- Email: [email protected]
Rheumatoid arthritis treated with the triple strong-stimulation technique of acupuncture and moxibustion at specific acupoints: A randomized controlled trial
World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
Contents lists available at ScienceDirect
World Journal of Acupuncture – Moxibustion journal homepage: www.elsevier.com/locate/wjam
Clinical Research
Rheumatoid arthritis treated with the triple strong-stimulation technique of acupuncture and moxibustion at specific acupoints: A randomized controlled trial Wen-zhong CAO () a,b,∗, Wei-xian ZHAO () c, Hui-ming GUO () b, Xue-mei ZHANG () b, Min-fang ZHANG () b, Xing-lei ZHANG () b, Li-na WEI () b Beijing Xingzhitang Academy of Traditional Chinese Medicine, Beijing 100020, China (, 100020, ) Beijing Xingzhitang Limited Company of Traditional Chinese Medicine Clinic, Beijing 100020, China (, 100020, ) c Department of Rheumatology and Immunology, Hebei Cangzhou Integrated Chinese and Western Medicine Hospital, Cangzhou 061001, Hebei, China ( , 061001, ) a
b
a r t i c l e
i n f o
Article history: Available online 4 January 2019 Keywords: Rheumatoid arthritis Strong stimulation with blood-letting Strong stimulation with cupping Strong stimulation with moxibustion Triple strong-stimulation technique Randomized controlled trial
∗
a b s t r a c t Objective: To explore the clinical therapeutic effects and the mechanism on rheumatic arthritis (RA) treated with the combination of the instruments and techniques of acupuncture and moxibusiton. Methods: A total of 60 RA patients were randomized into an observation group and a control group, 30 cases in each one. In the control group, diclofenac sodium sustained release tablets were prescribed for oral administration, 0.3 g each time, twice a day, methotrexate tablets (MTX) for oral administration, 10 mg each time, once a week and folic acid tablets for oral administration, 5 mg each time, once a week. In the observation group, besides the treatment with western medicines, simultaneously, the specific acupoints were selected and stimulated with the triple strong-stimulation therapy, in which, the strong bloodletting technique, the strong cupping technique and the strong moxibustion technique were combined together, with different instruments of acupuncture and moxibustion adopted. The treatment was given once every 3 days, consecutively for 10 times. In 30 days of treatment, the therapeutic effects were observed in the two groups. Separately, before and after treatment, the rheumatoid factors (RF), hypersensitive-C reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR), the scores of joint symptoms and physical signs as well as the disease activity score (DAS-28) were observed in the two groups. Results: Regarding RF, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 248.01 ± 79.81 vs 31.17 ± 29.01, the control group 254.11 ± 72.16 vs 66.42 ± 37.07, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding hs-CRP, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 26.12 ± 9.22 vs 8.98 ± 7.66, the control group 23.18 ± 7.18 vs 16.01 ± 5.02, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding ESR, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 30.56 ± 11.38 vs 12.58 ± 5.91, the control group 35.52 ± 9.67 vs 21.47 ± 6.91, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding DAS-28, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 8.89 ± 2.01 vs 3.01 ± 0.74, the control group 8.14 ± 1.38 vs 4.12 ± 0.96, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding the quantitative grading score of symptom, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 7.87 ± 1.69 vs 3.82 ± 1.96, the control group 7.77 ± 1.68 vs 5.01 ± 11.23, both P < 0.05). The
Corresponding author. E-mail address: [email protected] (W.-z. CAO).
https://doi.org/10.1016/j.wjam.2019.01.003 1003-5257/© 2019 Published by Elsevier B.V. on behalf of World Journal of Acupuncture Moxibustion House.
252
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
result in the observation group was lower significantly than the control group after treatment (P < 0.05). The total effective rate was 96.67% (29/30) in the observation group and was 80.0% (24/30) in the control group, indicating the statistical significant difference between the two groups (P < 0.01). Conclusion: Based on western medications, the triple strong-stimulation therapy of acupuncture and moxibustion at specific acupoints significantly relieves the joint symptoms, reduces the inflammatory reaction indicators and improves the clinical therapeutic effects on RA in the patients. © 2019 Published by Elsevier B.V. on behalf of World Journal of Acupuncture Moxibustion House.
authors fulfilled the design, implementation and operation of the trial as well as the evaluation of clinical effects. All of the medical staffs involved in the trial had been trained officially and strictly. The blind method was not adopted in the trial.
Introduction Rheumatoid arthritis (RA) is chiefly manifested as the symmetrical, chronic and multiple-joint inflammation with the joint synovial membrane invaded and the autoimmune disorder combined. The disease is the refractory disease, and with the progression of illness and effusive joint inflammatory reaction, it leads to joint deformity and even the disorders of the vital organs, such as the heart and lungs. In the treatment with western medicine, the nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids, antirheumatic drugs, immunosuppressors and biological agents predominate. These drugs have the definite therapeutic effects on RA, but the long-term medication results in many adverse reactions, severe toxic side effects as well as chronic damages in the liver, the kidney and the femoral head. The patients will be resistant to the medication if taking for a long time. In order to lay the foundation for the further research of the triple strong-stimulation therapy, the compound therapy of acupuncture and moxibustion with different instruments and techniques was used in the treatment and the clinical therapeutic effects were observed. In the trial, the triple strong-stimulation therapy was operated at the specific acupoint in the treatment of RA and the clinical therapeutic effects and the impacts on the inflammatory reaction indicators were observed. The report is as follows.
Inclusion criteria
1 In compliance with the latest classification criteria of RA [2]. 2 Aged in the range from 18 to 67 years. 3 The patients were cooperating with the sample collection, in the obedience by the observation and evaluation. They were willing to the participation in the research and had signed the Informed Consent on the collection of all of the blood samples and the therapeutic schemes. Exclusion criteria
1 Complicated with severe cardiocerebral disorders, immune deficiency, liver and kidney functional damage. 2 Suffering from the severe diseases that affect the quality of life. 3 Suffering from diabetes and acute uric acid. 4 Women in lactation or pregnancy. 5 Having taken biological agents in recent 3 months. 6 RA complicated with other connective tissue disorders. 7 Receiving the treatment with other drugs or other therapeutic methods. 8 With skin lesions, contact dermatitis and severe allergy to moxibustion. Dropping-out criteria
Clinical information
1 During the observation, the subjects failed to obey the treatment principle and had taken arbitrarily other drugs. 2 Due to the personal reason, the subjects failed to accomplish the therapeutic scheme and dropped out automatically. 3 The subjects had to discontinue the treatment because suffering from other disease during the treatment. 4 Failing to accurately evaluate the effects or failing to evaluate the effects or safety due to incomplete data.
