Dear Editor,Posterior reverse encephalopathy syndrome(PRES),manifests as a confusional state/delirium,convulsion,or acute blindness which illustrates in magnetic resonance imaging(MRI)typical bilateral white matter le...Dear Editor,Posterior reverse encephalopathy syndrome(PRES),manifests as a confusional state/delirium,convulsion,or acute blindness which illustrates in magnetic resonance imaging(MRI)typical bilateral white matter lesions.These clinical and radiological changes are reversible in two to three weeks,usually generated by acute hypertension,preeclampsia,eclampsia,immunosuppression,septicemia,and end-stage renal disease.PRES is commonly diagnosed in patients in their thirties.展开更多
BACKGROUND Posterior reversible encephalopathy syndrome(PRES)is a complex neurological disorder characterized by symptoms such as headaches,seizures,confusion,and visual disturbances.The pathophysiology of PRES involv...BACKGROUND Posterior reversible encephalopathy syndrome(PRES)is a complex neurological disorder characterized by symptoms such as headaches,seizures,confusion,and visual disturbances.The pathophysiology of PRES involves endothelial dysfunction,disrupted cerebral autoregulation,and resulting vasogenic edema.Hypertension and other factors that alter cerebral autoregulation are critical in its development.Corticosteroids,widely used for their anti-inflammatory and immunosuppressive properties,play a controversial role in PRES.AIM To elucidate the dual role of corticosteroids in the context of PRES by critically evaluating the existing literature.Specifically,it seeks to assess the results of PRES induced by corticosteroid therapy and the efficacy and safety of corticosteroids in the treatment of PRES.By synthesizing case reports and series,this review aims to provide a comprehensive understanding of the mechanisms,clinical presentations,and management strategies associated with corticosteroid-related PRES.METHODS The review was carried out according to the PRISMA guidelines.The databases searched included Science Direct,PubMed,and Hinari.The search strategy encompassed terms related to corticosteroids and PRES.Studies were included if they were peer-reviewed articles examining corticosteroids in PRES,excluding non-English publications,reviews,and editorials.Data on patient demographics,clinical characteristics,imaging findings,corticosteroid regimens,and outcomes were extracted.The risk of bias was evaluated using the Joanna Briggs Institute tool for case reports.RESULTS A total of 56 cases of PRES(66.1%women,33.9%men)potentially induced by corticosteroids and 14 cases in which corticosteroids were used to treat PRES were identified.Cases of PRES reportedly caused by corticosteroids showed a mean age of approximately 25.2 years,with seizures,headaches,hypertension,and visual disturbances being common clinical sequelae.Magnetic resonance findings typically revealed vasogenic edema in the bilateral parieto-occipital lobes.High-dose or prolonged corticosteroid therapy was a significant risk factor.On the contrary,in the treatment cases,corticosteroids were associated with positive outcomes,including resolution of vasogenic edema and stabilization of symptoms,particularly in patients with underlying inflammatory or autoimmune diseases.CONCLUSION Corticosteroids have a dual role in PRES,capable of both inducing and treating the condition.The current body of literature suggests that corticosteroids may play a greater role as a precipitating agent of PRES rather than treating.Corticosteroids may induce PRES through hypertension and subsequent increased cerebral blood flow and loss of autoregulation.Corticosteroids may aid in the management of PRES:(1)Enhancing endothelial stability;(2)Antiinflammatory properties;and(3)Improving blood-brain barrier integrity.Mechanisms which may reduce or mitigate vasogenic edema formation.展开更多
BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characteriz...BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characterized by delayed onset of neurological and cognitive deficits,DPHLS presents substantial diagnostic and therapeutic challenges.AIM To consolidate current knowledge on pathophysiology,clinical features,diagnostic approaches,and management strategies for DPHLS,providing a comprehensive overview and highlighting gaps for future research.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines,we systematically searched PubMed,ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy.Inclusion criteria were original research articles,case reports,and case series involving human subjects with detailed clinical,neuroimaging,or pathological data on DPHLS.Data were extracted on study characteristics,participant demographics,clinical features,neuroimaging findings,pathological findings,treatment,and outcomes.The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.RESULTS A total of 73 cases were reviewed.Common comorbidities included schizoaffective disorder,bipolar disorder,hypertension,and substance use disorder.The primary causes of hypoxia were benzodiazepine overdose,opioid overdose,polysubstance overdose,and carbon monoxide(CO)poisoning.Symptoms frequently include decreased level of consciousness,psychomotor agitation,cognitive decline,parkinsonism,and encephalopathy.Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter,sometimes involving the basal ganglia and the globus pallidus.Magnetic resonance spectroscopy often showed decreased N-acetylaspartate,elevated choline,choline-to-creatinine ratio,and normal or elevated lactate.Treatment is often supportive,including amantadine,an antioxidant cocktail,and steroids.Hyperbaric oxygen therapy may be beneficial in those with CO poisoning.Parkinsonism was often treated with levodopa.Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations.Early recognition and appropriate management are crucial to improving patient outcomes.Future research should focus on standardizing diagnostic criteria,using advanced imaging techniques,and exploring therapeutic interventions to improve understanding and treatment of DPHLS.Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.展开更多
Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela ...Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.展开更多
Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy(SAE).OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury.However,its regulat...Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy(SAE).OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury.However,its regulatory function in microglial pyroptosis and involvement in SAE remains unclear.In this study,we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury.Furthermore,OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice.Mechanistically,OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation,thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation.In conclusion,this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.展开更多
Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed asse...Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.展开更多
Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid...Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid(RA)can suppress the neurotoxic effects of CO.This study further explores,in vivo and in vitro,the molecular mechanisms by which RA alleviates CO-induced central nervous system damage.Methods:A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO,and a DEACMP animal model was established in adult Kunming mice.Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and Annexin V/propidium iodide(PI)double staining.The transcriptional and protein expression of each gene was detected using real time fluorescence quantitative PCR(RT-qPCR)and Western blotting.Long noncoding RNA(lncRNA)SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes.In DEACMP mice,SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression.Results:RA at 10 and 20μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes,downregulation of SNHG15 and LINGO-1,and upregulation of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)(all P<0.05).Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity(all P<0.05).Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels(all P<0.05).Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP(all P<0.05).Conclusion:RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes,thereby reducing central nervous system injury and exerting neuroprotective effects.LncRNA SNHG15 and LINGO-1 are key molecules mediating RA induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway.These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.展开更多
Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality r...Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life.Systemically,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral homeostasis.Key circulating neurotoxins are ammonia and inflammatory mediators.In the brain,pathophysiology is less well understood,but is thought to be driven by glial cell dysfunction.Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation.Based on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress.Microglia,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain microenvironment.Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma.Furthermore,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death.Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic encephalopathy.In this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.展开更多
Imidacloprid,a neonicotinoid insecticide,is widelyused in agriculture as a safer alternative to highly toxicorganophosphates.It targets nicotinic acetylcholinereceptors in pests and is generally low in toxicity tohuma...Imidacloprid,a neonicotinoid insecticide,is widelyused in agriculture as a safer alternative to highly toxicorganophosphates.It targets nicotinic acetylcholinereceptors in pests and is generally low in toxicity tohumans.However,large ingestions can cause severe,life-threatening complications,with no establishedtreatment protocols.Though rarely fatal,imidaclopridpoisoning is increasingly reported in agricultural regions,particularly in Southeast Asia,with most cases involvingsuicide attempts.展开更多
BACKGROUND:Sepsis-associated encephalopathy(SAE)is a diff use dysfunction of the nervous system resulting from sepsis originating outside the central nervous system.Elderly individuals(≥65 years of age)constitute a p...BACKGROUND:Sepsis-associated encephalopathy(SAE)is a diff use dysfunction of the nervous system resulting from sepsis originating outside the central nervous system.Elderly individuals(≥65 years of age)constitute a particularly vulnerable population comprised by a high burden of underlying diseases and complications,which frequently leads to underdiagnosis or misdiagnosis.These patients are at increased risk of long-term or permanent central nervous system impairment,making rapid and accurate diagnosis and treatment especially critical.The review is expected to promote improvements in the diagnosis and treatment of SAE in elderly patients,ultimately achieving more standardized and effi cient SAE management.METHODS:We performed a literature search in four databases-PubMed,Embase,China National Knowledge Infrastructure(CNKI),and Wanfang-from inception to April 2025 using bilinguals(Chinese and English).RESULTS:The diagnostic criteria for SAE in elderly individuals include the following:(1)sepsis;(2)new-onset neurological dysfunction;and(3)exclusion of other causes of neurological dysfunction.Physicians should develop tailored empiric anti-infective plans for elderly SAE patients,considering comorbidities,organ function,infection site,local bacterial spectrum,and resistance.The treatment protocol can be adjusted once the pathogen is identifi ed.Stabilizing hemodynamics and ensuring cerebral perfusion are two fl uid resuscitation strategies used in elderly SAE patients.An individualized approach to fl uid resuscitation using restrictive fl uid volumes should be employed.Supportive treatment for elderly SAE patients focuses on improving tissue perfusion/oxygenation,controlling blood glucose levels,and correcting internal imbalances.Early rehabilitation,nutritional support,cognitive training,and family-based emotional support are important components of comprehensive care.CONCLUSION:The diagnosis and management of SAE in elderly patients support early recognition and timely intervention.展开更多
BACKGROUND Hepatic encephalopathy(HE)is a primary complication following transjugular intrahepatic portosystemic shunt(TIPS),but the utility of pharmacological prophylaxis for HE is unclear.AIM To assess the HE incide...BACKGROUND Hepatic encephalopathy(HE)is a primary complication following transjugular intrahepatic portosystemic shunt(TIPS),but the utility of pharmacological prophylaxis for HE is unclear.AIM To assess the HE incidence post-TIPS across various groups and the prophylactic efficacies of various medications.METHODS A thorough literature search was performed in PubMed,Web of Science,EMBASE,and the Cochrane Library databases from their inception to November 24,2024,to collect data regarding HE incidence.The main outcome was HE incidence post-TIPS.A meta-analysis using a random effects model was performed to obtain odds ratios(ORs)and 95%confidence intervals.Statistical analyses were conducted using Stata and RevMan software.RESULTS This meta-analysis included nine studies with 1140 patients;647 received pharmacological agents including lactulose,rifaximin,albumin,and l-ornithin-l-aspartate,and 493 did not(controls).(1)In the single-group meta-analysis,the control group had higher short-and long-term HE rates than the drug intervention group.Among patients with and without prior HE,the non-intervention group's HE rates were also higher;(2)Pharmacological prevention post-TIPS significantly reduced HE incidence[OR=0.59(0.45,0.77),P=0.0001].Compared with the no prophylaxis,rifaximin reduced the risk of HE after TIPS[OR=0.52(0.29,0.95),P=0.03],but lactulose did not;(3)In patients without prior HE,pharmacological prevention significantly reduced post-TIPS HE incidence[OR=0.62(0.41,0.95),P=0.03];and(4)Network meta-analysis showed no significant differences among five prevention strategies.CONCLUSION The HE incidence after TIPS was relatively high,and the use of drugs after TIPS may reduce the HE incidence.However,research,especially large-scale randomized controlled trials,is still lacking.展开更多
