Effect of Self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction Combined with Tramadol on TCM Symptom Scores and RLS Severity of patients with Restless Legs Syndrome

Objective: To investigate the effect of self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction on Traditional Chinese Medicine (TCM) symptom scores and RLS Severity of patients with restless legs syndrome (RLS). Methods: This was a clinical comparative study. Eighty patients with RLS admitted to Baoding No.1 Central Hospital from January 2022 to December 2022 were randomly divided into observation group and control group(n=40). Patients in the control group were given basic and oral tramadol treatment, while those in the observation group were given self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction based on the treatment in the control group. The differences of TCM symptom scores, RLS severity (IRLS), quality of life (QOL-RLS), sleep quality (PSQI) and clinical efficacy between the two groups were compared. Results: Before treatment, no statistically significant differences were observed in the TCM symptom scores, IRLS scores, QOL-RLS scores and PSQI scores between the two groups (p>0.05). After treatment, the above scores decreased significantly in both groups, with a higher degree of decrease in the observation group than in the control group, indicating statistically significant differences (p<0.05). The QOL-RLS scores were significantly higher in the observation group than in the control group, with a statistically significant difference (p<0.05). The overall response rate in the observation group was 95.00%, which was higher than that in the control group (80.00%), with a statistically significant difference (p<0.05). Conclusion: Self-developed Ye’an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction leads to numerous benefits in the treatment of RLS, such as obviously ameliorating patients’ clinical symptoms, reducing RLS severity, and improving their quality of life and sleep quality.


INTRODUCTION
Restless legs syndrome (RLS) refers to a chronic neurological sensorimotor disorder in which the main symptoms are a strong desire for limb movement and abnormal sensation during sleep or quiet.The symptoms are most common in the lower limbs and can also involve the upper limbs, which are often accompanied by unbearable discomfort such as acupuncture, itching, creeping sensation, soreness and pain. 1 RLS was first described by Tomas Willis, a British doctor, in 1685, and was named and described in more detail by Karl Axel Ekbom who was a Swedish doctor in 1944, so RLS is also called Willi-Ekbom Disease (WED). 2 RLS makes inroads on 1.2%-15% of the population and is common in Europe and the United States, with a lower prevalence in Asian countries.Moreover, its prevalence differs significantly between men and women, with a significantly higher prevalence in women than in men, and it will gradually increase with age.4][5] There are many options available for the treatment of RLS.In Western medicine, drugs are mainly used to relieve or control clinical symptoms 6 , but there are drawbacks such as drug resistance, dependence and side effects that can easily occur with long-term medication.
In contrast, Traditional Chinese Medicine (TCM) takes the overall concept and dialectical treatment as the guiding ideology.Currently, RLS is classified as "arthralgia" in TCM, with its pathogenesis being deficiency of liver and kidney and deficiency of qi and blood.To address this, Jiawei Shaoyao Gancao Decoction can be used for its effects of nourishing yin, nourishing liver and softening tendons, dredging channels and activating collaterals and balancing qi and blood.In this study, the clinical effect of self-developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction on RLS and its influence on TCM symptom scores and RLS severity were investigated.

METHODS
This was a clinical comparative study.Eighty patients with RLS who met the inclusion and exclusion criteria in Baoding No. Basic treatment: Patients were given sleep hygiene, behavioral therapy and elimination of substances that may exacerbate RLS symptoms, such as smoking, alcohol consumption and certain drugs.Patients in the control group were given oral tramadol hydrochloride tablets 50 mg each time, three times/day on the basis of the basic treatment.Those in the observation group were treated with self-developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction on top of the treatment in the control group.The composition of the formula was as follows: 30-g of Radix Paeoniae

A h e a d o f F i n a l P u b l i c a t i o n
Statistical analysis: All the data in this study were statistically analyzed by SPSS 21.0 software.The measurement data were expressed by mean standard deviation ( ), and t test was used for comparison between groups.Counting data were expressed by the percentage of cases [n (%)], and χ 2 test or Fisher's exact probability was used for comparison between groups.Rank sum test was used for grade data, with p<0.05 indicating a statistically significant difference.

RESULTS
No statistically significant differences were observed in the basic data between the two groups, which were comparable (p>0.05).See Table-I for details.Before treatment, no statistically significant differences were observed in the TCM symptom scores between the two groups (p>0.05).After treatment, the TCM symptoms scores decreased significantly in both groups, with a higher degree of decrease in the observation group than in the control group, indicating a statistically significant difference (p<0.05).Table-II.
Before treatment, no statistically significant differences were observed in the IRLS scores between the two groups (p>0.05).After treatment, the IRLS scores decreased significantly in both groups, with a higher degree of decrease in the obser Table-III.
Before treatment, no statistically significant differences were observed in the QOL-RLS scores between the two groups (p>0.05).After treatment, the QOL-RLS scores decreased significantly in both groups, with a higher degree of decrease in the observation group than in the control group, indicating a statistically significant difference (p>0.05).Table-IV.
Before treatment, no statistically significant differences were observed in the PSQI scores between the two groups (p>0.05).After treatment, the PSQI scores decreased significantly in both groups, with a higher degree of decrease in the obser Table-V.
After treatment, the symptoms of the two groups were improved to varying degrees.The overall response rate of the patients in the observation

A h e a d o f F i n a l P u b l i c a t i o n
group was 95.00%, which was higher than that in the control group (80.00%), with a statistically significant difference (p>0.05).Table-VI