General data From January 1, 2014 to December 31, 2017, 60 outpatients and inpatients were collected from Beijing Xingzhitang Academy of Traditional Chinese Medicine (57 cases) and the Department of Rheumatology and Immunology from Hebei Cangzhou Integrated Chinese and Western Medicine Hospital (3 cases, 1 case of them was enrolled in the observation group and 2 cases in the control group). Of 60 cases, there were 11 males and 49 females, aged from 18 to 67 years, (52 ± 14) years old in average. The duration of illness was ranged from 1 to 22 years, (10.0 ± 5.9) years in average. According to the random number table, 60 cases were divided into an observation group and a control group, 30 cases in each one. The patients in the two groups were all in compliance with the classification criteria of RA co-proposed by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) [1]. There was no significant difference in the general data in the patients between the two groups (P > 0.05), indicating the comparability between the two groups (see Table 1 for details). The
Methods Control group The patients were treated with the medication with methotrexate tablets (MTX, 2.5 mg /tablets, Shanghai Sine Pharmaceutical Co. LTD. Approval Number 601340H), 10 mg each time, once a week; diclofenac sodium sustained release tablets (0.3 g/capsule, manufactured by Sino-US Tianjin GlaxoSmithKline Pharmaceutical Co., LTD. Approval Number H1090 0 089), 0.3 g each time, twice a day; folic acid tablets (5 mg/tablet, manufactured by Jiangsu Yabang Aipusen Pharmaceutical Co. LTD. Approval Number H32023288),
Table 1 Comparison of the general data of the RA patients between the two groups. Group
Observation Control
Patients
30 30
Gender (cases)
Age (years)
Male
Female
Youngest
Oldest
Average (X¯ ± S)
Duration of illness (years) Shortest
Longest
Average (X¯ ± S)
6 5
25 24
20 18
67 65
56 ± 14 54 ± 11
1 1
22 21
11.4 ± 6.8 10.1 ± 7.2
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
5 mg each time, once a week. In order to reduce the adverse reactions, i.e. the side effects of gastrointestinal tract and liver function damage, the drugs mentioned above were taken after meal. The medication for 30 days was as one session. Observation group On the base of the treatment of the control group, the specific acupoints were selected and stimulated with the triple strongstimulation therapy, in which, the strong bloodletting technique, strong cupping technique and strong moxibustion technique were combined together. Manipulations: Dàzhu¯ı ( GV 14) and Ashi points which locate around the knuckles. The patient was in the position that was suitable for the operation of the triple strongstimulation therapy. The acupoints were sterilized routinely. The small three-edged needle for single use was selected for the bloodletting. The skin around the acupoint was fixed with the thumb and the index figure of one hand. The three-edged needle was held like holding the pen with another hand, holding the needle body with the thumb and the index finger tightly and the needle tip exposed by 2 mm. The needle was inserted swiftly 1–2 mm deep beneath the skin and the acupoint was stimulated by several times of pricking. Afterwards, the flash cupping technique with a large cup was applied to the pricking sites. The operator shook and tapped the cup strongly before removed it from the body. In the cup removal, the cup was firstly tilted in the centripetal direction and then, it was removed off the body in the anticentripetal direction swiftly. The flash cupping technique was repeated for 5–10 times. Finally, the cup was retained for 5–10 min. The bleeding was observed carefully and blood volume was controlled as 3–5 mL. The most important step of the triple strong-stimulation therapy was the strong moxibustion technique. The moxa stick was selfprepared with the aged moxa wool, 20 cm in length, 2 cm in diameter and 25–27 g in weight. Right after the cup removed, the strong-moxibustion technique was operated. Five moxa sticks were tightened together and ignited. The ignited moxa sticks were held above the center of the cupping site, 5 cm far from the skin, moved up and down, avoiding skin burns, for 20–30 min in generally. The optimal duration of moxibustion was determined by whether the local skin turned red. In each treatment, GV 14 must be selected and 1–2 Ashi points, i.e. the painful points around the swelling joints were combined. The treatment was given once every 3 days, consecutively for 10 times. Precautions: this therapy should be adopted with caution if the patient had severe traumatic injury of the neck and shoulder, thrombocytopenia and hematopathy or had undergone a major surgery in recent 2 weeks. If blisters occurred accidentally at GV 14 or Ashi points after cupping or strong moxibustion, the ointment for scald was used locally. The very severe case should be treated in the Burns Department and the triple strong-moxibustion therapy could be given after healing. The pigmentation occurred after blister healing and it was absorbed automatically. After treated with the triple strong-moxibustion therapy, the patients were advised to avoid spicy and cold food, cold invasion, cold bath as well as profuse sweating. The therapeutic effects were evaluated after 1-month treatment in the two groups. Effect observation Observation indicators (1) Rheumatoid factor (RF) (the kit was bought from EUROIMMUN Medical Laboratory Diagnostics Stock Company). Separately, before treatment and on the next day after treatment, the fasting blood was collected after getting up in the morn-
253
ing. The immune scatter turbidity method was adopted in the determination. The concrete operation procedure for RF determination was in accordance with the instruction on the kit. (2) Hypersensitive C-reactive protein (hs-CRP) (the kit was bought from EUROIMMUN Medical Laboratory Diagnostics Stock Company). Separately, before treatment and on the next day after treatment, the fasting blood was collected after getting up in the morning. The immunofluorescence dry quantitative method was adopted in the determination. The concrete operation procedure for hs-CRP determination was in accordance with the instruction on the kit. (3) Erythrocyte sedimentation rate (ERS) (the kit was bought from EUROIMMUN Medical Laboratory Diagnostics Stock Company). Separately, before treatment and on the next day after treatment, the fasting blood was collected after getting up in the morning. The Westergren method was adopted. The concrete operation procedure for ESR determination was in accordance with the instruction on the kit. (4) Quantitative criteria of the symptom and physical sign scores. In reference to Guidelines and principles for clinical research of new drugs of traditional Chinese medicine issued by the Ministry of Health, China [2], the concrete symptoms and physical signs were scored. Scoring criteria: according to the severity of main clinical manifestations, symptoms and physical signs in RA patients, four grades are divided, i.e. normal, mild, moderate and severe, scored as 0, 2, 4 and 6 separately. The primary symptoms and physical signs include joint pain, joint swelling, palpable pain and tenderness of joint, morning stiffness of joint and limited movement of joint. The secondary symptoms and physical signs are repeated fever, reduced appetite, emaciation, cold or feverish joint, subcutaneous nodes, aversion to wind and cold, short breath, dislike to speak and low spirits. The researchers in the team observed and recorded carefully the symptoms and physical signs as well as evaluated the qualitative grade in the patients before and after treatment. (5) Disease activity score of rheumatoid arthritis (DAS-28) [4]. In reference to PREVOO calculation method, DAS 28 = 0.56 × Num.oftenderjoint + 0.28 × Num of swelling joint+ 0.7 × In (ESR) + 0.16. DAS-28 includes the scores of 28 joints, i.e. shoulders, elbows, wrists, phalangeal joints of hands, proximal interphalangeal joints of hands and knee joints. DAS-28 score > 5.1 indicates the active illness, < 3.2 indicates low activity and < 2.6 indicates slow activity. One evaluation was conducted before treatment and after 30-day treatment separately. Effect evaluation criteria The relevant criteria on the therapeutic effects in Guidelines and principles for clinical research of new drugs of traditional Chinese medicine [3] were taken as reference. Quantitative criteria of the symptom and physical sign scores were as therapeutic effect criteria. Remarkably effective: the improvement rate of the primary and secondary symptoms and physical signs ≥ 75%, the laboratory physiochemical determination indicators were normal, improved obviously or close to the normal. Improved: 50%≤ the improvement rate of the primary and secondary symptoms and physical signs < 75%, and the laboratory physiochemical determination indicators were improved obviously. Effective: 30% ≤ the improvement rate of the primary and secondary symptoms and physical
254
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
Table 2 Comparison of the results of RF, hs-CRP and ESR, the scores of ADS-28, symptoms and physical signs in RA patients of the two groups (x¯ ± s). Group
Patients
Time
RF (μmol/L)
hs-CRP (mg/L)
ESR (mm/1 h)
DAS-28 (scores)
Observation
30
Control
30
Before treatment After treatment Before treatment After treatment
248.01 ± 79.81 31.17 ± 29.01a , b 254.11 ± 72.16 66.42 ± 37.07 a
26.12 ± 9.22 8.98 ± 7.66 a , b 23.18 ± 7.18 16.01 ± 5.02 a
30.56 ± 11.38 12.58 ± 5.91 a , b 35.52 ± 9.67 21.47 ± 6.91 a
8.89 ± 2.01 3.01 ± 0.74 a , b 8.14 ± 1.38 4.12 ± 0.96 a
a b
Quantitative grading of symptom (scores) 7.87 ± 1.69 3.82 ± 1.96 a , b 7.77 ± 1.68 5.01 ± 11.23 a
Compared with that before treatment of the same group, P < 0.05. Compared with that in the control group after treatment, P < 0.05.