The gut microbiota plays a pivotal role in the pathogenesis of liver diseases,particularly hepatic encephalopathy(HE),in which dysbiosis contributes to ammonia production,systemic inflammation,and neurocognitive dysfu...The gut microbiota plays a pivotal role in the pathogenesis of liver diseases,particularly hepatic encephalopathy(HE),in which dysbiosis contributes to ammonia production,systemic inflammation,and neurocognitive dysfunction.Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity.This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease,focusing on traditional approaches such as non-absorbable disaccharides(lactulose,lactitol),antibiotics(rifaximin),and probiotics as well as novel interventions,including postbiotics,synbiotics,and fecal microbiota transplantation.Additionally,bile acid modulators,short-chain fatty acid derivatives,and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis.We also discussed the implications of gut microbiota modulation in conditions beyond HE,such as metabolic dysfunction-associated steatotic liver disease and cirrhosis.By integrating gut microbiotatargeted therapies into liver disease management,we may develop more effective,personalized approaches to improve patient outcomes and reduce complications.展开更多
BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatri...BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.展开更多
Hyperglycemia in individuals with diabetes causes cognitive impairment,called diabetic encephalopathy(DE).The pathogenesis of DE is closely related to angiopathy,and effective treatment is highly desirable.The botanic...Hyperglycemia in individuals with diabetes causes cognitive impairment,called diabetic encephalopathy(DE).The pathogenesis of DE is closely related to angiopathy,and effective treatment is highly desirable.The botanical agent berberine(BBR)effectively lowers blood glucose in diabetic patients.Here,we show for the first time that BBR significantly improved cognitive function in type 2 diabetic encephalopathy KK-Ay(2DEK)mice.High-resolution imaging via fluorescence micro-optical sectioning tomography(fMOST)revealed that the integrity of brain vessels was improved by BBR treatment.The improvements in average vessel diameter,vessel length,and total vessel volume were significant in the parietal association cortex(PtA),as well as in the CA1 and CA3 regions.A mechanistic study revealed that oral BBR inhibited δ-valerobetaine(δ-VB,a metabolite of the gut microbiota)production in the intestine.As intestinal δ-VB can enter the circulation and activate the Toll-like receptor-4(TLR-4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa B(NF-jB)inflammatory pathway in the epithelial cells of blood vessels through interacting with TLR-4,BBR might reduce the intestinal level of δ-VB to protect the cerebral blood vessels of DE mice and improve their brain function.Fecal microbiota transplantation(FMT)using the gut microbiota from BBR-treated mice confirmed the vital role of the gut microbiota.BBR showed a wide range of effects on the gut flora,also increasing short-chain fatty acid(SCFA)production and decreasing lipopolysaccharide(LPS)levels in the intestine by adjusting the abundance of SCFA-or LPS-producing bacteria.The observed therapeutic efficacy in vivo revealed a synergistic effect of BBR on the gut microbiota.Conclusively,we found an association between the gut microbiota and blood vessels,of which intestinal δ-VB might be a chemical link.Mainly through downregulating δ-VB in the intestine,BBR protected cerebral vessels and alleviated DE.展开更多
BACKGROUND Hepatic encephalopathy(HE)affects more than 30%of patients with cirrhosis.Extrahepatic portosystemic shunt(EHPSS)has been suggested to be a contributing factor to HE recurrence and mortality.Therefore,early...BACKGROUND Hepatic encephalopathy(HE)affects more than 30%of patients with cirrhosis.Extrahepatic portosystemic shunt(EHPSS)has been suggested to be a contributing factor to HE recurrence and mortality.Therefore,early detection and intervention in EHPSS may improve patient outcomes.AIM To evaluate the effects of shunt embolization on mortality and HE recurrence.METHODS In this retrospective case-control study,16 cirrhotic patients with HE treated at a tertiary care center from January 2012 to August 2022 were included.Outcomes in eight patients who underwent embolization of EHPSS were compared with those in eight patients receiving standard care without embolization.Data on baseline characteristics,HE recurrence,and overall survival were collected and analyzed using Kaplan-Meier and log-rank tests.RESULTS Baseline characteristics were comparable between the groups.The 1-year overall survival rate was significantly higher in the treatment group(0.50)than in the control group(0.33).The HE recurrence-free rate was also higher in the treatment group(1.00)than in the control group(0.17).The median survival duration was longer in the treatment group{not reached[95%confidence interval(CI):23.84 to not available(NA)]}than in the control group[15.02 months(95%CI:9.86 to NA)](P=0.006).Similarly,the recurrence-free duration was longer in the treatment group[63.09 months(95%CI:63.09 to NA)]than in the control group[9.21 months(95%CI:4.47 to NA)](P=0.006).EHPSS embolization significantly reduced 1-year HE recurrence(hazard ratio=0.09;95%CI:0.01-0.75;P=0.026).CONCLUSION EHPSS embolization significantly improves 1-year survival and prevents recurrence of HE in cirrhotic patients.Routine computed tomography and early embolization are clinically beneficial.展开更多
BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study...BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.METHODS We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut microbiome.According to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE.The data were analyzed using RevMan and STATA.RESULTS Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic tools.CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ.Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.展开更多
In this editorial we comment on the article by Jiang et al.We focus on the Ence-phalApp Stroop test which is an innovative,smartphone-based tool specifically designed for screening minimal hepatic encephalopathy(MHE)i...In this editorial we comment on the article by Jiang et al.We focus on the Ence-phalApp Stroop test which is an innovative,smartphone-based tool specifically designed for screening minimal hepatic encephalopathy(MHE)in cirrhosis patients.Traditional MHE screening methods,while highly sensitive and specific,are often complex,time-consuming,and require controlled environmental con-ditions,limiting their widespread clinical use.The EncephalApp Stroop test si-mplifies the screening process,enhances diagnostic efficiency,and is applicable across diverse cultural contexts.However,the combination of additional bio-markers could further improve diagnostic accuracy.Despite its promising po-tential,more multicenter clinical studies are required to validate its effectiveness and applicability on a global scale.展开更多
