Folia neuropathologica最新文献

{"title":"11β-hydroxysteroid dehydrogenase type 1 as a predictive biomarker for glucocorticoid treatment response in inflammatory myopathies.","authors":"Ali Kabli, Ahmed Bamaga, Raed Gasemaltayeb, Mohammed Karami, Alaa Alkhotani, Majid Almansouri, Hussain Noorwali, Motaz Fadul, Adnan Badahdah, Riffat Mehboob, Abdulaziz Alqarni, Khalid Khashoggi, Amal Alkhotani, Amany Fathaddin, Amber Hassan, Humaira Waseem, Maher Kurdi","doi":"10.5114/fn.2026.163679","DOIUrl":"https://doi.org/10.5114/fn.2026.163679","url":null,"abstract":"<p><strong>Introduction: </strong>Glucocorticoid therapy is commonly used in inflammatory myopathies (IMs); however, patients' responses are variable, and predictive biomarkers remain unavailable. 11  -hydroxysteroid dehydrogenase type 1 (11  -HSD1), a key enzyme regulating intracellular glucocorticoid activation, may influence treatment response. This study evaluated the relationship between muscle 11  -HSD1 expression and clinical response to glucocorticoid therapy.</p><p><strong>Material and methods: </strong>This study included 32 patients with biopsy-confirmed IMs, of whom 25 received post-biopsy prednisolone (0.5-1 mg/kg/day) for approximately 8 months without glucocorticoid-sparing agents. Clinical response was evaluated based on muscle strength, symptom improvement, and creatinine kinase (CK) reduction. Muscle 11  -HSD1 expression was assessed and categorized as low-medium or high. Associations between enzyme expression and response to glucocorticoid were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of 11  -HSD1 expression.</p><p><strong>Results: </strong>Among the 25 treated patients with glucocorticoid therapy, 21 (84.0%) demonstrated clinical improvement, while 4 (16.0%) showed no clinical response. Baseline diagnostic subtypes and MHC class I expression were not significantly associated with treatment outcome (p = 0.37 and p = 0.59, respectively). In contrast, high 11  -HSD1 expression was significantly associated with clinical improvement (66.7% vs. 0% in non-responders; p = 0.026). High 11  -HSD1 expression was associated with increased odds of response (OR = 17.4, 95% CI: 0.77-392). ROC analysis demonstrated good predictive performance (AUC = 0.83).</p><p><strong>Conclusions: </strong>Elevated muscle 11  -HSD1 expression before glucocorticoid therapy was associated with an improved clinical response after therapy in IMs. These findings support the potential role of 11  -HSD1 as a predictive biomarker.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 2","pages":"142-149"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIM38-mediated ubiquitination of IκBα promotes glioma development by activating the NF-κB signaling pathway","authors":"Peng Yang, Huiyong Li","doi":"10.5114/fn.2026.159126","DOIUrl":"https://doi.org/10.5114/fn.2026.159126","url":null,"abstract":"Introduction: Glioma constitutes approximately 50% of primary brain tumors.This study aimed to analyze the mechanism by which TRIM38 contributes to the progression of glioma.Material and methods: The LN229 and T98G glioma cell lines were purchased.To evaluate cell malignant behaviors, Cell Counting and Transwell assays were employed.Levels of TRIM38 and IB were quantified by RT-qPCR and Western blotting, respectively.Co-immunoprecipitation analyses were conducted to investigate the relationship between TRIM38 and IB.Results: The findings demonstrated that TRIM38 was overexpressed in LN229 and T98G glioma cell lines.The silencing of TRIM38 inhibited malignant behaviors, whereas overexpression of TRIM38 had a stimulatory effect on these processes.Moreover, TRIM38 knockdown suppressed glioma growth in vivo.Co-immunoprecipitation assays confirmed that TRIM38 could bind to IB.Notably, TRIM38 increased the ubiquitination of IB, leading to its protein degradation and subsequent enhancement of IB phosphorylation, which activated the NF-B pathway.JSH-23 treatment counteracted TRIM38 roles in glioma cells.Conclusions: In summary, high levels of TRIM38 promoted glioma progression by increasing the ubiquitination of IB, thereby reducing IB protein stability and expression, and stimulating IB phosphorylation.This ultimately activated the NF-B pathway, exacerbating the malignant behavior of glioma cells.","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.termedia.pl/Journal/-20/pdf-57529-10?filename=TRIM38.