Table 3 Comparison of the clinical therapeutic effects on RA in the patients of the two groups (cases). Groups
Patients
Remarkably effective
Improved
Effective
No effect
Total effective rate (%)
Observation Control
30 30
12 5
11 8
6 11
1 6
96.67a 80.00
a
Compared with the control group, P < 0.01.
signs <50%, and the laboratory physiochemical determination indicators were improved. No effect: the improvement rate of the primary and secondary symptoms and physical signs < 30% and the laboratory physiochemical determination indicators were not improved. The improvement rate of the primary and secondary symptoms and physical signs was determined by the percentage of the improvements in the primary and secondary symptoms and physical signs in the RA patients. [(Score of symptoms and physical signs before treatment − Score symptoms and physical signs after treatment)] ÷ Score of symptoms and physical signs before treatment × 100%. Statistical treatment SPSS 17.00 software was adopted. The measurement data was expression as mean ± standard deviation (ÿx ± s). The paired t test or one-way analysis of variance was adopted. For the enumeration data or the one-way ranked ordinal data, the x2 test for the data of paired fourfold table was applied. The test level was α = 0.05 and P < 0.05 indicated significant difference. Results The results of RF, hs-CRP and ESR as well as the scores of ADS-28, symptoms and physical signs of RA patients in the two groups The differences were not significant in the results of RF, hs-CRP and ESR as well as the scores of ADS-28, symptoms and physical signs between the RA patients in the two groups before treatment (all P > 0.05), indicating the comparability. Compared with the results before treatment, the levels of RF, hs-CRP and ESR, as well as the DAS-28 scores and the quantitative grading scores of symptoms in the RA patients were all reduced after treatment in the two groups (all P < 0.05). Compared with the control group, the levels of RF, hs-CRP and ESR, as well as the DAS-28 scores and the quantitative grading scores of symptoms in the RA patients were more improved in the observation group after treatment (all P < 0.05, see Table 2). Comparison of the clinical therapeutic effects in the RA patients between the two groups After treatment, with the statistical treatment, the total effective rate was 96.67% in the observation group and was 80.00% in the control group. The total effective rate in the observation group was significantly better than the control group (P < 0.01, Table 3).
Discussion RA is in the category of bi syndrome in traditional Chinese medicine (TCM). Regarding the etiology of this disease in TCM, the medical scholars of dynasties believe that the person with the congenital imbalance of the nutrient and defensive qi and the insufficiency of anti-pathogenic qi is easily attacked by the pathogenic wind, cold, damp and heat. The pathogenic factors are obstructed in muscles, bones, joints and meridians, resulting in retarded qi and blood circulation. The long-term illness affects the liver and the kidney and injured tendons and bones. Consequently, the intractable bi syndrome occurs. Y¯ıxué Rùmén (, Introduction to Medicine) says that the intractable bi syndrome results from the interaction of the pathogenic wind, cold and damp, with the tendon and bone damage involved. In pathogenesis, this disease is differentiated as the deficiency in the primary and the excess in secondary. The deficiency in the primary refers to the deficiency of the liver, spleen and kidney and the excess in the secondary to the stagnation and blockage by the pathogenic wind, cold, damp and phlegm. RA is the autoimmune disorder with the high morbidity at present and the females are more the males. The morbidity in females is 2–3 times as same as the males. RA happens at any age, frequently at the age of 40–60 years, which had been proved in the clinical data of this trial. At early stage, the joint synovium is invaded and the inflammatory reaction occurs. With the progress of the disease, more joints are affected and the joint deformity happens, in which, the deformity of hands and feet is common. Except the joint disorders, the other common clinical manifestations are fever, rheumatoid node, rheumatoid vasculitis, lymph swelling and even the severe disorders of the vital organs, i.e. the heart, lung and kidney. In western medicine, the first-line common drugs for RA are nonsteroidal anti-inflammatory drugs and the second-line drugs are the anti-rheumatic drugs for relieving the illness and alleviating or reliving pain. These medications alleviate joint stiffness, joint swelling and motor impairment and control the progress of sickness [4]. But, these chemical agents greatly affect the organs, i.e. the liver and the kidney. Specially, the probability of the chronic damages induced in the patients with long-term medication is much high and it is difficult for the patients to be well complied with the medication. According to the instructions in the guideline for the diagnosis and treatment of RA in China in 2018, MTX is the anchor drug and it is the publically-recognized firstline drug in the guidelines at home and abroad, acting on immune inhibition and rapid anti-inflammation. But, the drug-induced
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
hepatic toxicity and myelosuppression are very common. The researches in Chinese population show that the adverse reaction of small-dose MTX (≤10 mg a week) is mild and the long-term tolerance is satisfactory. Diclofenac sodium sustained release tablets are the nonsteroidal and anti-inflammatory drug, with strong effects and refer to the fenamic acids, working on reducing joint pain and swollen joint. But the drug induces gastrointestinal side effects. Folic acid is generally supplemented during treatment to reduce gastrointestinal side effects and liver damage. In this research, the western drugs were adopted in the control group according to the guideline and the first-line medication, i.e. MTX, diclofenac sodium sustained release tablets and folic acids. On the base of the treatment in the control group, the instruments and the techniques of acupuncture and moxibusiton were combined together in the intervention of RA in the observation group. The specific acupoints were selected and stimulated with the triple strong-stimulation therapy. The test indicators and the symptom quantitative grading scores were observed and the clinical effects were compared in the two groups so as to provide more choices and better therapeutic schemes for RA patients [5]. The clinical therapeutic effects and mechanism of the triple strong-stimulation therapy at GV 14 and the supplementary points were explored in the treatment of RA [6]. GV 14, at the governor vessel, locates at the nape region, the high position of the body, regarding as the yang within yang. It is the meeting point of the governor vessel with the three yang meridians of hand and foot. The governor vessel is the sea of the yang meridians and governs yang qi of the whole body. GV 14 is the crucial point for yang qi strengthening