BACKGROUND Several conditions may present with acute neurological symptoms,thus mimicking the presentation of stroke.Although the underlying disorder can be diagnosed after careful medical,neurological,and radiologica...BACKGROUND Several conditions may present with acute neurological symptoms,thus mimicking the presentation of stroke.Although the underlying disorder can be diagnosed after careful medical,neurological,and radiological examinations,a few conditions,such as Wernicke encephalopathy(WE),may present a particular diagnostic difficulty.WE is a neurological disorder caused by deficiency of thiamine(B1 vitamin),most often resulting from alcoholism,malnutrition,hyperemesis gravidarum or bariatric surgery.The diagnosis of WE in a certain historical,clinical setting is easily suggested,but in a few cases presenting with acute neurological deficits,it can be particularly challenging.CASE SUMMARY We present the case of a 63-year-old man who was brought to the emergency department after developing weakness of the left extremities,dizziness and a confusional state,which had lasted for approximately 30 minutes.The patient had a similar episode of a confusional state approximately two months earlier;at that time,a transient ischemic attack was suspected and he was started on aspirin.The initial clinical evaluation and imaging findings were unremarkable for stroke,but the patient’s symptoms,history of chronic alcohol abuse and abnormal liver function tests prompted the consideration of WE.Magnetic resonance imaging findings in subthalamic areas and electroencephalogram data of diffuse delta activity supported this diagnosis.CONCLUSION Through this case report,we aim to underscore the importance of considering WE as a differential diagnosis in patients presenting with symptoms suggestive of stroke,especially when the presentation is atypical or when risk factors for thiamine deficiency are present.Since intravenous thiamine significantly improves outcomes,delayed recognition and treatment in some cases might be deleterious.展开更多
Transjugular intrahepatic portosystemic shunt(TIPS)is widely used to treat portal hypertension and its complications patients with cirrhosis.However,managing post-TIPS hepatic encephalopathy(HE)remains a major clinica...Transjugular intrahepatic portosystemic shunt(TIPS)is widely used to treat portal hypertension and its complications patients with cirrhosis.However,managing post-TIPS hepatic encephalopathy(HE)remains a major clinical challenge.HE is characterized by a high incidence and a complex pathogenesis,influenced by various factors.Therefore,careful patient assessment and selection for TIPS is essential.While previous studies have identified several factors contributing to the occurrence of post-TIPS HE,there is a gap in the comprehen-sive integration of surgical procedural parameters and metabolic mechanisms within a multidimensional analysis.This minireview aims to optimize treatment protocols and refine management strategies by conducting a comprehensive analysis of risk factors,ultimately aiming to reduce the incidence of post-TIPS HE.展开更多
Acute Bilirubin Encephalopathy(ABE)is a significant threat to neonates and it leads to disability and high mortality rates.Detecting and treating ABE promptly is important to prevent further complications and long-ter...Acute Bilirubin Encephalopathy(ABE)is a significant threat to neonates and it leads to disability and high mortality rates.Detecting and treating ABE promptly is important to prevent further complications and long-term issues.Recent studies have explored ABE diagnosis.However,they often face limitations in classification due to reliance on a single modality of Magnetic Resonance Imaging(MRI).To tackle this problem,the authors propose a Tri-M2MT model for precise ABE detection by using tri-modality MRI scans.The scans include T1-weighted imaging(T1WI),T2-weighted imaging(T2WI),and apparent diffusion coefficient maps to get indepth information.Initially,the tri-modality MRI scans are collected and preprocessesed by using an Advanced Gaussian Filter for noise reduction and Z-score normalisation for data standardisation.An Advanced Capsule Network was utilised to extract relevant features by using Snake Optimization Algorithm to select optimal features based on feature correlation with the aim of minimising complexity and enhancing detection accuracy.Furthermore,a multi-transformer approach was used for feature fusion and identify feature correlations effectively.Finally,accurate ABE diagnosis is achieved through the utilisation of a SoftMax layer.The performance of the proposed Tri-M2MT model is evaluated across various metrics,including accuracy,specificity,sensitivity,F1-score,and ROC curve analysis,and the proposed methodology provides better performance compared to existing methodologies.展开更多
文摘Dear Editor,Posterior reverse encephalopathy syndrome(PRES),manifests as a confusional state/delirium,convulsion,or acute blindness which illustrates in magnetic resonance imaging(MRI)typical bilateral white matter lesions.These clinical and radiological changes are reversible in two to three weeks,usually generated by acute hypertension,preeclampsia,eclampsia,immunosuppression,septicemia,and end-stage renal disease.PRES is commonly diagnosed in patients in their thirties.
文摘BACKGROUND Posterior reversible encephalopathy syndrome(PRES)is a complex neurological disorder characterized by symptoms such as headaches,seizures,confusion,and visual disturbances.The pathophysiology of PRES involves endothelial dysfunction,disrupted cerebral autoregulation,and resulting vasogenic edema.Hypertension and other factors that alter cerebral autoregulation are critical in its development.Corticosteroids,widely used for their anti-inflammatory and immunosuppressive properties,play a controversial role in PRES.AIM To elucidate the dual role of corticosteroids in the context of PRES by critically evaluating the existing literature.Specifically,it seeks to assess the results of PRES induced by corticosteroid therapy and the efficacy and safety of corticosteroids in the treatment of PRES.By synthesizing case reports and series,this review aims to provide a comprehensive understanding of the mechanisms,clinical presentations,and management strategies associated with corticosteroid-related PRES.METHODS The review was carried out according to the PRISMA guidelines.The databases searched included Science Direct,PubMed,and Hinari.The search strategy encompassed terms related to corticosteroids and PRES.Studies were included if they were peer-reviewed articles examining corticosteroids in PRES,excluding non-English publications,reviews,and editorials.Data on patient demographics,clinical characteristics,imaging findings,corticosteroid regimens,and outcomes were extracted.The risk of bias was evaluated using the Joanna Briggs Institute tool for case reports.RESULTS A total of 56 cases of PRES(66.1%women,33.9%men)potentially induced by corticosteroids and 14 cases in which corticosteroids were used to treat PRES were identified.Cases of PRES reportedly caused by corticosteroids showed a mean age of approximately 25.2 years,with seizures,headaches,hypertension,and visual disturbances being common clinical sequelae.Magnetic resonance findings typically revealed vasogenic edema in the bilateral parieto-occipital lobes.High-dose or prolonged corticosteroid therapy was a significant risk factor.On the contrary,in the treatment cases,corticosteroids were associated with positive outcomes,including resolution of vasogenic edema and stabilization of symptoms,particularly in patients with underlying inflammatory or autoimmune diseases.CONCLUSION Corticosteroids have a dual role in PRES,capable of both inducing and treating the condition.The current body of literature suggests that corticosteroids may play a greater role as a precipitating agent of PRES rather than treating.Corticosteroids may induce PRES through hypertension and subsequent increased cerebral blood flow and loss of autoregulation.Corticosteroids may aid in the management of PRES:(1)Enhancing endothelial stability;(2)Antiinflammatory properties;and(3)Improving blood-brain barrier integrity.Mechanisms which may reduce or mitigate vasogenic edema formation.
