Febrile infection-related epilepsy syndrome is an inflammation-related acute encephalopathy that occurs in previously healthy children and adolescents.It is clinically characterized by super-refractory status epilepticus that occurs after a febrile infection and is often associated with poor prognosis.In recent years,with a deeper understanding of this disease,the treatment approaches have shifted to early and timely immunotherapy and comprehensive support on the basis of standardized anti-epileptic seizure treatment.This review comprehensively elaborates the definition,clinical characteristics,auxiliary examinations,pathogenesis,diagnosis and evaluation,treatment,prognosis,and future research directions of febrile infection-related epilepsy syndrome,aiming to enhance under-standing and improve prognosis.

Objective:To investigate the important clinical features and prognosis of febrile infection-related epilepsy syndrome(FIRES).Methods:A retrospective analysis was performed for the data of 15 children with FIRES who were hospitalized and treated in Peking University First Hospital from March 2022 to June 2024,including clinical features,treatment regimens,and prognosis,and follow-up was performed by telephone.Results:The median duration of status epilepticus was 15 days for all children.Of all 15 children,14(93.3%)were comorbid with disturbance of consciousness,8(53.3%)were comorbid with respiratory failure and underwent endotra-cheal incubation,and 13(86.7%)had been admitted to the intensive care unit.In the acute stage,7 children underwent the examination of various inflammatory factors in blood and cerebrospinal fluid,including interleukin(IL)-1β,IL-2,IL-4,IL-5,IL-6,IL-8,IL-10,and tumor necrosis factor-α,and all 7 children had significant increases in the levels of inflammatory factors in cerebrospinal fluid,which were significantly higher than the levels of inflammatory factors in serum.Of all 15 children,12(80%)had diffuse slow wave changes on electroencephalography,and migrating focal seizures were detected in 7 children(46.7%).Cranial magnetic resonance im-aging(MRI)manifestations in the acute stage included temporal and insular cortical edema(60%),abnormal white matter signal(33.3%),and claustrum sign(13.3%),and MRI features in the chronic stage included the deepening of cerebral sulci(75%)and ventricular dilatation(33.3%).The treatment in the acute stage in-cluded intravenous drip of gamma-globulin and high-dose methyl-prednisolone in 15 children(effective in 2 children),ketogenic diet in 4 children(effective in 1 child),tocilizumab in 5 children(effective in 3 children),and anakinra in 2 children(effective in 1 child).As of the last follow-up,the median duration of disease was 14.0 months(4-65 months)for all patients,and only 2 children achieved complete seizure control,while the remaining 13 children had refractory epilepsy.Cognitive impairment was observed in 93.3%of the children.Conclusion:FIRES often has acute and severe conditions,and first-line immunotherapies often have a poor therapeutic ef-fect.Tocilizumab and anakinra may be effective in some patients with seizures in the acute stage.

Objective:To investigate the cranial magnetic resonance imaging(MRI)characteristics of children with febrile infection-related epilepsy syndrome(FIRES).Methods:A retrospective analysis was performed for the imaging characteristics of children with FIRES who were admitted to Department of Pediatrics,Peking University First Hospital,from November 2020 to August 2024,includ-ing the characteristic manifestation of claustrum sign on cranial MRI.Results:A total of 86 children with a confirmed diagnosis of FIRES were included,among whom there were 65 boys(75.6%)and 21 girls(24.4%),with a median age of onset of 6.35(4.4,8.32)years.Among these children,14(16.3%)had normal cranial MRI findings in the acute stage,with T2 FLAIR changes as the most common abnormal manifestation(39.5%),and 30 children(34.9%)experienced brain atrophy,with a median time of 44(34,72)days for the onset of brain atrophy for the first time.There were 22 children(25.6%)with positive bilateral claustrum sign on cranial MRI,which manifested as symmetrical T2 FLAIR hyperintensity with limited diffusion in the bilateral claustrum,and the median time to the first appearance of claustrum sign was 11(7,15)days,while the median time to negative conversion of claustrum sign was 33(24,50)days.The claustrum sign disappeared after the relief of status epilepticus in the acute stage in most children.Among the children in this study,71 entered the chronic stage during follow-up,3 had normal cranial MRI results during the course of the disease,and 34 had brain atrophy for the first time in the chronic stage,with a median time of 186(115,429)days to the first appearance of brain atrophy on cranial MRI,while of all 86 children,64(80.0%)experienced brain atrophy on cranial MRI in the acute stage and the chronic stage.Conclusion:Children with FIRES have diverse cranial MRI characteristics.There might be normal MRI manifestations at the beginning of the disease,and positive bilateral claustrum sign might be the specific manifestation in the acute stage.Changes in the claustrum disappear after the relief of status epilepticus in most cases,and most patients may progress to brain atrophy in the chronic stage.

