Doxorubicin (DOX)-induced cardiotoxicity and sepsis-induced myocardial injury (SIMI) represent significant clinical challenges in patients undergoing chemotherapy, sharing a common pathological basis of oxidative stress and mitochondrial dysfunction. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently been shown to play a critical role in DOX-induced cardiotoxicity and lipopolysaccharide (LPS)-induced SIMI. This article systematically reviews the mechanisms underlying myocardial injury caused by DOX and sepsis, identifying ferroptosis as a central common pathway. DOX triggers a burst of reactive oxygen species within mitochondria and inhibits glutathione peroxidase 4 (GPX4) activity through redox cycling of its quinone group and high-affinity accumulation in mitochondrial cardiolipin. LPS, by activating pattern recognition receptors and related inflammatory signaling pathways, provokes a cytokine storm and mitochondrial dysfunction. Both can disrupt the core regulatory axis of cysteine-glutathione (GSH)-GPX4, synergistically promoting ferroptosis in cardiomyocytes. Moreover, epigenetic regulation plays a key role in DOX- and LPS-induced cardiomyocyte ferroptosis and may serve as a promising therapeutic target. A deeper understanding of the ferroptosis mechanism and its epigenetic regulatory network in the synergistic injury induced by DOX and sepsis is of great importance for developing novel strategies to mitigate chemotherapy-related cardiotoxicity and improve outcomes in cancer patients with concurrent infections.

OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription （ZSHXP） ameliorates cognitive dysfunction in rats with vascular dementia （VD） induced by the bilateral common carotid artery ligation （2-VO model rats） through regulating the glucose-regulated protein 78 （GRP78）/protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4） signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley （SD） rats were randomly divided into six groups： Sham group， Model group， donepezil hydrochloride group （0.45 mg·kg^-1）， and ZSHXP groups at low （8.90 g·kg^-1）， medium （17.80 g·kg^-1）， and high （35.60 g·kg^-1） doses，with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats， and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin （HE） and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy （TEM） was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen （NeuN） with GRP78 and βⅢ Tubulin with gasdermin D （GSDMD） in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress （ERS）-related proteins including GRP78， PERK， ATF4， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， C/EBP homologous protein （CHOP）， NOD-like receptor protein 3 （NLRP3）， Caspase-1 and GSDMD. ResultsCompared with the sham operation group， the model group showed a significantly prolonged escape latency （P<0.01）， a significant decrease in the number of platform crossings and the residence time in the target quadrant （P<0.01）， and a markedly reduced recognition index （P<0.01）. Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity， deformed and shrunken cell bodies， and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously， accompanied by abnormal dilation and swelling， and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78， p-PERK/PERK， ATF4， CHOP， NLRP3， GSDMD and Caspase-1 in the model group were significantly elevated （P<0.01）. Compared with the model group， the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency （P<0.01） and an increased number of platform crossings （P<0.05， P<0.01）. The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups （P<0.05， P<0.01）， with a significantly improved recognition index （P<0.01）. In the donepezil hydrochloride group and all ZSHXP groups， the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group， the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group， the protein expressions of GRP78， ATF4 and CHOP were increased （P<0.01）， while the expression of p-PERK/PERK was decreased （P<0.05）. In the ZSHXP low-dose group， the expressions of GRP78， p-PERK/PERK and CHOP were elevated （P<0.05， P<0.01）. The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK， ATF4 and CHOP （P<0.01）， and the high-dose group had a markedly reduced GRP78 protein expression （P<0.01）. In the donepezil hydrochloride group， the Caspase-1 protein expression was increased （P<0.01） and the NLRP3 protein expression was decreased （P<0.01）. In the ZSHXP low-dose group， the GSDMD expression was elevated （P<0.01） while the NLRP3 protein expression was reduced （P<0.01）. After treatment with medium and high doses of ZSHXP， the protein expression levels of NLRP3， GSDMD and Caspase-1 were significantly decreased （P<0.01）. ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway， which ameliorates ERS and inhibits neuronal pyroptosis.