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147891010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroectodermal interleukin 12 signaling attenuates spinal cord inflammation and demyelination.","authors":"Arshad Mehmood, Miraj Din, Muhammad Munawer, Sunil Shah, Xiaohui Liu, Hui Jiang, Xuemei Wang","doi":"10.5114/fn.2026.158745","DOIUrl":"10.5114/fn.2026.158745","url":null,"abstract":"<p><strong>Introduction: </strong>Interleukin 12 (IL-12) is a driver of type 1 immunity. Interleukin 12 reduces inflammation in an autoimmune condition in the spinal cord. The aim of this study was to investigate the therapeutic effect of IL-12 in the experimental autoimmune encephalomyelitis model.</p><p><strong>Material and methods: </strong>Interleukin 12 expression was mapped in neurons, oligodendrocytes, natural killer cells, and T lymphocyte cells in the spinal cord of experimental autoimmune encephalomyelitis mice.</p><p><strong>Results: </strong>Interleukin 12 ablation in neurons, oligodendrocytes, natural killer, and T lymphocyte cells in mice and their susceptibility to experimental autoimmune encephalomyelitis showed that the neuroprotective role of IL-12 is mediated by neuroectoderm-derived cells - neurons.</p><p><strong>Conclusions: </strong>Single-nucleus RNA sequencing revealed an IL-12 receptor-induced neuroprotective effect that prevents neurodegeneration, sustains trophic factor release in neuroinflammation, and maintains spinal cord integrity.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 1","pages":"63-72"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MK-2206 dihydrochloride ameliorates the neuronal function in spinal cord injured rats by reducing oxidative stress and modulating the PI3K/Akt pathway.","authors":"Jinjuan Wang, Juanrong Zhou, Alok Tripathi","doi":"10.5114/fn.2025.158298","DOIUrl":"10.5114/fn.2025.158298","url":null,"abstract":"<p><strong>Introduction: </strong>Spinal cord injury (SCI) is one of the major causes of paralysis and physical inability, and its management remains a challenge. The present study evaluated the effect of MK-2206 dihydrochloride in rats with SCI.</p><p><strong>Material and methods: </strong>An impactor device was used to induce SCI, which was treated with MK-2206 12 mg/kg, s.c., daily for 10 days. The effect of MK-2206 on SCI was determined by estimating the locomotor function, inflammatory mediators, and oxidative stress parameters in all groups of rats. Western blot assay was performed to estimate the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) protein in the spinal tissue of SCI rats. Moreover, the effect of MK-2206 on the apoptosis of spinal tissue of SCI rats was assessed.</p><p><strong>Results: </strong>Study data suggest that treatment with MK-2206 reverses the alteration in the neuronal function in SCI rats. Cytokines and oxidative stress were observed to be ameliorated in the MK-2206-treated group compared to the SCI group. Moreover, treatment with MK-2206 attenuated PI3K and Akt protein expression in the spinal tissue of SCI rats. Treatment with MK-2206 significantly reduced the apoptosis of spinal tissue in SCI rats.</p><p><strong>Conclusions: </strong>The data suggest that treatment with MK-2206 prevents injury to the neuronal tissue in SCI rats by modulating the PI3k/Akt pathway.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 1","pages":"87-93"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147767039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipoic acid remodels neurovascular units through the AMPK/NLRP3 signaling pathway after cerebral infarction.","authors":"Yaoru Li, Kai Yu, Lan Zhang, Jian Zhang, Meng Li","doi":"10.5114/fn.2025.155686","DOIUrl":"10.5114/fn.2025.155686","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic stroke (IS) is a disease caused by blood circulation disorders in the brain, ischemia, and hypoxia, resulting in ischemic necrosis or softening of localized brain tissue. Lipoic acid (ALA) is effective in resisting oxidative stress and alleviating the inflammatory response. This study evaluated the mechanism and effects of ALA on neurovascular unit remodeling after cerebral infarction.</p><p><strong>Material and methods: </strong>In male C57BL/6 mice, cerebral infarction was induced using distal middle cerebral artery occlusion (dMCAO). In an in vitro model, cells were allocated to control, model, low dose, medium dose, and high dose groups. Infarct volume analysis, Evans blue extravasation, and enzyme-linked immunosorbent assay (ELISA) kits were used to evaluate the effects of ALA on IS. Cell Counting Kit-8 (CCK-8), 5-ethynyl 2'-deoxyuridine staining (EDU) staining, Western blot and immunohistochemistry were used to evaluate the mechanism of ALA in IS.