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.

Treatment of Functional Retrograde Ejaculation with Acupuncture and TCM Herbal Drugs

Acupuncture at the Taichong (LR 3), Sanyinjiao (SP 6) and Ciliao (BL 32) points combined with TCM drugs for soothing the liver, replenishing the kidney, freeing the seminal passage, and eliminating the stasis showed effective for functional retrograde ejaculation in 25 cases. The total effective rate of 68.0% was significantly better than imipramine used in the control group (P<0.05).

Treatment of Dizziness by Massotherapy and Traditional Chinese Drugs——A Report of 110 cases

Note: HLY = hyperactivity of the liver-yang, STPMJ = stagnation of turbid phlegm in middle-Jiao, DQB = deficiency of qi and blood, DKE = deficiency of the kidney-essence, OCBS = obstruction of collaterals by blood

Knowledge about the Management of Anti-Epileptic Drug Treatment among General Practitioners in Brazzaville, Congo

Background: Epilepsy is a chronic brain disorder. It often leads to disabilities and handicaps. In Africa, epilepsy is almost exclusively treated by general practitioners (GPs) because of a shortage of epilepsy specialists. It is therefore important to know the level of knowledge about epilepsy among GPs in order to improve their skills. Objectives: To assess the level of knowledge about the management of anti-epileptic drug treatment among GPs in Brazzaville;to investigate the relationship between demographic factors and GPs’ knowledge. Methods: This was a cross-sectional analytical study. It was conducted from 20 July to 1 September 2021. It focused on GPs working in public hospitals and private care centers in Brazzaville. Information on treatment aspects was collected through a standardized 11-item questionnaire. Results: Among the 137 participants, there were 84 (61.3%) men and 53 (38.7%) women. Of these participants, 36 (26.3%) were trained in Congo versus 101 (73.7%) in other countries. Only 21 (15.3%) GPs had good knowledge about the management of anti-epileptic drug treatment. The overall average knowledge score among GPs was low (31.4%). No significant associations were found between low and good levels of knowledge and gender (OR = 1.03;95% CI = 0.40 - 2.68;p = 1.000), age groups (OR 0.05), training country (OR = 0.62;95% CI = 0.19 - 1.98;p = 0.591), practice hospital (OR = 0.40;95% CI = 0.05 - 3.20;p = 0.695) and duration of professional experience (OR 0.05). Conclusion: The study population has insufficient knowledge about the management of anti-epileptic drug treatment. Demographic factors have no impact on GPs’ knowledge. Epilepsy education programs are needed to improve GPs’ knowledge and skills.

Drug treatment of functional dyspepsia

Symptomatic improvement of patients with functional dyspepsia after drug therapy is often incomplete and obtained in not more than 60% of patients. This is likely because functional dyspepsia is a heterogeneous disease. Although great advance has been achieved with the consensus definitions of the Rome I and II criteria, there are still some aspects about the definition of functional dyspepsia that require clarification. The Rome criteria explicitly recognise that epigastric pain or discomfort must be the predominant complaint in patients labelled as suffering from functional dyspepsia. However, this strict definition can create problems in the daily primary care clinical practice, where the patient with functional dyspepsia presents with multiple symptoms. Before starting drug therapy it is recommended to provide the patient with an explanation of the disease process and reassurance. A thorough physical examination and judicious use of laboratory data and endoscopy are also indicated. In general, the approach to treat patients with functional dyspepsia based on their main symptom is practical and effective. Generally, patients should be treated with acid suppressive therapy using proton-pump inhibitors if the predominant symptoms are epigastric pain or gastroesophageal reflux symptoms. Although the role of Helicobacter pylori （H pylon） in functional dyspepsia continues to be a matter of debate, recent data indicate that there is modest but clear benefit of eradication of H pylori in patients with functional dyspepsia. In addition, H pylori is a gastric carcinogen and if found it should be eliminated. Although there are no specific diets for patients with FD, it may be helpful to guide the patients on healthy exercise and eating habits.

