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.

Presymptomatic Diagnosis and Gene Therapy for Alzheimer’s Disease: Genomic, Therapeutic, and Ethical Aspects—A Systematic Review

Over the past three decades, genomic and epigenetic sciences have identified more than 70 genes involved in the molecular pathophysiology of Alzheimer’s disease (AD). DNA methylation, abnormal histone and chromatin regulation and the action of various miRNAs induce AD. The identification of mutated genes has paved the way for the development of diagnostic kits and the initiation of gene therapy trials. However, despite major advances in neuroscience research, there is yet no suitable treatment for AD. Therefore, the early diagnosis of this neurodegenerative disease raises several ethical questions, including the balance between the principle of non-maleficence and the principle of beneficence. The aims of this research were to present the genomic and ethical aspects of AD, and to highlight the ethical principles involved in its presymptomatic diagnosis and therapy. A systematic review of the literature in PubMed, Google Scholar and Science Direct was carried out to outline the genomic aspects and ethical principles relating not only to the presymptomatic diagnosis of AD, but also to its gene therapy. A total of 16 publications were selected. AD is a multifactorial disease that can be genetically classified into Sporadic Alzheimer’s Disease and Familial Alzheimer’s Disease based on family history. Gene therapy targeting specific disease-causing genes is a promising therapeutic strategy. Advancements in artificial intelligence applications may enable the prediction of AD onset several years in advance. While early diagnosis of AD may empower patients with full decision competence for early decision-making, it also carries implications for the patient’s family members, who are at risk of developing the disease, potentially becoming a source of confusion or anxiety. AD has a significant impact on the life of individuals at risk and their families. Given the absence of disease modifying therapy, genetic screening and early diagnosis for this condition raise ethical issues that must be carefully considered in the context of fundamental bioethical principles, including autonomy, beneficence, non-maleficence, and justice.

Advances in early diagnosis and therapy of pancreatic cancer

BACKGROUND: Pancreatic cancer remains a devastating disease with a 5-year survival rate of less than 5%. Recent advances in diagnostic methods and therapeutic approaches have increased the possibility of improving the existing poor prognosis. DATA SOURCES: English-language articles reporting early diagnosis and therapy of pancreatic cancer were searched from the MEDLINE and PubMed databases, Chinese-language articles were from CHKD (China Hospital Knowledge Database) RESULT: The current literature about pancreatic cancer was reviewed from three aspects: statistics, screening and early detection, and therapy. CONCLUSIONS: Early detection and screening of pancreatic cancer currently should be limited to high risk patients Surgical resection is the only curative approach available, with some recent improvement in outcomes. Gemcitabine has been a standard treatment during the last decade. Gemcitabine based combination treatment, especially combined with newer molecular targeted agents, is promising. The rationale for radiotherapy is controversial, but with the recent development of modern radiation delivery techniques, radiotherapy should be intensified. Patients with borderline pancreatic cancer could benefit from neoadjuvant therapy but more evidence is needed and the best neoadjuvant regimen is still to be determined.

Hepatic epithelioid hemangioendothelioma:Update on diagnosis and therapy

With an estimated incidence of only 1-2 cases in every 1 million people,hepatic epithelioid hemangioendothelioma(HEHE)is a rare vascular endothelial cell tumor occurring in the liver and consisting of epithelioid and histiocyte-like vascular endothelial cells in mucus or a fibrotic matrix.HEHE is characterized as a low-to-moderate grade malignant tumor and is classified into three types:solitary,multiple,and diffuse.Both the etiology and characteristic clinical manifestations of HEHE are unclear.However,HEHE has a characteristic appearance on imaging including ultrasound,magnetic resonance imaging,and positron emission tomography/computerized tomography.Still,its diagnosis depends mainly on pathological findings,with immunohistochemical detection of endothelial markers cluster of differentiation 31(CD31),CD34,CD10,vimentin,and factor VIII antigen as the basis of diagnosis.Hepatectomy and/or liver transplantation are the first choice for treatment,but various chemotherapeutic drugs are reportedly effective,providing a promising treatment option.In this review,we summarize the literature related to the diagnosis and treatment of HEHE,which provides future perspectives for the clinical management of HEHE.

