Investigation of the mechanism of action of Sanwu Huangqin Tang in the treatment of restless leg syndrome based on network pharmacology,molecular docking technology and molecular dynamics simulation

Background:Through the use of network pharmacology and molecular docking approaches,this study will examine the pharmacological effects of Sanwu Huangqin Tang on restless legs syndrome in order to better understand the mechanism of action of Traditional Chinese medicine(TCM)on RLS.Method:Utilise the TCMSP database to collect and select the drug components of Sanwu Huangqin Tang,and the Uniprot database to identify pertinent targets;RLS-related disease targets were obtained from GeneCards,DrugBank,and OMIM databases;and STRING and Cytoscape 3.9.1 software were used to generate an interaction network.KEGG pathway analysis and GO enrichment analysis were performed utilizing the DAVID database.Use Autodock for analyzing the relationships between targets and core components.Result:By using a network pharmacology approach,83 active ingredients and 50 drug-disease intersecting targets were derived for Sanwu Huangqin Tang.The molecular docking results showed that the drug components had strong affinity with the average target targets.Conclusions:This study provides new insights into the mechanism through which Traditional Chinese Medicine(TCM)treats Restless Legs Syndrome(RLS).Furthermore,it lays the foundation for additional research into the mechanism of treatment for RLS through the intervention that addresses various targets and pathways using the active ingredients identified by Sanwu Huangqin Tang.

Acupuncture Treatment of Restless Leg Syndrome

Case HistoryMr. Michael Fischer, aged 55 years, a German electrical engineer, paid his first visit on Dec. 7th, 1997, with the chief complaint of pain in the right lower limb for two months.

Restless head syndrome:A retrospective study

BACKGROUND Restless legs syndrome(RLS)is characterized by an urge to move with an unpleasant sensation in the lower limbs.RLS typically affects the legs.However,it can also affect several other body regions,such as the arms,abdomen,face,neck,head,and genital area.There are only a few reports of the RLS variant affecting the head.AIM To assess the epidemiological,clinical,and other aspects of the RLS variant affecting the head.METHODS We conducted a retrospective study of 17 adult patients(>18 years)who met the RLS criteria and simultaneously experienced RLS-like symptoms in the head.RESULTS The median age at which symptoms appeared was 41.6 years.Males and females were equally affected(1.1:1).All 17 patients had uncomfortable sensations in the lower legs.Insomnia or disturbed sleep was the most common comorbidity(n=16,88.2%).However,headache was the most common presenting or primary symptom(n=10,70.5%).Dizziness or an abnormal sensation in the head was the second most common presenting symptom(5 patients,29.4%).Other presenting features were leg pain,backache,and generalized body pain.All patients responded favorably to dopaminergic medications.CONCLUSION If RLS-related unpleasant sensations and pain are felt in the head,they may be misinterpreted as headache,dizziness,or psychosomatic symptoms.RLS and headaches in a subset of patients may be two phenotypic manifestations of the same disorder.

Restless legs syndrome is contributing to fatigue and low quality of life levels in hemodialysis patients

AIM To examine whether hemodialysis(HD) patients with restless legs syndrome(RLS) are subjects of greater fatigue and impaired quality of life(QoL) compared to HD patients without RLS.METHODS Eighty five stable HD patients participated in this study. According to their RLS status, the patients were dividedinto the RLS group(n = 23) and the non-RLS group(n = 62). QoL, fatigue, sleep quality, daily sleepiness and depression symptoms were assessed by using various questionnaires. Finally, biochemical parameters including iron, ferritin, hemoglobin, hematocrit and parathormone were assessed. RESULTS The HD patients with RLS scored worse in all the questionnaires used in the study(P < 0.05). The patients with RLS were more likely to receive the HD therapy on the morning shift, whilst 43.5% of the RLS patients reported to experience the RLS symptoms also during HD. The severity of RLS was correlated with fatigue, depression score and sleep quality(P < 0.05). CONCLUSION HD patients with RLS are subject to lower QoL related parameters and greater fatigue compared to HD patients without RLS. RLS should be successfully managed in order to improve the QoL of the sufferers.