DISCUSSION
It was shown in this study that the TCM syndrome scores and IRLS scores of patients in the two groups were significantly decreased compared with those before treatment.The degree of decrease in the observation group was better than that in the control group (p<0.05),indicating that the observation group had better effects in improving the clinical symptoms such as numbness of limbs, weakness of limbs, soreness and pain, insomnia and dreaminess, which was related to the mechanism of nourishing blood and promoting blood circulation, relieving pain and removing blood stasis and dredging collaterals in Jiawei Shaoyao Gancao Decoction.After treatment, the QOL-RLS scores of patients in both groups were higher than those before treatment, while the PSQI scores were significantly lower than those before treatment.Moreover, the improvement of QOL-RLS scores and PSQI scores in the observation group was better than that in the control group (p<0.05).The results showed that the quality of life and sleep of patients with RLS were significantly improved after treatment with Jiawei Shaoyao Gancao Decoction, and its mechanism was related to that Jiawei Shaoyao Gancao Decoction could significantly relieve RLS symptoms, and the RLS symptoms of patients were improved.After treatment, the overall response rate of the patients in the observation group was higher than that in the control group (p<0.05), which further showed that the application of Jiawei Shaoyao Gancao Decoction in the treatment of RLS could effectively relieve the clinical symptoms of patients, regulate their sleep disorders, improve the relationship between them and promote benign recovery.
RLS is a sensory dyskinesia disease and a common disease of the clinical nervous system. 8Its clinical symptoms are often separated from physical signs, with the most prominent clinical manifestation being the strange sensation in the deep part of one or both limbs, such as unbearable acid, swelling, numbness or insect bite, ant drilling, or pain such as knife cutting, over-current and tearing.Patients suffering from RLS are unable to relieve the discomfort by resting, forcing them to relieve after activities such as patting, moving the affected limb or walking, which often leads to sleep disorders and anxiety.RLS discomfort symptoms interact with sleep and anxiety to form a vicious circle, which seriously affects patients' normal work and life. 9- 12Despite numerous clinical studies on the etiology and pathogenesis of RLS, none of them are clear and definitive.4][15] RLS has no exact TCM disease name, but its symptoms are similar to "blood arthralgia" and "sore leg" described in Synopsis of the Golden Chamber and Neijing.At present, most TCM scholars classify it as "arthralgia syndrome", which is marked by three evils of wind-cold-dampness, stagnation of qi-flowing, and dystrophy of meridians.The original symptoms are deficiency of liver and kidney, deficiency of qi and blood and yin and yang, and the treatment is to regulate liver, nourish blood and soothe the nerves. 16haoyao Gancao Decoction is a classic prescription from Treatise on Febrile Diseases to treat "foot contracture" 17,18 , which has the effect of "restoring its yin" if the syncope becomes warmer enough, it is even more like Shaoyao Gancao Decoction.The prescription is composed of Paeonia lactiflora and Radix Glycyrrhizae Moxibustion, and the Paeonia lactiflora is sour and cold, which softens the liver and relieves pain, nourishes blood and astringes yin.In this study, the self-developed Ye'an Analgetic Decoction is composed of Radix Astragali, Fructus Chaenomelis, Caulis Spatholobi, Radix Angelicae Sinensis, Radix Achyranthis Bidentatae, Radix Salviae Miltiorrhizae, Flos Carthami, parched Semen Persicae, Lumbricus and Ramulus Cinnamomi.Caulis Spatholobi can dredge collaterals, relieve pain, enrich blood and promote blood circulation; Angelica regulates menstruation, relieves pain, enriches blood and promotes blood circulation; Carthamus tinctorius has the functions of removing blood stasis, relieving pain, dredging The combination of all kinds of drugs has the effects of nourishing blood and activating blood, nourishing yin and softening liver, removing blood stasis and dredging collaterals.[19][20][21] Limitations: It includes fewer observation cases with short follow-up time, so it is necessary to expand the sample size and extend the follow-up time to further evaluate its clinical effect. In adition, only the clinical efficacy was observed in this study, which led to the observation indexes being subjectively influenced by patients and the indexes being difficult to quantify, so further studies are still needed to improve them in the future.

CONCLUSION
Self-developed Ye'an Analgetic Decoction/Jiawei Shaoyao Gancao Decoction leads to favorable clinical results in the treatment of RLS, such as effectively ameliorating the clinical symptoms of RLS patients, reducing RLS severity, and improving their quality of life and sleep, which is worthy of clinical promotion.
Scores and RLS Severity of patients with Restless Legs Syndrome 1Central Hospital from January 2022 to December 2022 were selected as subjects and were randomly divided into two groups: the observation group and the control group, with 40 cases in each group.

Table - I
: Comparison of general information between the two groups.
Note: * indicates p>0.05 compared with the control group; ※ indicates p<0.05 compared with the control group of the same period, △ indicates p<0.05 compared with the pre-treatment group.Note: ※ indicates p<0.05 compared with the control group, △ indicates p<0.05 compared with that before treatment.Note: ※ indicates p<0.05 compared with the control group, △ indicates p<0.05 compared with that before treatment.

Table - V
: Comparison of PSQI scores between the two groups before and after treatment ( , points).Scores and RLS Severity of patients with Restless Legs Syndrome channels and promoting blood circulation; Peach kernel can remove blood stasis and promote blood circulation; Lumbricus can relieve pain and dredge collaterals; Astragalus qi and blood; Achyranthes bidentata, Papaya, Salvia Miltiorrhiza and Ramulus Cinnamomi dredge meridians and reach limbs.