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 ...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.展开更多
Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes ...Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes of diabetes classified by the international World Health Organization standards.Although GDM patients constitute a small proportion of the total number of diabetes cases,the incidence of GDM has risen significantly over the past decade,posing substantial risk to pregnant women and infants.Therefore,it warrants considerable attention.The pathogenesis of GDM is generally considered to resemble that of type II diabetes,though it may have distinct characteristics.Analyzing blood biochemical proteins in the context of GDM can help elucidate its pathogenesis,thereby facilitating more effective prevention and management strategies.This article reviews this critical clinical issue to enhance the medical community's sufficient understanding of GDM.展开更多
Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datas...Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.展开更多
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. py...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.展开更多
This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these...This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.展开更多
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 a...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.展开更多
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 ca...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.展开更多
Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more...Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.展开更多
BACKGROUND: Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of ...BACKGROUND: Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.DATA SOURCES: Studies published between 1st January 1991 and 31st December 2015 were identified with Pub Med, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings: “acute pancreatitis, necrosis, mortality, pathogenesis, incidence” and the terms “open necrosectomy and minimally invasive necrosectomy”.The National Institute of Clinical Excellence(NICE) Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks.RESULTS: The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology,acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed.The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach.CONCLUSIONS: Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the latest UK guidelines for management of severe acute pancreatitis.展开更多
Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal isch...Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion,and ocular ischemic syndrome. Uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and likely predominant agent involved in the pathogenesis of intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis and neovascular glaucoma is divided into four stages: prerubeosis, preglaucoma, open angle glaucoma, and angle-closure glaucoma.展开更多
Coronavirus disease 2019(COVID-19)is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The emergence of SARS-CoV-2 has been marked as the third introduction of a ...Coronavirus disease 2019(COVID-19)is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus(SARS-CoV)and the Middle East respiratory syndrome coro-navirus(MERS-CoV)in the twenty-first century.In this minireview,we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis,diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections,which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.展开更多
Patients with inflammatory bowel disease(IBD)are at increased risk for developing colorectal cancer(CRC),although the overall incidence of IBD-associated CRC has been diminishing in recent decades in western countries...Patients with inflammatory bowel disease(IBD)are at increased risk for developing colorectal cancer(CRC),although the overall incidence of IBD-associated CRC has been diminishing in recent decades in western countries.As demonstrated in previous studies,the risk of CRC in IBD increases with longer duration,extent of colitis,a familial history of CRC,coexistent primary sclerosing cholangitis,and the degree of inflammation.The pathogenesis of CRC in IBD is poorly understood.Similar to sporadic CRC,IBD-associated CRC is a consequence of sequential episodes of genomic alteration.Multiple inter-related pathways,including immune response by mucosal inflammatory mediators,oxidative stress,and intestinal microbiota,are also involved the pathogenesis of IBD-associated CRC.Continuing colonic inflammation appears to be a factor in the development of CRC;therefore,anti-inflammatory agents such as5-aminosalicylate compounds and immune modulators have been considered as potential chemopreventive agents.Colonoscopic surveillance is widely accepted as being effective in reducing the risk of IBD-associated CRC,although no clear evidence has confirmed that surveillance colonoscopy prolongs survival in patients with extensive colitis.The traditional recommendation has been quadrantic random biopsies throughout the entire colon;however,several guidelines now have endorsed chromoendoscopy with a target biopsy because of increasing diagnostic yields and reduced workloads for endoscopists and pathologists.New technologies such as narrow band imaging,confocal endomicroscopy,and autofluorescence imaging have not yet been confirmed as surveillance strategies in IBD.展开更多
Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal...Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches.展开更多