Prevalence of restless legs syndrome in patients with irritable bowel syndrome

AIM:To determine the prevalence of restless legs syndrome(RLS)in patients with irritable bowel syndrome(IBS).METHODS:Patients with diarrhea-predominant IBS(n=30),constipation-predominant IBS(n=30),or mixed-symptom IBS(n=30)were recruited from the community between March 2008 and February 2009.Rifaximin 200 mg three times daily was administered empirically to alleviate small intestinal bowel over-growth in all patients.The presence of RLS was assessed via an RLS questionnaire and polysomnography.RESULTS:Twentysix patients with IBS(29%)were diagnosed with RLS using the RLS questionnaire.Twenty-four of the 26 patients(92%)underwent polysomnog-raphy,and all had confirmation of RLS.A greater percentage of patients with RLS had diarrhea-predominant IBS(62%)compared with patients with constipation-predominant IBS(4%)or mixed-symptom IBS(33%).CONCLUSION:Restless legs syndrome is prevalent in patients with IBS,especially those with diarrheal symptoms.Assessment of concomitant disorders may improve diagnosis and expand relevant treatment options for patients.

An Analysis of Medication Rules of Chinese Medicine for Restless Legs Syndrome Based on Data Mining

Objective: Based on data mining, to explore the medication rules of Chinese medicine for the treatment of restless legs syndrome(RLS). Methods: The CNKI, WANFANG, and VIP were taken as data sources, and "restless legs syndrome, RLS" as the key words, and "Chinese medicine, Chinese materia medica, traditional Chinese medicine(TCM), traditional Chinese and Western medicine" as sub key words, the data was extracted from the journals and literature related to the treatment of RLS by TCM from the establishment of the database to 2020, and data mining techniques(frequency analysis, cluster analysis, association rules) were used to analyze the core drugs and drug pair(group) rules. Results: A total of 87 prescriptions met the requirements of this study, involving 142 Chinese herbal medicines. The top 5 Chinese herbal medicines with a higher frequency of use were Radix Paeoniae Alba, Radix Glycyrrhizae, Radix Angelicae Sinensis, Fructus Chaenomelis and Radix Astragali seu Hedysari. The four Qi(气) of the medicine were mainly warm and neutral, the five flavors were mainly sweet, bitter, and pungent. The main channels of the meridian were mainly the liver meridian, spleen meridian and heart meridian. The medication categories were mainly tonifying deficiency herbs, blood activating and removing blood stasis herbs, and eliminating wind and dampness herbs. The association rule analysis yielded 24 Chinese medicine combinations with high support, and the hierarchical cluster analysis yielded a total of 5 clusters. Conclusion: TCM treatment of RLS is based on tonifying deficiency herbs, especially to replenish Qi and blood throughout the course of the disease, supplemented by herbs for promoting blood circulation and removing blood stasis, and herbs for eliminating wind and dampness, as well as combined with herbs for reliving superficies and herbs for calming the liver to stop the wind.

Dopamine agonist responsive burning mouth syndrome:Report of eight cases

BACKGROUND Burning mouth syndrome(BMS)is characterized by burning sensation of the oral mucosa.There is a lack of effective treatment.In recent years,a special subtype of BMS has been reported,in which oral burning sensation is alleviated after chewing,speaking,or dopaminergic drug delivery.Currently,there are few reports about the subtype of BMS in China.This study was a retrospective analysis of the clinical data of BMS patients sensitive to dopamine agonist at our hospital,aiming to improve the recognition on this disease.CASE SUMMARY Eight patients diagnosed with dopamine agonist responsive BMS at the Liaocheng People's Hospital from January 1,2017 to June 30,2020 were recruited.The clinical manifestations,treatment,and prognosis were retrospectively analyzed.There were three male and five females in the eight patients.The median age was 56 years(range,46-65 years).All the eight patients showed burning pain in the mouth.The symptoms were mild in the morning and severe in the evening,and alleviated after chewing,talking,and other oral activities.Four patients were accompanied by restless legs syndrome(RLS).Family history of RLS was positive in two patients.All patients were treated with pramipexol,and symptoms were basically relieved after 2-8 wk.CONCLUSION Dopamine agonist responsive BMS is a special subtype of BMS,which is alleviated after oral activities.Dopamine receptor agonist is an effective treatment.

