathological changes of the colonic mucosa tissue were observed after HE staining, and the tissue damage index (TDI, 0 to 6 points) was given. The levels of serum NLRP3, interleukin (IL)-1ß and IL-18 were measured by ELISA, and the expression levels of NLRP3, Caspase-1, apoptosis-associated speck-like protein (ASC), IL-1ß and IL-18 mRNAs were measured by fluorescence quantitative PCR. The expression levels of NLRP3 and Caspase-1 proteins in the colon tissues were measured by Western blot, and the immunoactivity of colonic ASC was detected by immunohistochemistry. RESULTS: Compared with the control group, the rats' body mass and colonic length were significantly decreased (P<0.01), and DAI score, CMDI score, TDI score, contents of serum NLRP3, IL-1ß and IL-18, expression levels of colonic NLRP3, ASC, Caspase-1, IL-1ß and IL-18 mRNAs, and NLRP3 and Caspase -1 proteins as well as colonic ASC immunoactivity were significantly up-regulated in the model group (P<0.01). Compared with the model group, both SASP and acupoint CE groups had a significant increase in body mass and colonic length (P<0.01), and a marked decrease in DAI score, CMDI score, TDI score, contents of serum NLRP3, IL-1ß and IL-18, expression levels of NLRP3, ASC, Caspase-1, IL-1ß and IL-18 mRNAs and NLRP3 and Caspase-1 proteins and ASC immunoactivity (P<0.01). The above indexes were improved in the acupoint CE group in relevant to those of the non-acupoint CE group (P<0.01). HE staining of colonic mucosal tissue showed obvious ulcerative surface, destroyed recess, disordered arrangement of glands, mucosal edema and congestion, infiltration of a large number of inflammatory cells in the model group, which was obviously milder in both SASP and acupoint CE groups. CONCLUSION: Acupoint embedding can alleviate colonic injury and inhibit inflammatory reaction in rats with "deficiency-stasis" type UC by down-regulating colonic NLRP3/Caspase-1 signaling.

[Effect of catgut implantation on macrophage CD68, tumor necrosis factor-α and interleukin-1ß in "Zusanli" (ST 36) region of rats].

OBJECTIVE: To observe the expression of local macrophages and related cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) after catgut implantation in "Zusanli"(ST 36) in rats, so as to explore its underlying mechanisms in inducing therapeutic effect. METHODS: A total of 110 male SD rats were randomly divided into blank control group (n=10), catgut embedding (CE) group (n=50), and sham CE group (n=50). The CE and sham CE groups were randomly divided into 8 h, 3 d, 7 d, 14 d and 21 d subgroups after the intervention (n=10 in each time point group). Rats of the CE group were uniformly subjected into catgut embedding at ST36 once, and those of the sham CE group received embedding needle puncture at ST36 without catgut retention, and the blank control group was only grasped and fixed without other treatments. Tissues from the ST36 area in each group were collected at the corresponding time points, and the expression of CD68 in macrophages in the acupoint area was detected by immunofluorescence, the contents of TNF-α and IL-1ß in the acupoint area were detected by ELISA. RESULTS: Following catgut embedment at ST36, the contents of TNF-α and IL-1ß, and macrophage CD68 expression level began to increase at 8 h, peaked at 3 d, and then gradually decreased at 7, 14, and 21 d, being still higher in the CE group than in the blank control group at 21 d (P<0.05). Compared with the blank control group, the contents of TNF-α and IL-1ß, and macrophage CD68 expression were significantly increased at 8 h, and 3, 7, 14 and 21 d in the CE group (P<0.05). Following sham CE at ST36, the content of TNF-α at 8 h and 3 d, IL-1ß at 8 h and 3, 7 and 14 d, and expression of CD68 at 8 h were significantly increased in comparison with the blank control group (P<0.05). Comparison between the CE and sham CE groups showed that the contents of IL-1ß at 3, 7, 14 and 21 d, and contents of TNF-α，CD68 expression at 8 h, and 3, 7, 14 and 21 d were significantly higher in the CE group than in the sham CE group (P<0.05). CONCLUSION: Catgut embedding at ST36 can induce an increase levels of inflammatory cytokines TNF-α, IL-1ß and macrophage CD68 in the local microenvironment in rats, which may contribute to its functions in initiating therapeutic effect.

