Yi-Kang Yu,Zheng Liu,Tian-Hang Chen,Yan-Yan Mou,Jing-Min Ji,Bo-Cheng Liang,Chao Xu*

1Second Clinical College of Zhejiang Chinese Medical University,Second Affiliated Hospital,Hangzhou,China.2College of Life of Zhejiang Chinese Medical University,Hangzhou,China.3First Clinical Medical College of Zhejiang Chinese Medical University,Hangzhou,China.4School of Basic Medicine,Zhejiang Chinese Medical University,Hangzhou,China.

Abstract: Objective:To explore the effect of Guipi Decoction Combined with non steroidal anti-inflammatory drugs on sleep time of elderly patients with traumatic pain and Qi deficiency constitution during hospitalization.Methods:A total of 52 elderly patients hospitalized in the orthopedic (trauma) ward of the Second Affiliated Hospital of Zhejiang Chinese Medical University from November 2020 to may 2021 were randomly divided into control group and treatment group.Patients in the control group were treated with loxoprofen sodium tablets immediately after admission,and placebo was added to loxoprofen sodium tablets from the second day of admission;The patients in the treatment group were treated with loxoprofen sodium tablets after admission.Guipi Decoction was added on the basis of loxoprofen sodium tablets from the second day of admission.Before and after admission,all patients used the TCM constitution classification judgment table to evaluate the score of qi deficiency and VAS;From the first day to the fourth day after admission,the bracelet was worn to monitor the sleep time (total sleep time,deep sleep time,light sleep time and awakening times) every night.The patients were scored by VAS after taking drugs every morning.Results:Finally 25 patients in the control group and 24 patients in the treatment group completed the experiment.There was no significant difference in gender,age,fracture location,chronic medical history VAS score and TCM Qi deficiency constitution score,between two groups at admission(P >0.05).At the time of discharge,the score of qi deficiency constitution in the treatment group was 33.724 ±12.634;The TCM Qi deficiency constitution score of the control group was 42.25 ± 15.912,and there was significant difference between the two groups (P <0.05);and there was significant difference in VAS score between the two groups at discharge (P <0.05).There were significant differences in total sleep time,light sleep time,deep sleep time and night awakening times between the two groups on the second,third and fourth day of admission(P <0.05).Conclusion:1.Guipi Decoction can significantly improve the sleep time of patients with Qi deficiency acute traumatic pain.2.Guipi Decoction can not only improve the constitution of patients with Qi deficiency bias,but also improve the VAS score at discharge.

Keywords:Guipi Decoction;pain;Qi deficiency;TCM Constitution;integrated traditional Chinese and Western medicine;sleep time

Introduction

Due to the physiological characteristics of the decline of bone mineral density in the elderly and the increase of the elderly population in China,the incidence of acute trauma in the elderly population shows an upward trend.Acute trauma can trigger a series of body reactions,such as local pain,inflammation and stress response.Pain is a major manifestation after trauma,which can cause the decline of patients' quality of life during the day and affect their sleep at night.Some studies have pointed out that the pain caused by acute physical injury and traumatic diseases can enhance the patients' feeling of chronic pain in the future and have an adverse impact on the patients' rehabilitation [1-3].The long-term pain caused by acute pain can not be effectively solved,which can further affect the patients' daily functional activities and sleep time,and then lead to physical problems such as weakness and loss of function,as well as psychological problems such as anxiety and depression [3].In elderly patients,physique and sleep time have an important impact on whether the elderly are weak.Cui Guanghui and others pointed out that the existence of sleep disorder and biased physique are the influencing factors of the elderly,and sleep quality and TCM physique type have additive interaction on the elderly [4].Yang Jie et al.Pointed out that qi deficiency constitution accounts for 30.20% of the general population with poor sleep quality,indicating that qi deficiency constitution has an impact on sleep time [5].For mild to moderate traumatic acute pain,non steroidal anti-inflammatory drugs are commonly used in orthopedics,and analgesic drugs and sleeping drugs are used according to the severity of pain.However,due to their physiological characteristics,elderly patients are often difficult to tolerate the treatment of high-dose analgesic drugs,and are prone to sleeping drug dependence.Traditional Chinese medicine as a supplementary and alternative therapy has good development value.

