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.

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 Pathogenesis and Treatment Progress of Androgenic Alopecia

Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.

Pathogenesis,clinical manifestations,diagnosis,and treatment progress of achalasia of cardia

Achalasia cardia,type of esophageal dynamic disorder,is a relatively rare primary motor esophageal disease characterized by the functional loss of plexus ganglion cells in the distal esophagus and lower esophageal sphincter.Loss of function of the distal and lower esophageal sphincter ganglion cells is the main cause of achalasia cardia,and is more likely to occur in the elderly.Histological changes in the esophageal mucosa are considered pathogenic;however,studies have found that inflammation and genetic changes at the molecular level may also cause achalasia cardia,resulting in dysphagia,reflux,aspiration,retrosternal pain,and weight loss.Currently,the treatment options for achalasia focus on reducing the resting pressure of the lower esophageal sphincter,helping to empty the esophagus and relieve symptoms.Treatment measures include botulinum toxin injection,inflatable dilation,stent insertion,and surgical myotomy(open or laparoscopic).Surgical procedures are often subject to controversy owing to concerns about safety and effectiveness,particularly in older patients.Herein,we review clinical epidemiological and experimental data to determine the prevalence,pathogenesis,clinical presentation,diagnostic criteria,and treatment options for achalasia to support its clinical management.

Advances and future directions in keloid research:Pathogenesis,diagnosis and personalized treatment strategies

Keloids,which are abnormal manifestations of wound healing,can result in significant functional impairment and aesthetic deformities.The pathogenesis of keloids is multifaceted and complex and influenced by various factors,such as genetics,the environment,and immune responses.The evolution of keloid treatment has progressed from traditional surgical excision to a contemporary combination of therapies including injection and radiation treatments,among others.This article provides a comprehensive review of keloid pathogenesis and treatment,emphasizing the latest advances in the field.Ultimately,this review underscores the necessity for continued research to enhance our understanding of keloid pathogenesis and to devise more effective treatments for this challenging condition.

Comparing the effectiveness of pattern differentiation treatment and fixed formula treatment for perimenopausal syndrome with Chinese herbal medicine:A study protocol

Objective:To further understand and compare the effectiveness of pattern differentiation treatment and fixed prescription treatment in perimenopausal syndrome.Methods:The study will be conducted in the Hong Kong Federation of Trade Unions Workers'Medical Clinics,Hong Kong Baptist University Chinese Medicine Clinic cum Training and Research Centre(Hong Kong,China).One hundred Chinese women,aged 45-55 years,will be recruited.The participants will be randomized into 2 groups.The intervention group will be administered medication,based on pattern differentiation,by qualified traditional Chinese medicine(TCM)practitioners.After each evaluation,TCM practitioners will evaluate and revise the prescription,based on the participants'patterns.The control group will be given the standard formula,i.e.,the Erxian decoction,which contains 6 herbs.The treatment period and the follow-up period will be 8 weeks each.The primary assessment outcome measure will be the Kupperman Index,and the secondary outcome measure will be the Menopause-specific Quality of Life Questionnaire score.Conclusion:Pattern-differentiated treatment is the basic principle of TCM to understand and treat diseases.The study will show the pattern-differentiated treatment is effectiveness than the fixed prescription.

Pathogenesis, Rehabilitation Assessment, Treatment Status, and Research Progress of Vascular Dementia

Given the global trends in population aging,the prevalence of vascular dementia(VD)is increasing year by year.VD has become the second most common type of dementia and can seriously threaten the quality of life of patients.Since VD is preventable,it is important to study VD clinically in order to improve the prognosis of patients.In recent years,a large number of studies have been carried out at home and abroad,focusing on the pathogenesis,rehabilitation assessment,and treatment of VD.This article is a concise overview of these studies.

