| ObjectiveThis study is divided into three parts.Part I is to explore the use of the human body’s weak magnetic field data detected by the biomagnetic induction device as an objective indicator of chronic insomnia deficiency and excess syndrome.Based on human body’s weak magnetic field data,a diagnostic model for chronic insomnia with deficiency syndrome is constructed and the feasibility of using biological magnetic induction devices for traditional Chinese medicine assistance in chronic insomnia is explored;Part II is a single-blind randomized parallel control study on the treatment of deficiency syndrome chronic insomnia with biomagnetic induction devices,comparing the effects of weak constant magnetic fields emitted by biomagnetic induction devices and placebo treatment,and the effect of biomagnetic induction devices on treatment.Preliminary analysis of the curative effect and safety of deficiency syndrome chronic insomnia will provide a reference for clinical exploration of a new non-drug therapy for chronic insomnia and later clinical research.Part III is the study of non-targeted metabolomics in serum,analyzing the mechanism of biomagnetic induction device in treating chronic insomnia of deficiency syndrome,and providing scientific basis for the treatment of chronic insomnia of deficiency syndrome with biomagnetic induction device.MethodsPart I:Using a cross-sectional design,the International Classification of Sleep Disorders edition 3(ICSD-3)was used as the diagnostic criteria for chronic insomnia,and the"Diagnostic and Curative Criteria for Syndromes of Traditional Chinese Medicine" centered on spleen deficiency syndrome,Heart and gallbladder qi deficiency,yin deficiency and fire hyperactivity are deficiency syndrome chronic insomnia;liver depression turning into fire and phlegm-heat internal disturbance are non-deficiency syndrome chronic insomnia.The diagnosis was jointly completed by two doctors with intermediate professional titles or above.If there was a difference in the diagnosis results between the two doctors,the diagnosis results of the third senior professional title doctor should prevail.The included chronic patients were divided into deficiency syndrome chronic insomnia group and non-deficiency syndrome chronic insomnia group,and the biomagnetic induction device was used to detect the two groups.The weak magnetic field data of the human body with statistical difference(P<0.05)between the groups were screened by the Mann-Whitney U rank sum test.The CHAID,CART,and C5.0 algorithms in SPSS Modeler 18.0 software were used to construct a decision tree diagnostic model for weak magnetic field data of chronic insomnia with deficiency syndrome,with two groups of chronic insomnia syndrome types as target variables and weak magnetic field data with differences between groups as independent variables.The model was randomly divided into training and testing sets in a 7:3 ratio.The test set results of the algorithm with the highest efficiency in the test set were compared with the diagnostic results according to the research diagnostic criteria,the diagnostic test parameters were calculated,and the model was evaluated.Part Ⅱ:Using a randomized,single-blind,parallel controlled trial to observe the curative effect and safety of biological magnetic induction device in treating chronic insomnia of deficiency syndrome.Subjects were randomly divided into a test group and a control group at a ratio of 1:1.The test group was treated with a weak constant magnetic field emitted by a biomagnetic induction device;the control group was treated with a placebo of a biomagnetic induction device.Treatment was performed 5 times a week,40 minutes each time,for two weeks,followed up for 4 weeks.Pittsburgh Sleep Quality Index(PSQI)score reduction after treatment was used as the primary endpoint to evaluate sleep improvement before and after treatment;PSQI and various factors,Insomnia Severity Index(ISI),Insomnia TCM Quality of Life Scale(TCMQLI-21)multi-time point measurement results were used as secondary endpoint to evaluate sleep improvement during treatment and follow-up;generalized anxiety disorder scale(GAD-7),patient health questionnaire-9(PHQ-9)multi-time point The measurement results were used as secondary endpoint to evaluate the emotional improvement during treatment and followup;TCM symptoms before and after treatment were used as secondary endpoint to evaluate the improvement of TCM symptoms;human body weak magnetic field data before and after treatment were used to evaluate the effect of weak constant magnetic field therapy on human body weak magnetic field Adjustment effect;blood routine,liver and kidney function,electrocardiogram,and adverse reaction records were used as safety indicators to evaluate the safety of treatment.PSQI,ISI,TCMQLI-21,GAD-7,and PHQ-9 scale information were collected before treatment,at the first week of treatment,at the end of treatment,at two-week follow-up,and at four-week follow-up;before treatment and at the end of treatment,TCM symptoms,Human body weak magnetic field data and safety indicators.Through the analysis of each outcome index,the curative effect and safety of biomagnetic induction device in treating chronic insomnia of deficiency syndrome were evaluated.Part III:From the test group subjects,we selected 24 subjects with significant PSQI score reduction,and selected 24 subjects from the control group with similar age,gender composition,and PSQI total scores before treatment,and collect treatment data respectively.We collected blood samples from patients in the two groups before and after treatment.This study used the UFLC-Q-TOF-MS/MS liquid chromatography-mass spectrometry system for serum untargeted metabolomics detection,and passed the Analyst (?) 