Objective:To investigate the efficacy and safety of ketogenic diet,anakinra,and tocilizumab in the treatment of febrile infection-related epilepsy syndrome(FIRES)through a meta-analysis.Methods:With FIRES,ketogenic diet,anakinra,and tocili-zumab as search terms,the databases of PubMed,Embase,Web of Science,the Cochrane Library,Clinicalttrials.gov,CNKI,Wanfang Data,and VIP were searched for related articles published up to December 13,2024.Two reviewers independently screened the ar-ticles according to the inclusion and exclusion criteria and assessed the risk of bias of the studies included.Review Manager was used to perform the meta-analysis.Results:Among the 549 studies,45 case reports and case series met the inclusion criteria,and there were 45 retrospective studies in total,among which 25,8,and 17 were included in the ketogenic diet group,the tocilizumab group,and the anakinra group,respectively,with 66 patients in the ketogenic diet group,8 in the the tocilizumab group,and 54 in the anakinra group.There were 3 case reports,in which all 3 patients were treated with tocilizumab and anakinra.The meta-analysis showed that in the treatment of FIRES in the acute stage,ketogenic diet,anakinra,and tocilizumab showed a response raet of 68%(95%CI=51%-85%,I 2=71%,P<0.01),57%(95%CI=35%-80%,I 2=71%,P<0.01),and 100%(95%CI=79%-100%,I 2=0%,P=1.00),respec-tively,with no statistical differences between studies.The survival rate was 96%(95%CI=89%-100%,I 2=0%,P=1.00)in the keto-genic diet group,96%(95%CI=89%-100%,I 2=0%,P=1.00)in the FIRES,and ketogenic diet and anakinra treatment have a relatively high incidence rate of adverse reactions.Hypoglycemia and infec-tion are adverse reactions commonly observed during treatment.

Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Objective:To establish a mouse model of spinal cord injury(SCI),and to investigate the effect of electroacupuncture(EA)intervention on cell apoptosis after acute SCI and its mechanism.Methods:Female C57BL/6 mice were used to establish a model of SCI,and after successful modeling,the mice were randomly divided into SCI group,EA group,and Rosiglitazone group(R group);a sham-operation group(Sham group)was also established.After successful modeling,the mice in the EA group were given EA at bilat-eral Jiaji points and Zusanli once a day for 14 days,those in the R ture,and the number of surviving cells.The EA group and the R group had a significant reduction in the expression of caspase-3 and significant increases in the expression of PPARγ and CD36,and the EA group had significant reductions in the expression of Hba-a1 and Hbb-bt.In addition,RNA-Seq and TMT/iTRAQ techniques,significant analysis,Venn analysis,and dual-omics analysis identi-fied Hba-a1 and Hbb-bt as the target genes of EA.The KEGG pathway enrichment analysis showed that EA had a significant effect on the PPAR signaling pathway.Conclusion:By regulating the PPARγ-CD36 signaling pathway,EA can promote the clearance of Hba-a1 and Hbb-bt after SCI,reduce the expression level of caspase-3,alleviate cell apoptosis,and facilitate the recovery of spinal cord nerve function.

