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.

Using multi-omics analysis to explore diagnostic tool and optimize drug therapy selection for patients with glioma based on cross-talk gene signature

Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.

Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

Current status of drug therapy for alveolar echinococcosis

Alveolar echinococcosis(AE)is a chronic zoonotic parasitic disease caused by infection with Echinococcus multilocularis.AE is associated with a high mortality rate and poses a significant threat to human health.The primary treatment for AE is surgical resection of the lesions;however,owing to its long incubation period and insidious disease progression,many patients are diagnosed only after the onset of complications such as liver cirrhosis,jaundice,and portal hypertension,which preclude curative surgical intervention.For patients who are unwilling or unable to undergo surgery,lifelong administration of anti-AE medications is necessary.Benzimidazole compounds,such as albendazole and mebendazole,are the current mainstays of treatment,offering good efficacy.Nevertheless,these medications primarily inhibit parasite proliferation rather than eradicate the infection,and their long-term use can lead to significant drug-related toxic effects.Consequently,there is an urgent need to develop new therapeutic strategies that convey better efficacy and reduce the adverse effects associated with current treatments.Recent advancements in AE therapy include novel synthetic compounds such as antiviral agents,antibiotics,antineoplastic agents,immunosuppressants,and antiangiogenic agents,as well as natural compounds derived from traditional Chinese and Tibetan medicine.These new drugs show promising clinical potential because they interfere with parasitic metabolic pathways and cellular structures.This review aims to discuss recent research on AE drug therapy,including mechanisms of action,dosing regimens,signalling pathways,and therapeutic outcomes,with a goal of providing new insights and directions for the development of anti-AE drugs and summarizing current advancements in AE pharmacotherapy.

Research Progress of Atomizers and Drugs Used in Atomization Therapy

At present,the commonly used treatment methods for chronic respiratory diseases are drug,oxygen,interventional and atomization therapy.Atomization therapy is the most widely used because of its characteristics of fast effect,high local drug concentration,less drug dosage,convenient application and few systemic adverse reactions.In this paper,the mechanism,characteristics,commonly used drugs and clinical application of atomization therapy are discussed.

SCN1A rs6732655A/T polymorphism:Diagnostic and therapeutic insights for drug-resistant epilepsy

BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance.

Did pediatric drug development advance epilepsy treatment in young patients?It is time for new research goals

Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.

Research Progress of Drug Therapy for Diabetes

Diabetes is mainly a series of symptoms of glucose metabolism disorder caused by relative or absolute insufficiencies of insulin.Most patients are accompanied by protein,fat,water and electrolyte disorders,including diabetes type 1 and diabetes type 2,of which diabetes type 2 accounts for more than 90%.The incidence rate of diabetes is high,the course of disease is long,and it is difficult to cure.Most patients need long-term medication.This study analyzed the clinical manifestations and predisposing factors of diabetes,and explored the progress of drug treatment of diabetes,which is summarized as follows.

Observation on the Clinical Effect of Applying Venetoclax Combined with Demethylation Drug Therapy in Patients with Acute Myeloid Leukemia

Objective: To investigate the therapeutic effect of applying venetoclax combined with demethylating drugs in treating patients with acute myeloid leukemia (AML). Methods: Eighty cases of AML patients treated with venetoclax combined with demethylating drugs in our hospital were selected from March 2021 to March 2024, including 40 cases of primary treatment patients and 40 cases of relapsed and refractory patients. The efficacy and safety of the combined drug therapy was analyzed. Results: The primary treatment group was presented with a complete remission (CR) rate of 40.5%, partial remission (PR) rate of 47.50%, no response (NR) rate of 12.50%, and a remission rate of 87.50%. The relapsed- refractory group was presented with a CR rate of 37.50%, PR rate of 42.50%, NR rate of 17.50%, and a remission rate of 87.50%. There was no statistical significance between the groups (P > 0.05). The hematological adverse reactions of the combined treatment for AML were leukopenia and the non-hematological adverse reactions were mainly infections, with an incidence rate of 87.50%. Conclusion: The efficacy of venetoclax combined with demethylating drugs in AML was remarkable and the treatment regimen can be adjusted according to the treatment-resistant response.

Advances in Transdermal Drug Delivery for Cancer Therapy

Transdermal drug delivery offers a promising alternative to traditional cancer therapies by providing a non-invasive,controlled,and targeted delivery of therapeutic agents.This paper explores the advancements,benefits,and challenges associated with transdermal drug delivery systems(TDDS)in cancer treatment.It highlights the mechanisms of action,key technologies,and the potential impact on patient outcomes.By examining recent studies and clinical trials,this paper aims to provide a comprehensive overview of the efficacy,safety,and prospects of transdermal drug delivery in oncology.

Role of autophagy in tumorigenesis,metastasis,targeted therapy and drug resistance of hepatocellular carcinoma

Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.

Clinical effects of psychological intervention and drug therapy against peptic ulcer

Objective:To evaluate the clinical effects of psychological interventions and drug therapy against peptic ulcer.Methods:96 patients with peptic ulcer were divided into control group with Tagamet 800 mg per evening p.o.and trial group with psychological intervention on the basis of drug treatment.Results:There were significant differences between the two groups(P【0.05), the trial group showed that the anxiety and depression cases declined obviously and effective rate of ulcer therapy was much higlier than control group.Conclusions:In sum,psychological intervention combined with drug therapy provides an effective method for ulcer treatment.

