Brain Hemorrhages最新文献

{"title":"Stromal vascular fraction cell therapy: A promising therapeutic method for intracerebral hemorrhage","authors":"Ilgiz Gareev , Ozal Beylerli , Albert Sufianov , Valentin Pavlov , Huaizhang Shi","doi":"10.1016/j.hest.2025.01.002","DOIUrl":"10.1016/j.hest.2025.01.002","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) is one of the most devastating and life-threatening forms of stroke, characterized by bleeding within the brain parenchyma. The condition is associated with a high mortality rate and significant long-term disabilities among survivors, underscoring the urgent need for innovative therapeutic strategies that go beyond managing symptoms to actively promote brain repair and functional recovery. Current treatment options are largely limited to supportive care, including surgical interventions to alleviate intracranial pressure and management of underlying risk factors such as hypertension. These approaches, however, fail to address the extensive neurological damage caused by ICH. Emerging evidence highlights the potential of stromal vascular fraction (SVF) cell therapy as a novel regenerative treatment for ICH. SVF, derived from adipose tissue through enzymatic digestion, is a heterogeneous mixture of cells, including mesenchymal stem cells (MSCs), endothelial cells, pericytes, immune cells, and progenitor cells. This cellular composition contributes synergistically to the repair and regeneration of damaged tissues. The mechanisms of action of SVF encompass inflammation modulation, neuroprotection, angiogenesis, and immunomodulation. MSCs within SVF release anti-inflammatory cytokines such as interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), reducing secondary injury caused by excessive inflammation. Endothelial cells and pericytes promote the formation of new blood vessels, restoring oxygen and nutrient supply to ischemic regions. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) further support neuronal survival and repair of neural circuits. Preclinical studies in animal models have consistently demonstrated the efficacy of SVF therapy, including reductions in brain edema, oxidative stress, and inflammatory cytokines, alongside improvements in angiogenesis, neuronal survival, and functional recovery. Early-phase clinical trials and case studies provide preliminary evidence of safety, feasibility, and potential therapeutic benefits in human patients with acute and chronic ICH. However, significant challenges remain, including the variability in SVF composition, optimal delivery methods, timing of intervention, and long-term safety considerations. This review comprehensively examines the biological properties of SVF, the mechanisms underlying its therapeutic effects, and the preclinical and clinical evidence supporting its use in ICH. Additionally, it explores future directions, including the development of standardized protocols, optimization of delivery techniques, integration with combination therapies, and the potential for personalized medicine approaches. As ongoing research and clinical trials refine these strategies, SVF therapy holds transformative potential to revolutionize ICH treatment by addressing its complex pathophysiology and i","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 3","pages":"Pages 110-120"},"PeriodicalIF":1.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of 3D printing technology-assisted neuroendoscopic surgery for hypertensive intracerebral hemorrhage in primary hospitals","authors":"Jiandong Wu ,&nbsp;Yuhui Gong ,&nbsp;Jinhong Qian,&nbsp;Xiaoyu Tang,&nbsp;Peng Deng,&nbsp;Haolong Ding,&nbsp;Zhiliang Ding,&nbsp;Mian Ma","doi":"10.1016/j.hest.2024.08.002","DOIUrl":"10.1016/j.hest.2024.08.002","url":null,"abstract":"<div><h3>Objective</h3><div>We aimed to investigate the clinical effectiveness of integrating 3D-printing technology with neuroendoscopy for treating hypertensive intracerebral hemorrhage (HICH).</div></div><div><h3>Methods</h3><div>Between November 2020 and November 2023, a total of 105 HICH cases were selected and categorized into the conventional surgery group and the neuroendoscopic surgery. General data, Glasgow Coma Scale (GCS), National institutes of health neurological impairment score (NIHSS), preoperative hematoma volume, intracerebral parenchymal and intraventricular hematoma (IVH) clearance rates, Modified Graeb Scale (mGS), postoperative rebleeding rate, intracranial infection, and Modified Rankin Scale (mRS) were collected to assess the therapeutic effectiveness.</div></div><div><h3>Results</h3><div>There were no significant statistical differences in gender, age, preoperative GCS scores, NIHSS or hematoma volume between the neuroendoscopic surgery and conventional surgery group. The postoperative results indicated that the clearance rate of intracerebral parenchymal and IVH in neuroendoscopic surgery group was notably higher than the conventional surgery group. The neuroendoscopic surgery group achieved superior outcomes in terms of bone flap area, operation time, extubation time, and average hospital stay compared to the conventional surgery group (P &lt; 0.05). Following a 3-month follow-up, there was no significant difference in the mRS and NIHSS between the two groups. However, when the patients with IVH (mGS≥10) indicated better postoperative outcomes in the neuroendoscopic surgery group (P &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>The integration of neuroendoscopic minimally invasive surgery with 3D-printing technology for treating HICH demonstrated high efficacy for removing intracerebral and IVH. This approach incurred less trauma compared to traditional craniectomy surgery, affording shortened surgical and hospitalization durations. Consequently, it appears to be a highly efficacious method for treating HICH, particularly in cases involving IVH.