Objective:To investigate the inhibitory effect of Xiaojianzhong Granule(XJZG)on food allergy(FA)and related mecha-nisms in terms of gut microbiota,zonula occluden-1(ZO-1),and Occludin.Methods:A total of 24 specific pathogen-free female BALB/c mice were randomly divided into normal group,model group,prevention group,and treatment group,with 6 mice in each group.The mice in the prevention group were given XJZG by gavage at a standard dose of 5.85 g/kg/day from 3 days before the first challenge till 4 hours before the last challenge;the mice in the treatment group were given XJZG at the double dose for 3 days based on the allergy score;the mice in the other groups were given an equal volume of distilled water by gavage.At the end of the experiment,al-lergy score and anal temperature were measured;flow cytometry was used to measure eosinophils and mast cells in mesenteric lymph nodes(MLNs);toluidine blue staining was performed for mast cells in jejunal tissue;immunohistochemistry was used to measure the expression of ZO-1 and Occludin;16S rRNA sequencing was per-formed to analyze the microbiota in the intestinal content;high-performance liquid chromatography-mass spectrometry was used to measure the content of short-chain fatty acids(SCFAs)in jejunal lavage fluid.Results:Compared with the model group,the prevention group and the treatment group had significant reductions in al-lergy score(P=0.000,P=0.000),anal temperature(P=0.002,P=0.000),the proportion of eosinophils and mast cells in MLNs(P<0.05),and mast cell infiltration in jejunal tissue(P=0.000,P=0.000).Compared with the normal group,the model group had signifi-cant increases in the relative abundances of Erysipelaceae and Turicibacter,while the prevention group and the treatment group had disappearance of Erysipelaceae and Turicibacter and an increase in the relative abundance of Porphyromonadaceae.Compared with the normal group,the model group had a significant reduction in the content of propionate in jejunal lavage fluid(P=0.014),and compared with the model group,the prevention group had a significant increase in the content of propionate in jejunal lavage fluid(P=0.024),as well as a significant increase in the treatment group(P=0.008).In the model group,the expression of ZO-1 was downregulated(P=0.010),and the expression of Occludin was significantly downregulated(P=0.002),while the expression of ZO-1 and Occludin re-turned to normal levels in the prevention group and the treatment group(P=0.001,P=0.013;P=0.025,P=0.015).Conclusion:XJZG can change the composition and abundance of gut microbiota,increase the concentration of SCFAs,upregulate the expression of ZO-1 and Occludin,promote the repair of intestinal barrier,and inhibit food allergy.

Objective:To investigate whether biochanin A(BCA)has a protective effect against dextran sodium sulfate(DSS)-in-duced ulcerative colitis(UC)in mice.Methods:Thirty C57BL/6N mice were randomly divided into normal control group,DSS model group,sulfasalazine(SASP)-positive drug control group,and low/medium/high-dose(5 mg/kg,10 mg/kg,and 20 mg/kg)BCA groups.The mouse model of UC was induced by administering 2.5%DSS aqueous solution for 7 days.During the experimental period,both the normal control and model groups were given 0.5%carboxymethyl cellulose sodium solution daily by gavage.The positive control group was given 100 mg/kg SASP,while the BCA groups were given BCA suspensions at doses of 5 mg/kg,10 mg/kg,and 20 mg/kg.The ad-ministration lasted for 10 days.Body weight changes and fecal status of the mice were recorded every day;the colon was dissected,col-lected,and measured for its length.The colon was stained with Hematoxylin-Eosin for pathomorphological study.Quantitative poly-merase chain reaction was used to determine the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)in the colon.Immunofluorescence was used to determine the expression of tight junction proteins,zonula occluden-1(ZO-1)and occludin,in the colon.Results:It showed that 5 mg/kg and 10 mg/kg BCA significantly alleviated weight loss in mice with UC,while 5 mg/kg,10 mg/kg,and 20 mg/kg BCA reduced the disease activity index scores.Additionally,BCA showed similar effects to SASP in improving the structure and reducing the shortening of the colon in mice with UC.Compared with the model group,all BCA groups had significantly decreased TNF-α(P=0.024、P=0.060、P=0.003)and IL-6(P=0.002、P<0.001、P<0.001)and significantly increased IL-10(P=0.006、P=0.003、P<0.001),with varying degrees of up-regulated expression of tight junction proteins.Conclusion:BCA can effectively alleviate DSS-induced symptoms,reduce intes-tinal damage,and protect the intestinal barrier in mice with UC.

