简介：AbstractDesmoplakin (DSP), encoded by the DSP gene, is the main desmosome component and is abundant in the myocardial tissue. There are three DSP isoforms that assume the role of supporting structural stability through intercellular adhesion. It has been found that DSP regulates the transcription of adipogenic and fibrogenic genes, and maintains appropriate electrical conductivity by regulating gap junctions and ion channels. DSP is essential for normal myocardial development and the maintenance of its structural functions. Studies have suggested that DSP gene mutations are associated with a variety of hereditary cardiomyopathy, such as arrhythmia cardiomyopathy, dilated cardiomyopathy (DCM), left ventricular noncompaction, and is also closely associated with the Carvajal syndrome, Naxos disease, and erythro-keratodermia-cardiomyopathy syndrome with skin and heart damage. The structure and function of DSP, as well as the clinical manifestations of DSP-related cardiomyopathy were reviewed in this article.

简介：“Forcedlearning”referstothefactinChinathatsomestudentsareforcedtolearnbyparentsandteachers,regardlessoftheirownwishes.Sometimes,someparentsandteachersevenforcestudentstolearnthroughdisciplinaryactions.Specifically,studentsareimposedinthefollowingfouraspectsbyparentsandteachers:learningtime,learningcontents,learningfrequency,andlearningdifficulty,soitcausedbadconsequencesthatsomestudents’studytooktoomuchtime,coveredexcesscontents,isrepeatedtoomuchandistoodifficult.“Forcinglearning”destroyedthenatureofstudents,overdrewstudents’potential,andharmedstudents’physicalandmentalhealth.Inordertochangethisexistingsituationof“forcedlearning”,parentsandteachersshouldclarifythenatureofknowledgeandbroadenthewaystudentsacquireknowledge,activatestudents’innerstudymotive,andguidethemtolearnconsciouslyandactively,createaharmoniouseducationalenvironment,andmakefulluseofstudents’“children”nature;parentsandteachersstrengthencooperationtogivestudentsscientificguidanceonpsychology,emotion,andlearning.

简介：AbstractAutoimmune diseases with hematological manifestations are often characterized by chronicity and relapses despite treatment, and the underlying pathogenetic mechanisms remain unknown. Epigenetic alterations play a vital role in the deregulation of immune tolerance and the development of autoimmune diseases. In recent years, study of epigenetic mechanisms in both adult and childhood autoimmune disorders has been seeking to explain the pathophysiology of these heterogeneous diseases and to elucidate the interaction between genetic and environmental factors. Various mechanisms, including DNA methylation, histone modifications (chromatin remodeling), and noncoding RNAs (ncRNAs), have been studied extensively in the context of autoimmune diseases. This paper summarizes the epigenetic patterns in some of the most common childhood autoimmune disorders with hematological manifestations, based on epigenetic studies in children with primary immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), and juvenile idiopathic arthritis (JIA). Research findings indicate that methylation changes in genes expressed on T cells, modifications at a variety of histone sites, and alterations in the expression of several ncRNAs are involved in the pathogenesis of these diseases. These mechanisms not only determine the development of these diseases but also affect the severity of the clinical presentation and biochemical markers. Further studies will provide new tools for the prevention and diagnosis of childhood autoimmune disorders, and possible novel treatment options.

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简介：Multiplesclerosis(MS)isachronicimmune-mediatedinnammatory-demyelinatingdisorderofthecentralnervoussystem,withastrongneurodegenerativecomponent.ThequestionwhetherneurodegenerationinMSisindependentorrelatedtoneuroinflammationhasbeenlongdebated,butnotyetfullyclarified.Furthermore,littleisstillknownonhowneuroinflammationandneurodegenerationinMSarerelatedtopotentialregenerativeprocesses.Inthisperspective,webrieflydiscussmainclinical,pathologicalandexperimentalevidenceontherelationshipbetweenneuroinflammationandneurodegenerationinMS,andontheirconnectionwithregeneration.WediscussthattheseprocessesinMSmightrepresentintercorrelatedmanifestationsoftheimmuneresponse,especiallyoftheinnateimmunity.

