Hui JI, Xiaohong NIU

The Affiliated Chinese and Western Medicine Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing 210014, China

Abstract [Objectives] To explore the effects of Guizhi Shaoyao Zhimu Decoction on laboratory indicators and immune functions of patients with rheumatoid arthritis. [Methods] A total of 110 patients with rheumatoid arthritis admitted to the Second Department of Orthopedics, the Affiliated Chinese and Western Medicine Hospital of Nanjing, Nanjing University of Chinese Medicine from December 2014 to December 2016 were selected as the research objects and divided into a control group and an observation group using the random number table method, with 55 cases in each group. The control group was treated with conventional western medicine, and the observation group was treated with Guizhi Shaoyao Zhimu Decoction on the basis of the control group. Both groups were treated for one month. The clinical effects, improvement of clinical symptoms, laboratory indicators and immune function indicator levels between the two groups were compared; the incidence of adverse reactions in the two groups was counted. [Results] The total effective rate of the observation group was 92.73%, higher than that of the control group (78.18%) (P<0.05). Compared with that before treatment, after one month of treatment, the grip strength of the two groups increased, and the observation group was greater than the control group (P<0.05); the morning stiffness time and 20 m walking time of both groups were shortened, and the observation group was shorter than the control group (P<0.05); the number of joint tenderness, joint swelling, ESR, MPV, PDW, serum CRP, plasma IgA, IgG, IgM, RF levels in both groups decreased, and the observation group was lower than the control group (P<0.05); the serum C3 levels in both groups increased, and the observation group was higher than the control group (P<0.05). During the treatment, the incidence of adverse reactions in the observation group was 0.00%, which was lower than that in the control group (10.91%, P<0.05). [Conclusions] Using Guizhi Shaoyao Zhimu Decoction to treat rheumatoid arthritis can improve the laboratory indicators of patients, and enhance their immune functions, improve the curative effect, and the safety is high.

Key words Rheumatoid arthritis, Guizhi Shaoyao Zhimu Decoction, Laboratory indicators, Immune functions

1 Introduction

Rheumatoid arthritis is an autoimmune disease, which is clinically manifested as joint swelling and pain, joint deformity, osteoporosis,etc., and recurs easily. In severe cases, labor capacity can be lost, thus affecting the physical and mental health of patients[1-2]. Clinically, western medicine is often used for symptomatic treatment, but the treatment effect is not ideal. Traditional Chinese medicine believes that patients with rheumatoid arthritis have insufficient healthy qi, accompanied with pathogenic qi invasion, resulting in poor circulation of qi and blood in the body. This belongs to the category of "impediment disease" in the theory of traditional Chinese medicine, and should be treated on the principle of dispelling wind and dampness, activating blood and resolving stasis. Guizhi Shaoyao Zhimu Decoction has the effects of dissipating cold, dispelling dampness, unblocking meridians and activating collaterals. Researches have shown that Guizhi Shaoyao Zhimu Decoction is evidently effective in treating rheumatoid arthritis[3-4]. This research explored the effects of Guizhi Shaoyao Zhimu Decoction on the laboratory indicators and immune functions of patients in the treatment of rheumatoid arthritis, in order to provide an effective basis for clinical optimization of the treatment plan for rheumatoid arthritis.

2 Data and methods

2.1 General dataWe selected a total of 110 patients with rheumatoid arthritis admitted to the Second Department of Orthopedics, the Affiliated Chinese and Western Medicine Hospital of Nanjing, Nanjing University of Chinese Medicine from December 2014 to December 2016 as the research objects and divided them into a control group and an observation group using the random number table method, with 55 cases in each group. In the control group, there were 29 males and 26 females; they were 42-69 years old, and the average age was (54.7±3.3) years old; the disease course was 1-11 years, and the average disease course was (4.5±1.7) years; in the observation group, there were 30 males and 25 females; they were 44-70 years old, and the average age was (54.2±3.6) years old; the disease course was 1-10 years, and the average disease course was (4.4±1.6) years. The main baseline data of the two groups were not statistically different after statistical analysis (P>0.05), and they were comparable. This research was reviewed and approved by the Medical Ethics Committee of our hospital (ethics approval number: 201807001).

2.2 Diagnostic criteriaWestern medicine complies with the relevant diagnostic criteria formulated by the American College of Rheumatology[5]; Chinese medicine complies with the diagnostic criteria in theGuidingPrinciplesforClinicalResearchonNewDrugsofTraditionalChineseMedicines[6].

2.3 Inclusion criteriaThose who were not more than 70 years old; those whose course of disease was less than 15 years; those who had no history of allergies to the drugs used in this research; those who had good compliance; those who gave informed consent to this research.

2.4 Exclusion criteriaThose who had severe cardiovascular, liver, kidney and other system complications; those who had severe joint deformities and lost labor capacity; those who were taking relevant treatment medicines; those who had mental disease; those who had incomplete medical records; those women who were pregnant or breastfeeding.