</p><p><strong>Results: </strong>This study found that the cerebral infarct volume of the ALA treatment group was similar to dMCAO mice. Treatment with ALA reduced the area of Evans blue compared with dMCAO mice at 7 days, and promoted astrocyte and pericyte proliferation in the peri-infarct area at 28 days. Meanwhile, treatment with ALA also increased vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and claudin-5 protein expression levels, suppressed Ang-2 and matrix metalloproteinase-9 (MMP-9) protein expression levels, reduced neuronal apoptosis inhibitory protein (NAIP), leucine-rich repeat (LRR), and PYD domain-containing protein 3 (NLRP3) expression levels, and induced phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression levels in cerebral infarction mice (all p < 0.05). On the other hand, ALA restored cell growth and the number of EDU cells, promoted cell migration, elevated superoxide dismutase (SOD) activity, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inhibited inflammation levels in the in vitro model (all p < 0.05). Treatment with ALA also suppressed NLRP3 and Ang-2 protein expression, reduced MMP-9 protein expression, and induced VEGF, Ang-1, claudin-5, and p-AMPK protein expression levels in the in vitro model (all p < 0.05).</p><p><strong>Conclusions: </strong>ALA improved neurovascular unit remodeling after cerebral infarction through anti-inflammation effects via the AMPK/NLRP3 signaling pathway.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":" ","pages":"73-86"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adult-type diffuse gliomas: examining WHO CNS5 through the genomic data.","authors":"Salwa Hareem, Meghana Korikani, Krishna Puligundla, Rama Kancha","doi":"10.5114/fn.2026.161198","DOIUrl":"https://doi.org/10.5114/fn.2026.161198","url":null,"abstract":"","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 2","pages":"209-112"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TUG1 suppresses neural repair subsequent to cerebral hemorrhage via the miR-381-3p/BDNF axis.","authors":"Fei Li, Xin Zhang, Hong Jiang, Hui Zhang, Qian Chen","doi":"10.5114/fn.2025.154414","DOIUrl":"10.5114/fn.2025.154414","url":null,"abstract":"<p><p>Intracerebral hemorrhage (ICH) has a high rate of death and disability. LncRNA-TUG1 is essential for the pathological changes secondary to ICH. The purpose of this work was to investigate the possible mechanism by which TUG1 inhibits neural repair subsequent to ICH through adjusting miR-381-3p/brain-derived neurotrophic factor (BDNF). After the ICH model was created, miR-381-3p agomir and pcDNA-TUG1 were injected. The neural function of rats was estimated using the modified neurological severity score. To quantify the expression of genes and proteins, western blotting, immunohistochemistry, and qRT-PCR were used. To confirm the interaction between TUG1 and miR-381-3p and between miR-381-3p and BDNF mRNA, a luciferase reporter assay was employed. In rats treated with miR-381-3p agomir, a trend of improvement in neurological dysfunction was observed, while the pcDNA-TUG1-treated ones showed deterioration. Furthermore, miR-381-3p agomir increased, while pcDNA-TUG1 reduced the expression level of BDNF in ICH rats. TUG1 and BDNF mRNA were validated to attach directly to miR-381-3p. Overexpressing TUG1 inhibited the level of BDNF by sponging miR-381-3p and antagonized its protective effect on neural repair in ICH rats. Our study suggests that TUG1 can sponge miR-381-3p to downregulate BDNF expression and inhibit neural repair following ICH, demonstrating a potential signaling pathway that is conducive to a better understanding of the pathological mechanisms of ICH.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 1","pages":"23-30"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MUC1 overexpression in glioma correlated with tumor malignancy and poor prognosis.","authors":"Abdul Wahab Jamali, Arshad Mehmood, Shiyang Zhang, Yan Hongshan, X P Liu, Zhang Zhanzhan, Liqiang Liu","doi":"10.5114/fn.2026.158389","DOIUrl":"10.5114/fn.2026.158389","url":null,"abstract":"<p><p>Mucin 1 (MUC1), a transmembrane glycoprotein, is aberrantly expressed in multiple cancers and implicated in tumor progression. This study investigated MUC1 expression in glioma tissues and cell lines, its correlation with tumor malignancy, and the effect of differential expression on patient prognosis. Bioinformatics analysis using the GEPIA database evaluated MUC1 expression in pan-cancer and its effect on the prognosis of glioma patients. Clinical samples from 9 glioma patients with WHO grades II-IV and 2 normal brain tissues with traumatic brain injury controls were analyzed via immunohistochemistry. RT-qPCR and Western blot were used to analyze MUC1 expression in glioblastoma (GBM) cell lines (U251, U87, A172, LN229) and normal human astrocytes (NHA). MUC1 was significantly overexpressed in glioma tissues compared to normal brain tissue (p < 0.05), with higher expression correlating with advanced tumor grade. High MUC1 levels predicted poor patient survival (p < 0.01). GBM cell lines exhibited elevated MUC1 mRNA and protein levels vs. NHA (p < 0.001). MUC1 correlation with glioma malignancy and patient outcomes represents a prognostic biomarker and potential therapeutic target, underscoring its relevance in neuropathology practice.