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简介：AbstractAdult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell lymphoma caused by the human T lymphotropic virus type-1. The skin is affected in approximately half of ATLL patients, and skin lesions may be the first manifestation of the disease. The skin lesions of ATLL are polymorphous, and depend on the type of skin eruption, which makes it possible for doctors to predict the prognosis of the disease based on the characteristics of skin lesions. In this review article, we describe the clinical manifestations and histopathological patterns of skin lesions in ATLL, focus on its diagnostic and prognostic significance, and also summarize the advances in the treatment of ATLL.

简介：Nonceliacglutensensitivity(NCGS)isasyndromecharacterizedbyacohortofsymptomsrelatedtotheingestionofgluten-containingfoodinsubjectswhoarenotaffectedbyceliacdisease(CD)orwheatallergy.Thepossibilityofsystemicmanifestationsinthisconditionhasbeensuggestedbysomereports.Inmostcasestheyarecharacterizedbyvaguesymptomssuchas‘foggymind’,headache,fatigue,jointandmusclepain,legorarmnumbnessevenifmorespecificcomplaintshavebeendescribed.NCGShasanimmune-relatedbackground.IndeedthereisastrongevidencethataselectiveactivationofinnateimmunitymaybethetriggerforNCGSinflammatoryresponse.ThemostcommonlyautoimmunedisordersassociatedtoNCGSareHashimotothyroiditis,dermatitisherpetiformis,psoriasisandrheumatologicdiseases.ThepredominanceofHashimotothyroiditisrepresentsaninterestingfinding,sinceithasbeenindirectlyconfirmedbyanItalianstudy,showingthatautoimmunethyroiddiseaseisariskfactorfortheevolutiontowardsNCGSinagroupofpatientswithminimalduodenalinflammation.Onthesebases,anautoimmunestigmainNCGSisstronglysupported;itcouldbeacharacteristicfeaturethatcouldhelpthediagnosisandbesimultaneouslymanaged.ApossibleneurologicalinvolvementhasbeenunderlinedbyNCGSassociationwithglutenataxia,glutenneuropathyandglutenencephalopathy.NCGSpatientsmayshowevenpsychiatricdiseasessuchasdepression,anxietyandpsychosis.Finally,alinkwithfunctionaldisorders(irritablebowelsyndromeandfibromyalgia)isatopicunderdiscussion.Inconclusion,thenoveltyofthismatterhasgeneratedanexpansionofliteraturedatawiththeunavoidableconsequencethatsomereportsareoftenbasedonlowlevelsofevidence.Therefore,onlystudiesperformedonlargesampleswiththeinclusionofcontrolgroupswillbeabletoclearlyestablishwhetherthelargeinformationfromtheliteratureregardingextra-intestinalNCGSmanifestationscouldbesupportedbyevidence-basedagreements.

简介：AbstractThe common cerebral small vessel disease (CSVD) neuroimaging features visible on conventional structural magnetic resonance imaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. The CSVD neuroimaging features have shared and distinct clinical consequences, and the automatic quantification methods for these features are increasingly used in research and clinical settings. This review article explores the recent progress in CSVD neuroimaging feature quantification and provides an overview of the clinical consequences of these CSVD features as well as the possibilities of using these features as endpoints in clinical trials. The added value of CSVD neuroimaging quantification is also discussed for researches focused on the mechanism of CSVD and the prognosis in subjects with CSVD.