Acupoint Catgut Embedding Diminishes Fibromyalgia Pain through TRPV1 in the Mouse Brain.

BACKGROUND: Chronic pain refers to pain that persists for over three months. Chronic pain may restrict activities of daily living, including work, learning, social life, and can lead to anxiety, depression, and sleep disturbance. Imaging data have demonstrated that central sensitization often occurs in the brain of patients with chronic pain, which arises from imbalanced neurotransmission in the central nervous system. Transient receptor potential vanilloid 1 (TRPV1) is an ion channel to serve as an inflammatory detector in the brain. We aim to determine the properties of acupoint catgut embedding (ACE) on cold stress-induced mice fibromyalgia (FM) and surveyed the character of TRPV1 and linked molecules in chronic FM pain. METHODS: Intermittent cold stress (ICS) was used to induce mice FM model. Mice were subgrouped into normal mice, ICS-induced FM group, FM mice with ACE, and FM in Trpv1-⁣/- group. ACE is a novel acupuncture technique that provides convenience and continuous nerve stimulation that has been reported effective on pain management. RESULTS: Our behavioral experiments showed similar levels of pain response among all groups before treatment. After ICS, prolonged mechanical and thermal pain was initiated (mechanical threshold: 1.96 ± 0.12 g; thermal latency: 4.86 ± 0.21 s) and were alleviated by ACE treatment and TRPV1 gene deletion. Inflammatory mediators were increased in the plasma of FM mice, while TRPV1 and related kinases were amplified in the hypothalamus and cerebellum. These changes were ameliorated in the ACE-treated and Trpv1-⁣/- groups. CONCLUSIONS: These novel findings suggest that chronic FM pain can be modulated by ACE or TRPV1 gene deletion. The analgesic effect of ACE through the TRPV1 pathway may reflect its potential as a therapeutic target for FM treatment.

Effect of catgut embedding at acupoints versus non-acupoints in abdominal obesity: a randomized clinical trial.

OBJECTIVE: To explore the difference of catgut embedding effect between acupoints and non-acupoints in patients with abdominal obesity (AO). METHODS: In this multicenter, double-blind, randomized controlled trial, all subjects were randomly assigned into the acupoint catgut embedding (ACE) group and control group (catgut embedding at non-acupoints). With a 12-week actual intervention period and a 4-week period of follow-up. Waist circumference (WC), body weight, body mass index (BMI), hip circumference (HC) and appetite were applied and assessed at baseline and after 6, 12 and 16 weeks. RESULTS: After the total intervention phase (12 weeks), the WC, body weight, BMI, HC and visual analogue scale scores of appetite, decreased significantly in the two groups as compared to the baseline (0.001). Meanwhile, after the 4-week follow-up, the indicators still decreased significantly in the ACE group (0.001). At 12 and 16 weeks, catgut embedding at acupoints showed significantly advantages to non-acupoints in WC and appetite (0.05). No serious adverse events were observed in ACE group and control group. CONCLUSIONS: Catgut embedding at acupoints and non-acupoints are all effective and safe for AO. ACE can effectively treat AO as expected and deliver lasting results.

The effect of acupoint catgut embedding and drug therapy on hyperlipidemia: a meta-analysis of randomized controlled trials.