Objective:To investigate the role and possible mechanism of triggering receptor expressed on myeloid cells-1(TREM-1)in the inflammatory response of rat vascular smooth muscle cells(VSMCs)mediated by trimethylamine N-oxide(TMAO).Methods:VSMCs were treated with TMAO at different concentrations(0,100,300,600,900,1 200,1 500 μmol/L)for 24 hours.VSMCs were transfected with the siRNA interference plasmid targeting the TREM-1 gene(si-TREM-1)and its negative control interference plas-mid(si-NC),and 600 μmol/L TMAO was used to induce inflammatory response in VSMCs,combined with the intervention with the nuclear factor-kappa B(NF-κB)activator phorbol myristate acetate(PMA)for 24 hours.CCK-8 assay was used to measure cell prolif-erative activity;ELISA was used to measure the levels of interleu-kin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)in cell supernatant;qRT-PCR was used to measure the mRNA expression levels of TREM-1,cyclooxygenase-2(COX-2),intercellular adhesion molecule-1(ICAM-1),IL-1β,IL-6,and TNF-α in cells,and Western blot was used to measure the protein expression levels of TREM-1,COX-2,ICAM-1,NF-κB p65,and p-NF-κB p65(Ser536)in cells.Results:Treatment with TMAO at different concentrations had no significant impact on the prolifera-tive activity of VSMCs(P=0.375),but it significantly upregulated the levels of IL-1β,IL-6,and TNF-α in supernatant and the mRNA and protein expression levels of TREM-1,COX-2,and ICAM-1 in cells(all P<0.01)in a concentration-dependent manner.Silencing of the TREM-1 gene significantly inhibited the increases in the levels of IL-1β,IL-6,and TNF-α in the supernatant of VSMCs in-duced by TMAO,and it also suppressed the upregulation of the mRNA expression levels of COX-2,ICAM-1,IL-1β,IL-6,and TNF-α and the ratio of p-NF-kB p65/NF-kB p65 in VSMCs(all P<0.01).However,PMA intervention significantly reversed the role of si-lencing the TREM-1 gene on TMAO-induced inflammatory response in VSMCs.Conclusion:Silencing of the TREM-1 gene can in-hibit TMAO-induced inflammatory response in VSMCs,possibly by inhibiting the activation of the NF-κB pathway.

Objective:Malnutrition is prevalent among patients with chronic obstructive pulmonary disease(COPD)and closely associ-ated with adverse outcomes.This study aimed to evaluate the effectiveness of three nutritional indices in predicting all-cause mortality among COPD patients.Methods:Based on the National Health and Nutrition Examination Survey(NHANES),this study included 1640 patients with COPD surveyed from 1999 to 2018.The optimal cutoff values for controlling nutritional status(CONUT)score,geri-atric nutritional risk index(GNRI),and prognostic nutritional index(PNI)were determined using receiver operating characteristic curves.The predictive value of these nutritional indices was assessed using the area under the receiver operating characteristic curve and C-index.Their predictive abilities were compared using the net reclassification improvement and integrated discrimination improvement.A Cox regression analysis was conducted to explore the association of the three nutritional indices with all-cause mortality.Results:Log-rank tests revealed lower overall survival rates in patients with higher nutritional risks(P<0.001).In multivariate Cox regression adjusting for all covariates,CONUT score(hazard ratio[HR]=1.31,95%CI=1.03-1.67,P=0.030),GNRI(HR=2.02,95%CI=1.26-3.24,P=0.004),and PNI(HR=2.05,95%CI=1.53-2.75,P<0.001)were independently associated with all-cause mortality.Conclusion:This study confirms that the three nutritional indices are effective predictors of all-cause mortality in COPD patients.Compared with PNI,CONUT score and GNRI demonstrate im-proved predictive abilities,and they are recommended for routine screening for high-risk malnutrition in COPD patients.