2.5 Withdrawal and rejection criteriaThose who could not take medicines as scheduled during the research; those who withdrew voluntarily.

2.6 Research methodsThe control group was treated with conventional western medicine, Celecoxib Capsules (sub-packaged by Pfizer Pharmaceuticals LLC, National Medicine Permit No. J20120063), taking orally, 1 capsule/time, 2 times/d; Methotrexate Tablets (Hunan Zhengqing Pharmaceutical Group Co., Ltd., National Medicine Permit No. H19983205), taking orally, 1 tablet/time, 1 time/week. The observation group was treated with Guizhi Shaoyao Zhimu Decoction on the basis of the control group. The prescription was: Coicis Semen 30 g, Zingiberis Rhizoma Recens and Atractylodis Macrocephalae Rhizoma 15 g each, Cinnamomi Ramulus, Ephedrae Herba, Anemarrhenae Rhizoma, and Saposhnikoviae Radix 12 g each, Aconm Lateralis Radix Praeparaia and Angelicae Pubescentis Radix 10 g each, Paeoniae Radix Alba 9 g, Glycyrrhizae Radix et Rhizoma 6 g, boiled and decocted, 2 times/d, taking 2 times in the morning and evening. Both groups were treated for one month.

2.7 Observation indicators(i) The improvement of grip strength, number of joint tenderness, joint swelling, morning stiffness time, 20 m walking time,etc. before treatment and after one month of treatment were counted. (ii) Before treatment and after one month of treatment, fasting venous blood 5 mL was collected in the two groups, one part of which was separated from serum, and the other part of which was treated with anticoagulation; Westergren method, automatic biochemical analyzer, immunoturbidimetry method, and enzyme-linked immunosorbent assay were used to detect and compare the changes in erythrocyte sedimentation rate (ESR), mean platelet volume (MPV), platelet distribution width (PDW), serum C-reactive protein (CRP) and other laboratory indicators as well as plasma immunoglobulins IgA, IgG, IgM, complement C3, rheumatoid factor (RF) and other immune function indicators in the two groups before and after treatment. (iii) The incidence of adverse reactions in the two groups during treatment was compared.

2.8 Efficacy evaluation criteriaThe efficacy evaluation was made with reference to theGuidingPrinciplesforClinicalResearchonNewDrugsofTraditionalChineseMedicines[6]for the efficacy evaluation criteria for the two groups of patients, in which cure means that laboratory indicators return to normal levels, joint swelling and pain, joint deformity, osteoporosis and other clinical symptoms disappear; evident effectiveness laboratory indicators are close to normal , joint swelling and pain, joint deformity, osteoporosis and other clinical symptoms are significantly improved; effective for improvement of laboratory indicators, joint swelling and pain, joint deformity, osteoporosis and other clinical symptoms are reduced; invalid for the above clinical symptoms and signs improve. Total effective rate (%) = Number of (Cured+Markedly effective+Effective) cases/Total number of cases × 100%.

3 Results

3.1 Comparison of clinical effectsAfter one month of treatment, the total effective rate of clinical treatment in the observation group was 92.73%, which was significantly higher than 78.18% in the control group (P<0.05), as shown in Table 1.

Table 1 Comparison of clinical effects between two groups of patients [case (%), n=55]

3.2 Comparison of clinical symptom improvementCompared with that before treatment, after one month of treatment, the grip strength of both groups increased, and the observation group was greater than the control group (P<0.05); the number of joint tenderness and joint swelling in the both groups decreased, and the observation group was lower than the control group (P<0.05); the morning stiffness time and 20 m walking time of both groups were shortened, and the observation group was shorter than the control group (P<0.05).

3.3 Comparison of laboratory indicator levelsCompared with that before treatment, after one month of treatment, the ESR, MPV, PDW, and serum CRP of the both groups decreased, and the observation group was lower than that of the control group (P<0.05), as shown in Table 3.

3.4 Comparison of immune function indicator levelsCompared with that before treatment, after one month of treatment, the levels of plasma IgA, IgG, IgM, and RF in both groups decreased, and the observation group was lower than that of the control group (P<0.05); the plasma C3 levels in both groups increased, and observation group was higher than that of the control group (P<0.05), as shown in Table 4.

Table 2 Comparison of clinical symptom improvement between two groups of patients n=55)

Table 3 Comparison of laboratory indicator levels between two groups of patients n=55)

Table 4 Comparison of immune function indicator levels between two groups of patients n=55)

3.5 Comparison of the adverse reactionsDuring the treatment, the incidence of adverse reactions in the observation group was 0.00%, which was lower than that in the control group,10.91% (6/55) (x2=2 336,P<0.05)

4 Discussion

Rheumatoid arthritis is characterized by slow development and a long course of disease. It has a certain impact on the patient’s working ability, physiological function, physical and mental health and family economic status. At present, there are no specific drugs for the treatment of the rheumatoid arthritis. Western medicine mainly uses drugs such as methotrexate, which can relieve the clinical symptoms to a certain extent, but patients will have serious adverse reactions after long-term use[7-8]. Therefore, clinically, it is recommended to integrate traditional Chinese and Western medicines for treatment. According to the theory of traditional Chinese medicine, the rheumatoid arthritis belongs to "impediment disease" and "joint-running wind disease". Patients with rheumatoid arthritis are physically weak, invaded by wind, cold, and dampness. Pathogenic qi enters the meridians and collaterals and stays at the joints. Then, qi and blood movement is blocked, leading to pathological reactions such as poor joint flexion and extension, pain and numbness. The pathogenic qi stays in the body and also damages the bones, causing them to deform and dysfunction. As stated inPlainQuestions, wind, cold, and dampness invade the body and lead to the impediment disease[9-10].