Restless legs syndrome secondary to pontine infarction:Clinical analysis of five cases

Objective: Pontine infarction is a common type of stroke in the cerebral deep structures, resulting from occlusion of small penetrating arteries, may manifest as hemi-paralysis, hemi-sensory deficit, ataxia, vertigo, and bulbar dysfunction, but patients presenting with restless legs syndrome (RLS) are extremely rare. Herein, we reported five cases with RLS as a major manifestation of pontine infarction.Methods: Five cases of pontine infarction related RLS were collected from July 2013 to February 2016. The diagnosis of RLS was made according to criteria established by the International RLS Study Group (IRLSSG) in 2003. Neurological functions were assessed according to the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Severity of RLS was based on the International RLS Rating Scale (IRLS-RS). Sleep quality was assessed by Epworth Rating Scale (ERS), and individual emotional and psychological states were assessed by Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale (HAS).Results: The laboratory data at the onset including hemoglobin, serum concentration of homocysteine, blood urea nitrogen (BUN), creatinine, electrolytes, and thyroid hormones were normal. The electroencephalogram (EEG), lower-extremity somatosensory evoked potential (SEP), and nerve conduction velocity (NCV) in four limbs were normal. The average period of follow-up was 34.60 ± 12.76 months. The MRI examination showed acute or subacute pontine infarction lesions, 3 cases in the rostral inner side, 1 case in the rostral lateral and inner side, and 1 case in rostral lateral side. The neurological deficits included weakness in 4 cases, contralateral sensory deficit in 1 case, and ataxia in 2 cases. All 5 patients presented with symptom of RLS at or soon after the onset of infarction and 4 patients experienced uncomfortable sensations in the paralyzed limbs contralateral to the ischemic lesion. Their neurological deficits improved significantly 2 weeks later, but the symptoms of RLS did not resolve. Among them, 3/5 patients were treated with dopaminergic drugs. At the end of the follow-up, RLS symptom eventually resolved in 3 patients but persisted in two. The IRLS-RS, NIHSS and mRS scores were significantly lower at the onset than those at the last follow-up (P=0.035, 0.024 and 0.049, respectively). However, there was no significant difference in the ERS, HDS and HAS scores (P=0.477, 0.226 and 0.778, respectively).Conclusion: RLS can be an onset manifestation of pontine infarction, clinicians should be aware of this potential symptom. RLS usually occurs in the paralyzed limbs contralateral to the infarction lesion. The pathogenesis still needs further investigation.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Restless Legs Syndrome

