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.

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.

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.

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.