If the rheumatoid arthritis persists and does not heal, it will damage the qi and blood and visceral organs for a long time. Guizhi Shaoyao Zhimu Decoction, developed by famous physician Zhang Zhongjing in the Eastern Han Dynasty, is mainly used for treatment of rheumatism impediment disease. In the prescription, Cinnamomi Ramulus matched with Ephedrae Herba and Saposhnikoviae Radix has the function of warming the cold and dispelling the exterior, Cinnamomi Ramulus matched with Aconm Lateralis Radix Praeparaia has the function of assisting yang and dispelling dampness, warming the meridian and dissipating the cold; Paeoniae Radix Alba and Anemarrhenae Rhizoma have the function of replenishing yin and clearing away the heat, harmonizing the yin and treat the impediment from the interior; Angelicae Pubescentis Radix, Atractylodis Macrocephalae Rhizoma and Coicis Semen have the function of dispelling dampness and freeing the collateral vessels, Glycyrrhizae Radix et Rhizoma and Zingiberis Rhizoma Recens have the function of harmonizing the spleen and stomach. The combination of all these medicines realizes the harmony between yang and yin, achieves the effect of warming the meridian and dispelling cold, nourishing yin and clearing away the heat. According to results of this research, after one month of treatment, the total effective rate of clinical treatment in the observation group was higher than that of the control group, and the grip strength was greater than that of the control group; the number of joint tenderness and joint swelling decreased, suggesting that Guizhi Shaoyao Zhimu Decoction can improve the clinical symptoms of patients with rheumatoid arthritis, and the effect is significant. This is possibly because the active component aconitine in the prescription has anti-inflammatory effects and can inhibit joint pain; the effective components of paeoniflorin and gallic acid can promote dysmenorrhea and promote blood circulation, which is conducive to joint stretching activities[11-12]. For patients with rheumatoid arthritis, the circulation of qi and blood is blocked, the joints are often in a state of hypercoagulability, and local blood circulation is not smooth, which is not conducive to joint rehabilitation[13]. According to the results of this research, compared with that before treatment, after one month of treatment, the ESR, MPV, PDW and serum CRP levels of observation group were lower than those of the control group, suggesting that Guizhi Shaoyao Zhimu Decoction can improve blood circulation in patients with rheumatoid arthritis, which may be related to the anti-inflammatory effect of paeonol, and the active component of Paeoniae Radix Alba in the prescription can inhibit platelet aggregation; the Aconm Lateralis Radix Praeparaia in the prescription can increase blood flow and improve microcirculation disorders[14-15].

Patients with rheumatoid arthritis will develop humoral immune hyperactivity and produce a large amount of immunoglobulins, resulting in the loss of Th1/Th2 balance, the immune function disorder of the body, and joint tissue injury. The results showed that after one month of treatment, the plasma IgA, IgG, IgM, and RF levels in the observation group were lower than those in the control group, while plasma C3 levels were higher than those in the control group, suggesting that Guizhi Shaoyao Zhimu Decoction can upregulate the immune function of patients with rheumatoid joints, which is consistent with the research results of Yang Aipingetal.[16]. It may be that the extract of Aconm Lateralis Radix Praeparaia in the prescription can increase the content of complement; the active components such as coumarin and organic acids in Cinnamomi Ramulus have anti-viral, anti-inflammatory and anti-tumor functions, thus improve the body’s immunity; the active components of saponins in Anemarrhenae Rhizoma have anti-pathogenic, blood sugar lowering, and anti-cancer effects, and thus can regulate the body’s immunity[17-19]. In addition, the observation group had no obvious adverse reactions during the treatment of the both groups of patients in this research. The control group had adverse reactions such as nausea, diarrhea, and dry mouth. The adverse reaction rate was 10.91%, which was significantly higher than that of the observation group, indicating that Guizhi Shaoyao Zhimu Decoction has no adverse reactions to patients with rheumatoid arthritis, and can reduce the adverse reactions of conventional western medicines. It is safe and effective, which is consistent with the research results of Liu Xiaowei[20].

In summary, Guizhi Shaoyao Zhimu Decoction can improve rheumatoid arthritis, can significantly improve the patient’s laboratory indicators, enhance their immune functions, and then help improve the efficacy, and has high safety and is worth promotion.