Japanese encephalitis(JE),a vector-borne disease caused by the Japanese encephalitis virus(JEV),remains a major public health concern in South and Southeast Asia[1].JEV,a Flaviviridae family virus,is primarily transmi...Japanese encephalitis(JE),a vector-borne disease caused by the Japanese encephalitis virus(JEV),remains a major public health concern in South and Southeast Asia[1].JEV,a Flaviviridae family virus,is primarily transmitted by Culex mosquitoes,especially the Culex vishnui subgroup,which breeds extensively in rice fields[1].Birds(Ardeidae family)act as natural reservoirs,while pigs serve as amplifying hosts,and humans are incidental hosts[1].展开更多
BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impa...BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.展开更多
Nipah is a deadly viral infection which has come to the news highlight recently,due to its fresh onslaught in Southern India.As the world continues to recover from coronavirus disease 2019,the World Health Organizatio...Nipah is a deadly viral infection which has come to the news highlight recently,due to its fresh onslaught in Southern India.As the world continues to recover from coronavirus disease 2019,the World Health Organization has identified a list of high-priority pathogens with the potential to cause future pandemics.Among them is the Nipah virus(NiV),which poses a significant threat.Even a small out-break could trigger widespread panic among the public.The emergence and re-emergence of NiV among other zoonotic infections is a stern reminder of the im-portance of One health concept.展开更多
BACKGROUND Acyclovir(ACV)-resistant herpes simplex virus(HSV)strains have emerged and gradually increased in number.Prolonged treatment,such as for immunocompromised patients,has been observed on many occasions to lea...BACKGROUND Acyclovir(ACV)-resistant herpes simplex virus(HSV)strains have emerged and gradually increased in number.Prolonged treatment,such as for immunocompromised patients,has been observed on many occasions to lead to the development of resistance.Additionally,some strains of HSV exist that are ACV resistant,and they can cause severe complications that may be impossible to treat with current therapies.We report the first case of ACV-resistant herpes encephalitis(ARHE)recurring in an immunocompromised adult patient without neurosurgical intervention.CASE SUMMARY A 58-year-old man with a fever of 38°C had tremors.Evaluation revealed 14 points on the Glasgow Coma Scale with 39°C fever but unremarkable physical examination.Diagnosis was infection of unknown origin;fever continued,and the Glasgow Coma Scale worsened to 8.Imaging showing a high-intensity area between the left temporal lobe and insular cortex suggested herpes encephalitis.ACV was started.Cerebrospinal fluid(CSF)was positive for HSV DNA,confirming the diagnosis.However,unresolved symptoms suggested ARHE;therefore,we initiated vidarabine treatment.Later testing confirmed ARHE.Foscarnet was started based on a hospital day 25 blood test revealing pancytopenia,possibly from vidarabine.Consciousness improved,and the patient moved to rehabilitation.However,symptoms worsened,suggesting recurrence.Diffusion-weighted magnetic resonance imaging revealed a high high-intensity area around the right temporal lobe;CSF was positive for HSV DNA,confirming recurrent herpes encephalitis.ACV and foscarnet were initiated.Fever decreased,consciousness improved,and HSV DNA on hospital days 78 and 93 was CSF negative.Treatment was terminated on hospital day 86.CONCLUSION ARHE recurred in the patient following remission;therefore,it is necessary to discuss the length of the treatment period.展开更多
Addressing the challenges of difficult early diagnosis and the incomplete prognosis evaluation system for Autoimmune Encephalitis(AE),this study comprehensively reviews the relevant indicators for early diagnosis and ...Addressing the challenges of difficult early diagnosis and the incomplete prognosis evaluation system for Autoimmune Encephalitis(AE),this study comprehensively reviews the relevant indicators for early diagnosis and prognosis evaluation of AE.The analysis reveals that multiple indicators currently exhibit unique value in the diagnosis and treatment of AE,but each has its limitations.This article aims to systematically review these indicators and clarify their current application in clinical practice,to help improve the accuracy of early diagnosis and prognosis evaluation of AE,and provide a theoretical basis for clinicians to develop more effective treatment strategies.展开更多
The Chandipura vesiculovirus(CHPV),a single-stranded,negative sense RNA arbovirus with five structural proteins-the G,N,M,P,and L proteins-is the source of Chandipura virus infection.Children between the ages of 9 mon...The Chandipura vesiculovirus(CHPV),a single-stranded,negative sense RNA arbovirus with five structural proteins-the G,N,M,P,and L proteins-is the source of Chandipura virus infection.Children between the ages of 9 months and 14 years old are the most common recipients of CHPV infection,which is primarily spread by sand flies(Sergentomyia,Phlebotomus species).The potential advantages of black seeds(N.sativa)in the treatment of patients with CHPV infection are the main topic of our current review.The majority of patients infected with CHPV experience neurological complications such as encephalitis and other neurological complications.Since there is currently no approved antiviral treatment,supportive care and symptomatic therapy are the primary methods used to manage CHPV-infected patients.Herbal candidates possessing antioxidant,immunomodulatory,antiviral,and anti-inflammatory qualities may aid in the treatment of CHPV infection.The antiviral,anti-inflammatory,antioxidant,and immunomodulatory qualities of black seeds(N.sativa)have been shown in a number of preclinical and clinical investigations;these attributes could be helpful in the treatment of CHPV infection.Black seeds(N.sativa)may help treat CHPV-infected patients in the early stages of their illness when used in conjunction with symptomatic therapy and supportive care.In patients infected with CHPV,additional randomized controlled clinical trials would assess the efficacy and safety of black seeds(N.sativa).展开更多