Beyond the stomach: An updated view of Helicobacter pylori pathogenesis, diagnosis, and treatment

Helicobacter pylori (H. pylori) is an extremely common, yet underappreciated, pathogen that is able to alter host physiology and subvert the host immune response, allowing it to persist for the life of the host. H. pylori is the primary cause of peptic ulcers and gastric cancer. In the United States, the annual cost associated with peptic ulcer disease is estimated to be $6 billion and gastric cancer kills over 700000 people per year globally. The prevalence of H. pylori infection remains high (> 50%) in much of the world, although the infection rates are dropping in some developed nations. The drop in H. pylori prevalence could be a double-edged sword, reducing the incidence of gastric diseases while increasing the risk of allergies and esophageal diseases. The list of diseases potentially caused by H. pylori continues to grow; however, mechanistic explanations of how H. pylori could contribute to extragastric diseases lag far behind clinical studies. A number of host factors and H. pylori virulence factors act in concert to determine which individuals are at the highest risk of disease. These include bacterial cytotoxins and polymorphisms in host genes responsible for directing the immune response. This review discusses the latest advances in H. pylori pathogenesis, diagnosis, and treatment. Up-to-date information on correlations between H. pylori and extragastric diseases is also provided.

Concept of the pathogenesis and treatment of cholelithiasis

Gallstone disease(GD) is a chronic recurrent hepatobiliary disease,the basis for which is the impaired metabolism of cholesterol,bilirubin and bile acids,which is characterized by the formation of gallstones in the hepatic bile duct,common bile duct,or gallbladder.GD is one of the most prevalent gastrointestinal diseases with a substantial burden to health care systems.GD can result in serious outcomes,such as acute gallstone pancreatitis and gallbladder cancer.The epidemiology,pathogenesis and treatment of GD are discussed in this review.The prevalence of GD varies widely by region.The prevalence of gallstone disease has increased in recent years.This is connected with a change in lifestyle:reduction of motor activity,reduction of the physical load and changes to diets.One of the important benefits of early screening for gallstone disease is that ultrasonography can detect asymptomatic cases,which results in early treatment and the prevention of serious outcomes.The pathogenesis of GD is suggested to be multifactorial and probably develops from complex interactions between many genetic and environmental factors.It suggests that corticosteroids and oral contraceptives,which contain hormones related to steroid hormones,may be regarded as a model system of cholelithiasis development in man.The achievement in the study of the physiology of bile formation and the pathogenesis of GD has allowed expanding indications for therapeutic treatment of GD.

Clostridium difficile and inflammatory bowel disease: Role in pathogenesis and implications in treatment

Clostridium difficile(C.difficile)is the leading cause of antibiotic associated colitis and nosocomial diarrhea.Patients with inflammatory bowel disease(IBD)are at increased risk of developing C.difficile infection(CDI),have worse outcomes of CDI-including higher rates of colectomy and death,and experience higher rates of recurrence.However,it is still not clear whether C.difficile is a cause of IBD or a consequence of the inflammatory state in the intestinal environment.The burden of CDI has increased dramatically over the past decade,with severe outbreaks described in many countries,which have been attributed to a new and more virulent strain.A parallel rise in the incidence of CDI has been noted in patients with IBD.IBD patients with CDI tend be younger,have less prior antibiotic exposure,and most cases of CDI in these patients represent outpatient acquired infections.The clinical presentation of CDI in these patients can be unique-including diversion colitis,enteritis and pouchitis,and typical findings on colonoscopy are often absent.Due to the high prevalence of CDI in patients hospitalized with an IBD exacerbation,and the prognostic implications of CDI in these patients,it is recommended to test all IBD patients hospitalized with a disease flare for C.difficile.Treatment includes general measures such as supportive care and infection control measures.Antibiotic therapy with either oral metronidazole,vancomycin,or the novel antibiotic-fidaxomicin,should be initiated as soon as possible.Fecal macrobiota transplantation constitutes another optional treatment for severe/recurrent CDI.The aim of this paper is to review recent data on CDI in IBD:role in pathogenesis,diagnostic methods,optional treatments,and outcomes of these patients.

Irritable bowel syndrome: Pathogenesis, diagnosis, treatment, and evidence-based medicine

Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder that affects 9%-23% of the population across the world. The percentage of patients seeking health care related to IBS approaches 12% in primary care practices and is by far the largest subgroup seen in gastroenterology clinics. It has been well documented that these patients exhibit a poorer quality of life and utilize the health care system to a greater degree than patients without this diagnosis. The pathophysiology of IBS is not clear. Many theories have been put forward, but the exact cause of IBS is still uncertain. According to the updated ROME III criteria, IBS is a clinical diagnosis and presents as one of the three predominant subtypes: (1) IBS with constipation (IBS-C); (2) IBS with diarrhea (IBS-D); and (3) mixed IBS (IBS-M); former ROME definitions refer to IBS-M as alternating IBS (IBS-A). Across the IBS subtypes, the presentation of symptoms may vary among patients and change over time. Patients report the most distressing symptoms to be abdominal pain, straining, myalgias, urgency, bloating and feelings of serious illness. The complexity and diversity of IBS presentation makes treatment difficult. Although there are reviews and guidelines for treating IBS, they focus on the efficacy of medications for IBS symptoms using high-priority endpoints, leaving those of lower priority largely unreported. Therefore, the aim of this review is to provide a comprehensive evidence-based review of the diagnosis, pathogenesis and treatment to guide clinicians diagnosing and treating their patients.

Celiac disease:Prevalence,diagnosis,pathogenesis and treatment

Celiac disease(CD) is one of the most common diseases,resulting from both environmental(gluten) and genetic factors [human leukocyte antigen(HLA) and nonHLA genes].The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world.However,the population with diabetes,autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD,at least in part,because of shared HLA typing.Gliadin gains access to the basal surface of the epithelium,and interact directly with the immune system,via both trans-and para-cellular routes.From a diagnostic perspective,symptoms may be viewed as either "typical" or "atypical".In both positive serological screening results suggestive of CD,should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet(GFD) to confirm the diagnosis.Positive anti-tissue transglutaminase antibody or antiendomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy.Currently,the only treatment available for CD individuals is a strict life-long GFD.A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide,prevent toxic gliadin peptide absorption,blockage of selective deamidation of specific glutamine residues by tissue,restore immune tolerance towards gluten,modulation of immune response to dietary gliadin,and restoration of intestinal architecture.

Alcoholic hepatitis: A comprehensive review of pathogenesis and treatment

Alcoholic hepatitis(AH)is an acute hepatic inflammation associated with significant morbidity and mortality.Current evidence suggests that the pathogenesis is the end result of the complex interplay between ethanol metabolism,inflammation and innate immunity.Several clinical scoring systems have been derived to predict the clinical outcomes of patients with AH;such as Child-Turcotte-Pugh score,the Maddrey discriminant function,the Lille Model,the model for end stage liver disease scores,and the Glasgow alcoholic hepatitis score.At present,Corticosteroids or pentoxifylline are the current pharmacologic treatment options;though the outcomes from the therapies are poor.Liver trans-plantation as the treatment of alcoholic hepatitis remains controversial,and in an era of organ shortage current guidelines do not recommend transplantation as the treatment option.Because of the limitations in the therapeutic options,it is no doubt that there is a critical need for the newer and more effective pharmacological agents to treat AH.

Concept on the pathogenesis and treatment of primary biliarycirrhosis

Primary biliary cirrhosis (PBC) is an organ-specific autoimmune disease that predominantly affects women and is characterized by chronic, progressive destruction of small intrahepatic bile ducts with portal inflammation and ultimately fibrosis, leading to liver failure in the absence of treatment. Little is known about the etiology of PBC. PBC is characterized by anti-mitochondrial antibodies and destruction of intrahepatic bile ducts. The serologic hallmark of PBC is the presence of auto-antibodies to mitochondria, especially to the E2 component of the pyruvate dehydrogenase complex (PDC). Current theories on the pathogenesis of PBC favor the hypothesis that the disease develops as a result of an inappropriate immune response following stimulation by an environmental or infectious agent. Some reports suggest that xenobiotics and viral infections may induce PBC. The pathogenetic mechanism is believed to be caused by a defect in immunologic tolerance, resulting in the activation and expansion of self-antigen specific T and B lymphocyte clones and the production of circulating autoantibodies in addition to a myriad of cytokines and other inflammatory mediators. This leads to ductulopenia and persistent cholestasis, by developing end-stage hepatic-cell failure. In this review are given our own and literary data about mechanisms of development of intrahepatic cholestasis and possible ways of its correction.

Differentiation therapy:a promisingstrategy for cancer treatment

Poor differentiation is an important hallnnark of cancer cells,and differentiation therapy holds great promise for cancer treatment.The restoration of IkB kinase a(IKKa)leads to the differentiation of nasopharyngeal carcinoma cells with reduced tumorigenicity.The findings by Yan et al.validate the polycomb protein enhancer of zeste homologue2(EZH2)as a target for intervention.