Treatment of epilepsy in China Formal or informal?

Antiepileptic drugs are the preferred treatment approach for epileptic patients. However, informal treatment is important for intractable epilepsy. In this study, 500 epileptic patients were recruited from the General Hospital of Beijing Military Area Command of Chinese PLA during the period of October 2009 to January 2012. These involved patients that had been medically treated for at least 1 year. Information on the initial treatment and changes to treatment regimens for each patient was collected through questionnaires. The survey results showed that 52.3% of the epileptic patients searched for treatment after the first seizure, and the mean numbers of seizures was 12.8; 59.8% of the epileptic patients were diagnosed at the first visit, and the mean onset time was 17 months after the first seizure. After diagnosis, patients were treated for an average of 20 days, and the median time was 1 day. Formal anti-epileptic drugs were selected as the first treatment regimen by 67.8% of patients, and 77.5% of these drugs were monotherapies. The mean and median numbers of seizure were respectively 36.9 and 3.0 times before the first regimen was changed. The regimen was changed within the first 6 months by 46.6% of patients, and after the first and second years of treatment, the proportions increased to 54.0% and 71.8%, respectively. In total, 78.5% of the regi- mens were changed to informal treatments. The informal treatment of epilepsy in China is common, being initiated by either patients or physicians. Enhancing epileptic treatment services in hospital, improving physicians＇ professional quality, and strengthening health propaganda may promote the normalization of drug treatment of epilepsy in China.

Diagnosis and treatment of heart failure with preserved left ventricular ejection fraction

Nearly six million people in United States have heart failure.Fifty percent of these people have normal left ventricular(LV)systolic heart function but abnormal diastolic function due to increased LV myocardial stiffness.Most commonly,these patients are elderly women with hypertension,ischemic heart disease,atrial fibrillation,obesity,diabetes mellitus,renal disease,or obstructive lung disease.The annual mortality rate of these patients is 8%-12%per year.The diagnosis is based on the history,physical examination,laboratory data,echocardiography,and,when necessary,by cardiac catheterization.Patients with obesity,hypertension,atrial fibrillation,and volume overload require weight reduction,an exercise program,aggressive control of blood pressure and heart rate,and diuretics.Miniature devices inserted into patients for pulmonary artery pressure monitoring provide early warning of increased pulmonary pressure and congestion.If significant coronary heart disease is present,coronary revascularization should be considered.

Analysis of a Dynamic Model of Host-parasite Interaction with Delay and Treatment

In this paper, the dynamic behaviors of a host-parasite model with intracellular delay and drug treatment is investigated. we obtain the basic reproductive ratio R0 , which determined the behaviors of the system. If R0<1, the infection-free equilibrium is globally asymptotic stability. If 1<R0<3, the infection equilibrium is locally asymptotic stability. If R0 > 3, by choosing the delay τ as a bifurcation parameter, the infection equilibrium bifurcate a family of periodic solution as τ crosses a critical value. Furthermore, we give some examples to verify our theoretical results and discuss the sensitivity of the drug efficacy and effect of the delay. In the finally, we give a brief discussion.

Incidence of Interpersonal Violence among Individuals with Drug Addiction Receiving Compulsory Treatment: A Survey at Two Drug Detention Centers in Hunan, China

Drug dependence is a serious global health problem.To assist individuals with drug addiction,China alone has established 678 Compulsory Detoxification Detention Centers （CDDCs） that treat over300,000i ndividuals who are required by national law to receive compulsory treatment;because community-based outpatient treatment failed.