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 1","pages":"94-104"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Floppy baby syndrome as the first presentation of HADDTS associated with CTBP1 mutation.","authors":"Maria Jędrzejowska, Monika Gos, Dariusz Rokicki, Elzbieta Jurkiewicz, Agnieszka Madej-Pilarczyk","doi":"10.5114/fn.2026.162176","DOIUrl":"10.5114/fn.2026.162176","url":null,"abstract":"<p><p>The CtBP1 protein is a transcriptional regulator that interacts with chromatin-modifying enzymes and modulates gene expression in various cellular pathways. The dominant negative de novo molecular variant c.1024C&gt;T, p.Arg342Trp in the CTBP1 gene is associated with hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome (HADDTS). Here we present a male patient with a recurrent hotspot mutation in the CTBP1 gene and a phenotype consistent with HADDTS. The patient presented with global developmental delay, floppy infant syndrome, ataxia, intellectual disability with speech disorder, facial dysmorphia, enamel defect, constipation, and cerebellar atrophy on brain imaging. This is the 18 th reported case of this ultra-rare disorder, and the first patient of Polish origin. Diagnosing neurodevelopmental disorders remains challenging; however, modern large-scale genetic tests and a diagnostic approach from genotype to phenotype enable the diagnosis of an increasing number of patients with rare diseases that present non-specifically but have a severe course.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 2","pages":"205-208"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etomidate protects against homocysteine-induced blood-brain barrier disruption via upregulation of Krüppel-like factor 2.","authors":"Bo Chen, Jun Zhou","doi":"10.5114/fn.2026.161199","DOIUrl":"https://doi.org/10.5114/fn.2026.161199","url":null,"abstract":"<p><p>As the second leading cause of death, stroke has a significant impact on public health. Homocysteine (Hcy), a non-essential sulfur-containing amino acid, has recently been found to aggravate brain injury in stroke. This effect is closely associated with oxidative stress (OS), blood-brain barrier (BBB) dysfunction, and endothelial cell damage. Etomidate, originally developed as a sedative, has demonstrated strong protective effects against OS and inflammation. However, its role in stroke remains underexplored. Our research aimed to investigate the potential effects of etomidate in treating Hcy-induced stroke. In C57BL/6 mice, Hcy (0.03 µmol/g, subcutaneous) was administered for one month alongside etomidate (3 mg/kg, intraperitoneal). BBB permeability was assessed via sodium fluorescein diffusion, while OS (GSH, MDA) and inflammation (TNF-a, IL-1b) were measured using spectrophotometry and ELISA. Occludin and KLF2 expression were analyzed by Western blot and immunostaining. In vitro, human brain microvascular endothelial cells (HBMVECs) were treated with Hcy (20 µM) and etomidate (2.5-5 µM), with barrier integrity evaluated via FITC-dextran assay and transepithelial/transendothelial electrical resistance (TEER) measurements. KLF2 knockdown was performed using lentiviral shRNA to confirm its mechanistic role. Hcy-challenged mice exhibited significantly decreased reduced GSH levels, increased MDA, TNF-a, and IL-1b levels, enhanced diffusion of sodium fluorescein, and reduced occludin expression. These changes were notably reversed by etomidate. In vitro, primary HBMVECs were stimulated with 20 µM Hcy, with or without etomidate (2.5 or 5 µM) for 24 hours. Hcy-treated HBMVECs showed significantly increased FITC-dextran intensity, decreased TEER, reduced occludin expression, and diminished KLF2 levels. These effects were notably reversed by etomidate. Moreover, the protective effects of etomidate on Hcy-induced occludin reduction and increased endothelial monolayer permeability were negated by KLF2 inhibition. In conclusion, etomidate exerts protective effects against Hcy-induced BBB disruption by upregulating KLF2.</p>","PeriodicalId":12370,"journal":{"name":"Folia neuropathologica","volume":"64 2","pages":"186-197"},"PeriodicalIF":1.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148905524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}