The Japanese encephalitis virus(JEV)causes Japanese encephalitis(JE),a severe disease that primarily affects children and induces significant central nervous system complications.With the widespread adoption of vaccin...The Japanese encephalitis virus(JEV)causes Japanese encephalitis(JE),a severe disease that primarily affects children and induces significant central nervous system complications.With the widespread adoption of vaccination in children,the incidence among older individuals has increased substantially.Despite this epidemiological shift,research on JEV infection in the elderly remains limited.We established JEV infection models using both aged and young mice to explore age-related differences in pathology and underlying mechanisms.Brain tissue samples were analyzed for pathological changes and viral tropism in major cell types.To further characterize immune response variations,we conducted transcriptomic sequencing on the brain tissues following JEV infection.Aged mice exhibited lower mortality,delayed disease progression,and milder brain pathology compared to young mice after JEV infection.Viral titers and infection rates of major brain cell types were similar in both groups.Transcriptomic analysis revealed diminished immune activation and weaker inflammatory responses in aged mice.Additionally,microglial activation and CD8^(+) T cell function were significantly reduced.Interestingly,JEV infection induced the selective recruitment of B cells in the brains of aged mice.These B cells may modulate the effects of CD8^(+) T cells in the disease process.Compared to young mice,aged mice showed enhanced resistance to JEV progression and reduced brain pathology.This resistance was associated with a weakened immune response in the aged brain,rather than differences in viral infection.The specific recruitment of B cells in the brains of aged mice may play a crucial role in limiting disease progression.展开更多
Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investi...Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant(lineage B.1.351).Methods K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant.Viral replication,pathological phenotypes,and brain transcriptomes were analyzed.Gene Ontology(GO)analysis was performed to identify altered pathways.Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.Results Pathological alterations were observed in the lungs of both mouse strains.However,only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection,accompanied by neuropathological injury and weight loss.GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses,including type I interferons,pro-inflammatory cytokines,Toll-like receptor signaling components,and interferon-stimulated genes.Neuroinflammation was evident,alongside activation of apoptotic and pyroptotic pathways.Furthermore,altered neural cell marker expression suggested viral-induced neuroglial activation,resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.Conclusion These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.展开更多
Objective:To explore the application effect of bundle management in the safe nursing of patients with autoimmune encephalitis.Methods:Seventy-five patients with autoimmune encephalitis who met the inclusion criteria i...Objective:To explore the application effect of bundle management in the safe nursing of patients with autoimmune encephalitis.Methods:Seventy-five patients with autoimmune encephalitis who met the inclusion criteria in our hospital from January 2024 to June 2024 were randomly divided into two groups:an observation group of 39 patients and a control group of 36 patients.The control group received routine nursing care,while the observation group implemented a bundle management strategy based on routine nursing care.Safety nursing outcomes,clinical symptom improvement time,hospital stay,and neurologic function recovery were observed in both groups.Results:The incidence of adverse events in the observation group was 12.82%,significantly lower than the 33.33%in the control group,with a statistically significant difference(P<0.05).There was no statistically significant difference in restraint usage and ICU transfer rates between the two groups(P>0.05).The clinical symptom improvement time,hospital stay,and neurologic function recovery in the observation group were significantly better than those in the control group,with a statistically significant difference(P<0.05).Conclusion:Through the bundle management model,effective connections can be ensured in various aspects of treatment and rehabilitation for patients with autoimmune encephalitis,providing patients with comprehensive and multi-level nursing services and improving their overall satisfaction and treatment effectiveness.展开更多