Recent Progress in Nanoscale Covalent Organic Frameworks for Cancer Diagnosis and Therapy

Covalent organic frameworks(COFs)as a type of porous and crystalline covalent organic polymer are built up from covalently linked and periodically arranged organic molecules.Their precise assembly,welldefined coordination network,and tunable porosity endow COFs with diverse characteristics such as low density,high crystallinity,porous structure,and large specific-surface area,as well as versatile functions and active sites that can be tuned at molecular and atomic level.These unique properties make them excellent candidate materials for biomedical applications,such as drug delivery,diagnostic imaging,and disease therapy.To realize these functions,the components,dimensions,and guest molecule loading into COFs have a great influence on their performance in various applications.In this review,we first introduce the influence of dimensions,building blocks,and synthetic conditions on the chemical stability,pore structure,and chemical interaction with guest molecules of COFs.Next,the applications of COFs in cancer diagnosis and therapy are summarized.Finally,some challenges for COFs in cancer therapy are noted and the problems to be solved in the future are proposed.

Translational research case studies:Development of antibodies for cancer diagnosis and therapy

Antibodies are primary tools in several areas of biomedical sciences, including basic research, diagnostics, and molecular therapeutics. Antibodies are widely used in diagnostic applications for clinical medicine. Analysis of cells and tissues in pathology laboratories includes the use of antibodies on tissue sections. Further, antibodies are making rapid inroads into medical therapeutics, driven by technological evolution from chimeric and humanized to fully human antibodies. The therapeutic antibody market has the potential to reach $30 billion by 2010. Our lab has developed a monoclonal antibody, named Met4 that was raised against the extracellular domain of Met specifically with the goal of measuring Met in FFPE tissues. The Met receptor kinase is expressed on the cell surface of a significant number and variety of human primary solid tumors and in their metastases. The characterization of the Met4 antibody suggests it should possess adequate performance for quantification of Met expression in clinical specimens. We have also generated a fully human Fab fragment against EGFR; conjugated it to taxol as an immuno-chemotherapy agent; and investigated its in vitro antitumor efficacy on EGFR positive A431 epidermoid carcinoma cells.

Nanomedicine has opened new avenues for cancer diagnosis and therapy

A crucial feature of nanoparticles,such as liposomes,magnetic nanoparticles,quantum dots,metallic nanoparticles,silica nanoparticles,polymersomes and dendrimers etc.,is their higher accumulation in the tumor than in normal tissues1-3.Various nanoparticles have been intensively used as vehicles to deliver

Irritable bowel syndrome: a disease still searching for pathogenesis, diagnosis and therapy

Irritable bowel syndrome(IBS) is the most frequently diagnosed functional gastrointestinal disorder in primary and secondary care. It is characterised by abdominal discomfort, pain and changes in bowel habits that can have a serious impact on the patient's quality of life. The pathophysiology of IBS is not yet completely clear. Genetic, immune, environmental, inflammatory, neurological and psychological factors, in addition to visceral hypersensitivity, can all play an important role, one that most likely involves the complex interactions between the gut and the brain(gut-brain axis). The diagnosis of IBS can only be made on the basis of the symptoms of the Rome Ⅲ criteria. Because the probability of organic disease in patients fulfilling the IBS criteria is very low, a careful medical history is critical and should pay particular attention to the possible comorbidities.Nevertheless, the severity of the patient's symptoms or concerns sometimes compels the physician to perform useless and/or expensive diagnostic tests, transforming IBS into a diagnosis of exclusion. The presence of alarming symptoms(fever, weight loss, rectal bleeding, significant changes in blood chemistry), the presence of palpable abdominal masses, any recent onset of symptoms in patient aged over 50 years, the presence of symptoms at night, and a familial history of celiac disease, colorectal cancer and/or inflammatory bowel diseases all warrant investigation. Treatment strategies are based on the nature and severity of the symptoms, the degree of functional impairment of the bowel habits, and the presence of psychosocial disorders. This review examines and discusses the pathophysiological aspects and the diagnostic and therapeutic approaches available for patients with symptoms possibly related to IBS, pointing out controversial issues and the strengths and weaknesses of the current knowledge.

Discussion of diagnosis and therapy strategy for pineal region tumors

Objective To define optimal diagnosis and theraputic strategy of pineal region tumors. Methods Clinicalmaterials of 154 cases with pineal region tumors were analyzed retrospectively. Results The patients with pineal region tumors often complained of increased intracranial pressure and ocular movement deficiency.

A Review on Artificial Micro/Nanomotors for Cancer-Targeted Delivery, Diagnosis, and Therapy

Micro/nanomotors have been extensively explored for efficient cancer diagnosis and therapy,as evidenced by significant breakthroughs in the design of micro/nanomotors-based intelligent and comprehensive biomedical platforms.Here,we demonstrate the recent advances of micro/nanomotors in the field of cancer-targeted delivery,diagnosis,and imaging-guided therapy,as well as the challenges and problems faced by micro/nanomotors in clinical applications.The outlook for the future development of micro/nanomotors toward clinical applications is also discussed.We hope to highlight these new advances in micro/nanomotors in the field of cancer diagnosis and therapy,with the ultimate goal of stimulating the successful exploration of intelligent micro/nanomotors for future clinical applications.