1.7 Workstation collects data.Data preprocessing such as noise reduction,chromatographic peak calibration and identification,etc.were performed on the data collected by the original instrument through the MetaboAnalyst R package,and the data were normalized and standardized.We Combined with relevant literature and online databases such as Chemspider database and HMDB database,differential metabolites were identified.SMCA-P 14.1 software was used for multivariate statistical analysis,and the difference between the two groups before and after treatment was screened by Student’s t-test(Student’s t-test)P<0.05 and the fold change(Fold Change)>2 or<0.5 as the cutoff value.Among the differential metabolites before and after treatment in the two groups,the same differential metabolites in the two groups may not be related to the weak constant magnetic field treatment issued by the biomagnetic induction device.The remaining differential metabolites in the test group were differential metabolites affected by weak constant magnetic field treatment.The KEGG database and MetaboAnalyst 5.0 were used to identify and enrich metabolic pathways for these differential metabolites.ResultsPart I:A total of 475 patients with chronic insomnia were included,214 patients with deficiency syndrome and 261 patients with non-deficiency syndrome.Mann-Whitney U rank sum test screened lvaoS1N1 and other 38 groups of weak magnetic field data with differences between groups from 792 groups of weak magnetic field data(P<0.05).The correct diagnosis rate of CHAID algorithm test set was 60.12%;the correct diagnosis rate of CART algorithm test set was 80.54%;the correct diagnosis rate of C5.0 algorithm test set was 81.94%.The C5.0 algorithm test set has the highest diagnostic accuracy,and the diagnostic test indicators are calculated based on the results of the C5.0 algorithm test set.The sensitivity of the diagnostic test indicators was 78.87%,the specificity was 84.93%,the positive predictive ratio was 83.58%,the positive likelihood ratio was 5.23,and the Youden index was 0.64.Part Ⅱ:A total of 72 chronic insomnia patients were included,and 61 cases completed the treatment and follow-up,including 31 cases in the experimental group and 30 cases in the control group.There was no statistical difference in the treatment baseline data between the two groups(P>0.05).Primary endpoint:The average score of the PSQI test group after treatment was 7.03 ± 3.33,and the average score of the control group was 10.53 ± 4.02 after treatment.There was a statistical difference in the total PSQI score between the two groups after treatment(P<0.001),and the test group was lower than the control group.Secondary endpoint:PSQI total score comparison between groups at multiple time points,the first week of treatment,there was a statistical difference(P<0.05),the experimental group was lower than the control group;at the end of treatment,there was a statistical difference(P<0.001),the experimental group group was lower than the control group;there was no statistical difference at other time points(P>0.05).Compared within the group,the test group was higher than each detection time point before treatment,and the differences were statistically significant(P<0.05).The control group was higher than that at each detection time point before treatment,and the differences were statistically significant(P<0.05)Sleep latency:There was no significant difference between groups at each time point(P>0.05).Compared within the group,the test group was higher than each detection time point before treatment,and the differences were statistically significant(P<0.05);the control group was higher than each detection time point before treatment,and there were statistically significant differences between before treatment and after the end of treatment,and after four weeks of follow-up.Scientific significance(P<0.05).Sleep time:compared between groups,in the first week of treatment,there was a statistical difference(P<0.05),the test group was lower than the control group;at the end of treatment,there was a statistical difference(P<0.05),the test group was lower than the control group;After a week of follow-up,there was a statistical difference(P<0.05),and the test group was lower than the control group.There was no statistical difference at other time points(P>0.05).Compared within the group,the experimental group was higher than each detection time point before treatment,and the difference was statistically significant(P<0.05),and the control group was higher than each detection time point before treatment,and the difference was statistically significant(P<0.05).Sleep efficiency:compared between groups,there was a statistical difference(P<0.05)in the first week of treatment,and the test group was lower than the control group;at the end of treatment,there was a statistical difference(P<0.05),and the test group was lower than the control group.There was no statistical difference at other time points(P>0.05).Compared within the group,the test group was higher than each detection time point before treatment,and the difference was statistically significant(P<0.05);there was no statistical difference at each detection time point in the control group(P>0.05).Sleep disorders:There was no significant difference in sleep disorders score at each time point between groups(P>0.05).Compared within the group,the score of sleep disorders in the experimental group before treatment was higher than that at each testing time point,and the difference was statistically significant(P<0.05).Sleep quality:Comparison between groups,in the first week of treatment,there was a statistical difference(P<0.05),the test group was lower than the control group;at the end of treatment,there was a statistical difference(P<0.05),the test group was lower than the control group;Follow-up after one week,there is a statistical difference(P<0.05),the test group is lower than the control group;follow-up after four weeks,there is a statistical difference(P<0.05),the test group is lower than the control group.Compared within the group,the test group was higher than each detection time point before treatment,and the difference was statistically significant(P<0.05);the control group was higher than each detection time point before treatment,and there were significant differences between the end of