Melittin acupoint injection in attenuating bone erosion in collagen-induced arthritis mice via inhibition of the RANKL/NF-κB signaling pathway.

Background: Rheumatoid arthritis (RA) is an autoimmune disease leading to chronic joint inflammation. Bone erosion is the most serious pathological condition of RA and the main cause of joint deformities and disability. Melittin acupoint injection (MAI) is an effective traditional Chinese medicine (TCM) method for RA treatment. This study aimed to investigate the effect of MAI on RA bone erosion and to elucidate the underlying mechanism. Methods: A collagen-induced arthritis (CIA) mouse model was established as the experimental subject. MAI was administrated once every other day for 28 days to mice with CIA. The effects of MAI on joint diseases were assessed by body weight, arthritis index (AI) score, swollen joint count (SJC) score, and hind paw thickness. Ankle radiological changes were captured by micro-computed tomography (micro-CT) and histological changes were observed by pathological staining. Organ histological changes, spleen index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine (Crea) levels of serum were tested to evaluate the toxicity of MAI. Cytokine expression levels were confirmed by enzyme-linked immunosorbent assay (ELISA) to evaluate the immunity of CIA mice. Results: MAI administration markedly improved the clinical signs of CIA in mice, including hind paw thickness, AI, and the number of swollen paw joints (most of them P<0.05 or even <0.01). According to histopathological analysis, MAI ameliorated inflammatory cell infiltration, synovial hyperplasia, pannus formation, and bone erosion (all P<0.01). Micro-CT and tartrate-resistant acid phosphatase (TRAP) staining (P<0.01) also revealed that MAI could relieve bone erosion via reducing the formation of osteoclasts. Not only could MAI relieve the immunological boost [P<0.05 for the high-dose MAI (HM) group], but also it had no liver or kidney side effects (P>0.05). In addition, it decreased the serum levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) and increased the serum levels of IL-4 and IL-10 (the majority of P<0.05 or even <0.01). Transcriptome sequencing results indicated that MAI affected the expression of osteoclast differentiation pathway genes, which was connected with the receptor activator of the nuclear factor κB ligand/nuclear factor kappa B (RANKL/NF-κB) pathway. Conclusions: Based on our findings, MAI could suppress joint inflammation and inhibit RANKL/NF-κB-mediated osteoclast differentiation to rescue bone erosion in CIA mice, suggesting that MAI can be a potentially therapeutic substance for RA.

Effects of combining acupuncture with exercise training on relieving dyspnea and improving exercise tolerance in chronic obstructive pulmonary disease patients: a protocol for a single-blind, randomized, sham-controlled trial.

BACKGROUND: Exercise training is beneficial for patients with chronic obstructive pulmonary disease (COPD). However, the effect of exercise training is limited by patients' impaired exercise capacity, exertional dyspnea and other respiratory problems. Acupuncture, as a reliable and safe therapy, is effective in reducing dyspnea, relieving respiratory muscle fatigue, and improving exercise capacity of COPD patients. However, it is not known whether the combination of exercise training and acupuncture reduces dyspnea and improves quality of life of COPD patients or induces more pronounced effects in dyspnea and exercise tolerance. This trial aims to determine whether acupuncture enhances the effect of exercise training in COPD patients compared to sham acupuncture. METHODS: In this single-blind, randomized, sham-controlled trial, 70 COPD patients will be enrolled and randomly assigned (1:1) to the following 2 groups: (I) real acupuncture and exercise training group; and (II) sham acupuncture and exercise training group. For acupoint selection, CV 4, CV 12, CV 17, ST 40, ST 16 and ST 25 will be used for all patients. For sham acupuncture group, Streitberger placebo needles will be used. A single-blind method will be adopted in this trial. Data collectors and statisticians will be blinded in this trial, only the acupuncturists will know the group allocation. The intervention will be conducted 3 times a week for 8 weeks, totaling 24 treatments. Patients will be evaluated at the baseline, after 14 treatments during the 5th week, after 24 treatments during the 8th week, and at a 5-month follow-up period. The primary outcomes will be assessed by a modified British medical research council questionnaire (mMRC), COPD assessment test (CAT), and 6-minute walk test (6MWT). The secondary outcomes will be measured by changes in variables from the lung function test, cardiopulmonary exercise testing, and blood gas analysis. Two-independent sample t-tests will be used to compare differences in the changes in all outcome measures after the intervention between two groups. Safety evaluation will be performed at each treatment visit and assessment by recording adverse events (AE) in the AE Report Form. DISCUSSION: This study will help to determine whether acupuncture increases the benefits obtained from exercise training in COPD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1900028627. Registered on December 29, 2019.

[Effect of electroacupuncture on small airway function in patients with stable chronic obstructive pulmonary disease].

OBJECTIVE: To observe the regulatory effect of electroacupuncture (EA) on small airway function and exercise tolerance in patients with stable chronic obstructive pulmonary disease (COPD). METHODS: A total of 62 patients with stable COPD were randomized into an observation group (31 cases, 1 case dropped off) and a control group (31 cases, 5 cases dropped off). On the base of routine medication and aerobic exercise, the patients of the two groups all received EA at Danzhong (CV 17), Rugen (ST 18), Guanyuan (CV 4), Zhongwan (CV 12), Tianshu (ST 25) and Yingchuang (ST 16). In the observation group, filiform needles were used and inserted perpendicularly, 3 mm in depth. In the control group, the placebo needling method was performed, in which the needle was not inserted through skin at each point. In both groups, electric stimulation with low-frequency electronic pulse instrument was exerted, with continuous wave, 2 Hz in frequency, lasting 30 min each time in the two groups. The treatment was given once every other day, 3 times a week, for 14 treatments totally. Before and after treatment, the following indexes were compared in patients between the two groups, i.e. the lung function indexes (forced expiratory volume in first second [FEV1], forced vital capacity [FVC], the ratio of FEV1 to FVC [FEV1/FVC], maximal voluntary ventilation [MVV], the percentage of maximal expiratory flow [MEF] at 25% of FVC exhaled [MEF25], MEF50 and MEF75 in predicted value), cardiopulmonary exercise test indexs (metabolic equivalent [METS], oxygen uptake per kg body weight [VO2/kg], minute ventilation [VE], the percentage of oxygen pulse [VO2/HR] in predictd value, maximal minute ventilation [VEmax], ventilatory equivalent for oxygen [VE/VO2], ventilatory equivalent for carbon dioxide [VE/VCO2]), 6-minute walk distance (6MWD), the total score of COPD assessment test (CAT), the modified British Medical Research Council (mMRC) score and COPD comprehensive grade. RESULTS: After treatment, FVC%, MVV%, MEF75%, MEF50%, VO2/kg%, METs%, VEmax, VO2/HR%, 6MW and the total CAT score were all improved as compared with those before treatment in the observation group (P<0.05, P<0.01). After treatment, MEF75% and the total CAT score were reduced as compared with those before treatment in the control group (P<0.05). After treatment, MVV%, MEF50%, VO2/kg%, METs%, VEmax and 6MWD in the observation group were all better than those in the control group (P<0.05, P<0.01). CONCLUSION: Electroacupuncture can improve the respiratory function and exercise tolerance in COPD patients through removing small airway obstruction and increasing ventilation.