of the governor vessel. It acts on defending the body, protecting yang, scatter wind and release the exterior, building up yang to eliminate cold in treatment. It is taken as the optimal acupoint for the deficiency of anti-pathogenic qi, the invasion of pathogenic wind, cold and damp as well as the consumptive disorders. Based on the specificity of GV 14, the triple strong-stimulation therapy with the combination of different instruments and techniques of acupuncture and moxibustion was adopted in the treatment of RA. The therapy worked on the etiology and pathogenesis of the disease. It tonifies the body for the deficiency syndrome and reduces the pathogens for the excess syndrome. It was proved in the clinical observation that this therapy achieved the definite short-term therapeutic effects and the longterm protective effects. In the triple strong-stimulation therapy, the strong bloodletting and the strong cupping are operated on the base of traditional technique. The technical requirements are strict in the operation. The three-edge needle is selected instead of filiform needle and the strong bloodletting at GV 14 and the specific Ashi points produced strong stimulation. This technique induces excessive qi and blood in the local area in a short time to lay the foundation for the effect activation of meridian and acupoint. The researches prove [7–10] that the bloodletting and cupping stimulates the body to release some hormones and neuropeptides, promotes metabolism and accelerates blood circulation. It has significant effects of analgesia, anti-spasm, tranquilization, anti-inflammation and anti-allergy. Hence, the strong-bloodletting and the strong cupping techniques are applicable in the treatment of RA. There are the quite complete theory and mature experiences in the treatment of RA with the strong-moxibustion technique [11,12]. The strong-moxibustion technique at the specific acupoints strengthens yang and eliminates cold, wind and damp. Additionally, it dilates blood vessels, increases blood flow, inhibits vascular permeability, reduces inflammatory exudation and accelerates the allergen absorption. This technique effectively promotes the cellular and body fluid immunity, hence increases the immune function of the body [13–16]. The strong-moxibustion technique breaks through the traditional therapeutic mode in which moxa stick or
255
moxa cone in the local area is used for the mild moxibustion. This technique is characterized as the short duration of operation, close distance to the affected site, high temperature generated in the affected area, large area and direct stimulation of moxibustion, focusing on the strong stimulation, aiming to shorten the duration of treatment and the transmission from quantitative change to the qualitative change. Hence, the strong effects of warming meridians and collaterals, eliminating cold and removing damp were displayed prominently in a short time in the triple strong-stimulation therapy. As a result, the immediate effects are significant, which have been proved in clinical observation. The triple strong-stimulation therapy presents the warming and tonification effects while eliminating the pathogens, reinforce healthy qi without lingering pathogenic qi, hence, the satisfactory therapeutic effects are achieved in the treatment of RA. The triple strong-stimulation therapy at GV 14 and the specific Ashi points were applied in the treatment of RA and the randomized controlled trial was adopted to observe the changes of RF, hs-CRP, ESR, DAS-28 as well as the scores of joint symptom and physical signs. The results indicated that the triple strong-stimulation therapy achieved the definite effects on RA. The results of the trial show that either the triple strongstimulation therapy at the specific acupoints or the western medication in the control group relieved the clinical symptoms and physical signs of RA to different extents. The improvements in the triple strong-stimulation therapy combined with western medication were significantly better than the western medicine (all P < 0.05 or P < 0.01). It is suggested that the triple strong-stimulation therapy at the specific acupoints on the base of the medication in western medicine more effectively relieves the joint symptoms and improves the clinical effects. It is the effective compound therapy of acupuncture and moxibustion and extensively applicable for the treatment of RA.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.wjam.2019.01.003.
References [1] Villeneuve E, Nam J, Emery P. 2010 ACR-EULAR classification criteria for rheumatoid arthritis. Rev Bras Reumatol 2010;50(5):481–3. [2] Zheng XY. Guidelines and principles for clinical research of new drugs of traditional Chinese medicine: trial. Beijing: China Medical Science Press; 2002. p. 115–19. [3] Prevoo ML, Van’t Hof MA, Kuper HH. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38(1):44–8. [4] Li Y, Qi WC. Comparison of the therapeutic effects on rheumatoid arthritis treated with leflunomide combined with 99Tc-MDP or metrotrexate. Contemp Med 2009;15(7):123–4. [5] Cao WZ. Triple strong stimulation therapy”: the innovative approach to the improvement of acupuncture effects on pain. Jiangxi J Trad Chin Med 2012;43(1):50–3. [6] Cao WZ, Li AM, Dai RW, Zhang ZG. Compilation and development of the property of Dazhui (GV 14). J Sichuan Trad Chin Med 2012(12):32–4. [7] Chen LD, Li J, Zhou JB. Significance of IL-17, IL-18, IL-6 and TNF-α in the patients with rheumatoid arthritis. Contemp Med 2010;16(7):13–14. [8] Wu JW, Tang XF. Clinical significance in the expressions of serm TNF-α , IL-17 and CRP in the patients with rheumatoid arthritis. Chongqing Med 2012;41(30):3211–12. [9] Chen KH, Li RB, Gan Y, Li K, Tan L, Yang JH, et al. Efficacy of treatment of moxibustion to rheumatoid arthritis patients and its impact to blood levels of IL6,CRP and RF. Int J Lab Med 2014(21):2897–8. [10] Hao F, Hu L, Wu ZJ, Luo L, Cai RL, He L, et al. Clinical study on relations between quantity and effect of moxibustion on ginger in treating active rheumatoid arthritis. Lishizhen Med Mater Med Res 2013;24(3):677–80. [11] Qin SF. Observations on the therapeutic effect of thunder-fire moxibustion on allergic rhinitis. Shanghai J Acupunct Moxibustion 2011;30(11):765–7.
256
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
[12] Yue BA, Bi YF. 172 cases of rheumatoid arthritis treated with long-snake moxibustion therapy. Shaanxi J Trad Chin Med 2007;28(11):1536–7. [13] Ding F. Simple moxibustion therapy in treatment of rheumatoid arthritis. J Clin Acupunct Moxibustion 2007;23(10):40–1. [14] Li JW, Liu JM, Ma ZY, Xiang YY, Feng YB, Xiang SY, et al. Clinical observation on treatment of rheumatoid arthritis with cake-separated mild moxibustion combined with western medicine. Chin Acupunct Moxibustion 2006;26(3):192–4.
[15] Gong FY. 33 cases of rheumatoid arthritis treated with herbal medicine-isolated moxibustion therapy. J Clin Acupunct Moxibustion 2007;23(5) 4242. [16] Tong HY, Li XB. Clinical research of knee osteoarthritis treated with isolated mild moxibustion. J Clin Acupunct Moxibustion 2006;22(12):10–12.
