Traditional Chinese medicine treatment of insomnia based on microbial-gut-brain axis theory

In recent years,insomnia has gradually become a common disease in society,which seriously affects people's quality of life.At present,with the deepening of research on intestinal microbiota-gut-brain axis in Western medicine,many studies suggest that regulating the gastrointestinal tract can treat brain-related diseases.It is found that brain-gut-bacteria axis plays an important role in the prevention and treatment of primary insomnia.At present,although the clinical treatment of insomnia with Western medicine can improve the insomnia symptoms of patients to a certain extent,there are still obvious adverse reactions,such as anxiety and depression,drug addiction,etc.,so long-term oral drug therapy cannot be carried out.Traditional Chinese medicine(TCM)and acu-puncture techniques have certain therapeutic effects on insomnia.TCM believes that the brain and gastrointestinal system are connected through the meridian,and the pathophysiology is closely related.This paper will discuss the theory and feasibility of TCM for the treatment of insomnia from the pathological relation-ship between brain-gut axis,intestinal flora and insomnia.

Challenges in integrating traditional Chinese medicine and gut microbiota research for insomnia treatment

The gut microbiome is an extensive variety of bacteria with a range of metabolic capabilities that can be pathogenic,beneficial,or opportunistic.Changes in the gut microbiota's composition can affect the link between gut integrity and host health as well as cause disruptions to numerous neurological systems.The second most prevalent mental health problem,insomnia has a negative social and economic impact.Currently,it is becoming increasingly obvious how crucial it is to preserve the delicate balance of gut microbiota to treat illness-related symptoms like insomnia.Although traditional Chinese medicine has proposed an effective strategy against insomnia through gut microbiota alteration in animal models,studies in human models are limited.This decreases the predictive value of the studies in terms of human outcomes.This editorial places an emphasis on cultural sensitivity rather than scientific reasoning that promotes the use of traditional Chinese medicine(TCM).We aim to emphasize the concern that promoting TCM could divert resources from conventional medical research,leading to suboptimal care.

Discussion on Traditional Chinese Medicine Treatment of Liver-Depression-Spleen-Deficiency Type Insomnia Based on the State-Target Theory and the Regulation of Microbiome-Gut-Brain Axis

Insomnia has become an urgent clinical problem in modern society.Current research has found that the gut flora-gut-brain axis plays an important role in regulating insomnia.The state-target theory is a product of the combination of traditional Chinese medicine and modern molecular biology technology.This paper clarifies the correlation between the state-target theory,the intestinal flora-gut-brain axis,and liver-depression-spleen-deficiency insomnia.The use of traditional Chinese medicine to regulate the structure and abundance of intestinal flora was also explored,aiming to integrate traditional Chinese medicine with Western medicine for the prevention and treatment of liver-depression-spleen-deficiency insomnia.

Unraveling the mechanism of action of Shangxia Liangji formula for treating insomnia:a metabolomics and network pharmacology approach

Background:Insomnia is a prevalent clinical condition and Shangxia Liangji formula(SXLJF)is a well-established method of treatment.Nevertheless,the specific mechanism of action of SXLJF remains unclear.Methods:The mouse model of insomnia was established by intraperitoneal injection of para-chlorophenylalanine.Forty-two mice were randomly divided into a negative control group,model group,SXLJF group(18.72 g/kg/day),and positive control group(diazepam,2 mg/kg)and treated with the corresponding drugs for 7 consecutive days.The open field test and pentobarbital-induced sleeping test were conducted.LC-MS-based untargeted metabolomics and network pharmacology were applied to explore the potential targets of SXLJF for treating insomnia.Finally,key targets were validated using RT-qPCR.Results:Behavioral tests demonstrated that SXLJF reduced the total distance,average velocity,central distance,and sleep latency,and prolonged sleep duration.Metabolomics and network pharmacology revealed potential targets,signaling pathways,metabolic pathways,and metabolites associated with the anti-insomnia effects of SXLJF.Specifically,tyrosine hydroxylase(TH)and tyrosine metabolism emerged as crucial metabolic pathways and targets,respectively.RT-qPCR results supported the role of TH in the mechanism of SXLJF in treating insomnia.Conclusion:In conclusion,TH and tyrosine metabolism may represent significant targets and pathways for SXLJF in treating insomnia.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Treating Comorbid Insomnia in Older Adults via Cognitive-Behavioural Treatment, Bright Light and Exercise