An Update on Management of Nonalcoholic Fatty Liver Disease&Nonalcoholic Steatohepapititis is the Time Ripe for Achieving Resolution of NAFLD&NASH Soon

We earlier reviewed how obesity has assumed an endemic/pandemic proportions that has resulted in escalating incidence and prevalence of associated escalating worldwide incidence of Metabolic Syndrome(MetS)with non alcoholic fatty liver disease(NAFLD),that is correlated with enhanced morbidity.Later we tried to detail how probiotics,L-Carnitine(LC),Nicotinamide Ribose(NR)Combination,along with Apical Sodium Dependent Bile Acids Transporter(ASBT)or Volixibat and Silybin,Vitamin D,Allyl Isothiocyanate(AITC),might aid in treating and understand the etiopathogenesis of NAFLD.The prevalence of NAFLD all over the world is approximately 25%,with that of non alcoholic steatohepapititis(NASH),varying from 1.5%=6.45%.Particularly NASH,specifically the ones associated with fibrosis possess a greater chance of generation of side effects that include progression to cirrhosis as well as liver-associated mortality.Despite an improvement was observed with vitamin E,Pioglitazone.liraglutide in histological appearance in liver randomized controlled clinical trials(RCT),at present no drugs exists that have received FDI approval for NASH.The aim of this review was to update the newer drugs getting evaluated,undergoing phase 2-3 trials.Currently there are Obeticholic acid,elafibranor,cenicriviroc,resmetriom,in addition to aramchol,that are the five agents that are getting analysed in big,histology dependent phase 3 trials.Hopefully within another 2-4 years,newer,efficacious drugs will be available for the therapy of NASH.Besides that a lot of phase 2 trials are continuing for different drugs.Further depending on outcomes of phase 2-3 trials,combination treatments are getting evaluated.For future therapeutic approaches would be made up of variations in NASH phenotypes,besides personalized approaches based on various NASH phenotypes in addition to response of every single patient.Further recently there were reports of utilization of curcumin with nonselective beta blocker for regression from cirrhosis(reviewed by us).Hopefully once there are approved therapies for NAFLD/NASH,we can work in that direction.

Clinical Research Progress of Crohn

Crohn’s Disease (CD) is a chronic recurrent inflammatory bowel disease with unknown etiology, most common in the terminal ileum and adjacent colon. In the past 30 years, the global prevalence of CD has continued to rise. Although the etiology is unknown, studies have shown that it is closely related to geographical environment, microfold cell damage, intestinal flora changes, epithelial barrier damage, immune dysfunction and low. The main clinical manifestations of CD are abdominal pain, chronic diarrhea, fatigue, fever and weight loss. At present, 5-aminosalicylic acid, antibiotics, glucocorticoids, immunosuppressants and biological agents are mainly used for treatment, but the drug effect is limited and the effect is not good. Recent studies have shown that Mesenchymal Stem Cells (MSC) can down-regulate immune response and promote tissue healing, which has certain safety and effectiveness in the treatment of moderate and severe CD, and has broad application prospects, but also has certain limitations. This paper summarizes the application and efficacy of related therapies in CD, providing a reference for clinicians.

Dimensions of Access to Antihypertensive Medications in Ceilandia,Distrito Federal,Brazil

Access can be understood as the sum of a number of elements of the interface between patients and the health care system. This study took a comprehensive approach to the dimensions of access to medications, employing indicators to evaluate the dimensions of access to antihypertensive medications in Ceilandia, DF, Brazil. This was a cross-sectional epidemiological study, administering questionnaires during home visits. The survey covered epidemiological and socioeconomic profiles, behavioral habits and the dimensions of access to antihypertensive medications comprising physical, financial, and geographic availability and accept ability according to the hypertensive population of Ceilandia. The total sample comprised 400 individuals and the hypertensive subset numbered 140 (35%). Indicators of physical availability of medications revealed that users found it difficult to acquire their drugs on almost one third of occasions and in some cases were unable to access any of these products. The greatest barriers to access were reported by users of pharmacies belonging to the Brazilian National Health Service (SUS) and on the “People’s Pharmacies” network. More than one third of the hypertensive sample spent their own money on medications they could not find at these pharmacies. The majority of the hypertensive subsets were overweight/obese, a minority engaged in physical activity and 40% were smokers/ex-smokers. More women reduced their salt intake. Men had higher incomes, educational level, and socioeconomic status. Failure to keep the public health care system supplied has prejudiced access to essential medications for hypertension treatment, transferring the costs onto users. This population has lifestyle habits that increase the risk of exacerbation of hypertension. These results reveal a need for effective public policies to ensure access to antihypertensive medications and involve users of the health care system in changing their habits and behaviors in order to achieve adequate and lasting control of systemic arterial hypertension.