简介：AbstractObjective:Skin diseases are common and striking features of patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and may vary considerably by ethnic and geographic regions and by the influence of highly active antiretroviral therapy (HAART). However, little information exists regarding the cutaneous manifestations of patients with HIV/AIDS in Bangladesh. This study was performed to elucidate the spectrum of cutaneous disorders in patients with HIV/AIDS in the era of HAART.Materials:This descriptive cross-sectional study was carried out in Chittagong Medical College Hospital, Bangladesh from January 2017 and December 2020. Diagnosed case of HIV/AIDS for HAART therapy and all cases of HIV/AIDS who are already on HAART therapy were included in this study. Descriptive statistical analysis was carried out by using frequencies and percentages.Results:Of 40 patients with HIV/AIDS, 22 (55.0%) were male and 18 (45.0%) were female. The patients ranged in age from 8 to 60 years, with a mean age of 38 ± 0.966 years. Among all age groups, the highest 19 (47.5%) patients were in the 31- to 40-year age group. Most of the patients were migrant workers [22/40 (55.0%)] with low socioeconomic status [32/40 (80.0%)], and the most common transmission mode was heterosexual activity [36/40 (90.0%)]. Most of the patients [32/40 (80.0%)] had mucocutaneous disorders, 30/40 (75.0%) had infective dermatoses, and 21/40 (52.5%) had non-infective inflammatory dermatoses. Eight of forty (20.0%) patients presented with three or more skin disorders. The most common infective dermatoses were fungal infections [15/40 (37.5%)], followed by viral infections [8/40 (20.0%)], bacterial infections [4/40 (10.0%)], and scabies [3/40 (7.5%)]. The most common non-infective dermatosis was generalized pruritus [6/40 (15.0%)], followed by prurigo simplex [4/40 (10.0%)], psoriasis [4/40 (10.0%)], eczema [3/40 (7.5%)], pruritic papular eruption [1/40 (2.5%)], seborrheic dermatitis [1/40 (2.5%)], urticaria [1/40 (2.5%)], and xerosis [1/40 (2.5%)]. Patients treated with HAART had decreased rates of oral candidiasis and herpes simplex but increased rates of drug reactions [19/40 (47.5%)]. The most common drug eruption following HAART was a morbilliform rash [11/40 (27.5%)], and the most common offending agent was nevirapine. The prevalence of mucocutaneous disorders was higher in patients with a CD4 cell count of <200 cells/mm3.Conclusions:A wide range of mucocutaneous disorders is observed in Bangladeshi patients with HIV/AIDS, and HAART has an impact on the spectrum of HIV/AIDS-associated mucocutaneous disorders. Skin and mucocutaneous disorders are seen at every stage of HIV/AIDS and are the initial presentation in most patients in Bangladesh. There is a need for increased attention to the diagnosis and treatment of skin diseases affecting the quality of life of patients with HIV/AIDS.

简介：AbstractIntroduction:Langerhans cell histiocytosis (LCH), the most common histiocytic disorder, characterized by the abnormal over production of histiocytes that tend to infiltrate single or multiple organ systems leading to significant tissue damage.Here we report a case of an adult patient who was diagnosed with LCH presenting as multisystem involvement.Case presentation:We describe a 23-year-old man suffering from central diabetes insipidus, "hemorrhoids", progressive hearing loss and a surge in weight. Physical examination revealed lesion involvement of the skin and mucous membranes, including the perianal area, gingiva, and external auditory canal. He was diagnosed as LCH, who achieved remission following a chemotherapy regimen.Discussion:LCH is common in children, but it is not surprising to see it in adults. The clinical manifestations of LCH are highly variable and may involve multiple organs and systems. While, skin involvement is the most obvious symptom, and dermatologists should be familiar with it. Chemotherapy is the first-line treatment for multisystem or multifocal single system adult LCH.Conclusion:Characteristic features of LCH involving the perianal area was described in this case which helped the dermatologist to make quick judgments. We also emphasize that a global concept should be established confronting with a patient with multiple complaints.