Objective:Senile calcific valvular disease of the heart is an endemic valvular heart disease in the elderly patients. The disease is mainly characterized by degenerative change, thickening, fibrosis and calcification ...Objective:Senile calcific valvular disease of the heart is an endemic valvular heart disease in the elderly patients. The disease is mainly characterized by degenerative change, thickening, fibrosis and calcification of the valvular connective tissue, which leads to the dysfunction of the valve and its stent. The pathogenesis of calcified valvular heart disease has not been fully elucidated, and it may be related to hemodynamics, atherosclerosis and sex. Echocardiography is the basic method and important basis for clinical diagnosis of calcified valvular heart disease, and it might detect the valvular thickening or calcification. This article aimed to analyze the pathogenesis of senile calcified valvular heart disease. At the same time, this research tried to review the progress on ultrasonic diagnosis of senile calcified valvular heart disease in order to provide references for clinical diagnosis and treatment.展开更多
Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,bl...Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,blood stasis,qi stagnation,and phlegm.Failure can be caused by deficiency or disease.The pathogenesis of this disease is caused by obstruction of the heart pulse,and its pathogenesis can be transformed into each other.The theory of traditional Chinese medicine believes that the general rule is not painful.Therefore,the treatment of coronary CTO lesions should be based on the combination of Tong and Tong tonic.The chronic complete occlusive disease of the coronary artery can be treated through Xuanbi Tongyang,Huoxue Tongluo,and Aroma Wentong.Based on the Chinese medicine's understanding of the etiology and pathogenesis of coronary CTO lesions,it provides a basis for the diagnosis and treatment of traditional Chinese medicine,solves the problems of interventional medicine in western medicine,and gives play to the unique advantages of traditional Chinese medicine for clinical diagnosis and treatment.展开更多
Contact dermatitis(CD) is the most common professional skin disease, with frequencies ranging from 24 to 170 every 100000 individuals. Approximately 20% of the United States population suffers from CD. CD can be class...Contact dermatitis(CD) is the most common professional skin disease, with frequencies ranging from 24 to 170 every 100000 individuals. Approximately 20% of the United States population suffers from CD. CD can be classified according to its origin and severity. ICD stands for irritant CD, whereas ACD means allergic CD. Their clinical presentation includes acute, sub-acute and chronic eczema. Despite their different origin, ICD and ACD often present similar clinical and histologic findings. The current gold standard for diagnosis is patchtesting. However, patch-testing is being questioned in terms of validity and reproducibility, as it relies heavily on the skill of the observer. Real-time reflectance confocal microscopy is a non-invasive imaging technique that bears strong promise for the study of CD, and it enables the evaluation of cellular and subcellular changes over time with similar resolution compared to that of conventional histology.展开更多
Retinal vein occlusion(RVO) is the second vascular retinal cause of visual loss and defined by the occlusion of a retinal vein. It is divided into branch retinal vein occlusion or central retinal vein occlusion, depen...Retinal vein occlusion(RVO) is the second vascular retinal cause of visual loss and defined by the occlusion of a retinal vein. It is divided into branch retinal vein occlusion or central retinal vein occlusion, depending on the location of occlusion. RVO has severe medical, financial and social implications on the patients. The diagnosis of the disease is easier nowadays with the use of spectral domain optical coherence tomography and fluorescein angiography. The treatment options for RVO have changed dramatically over the past few years with the introduction of the intravitreal injections of dexamethasone(Ozurdex), bevacizumab(Avastin), ranibizumab(Lucentis) and aflibercept(EYLEA), along with the panretinal laser photocoagulation, abandoning former treatment modalities and surgical solution. This manuscript is a review of current literature about RVO with emphasize on the pathophysiology, risk factors and prevention, diagnosis and sub-group categorization and treatments including medical and surgical. Since no official guidelines are available for the treatment of RVO patients, and considering the latest developments in the treatment options, and the variety of follow-up and treatment modalities, this manuscript aims to provide tools and knowledge to guide the physician in treating RVO patients, based on the latest publications from the literature and on several of the patients characteristics.展开更多