The earliest record of Guipi Decoction comes from Zhengti Lei Yao,written by Xue Ji in the Ming Dynasty,which records many common therapeutic prescriptions after fracture.It shows that the prescription has the effects of Supplementing Qi and blood,strengthening spleen and nourishing heart.Elderly patients have bleeding or occult blood loss after fracture.Traditional Chinese medicine believes that Qi can move blood and blood can carry gas.In addition to qi stagnation and blood stasis,acute trauma can also lead to Qi loss with blood and two injuries of Qi and blood,resulting in insomnia,palpitation and palpitation.In view of this etiology and pathogenesis,Guipi Decoction contains the meaning of "Qi can generate blood",mainly takes Qi tonifying drugs,takes into account the generation of blood,and has the effect of nourishing the heart and calming the mind.This study investigated the effect of Guipi Decoction Combined with non steroidal anti-inflammatory drugs on sleep time of elderly patients with traumatic pain with Qi deficiency constitution during hospitalization(Figure 1).

Figure 1 Flow chart of clinical observation

Data and methods

Research object and ethic

The elderly patients hospitalized in the orthopaedic (trauma)ward of the Second Affiliated Hospital of Zhejiang Chinese Medical University from November 2020 to may 2021 were selected.All patients and their families signed the patient's informed consent before the trial.The observational study was reviewed by the Ethics Committee of the Second Affiliated Hospital of Zhejiang Chinese Medical University(ethics number:2020-KL-161-01).

Inclusion criteria

a.Age≥60 years;

b.Had a history of acute trauma,was diagnosed as fracture by imaging,and came to our hospital for treatment within 24-48 hours;

c.According to the TCM constitution classification and judgment table [6] formulated by Professor Wang Qi of Beijing University of traditional Chinese medicine,the score of patients with Qi deficiency was evaluated and determined as "tendency is" or above(transformation score≥30 points);

d.According to the visual analog score (VAS) scale used clinically,all patients were scored for pain at the initial visit.The evaluation score was above moderate pain:the score was ≥4,the pain was obvious and intolerable,requiring the use of analgesic drugs,and the sleep was disturbed.

Exclusion criteria

a.Trauma combined with major diseases such as massive hemorrhage,cardiovascular and cerebrovascular accident,respiratory failure,liver and kidney injury;

b.Have long-term sleep disorders and take sleeping drugs recently;

c.Have a history of mental illness and recently take antidepressant and anxiety drugs;

d.Emergency surgery was performed after admission;

e.Mental deficiency or low,unable to complete the scale score or cooperate with the test;

f.Drug or alcohol dependence that interferes with the trial medication.

Falling off and suspension

a.Failure to complete sleep monitoring for four days or more due to various reasons;

b.Discontinue drug treatment for various reasons or do not use drugs according to the test requirements;

c.Serious adverse events and other symptoms interfering with the test occurred during the treatment.

Evaluation of qi deficiency constitution

According to the TCM constitution classification and judgment table,the degree of symptoms is divided into:No,few,sometimes,often and always,which are respectively divided into 1,2,3,4 and 5;The evaluation symptoms of qi deficiency quality are:8 items:easy to fatigue,easy to shortness of breath,easy to panic,easy to dizziness,easy to catch a cold,lazy to speak,weak voice and easy to sweat;Where the original score=the sum of the scores of each item.Conversion score=(Original Score -number of entries)/(number of entries)×4×100.If the score of transformation method is ≥30,it is judged as "tendency is" and if the score is ≥40,it is judged as "yes".

Random grouping

Use SAS 9.2 statistical software package to generate random grouping codes,hide all codes in closed and opaque envelopes,open the envelopes according to the order of patient visits,and get the random number and grouping scheme.

Interventions

Control group:After admission,loxoprofen sodium tablets(Lesong,Shanghai first three Co.,Ltd.,drug approval No.:gyzz h20030769) (60mg/tablet),60mg each time,3 times/d.From the second day of admission,placebo was added to loxoprofen sodium tablets,i.e.180g Huai wheat,formula granules,1 bag/time,2 times/d (after getting up and before going to bed),dissolved in 150ml boiled water,washed and taken continuously for 2 weeks.