Western equine encephalitis virus(WEEV)is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas.WEEV binds protocadherin 10(PCDH10)as a receptor,and highly virulent ancestral WE...Western equine encephalitis virus(WEEV)is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas.WEEV binds protocadherin 10(PCDH10)as a receptor,and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor(LDLR)-related proteins.As WEEV declined as a human pathogen in North America over the past century,isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors.To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence,we determined cryoelectron microscopy structures of WEEV bound to human PCDH10,avian PCDH10,and human very-low-density lipoprotein receptor(VLDLR).We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors.A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain.Because WEEV recently re-emerged in South America after decades of inactivity,our findings have important implications for outbreak preparedness.展开更多
BACKGROUND Worldwide,there has been a steady increase in the number of cases of pulmonary cryptococcosis diagnosed in immunocompetent patients,where symptoms can range from mild to severe.Clinical and radiological dis...BACKGROUND Worldwide,there has been a steady increase in the number of cases of pulmonary cryptococcosis diagnosed in immunocompetent patients,where symptoms can range from mild to severe.Clinical and radiological distinction of disease may be made when compared with immunodeficient cases and in those presenting with primary lung carcinoma.In the latter case confusion can lead to initial misdiagnosis and delayed treatment.We report a case of disseminated cryptococcosis in an immunocompetent patient which mimicked a primary lung carcinoma with brain metastases.CASE SUMMARY A 51-year-old male farmer with a 30-year smoking history presented with a twoweek history of productive cough,streaky hemoptysis,and low-grade fever.He had no history of immunosuppression,tuberculosis,or specific risk factors.Chest computed tomography revealed a posterior basal left lower lobe mass,but tumor markers and transbronchial tests were negative.Brain magnetic resonance imaging showed an enhancing left frontal lobe lesion,raising suspicion for metastatic lung cancer.However,computed tomography-guided biopsy confirmed fungal pneumonia with“titan”cells,and a positive serum cryptococcal antigen test confirmed Cryptococcus neoformans infection.Bronchoscopy and lavage detected fungal spores,while cerebrospinal fluid cytology and culture were negative.Fluconazole(0.4 mg/day)was initiated,but progressive central nervous system lesions required amphotericin B.A six-week combination of fluconazole(600 mg/day)and flucytosine led to resolution.At 24-month follow-up,he remained asymptomatic with no recurrence.CONCLUSION Cryptococcosis is increasing in immunocompetent individuals in China and should be considered in pneumonia and lung or brain lesions.展开更多
Tick-borne encephalitis virus(TBEV)is a re-emerging pathogen in Kazakhstan,where the increasing risk of its spread underscores the need for improved healthcare preparedness,including the development of local vaccines....Tick-borne encephalitis virus(TBEV)is a re-emerging pathogen in Kazakhstan,where the increasing risk of its spread underscores the need for improved healthcare preparedness,including the development of local vaccines.However,the absence of reference TBEV strains in the country presented a major challenge.To address this,we generated a prototype strain(Vasilchenko)of the Siberian TBEV genotype,predominant in Kazakhstan,using synthetic genome and molecular infectious clone technology.A DNA-launched TBEV molecular clone was assembled from DNA fragments,enabling virus rescue upon plasmid transfection.During the propagation of the post-transfection virus in cell culture,a single amino acid substitution(E51K)in the envelope protein emerged,resulting in a 100-fold increase in the titer of the mutant variant.In vivo,this mutation significantly attenuated virulence:while wild-type TBEV caused 100%mortality in BALB/c mice,the E51K variant was non-lethal and exhibited reduced viremia,suggesting impaired neuroinvasiveness.To further exploit this attenuated,high-titer virus,we developed a GFP-expressing reporter TBEV variant.Using this reporter system,we demonstrated that favipiravir possesses antiviral activity against TBEV,with inhibitory concentrations within a pharmacologically relevant range.In conclusion,synthetic genomics enabled the generation of a reference TBEV strain to replenish Kazakhstan's collections.The E51K mutation enhances viral replication in vitro while attenuating pathogenicity in vivo,and the derived reporter virus is suitable for antiviral compound screening.展开更多