Hemophagocytic lymphohistiocytosis(HLH) is a hyperinflammatory syndrome that develops as a primary(familial/hereditary) or secondary(non-familial/hereditary) disease characterized in the majority of the cases by hered...Hemophagocytic lymphohistiocytosis(HLH) is a hyperinflammatory syndrome that develops as a primary(familial/hereditary) or secondary(non-familial/hereditary) disease characterized in the majority of the cases by hereditary or acquired impaired cytotoxic T-cell(CTL) and natural killer responses. The molecular mechanisms underlying impaired immune homeostasis have been clarified, particularly for primary diseases. Familial HLH(familial hemophagocytic lymphohistiocytosis type 2-5, Chediak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2) develops due to a defect in lytic granule exocytosis, impairment of(signaling lymphocytic activation molecule)-associated protein, which plays a key role in CTL activity [e.g., X-linked lymphoproliferative syndrome(XLP) 1], or impairment of X-linked inhibitor of apoptosis, a potent regulator of lymphocyte homeostasis(e.g., XLP2). The development of primary HLH is often triggered by infections, but not in all. Secondary HLH develops in association with infection, autoimmune diseases/rheumatological conditions and malignancy. The molecular mechanisms involved in secondary HLH cases remain unknown and the pathophysiology is not the same as primary HLH. For either primary or secondary HLH cases, immunosuppressive therapy should be given to control the hypercytokinemia with steroids, cyclosporine A, or intravenous immune globulin, and if primary HLH is diagnosed, immunochemotherapy with a regimen containing etoposide or anti-thymocyte globulin should be started. Thereafter, allogeneic hematopoietic stem-cell transplantation is recommended for primary HLH or secondary refractory disease(especially EBVHLH).展开更多
Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the p...Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the past decades,these infections have proven to be a significant challenge to health systems worldwide,particularly following the considerable geographic expansion of the dengue virus(DENV)and its most recent outbreak in Latin America as well as the difficult-tocontrol outbreaks of yellow fever virus(YFV),chikungunya virus(CHIKV),and Zika virus(ZIKV),leaving behind a substantial portion of the population with complications related to these infections.Currently,the world is experiencing a period of intense globalization,which,combined with global warming,directly contributes to wider dissemination of arbovirus vectors across the globe.Consequently,all continents remain on high alert for potential new outbreaks.Thus,this review aims to provide a comprehensive understanding of the pathogenesis of the four main arboviruses today(DENV,ZIKV,YFV,and CHIKV)discussing their viral characteristics,immune responses,and mechanisms of viral evasion,as well as important clinical aspects for patient management.This includes associated symptoms,laboratory tests,treatments,existing or developing vaccines and the main associated complications,thus integrating a broad historical,scientific and clinical approach.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
基金supported by the National Natural Science Foundation of China,No.32130060(to XG).
文摘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.
基金Supported by National Natural Science Foundation of China,No.32060182Qiannan Prefecture Science and Technology Plan Project in China:Qiannan Kehe She Zi[2022]No.1.
文摘Gestational diabetes mellitus(GDM)refers to varying degrees of abnormal glucose metabolism that occur during pregnancy and excludes patients pre-viously diagnosed with diabetes.GDM is a unique among the four subtypes of diabetes classified by the international World Health Organization standards.Although GDM patients constitute a small proportion of the total number of diabetes cases,the incidence of GDM has risen significantly over the past decade,posing substantial risk to pregnant women and infants.Therefore,it warrants considerable attention.The pathogenesis of GDM is generally considered to resemble that of type II diabetes,though it may have distinct characteristics.Analyzing blood biochemical proteins in the context of GDM can help elucidate its pathogenesis,thereby facilitating more effective prevention and management strategies.This article reviews this critical clinical issue to enhance the medical community's sufficient understanding of GDM.
基金supported by the Project of the 940 Hospital of the Joint Logistics Support Force of the Chinese PLA(no.2021yxky057).
文摘Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.
文摘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.
文摘This review focuses on research findings in the area of diagnosis and pathogenesis of hepatitis C virus(HCV)infection over the last few decades.The information based on published literature provides an update on these two aspects of HCV.HCV infection,previously called blood transmitted non-A,non-B infection,is prevalent globally and poses a serious public health problem worldwide.The diagnosis of HCV infection has evolved from serodetection of non-specific and low avidity anti-HCV antibodies to detection of viral nucleic acid in serum using the polymerase chain reaction(PCR)technique.Current PCR assays detect viral nucleic acid with high accuracy and the exact copy number of viral particles.Moreover,multiplex assays using real-time PCR are available for identification of HCV-genotypes and their isotypes.In contrast to previous methods,the newly developed assays are not only fast and eco-nomic,but also resolve the problem of the window period as well as differentiate present from past infection.HCV is a non-cytopathic virus,thus,its pathogenesis is regulated by host immunity and metabolic changes including oxidative stress,insulin resistance and hepatic steatosis.Both innate and adaptive immunity play an important role in HCV pathogenesis.Cytotoxic lymphocytes demonstrate crucial activity during viral eradication or viral persistence and are influenced by viral proteins,HCV-quasispecies and several metabolic factors regulating liver metabolism.HCV pathogenesis is a very complex phenomenon and requires further study to determine the other factors involved.