There is no consensus on whether acupoint catgut embedding should be widely used as a treatment for hyperlipidemia. Acupoint catgut embedding is also not included in the guidelines for the treatment of hyperlipidemia. The purpose of this study was of two aspects: 1) to review recent research advances in the relationship between acupoint catgut embedding and hyperlipidemia, 2) to make a meta-analysis of the effects of acupoint catgut embedding on hyperlipidemia. We conducted a meta-analysis of studies extracted from PubMed, the Cochrane Library, Embase CNKI, Wanfang Data and VIP to identify randomized controlled trials (RCTs) evaluating the efficacy of acupoint catgut embedding on hyperlipidemia evaluated through screening, inclusion, data extraction and quality assessment. We performed a meta-analysis using Review Manager 5.3 software. A total of 9 RCTs, involving more than 500 adults over 18 years old, were included. Compared with acupoint catgut embedding, drugs resulted in TC [MD = -0.08, 95% CI (-0.20, 0.05), p = 0.41, I2 = 2%], in TG [MD =-0.04, 95% CI (-0.20, 0.11), p = 0.09, I2 = 43%], in HDL-C [MD = 0.02, 95% CI (-0.12, 0.16), p = 0.07, I2 = 50%], in LDL-C [MD = 0.16, 95% CI (0.02, 0.29), p = 0.17, I2 = 34%]. Based on the current evidence, acupoint catgut embedding is not significantly more effective than drugs in reducing hyperlipidemia. More randomized trials are needed to confirm this conclusion.

Brain-Imaging Mechanisms on Female Abdominal Obesity Treated by "Shu-Mu" Acupoint Catgut Embedding and Compatibility Relation: Study Protocol for a 12-Week Randomized Controlled Trial.

Background: Acupoint catgut embedding (ACE) has been proven to be effective and safe in the treatment of obesity, but few studies have been conducted involving its central mechanisms. Our previous study has demonstrated the effectiveness of Shu-Mu ACE in the treatment of abdominal obesity (AO). However, the neurological mechanism of Shu-Mu ACE for weight loss has not yet been elucidated. The mechanism of the combination of the Shu and Mu acupoints may be related to the central integrative effects of the brain. This paper aims to explore the potential neural mechanisms of Shu-Mu ACE in female patients with AO. Methods and Analysis: A total of 100 eligible female AO patients and 20 healthy female subjects will be recruited for this study. 100 AO patients will be randomly allocated to five groups: Shu-Mu ACE (Group A), Shu ACE (Group B), Mu ACE (Group C), sham ACE (Group D), and waiting-list (Group E). Treatment will be administrated once every two weeks for 12 weeks. The body mass index (BMI), waist circumference (WC), Visual Analog Scales (VAS) of appetite, Self-Rating Anxiety Scale (SAS), and Self-Rating Depression Scale (SDS) will be utilized to evaluate the clinical efficacy. Outcomes will be assessed at baseline and at each time point of treatment. Multimodal MRI will be performed at baseline and after 12-week treatment and the results will be used to investigate the neural mechanisms of ACE for obesity. Neurological changes and clinical data will be analysed for correlation. Discussions: This study hypothesized that Shu-Mu ACE therapy has a synergistic effect and may treat AO by modulating the neuropathological alterations in the brain. Our findings will demonstrate the neurological mechanism of AO treated by "Shu-Mu" Acupoint Catgut Embedding and compatibility relation. Trial Registration: This trial is registered at the Chinese Clinical Trial Registration Center (No. ChiCTR2100048920).

Acupoint catgut embedding for chronic non-specific low back pain: A protocol of randomized controlled trial.

Chronic non-specific low back pain (CNLBP) is one of the leading causes of disability worldwide. Acupoint embedding (ACE) is widely used in China for the treatment of chronic non-specific low back pain, but there are no rigorous randomized controlled trials (RCTs) to confirm the effectiveness and safety of ACE for chronic non-specific low back pain. In this study, we design a single-center, single-blind, prospective RCT, with the aim of evaluating the efficacy and safety of ACE for CNLBP. 82 participants with CNLBP will be randomized in a 1:1 ratio into an ACE group and a sham ACE group. Participants will receive either ACE treatment or sham ACE treatment at once every 2 weeks, for an 8-week period, and followed by 6 months of follow-up. The primary outcome will be the change in visual analog scale (VAS) scores before and after treatment. Secondary outcomes will include the Oswestry Disability Index (ODI), the Roland Morris Disability Questionnaire (RMDQ) and the Short Form 36-Health Survey (SF-36). Adverse events that occur during the course of the trial will be recorded. Data will be analyzed according to a predefined statistical analysis plan. This study was approved by the medical ethics committee of Guangzhou Panyu Hospital of Chinese Medicine (202230). Written informed consent from patients is required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR2200059245). Trial results will be published in a peer-reviewed academic journal. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2200059245.