Contents lists available at ScienceDirect
World Journal of Acupuncture – Moxibustion journal homepage: www.elsevier.com/locate/wjam
Clinical Research
Rheumatoid arthritis treated with the triple strong-stimulation technique of acupuncture and moxibustion at specific acupoints: A randomized controlled trial Wen-zhong CAO () a,b,∗, Wei-xian ZHAO () c, Hui-ming GUO () b, Xue-mei ZHANG () b, Min-fang ZHANG () b, Xing-lei ZHANG () b, Li-na WEI () b Beijing Xingzhitang Academy of Traditional Chinese Medicine, Beijing 100020, China (, 100020, ) Beijing Xingzhitang Limited Company of Traditional Chinese Medicine Clinic, Beijing 100020, China (, 100020, ) c Department of Rheumatology and Immunology, Hebei Cangzhou Integrated Chinese and Western Medicine Hospital, Cangzhou 061001, Hebei, China ( , 061001, ) a
b
a r t i c l e
i n f o
Article history: Available online 4 January 2019 Keywords: Rheumatoid arthritis Strong stimulation with blood-letting Strong stimulation with cupping Strong stimulation with moxibustion Triple strong-stimulation technique Randomized controlled trial
∗
a b s t r a c t Objective: To explore the clinical therapeutic effects and the mechanism on rheumatic arthritis (RA) treated with the combination of the instruments and techniques of acupuncture and moxibusiton. Methods: A total of 60 RA patients were randomized into an observation group and a control group, 30 cases in each one. In the control group, diclofenac sodium sustained release tablets were prescribed for oral administration, 0.3 g each time, twice a day, methotrexate tablets (MTX) for oral administration, 10 mg each time, once a week and folic acid tablets for oral administration, 5 mg each time, once a week. In the observation group, besides the treatment with western medicines, simultaneously, the specific acupoints were selected and stimulated with the triple strong-stimulation therapy, in which, the strong bloodletting technique, the strong cupping technique and the strong moxibustion technique were combined together, with different instruments of acupuncture and moxibustion adopted. The treatment was given once every 3 days, consecutively for 10 times. In 30 days of treatment, the therapeutic effects were observed in the two groups. Separately, before and after treatment, the rheumatoid factors (RF), hypersensitive-C reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR), the scores of joint symptoms and physical signs as well as the disease activity score (DAS-28) were observed in the two groups. Results: Regarding RF, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 248.01 ± 79.81 vs 31.17 ± 29.01, the control group 254.11 ± 72.16 vs 66.42 ± 37.07, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding hs-CRP, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 26.12 ± 9.22 vs 8.98 ± 7.66, the control group 23.18 ± 7.18 vs 16.01 ± 5.02, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding ESR, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 30.56 ± 11.38 vs 12.58 ± 5.91, the control group 35.52 ± 9.67 vs 21.47 ± 6.91, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding DAS-28, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 8.89 ± 2.01 vs 3.01 ± 0.74, the control group 8.14 ± 1.38 vs 4.12 ± 0.96, both P < 0.05). The result in the observation group was lower significantly than the control group after treatment (P < 0.05). Regarding the quantitative grading score of symptom, there were statistical significant differences before and after treatment in the observation group and the control group (the observation group 7.87 ± 1.69 vs 3.82 ± 1.96, the control group 7.77 ± 1.68 vs 5.01 ± 11.23, both P < 0.05). The
Corresponding author. E-mail address: [email protected] (W.-z. CAO).
https://doi.org/10.1016/j.wjam.2019.01.003 1003-5257/© 2019 Published by Elsevier B.V. on behalf of World Journal of Acupuncture Moxibustion House.
252
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
result in the observation group was lower significantly than the control group after treatment (P < 0.05). The total effective rate was 96.67% (29/30) in the observation group and was 80.0% (24/30) in the control group, indicating the statistical significant difference between the two groups (P < 0.01). Conclusion: Based on western medications, the triple strong-stimulation therapy of acupuncture and moxibustion at specific acupoints significantly relieves the joint symptoms, reduces the inflammatory reaction indicators and improves the clinical therapeutic effects on RA in the patients. © 2019 Published by Elsevier B.V. on behalf of World Journal of Acupuncture Moxibustion House.
authors fulfilled the design, implementation and operation of the trial as well as the evaluation of clinical effects. All of the medical staffs involved in the trial had been trained officially and strictly. The blind method was not adopted in the trial.
Introduction Rheumatoid arthritis (RA) is chiefly manifested as the symmetrical, chronic and multiple-joint inflammation with the joint synovial membrane invaded and the autoimmune disorder combined. The disease is the refractory disease, and with the progression of illness and effusive joint inflammatory reaction, it leads to joint deformity and even the disorders of the vital organs, such as the heart and lungs. In the treatment with western medicine, the nonsteroidal anti-inflammatory drugs (NSAID), glucocorticoids, antirheumatic drugs, immunosuppressors and biological agents predominate. These drugs have the definite therapeutic effects on RA, but the long-term medication results in many adverse reactions, severe toxic side effects as well as chronic damages in the liver, the kidney and the femoral head. The patients will be resistant to the medication if taking for a long time. In order to lay the foundation for the further research of the triple strong-stimulation therapy, the compound therapy of acupuncture and moxibustion with different instruments and techniques was used in the treatment and the clinical therapeutic effects were observed. In the trial, the triple strong-stimulation therapy was operated at the specific acupoint in the treatment of RA and the clinical therapeutic effects and the impacts on the inflammatory reaction indicators were observed. The report is as follows.
Inclusion criteria
1 In compliance with the latest classification criteria of RA [2]. 2 Aged in the range from 18 to 67 years. 3 The patients were cooperating with the sample collection, in the obedience by the observation and evaluation. They were willing to the participation in the research and had signed the Informed Consent on the collection of all of the blood samples and the therapeutic schemes. Exclusion criteria
1 Complicated with severe cardiocerebral disorders, immune deficiency, liver and kidney functional damage. 2 Suffering from the severe diseases that affect the quality of life. 3 Suffering from diabetes and acute uric acid. 4 Women in lactation or pregnancy. 5 Having taken biological agents in recent 3 months. 6 RA complicated with other connective tissue disorders. 7 Receiving the treatment with other drugs or other therapeutic methods. 8 With skin lesions, contact dermatitis and severe allergy to moxibustion. Dropping-out criteria
Clinical information
1 During the observation, the subjects failed to obey the treatment principle and had taken arbitrarily other drugs. 2 Due to the personal reason, the subjects failed to accomplish the therapeutic scheme and dropped out automatically. 3 The subjects had to discontinue the treatment because suffering from other disease during the treatment. 4 Failing to accurately evaluate the effects or failing to evaluate the effects or safety due to incomplete data.