Treatment group:after admission,use loxoprofen sodium tablets (Lesong,Shanghai first three Co.,Ltd.,drug approval No.:gyzz h20030769) (60mg/tablet),60mg each time,3times/ d.from the second day of admission,add Guipi Decoction on the basis of loxoprofen sodium tablets.Prescriptions:fried Atractylodes macrocephala 15g,Codonopsis pilosula 30g,Astragalus 30g,prepared Polygala tenuifolia 15g,Poria 20g,roasted licorice 6g,sour jujube 15g,Wood fragrance 12g,longan meat 15g,ginger 12g,jujube 15g.Formula granules,1 bag/time,2 times/d (after getting up and before going to bed),dissolved in 150ml of boiling water,washed and taken continuously for 2 weeks.

All patients did not take other sedative drugs during treatment,such as diazepam,clonazepam,estazolam,lorazepam,alprazolam,etc.

Observation indicators

Before and after admission,all patients used the TCM constitution classification judgment table to evaluate the score of qi deficiency and vas;Wear smart bracelets from the first day to the fourth day after admission (Xiaomi,Xiaomi Technology Co.,Ltd;Model:xmsh04nfc)to monitor the sleep time(total sleep time,deep sleep time,light sleep time and awakening times)every night,and score the patients with vas after taking drugs every morning.(Figure 2)

Data sorting and statistics

a.Data sorting

The basic information of patients (gender,age,diagnosis,etc.)and the measured observation indexes were collected and sorted by Excel software,and the clinical data database was constructed.

b.Statistical methods

SPSS25.0 software is used for statistical analysis of database data.If quantitative data conform to normal distribution,use±δ T-test was used for comparison between groups.The qualitative data are expressed by percentage.The group comparison of four grid table data adopts test.When the theoretical frequency is less than 5,Fisher exact test is used;r×C multi grid table data are compared between groupsχ2inspection.All values were kept to three decimal places,and the difference was statistically significant (P<0.05).

Result

Basic case data

From November 2020 to may 2021,a total of 52 cases meeting the requirements of this trial were included.They were randomly divided into 26 cases in the control group and 26 cases in the treatment group of integrated traditional Chinese and Western Medicine (hereinafter referred to as the treatment group).Among them,1 case in the control group fell off due to "midway withdrawal",2 cases in the treatment group fell off due to"unfinished scale score" and "midway withdrawal",and 25 cases in the final control group 24 cases in the treatment group completed the experiment.There was no significant difference in the abscission rate between the two groups(P>0.05)(Table 1).

Among the subjects who completed the test,there were 25 cases in the control group,including 6 males (24%) and 19 females (76%),aged 60-88 years,with an average age of 72.36±9.050 years,14 cases of upper limb (including upper arm,forearm,hand and shoulder),12 cases of lower limb (including thigh,hip,lower leg and foot),2 cases of trunk (including thoracic rib and spine) and 17 cases of single fracture,There were 8 cases of multiple fractures,1 case of open fractures and 24 cases of closed fractures;There were 15 cases of chronic diseases,including 8 cases of simple hypertension,2 cases of simple diabetes,2 cases of hypertension and diabetes,2 cases of hypertension complicated with osteoporosis,1 cases of hypertension complicated with diabetes mellitus and osteoporosis.At admission,there were 3 cases of qi deficiency (30 ≤transformation score <40) and 22 cases of qi deficiency(transformation score ≥40).The average physical score was 55.875±12.704;The average VAS score at admission was 6.76±1.165.

There were 24 cases in the treatment group,including 7 males(29.16%) and 17 females (70.83%),aged 60-95 years,with an average age of 73.25±10.343 years.There were 11 cases of upper limb (including upper arm,forearm,hand and shoulder),12 cases of lower limb (including thigh,hip,lower leg and foot),3 cases of trunk (including thoracic rib and spine),19 cases of single fracture and 5 cases of multiple fractures,There were 1 case of open fracture and 23 cases of closed fracture;There were 19 cases of chronic diseases,including 8 cases of simple hypertension,3 cases of simple diabetes,2 cases of simple osteoporosis,3 cases of hypertension complicated with diabetes mellitus,3 cases of hypertension complicated with osteoporosis,2 cases of hypertension complicated with diabetes mellitus and osteoporosis.At admission,there were 3 cases of qi deficiency (30 ≤transformation score <40) and 21 cases of qi deficiency(transformation score ≥ 40).The average physical score was 56.510±14.003;The average VAS score at admission was 6.792±1.179.