Macrophage senescence in health and diseases

Macrophage senescence,manifested by the special form of durable cell cycle arrest and chronic low-grade inflammation like senescence-associated secretory phenotype,has long been consid-ered harmful.Persistent senescence of macrophages may lead to maladaptation,immune dysfunction,and finally the development of age-related diseases,infections,autoimmune diseases,and malignancies.However,it is a ubiquitous,multi-factorial,and dynamic complex phenomenon that also plays roles in remodeled processes,including wound repair and embryogenesis.In this review,we summarize some general molecular changes and several specific biomarkers during macrophage senescence,which may bring new sight to recognize senescent macrophages in different conditions.Also,we take an in-depth look at the functional changes in senescent macrophages,including metabolism,autophagy,polarization,phagocytosis,antigen presentation,and infiltration or recruitment.Furthermore,some degenerations and diseases associated with senescent macrophages as well as the mechanisms or relevant genetic regulations of senescent macrophages are integrated,not only emphasizing the possibility of regulating macrophage senescence to benefit age-associated diseases but also has an implication on the finding of potential tar-gets ordrugs clinically.

A novel treatment for psoriatic arthritis:Janus kinase inhibitors

Psoriatic arthritis(PsA)is a type of chronic inflammatory arthritis which is associated with psoriasis.The early recognition and treatment for PsA are of critical importance.Janus kinase(JAK)inhibitors,as a kind of orally small molecules,have emerged as an encouraging class of drug in PsA treatment.This review provides a discussion of the role and current status of JAK inhibitors in the control of PsA.There are three JAK inhibitors approved for use in autoimmune diseases,for example,tofacitinib,baricitinib,and upadacitinib,and only tofacitinib has been approved in PsA treatment.The clinical trials of upadacitinib and filgotinib in PsA patients are undergoing.The efficacy and safety of these agents were briefly discussed.Although there are still issues in terms of their efficacy and safety currently,JAK inhibitors are expected to benefit more PsA patients in future.

Drug treatment of cerebral vasospasm after subarachnoid hemorrhage following aneurysms

Cerebral vasospasm (CVS) is a common and severe complication of aneurysmal subarachnoid hemorrhage (aSAH). Despite the improvement in treatment of aSAH, CVS complicating aSAH has remained the main cause of death. CVS begins most often on the third day after the ictal event and reaches the maximum on the 5th–7th postictal days. Several therapeutic modalities have been employed to prevent or reverse CVS. The aim of this review is to summate all the available drug treatment modalities for vasospasm.

Treatment of Recurrent Respiratory Infection with Chinese Drug Therapy of Tonifying-Shen(肾) and Solidifying Superficiality—A Clinical Case Report

Children recurrent respiratory infection （CRRI） indicates that children suffer from frequent infections along the upper or lower respiratory tract for a certain number of times. It is not an independent disease but a clinical syndrome mostly brought about by some basic diseases such as nonspecific immunity, specific immune suppression or deficiency disease, congenital bronchopulmonary dysplasia, vitamin or microelement deficiency, or is induced by some factors such as smoking, cross infection, and nursing errors.（2） Clinically, CRRI is commonly treated by anti-infective agents, symptomatic and supportive treatment, and immune-regulatory therapy. However, the therapeutic effectiveness is always imperfect, which could even lead to a premium on asthma, or nephritis, etc.