treatment,two-week follow-up,and four-week follow-up.Statistical difference(P<0.05).Daytime dysfunction:compared between groups,there was a statistical difference(P<0.05)at the end of treatment,and the test group was lower than the control group.There was no statistical difference at other time points(P>0.05).ISI total score:Compared between groups,there was a statistical difference(P<0.05)at the end of treatment,and the test group was lower than the control group.There was no statistical difference at other time points(P>0.05).Compared within the group,the test group was higher than each detection time point before treatment,and the differences were statistically significant(P<0.05).The control group was higher than that at each detection time point before treatment,and the differences were statistically significant(P<0.05).TCMQLI-21 total score:There was no significant difference between groups at each time point(P>0.05).Compared within the group,the experimental group was higher than each detection time point before treatment,and the difference was statistically significant(P<0.05)between before treatment and the first week of treatment,and at the end of treatment(P<0.05);There was a statistically significant difference between the first week of treatment and the end of treatment(P<0.05).GAD-7 total score:comparison between groups:no statistical difference at each time point(P>0.05).Compared within the group,the experimental group was higher than each detection time point before treatment,and the difference was statistically significant(P<0.05)between before treatment and the first week of treatment,and at the end of treatment(P<0.05);There was a statistically significant difference at the end of treatment(P<0.05).PHQ-9 total score:Compared between groups,there was no significant difference in PHQ-9 total score between the two groups at each time point(P>0.05).Compared within the group,the test group was higher than each detection time point before treatment,and the difference between before treatment and the end of treatment was statistically significant(P<0.05);the control group was higher than each detection time point before treatment,and the difference was statistically significant Scientific significance(P<0.05).Chinese medicine symptoms before and after treatment:In the experimental group,there were statistical differences in difficulty falling asleep,dreaminess,fatigue,loss of appetite,and loose stools(P<0.05);there were no statistical differences in 17 symptoms such as light sleep and early awakening(P>0.05).In the control group,there were statistical differences in difficulty in falling asleep and easy waking in sleep(P<0.05);there was no statistical difference in 20 symptoms such as dreaminess and early awakening(P>0.05)Weak magnetic field data before and after treatment:in the test group,There were statistical differences among seven indicators(P<0.05),including lvaoS1N1;There were no statistical difference in thirty-one indicators such as dnS1N1(P>0.05).In the control group,only lssS6N6 had statistical difference(P<0.05),others thirty-eight indicators had no statistical difference(P>0.05).Safety indicators before and after treatment:There was no statistical difference between the two groups(P<0.05),and there was no adverse reaction in the two groups.Part Ⅲ:A total of 77 differential metabolites affected by weak constant magnetic field treatment,such as oleamide,were screened out,including phenylpropane and polyketide compounds,benzene series,organic acids and derivatives,oxygen-containing organic compounds,and organic heterocycles Compounds,lipids and lipid-like molecules 6 classes of substances.50 differential metabolites including phosphatidylcholine(14:0/18:4(6Z,9Z,12Z,15Z))were up-regulated after treatment,and 27 differential metabolites such as L-glutamne were down-regulated after treatment.A total of 77 differential metabolites involved 17 metabolic pathways including glycerophospholipid metabolism.According to the enrichment analysis results,the main metabolic pathways affected by treatment were glycerophospholipid metabolism,alanine,aspartic acid and Glutamate metabolism(Alanine,aspartate and glutamate metabolism),tryptophan metabolism(Tryptophan metabolism).ConclusionPart Ⅰ:Deficiency syndrome chronic insomnia decision tree diagnosis model based on human weak magnetic field data has better diagnosis efficiency.The biological magnetic induction device can carry out TCM auxiliary syndrome differentiation for chronic insomnia syndrome of deficiency and excess.Part Ⅱ:After treatment,the sleep conditions of the two groups of chronic insomnia patients with deficiency syndrome improved,and the biomagnetic induction device showed a placebo effect,and the constant and weak magnetic field emitted by the biomagnetic induction device was better than the placebo treatment.The three symptoms of spleen and stomach weakness in patients with deficiency syndrome and chronic insomnia,fatigue,loss of appetite,and loose stools were improved after treatment.Compared with the control group,the weak magnetic field data of the test group also has more detection points that are different from those before treatment.It shows that the weak constant magnetic field emitted by the biological magnetic induction device may improve the weak state of the spleen and stomach by adjusting the weak magnetic field of the human body,and have a therapeutic effect on chronic insomnia due to deficiency syndrome.Biomagnetic induction device therapy is a safe and effective non-drug therapy for chronic insomnia.Part III:The weak constant magnetic field emitted by the biomagnetic induction device may reduce the expression and adjustment of inflammatory factors in patients with chronic insomnia with deficiency syndrome by adjusting the metabolism of glycerophospholipids,tryptophan,alanine,aspartic acid and glutamic acid Promote the secretion of neurotransmitters such as y-aminobutyric acid(GABA)and 5-hydroxytryptamine(5-HT),and play a role in improving sleep. |
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