Background: Insomnia occurs frequently in older adults. The underlying factors for the disorder are physiological changes of the sleep-wake cycle, comorbid diseases and drug treatment. Cognitive behavioural therapy (CBT I) combined with light therapy and physical activity can be effective in the treatment of comorbid insomnia in older adults. Methods: Sixty-three (63) insomnia patients (47 female, 16 male) with an average age of 66.6 years participated in the program. Before and after the treatment, the participants completed questionnaires to assess their sleep quality (PSQI), day-time sleepiness (ESS), mood (BDI) and well-being (WHO-5-Index). In addition, they kept sleep diaries for six weeks. Results: Pre-post comparisons revealed a significant improvement in sleep latency and sleep quality, as well as a significant reduction of day-time sleepiness. In patients with both insomnia and depression, all depression scores improved slightly but significantly. Conclusions: Non-pharmacological combination treatment using CBT I, light therapy and physical activity seemed to be effective in older adults with comorbid insomnia and improve additionaly depressive symptoms.

The Characteristics of the Drug Composition in the Treatment of Insomnia by External Bath Prescription of Traditional Chinese Medicine

[Objectives]The research aimed to carry out a retrospective analysis on the characteristics of the drug composition in the treatment of insomnia by external bath prescription of traditional Chinese medicine,to provide ideas for the research and development of new Chinese medicine for insomnia.[Methods]The external bath prescriptions of traditional Chinese medicine related to insomnia were collected,and the appearance frequency of drug was analyzed,and statistical analysis of drug with high appearance frequency was conducted.[Results]In the external bath prescriptions of traditional Chinese medicine related to insomnia,the top ten herbs with high appearance frequency were as follows:Chaozaoren,Drgonsbones,Margaritifera,Yejiaoteng,Schisandrae Chinensis Fructus,Lilii Bulbus,Platycladi Semen,Poria,Coptidis Rhizoma,and Scutellariae Radix.According to the classification by efficacy,these herbs mostly have the effects of calming,nourishing and heat clearing.[Conclusions]Traditional Chinese medicine is most closely related to heart,kidney,liver and other viscera.Tranquilizing and sedative drugs should be chosen,which corresponds with the understanding on pathogenesis of insomnia in traditional Chinese medical science,and embodies the characteristics of external bath prescription of traditional Chinese medicine in the treatment of insomnia.

Depression Anxiety Outcome: Insomnia and Up-to-date Treatments

Based on his teaching experiences and clinical observations at Mental Health Centers,the author presents shortly the results of his clinical researches and will discuss on“psychopathological effects of depression and anxiety on insomnia”and very summarily on the treatment.The studies and lectures at the University Hospitals:Ir.,IL,USA and France,especially during the last decades,have enriched this study research.The experiences and researches have clearly shown that depression and anxiety resulting from catastrophic life events,exert pathological effects not only on cognitive and cardiovascular system but have also psychopathological effects on internal organs such as pineal gland with its melatonin secretion which is considered as stimulator system to regulate the rhythm of wake-sleep.Major depression and anxiety,when accumulating and occurring together,can not only perturb the circadian rhythm,which leads to insomnia,but also in some extreme situations as observed,can engender behavior and personality disorders that in some cases lead to suicide.Concerning the treatments in some cases in which the parents in major depression are suffering from the death of children,in parallel of pharmacotherapy,or other family care and treatments,the author proposed“Child Replacement”plan in period of mourning.Among the various drugs effective for treatment of insomnia we indicate:Agomelatine-Mianserine-Amitriptyline-Doxepin-Fluoxetine,well interesting to be noted.

BRIEF INTRODUCTION TO THEORETICAL INTENTION OF "NEEDLING METHOD FOR TRANQUILLIZATION AND CALMING THE MIND" FOR TREATMENT OF INSOMNIA

A set of scientific theories and an effective acupuncture therapy for insomnia about ＂the needling method for tranquillization and calming the mind＂ are gradually formed through many years＇theoretical and clinical studies. In this paper, the theoretical intention about ＂the needling method for tranquillization and calming the mind＂ for treatment of insomnia are briefly introduced mainly from the cause of disease, pathogenesis, therapeutic method and characteristics of composition of a prescription, etc. in order to provide a new train of thoughts and a new method for working out scientific and standard prescriptions in the treatment of insomnia.