Objective To provide a scientific basis for vector prevention and control in port areas, vector monitoring has been conducted continuously to characterize the composition, density, and seasonal fluctuations of vectors across 21 port-areas of Shandong province from 2017 to 2023. Methods In accordance with the Regional Vector Monitoring Plan for Frontier Ports, vector surveillance of mosquitoes, flies, cockroaches, rodents, and other disease vectors was performed. Data were analyzed to describe vector community composition and identify seasonal fluctuations. Results A total of 601 rodents belonging to 1 family, 4 genera, and 4 species were captured. Three dominant rodent species inhabit port areas. In addition, 88 104 mosquitoes were captured and classified into 3 subfamilies, 4 genera, and 12 species; 38 959 flies were trapped and classified into 8 families,31 genera, and 51 species, including 9 dominant fly species in port-areas; and 54 672 captured cockroaches were classified into 2 families,4 genera, and 4 species, with Blattella germanica as the dominant species. Conclusions Significant vector community changes(P＜0.005)have been identified after the epidemic. To improve the pertinence and efficacy of port health quarantine work, continuous and strong attention should be paid to vector compositions and population densities at Shandong ports.

Objective To evaluate the ambient dose equivalent rates of photons and neutrons inside and outside the door of a 10 MV accelerator room, and to report the shielding effect of boron-containing polyethylene as maze wall lining. Methods The ambient dose equivalent rates of photons and neutrons inside and outside the door of an accelerator room were taken as the research subject. The Kersey, Falcão, and modified Kersey methods were used to calculate the ambient dose equivalent rates of neutrons and neutron capture gamma rays inside and outside the door of the room before and after renovation. Measurements were made using an X-ray/γ-ray dose rate instrument and a neutron ambient dose equivalent rate meter. Calculated and measured results were compared. Results Before renovation, the measured neutron dose rate inside the door was 409 μSv/h, while the calculated values were 323 μSv/h (Kersey method), 428 μSv/h (Falcão method), and 219 μSv/h (modified Kersey method). The Falcão method yielded a value closest to the measured value, while the Kersey and the modified Kersey methods underestimated the value by 21% and 46%, respectively. After the installation of boron-containing polyethylene plates, the measured neutron dose rate inside the door was 190 μSv/h, with a 54% reduction. The neutron and photon ambient dose equivalent rates outside the door were 5.8 μSv/h and 6.0 μSv/h, respectively, before renovation, and 0.14 μSv/h and 1.6 μSv/h, respectively, after renovation. Conclusion For a 10 MV accelerator room, neutron shielding and protection measurements are necessary, especially for rooms with short mazes. The Falcão method provides the best estimate of neutron dose rates inside and outside the door. Using boron-containing polyethylene plates as maze wall lining is an economical and effective shielding method.

Objective To explore the diagnostic value of exhaled volatile organic compounds (VOCs) for cystic fibrosis (CF). Methods A systematic search was conducted in PubMed, EMbase, Web of Science, Cochrane Library, CNKI, Wanfang, VIP, and SinoMed databases up to August 7, 2024. Studies that met the inclusion criteria were selected for data extraction and quality assessment. The quality of included studies was assessed by the Newcastle-Ottawa Scale (NOS), and the risk of bias and applicability of included prediction model studies were assessed by the prediction model risk of bias assessment tool (PROBAST). Results A total of 10 studies were included, among which 5 studies only identified specific exhaled VOCs in CF patients, and another 5 developed 7 CF risk prediction models based on the identification of VOCs in CF. The included studies reported a total of 75 exhaled VOCs, most of which belonged to the categories of acylcarnitines, aldehydes, acids, and esters. Most models (n=6, 85.7%) only included exhaled VOCs as predictive factors, and only one model included factors other than VOCs, including forced expiratory flow at 75% of forced vital capacity (FEF75) and modified Medical Research Council scale for the assessment of dyspnea (mMRC). The accuracy of the models ranged from 77% to 100%, and the area under the receiver operating characteristic curve ranged from 0.771 to 0.988. None of the included studies provided information on the calibration of the models. The results of the Prediction Model Risk of Bias Assessment Tool (PROBAST) showed that the overall bias risk of all predictive model studies was high, and the overall applicability was unclear. Conclusion The exhaled VOCs reported in the included studies showed significant heterogeneity, and more research is needed to explore specific compounds for CF. In addition, risk prediction models based on exhaled VOCs have certain value in the diagnosis of CF, but the overall bias risk is relatively high and needs further optimization from aspects such as model construction and validation.