BACKGROUND Autoimmune encephalitis(AE)is a rare and recently described neuroinflammatory disease associated with specific autoantibodies.Anti-leucine-rich glioma inactivated 1(anti-LGI1)encephalitis is a rare but trea...BACKGROUND Autoimmune encephalitis(AE)is a rare and recently described neuroinflammatory disease associated with specific autoantibodies.Anti-leucine-rich glioma inactivated 1(anti-LGI1)encephalitis is a rare but treatable type of AE discovered in recent years.Alzheimer’s disease(AD)is a degenerative brain disease and the most common cause of dementia.AD may undergo a series of pathological physiological changes in brain tissue 20 years before the onset of typical symptoms.The stage of mild cognitive impairment(MCI)that occurs during this process,known as MCI due to AD,is the earliest stage with clinical symptoms.MCI is typically categorized into two subtypes:Amnestic MCI(aMCI)and non-aMCI.CASE SUMMARY This report describes a patient with rapid cognitive impairment,diagnosed with anti-LGI1 antibody-mediated AE and aMCI,and treated at Peking University Shenzhen Hospital in March 2023.The patient was hospitalized with acute memory decline for more than 3 months.Both the cerebrospinal fluid and serum were positive for anti-LGI1 antibodies,biomarkers of AD coexisting in the patient’s cerebrospinal fluid.Following combination treatment with immunoglobulin therapy and glucocorticoid,plus inhibition of acetylcholinesterase,the patient’s cognitive function significantly improved.Throughout the 3-month follow-up period,a sustained improvement in cognitive function was observed.The results of serum anti-LGI1 antibody were negative.CONCLUSION This case has raised awareness of the possible interaction between AE and early AD(including MCI due to AD),and alerted clinicians to the possibility of concurrent rare and common diseases in patients presenting with cognitive impairment.展开更多
Candida albicans(C.abicans),вcommon pathogenic fungus in nature,has enough cæpity to cause Severe brain infection through various mesns under immunocompromised conditions.Currently,stablishing a basic animal dis...Candida albicans(C.abicans),вcommon pathogenic fungus in nature,has enough cæpity to cause Severe brain infection through various mesns under immunocompromised conditions.Currently,stablishing a basic animal disesse model has become the main rsrch tool,which isconducive to simulat ing fungal encephalitis effectively.However,the widely used bloodbarne infection model established by intravenoOus(I.V)injection in mice usually results in systenic infecions but cannot simulate significant bradn inflammation.Here,we developed&fungal en-cephaltis model by intracerebroventriaular(L.C.V)injection af C.albicansto better simulate the significant harm und consequencEs.Compared with I.V,a greater number of colony-for ming units(CFUa)in the brain was induced following I.CV.Magnetic resonane imaging MRM resulta revesled more obvious inflammatinn in the external capsule area of the brain.Menwhile,be havioral experiments with the Y-meze also indicated that abnormal activity behavior further relected significant short-term mamory impairment after I.C.Vof C.albicans.In summary,these studies not onby provide a novel fungal encephalitis model for understanding the pathogenesis mechanism of this disease but also lay a solid foundation for future effective tretment.展开更多
Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional seve...Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.展开更多
BACKGROUND Acute disseminated encephalomyelitis(ADEM),which is rare,primarily affects children.It usually manifests as acute encephalopathy and multifocal neurological impairments after infection or vaccination.Diagno...BACKGROUND Acute disseminated encephalomyelitis(ADEM),which is rare,primarily affects children.It usually manifests as acute encephalopathy and multifocal neurological impairments after infection or vaccination.Diagnosis is still difficult due to the clinical and radiological similarity to other central nervous system disorders.Adult-onset ADEM calls for thorough reporting in order to improve diagnosis and treatment.CASE SUMMARY A 55-year-old man with hypertension had a high fever,intense headache and a steady decline in his neurological function after two weeks.Left facial paralysis was the initial symptom,which progressed to left hemiparesis,reduced consciousness level,photophobia,phonophobia,vomiting,and a focal seizure in the right leg.He had no history of autoimmune disease,vaccinations,or infections.Investigations showed negative infectious/autoimmune serology,mild cerebrospinal fluid lymphocytic pleocytosis(protein 76 mg/dL),and lymphopenia.Brain magnetic resonance imaging without contrast revealed bilateral,symmetrical T2/fluid-attenuated inversion recovery hyperintensities,primarily in the middle cerebellar peduncles,with minor involvement in the pontine and periventricular regions.Neoplastic,metabolic,vascular,and infectious conditions were not included.The patient showed spontaneous neurological improvement by Week 3 with near-complete motor recovery(limb strength 4/5)after methylprednisolone and rehabilitation,despite logistical delays in starting immunotherapy.The monophasic course and radiological/clinical remission were supported by idiopathic ADEM.CONCLUSION This case shows an uncommon,idiopathic,cerebellar-predominant ADEM variation in an adult without conventional triggers.It emphasizes the diagnostic difficulty in distinguishing ADEM from mimics(such as stroke or infection)in adults.Spontaneous improvement before treatment,although early detection is still crucial,should be highlighted,although early detection is still crucial.Increased clinician awareness,fair access to neuroimaging,and focused research on adult ADEM are crucial to fill these gaps and improve outcomes in places with limited resources.展开更多
文摘Japanese encephalitis(JE),a vector-borne disease caused by the Japanese encephalitis virus(JEV),remains a major public health concern in South and Southeast Asia[1].JEV,a Flaviviridae family virus,is primarily transmitted by Culex mosquitoes,especially the Culex vishnui subgroup,which breeds extensively in rice fields[1].Birds(Ardeidae family)act as natural reservoirs,while pigs serve as amplifying hosts,and humans are incidental hosts[1].