There was no significant difference in gender,age,fracture location,chronic medical history,VAS score at admission and TCM Constitution score among all patients who completed the test (P>0.05)(Table 2).

Comparison of sleep quality between the two groups

There was no significant difference in VAS score and TCM Qi deficiency constitution score between the two groups at admission(P > 0.05) (see Table 1 for specific data). The TCM Qi deficiencyconstitution score of the treatment group at discharge was33.724±12.634; The physical fitness score of qi deficiency in thecontrol group was 42.25±15.912. There was significant differencein TCM Qi deficiency constitution score between the two groups atdischarge (P <0.05); There was significant difference in TCM Qideficiency constitution score between the two groups (P <0.05).

the patient's sleep time and receive the patient's sleep data through the mobile phone software app.

There was no significant difference in VAS scores between the control group and the treatment group at admission,the first day,the second day,the third day and the fourth day (P>0.05);However,there was significant difference in VAS score between the two groups at discharge (P<0.05) (Table 3).

Discussion

Pain is closely related to sleep, because patients' physical comfort and psychological state can significantly affect the quality of sleep.Studies have pointed out that pain can trigger a series of physical discomfort feelings of patients, including changes in mental state,such as anxiety, depression and other emotions. Once the pain becomes chronic, it will have a great impact on the quality of life of patients [7].According to the theory of traditional Chinese medicine, pain is divided into "deficiency" and "excess". The deficiency takes "dishonour is pain", and the excess takes "impassability is pain" as the pathogenesis of pain [8].Elderly patients are often accompanied by "weakness" due to their physiological conditions. Most of the elderly have "Qi Deficiency" and sleep disorders to a certain extent [3].Therefore, some elderly people with "weakness" and "Qi Deficiency" constitution are easy to induce or aggravate sleep disorders on the basis of pain and Qi and blood deficiency.

Comparison of VAS score and TCM Qi deficiency constitution score between the two groups

There was no significant difference in VAS score and TCM Qi discomfort feelings of patients,including changes in mental state,such as anxiety,depression and other emotions.Once the pain becomes chronic,it will have a great impact on the quality of life of patients [7].According to the theory of traditional Chinese medicine,pain is divided into "deficiency" and "excess".The deficiency constitution score between the two groups at admission(P>0.05) (see Table 1 for specific data).The TCM Qi deficiency constitution score of the treatment group at discharge was 33.724±12.634;The physical fitness score of qi deficiency in the control group was 42.25±15.912.There was significant difference in TCM Qi deficiency constitution score between the two groups at discharge (P<0.05);There was significant difference in TCM Qi deficiency constitution score between the two groups (P<0.05).deficiency takes "dishonour is pain",and the excess takes"impassability is pain" as the pathogenesis of pain [8].Elderly patients are often accompanied by "weakness" due to their physiological conditions.Most of the elderly have "Qi Deficiency"and sleep disorders to a certain extent[3].Therefore,some elderly people with "weakness" and "Qi Deficiency" constitution are easy to induce or aggravate sleep disorders on the basis of pain and Qi and blood deficiency.

Table 1 Comparison of exfoliation and enrollment rates between the two groups

Table 2 Comparison of baseline data between the two groups

Table 3 VAS score and TCM Qi deficiency constitution score between the two groups

Table 4 Sleep quality between the two groups

Guipi Decoction is the main prescription for the treatment of"deficiency of both heart and spleen" with insomnia.It was first derived from the classic book of orthopedics and traumatology"Zhengti Lei Yao",which is used to treat sleep disorders caused by the injury of blood and Qi of fractured heart and spleen.The Guipi Decoction consists of 12 herbs from their plant sources ：Atractylodes macrocephala Koidz,Codonopsis pilosula (Franch.)Nannf.,Astragalus mongholicus Bunge,Polygala tenuifolia Willd,Glycyrrhiza uralensis Fisch,Poria cocos (Schw.) Wolf,Angelica sinensis,Ziziphus jujuba var.spinosa (Bunge),ucklandia lappa Decne,Dimocarpus longan Lour.,Zingiber officinale Roscoe and iziphus jujuba Mill.(Figure 3)In these herbs,416,11,88,148,242,87,86,73,195 and 40 components can be queried in the known compound database respectively,including volatile oils,triterpenoids,alkaloids,flavonoids,phenylpropanoids,steroids,sugars,coumarins,phthalides and quinone compounds [9].There are many clinical studies on the effect of the ingredients in the prescription on insomnia,such as 36 patients with insomnia of heart and spleen deficiency type were treated with zopiclone,and the other 36 patients were treated with Guipi Decoction plus zopiclone.After 60 days,the treatment effective rate of patients in Guipi Decoction plus zopiclone group was 94.44%,compared with 50% in zopiclone group,The treatment effect is obviously better[10].In another study,57 patients with intractable insomnia were treated with modified Guipi Decoction.The effective rate was 96.5%,and that in diazepam tablet group was 80.0%.The effect of modified Guipi Decoction on insomnia was significantly better than that in diazepam group [11].