文摘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.
文摘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.
基金Yusuf Bayraktar, MD, Gastroenterology Department, Hacettepe University School of Medicine, Ankara, Turkey. bayrak@hacettepe.edu.trTelephone: +90-312-3051712 Fax: +90-312-3051490
文摘Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.
文摘BACKGROUND: Severe acute pancreatitis is a subtype of acute pancreatitis, associated with multiple organ failure and systemic inflammatory response syndrome. In this qualitative review we looked at the principles of pathogenesis, classification and surgical management of severe acute pancreatitis. We also looked at the current shift in paradigm in the management of severe acute pancreatitis since the guideline developed by the British Society of Gastroenterology.DATA SOURCES: Studies published between 1st January 1991 and 31st December 2015 were identified with Pub Med, MEDLINE, EMBASE and Google Scholar online search engines using the following Medical Subject Headings: “acute pancreatitis, necrosis, mortality, pathogenesis, incidence” and the terms “open necrosectomy and minimally invasive necrosectomy”.The National Institute of Clinical Excellence(NICE) Guidelines were also included in our study. Inclusion criteria for our clinical review included established guidelines, randomized controlled trials and non-randomized controlled trials with a follow-up duration of more than 6 weeks.RESULTS: The incidence of severe acute pancreatitis within the UK is significantly rising and pathogenetic theories are still controversial. In developed countries, the most common cause is biliary calculi. The British Society of Gastroenterology,acknowledges the Revised Atlanta criteria for prediction of severity. A newer Determinant-based system has been developed.The principle of surgical management of acute necrotizing pancreatitis requires intensive care management, identifying infection and if indicated, debridement of any infected necrotic area. The current procedures opted for include standard surgical open necrosectomy, endoscopic necrosectomy and minimally invasive necrosectomy. The current paradigm is shifting towards a step-up approach.CONCLUSIONS: Severe acute pancreatitis is still a subject of grey areas in its surgical management even though new studies have been recorded since the origin of the latest UK guidelines for management of severe acute pancreatitis.
文摘Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion,and ocular ischemic syndrome. Uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and likely predominant agent involved in the pathogenesis of intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis and neovascular glaucoma is divided into four stages: prerubeosis, preglaucoma, open angle glaucoma, and angle-closure glaucoma.
基金support from the National Natural Science Foundation of China(projectNo.81970029)the Fundamental Research Funds for the Central Universities of China(TheEmergency Projects on COVID-19.project No.xzy032020042)。
文摘Coronavirus disease 2019(COVID-19)is a kind of viral pneumonia which is caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The emergence of SARS-CoV-2 has been marked as the third introduction of a highly pathogenic coronavirus into the human population after the severe acute respiratory syndrome coronavirus(SARS-CoV)and the Middle East respiratory syndrome coro-navirus(MERS-CoV)in the twenty-first century.In this minireview,we provide a brief introduction of the general features of SARS-CoV-2 and discuss current knowledge of molecular immune pathogenesis,diagnosis and treatment of COVID-19 on the base of the present understanding of SARS-CoV and MERS-CoV infections,which may be helpful in offering novel insights and potential therapeutic targets for combating the SARS-CoV-2 infection.
文摘Patients with inflammatory bowel disease(IBD)are at increased risk for developing colorectal cancer(CRC),although the overall incidence of IBD-associated CRC has been diminishing in recent decades in western countries.As demonstrated in previous studies,the risk of CRC in IBD increases with longer duration,extent of colitis,a familial history of CRC,coexistent primary sclerosing cholangitis,and the degree of inflammation.The pathogenesis of CRC in IBD is poorly understood.Similar to sporadic CRC,IBD-associated CRC is a consequence of sequential episodes of genomic alteration.Multiple inter-related pathways,including immune response by mucosal inflammatory mediators,oxidative stress,and intestinal microbiota,are also involved the pathogenesis of IBD-associated CRC.Continuing colonic inflammation appears to be a factor in the development of CRC;therefore,anti-inflammatory agents such as5-aminosalicylate compounds and immune modulators have been considered as potential chemopreventive agents.Colonoscopic surveillance is widely accepted as being effective in reducing the risk of IBD-associated CRC,although no clear evidence has confirmed that surveillance colonoscopy prolongs survival in patients with extensive colitis.The traditional recommendation has been quadrantic random biopsies throughout the entire colon;however,several guidelines now have endorsed chromoendoscopy with a target biopsy because of increasing diagnostic yields and reduced workloads for endoscopists and pathologists.New technologies such as narrow band imaging,confocal endomicroscopy,and autofluorescence imaging have not yet been confirmed as surveillance strategies in IBD.