Background： Repetitive transcranial magnetic stimulation （rTMS） is a noninvasive technique used to alter cortex excitability that has been proposed as an efficient method for treating brain hyperexcitability or hypoexcitability disorders. Tile aim of this study was to investigate whether high-fi-equency rTMS could have any beneficial effects in restless legs syndrome （RLS）. Methods： Fourteen patients with RLS were given high-frequency rTMS （15 Hz, 100% motor threshold） to tile leg representation motor cortex area of the frontal lobe for 14 sessions over 18 days. Patients were diagnosed according to the international criteria proposed by the International Restless Legs Syndrome Study Group in 2003. The International RLS Rating Scale （1RLS-RS）, Pittsburgh Sleep Quality Index （PSQI）, Hamilton Anxiety Scale （llAMA） and Hamilton Depression Scale were used to evaluate the severity of RLS, sleep quality, anxiety and depression, respectively. The scale scores were evaluated at four-time points （baseline, end of the 14th session, and at 1- and 2-month posttreatrnent）. One-way analysis of variance was used to compare scale scores at different time points. Results： There was significant improvement in the 1RLS-RS （from 23.86 ± 5.88 to 11.21 ± 7.23, P 〈 0.05）, PSQ1 （frorn 15.00 ± 4.88 to 9.29 ± 3.91, P 〈 0.05）, and HAMA （from 17.93 ± 7.11 to 10.36 ± 7.13, P 〈 0.05） scale scores at the end of 14th session, with ongoing effects lasting for at least 2 months. Conclusions： High-17equency rTMS can markedly alleviate the motor system symptoms, sleep disturbances, and anxiety in RLS patients. These restllts suggest that rTMS might be an option for treating RLS.

Treatment of 49 Cases of Restless Legs Syndrome by Acupuncture plus Acupoint Injection

Summary： Acupuncture and moxibustion therapy was used to treat 49 cases of restless legs syndrome. Yanglingquan （GB 34）, Jinggu（BL 64）, Chengshan （BL 57）, Chengjin （BL 56） and Shangqiu （SP 5） were the main acupoints; Ganshu （BL 18）, Shenshu （BL 23） and Taixi （ KI 3） were matched to the type of deficiency of liver and kidney yin; Xuehai （SP 10） and Sanyinjiao （SP 6） were matched to the type of cold-dampness entering interior. Chengshan （BL 57） and Chengjin （BL 56） were needled. After the arrival of qi, warm needling was done. Bilateral Chengshan （BL 57） were injected with complex prescription Radix Salviae Miltiorrhizae （丹参）injection. The clinical symptoms of 41 cases disappeared totally, the clinical symptoms of 7 cases disappeared and the clinical symptoms of 1 case disappeared partly.

Clinical Observation of Warm Acupuncture at Biguan(ST 31)in Treating Post-apoplectic Restless Legs Syndrome

Objective：To investigate the efficacy of warm acupuncture at Biguan（ST 31） in treating post-apoplectic restless legs syndrome. Methods： Fifty patients were randomly divided into treatment and control groups by a waiting control method in order of hospitalization. The treatment group received deep acupuncture at point Biguan（ST 31） plus moxibustion and the control group took Ldopa orally. The curative effects were compared after 28 days＇ treatment. Results.The total efficacy rate was 76.00% in the treatment group and 26.00% in the control group. There was a significant difference. Conclusion：Warm acupuncture at Biguan（ST 31） is effective in treating post apoplectic restless legs syndrome.

Sleep disorders and chronic kidney disease

Sleep disorders have a profound and well-documented impact on overall health and quality of life in the general population. In patients with chronic disease, sleep disorders are more prevalent, with an additional morbidity and mortality burden. The complex and dynamic relationship between sleep disorders and chronic kidney disease(CKD) remain relatively little investigated. This article presents an overview of sleep disorders in patients with CKD, with emphasis on relevant pathophysiologic underpinnings and clinical presentations. Evidence-based interventions will be discussed, in the context of individual sleep disorders, namely sleep apnea, insomnia, restless leg syndrome and excessive daytime sleepiness. Limitations of the current knowledge as well as future research directions will be highlighted, with a final discussion of different conceptual frameworks of the relationship between sleep disorders and CKD.