文摘BACKGROUND Paraneoplastic limbic encephalitis(LE)is an inflammatory condition that affects the limbic system,cerebellum,and peripheral nervous system.It causes a range of symptoms including short-term memory loss,impaired cognitive function,behavioral and psychological disorders,and seizures.Paraneoplastic LE can occur when an immune response is activated due to antibodies targeting gammaaminobutyric acid(GABA)B receptor(GABABR)interacting with antigens on tumor cells and the nervous system,resulting in tumors primarily as small cell lung carcinoma(SCLC).CASE SUMMARY We discuss two cases of GABABR antibody-related LE resulting from SCLC.The patients’symptoms were managed with immunotherapy but ended in premature death due to chemotherapy-related complications.CONCLUSION Paraneoplastic syndrome is a notable cause of LE.Early intravenous immunoglobulin therapy may lead to temporary remission.
文摘Nipah is a deadly viral infection which has come to the news highlight recently,due to its fresh onslaught in Southern India.As the world continues to recover from coronavirus disease 2019,the World Health Organization has identified a list of high-priority pathogens with the potential to cause future pandemics.Among them is the Nipah virus(NiV),which poses a significant threat.Even a small out-break could trigger widespread panic among the public.The emergence and re-emergence of NiV among other zoonotic infections is a stern reminder of the im-portance of One health concept.
基金Supported by the Japan Society for the Promotion of Science KAKENHI Grant,No.JP24K15491.
文摘BACKGROUND Acyclovir(ACV)-resistant herpes simplex virus(HSV)strains have emerged and gradually increased in number.Prolonged treatment,such as for immunocompromised patients,has been observed on many occasions to lead to the development of resistance.Additionally,some strains of HSV exist that are ACV resistant,and they can cause severe complications that may be impossible to treat with current therapies.We report the first case of ACV-resistant herpes encephalitis(ARHE)recurring in an immunocompromised adult patient without neurosurgical intervention.CASE SUMMARY A 58-year-old man with a fever of 38°C had tremors.Evaluation revealed 14 points on the Glasgow Coma Scale with 39°C fever but unremarkable physical examination.Diagnosis was infection of unknown origin;fever continued,and the Glasgow Coma Scale worsened to 8.Imaging showing a high-intensity area between the left temporal lobe and insular cortex suggested herpes encephalitis.ACV was started.Cerebrospinal fluid(CSF)was positive for HSV DNA,confirming the diagnosis.However,unresolved symptoms suggested ARHE;therefore,we initiated vidarabine treatment.Later testing confirmed ARHE.Foscarnet was started based on a hospital day 25 blood test revealing pancytopenia,possibly from vidarabine.Consciousness improved,and the patient moved to rehabilitation.However,symptoms worsened,suggesting recurrence.Diffusion-weighted magnetic resonance imaging revealed a high high-intensity area around the right temporal lobe;CSF was positive for HSV DNA,confirming recurrent herpes encephalitis.ACV and foscarnet were initiated.Fever decreased,consciousness improved,and HSV DNA on hospital days 78 and 93 was CSF negative.Treatment was terminated on hospital day 86.CONCLUSION ARHE recurred in the patient following remission;therefore,it is necessary to discuss the length of the treatment period.
文摘Addressing the challenges of difficult early diagnosis and the incomplete prognosis evaluation system for Autoimmune Encephalitis(AE),this study comprehensively reviews the relevant indicators for early diagnosis and prognosis evaluation of AE.The analysis reveals that multiple indicators currently exhibit unique value in the diagnosis and treatment of AE,but each has its limitations.This article aims to systematically review these indicators and clarify their current application in clinical practice,to help improve the accuracy of early diagnosis and prognosis evaluation of AE,and provide a theoretical basis for clinicians to develop more effective treatment strategies.