文摘Acute recurrent pancreatitis (ARP) refers to a clinical entity characterized by episodes of acute pancreatitis which occurs on more than one occasion. Recurrence of pancreatitis generally occurs in a setting of normal morpho-functional gland, however, an established chronic disease may be found either on the occasion of the first episode of pancreatitis or during the follow-up. The aetiology of ARP can be identified in the majority of patients. Most common causes include common bile duct stones or sludge and bile crystals; sphincter of oddi dysfunction; anatomical ductal variants interfering with pancreatic juice outflow; obstruction of the main pancreatic duct or pancreatico-biliary junction; genetic mutations; alcohol consumption. However, despite diagnostic technologies, the aetiology of ARP still remains unknown in up to 30% of cases: in these cases the term “idiopathic” is used. Because occult bile stone disease and sphincter of oddi dysfunction account for the majority of cases, cholecystectomy, and eventually the endoscopic biliary and/or pancreatic sphincterotomy are curative in most of cases. Endoscopic biliary sphincterotomy appeared to be a curative procedure per se in about 80% of patients. Ursodeoxycholic acid oral treatment alone has also been reported effective for treatment of biliary sludge. In uncertain cases toxin botulin injection may help in identifying some sphincter of oddi dysfunction, but this treatment is not widely used. In the last twenty years, pancreatic endotherapy has been proven effective in cases of recurrent pancreatitis depending on pancreatic ductal obstruction, independently from the cause of obstruction, and has been widely used instead of more aggressive approaches.
文摘Objective:Senile calcific valvular disease of the heart is an endemic valvular heart disease in the elderly patients. The disease is mainly characterized by degenerative change, thickening, fibrosis and calcification of the valvular connective tissue, which leads to the dysfunction of the valve and its stent. The pathogenesis of calcified valvular heart disease has not been fully elucidated, and it may be related to hemodynamics, atherosclerosis and sex. Echocardiography is the basic method and important basis for clinical diagnosis of calcified valvular heart disease, and it might detect the valvular thickening or calcification. This article aimed to analyze the pathogenesis of senile calcified valvular heart disease. At the same time, this research tried to review the progress on ultrasonic diagnosis of senile calcified valvular heart disease in order to provide references for clinical diagnosis and treatment.
基金National natural science foundation of China(No.81774247)
文摘Chronic total occlusive disease of the coronary artery belongs to the category of"chest palsy"and"true heart pain"in traditional Chinese medicine.Its etiology has two aspects:deficiency of blood,blood stasis,qi stagnation,and phlegm.Failure can be caused by deficiency or disease.The pathogenesis of this disease is caused by obstruction of the heart pulse,and its pathogenesis can be transformed into each other.The theory of traditional Chinese medicine believes that the general rule is not painful.Therefore,the treatment of coronary CTO lesions should be based on the combination of Tong and Tong tonic.The chronic complete occlusive disease of the coronary artery can be treated through Xuanbi Tongyang,Huoxue Tongluo,and Aroma Wentong.Based on the Chinese medicine's understanding of the etiology and pathogenesis of coronary CTO lesions,it provides a basis for the diagnosis and treatment of traditional Chinese medicine,solves the problems of interventional medicine in western medicine,and gives play to the unique advantages of traditional Chinese medicine for clinical diagnosis and treatment.
文摘Contact dermatitis(CD) is the most common professional skin disease, with frequencies ranging from 24 to 170 every 100000 individuals. Approximately 20% of the United States population suffers from CD. CD can be classified according to its origin and severity. ICD stands for irritant CD, whereas ACD means allergic CD. Their clinical presentation includes acute, sub-acute and chronic eczema. Despite their different origin, ICD and ACD often present similar clinical and histologic findings. The current gold standard for diagnosis is patchtesting. However, patch-testing is being questioned in terms of validity and reproducibility, as it relies heavily on the skill of the observer. Real-time reflectance confocal microscopy is a non-invasive imaging technique that bears strong promise for the study of CD, and it enables the evaluation of cellular and subcellular changes over time with similar resolution compared to that of conventional histology.