Learning from berberine: Treating chronic diseases through multiple targets

Although advances have been made, chemotherapy for chronic, multifactorial diseases such as cancers, Alzheimer's disease, cardiovascular diseases and diabetes is far from satisfactory. Agents with different mechanisms of action are required. The botanic compound berberine(BBR) has been used as an over-the-counter antibacterial for diarrhea in China for many decades. Recent clinical studies have shown that BBR may be therapeutic in various types of chronic diseases. This review addresses BBR's molecular mechanisms of action and clinical efficacy and safety in patients with type 2 diabetes, hyperlipidemia, heart diseases, cancers and inflammation. One of the advantages of BBR is its multiple-target effects in each of these diseases. The therapeutic efficacy of BBR may reflect a synergistic regulation of these targets, resulting in a comprehensive effect against these various chronic disorders. The safety of BBR may be due to its harmonious distribution into those targets. Although the single-target concept is still the principle for drug discovery and research, this review emphasizes the concept of a multiple target strategy, which may be an important approach toward the successful treatment of multifactorial chronic diseases.

Epidemiological study of community- and hospital-acquired intraabdominal infections

Purpose： To investigate and analyze the clinical and etiological characteristics of community-acquired intraabdominal infections （CIAIs） and hospital-acquired or nosocomial intraabdominal infections （NIAIs） in a comprehensive hospital, to understand the characteristics, pathogen composition, and drug resistance of CIAls as well as NIAIs, and to provide a reference for clinical treatment. Methods： We collected the clinical data of patients with intraabdominal infections admitted to our hospital from June 2013 to June 2014. In vitro drug sensitivity tests were conducted to separate pathogens, and the data were analyzed using the WHONET 5.4 software and SPSS 13.0 software. Results： A total of 221 patients were enrolled in the study, including 144 with CIAls （55 mild-moderate and 89 severe） and 77 with NIAIs. We isolated 322 pathogenic strains, including 234 strains of gramnegative bacteria, 82 strains of gram-positive bacteria, and 6 strains of fungi. Based on clinical features, NIAIs and severe ClAls presented significantly higher values in age, length of hospital stay, mortality, and the incidence of severe intra-abdominal infection than mild-moderate CIAIs （p 〈 0.05）. There was no significant difference in the prognosis between NIAIs and severe CIAIs. Primary diseases leading to CIAIs and NIAIs mostly were hepatobiliary diseases and gastrointestinal diseases respectively. Bacteria isolated from various types of IAls mainly were Enterobacteriaceae; mild-moderate CIAIs mostly were mono-infection of gram-negative bacteria; NIAIs mostly were mixed infections of gram-negative and grampositive bacteria; and severe CIAls were from either type of infection. The rate of Extended Spectrum β-Lactamase-producing Escherichia coil and Klebsiella pneurnoniae was much higher in NIAIs than in CIAIs （p 〈 0.05）. The antimicrobial drug sensitivity of gram-negative bacteria isolated from NIAIs was significantly lower than that of CIAIs. Conclusion： CIAIs and NIAIs have their own unique clinical features and epidemiological features of pathogens which should be considered during the initial empiric therapy for the rational use of anti- microbial drugs. Regional IAls pathogenic bacteria have their own features in drug resistance, slightly different from some recommendations of 2010 Infectious Diseases Society of America guidelines.

Towards efficiency in rare disease research： what is distinctive and important？

Characterized by their low prevalence, rare diseases are often chronically debilitating or life threatening. Despite their low prevalence, the aggregate number of individuals suffering from a rare disease is estimated to be nearly 400 million worldwide.Over the past decades, efforts from researchers, clinicians, and pharmaceutical industries have been focused on both the diagnosis and therapy of rare diseases. However, because of the lack of data and medical records for individual rare diseases and the high cost of orphan drug development, only limited progress has been achieved. In recent years, the rapid development of next-generation sequencing(NGS)-based technologies, as well as the popularity of precision medicine has facilitated a better understanding of rare diseases and their molecular etiology. As a result, molecular subclassification can be identified within each disease more clearly, significantly improving diagnostic accuracy. However, providing appropriate care for patients with rare diseases is still an enormous challenge. In this review, we provide a brief introduction to the challenges of rare disease research and make suggestions on where and how our efforts should be focused.