简介：AbstractIn malaria-endemic regions, people often get exposed to various pathogens simultaneously, generating co-infection scenarios. In such scenarios, overlapping symptoms pose serious diagnostic challenges. The delayed diagnosis may lead to an increase in disease severity and catastrophic events. Recent coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected various areas globally, including malaria-endemic regions. The Plasmodium and SARS-CoV-2 co-infection and its effect on health are yet unexplored. We present a case report of a previously healthy, middle-aged individual from the malaria-endemic area who suffered SARS-CoV-2 and Plasmodium falciparum co-infection. The patient developed severe disease indications in a short time period. The patient showed neurological symptoms, altered hematological as well as liver-test parameters, and subsequent death in a narrow time span. We hereby discuss the various aspects of this case regarding treatment and hematological parameters. Further, we have put forward perspectives related to the mechanism behind severity and neurological symptoms in this fatal parasite-virus co-infection case. In malaria-endemic regions, due to overlapping symptoms, suspected COVID-19 patients should also be monitored for diagnosis of malaria without any delay. The SARS-CoV-2 and Plasmodium co-infection could increase the disease severity in a short time span. In treatment, dexamethasone may not help in severe cases having malaria as well as COVID-19 positive status and needs further exploration.

简介：AbstractImportance:The Coronavirus disease 2019 (COVID-19) global pandemic poses a considerable challenge for pediatricians.Objective:This study aimed to identify the epidemiological characteristics and clinical features of pediatric patients with COVID-19 in China.Methods:This multicenter retrospective study included pediatric patients from 46 hospitals in China, covering 12 provinces and two municipalities. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were analyzed.Results:In total, 211 pediatric patients with COVID-19 were included in this study. The median age was 7.0 years (range: 22 days to 18 years). Approximately 16.3% of the patients exhibited asymptomatic infections, 23.0% had upper respiratory tract infections, and 60.7% had pneumonia, including two with severe pneumonia and one with critical illness. Approximately 78.7% of the pediatric patients occurred in familial clusters. The most three common symptoms or signs at onset in children with COVID-19 were fever (54.5%), cough (49.3%), and pharyngeal congestion (20.8%). Only 17.6% of the patients presented with decreased lymphocyte count, whereas 13.6% had increased lymphocyte count. Among the patients with pneumonia who exhibited abnormal chest computed tomography findings, 18.2% (23/127) of the patients had no other symptoms. Generally, the chest radiographs showed abnormalities that affected both lungs (49.6%); ground-glass opacity (47.2%) was the most common manifestation. The cure and improvement rates were 86.7% (183/211) and 13.3% (28/211), respectively. Only one patient with an underlying condition received invasive mechanical ventilation; none of the patients died.Interpretation:Similar to adults, children of all age groups are susceptible to COVID-19. Fortunately, most pediatric patients have mild symptoms or remain asymptomatic, despite the high incidence of pneumonia. Decreased proportions of white blood cells and lymphocytes are less frequent in children than in adults.

简介：AbstractBackground:IgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease.Case presentation:Two ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave's disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.Conclusions:A high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

简介：AbstractBackground:IgG4-related hypertrophic pachymeningitis is a relative newly recognized and rare manifestation of IgG4-related disease, an immune-mediated fibroinflammatory tumefactive disorder. Fewer than 80 patients have been reported in the literature, and it can mimic common neurosurgical conditions. We describe the clinical presentation of two patients that were initially considered to have a subdural collection, tuberculous meningitis, and a cervical spinal meningioma, but were eventually diagnosed with this disease.Case presentation:Two ethnic Chinese men, 86 and 62 years old, experienced a 4-week history of headache. Both patients had a history of autoimmune disease, namely glomerulonephritis and Grave's disease, respectively. Magnetic resonance brain imaging revealed diffuse dural thickening with the latter patient exhibiting homogeneous and intense gadolinium-contrast enhancement. Since the 86-year-old patient also had progressive bilateral visual loss, giant cell arteritis was suspected and a 2-week course of glucocorticoid therapy was prescribed, but his symptoms failed to improve. The 62-year-old patient also had accompanying low-grade fever and was treated empirically as having tuberculous meningitis although there were no confirmatory microbiological findings. This patient further developed right hemiparesis, and additional imaging revealed a C4/5 intradural-extramedullary contrast-enhancing lesion resembling a meningioma causing cord compression. Both patients underwent neurosurgical intervention with the former undergoing a dural biopsy and the latter having the cervical lesion resected. The final diagnosis was IgG4-related hypertrophic pachymeningitis with the hallmark histological features of lymphoplasmacytic infiltration of IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. In addition, their serum IgG4 levels were elevated (i.e., > 135 mg/dL). Both patients received at least 6 months of glucocorticoid therapy while the latter also had azathioprine. Their symptoms improved significantly and recurrent lesions were not detected on follow-up imaging.Conclusions:A high index of suspicion for this condition is suggested when a male patient with a history of autoimmune disease and compatible radiological findings, experiences subacute headache that is disproportionate to the degree of dural involvement. Neurosurgeons should consider early meningeal biopsy to establish a definitive histological diagnosis in order for early effective immunosuppressive treatment to be initiated and to avoid unnecessary morbidity.