文摘BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characterized by delayed onset of neurological and cognitive deficits,DPHLS presents substantial diagnostic and therapeutic challenges.AIM To consolidate current knowledge on pathophysiology,clinical features,diagnostic approaches,and management strategies for DPHLS,providing a comprehensive overview and highlighting gaps for future research.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines,we systematically searched PubMed,ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy.Inclusion criteria were original research articles,case reports,and case series involving human subjects with detailed clinical,neuroimaging,or pathological data on DPHLS.Data were extracted on study characteristics,participant demographics,clinical features,neuroimaging findings,pathological findings,treatment,and outcomes.The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.RESULTS A total of 73 cases were reviewed.Common comorbidities included schizoaffective disorder,bipolar disorder,hypertension,and substance use disorder.The primary causes of hypoxia were benzodiazepine overdose,opioid overdose,polysubstance overdose,and carbon monoxide(CO)poisoning.Symptoms frequently include decreased level of consciousness,psychomotor agitation,cognitive decline,parkinsonism,and encephalopathy.Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter,sometimes involving the basal ganglia and the globus pallidus.Magnetic resonance spectroscopy often showed decreased N-acetylaspartate,elevated choline,choline-to-creatinine ratio,and normal or elevated lactate.Treatment is often supportive,including amantadine,an antioxidant cocktail,and steroids.Hyperbaric oxygen therapy may be beneficial in those with CO poisoning.Parkinsonism was often treated with levodopa.Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations.Early recognition and appropriate management are crucial to improving patient outcomes.Future research should focus on standardizing diagnostic criteria,using advanced imaging techniques,and exploring therapeutic interventions to improve understanding and treatment of DPHLS.Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.
文摘Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.
基金supported by the Jiangsu Provincial Medical Key Discipline(Laboratory)Cultivation Unit(JSDW202249)the Natural Science Foundation of Jiangsu Province(BK20211108)+4 种基金a Scientific Research Project of the Health Commission of Nantong(MS2023035)Nantong Natural Science Foundation(JC2023114)the Scientific Research Innovation Team of Kangda College of Nanjing Medical University(KD2022KYCXTD005)Nantong University Clinical Medicine Special Project(2022JY005)the Postgraduate Research&Practice Innovation Program of Jiangsu province(KYCX23_3416).
文摘Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy(SAE).OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury.However,its regulatory function in microglial pyroptosis and involvement in SAE remains unclear.In this study,we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury.Furthermore,OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice.Mechanistically,OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation,thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation.In conclusion,this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
基金supported by a grant from the Health Research New Zealand(HRC)22/559(to AJG and LB)。
文摘Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.
基金supported by the Natural Science Foundation of Hunan Province(2021JJ31089)the Scientific Research Project of Health Commission of Hunan Province(202203104548),China。
文摘Objective:The neurotoxicity of carbon monoxide(CO)to the central nervous system is a key pathogenesis of delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Our previous study found that retinoic acid(RA)can suppress the neurotoxic effects of CO.This study further explores,in vivo and in vitro,the molecular mechanisms by which RA alleviates CO-induced central nervous system damage.Methods:A cytotoxic model was established using the mouse hippocampal neuronal cell line HT22 and primary oligodendrocytes exposed to CO,and a DEACMP animal model was established in adult Kunming mice.Cell viability and apoptosis of hippocampal neurons and oligodendrocytes were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay and Annexin V/propidium iodide(PI)double staining.The transcriptional and protein expression of each gene was detected using real time fluorescence quantitative PCR(RT-qPCR)and Western blotting.Long noncoding RNA(lncRNA)SNHG15 and LINGO-1 were knocked down or overexpressed to observe changes in neurons and oligodendrocytes.In DEACMP mice,SNHG15 or LINGO-1 were knocked down to assess changes in central nervous tissue and downstream protein expression.Results:RA at 10 and 20μmol/L significantly reversed CO-induced apoptosis of hippocampal neurons and oligodendrocytes,downregulation of SNHG15 and LINGO-1,and upregulation of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB)(all P<0.05).Overexpression of SNHG15 or LINGO-1 weakened the protective effect of RA against CO-induced cytotoxicity(all P<0.05).Knockdown of SNHG15 or LINGO-1 alleviated CO-induced apoptosis of hippocampal neurons and oligodendrocytes and upregulated BDNF and TrkB expression levels(all P<0.05).Experiments in DEACMP model mice showed that knockdown of SNHG15 or LINGO-1 mitigated central nervous system injury in DEACMP(all P<0.05).Conclusion:RA alleviates CO-induced apoptosis of hippocampal neurons and oligodendrocytes,thereby reducing central nervous system injury and exerting neuroprotective effects.LncRNA SNHG15 and LINGO-1 are key molecules mediating RA induced inhibition of neuronal apoptosis and are associated with the BDNF/TrkB pathway.These findings provide a theoretical framework for optimizing the clinical treatment of DEACMP and lay an experimental foundation for elucidating its molecular mechanisms.