文摘The Chandipura vesiculovirus(CHPV),a single-stranded,negative sense RNA arbovirus with five structural proteins-the G,N,M,P,and L proteins-is the source of Chandipura virus infection.Children between the ages of 9 months and 14 years old are the most common recipients of CHPV infection,which is primarily spread by sand flies(Sergentomyia,Phlebotomus species).The potential advantages of black seeds(N.sativa)in the treatment of patients with CHPV infection are the main topic of our current review.The majority of patients infected with CHPV experience neurological complications such as encephalitis and other neurological complications.Since there is currently no approved antiviral treatment,supportive care and symptomatic therapy are the primary methods used to manage CHPV-infected patients.Herbal candidates possessing antioxidant,immunomodulatory,antiviral,and anti-inflammatory qualities may aid in the treatment of CHPV infection.The antiviral,anti-inflammatory,antioxidant,and immunomodulatory qualities of black seeds(N.sativa)have been shown in a number of preclinical and clinical investigations;these attributes could be helpful in the treatment of CHPV infection.Black seeds(N.sativa)may help treat CHPV-infected patients in the early stages of their illness when used in conjunction with symptomatic therapy and supportive care.In patients infected with CHPV,additional randomized controlled clinical trials would assess the efficacy and safety of black seeds(N.sativa).
基金the National Natural Science Foundation of China(82172266to P.G.W.)Natural Science Foundation of Beijing(7232002 to N.G.).
文摘The Japanese encephalitis virus(JEV)causes Japanese encephalitis(JE),a severe disease that primarily affects children and induces significant central nervous system complications.With the widespread adoption of vaccination in children,the incidence among older individuals has increased substantially.Despite this epidemiological shift,research on JEV infection in the elderly remains limited.We established JEV infection models using both aged and young mice to explore age-related differences in pathology and underlying mechanisms.Brain tissue samples were analyzed for pathological changes and viral tropism in major cell types.To further characterize immune response variations,we conducted transcriptomic sequencing on the brain tissues following JEV infection.Aged mice exhibited lower mortality,delayed disease progression,and milder brain pathology compared to young mice after JEV infection.Viral titers and infection rates of major brain cell types were similar in both groups.Transcriptomic analysis revealed diminished immune activation and weaker inflammatory responses in aged mice.Additionally,microglial activation and CD8^(+) T cell function were significantly reduced.Interestingly,JEV infection induced the selective recruitment of B cells in the brains of aged mice.These B cells may modulate the effects of CD8^(+) T cells in the disease process.Compared to young mice,aged mice showed enhanced resistance to JEV progression and reduced brain pathology.This resistance was associated with a weakened immune response in the aged brain,rather than differences in viral infection.The specific recruitment of B cells in the brains of aged mice may play a crucial role in limiting disease progression.
基金supported by the National Key Research and Development Program of China(2023YFC3041500).
文摘Objective Patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection frequently develop central nervous system damage,yet the mechanisms driving this pathology remain unclear.This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant(lineage B.1.351).Methods K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant.Viral replication,pathological phenotypes,and brain transcriptomes were analyzed.Gene Ontology(GO)analysis was performed to identify altered pathways.Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.Results Pathological alterations were observed in the lungs of both mouse strains.However,only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection,accompanied by neuropathological injury and weight loss.GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses,including type I interferons,pro-inflammatory cytokines,Toll-like receptor signaling components,and interferon-stimulated genes.Neuroinflammation was evident,alongside activation of apoptotic and pyroptotic pathways.Furthermore,altered neural cell marker expression suggested viral-induced neuroglial activation,resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.Conclusion These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
文摘Objective:To explore the application effect of bundle management in the safe nursing of patients with autoimmune encephalitis.Methods:Seventy-five patients with autoimmune encephalitis who met the inclusion criteria in our hospital from January 2024 to June 2024 were randomly divided into two groups:an observation group of 39 patients and a control group of 36 patients.The control group received routine nursing care,while the observation group implemented a bundle management strategy based on routine nursing care.Safety nursing outcomes,clinical symptom improvement time,hospital stay,and neurologic function recovery were observed in both groups.Results:The incidence of adverse events in the observation group was 12.82%,significantly lower than the 33.33%in the control group,with a statistically significant difference(P<0.05).There was no statistically significant difference in restraint usage and ICU transfer rates between the two groups(P>0.05).The clinical symptom improvement time,hospital stay,and neurologic function recovery in the observation group were significantly better than those in the control group,with a statistically significant difference(P<0.05).Conclusion:Through the bundle management model,effective connections can be ensured in various aspects of treatment and rehabilitation for patients with autoimmune encephalitis,providing patients with comprehensive and multi-level nursing services and improving their overall satisfaction and treatment effectiveness.
文摘Western equine encephalitis virus(WEEV)is an arbovirus that historically caused large outbreaks of encephalitis throughout the Americas.WEEV binds protocadherin 10(PCDH10)as a receptor,and highly virulent ancestral WEEV strains also bind low-density lipoprotein receptor(LDLR)-related proteins.As WEEV declined as a human pathogen in North America over the past century,isolates have lost the ability to bind mammalian receptors while still recognizing avian receptors.To explain shifts in receptor dependencies and assess the risk of WEEV re-emergence,we determined cryoelectron microscopy structures of WEEV bound to human PCDH10,avian PCDH10,and human very-low-density lipoprotein receptor(VLDLR).We show that one to three E2 glycoprotein substitutions are sufficient for a nonpathogenic strain to regain the ability to bind mammalian receptors.A soluble VLDLR fragment protects mice from lethal challenge by a virulent ancestral WEEV strain.Because WEEV recently re-emerged in South America after decades of inactivity,our findings have important implications for outbreak preparedness.