Based on network pharmacology,molecular docking,and experimental validation,this study explored the mechanism by which Hypericum japonicum Thunb-Prunella vulgaris treat liver injury.Mice were randomly divided into four groups:a control group(CON),a model group(CCl4),a high-dose drug group(TXD-H),and a low-dose drug group(TXD-L).A mouse liver in-jury model was established using CCl4 induction.The pathological morphology of liver tissue was observed,and the serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Active ingredients of traditional Chinese medicine and targets related to these medicines and diseases were obtained from databases such as TCMSP,PubChem,Swiss Tar-get Prediction,GeneCards,and DisGeNET.The intersection of these targets was used to identify potential drug targets.A network diagram illustrating the relationships between"drug-active com-ponent-intersection target"was constructed using Cytoscape.Potential targets were analyzed using the STRING database for protein-protein interaction(PPI)analysis and the DAVID database for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking validation was performed using AutoDock Tools software.Subsequently,key target genes,including those related to the NLRP3 inflammasome and pyroptosis,were detected to validate the molecular docking results.Animal experimental results showed that compared to the CON group,serum AST and ALT activities in the CCl4 group mice were significantly increased(P＜0.01),while in the TXD-L group,serum AST and ALT activities were significantly decreased(P＜0.05)compared to the CCl4 group,and in the TXD-H group,AST and ALT activities were significantly decreased(P＜0.01).Through network pharmacology,135 potential targets were i-dentified,with key components found to be tetramethoxyluteolin,quercetin,kaempferol,luteolin and morin based on degree values,and key targets including TNF,SRC,AKT1,EGFR and ESR1.GO enrichment analysis yielded 304 entries,while KEGG enrichment analysis identified 91 biologi-cal pathways.Molecular docking results demonstrated strong binding between the main compo-nents of Hypericum japonicurn Thunb-Prunella vulgaris and key targets.qPCR results showed that compared to the CON group,the CCl4 group exhibited upregulated relative expression levels of SRC,EGFR,TNF-α,AKT1,and IL-18 mRNA,with significant increases in MyD88,NF-κB,IL-1β,NLRP3,Caspase-1,and ASC mRNA(P＜0.05),and significant upregulation of TLR4 and GS-DMD mRNA(P＜0.01).Compared to the CCl4 group,the TXD-H group displayed significant downregulation of EGFR,AKT1,TLR4,IL-1β,and GSDMD mRNA(P＜0.01),significant decrea-ses in TNF-α,MyD88,NF-κB,NLRP3,and ASC mRNA(P＜0.05),while SRC,IL-18,and Caspase-1 mRNA showed a downward trend.In conclusion,Hypericum japonicum Thunb-Prunel-la vulgaris exerts hepatoprotective effects through multiple components and pathways,among which inhibition of the NF-κB-NLRP3 pathway to reduce hepatocyte pyroptosis may be one of the important pathways for its protective effects.