Figure 3 Composition of Guipi Decoction

Modern pharmacological studies show that jujube kernel contains more than 50 bioactive compounds,including saponins,cyclic peptide alkaloids and C-glycosides,some of which show significant sedative and neuroprotective effects in pharmacological experiments [12,13].Spinosin is one of the two main bioactive components of jujube kernel specified in Chinese Pharmacopoeia.It can enhance pentobarbital induced sleep and play an anti anxiety role through GABA and serotonin systems in mice[14,15].Jujuboside A is another major bioactive component of jujube kernel specified in Chinese Pharmacopoeia.It inhibits the activity of acetylcholinesterase in hippocampus and improves a β 1–42 induced impairment of learning and memory function in mice[16].

This study observed the effect of Guipi Decoction Combined with non steroidal analgesic drugs commonly used in the treatment of acute traumatic pain on the sleep time of clinical patients.The results showed that there was no significant difference in sleep time,TCM Qi deficiency constitution score and VAS score between the treatment group and the control group on the first day of admission,but the sleep time of the treatment group was significantly improved after Guipi Decoction,that is,after the second day;Although the sleep time of the patients in the control group also improved to a certain extent after the treatment with Huaimai granule as placebo on the second day,by comparing the difference between the sleep time of the first day and the second day of the two groups,it can be considered that Guipi Decoction can improve the sleep time of the patients more significantly.In addition,after 2 weeks of treatment with Guipi Decoction,the TCM Qi deficiency constitution score of the treatment group was significantly different from that of the control group,indicating that Guipi Decoction can not only improve the Qi deficiency biased constitution of patients,but also improve the VAS score at discharge.

There are some deficiencies in this clinical observation.For example,fracture patients often need different surgical treatment within 1 week after admission,and some central analgesic drugs are added after surgery.Therefore,the observation of patients'sleep time often needs to be carried out before surgery.Therefore,in this study,the sleep observation of all patients was only carried out for 4 days,which could not be observed for a long time during hospitalization;In addition,this study can not rule out the interference of other treatments such as surgery and other drugs used for basic diseases on the VAS score and TCM Qi deficiency constitution score at discharge.But in general,Guipi Decoction has a good effect on the sleep improvement of patients with early traumatic pain,and has a good effect on the improvement of qi deficiency biased constitution of patients in traditional Chinese medicine.

In general,the intervention of traditional Chinese medicine in the treatment of acute pain and the improvement of sleep quality during hospitalization can strengthen the patients' sense of trust in traditional Chinese medicine treatment and have a good psychological state to deal with pain in the future.Due to the universality of pain,more and more treatments begin to focus not only on the development of analgesic schemes,but also on the improvement of patients' mental health and quality of life.Good sleep is also conducive to patients' rehabilitation [17,18].Therefore,Guipi Decoction Combined with non steroidal drugs,a combination of Chinese and Western medicine,can not only be used to improve the sleep of elderly patients with Qi deficiency acute trauma and pain,but also be used for Qi deficiency insomnia caused by other diseases,which is also a practical play to the theory of "simultaneous treatment of different diseases" in traditional Chinese medicine.

Conclusions

Guipi Decoction to improve sleep is one of the commonly used alternative therapy,this study through the Guipi Decoction with non-steroidal anti-inflammatory drugs,not only for pain patients during hospital sleep,and after hospital for the improvement of traditional Chinese medicine constitution,these improvements mainly reflected in the night sleep time,VAS score and traditional Chinese medicine constitution score.This treatment method of integrated traditional Chinese and western medicine deserves promotion.

Acknowledgement:general scientific research project of Zhejiang Provincial Department of education in 2020;Project No.:Y202044448