基金supported by grants from the Research Foundation–Flanders(11A6420N,1268823N to WC and LVH)a FWO Junior Research Project Grant(G055121N to REV)VIB.AG is a senior clinical researcher of the Research Foundation–Flanders(1805718N)。
文摘Hepatic encephalopathy,defined as neuropsychiatric dysfunction secondary to liver disease,is a frequent decompensating event in cirrhosis.Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life.Systemically,liver disease,liver function failure,portosystemic shunting,and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation,which impairs cerebral homeostasis.Key circulating neurotoxins are ammonia and inflammatory mediators.In the brain,pathophysiology is less well understood,but is thought to be driven by glial cell dysfunction.Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation.Based on a large body of mostly in vitro evidence,ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress.Microglia,the brain resident macrophages,have been linked to the translation of systemic inflammation to the brain microenvironment.Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma.Furthermore,state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death.Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to well-established and novel cellular and molecular alterations in hepatic encephalopathy.In this review,we therefore give a current and comprehensive overview of causes,features,and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy,including areas of interest for future investigation.
文摘Imidacloprid,a neonicotinoid insecticide,is widelyused in agriculture as a safer alternative to highly toxicorganophosphates.It targets nicotinic acetylcholinereceptors in pests and is generally low in toxicity tohumans.However,large ingestions can cause severe,life-threatening complications,with no establishedtreatment protocols.Though rarely fatal,imidaclopridpoisoning is increasingly reported in agricultural regions,particularly in Southeast Asia,with most cases involvingsuicide attempts.
基金supported by the Beijing Clinical Key Specialty Project(2023).
文摘BACKGROUND:Sepsis-associated encephalopathy(SAE)is a diff use dysfunction of the nervous system resulting from sepsis originating outside the central nervous system.Elderly individuals(≥65 years of age)constitute a particularly vulnerable population comprised by a high burden of underlying diseases and complications,which frequently leads to underdiagnosis or misdiagnosis.These patients are at increased risk of long-term or permanent central nervous system impairment,making rapid and accurate diagnosis and treatment especially critical.The review is expected to promote improvements in the diagnosis and treatment of SAE in elderly patients,ultimately achieving more standardized and effi cient SAE management.METHODS:We performed a literature search in four databases-PubMed,Embase,China National Knowledge Infrastructure(CNKI),and Wanfang-from inception to April 2025 using bilinguals(Chinese and English).RESULTS:The diagnostic criteria for SAE in elderly individuals include the following:(1)sepsis;(2)new-onset neurological dysfunction;and(3)exclusion of other causes of neurological dysfunction.Physicians should develop tailored empiric anti-infective plans for elderly SAE patients,considering comorbidities,organ function,infection site,local bacterial spectrum,and resistance.The treatment protocol can be adjusted once the pathogen is identifi ed.Stabilizing hemodynamics and ensuring cerebral perfusion are two fl uid resuscitation strategies used in elderly SAE patients.An individualized approach to fl uid resuscitation using restrictive fl uid volumes should be employed.Supportive treatment for elderly SAE patients focuses on improving tissue perfusion/oxygenation,controlling blood glucose levels,and correcting internal imbalances.Early rehabilitation,nutritional support,cognitive training,and family-based emotional support are important components of comprehensive care.CONCLUSION:The diagnosis and management of SAE in elderly patients support early recognition and timely intervention.
文摘BACKGROUND Hepatic encephalopathy(HE)is a primary complication following transjugular intrahepatic portosystemic shunt(TIPS),but the utility of pharmacological prophylaxis for HE is unclear.AIM To assess the HE incidence post-TIPS across various groups and the prophylactic efficacies of various medications.METHODS A thorough literature search was performed in PubMed,Web of Science,EMBASE,and the Cochrane Library databases from their inception to November 24,2024,to collect data regarding HE incidence.The main outcome was HE incidence post-TIPS.A meta-analysis using a random effects model was performed to obtain odds ratios(ORs)and 95%confidence intervals.Statistical analyses were conducted using Stata and RevMan software.RESULTS This meta-analysis included nine studies with 1140 patients;647 received pharmacological agents including lactulose,rifaximin,albumin,and l-ornithin-l-aspartate,and 493 did not(controls).(1)In the single-group meta-analysis,the control group had higher short-and long-term HE rates than the drug intervention group.Among patients with and without prior HE,the non-intervention group's HE rates were also higher;(2)Pharmacological prevention post-TIPS significantly reduced HE incidence[OR=0.59(0.45,0.77),P=0.0001].Compared with the no prophylaxis,rifaximin reduced the risk of HE after TIPS[OR=0.52(0.29,0.95),P=0.03],but lactulose did not;(3)In patients without prior HE,pharmacological prevention significantly reduced post-TIPS HE incidence[OR=0.62(0.41,0.95),P=0.03];and(4)Network meta-analysis showed no significant differences among five prevention strategies.CONCLUSION The HE incidence after TIPS was relatively high,and the use of drugs after TIPS may reduce the HE incidence.However,research,especially large-scale randomized controlled trials,is still lacking.
文摘The gut microbiota plays a pivotal role in the pathogenesis of liver diseases,particularly hepatic encephalopathy(HE),in which dysbiosis contributes to ammonia production,systemic inflammation,and neurocognitive dysfunction.Emerging evidence suggests that targeting the gut-liver axis through pharmacological and microbiota-based interventions can mitigate liver disease progression and HE severity.This review explored the latest therapeutic strategies aimed at modulating gut microbiota in liver disease,focusing on traditional approaches such as non-absorbable disaccharides(lactulose,lactitol),antibiotics(rifaximin),and probiotics as well as novel interventions,including postbiotics,synbiotics,and fecal microbiota transplantation.Additionally,bile acid modulators,short-chain fatty acid derivatives,and microbiome-targeted small molecules are being investigated for their potential to restore gut-liver homeostasis.We also discussed the implications of gut microbiota modulation in conditions beyond HE,such as metabolic dysfunction-associated steatotic liver disease and cirrhosis.By integrating gut microbiotatargeted therapies into liver disease management,we may develop more effective,personalized approaches to improve patient outcomes and reduce complications.
基金the Shanghai Municipal Health Commission Medical New Technology Research and Translation Seed Program,No.2024ZZ2052Scientific Research Project funded by Shanghai Fifth People’s Hospital,Fudan University,No.2023WYRH03 and No.2025GZRFY05+2 种基金Shanghai Putuo District Health System Clinical Medicine Discipline Construction Project,No.2024tszk01Shanghai Health System Key Discipline,No.2024ZDXK0005Shanghai Minhang District Health and Family Planning Commission,No.2024MWDXK01.