文摘Retinal vein occlusion(RVO) is the second vascular retinal cause of visual loss and defined by the occlusion of a retinal vein. It is divided into branch retinal vein occlusion or central retinal vein occlusion, depending on the location of occlusion. RVO has severe medical, financial and social implications on the patients. The diagnosis of the disease is easier nowadays with the use of spectral domain optical coherence tomography and fluorescein angiography. The treatment options for RVO have changed dramatically over the past few years with the introduction of the intravitreal injections of dexamethasone(Ozurdex), bevacizumab(Avastin), ranibizumab(Lucentis) and aflibercept(EYLEA), along with the panretinal laser photocoagulation, abandoning former treatment modalities and surgical solution. This manuscript is a review of current literature about RVO with emphasize on the pathophysiology, risk factors and prevention, diagnosis and sub-group categorization and treatments including medical and surgical. Since no official guidelines are available for the treatment of RVO patients, and considering the latest developments in the treatment options, and the variety of follow-up and treatment modalities, this manuscript aims to provide tools and knowledge to guide the physician in treating RVO patients, based on the latest publications from the literature and on several of the patients characteristics.
文摘Hemophagocytic lymphohistiocytosis(HLH) is a hyperinflammatory syndrome that develops as a primary(familial/hereditary) or secondary(non-familial/hereditary) disease characterized in the majority of the cases by hereditary or acquired impaired cytotoxic T-cell(CTL) and natural killer responses. The molecular mechanisms underlying impaired immune homeostasis have been clarified, particularly for primary diseases. Familial HLH(familial hemophagocytic lymphohistiocytosis type 2-5, Chediak-Higashi syndrome, Griscelli syndrome type 2, Hermansky-Pudlak syndrome type 2) develops due to a defect in lytic granule exocytosis, impairment of(signaling lymphocytic activation molecule)-associated protein, which plays a key role in CTL activity [e.g., X-linked lymphoproliferative syndrome(XLP) 1], or impairment of X-linked inhibitor of apoptosis, a potent regulator of lymphocyte homeostasis(e.g., XLP2). The development of primary HLH is often triggered by infections, but not in all. Secondary HLH develops in association with infection, autoimmune diseases/rheumatological conditions and malignancy. The molecular mechanisms involved in secondary HLH cases remain unknown and the pathophysiology is not the same as primary HLH. For either primary or secondary HLH cases, immunosuppressive therapy should be given to control the hypercytokinemia with steroids, cyclosporine A, or intravenous immune globulin, and if primary HLH is diagnosed, immunochemotherapy with a regimen containing etoposide or anti-thymocyte globulin should be started. Thereafter, allogeneic hematopoietic stem-cell transplantation is recommended for primary HLH or secondary refractory disease(especially EBVHLH).
基金Supported by the Permanecer Program(part of the actions of the Office of Affirmative Actions)Education and Diversity of the Dean of Student Assistance at the Federal University of Bahia(UFBA)and CNPq Research Productivity Fellow.
文摘Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and mortality.Over the past decades,these infections have proven to be a significant challenge to health systems worldwide,particularly following the considerable geographic expansion of the dengue virus(DENV)and its most recent outbreak in Latin America as well as the difficult-tocontrol outbreaks of yellow fever virus(YFV),chikungunya virus(CHIKV),and Zika virus(ZIKV),leaving behind a substantial portion of the population with complications related to these infections.Currently,the world is experiencing a period of intense globalization,which,combined with global warming,directly contributes to wider dissemination of arbovirus vectors across the globe.Consequently,all continents remain on high alert for potential new outbreaks.Thus,this review aims to provide a comprehensive understanding of the pathogenesis of the four main arboviruses today(DENV,ZIKV,YFV,and CHIKV)discussing their viral characteristics,immune responses,and mechanisms of viral evasion,as well as important clinical aspects for patient management.This includes associated symptoms,laboratory tests,treatments,existing or developing vaccines and the main associated complications,thus integrating a broad historical,scientific and clinical approach.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.