文摘BACKGROUND Worldwide,there has been a steady increase in the number of cases of pulmonary cryptococcosis diagnosed in immunocompetent patients,where symptoms can range from mild to severe.Clinical and radiological distinction of disease may be made when compared with immunodeficient cases and in those presenting with primary lung carcinoma.In the latter case confusion can lead to initial misdiagnosis and delayed treatment.We report a case of disseminated cryptococcosis in an immunocompetent patient which mimicked a primary lung carcinoma with brain metastases.CASE SUMMARY A 51-year-old male farmer with a 30-year smoking history presented with a twoweek history of productive cough,streaky hemoptysis,and low-grade fever.He had no history of immunosuppression,tuberculosis,or specific risk factors.Chest computed tomography revealed a posterior basal left lower lobe mass,but tumor markers and transbronchial tests were negative.Brain magnetic resonance imaging showed an enhancing left frontal lobe lesion,raising suspicion for metastatic lung cancer.However,computed tomography-guided biopsy confirmed fungal pneumonia with“titan”cells,and a positive serum cryptococcal antigen test confirmed Cryptococcus neoformans infection.Bronchoscopy and lavage detected fungal spores,while cerebrospinal fluid cytology and culture were negative.Fluconazole(0.4 mg/day)was initiated,but progressive central nervous system lesions required amphotericin B.A six-week combination of fluconazole(600 mg/day)and flucytosine led to resolution.At 24-month follow-up,he remained asymptomatic with no recurrence.CONCLUSION Cryptococcosis is increasing in immunocompetent individuals in China and should be considered in pneumonia and lung or brain lesions.
基金supported by funds from the scientific and technical program BR218004/0223“Improving measures to ensure biological safety in Kazakhstan:counteracting dangerous and especially dangerous infections”.Part of this work carried out in Russian Federation was supported by internal grant funding from the Scientific Centre for Family Health and Human Reproduction Problems:grant number 121022500179-0.Title:“Molecular,Organismal,and Population Patterns of the Epidemic Process of Anthropozoonotic and Transmissible Infections in the Territory of Northern Asia and Adjacent Areas”.
文摘Tick-borne encephalitis virus(TBEV)is a re-emerging pathogen in Kazakhstan,where the increasing risk of its spread underscores the need for improved healthcare preparedness,including the development of local vaccines.However,the absence of reference TBEV strains in the country presented a major challenge.To address this,we generated a prototype strain(Vasilchenko)of the Siberian TBEV genotype,predominant in Kazakhstan,using synthetic genome and molecular infectious clone technology.A DNA-launched TBEV molecular clone was assembled from DNA fragments,enabling virus rescue upon plasmid transfection.During the propagation of the post-transfection virus in cell culture,a single amino acid substitution(E51K)in the envelope protein emerged,resulting in a 100-fold increase in the titer of the mutant variant.In vivo,this mutation significantly attenuated virulence:while wild-type TBEV caused 100%mortality in BALB/c mice,the E51K variant was non-lethal and exhibited reduced viremia,suggesting impaired neuroinvasiveness.To further exploit this attenuated,high-titer virus,we developed a GFP-expressing reporter TBEV variant.Using this reporter system,we demonstrated that favipiravir possesses antiviral activity against TBEV,with inhibitory concentrations within a pharmacologically relevant range.In conclusion,synthetic genomics enabled the generation of a reference TBEV strain to replenish Kazakhstan's collections.The E51K mutation enhances viral replication in vitro while attenuating pathogenicity in vivo,and the derived reporter virus is suitable for antiviral compound screening.
基金Supported by the Shenzhen Science and Technology Program,No.JCYJ20220818102810022Shenzhen University Teaching Reform fund,No.JG2023166+1 种基金National Natural Science Foundation of China,No.12231018Science and Technology Innovation 2030-Major Project,No.2021ZD0201805.