General data From January 1, 2014 to December 31, 2017, 60 outpatients and inpatients were collected from Beijing Xingzhitang Academy of Traditional Chinese Medicine (57 cases) and the Department of Rheumatology and Immunology from Hebei Cangzhou Integrated Chinese and Western Medicine Hospital (3 cases, 1 case of them was enrolled in the observation group and 2 cases in the control group). Of 60 cases, there were 11 males and 49 females, aged from 18 to 67 years, (52 ± 14) years old in average. The duration of illness was ranged from 1 to 22 years, (10.0 ± 5.9) years in average. According to the random number table, 60 cases were divided into an observation group and a control group, 30 cases in each one. The patients in the two groups were all in compliance with the classification criteria of RA co-proposed by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) [1]. There was no significant difference in the general data in the patients between the two groups (P > 0.05), indicating the comparability between the two groups (see Table 1 for details). The
Methods Control group The patients were treated with the medication with methotrexate tablets (MTX, 2.5 mg /tablets, Shanghai Sine Pharmaceutical Co. LTD. Approval Number 601340H), 10 mg each time, once a week; diclofenac sodium sustained release tablets (0.3 g/capsule, manufactured by Sino-US Tianjin GlaxoSmithKline Pharmaceutical Co., LTD. Approval Number H1090 0 089), 0.3 g each time, twice a day; folic acid tablets (5 mg/tablet, manufactured by Jiangsu Yabang Aipusen Pharmaceutical Co. LTD. Approval Number H32023288),
Table 1 Comparison of the general data of the RA patients between the two groups. Group
Observation Control
Patients
30 30
Gender (cases)
Age (years)
Male
Female
Youngest
Oldest
Average (X¯ ± S)
Duration of illness (years) Shortest
Longest
Average (X¯ ± S)
6 5
25 24
20 18
67 65
56 ± 14 54 ± 11
1 1
22 21
11.4 ± 6.8 10.1 ± 7.2
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
5 mg each time, once a week. In order to reduce the adverse reactions, i.e. the side effects of gastrointestinal tract and liver function damage, the drugs mentioned above were taken after meal. The medication for 30 days was as one session. Observation group On the base of the treatment of the control group, the specific acupoints were selected and stimulated with the triple strongstimulation therapy, in which, the strong bloodletting technique, strong cupping technique and strong moxibustion technique were combined together. Manipulations: Dàzhu¯ı ( GV 14) and Ashi points which locate around the knuckles. The patient was in the position that was suitable for the operation of the triple strongstimulation therapy. The acupoints were sterilized routinely. The small three-edged needle for single use was selected for the bloodletting. The skin around the acupoint was fixed with the thumb and the index figure of one hand. The three-edged needle was held like holding the pen with another hand, holding the needle body with the thumb and the index finger tightly and the needle tip exposed by 2 mm. The needle was inserted swiftly 1–2 mm deep beneath the skin and the acupoint was stimulated by several times of pricking. Afterwards, the flash cupping technique with a large cup was applied to the pricking sites. The operator shook and tapped the cup strongly before removed it from the body. In the cup removal, the cup was firstly tilted in the centripetal direction and then, it was removed off the body in the anticentripetal direction swiftly. The flash cupping technique was repeated for 5–10 times. Finally, the cup was retained for 5–10 min. The bleeding was observed carefully and blood volume was controlled as 3–5 mL. The most important step of the triple strong-stimulation therapy was the strong moxibustion technique. The moxa stick was selfprepared with the aged moxa wool, 20 cm in length, 2 cm in diameter and 25–27 g in weight. Right after the cup removed, the strong-moxibustion technique was operated. Five moxa sticks were tightened together and ignited. The ignited moxa sticks were held above the center of the cupping site, 5 cm far from the skin, moved up and down, avoiding skin burns, for 20–30 min in generally. The optimal duration of moxibustion was determined by whether the local skin turned red. In each treatment, GV 14 must be selected and 1–2 Ashi points, i.e. the painful points around the swelling joints were combined. The treatment was given once every 3 days, consecutively for 10 times. Precautions: this therapy should be adopted with caution if the patient had severe traumatic injury of the neck and shoulder, thrombocytopenia and hematopathy or had undergone a major surgery in recent 2 weeks. If blisters occurred accidentally at GV 14 or Ashi points after cupping or strong moxibustion, the ointment for scald was used locally. The very severe case should be treated in the Burns Department and the triple strong-moxibustion therapy could be given after healing. The pigmentation occurred after blister healing and it was absorbed automatically. After treated with the triple strong-moxibustion therapy, the patients were advised to avoid spicy and cold food, cold invasion, cold bath as well as profuse sweating. The therapeutic effects were evaluated after 1-month treatment in the two groups. Effect observation Observation indicators (1) Rheumatoid factor (RF) (the kit was bought from EUROIMMUN Medical Laboratory Diagnostics Stock Company). Separately, before treatment and on the next day after treatment, the fasting blood was collected after getting up in the morn-
253
ing. The immune scatter turbidity method was adopted in the determination. The concrete operation procedure for RF determination was in accordance with the instruction on the kit. (2) Hypersensitive C-reactive protein (hs-CRP) (the kit was bought from EUROIMMUN Medical Laboratory Diagnostics Stock Company). Separately, before treatment and on the next day after treatment, the fasting blood was collected after getting up in the morning. The immunofluorescence dry quantitative method was adopted in the determination. The concrete operation procedure for hs-CRP determination was in accordance with the instruction on the kit. (3) Erythrocyte sedimentation rate (ERS) (the kit was bought from EUROIMMUN Medical Laboratory Diagnostics Stock Company). Separately, before treatment and on the next day after treatment, the fasting blood was collected after getting up in the morning. The Westergren method was adopted. The concrete operation procedure for ESR determination was in accordance with the instruction on the kit. (4) Quantitative criteria of the symptom and physical sign scores. In reference to Guidelines and principles for clinical research of new drugs of traditional Chinese medicine issued by the Ministry of Health, China [2], the concrete symptoms and physical signs were scored. Scoring criteria: according to the severity of main clinical manifestations, symptoms and physical signs in RA patients, four grades are divided, i.e. normal, mild, moderate and severe, scored as 0, 2, 4 and 6 separately. The primary symptoms and physical signs include joint pain, joint swelling, palpable pain and tenderness of joint, morning stiffness of joint and limited movement of joint. The secondary symptoms and physical signs are repeated fever, reduced appetite, emaciation, cold or feverish joint, subcutaneous nodes, aversion to wind and cold, short breath, dislike to speak and low spirits. The researchers in the team observed and recorded carefully the symptoms and physical signs as well as evaluated the qualitative grade in the patients before and after treatment. (5) Disease activity score of rheumatoid arthritis (DAS-28) [4]. In reference to PREVOO calculation method, DAS 28 = 0.56 × Num.oftenderjoint + 0.28 × Num of swelling joint+ 0.7 × In (ESR) + 0.16. DAS-28 includes the scores of 28 joints, i.e. shoulders, elbows, wrists, phalangeal joints of hands, proximal interphalangeal joints of hands and knee joints. DAS-28 score > 5.1 indicates the active illness, < 3.2 indicates low activity and < 2.6 indicates slow activity. One evaluation was conducted before treatment and after 30-day treatment separately. Effect evaluation criteria The relevant criteria on the therapeutic effects in Guidelines and principles for clinical research of new drugs of traditional Chinese medicine [3] were taken as reference. Quantitative criteria of the symptom and physical sign scores were as therapeutic effect criteria. Remarkably effective: the improvement rate of the primary and secondary symptoms and physical signs ≥ 75%, the laboratory physiochemical determination indicators were normal, improved obviously or close to the normal. Improved: 50%≤ the improvement rate of the primary and secondary symptoms and physical signs < 75%, and the laboratory physiochemical determination indicators were improved obviously. Effective: 30% ≤ the improvement rate of the primary and secondary symptoms and physical
254
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
Table 2 Comparison of the results of RF, hs-CRP and ESR, the scores of ADS-28, symptoms and physical signs in RA patients of the two groups (x¯ ± s). Group
Patients
Time
RF (μmol/L)
hs-CRP (mg/L)
ESR (mm/1 h)
DAS-28 (scores)
Observation
30
Control
30
Before treatment After treatment Before treatment After treatment
248.01 ± 79.81 31.17 ± 29.01a , b 254.11 ± 72.16 66.42 ± 37.07 a
26.12 ± 9.22 8.98 ± 7.66 a , b 23.18 ± 7.18 16.01 ± 5.02 a
30.56 ± 11.38 12.58 ± 5.91 a , b 35.52 ± 9.67 21.47 ± 6.91 a
8.89 ± 2.01 3.01 ± 0.74 a , b 8.14 ± 1.38 4.12 ± 0.96 a
a b
Quantitative grading of symptom (scores) 7.87 ± 1.69 3.82 ± 1.96 a , b 7.77 ± 1.68 5.01 ± 11.23 a
Compared with that before treatment of the same group, P < 0.05. Compared with that in the control group after treatment, P < 0.05.