文摘BACKGROUND Sepsis-associated encephalopathy(SAE)is a common complication of sepsis,characterized by cognitive impairment,altered consciousness,and psychiatric symptoms,including anxiety and depression.These psychiatric symptoms often exacerbate the overall prognosis and quality of life of affected patients.However,the underlying metabolic and proteomic features associated with SAE-induced psychiatric symptoms remain poorly understood.AIM To investigate the clinical manifestations of anxiety and depression in patients with sepsis and SAE and to explore their associated metabolic and proteomic characteristics.METHODS A total of 88 patients were enrolled,comprising 30 healthy controls,29 patients with sepsis,and 29 with SAE.Anxiety and depression symptoms were evaluated using the Hamilton anxiety rating scale(HAM-A)and Hamilton depression rating scale(HAM-D)in sepsis and SAE.Cognitive function was assessed using the Montreal Cognitive Assessment(MoCA),and quality of life was measured using the 36-Item Short Form Health Survey.Plasma samples were analyzed for metabolomic and proteomic profiling.Metabolic alterations were identified through liquid chromatography-mass spectrometry,while protein expression was assessed using Olink targeted proteomics.RESULTS Compared to the sepsis group,patients with SAE exhibited significantly higher levels of anxiety(HAM-A:15.2±4.0 vs 10.4±3.0,P=0.012)and depression(HAM-D:16.0±3.5 vs 9.1±2.3,P=0.003).Cognitive function,as measured by MoCA,was notably impaired in the SAE group(MoCA:18.5±4.0 vs 24.5±3.2,P=0.007).Quality of life scores,particularly in physical functioning,emotional well-being,and mental health,were significantly lower in patients with SAE.Metabolomic and proteomic analyses revealed substantial alterations in oxidative stress and nicotinamide adenine dinucleotide(NAD+)metabolism pathways,with cluster of differentiation(CD)38 emerging as a potential biomarker associated with psychiatric symptoms in SAE.Further validation in an independent cohort confirmed the diagnostic relevance of CD38.CONCLUSION This study highlights the significant psychological burden of SAE,manifested as anxiety and depression.Multiomics analysis identified distinct metabolic alterations,particularly in NAD+metabolism,that may contribute to psychiatric symptom development and progression.Furthermore,CD38 was identified as a promising biomarker for the early detection of SAE,providing potential avenues for early intervention and therapeutic targeting.
基金funded by the National Key Research and Devel-opment Program of China(2022YFA0806400)the CAMS Innova-tion Fund for Medical Sciences(CIFMS)(2023-I2M-2-006,2021-1-I2M-027,and 2021-1-I2M-028)+1 种基金the National Natural Science Foundation of China(82173888 and 81973290)the Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD Study(Z141102004414062).
文摘Hyperglycemia in individuals with diabetes causes cognitive impairment,called diabetic encephalopathy(DE).The pathogenesis of DE is closely related to angiopathy,and effective treatment is highly desirable.The botanical agent berberine(BBR)effectively lowers blood glucose in diabetic patients.Here,we show for the first time that BBR significantly improved cognitive function in type 2 diabetic encephalopathy KK-Ay(2DEK)mice.High-resolution imaging via fluorescence micro-optical sectioning tomography(fMOST)revealed that the integrity of brain vessels was improved by BBR treatment.The improvements in average vessel diameter,vessel length,and total vessel volume were significant in the parietal association cortex(PtA),as well as in the CA1 and CA3 regions.A mechanistic study revealed that oral BBR inhibited δ-valerobetaine(δ-VB,a metabolite of the gut microbiota)production in the intestine.As intestinal δ-VB can enter the circulation and activate the Toll-like receptor-4(TLR-4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa B(NF-jB)inflammatory pathway in the epithelial cells of blood vessels through interacting with TLR-4,BBR might reduce the intestinal level of δ-VB to protect the cerebral blood vessels of DE mice and improve their brain function.Fecal microbiota transplantation(FMT)using the gut microbiota from BBR-treated mice confirmed the vital role of the gut microbiota.BBR showed a wide range of effects on the gut flora,also increasing short-chain fatty acid(SCFA)production and decreasing lipopolysaccharide(LPS)levels in the intestine by adjusting the abundance of SCFA-or LPS-producing bacteria.The observed therapeutic efficacy in vivo revealed a synergistic effect of BBR on the gut microbiota.Conclusively,we found an association between the gut microbiota and blood vessels,of which intestinal δ-VB might be a chemical link.Mainly through downregulating δ-VB in the intestine,BBR protected cerebral vessels and alleviated DE.
基金approved by Chungbuk National University Hospital Institutional Review Board in Cheongju,Chugbuk,South Korea(No.CBNUH2022-09-013-HE001).
文摘BACKGROUND Hepatic encephalopathy(HE)affects more than 30%of patients with cirrhosis.Extrahepatic portosystemic shunt(EHPSS)has been suggested to be a contributing factor to HE recurrence and mortality.Therefore,early detection and intervention in EHPSS may improve patient outcomes.AIM To evaluate the effects of shunt embolization on mortality and HE recurrence.METHODS In this retrospective case-control study,16 cirrhotic patients with HE treated at a tertiary care center from January 2012 to August 2022 were included.Outcomes in eight patients who underwent embolization of EHPSS were compared with those in eight patients receiving standard care without embolization.Data on baseline characteristics,HE recurrence,and overall survival were collected and analyzed using Kaplan-Meier and log-rank tests.RESULTS Baseline characteristics were comparable between the groups.The 1-year overall survival rate was significantly higher in the treatment group(0.50)than in the control group(0.33).The HE recurrence-free rate was also higher in the treatment group(1.00)than in the control group(0.17).The median survival duration was longer in the treatment group{not reached[95%confidence interval(CI):23.84 to not available(NA)]}than in the control group[15.02 months(95%CI:9.86 to NA)](P=0.006).Similarly,the recurrence-free duration was longer in the treatment group[63.09 months(95%CI:63.09 to NA)]than in the control group[9.21 months(95%CI:4.47 to NA)](P=0.006).EHPSS embolization significantly reduced 1-year HE recurrence(hazard ratio=0.09;95%CI:0.01-0.75;P=0.026).CONCLUSION EHPSS embolization significantly improves 1-year survival and prevents recurrence of HE in cirrhotic patients.Routine computed tomography and early embolization are clinically beneficial.