Sleep-associated movement disorders and the risk of cardiovascular disease: A systematic review and metaanalysis

AIM:To investigate whether an association exists between sleep-associated movement disorders and cardiovascular disease(CVD).METHODS:Several studies have observed the relationship of sleep-associated movement disorders such as restless legs syndrome(RLS)and periodic limb movements during sleep with CVD,but the results were still contradictory.We performed an extensive literature search on Pub Med,Medline and Web of Science published from inception to December 2014.Additional studies were manually searched from bibliographies of retrieved studies.Meta-analyses were conducted with Stata version 12.0(Stata Corp,College Station,Texas).Pooled odds ratios(ORs)and 95%CIs were calculated to assess the strength of association using the random effects model.Sensitivity and subgroup analyses were performed to explore the underlying sources of heterogeneity.The publication bias was detected using Egger’s test and Begg’s test.RESULTS:A total of 781 unique citations were indentified from electronic databases and 13 articles in English were finally selected.Among these studies,nine are cohort studies;two are case-control studies;and two are cross-sectional studies.The results showed that the summary OR of CVD associated with sleepassociated movement was 1.51(95%CI:1.29-1.77)in a random-effects model.There was significant heterogeneity between individual studies(P for heterogeneity=0.005,I2=57.6%).Further analysis revealed that a large-scale cohort study may account for this heterogeneity.A significant association was also found between RLS and CVD(OR=1.54,95%CI:1.24-1.92).In a fixed-effects model,we determined a significant relationship between sleep-associatedmovement disorders and coronary artery disease(CAD)(OR=1.34,95%CI:1.16-1.54;P for heterogeneity=0.210;I2=30.0%).Our meta-analysis suggests that sleep-associated movement disorders are associated with prevalence of CVD and CAD.CONCLUSION:This finding indicates that sleep-associated movement disorders may prove to be predictive of underlying CVD.

Sleep disorders and its related risk factors in patients undergoing chronic peritoneal dialysis

Background The prevalence of sleep disorders has been shown to be high in patients with chronic dialysis patients and may contribute to impaired quality of life and higher mortality in this population.However,there are few data on the relationship of sleep disorders and their risk factors in chronic dialysis patients.The aim of this study was to evaluate the relationship of sleep disorders and their risk factors in chronic dialysis patients.Methods A total of 42 continuous ambulatory peritoneal dialysis （CAPD） patients were involved in this cross-sectional study.Sleep quality was assessed by the Pittsburgh Sleep Quality Index （PSQI）.Restless legs syndrome （RLS） was diagnosed according to the criteria of the International Restless Legs Syndrome Study Group.And depression was assessed by Hamilton depression scale.General information and laboratory data were collected.Results The prevalence of sleep disorders was 47.6％ in the CAPD patients.According to the PSQI,the 42 CAPD patients were divided into sleep disturbance group and non-sleep disorders group.There were no significant differences in age,gender,dialysis duration,hemoglobin,serum creatinine,urea nitrogen,β2-microglobulin,parathyroid hormone,calcium,and phosphorus between CAPD patients with sleep disorders and those without sleep disorders.But the level of serum albumin （AIb） in CAPD patients with sleep disorders was significantly lower than that in CAPD patients without sleep disorders （31.3±1.4 vs.34.3±3.7,t=3.603,P=0.001）.And the prevalence of RLS and depression was significantly higher than that in CAPD patients without sleep disorders （RLS：11/22 vs.1/20,x2=10.395,P=0.001; depression：7/22 vs.1/20,x2=4.886,P=0.027）.In CAPD patients with RLS,the prevalence of sleep disorders was significantly higher than that in CAPD patients without RLS （11/22 vs.11/30,x2=10.395,P=0.001）.And in CAPD patients with depression,the prevalence of sleep disorders was significantly higher than that in CAPD patients without depression （7/8 vs.15/34,x2=4.886,P=0.027）.In CAPD patients,bivariate correlation analysis showed that sleep disorders was negatively correlated with serum AIb （r=-0.606,P=0.000） and positively correlated with RLS （r=0.497,P=0.001） and depression （r=0.341,P=0.029）.Multivariate regression analysis revealed that the odds ratio of RLS,depression,and low serum AIb was 22.900,42.209,and 0.597,respectively.Conclusions The prevalence of sleep disorders was relatively high in CAPD patients.RLS,depression,and low serum AIb were the risk factors for CAPD patients with sleep disorders.