Nanotechnology-based combination therapy for overcoming multidrug-resistant cancer

Multidrug resistance(MDR) is a major obstacle to successful cancer treatment and is crucial to cancer metastasis and relapse.Combination therapy is an effective strategy for overcoming MDR. However, the different pharmacokinetic(PK) profiles of combined drugs often undermine the combination effect in vivo, especially when greatly different physicochemical properties(e.g.,those of macromolecules and small drugs) combine. To address this issue, nanotechnology-based codelivery techniques have been actively explored. They possess great advantages for tumor targeting, controlled drug release, and identical drug PK profiles. Thus,a powerful tool for combination therapy is provided, and the translation from in vitro to in vivo is facilitated. In this review, we present a summary of various combination strategies for overcoming MDR and the nanotechnology-based combination therapy.

Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.

Recent progress on nanoparticle-based drug delivery systems for cancer therapy

The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.

Current and future antiviral drug therapies of hepatitis B chronic infection

Despite significant improvement in the management of chronic hepatitis B virus(HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon(IFN)-α and monotherapy with five nucleos(t)ide analogues(NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish long-term control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection.

Constipation-predominant irritable bowel syndrome: A review of current and emerging drug therapies

Irritable bowel syndrome(IBS) is a highly prevalent medical condition that adversely affects patient quality of life and constitutes a significant economic burden on healthcare resources. A large proportion of patients suffer from the constipation subtype of IBS(IBS-C), most commonly afflicting older individuals and those with a lower socioeconomic status. Conventional pharmacologic and nonpharmacologic treatment options have limited efficacies and/or significant adverse events, which lead to increased long-term health care expenditures. Failure to effectively treat IBS-C patients over the past decades has largely been due to a poor understanding of disease pathophysiology, lack of a global view of the patient, and an inappropriate selection of patients and treatment endpoints in clinical trials. In recent years, however, more effective and safer drugs have been developed for the treatment of IBS-C. The advancement in the area of pharmacologic treatment is based on new knowledge of the pathophysiologic basis of IBS-C and the development of drugs with increased selectivity within pharmacologic classes with recognized efficacies. This narrative review covers the spectrum of available drugs and their mechanisms of action, as well as the efficacy and safety profiles of each as determined in relevant clinical trials that have investigated treatment options for IBS-C and chronic constipation. A brief summary of laxative-based treatment options is presented, followed by up-to-date assessments for three classes of drugs: prokinetics, prosecretory agents, and bile acid modulators.

A Review on Nano-Based Drug Delivery System for Cancer Chemoimmunotherapy

Although notable progress has been made on novel cancer treatments,the overall survival rate and therapeutic effects are still unsatisfactory for cancer patients.Chemoimmunotherapy,combining chemotherapeutics and immunotherapeutic drugs,has emerged as a promising approach for cancer treatment,with the advantages of cooperating two kinds of treatment mechanism,reducing the dosage of the drug and enhancing therapeutic effect.Moreover,nano-based drug delivery system(NDDS)was applied to encapsulate chemotherapeutic agents and exhibited outstanding properties such as targeted delivery,tumor microenvironment response and site-specific release.Several nanocarriers have been approved in clinical cancer chemotherapy and showed significant improvement in therapeutic efficiency compared with traditional formulations,such as liposomes(Doxil R,Lipusu R),nanoparticles(Abraxane R)and micelles(Genexol-PM R).The applications of NDDS to chemoimmunotherapy would be a powerful strategy for future cancer treatment,which could greatly enhance the therapeutic efficacy,reduce the side effects and optimize the clinical outcomes of cancer patients.Herein,the current approaches of cancer immunotherapy and chemoimmunotherapy were discussed,and recent advances of NDDS applied for chemoimmunotherapy were further reviewed.

The appliances and prospects of aurum nanomaterials in biodiagnostics, imaging, drug delivery and combination therapy

Aurum nanomaterials(ANM), combining the features of nanotechnology and metal elements, have demonstrated enormous potential and aroused great attention on biomedical applications over the past few decades. Particularly, their advantages, such as controllable particle size, flexible surface modification, higher drug loading, good stability and biocompatibility, especially unique optical properties, promote the development of ANM in biomedical field. In this review, we will discuss the advanced preparation process of ANM and summarize their recent applications as well as their prospects in diagnosis and therapy. Besides, multi-functional ANM-based theranostic nanosystems will be introduced in details, including radiotherapy(RT), photothermal therapy(PTT), photodynamic therapy(PDT), immunotherapy(IT), and so on.

Multiple hurdle mechanism and blood-brain barrier in epilepsy:glucocorticoid receptor-heat shock proteins on drug regulation

Epilepsy is a complex neurologic condition which affects over 50 million people worldwide.Pharmacotherapy,primarily involving the use of anti-seizure drugs(ASDs),is an essential part of controlling seizures.However,nearly 30%of patients develop drug-resistant epilepsy,clinically defined as the persistence of seizure following trials of two ASDs(Kwan et al.,2010).Although several hypotheses have been proposed to explain this phenomenon,the mechanism of drug-resistant epilepsy still remains unclear.