文摘BACKGROUND The gut microbiome is associated with hepatic encephalopathy(HE),but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent.AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE.METHODS We searched the PubMed,Web of Science,EMBASE,and Cochrane databases using two keywords,HE,and gut microbiome.According to the inclusion and exclusion criteria,suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE.The data were analyzed using RevMan and STATA.RESULTS Seventeen studies were included:(1)A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE[-0.20,95%confidence interval(CI):-0.28 to-0.13,I2=20%];(2)The relative abundances of Lachnospiraceae(-2.73,95%CI:-4.58 to-0.87,I2=38%)and Ruminococcaceae(-2.93,95%CI:-4.29 to-1.56,I2=0%)in liver cirrhosis patients with HE was significantly lower than those in patients without HE;(3)In patients with HE,Enterococcus,Proteobacteria,Enterococcaceae,and Enterobacteriaceae proportions increased,but Ruminococcaceae,Lachnospiraceae,Prevotellaceae,and Bacteroidetes proportions decreased;(4)Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected;and(5)Differential gut microbiomes may serve as diagnostic and prognostic tools.CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ.Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.
基金Supported by The Basic and Clinical Integration Project of Xi'an Jiaotong University,No.YXJLRH2022067.
文摘In this editorial we comment on the article by Jiang et al.We focus on the Ence-phalApp Stroop test which is an innovative,smartphone-based tool specifically designed for screening minimal hepatic encephalopathy(MHE)in cirrhosis patients.Traditional MHE screening methods,while highly sensitive and specific,are often complex,time-consuming,and require controlled environmental con-ditions,limiting their widespread clinical use.The EncephalApp Stroop test si-mplifies the screening process,enhances diagnostic efficiency,and is applicable across diverse cultural contexts.However,the combination of additional bio-markers could further improve diagnostic accuracy.Despite its promising po-tential,more multicenter clinical studies are required to validate its effectiveness and applicability on a global scale.
文摘BACKGROUND Several conditions may present with acute neurological symptoms,thus mimicking the presentation of stroke.Although the underlying disorder can be diagnosed after careful medical,neurological,and radiological examinations,a few conditions,such as Wernicke encephalopathy(WE),may present a particular diagnostic difficulty.WE is a neurological disorder caused by deficiency of thiamine(B1 vitamin),most often resulting from alcoholism,malnutrition,hyperemesis gravidarum or bariatric surgery.The diagnosis of WE in a certain historical,clinical setting is easily suggested,but in a few cases presenting with acute neurological deficits,it can be particularly challenging.CASE SUMMARY We present the case of a 63-year-old man who was brought to the emergency department after developing weakness of the left extremities,dizziness and a confusional state,which had lasted for approximately 30 minutes.The patient had a similar episode of a confusional state approximately two months earlier;at that time,a transient ischemic attack was suspected and he was started on aspirin.The initial clinical evaluation and imaging findings were unremarkable for stroke,but the patient’s symptoms,history of chronic alcohol abuse and abnormal liver function tests prompted the consideration of WE.Magnetic resonance imaging findings in subthalamic areas and electroencephalogram data of diffuse delta activity supported this diagnosis.CONCLUSION Through this case report,we aim to underscore the importance of considering WE as a differential diagnosis in patients presenting with symptoms suggestive of stroke,especially when the presentation is atypical or when risk factors for thiamine deficiency are present.Since intravenous thiamine significantly improves outcomes,delayed recognition and treatment in some cases might be deleterious.
基金Supported by Hefei Natural Science Foundation,No.202341.
文摘Transjugular intrahepatic portosystemic shunt(TIPS)is widely used to treat portal hypertension and its complications patients with cirrhosis.However,managing post-TIPS hepatic encephalopathy(HE)remains a major clinical challenge.HE is characterized by a high incidence and a complex pathogenesis,influenced by various factors.Therefore,careful patient assessment and selection for TIPS is essential.While previous studies have identified several factors contributing to the occurrence of post-TIPS HE,there is a gap in the comprehen-sive integration of surgical procedural parameters and metabolic mechanisms within a multidimensional analysis.This minireview aims to optimize treatment protocols and refine management strategies by conducting a comprehensive analysis of risk factors,ultimately aiming to reduce the incidence of post-TIPS HE.
文摘Acute Bilirubin Encephalopathy(ABE)is a significant threat to neonates and it leads to disability and high mortality rates.Detecting and treating ABE promptly is important to prevent further complications and long-term issues.Recent studies have explored ABE diagnosis.However,they often face limitations in classification due to reliance on a single modality of Magnetic Resonance Imaging(MRI).To tackle this problem,the authors propose a Tri-M2MT model for precise ABE detection by using tri-modality MRI scans.The scans include T1-weighted imaging(T1WI),T2-weighted imaging(T2WI),and apparent diffusion coefficient maps to get indepth information.Initially,the tri-modality MRI scans are collected and preprocessesed by using an Advanced Gaussian Filter for noise reduction and Z-score normalisation for data standardisation.An Advanced Capsule Network was utilised to extract relevant features by using Snake Optimization Algorithm to select optimal features based on feature correlation with the aim of minimising complexity and enhancing detection accuracy.Furthermore,a multi-transformer approach was used for feature fusion and identify feature correlations effectively.Finally,accurate ABE diagnosis is achieved through the utilisation of a SoftMax layer.The performance of the proposed Tri-M2MT model is evaluated across various metrics,including accuracy,specificity,sensitivity,F1-score,and ROC curve analysis,and the proposed methodology provides better performance compared to existing methodologies.