Mechanism of Zixinyin oral liquid in the treatment of insomnia based on network pharmacology and molecular docking

Objective:To explore the molecular mechanism of Zixinyin oral liquid(ZOL)in the treatment of insomnia.Methods:The compounds and action targets of four herbal medicines in ZOL were collected via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.Genes corresponding to the targets were queried from the UniProt database.Genecards database was searched to screen the related targets of insomnia.A Gene Ontologyfunction enrichment analysis and a Kyoto Encyclopedia of Genes and Genomespathway enrichment analysis were performed by Database for Annotation,Visualization and Integrated Discovery.AutoDock software was used for molecular docking to verify the results of network analysis.Results:A total of 47 effective compounds and 187 potential targets of ZOL were screened out from the four drugs.A total of 2592 disease targets were screened out from the genecards database,and there were 1576 genes whose relevance score≥0.5.46 genes were obtained by taking the intersection of 187 potential targets of ZOL and 1,576 targets of insomnia.A total of 3,405 entries were obtained from Gene Ontologyfunctional enrichment(P<0.05).A total of 195 signaling pathways were obtained through a Kyoto Encyclopedia of Genes and Genomespathway analysis(P<0.05).Tumor necrosis factor,interleukin 17and hypoxia inducible factor-1signaling pathways were closely related to insomnia.The results of molecular docking show that all the core compounds of ZOL had a certain degree of affinity with gamma-aminobutyric acid receptor subunit alpha-1(GABRA1)and tumor necrosis factor-α(TNF-α).Paeoniflorgenone shows the highest affinity with GABRA1,and beta-sitosterol shows the highest affinity withTNF-α.ZOLmay have a therapeutic effect on insomnia through its action on targets such as GABRA1 and TNF-α,meanwhile regulating many signaling pathways.

Combination treatment of inflammatory bowel disease:Present status and future perspectives

The treatment of patients with inflammatory bowel disease(IBD),especially those with severe or refractory disease,represents an important challenge for the clinical gastroenterologist.It seems to be no exaggeration to say that in these patients,not only the scientific background of the gastroenterologist is tested,but also the abundance of“gifts”that he should possess(insight,intuition,determ-ination,ability to take initiative,etc.)for the successful outcome of the treatment.In daily clinical practice,depending on the severity of the attack,IBD is treated with one or a combination of two or more pharmaceutical agents.These combin-ations include not only the first-line drugs(e.g.,mesalazine,corticosteroids,antibiotics,etc)but also second-and third-line drugs(immunosuppressants and biologic agents).It is a fact that despite the significant therapeutic advances there is still a significant percentage of patients who do not satisfactorily respond to the treatment applied.Therefore,a part of these patients are going to surgery.In recent years,several small-size clinical studies,reviews,and case reports have been published combining not only biological agents with other drugs(e.g.,immunosuppressants or corticosteroids)but also the combination of two biologi-cal agents simultaneously,especially in severe cases.In our opinion,it is at least a strange(and largely unexplained)fact that we often use combinations of drugs in a given patient although studies comparing the simultaneous administration of two or more drugs with monotherapy are very few.As mentioned above,there is a timid tendency in the literature to combine two biological agents in severe cases unresponsive to the applied treatment or patients with severe extraintestinal manifestations.The appropriate dosage,the duration of the administration,the suitable timing for checking the clinical and laboratory outcome,as well as the treatment side-effects,should be the subject of intense clinical research shortly.In this editorial,we attempt to summarize the existing data regarding the already applied combination therapies and to humbly formulate thoughts and suggestions for the future application of the combination treatment of biological agents in a well-defined category of patients.We suggest that the application of biomarkers and artificial intelligence could help in establishing new forms of treatment using the available modern drugs in patients with IBD resistant to treatment.

Treatment of insomnia by differentiation of yang deficiency syndrome

Insomnia has become one of the common clinical diseases.In recent years,it has been found that patients with insomnia of Yang deficiency type are more and more common,and the trend of rejuvenation gradually appears,which seriously affects the normal progress of people's life,work and study.Clinical treatment through syndrome differentiation,mainly from the heart,spleen,kidney three viscera yang deficiency,on the basis of the warm yang method to add Qianzhen tranquilizing products,and pay attention to multiple organs as diseases,add moisture,blood The qi thing,while not forgetting the psychological counseling,adjusting the body and mind,and achieving a certain clinical effect,can provide ideas for the treatment of this disease.

Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

Scalp and Body Acupuncture for Treatment of Senile Insomnia—A Report of 83 Cases

The author has in recent years treated 83 cases of senile insomnia with scalp and body acupuncture. Meanwhile, 35 cases in the control group were treated with western and Chinese drugs. The therapeutic results in the treatment group were superior to that of nitrazapam and An Shen Bu Nao Ye (安神补脑液Sedative and Brain-invigorating Fluid) used in the control group. A report of the treatment follows. ……

Meta-analysis of randomized controlled trials of acupuncture in the treatment of menopausal insomnia

Objective:We aimed to investigate the safety and efficacy of acupuncture in the treatment of climacteric insomnia compared with western medicine through a comprehensive metaanalysis.Methods:Literature retrieval,research selection and data extraction were done independently and in duplicate.Effect-size estimates are expressed as risk ratio(RR)and 95%confidence interval(CI).Results:Summary data from 27 articles,involving a total of 2349 menopausal women,were meta-analyzed.The overall analysis showed that the clinical cure rate(RR=1.85,95%CI:1.57~2.18,P<0.001)of acupuncture was 1.85 times higher than western medicine,and the markedly effective rate was 1.3 times higher than that of westernmedicine(RR=1.30,95%CI:1.09~1.54,P=0.003).In terms of Pittsburgh Sleep quality Index((PSQI)),simple acupuncture is superior to western medicine in sleep quality,falling asleep time,sleep time,sleep efficiency and daytime dysfunction.In the evaluation of adverse reactions,the incidence of adverse events in the acupuncture-related therapy group(3.5%)was lower than that in the western medicine group(12.5%).Conclusion:The results of metaanalysis show that the clinical efficacy of acupuncture in the treatment of climacteric insomnia is better than that of western medicine which has better efficacy and safety.The acupuncture therapy is suitable for clinical.

Clinical Observation on the Treatment of Insomnia in Germany with Deficiency of Heart and Spleen by the Ear Bean Therapy

Objective: To observe the effect of insomnia patients with deficiency of heart and spleen in Germany by the therapy of ear points pressing with bean. Methods: A total of 80 cases of insomnia with deficiency of heart and spleen in Germany were divided into the observation group and the control group, with 40 cases in each group. The patients in the control group were treated with oral modified Guipi Decoction(归脾汤), while the patients in the observation group were treated with oral traditional Chinese medicine(TCM) and the therapy of ear points pressing with bean. The efficacy, sleep quality, the TCM syndromes score and the incidence of adverse reactions were compared between the two groups. Results: The effective rate in the observation group was higher than that in the control group, and there was statistical difference between the two group(P<0.05). After treatment, the Pittsburgh sleep quality index scale(PSQI) score, insomnia severity index(ISI) score and the TCM syndromes score in the two groups were decreased sharply(P<0.01), and those scores in the observation group were lower than that in the control group(P<0.05). There was no adverse reaction between the two groups. Conclusion: The therapy of ear points pressing with bean is effective on insomnia in Germany, which is worth further study and promotion.

A review of the treatment for insomnia in patients with cancers

Sleep disturbance is considered a prominent problem in cancer patients with a detrimental effect on health outcomes,which accompanies a decline in reduces the quality of life,functional status,and even accelerates progressive of cancer.Therefore,in order to develop new ways to improve the sleeping situations and the quality of life in cancer patients,it is necessary to understand the status of sleep quality in cancer patients and seek more measures of sleep quality evaluation from different cultural backgrounds.This review summarized the common methods used to improve sleep quality and relieve the pain of cancer patients.In addition,the status of sleep disturbance in patients with cancer is described.

Gut flora in multiple sclerosis:implications for pathogenesis and treatment

Multiple sclerosis is an inflammatory disorder chara cterized by inflammation,demyelination,and neurodegeneration in the central nervous system.Although current first-line therapies can help manage symptoms and slow down disease progression,there is no cure for multiple sclerosis.The gut-brain axis refers to complex communications between the gut flo ra and the immune,nervous,and endocrine systems,which bridges the functions of the gut and the brain.Disruptions in the gut flora,termed dys biosis,can lead to systemic inflammation,leaky gut syndrome,and increased susceptibility to infections.The pathogenesis of multiple sclerosis involves a combination of genetic and environmental factors,and gut flora may play a pivotal role in regulating immune responses related to multiple scle rosis.To develop more effective therapies for multiple scle rosis,we should further uncover the disease processes involved in multiple sclerosis and gain a better understanding of the gut-brain axis.This review provides an overview of the role of the gut flora in multiple scle rosis.

Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.