简介：AbstractIntroduction:The gap junction beta 6 (GJB6) gene encodes connexin 30. This protein plays critical role in tissues and is responsible for the formation of gap junctions, which have a wide variety of physiological functions. Disease-associated variants of GJB6 cause non-syndromic hearing loss (HL) and skin lesions.We herein describe a Turkish girl who was diagnosed with HL and in whom genetic analysis revealed a causal variant of GJB6.Case presentation:The 1-year-old girl patient was diagnosed with bilateral HL when she was 1 month old. Apart from this, the patient’s motor/mental development and physical examination were normal. As a result of the analysis with the multi-gene panel, the causative genomic change, c.175G>A(p.Gly59Arg) in the GJB6 gene was determined as heterozygous. Segregation analysis proved the same genotype in the patient’s mother and grandfather. The patient’s mother and grandfather had bilateral HL and palmoplantar hyperkeratosis phenotype. The patient was diagnosed with Clouston syndrome, and genetic counseling was provided to her family.Discussion:Causal variants of GJB6 cause skin manifestations and signs of HL. Molecular diagnosis of these patients is a valuable tool for clinicians in reaching their optimal treatment and clinical management.Conclusion:In syndromic cases in which many organs are affected, the determination of the causative gene is important in directing the patients to appropriate observation, screening, and treatment strategies.

简介：AbstractImportance:The phenotypes of ATP1A3 gene mutations are diverse. Relapsing encephalopathy with cerebellar ataxia and fever-induced paroxysmal weakness and encephalopathy (FIPWE) are considered non-classical phenotypes caused by p.Arg756 mutations of ATP1A3.Objective:To summarize the clinical manifestations, treatment, and follow-up of Chinese patients with p.Arg756 mutations of ATP1A3.Methods:We analyzed the clinical features, treatment, and genotypes of eight children with p.Arg756 mutations of ATP1A3 who were treated in Beijing Children’s Hospital from January 2014 to December 2019.Results:Eight patients (six boys and two girls) were included; seven had been misdiagnosed with encephalitis. The age of onset ranged from 0.8 to 4.5 years. All patients had encephalopathy and had at least one episode of FIPWE. Cerebellar ataxia was present in nine episodes. Reversible splenial lesions of the corpus callosum were found in two patients in the acute phase. Three types of heterozygous ATP1A3 mutations were found: c.2267G > T (p.R756L) (patient 3 [P3]), c.2266C > T (p.R756C) (P2 and P4), and c.2267G > A (p.R756H) (P1, P5, P6, P7, and P8). Six mutations were de novo; two mutations were inherited. Both patients with p.R756C and one patient (P7) with p.R756H had four episodes of severe ataxia as the main manifestations. However, in the other three episodes, limb weakness was more prominent than ataxia. P5 with p.R756H exhibited overlap with FIPWE and rapid-onset dystonia-parkinsonism.Interpretation:Acute encephalopathy followed by febrile disease was characteristic of the disease in patients with p.Arg756 mutations of ATP1A3. However, the weakness and ataxia were variable. Phenotypic crossover and overlap were observed among these patients.

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