Nanotechnology and Nanomedicine: A Promising Avenue for Lung Cancer Diagnosis and Therapy

Lung cancer is a leading cause of cancer-related death worldwide,with a very poor overall five-year survival rate.The intrinsic limitations associated with the conventional diagnosis and therapeutic strategies used for lung cancer have motivated the development of nanotechnology and nanomedicine approaches,in order to improve early diagnosis rate and develop more effective and safer therapeutic options for lung cancer.Cancer nanomedicines aim to individualize drug delivery,diagnosis,and therapy by tailoring them to each patient’s unique physiology and pathological features—on both the genomic and proteomic levels—and have attracted widespread attention in this field.Despite the successful application of nanomedicine techniques in lung cancer research,the clinical translation of nanomedicine approaches remains challenging due to the limited understanding of the interactions that occur between nanotechnology and biology,and the challenges posed by the toxicology,pharmacology,immunology,and largescale manufacturing of nanoparticles.In this review,we highlight the progress and opportunities associated with nanomedicine use for lung cancer treatment and discuss the prospects of this field,together with the challenges associated with clinical translation.

Diagnosis and management of interstitial pneumonitis associated with interferon therapy for chronic hepatitis C

Interstitial pneumonitis(IP) is an uncommon pulmonary complication associated with interferon(IFN) therapy for chronic hepatitis C virus(HCV) infection.Pneumonitis can occur at any stage of HCV treatment,ranging from 2 to 48 wk,usually in the first 12 wk.Its most common symptoms are dyspnoea,dry cough,fever,fatigue,arthralgia or myalgia,and anorexia,which are reversible in most cases after cessation of IFN therapy with a mean subsequent recovery time of 7.5 wk.Bronchoalveolar lavage in combination with chest high resolution computed tomography has a high diagnostic value.Prompt discontinuation of medication is the cornerstone,and corticosteroid therapy may not be essential for patients with mild-moderate pulmonary functional impairment.The severity of pulmonary injury is associated with the rapid development of IP.We suggest that methylprednisolone pulse therapy followed by low dose prednisolone for a short term is necessary to minimize the risk of fatal pulmonary damage if signs of significant pulmonary toxicity occur in earlier stage.Clinicians should be aware of the potential pulmonary complication related to the drug,so that an early and opportune diagnosis can be made.

Liquid biopsy:Precise diagnosis and therapy for cholangiocarcinoma

The following letter to the editor highlights the review titled“Liquid biopsy in cholangiocarcinoma:Current status and future perspective”in World J Gastrointest Oncol 2021;13:332-350.It is necessary to realize individualized therapy to improve the clinical prognosis of patients with cholangiocarcinoma.

Nanozymes:Versatile Platforms for Cancer Diagnosis and Therapy

Natural enzymes usually suffer from high production cost,ease of denaturation and inactivation,and low yield,making them difficult to be broadly applicable.As an emerging type of artificial enzyme,nanozymes that combine the characteristics of nanomaterials and enzymes are promising alternatives.On the one hand,nanozymes have high enzyme-like catalytic activities to regulate biochemical reactions.On the other hand,nanozymes also inherit the properties of nanomaterials,which can ameliorate the shortcomings of natural enzymes and serve as versatile platforms for diverse applications.In this review,various nanozymes that mimic the catalytic activity of different enzymes are introduced.The achievements of nanozymes in different cancer diagnosis and treatment technologies are summarized by highlighting the advantages of nanozymes in these applications.Finally,future research directions in this rapidly developing field are outlooked.

Connecting Calcium-Based Nanomaterials and Cancer:From Diagnosis to Therapy

As the indispensable second cellular messenger,calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins.The importance of calcium ions(Ca^(2+))makes its“Janus nature”strictly regulated by its concentration.Abnormal regulation of calcium signals may cause some diseases;however,artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role.“Calcium overload,”for example,is characterized by excessive enrichment of intracellular Ca^(2+),which irreversibly switches calcium signaling from“positive regulation”to“reverse destruction,”leading to cell death.However,this undesirable death could be defined as“calcicoptosis”to offer a novel approach for cancer treatment.Indeed,Ca^(2+)is involved in various cancer diagnostic and therapeutic events,including calcium overload-induced calcium homeostasis disorder,calcium channels dysregulation,mitochondrial dysfunction,calcium-associated immunoregulation,cell/vascular/tumor calcification,and calcification-mediated CT imaging.In paral-lel,the development of multifunctional calcium-based nanomaterials(e.g.,calcium phosphate,calcium carbonate,calcium peroxide,and hydroxyapatite)is becoming abundantly available.This review will highlight the latest insights of the calcium-based nanomaterials,explain their application,and provide novel perspective.Identifying and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.