Table 3 Comparison of the clinical therapeutic effects on RA in the patients of the two groups (cases). Groups
Patients
Remarkably effective
Improved
Effective
No effect
Total effective rate (%)
Observation Control
30 30
12 5
11 8
6 11
1 6
96.67a 80.00
a
Compared with the control group, P < 0.01.
signs <50%, and the laboratory physiochemical determination indicators were improved. No effect: the improvement rate of the primary and secondary symptoms and physical signs < 30% and the laboratory physiochemical determination indicators were not improved. The improvement rate of the primary and secondary symptoms and physical signs was determined by the percentage of the improvements in the primary and secondary symptoms and physical signs in the RA patients. [(Score of symptoms and physical signs before treatment − Score symptoms and physical signs after treatment)] ÷ Score of symptoms and physical signs before treatment × 100%. Statistical treatment SPSS 17.00 software was adopted. The measurement data was expression as mean ± standard deviation (ÿx ± s). The paired t test or one-way analysis of variance was adopted. For the enumeration data or the one-way ranked ordinal data, the x2 test for the data of paired fourfold table was applied. The test level was α = 0.05 and P < 0.05 indicated significant difference. Results The results of RF, hs-CRP and ESR as well as the scores of ADS-28, symptoms and physical signs of RA patients in the two groups The differences were not significant in the results of RF, hs-CRP and ESR as well as the scores of ADS-28, symptoms and physical signs between the RA patients in the two groups before treatment (all P > 0.05), indicating the comparability. Compared with the results before treatment, the levels of RF, hs-CRP and ESR, as well as the DAS-28 scores and the quantitative grading scores of symptoms in the RA patients were all reduced after treatment in the two groups (all P < 0.05). Compared with the control group, the levels of RF, hs-CRP and ESR, as well as the DAS-28 scores and the quantitative grading scores of symptoms in the RA patients were more improved in the observation group after treatment (all P < 0.05, see Table 2). Comparison of the clinical therapeutic effects in the RA patients between the two groups After treatment, with the statistical treatment, the total effective rate was 96.67% in the observation group and was 80.00% in the control group. The total effective rate in the observation group was significantly better than the control group (P < 0.01, Table 3).
Discussion RA is in the category of bi syndrome in traditional Chinese medicine (TCM). Regarding the etiology of this disease in TCM, the medical scholars of dynasties believe that the person with the congenital imbalance of the nutrient and defensive qi and the insufficiency of anti-pathogenic qi is easily attacked by the pathogenic wind, cold, damp and heat. The pathogenic factors are obstructed in muscles, bones, joints and meridians, resulting in retarded qi and blood circulation. The long-term illness affects the liver and the kidney and injured tendons and bones. Consequently, the intractable bi syndrome occurs. Y¯ıxué Rùmén (, Introduction to Medicine) says that the intractable bi syndrome results from the interaction of the pathogenic wind, cold and damp, with the tendon and bone damage involved. In pathogenesis, this disease is differentiated as the deficiency in the primary and the excess in secondary. The deficiency in the primary refers to the deficiency of the liver, spleen and kidney and the excess in the secondary to the stagnation and blockage by the pathogenic wind, cold, damp and phlegm. RA is the autoimmune disorder with the high morbidity at present and the females are more the males. The morbidity in females is 2–3 times as same as the males. RA happens at any age, frequently at the age of 40–60 years, which had been proved in the clinical data of this trial. At early stage, the joint synovium is invaded and the inflammatory reaction occurs. With the progress of the disease, more joints are affected and the joint deformity happens, in which, the deformity of hands and feet is common. Except the joint disorders, the other common clinical manifestations are fever, rheumatoid node, rheumatoid vasculitis, lymph swelling and even the severe disorders of the vital organs, i.e. the heart, lung and kidney. In western medicine, the first-line common drugs for RA are nonsteroidal anti-inflammatory drugs and the second-line drugs are the anti-rheumatic drugs for relieving the illness and alleviating or reliving pain. These medications alleviate joint stiffness, joint swelling and motor impairment and control the progress of sickness [4]. But, these chemical agents greatly affect the organs, i.e. the liver and the kidney. Specially, the probability of the chronic damages induced in the patients with long-term medication is much high and it is difficult for the patients to be well complied with the medication. According to the instructions in the guideline for the diagnosis and treatment of RA in China in 2018, MTX is the anchor drug and it is the publically-recognized firstline drug in the guidelines at home and abroad, acting on immune inhibition and rapid anti-inflammation. But, the drug-induced
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
hepatic toxicity and myelosuppression are very common. The researches in Chinese population show that the adverse reaction of small-dose MTX (≤10 mg a week) is mild and the long-term tolerance is satisfactory. Diclofenac sodium sustained release tablets are the nonsteroidal and anti-inflammatory drug, with strong effects and refer to the fenamic acids, working on reducing joint pain and swollen joint. But the drug induces gastrointestinal side effects. Folic acid is generally supplemented during treatment to reduce gastrointestinal side effects and liver damage. In this research, the western drugs were adopted in the control group according to the guideline and the first-line medication, i.e. MTX, diclofenac sodium sustained release tablets and folic acids. On the base of the treatment in the control group, the instruments and the techniques of acupuncture and moxibusiton were combined together in the intervention of RA in the observation group. The specific acupoints were selected and stimulated with the triple strong-stimulation therapy. The test indicators and the symptom quantitative grading scores were observed and the clinical effects were compared in the two groups so as to provide more choices and better therapeutic schemes for RA patients [5]. The clinical therapeutic effects and mechanism of the triple strong-stimulation therapy at GV 14 and the supplementary points were explored in the treatment of RA [6]. GV 14, at the governor vessel, locates at the nape region, the high position of the body, regarding as the yang within yang. It is the meeting point of the governor vessel with the three yang meridians of hand and foot. The governor vessel is the sea of the yang meridians and governs yang qi of the whole body. GV 14 is the crucial point for yang qi strengthening of the governor vessel. It