文摘BACKGROUND Autoimmune encephalitis(AE)is a rare and recently described neuroinflammatory disease associated with specific autoantibodies.Anti-leucine-rich glioma inactivated 1(anti-LGI1)encephalitis is a rare but treatable type of AE discovered in recent years.Alzheimer’s disease(AD)is a degenerative brain disease and the most common cause of dementia.AD may undergo a series of pathological physiological changes in brain tissue 20 years before the onset of typical symptoms.The stage of mild cognitive impairment(MCI)that occurs during this process,known as MCI due to AD,is the earliest stage with clinical symptoms.MCI is typically categorized into two subtypes:Amnestic MCI(aMCI)and non-aMCI.CASE SUMMARY This report describes a patient with rapid cognitive impairment,diagnosed with anti-LGI1 antibody-mediated AE and aMCI,and treated at Peking University Shenzhen Hospital in March 2023.The patient was hospitalized with acute memory decline for more than 3 months.Both the cerebrospinal fluid and serum were positive for anti-LGI1 antibodies,biomarkers of AD coexisting in the patient’s cerebrospinal fluid.Following combination treatment with immunoglobulin therapy and glucocorticoid,plus inhibition of acetylcholinesterase,the patient’s cognitive function significantly improved.Throughout the 3-month follow-up period,a sustained improvement in cognitive function was observed.The results of serum anti-LGI1 antibody were negative.CONCLUSION This case has raised awareness of the possible interaction between AE and early AD(including MCI due to AD),and alerted clinicians to the possibility of concurrent rare and common diseases in patients presenting with cognitive impairment.
基金financially supported by the ResearchInitiation Ftnd Project at Hainan University(Grant Nos.KYQD(ZR)20078 and KYQD(ZR)23179).
文摘Candida albicans(C.abicans),вcommon pathogenic fungus in nature,has enough cæpity to cause Severe brain infection through various mesns under immunocompromised conditions.Currently,stablishing a basic animal disesse model has become the main rsrch tool,which isconducive to simulat ing fungal encephalitis effectively.However,the widely used bloodbarne infection model established by intravenoOus(I.V)injection in mice usually results in systenic infecions but cannot simulate significant bradn inflammation.Here,we developed&fungal en-cephaltis model by intracerebroventriaular(L.C.V)injection af C.albicansto better simulate the significant harm und consequencEs.Compared with I.V,a greater number of colony-for ming units(CFUa)in the brain was induced following I.CV.Magnetic resonane imaging MRM resulta revesled more obvious inflammatinn in the external capsule area of the brain.Menwhile,be havioral experiments with the Y-meze also indicated that abnormal activity behavior further relected significant short-term mamory impairment after I.C.Vof C.albicans.In summary,these studies not onby provide a novel fungal encephalitis model for understanding the pathogenesis mechanism of this disease but also lay a solid foundation for future effective tretment.
文摘Human herpesvirus 6(HHV-6)is a common childhood infection but rarely causes severe complications.In immunocompetent children,conditions such as febrile convulsions and roseola infantum are typical,with occasional severe manifestations like meningoencephalitis and myocarditis.
文摘BACKGROUND Acute disseminated encephalomyelitis(ADEM),which is rare,primarily affects children.It usually manifests as acute encephalopathy and multifocal neurological impairments after infection or vaccination.Diagnosis is still difficult due to the clinical and radiological similarity to other central nervous system disorders.Adult-onset ADEM calls for thorough reporting in order to improve diagnosis and treatment.CASE SUMMARY A 55-year-old man with hypertension had a high fever,intense headache and a steady decline in his neurological function after two weeks.Left facial paralysis was the initial symptom,which progressed to left hemiparesis,reduced consciousness level,photophobia,phonophobia,vomiting,and a focal seizure in the right leg.He had no history of autoimmune disease,vaccinations,or infections.Investigations showed negative infectious/autoimmune serology,mild cerebrospinal fluid lymphocytic pleocytosis(protein 76 mg/dL),and lymphopenia.Brain magnetic resonance imaging without contrast revealed bilateral,symmetrical T2/fluid-attenuated inversion recovery hyperintensities,primarily in the middle cerebellar peduncles,with minor involvement in the pontine and periventricular regions.Neoplastic,metabolic,vascular,and infectious conditions were not included.The patient showed spontaneous neurological improvement by Week 3 with near-complete motor recovery(limb strength 4/5)after methylprednisolone and rehabilitation,despite logistical delays in starting immunotherapy.The monophasic course and radiological/clinical remission were supported by idiopathic ADEM.CONCLUSION This case shows an uncommon,idiopathic,cerebellar-predominant ADEM variation in an adult without conventional triggers.It emphasizes the diagnostic difficulty in distinguishing ADEM from mimics(such as stroke or infection)in adults.Spontaneous improvement before treatment,although early detection is still crucial,should be highlighted,although early detection is still crucial.Increased clinician awareness,fair access to neuroimaging,and focused research on adult ADEM are crucial to fill these gaps and improve outcomes in places with limited resources.