Nanotechnology in diagnosis and therapy of gastrointestinal cancer

Advances in nanotechnology have opened new frontiers in the diagnosis and treatment of cancer.Nanoparticle-based technology improves the precision of tumor diagnosis when combined with imaging,as well as the accuracy of drug target delivery,with fewer side effects.Optimized nanosystems have demonstrated advantages in many fields,including enhanced specificity of detection,reduced toxicity of drugs,enhanced effect of contrast agents,and advanced diagnosis and therapy of gastrointestinal(GI)cancers.In this review,we summarize the current nanotechnologies in diagnosis and treatment of GI cancers.The development of nanotechnology will lead to personalized approaches for early diagnosis and treatment of GI cancers.

Nanomedicine:diagnosis to therapy

It can be said that "small technology" becomes a very useful technology and is replacing the classical technology. Nanotechnology is an applied technology relating to management,construction,synthesis of devices in atomic or molecular level that poses the size between 1 and 100 nanometers.In this short article,the author will summarize important advent in nanodiagnosis and nanotherapy then further extrapolate this for the tropical medicine aspect.

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

How useful are biomarkers for the diagnosis of Alzheimer’s disease and especially for its therapy?

Alzheimer’s disease key facts:Alzheimer’s disease(AD)is a slowly progressive neurodegenerative disease with no available effective treatment.It is possible to distinguish an early-onset AD that affects a limited number of subjects of young age,and a sporadic or late-onset form of the disease that affects the vast majority of subjects who are diagnosed with AD.As life expectancy has increased considerably over the past century,the number of people diagnosed with AD has grown exponentially.So,AD and AD-related pathologies represent a huge social and economic burden.The number of individuals waiting for effective disease-modifying therapy is impressive.It is estimated that 50 million people worldwide live with dementia,the majority of these cases are caused by AD(World Health Organization,2021).In the US about 6 million individuals are living with AD,and more than 9 million people are in EU member states(OECD and European Union,2020).The costs of health care and long-term care are substantial.Given this massive societal impact,enormous efforts have been made to understand the pathogenetic mechanisms of the disease with the hope of identifying new targets and,therefore,developing effective drugs.

Serum midkine levels for the diagnosis and assessment of response to interventional therapy in patients with hepatocellular carcinoma

Objective:To explore the clinical significance of serum midkine(MDK) levels for the diagnosis of hepatocellular carcinoma(HCC) and evaluate the efficacy of interventional therapy.Methods:Eighty-four patients with HCC were enrolled in this retrospective study.They received an interventional treatment.A follow-up was performed every 2 months,using magnetic resonance imaging,to determine whether the treatment should be continued.Serum alpha-fetoprotein(AFP) and MDK levels were measured at the first diagnosis and during the follow-ups,and the HCC detection rates based on the cutoff values of these two measurements were compared.The relationships between AFP and MDK and the clinical tumor characteristics and changes in APK and MDK before and after treatment were also compared using a rank sum test and χ2 test,respectively.The prognostic significance of MDK for HCC was determined through regression analysis.A twosided P <0.05 was considered statistically significant.Results:MDK expression was detected in 95.24% of the cases.Subgroup analysis revealed MDK expression in95.35%,95.12%,85.19%,86.67%,and 83.33% of the AFP-positive,AFP-negative,stage A Barcelona clinic liver cancer(BCLC-A),BCLC-A/AFP-positive,and BCLC-A/AFP-negative cases,respectively.MDK expression after the interventional treatment(66.7%) was significantly lower than that before the treatment(95.2%).The mean posttreatment MDK level was 0.67 ng/mL in patients with a positive response to therapy as compared with 3.66 ng/mL in those with no positive response.All patients were followed up for 18 months,and those positive for MDK expression before the intervention were more likely to relapse than patients without MDK expression.Subgroup analysis revealed the highest recurrence rate for patients who were positive for MDK expression before and after treatment.Conclusions:Serum MDK may serve as a powerful complement to AFP in the diagnosis of HCC.MDK measurement may improve the detection rate of BCLC-A and AFP-negative HCC.Serum MDK may help to determine the vascular invasion and poor clinical staging of HCC tumors.Patients with MDK-positive HCC before treatment may be more prone to postoperative tumor progression.