Objective:To analyze the incidence of adverse treatment outcome of rifampicin-resistant tuberculosis (RR-TB) patients and influencing factors in 9 provinces in China.Methods:The information about the basic characteristics, diagnosis and treatment of RR-TB patients registered from January 1, 2017 to December 31, 2021 in 9 provinces (Beijing, Jilin, Shanghai, Jiangsu, Zhejiang, Hubei, Henan, Yunnan and Guizhou) were collected from the tuberculosis information management sub-system of China Disease Control and Prevention Information System for a descriptive analysis, and the influencing factors of adverse treatment outcome were identified by binary logistic regression analysis.Results:In 18 204 RR-TB patients in this study a total of 6 852 had adverse treatment outcomes (37.64%). Treatment failure occurred in 1 031 patients, 1 272 patients died, 2 284 patients were lost to follow-up, and 2 265 patients were not evaluated. The results of multivariate logistic regression analysis showed that being man (a OR=1.54, 95% CI: 1.43-1.66), age ≥65 years (a OR=2.42, 95% CI: 2.20-2.67), being from other ethnic groups (a OR=1.18, 95% CI: 1.03-1.35), being farmer (a OR=1.22, 95% CI: 1.13-1.32), being retired with honours or being retired (a OR=1.16, 95% CI: 1.00-1.35) and being floating population (a OR=1.23, 95% CI: 1.13-1.34), re-treatment (a OR=1.33, 95% CI: 1.24-1.42), long-term treatment therapy (a OR=3.26, 95% CI: 2.52-4.23), living in central provinces (a OR=2.76, 95% CI: 2.55-2.99), living in western provinces (a OR=2.31, 95% CI: 2.08-2.57) were the influencing factors for adverse treatment outcome of RR-TB. Conclusions:The incidence of adverse outcomes in RR-TB patients in 9 provinces in China was higher from 2017 to 2021. There were many influencing factors associated with adverse treatment outcome in RR-TB patients, especially the area specific factors. The national tuberculosis control program should strengthen the follow-up and treatment management of RR-TB in men, the elderly, floating population, people in central and western provinces and other key groups, actively promote the short-term treatment program and improve the allocation of medical resources to reduce the influencing for adverse treatment outcomes in RR-TB patient.

Objective:To explore the morphological characteristics of the corpus callosum (CC) in patients with unilateral medial temporal lobe epilepsy (mTLE) with hippocampal sclerosis (HS), and their correlation with hippocampal volume and clinical indicators.Methods:This was a cross-sectional study. Clinical (age of onset, disease duration, seizure frequency, seizure duration, etc.) and imaging data of 44 patients mTLE with unilateral HS confirmed by postoperative pathology and 42 healthy controls (HCs) recruited at West China Hospital of Sichuan University from June 2017 to May 2023 were analyzed retrospectively. Among the 44 patients, 19 had left-sided HS and 25 had right-sided HS. All subjects underwent high-resolution 3D T 1WI. Hippocampal volumes were obtained using FreeSurfer. ART was used to measure the morphological parameters of the CC for each participant, including total CC area, volume, perimeter, length, thickness, circularity, and the area of seven CC subregions defined by Witelson: rostrum, genu, body, anterior midbody, posterior midbody, isthmus and splenium. Differences in these metrics between two or three groups were compared using independent samples t-test or one-way ANOVA. Pearson or Spearman correlation analysis was used to observe the correlation between morphological features of the CC and hippocampal volume and other clinical indicators in patients with mTLE with unilateral HS. Results:Compared with HCs, patients with mTLE with unilateral HS had significantly reduced total CC area, CC circularity, as well as the area and thickness of the genu, anterior midbody, posterior midbody, isthmus, splenium, and the area of the rostrum ( P<0.05). Significant differences were observed in the total area, circularity, and subregional areas (genu, rostrum, anterior midbody, posterior midbody, splenium), as well as thickness (genu, anterior midbody, posterior midbody, isthmus) of the CC among mTLE with left-sided HS, mTLE with right-sided HS, and HCs ( P<0.05). When compared to HCs, the total area of the CC, circularity and the areas of the genu, rostrum, anterior midbody, posterior midbody, and splenium, and the thicknesses of the genu, anterior midbody, posterior midbody, and isthmus of the CC were significantly reduced in patients with mTLE with right-sided HS ( P<0.05), and the thicknesses of the midbody and isthmus of the CC were significantly reduced in patients with mTLE with left-sided HS compared to HCs ( P<0.05), and the two-by-two comparison of the rest of the indicators did not show statistically significant differences ( P>0.05). Correlation analysis showed that some morphological abnormalities in the CC in mTLE with unilateral HS patients were significantly correlated with age of onset, disease duration, seizure frequency, seizure duration, and hippocampal volume. Conclusions:mTLE with unilateral HS patients can exhibit morphological abnormalities in the CC, particularly in those with right-sided lesions. These abnormalities are significantly associated with seizure-related factors and hippocampal atrophy.