acts on defending the body, protecting yang, scatter wind and release the exterior, building up yang to eliminate cold in treatment. It is taken as the optimal acupoint for the deficiency of anti-pathogenic qi, the invasion of pathogenic wind, cold and damp as well as the consumptive disorders. Based on the specificity of GV 14, the triple strong-stimulation therapy with the combination of different instruments and techniques of acupuncture and moxibustion was adopted in the treatment of RA. The therapy worked on the etiology and pathogenesis of the disease. It tonifies the body for the deficiency syndrome and reduces the pathogens for the excess syndrome. It was proved in the clinical observation that this therapy achieved the definite short-term therapeutic effects and the longterm protective effects. In the triple strong-stimulation therapy, the strong bloodletting and the strong cupping are operated on the base of traditional technique. The technical requirements are strict in the operation. The three-edge needle is selected instead of filiform needle and the strong bloodletting at GV 14 and the specific Ashi points produced strong stimulation. This technique induces excessive qi and blood in the local area in a short time to lay the foundation for the effect activation of meridian and acupoint. The researches prove [7–10] that the bloodletting and cupping stimulates the body to release some hormones and neuropeptides, promotes metabolism and accelerates blood circulation. It has significant effects of analgesia, anti-spasm, tranquilization, anti-inflammation and anti-allergy. Hence, the strong-bloodletting and the strong cupping techniques are applicable in the treatment of RA. There are the quite complete theory and mature experiences in the treatment of RA with the strong-moxibustion technique [11,12]. The strong-moxibustion technique at the specific acupoints strengthens yang and eliminates cold, wind and damp. Additionally, it dilates blood vessels, increases blood flow, inhibits vascular permeability, reduces inflammatory exudation and accelerates the allergen absorption. This technique effectively promotes the cellular and body fluid immunity, hence increases the immune function of the body [13–16]. The strong-moxibustion technique breaks through the traditional therapeutic mode in which moxa stick or
255
moxa cone in the local area is used for the mild moxibustion. This technique is characterized as the short duration of operation, close distance to the affected site, high temperature generated in the affected area, large area and direct stimulation of moxibustion, focusing on the strong stimulation, aiming to shorten the duration of treatment and the transmission from quantitative change to the qualitative change. Hence, the strong effects of warming meridians and collaterals, eliminating cold and removing damp were displayed prominently in a short time in the triple strong-stimulation therapy. As a result, the immediate effects are significant, which have been proved in clinical observation. The triple strong-stimulation therapy presents the warming and tonification effects while eliminating the pathogens, reinforce healthy qi without lingering pathogenic qi, hence, the satisfactory therapeutic effects are achieved in the treatment of RA. The triple strong-stimulation therapy at GV 14 and the specific Ashi points were applied in the treatment of RA and the randomized controlled trial was adopted to observe the changes of RF, hs-CRP, ESR, DAS-28 as well as the scores of joint symptom and physical signs. The results indicated that the triple strong-stimulation therapy achieved the definite effects on RA. The results of the trial show that either the triple strongstimulation therapy at the specific acupoints or the western medication in the control group relieved the clinical symptoms and physical signs of RA to different extents. The improvements in the triple strong-stimulation therapy combined with western medication were significantly better than the western medicine (all P < 0.05 or P < 0.01). It is suggested that the triple strong-stimulation therapy at the specific acupoints on the base of the medication in western medicine more effectively relieves the joint symptoms and improves the clinical effects. It is the effective compound therapy of acupuncture and moxibustion and extensively applicable for the treatment of RA.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.wjam.2019.01.003.
References [1] Villeneuve E, Nam J, Emery P. 2010 ACR-EULAR classification criteria for rheumatoid arthritis. Rev Bras Reumatol 2010;50(5):481–3. [2] Zheng XY. Guidelines and principles for clinical research of new drugs of traditional Chinese medicine: trial. Beijing: China Medical Science Press; 2002. p. 115–19. [3] Prevoo ML, Van’t Hof MA, Kuper HH. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 1995;38(1):44–8. [4] Li Y, Qi WC. Comparison of the therapeutic effects on rheumatoid arthritis treated with leflunomide combined with 99Tc-MDP or metrotrexate. Contemp Med 2009;15(7):123–4. [5] Cao WZ. Triple strong stimulation therapy”: the innovative approach to the improvement of acupuncture effects on pain. Jiangxi J Trad Chin Med 2012;43(1):50–3. [6] Cao WZ, Li AM, Dai RW, Zhang ZG. Compilation and development of the property of Dazhui (GV 14). J Sichuan Trad Chin Med 2012(12):32–4. [7] Chen LD, Li J, Zhou JB. Significance of IL-17, IL-18, IL-6 and TNF-α in the patients with rheumatoid arthritis. Contemp Med 2010;16(7):13–14. [8] Wu JW, Tang XF. Clinical significance in the expressions of serm TNF-α , IL-17 and CRP in the patients with rheumatoid arthritis. Chongqing Med 2012;41(30):3211–12. [9] Chen KH, Li RB, Gan Y, Li K, Tan L, Yang JH, et al. Efficacy of treatment of moxibustion to rheumatoid arthritis patients and its impact to blood levels of IL6,CRP and RF. Int J Lab Med 2014(21):2897–8. [10] Hao F, Hu L, Wu ZJ, Luo L, Cai RL, He L, et al. Clinical study on relations between quantity and effect of moxibustion on ginger in treating active rheumatoid arthritis. Lishizhen Med Mater Med Res 2013;24(3):677–80. [11] Qin SF. Observations on the therapeutic effect of thunder-fire moxibustion on allergic rhinitis. Shanghai J Acupunct Moxibustion 2011;30(11):765–7.
256
W.-z. CAO, W.-x. ZHAO and H.-m. GUO et al. / World Journal of Acupuncture – Moxibustion 28 (2018) 251–256
[12] Yue BA, Bi YF. 172 cases of rheumatoid arthritis treated with long-snake moxibustion therapy. Shaanxi J Trad Chin Med 2007;28(11):1536–7. [13] Ding F. Simple moxibustion therapy in treatment of rheumatoid arthritis. J Clin Acupunct Moxibustion 2007;23(10):40–1. [14] Li JW, Liu JM, Ma ZY, Xiang YY, Feng YB, Xiang SY, et al. Clinical observation on treatment of rheumatoid arthritis with cake-separated mild moxibustion combined with western medicine. Chin Acupunct Moxibustion 2006;26(3):192–4.
[15] Gong FY. 33 cases of rheumatoid arthritis treated with herbal medicine-isolated moxibustion therapy. J Clin Acupunct Moxibustion 2007;23(5) 4242. [16] Tong HY, Li XB. Clinical research of knee osteoarthritis treated with isolated mild moxibustion. J Clin Acupunct Moxibustion 2006;22(12):10–12.