Evidence-based pathogenesis and treatment of ulcerative colitis:A causal role for colonic epithelial hydrogen peroxide

In this comprehensive evidence-based analysis of ulcerative colitis(UC),a causal role is identified for colonic epithelial hydrogen peroxide(H_(2)O_(2))in both the pathogenesis and relapse of this debilitating inflammatory bowel disease.Studies have shown that H_(2)O_(2) production is significantly increased in the non-inflamed colonic epithelium of individuals with UC.H_(2)O_(2) is a powerful neutrophilic chemo-tactic agent that can diffuse through colonic epithelial cell membranes creating an interstitial chemotactic molecular“trail”that attracts adjacent intra-vascular neutrophils into the colonic epithelium leading to mucosal inflammation and UC.A novel therapy aimed at removing the inappropriate H_(2)O_(2) mediated chemotactic signal has been highly effective in achieving complete histologic resolution of colitis in patients experiencing refractory disease with at least one(biopsy-proven)histologic remission lasting 14 years to date.The evidence implies that therapeutic intervention to prevent the re-establishment of a pathologic H_(2)O_(2) mediated chemotactic signaling gradient will indefinitely preclude neutrophilic migration into the colonic epithelium constituting a functional cure for this disease.Cumulative data indicate that individuals with UC have normal immune systems and current treatment guidelines calling for the suppression of the immune response based on the belief that UC is caused by an underlying immune dysfunction are not supported by the evidence and may cause serious adverse effects.It is the aim of this paper to present experimental and clinical evidence that identifies H_(2)O_(2) produced by the colonic epithelium as the causal agent in the pathogenesis of UC.A detailed explanation of a novel therapeutic intervention to normalize colonic H_(2)O_(2),its rationale,components,and formulation is also provided.

TCM Stage Differentiation Treatment of Diabetic Gangrene——An Observation on Microcirculatory Changes

Microcirculatory changes and therapeutic effects in 39 non-insulin dependent diabetes mellitus (NIDDM) cases were evaluated. Under the same basic treatment in both groups, the treatment group (21 cases) was treated with TCM drugs according to its stages and compared with the control group (18 cases, treated with 654-2). The results showed that the microcirculatory cumulative scores were significantly decreased in both groups (P<0.05), but the decrease in the treatment group was more marked (P<0.05). In the treatment group, 15 cases were cured, 3 markedly effective, 2 effective and 1 ineffective; while in the control group, 13 cases were cured, 1 markedly effective and 4 ineffective. Statistically, there is no significant difference between the 2 groups (P>0.05) in therapeutic effects.

Treatment of oral ulcer based on TCM syndrome differentiation

Oral ulcer is a kind of ulcerative injury that occurs in the oral mucosa and is very common in clinic.In severe case,it can affect the quality of life of the patients.Western medicine treatment of oral ulcer is often prone to relapse,while the effect of traditional Chinese medicine treatment is remarkable.

Regularity of syndrome differentiation and treatment of traditional Chinese medicine for Henoch-Schonlein purpura based on data mining techniques

Objective:This study aims to explore the regularity of syndrome differentiation and treatment of traditional Chinese medicine(TCM)for allergic purpura.Methods:CNKI,Weipu Chinese science and technology database,wanfang medical network database,and Chinese biomedical literature database were searched for eligible studies.Medical records including complete patient personal information,patient symptoms,TCM syndromes,treatment,and medication were included.The data was analyzed using the Chinese medicine heritage support platform provided by the Chinese Academy of Chinese medicine(V2.5).Results:Differentiation of health gas camp blood was the most commonly used method of differentiation of symptoms and signs in famous veteran TCM.The treatment included cooling blood,activating blood circulation,clearing heat and detoxifying toxins,removing blood stasis and stopping bleeding.Honeysuckle,Forsythia suspensa,cicada slough and other drugs were interrelated.Potential drug pair combinations and drug networks showed the basic drug composition of Qingying Decoction.According to the entropy cluster analysis,28 core drug combination and 12 new formulations were obtained.Conclusion:The regularity of syndrome differentiation and treatment of traditional Chinese medicine for Henoch-Schonlein purpura based on the famous and old TCM doctors was complex.Further researches are still needed.