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 3","pages":"Pages 103-109"},"PeriodicalIF":1.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144306657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intracranial pressure monitoring and minimally invasive surgery for intracerebral hemorrhage: Current status, challenges, and future","authors":"Ping Zhang ,&nbsp;Xinran Xu ,&nbsp;Chao Pan ,&nbsp;Yingxin Tang ,&nbsp;Wenjie Liu ,&nbsp;Zhouping Tang","doi":"10.1016/j.hest.2025.03.001","DOIUrl":"10.1016/j.hest.2025.03.001","url":null,"abstract":"<div><div>With the continuous advancement of medical technology, the treatment for intracerebral hemorrhage (ICH) has shifted from traditional open surgery to more precise minimally invasive surgery (MIS). This article will discuss the combination of intracranial pressure (ICP) monitoring and MIS in ICH management, as well as explore future development directions.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 2","pages":"Pages 61-63"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognosis of recovery and death within 1–6 months of spontaneous cerebellar hemorrhage undergoing suboccipital craniotomy","authors":"Phuong Xuan Nguyen ,&nbsp;Tung Duc Nguyen ,&nbsp;Cuong Manh Tran ,&nbsp;Tuan Cong Duong ,&nbsp;Ha Thi-Ngoc Doan ,&nbsp;Yen Trong Nguyen","doi":"10.1016/j.hest.2024.05.005","DOIUrl":"10.1016/j.hest.2024.05.005","url":null,"abstract":"<div><h3>Objective</h3><div>Suboccipital craniotomy is a considerable surgical approach for large spontaneous cerebellar hemorrhage, but its prognostic has not been comprehensively addressed. This study aims to report the surgical outcomes and factors related to the prognosis of recovery and death within 1–6 months of patients with spontaneous cerebellar hemorrhage.</div></div><div><h3>Methods</h3><div>We retrospectively studied 37 patients who underwent craniotomy due to spontaneous cerebellar hemorrhage from January 2019 to April 2022.</div></div><div><h3>Results</h3><div>The disease occurs at a mean age of 62.86 years old, with a male/female ratio of 4.26/1. Hemorrhage is mainly in the cerebellar hemisphere. Hospital stays averaged 13.32 days, with significant reductions in hematoma diameter and volume after surgery. The hospital mortality rate was 5.41 %, increasing to 45.95 % at 1 month post-discharge. Prognostic factors for death within 1 month include low Glasgow score, small hematoma diameter, and low hematoma volume. Factors associated with recovery include young age, absence of ventricle hemorrhage, and high Glasgow score.</div></div><div><h3>Conclusions</h3><div>Suboccipital craniotomy demonstrates a high efficacy in resolving hematomas with decreased complication rates, lower mortality, and improved patient recovery outcomes. Optimal surgical outcomes would be achieved with early intervention, particularly in younger patients.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 2","pages":"Pages 76-80"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Step-down infusion of barbiturate improves neurofunction in a new rat model of rebleeding subarachnoid hemorrhage","authors":"Sosho Kajiwara ,&nbsp;Yu Hasegawa ,&nbsp;Kana Fujimori ,&nbsp;Motohiro Morioka","doi":"10.1016/j.hest.2024.07.001","DOIUrl":"10.1016/j.hest.2024.07.001","url":null,"abstract":"<div><h3>Objective</h3><div>Rebleeding from a ruptured aneurysm is a risk factor for fatal prognosis in subarachnoid hemorrhage (SAH). A novel barbiturate treatment, step-down infusion of barbiturate (sd-B), was previously developed; it showed beneficial effects on patients with severe traumatic brain injuries. The present study established a rebleeding SAH model in rats and evaluated the effect of sd-B.</div></div><div><h3>Methods</h3><div>Fifty male Sprague-Dawley rats were divided into sham-operation with distilled water, sham-operation with barbiturate, SAH-rebleeding with distilled water, and SAH-rebleeding with barbiturate groups. For posttreatment with sd-B, thiamylal was intraperitoneally administered at 3 mg/kg/h on days 0–1, 2 mg/kg/h on days 1–2, and 1 mg/kg/h on days 2–3 after SAH using osmotic minipumps. We monitored neurofunction and case fatality as the primary endpoints and evaluated brain injuries, including brain edema and cortical neuronal cell death, as the secondary endpoints</div></div><div><h3>Results</h3><div>Posttreatment with sd-B improved the modified Garcia test, reduced the brain water content, and inhibited the loss of neuronal cells and microglial expressions in the rat model.</div></div><div><h3>Conclusions</h3><div>Our results revealed that sd-B ameliorated neurofunction and brain injuries on the rebleeding SAH model, suggesting that the novel treatment is a good candidate drug for patients with SAH with rebleeding.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 2","pages":"Pages 64-68"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141701290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cells in intracerebral hemorrhage","authors":"Irem Culha Taskin,&nbsp;Yao Yao","doi":"10.1016/j.hest.2025.02.001","DOIUrl":"10.1016/j.hest.2025.02.001","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH), the deadliest form of stroke, is characterized by bleeding into brain parenchyma and formation of hematoma. Currently, there is no treatment available for ICH. Inflammatory response is a key pathology of ICH and plays a dual role in ICH---contributing to both secondary brain injury and recovery processes. This review discusses different types (both brain-resident and infiltrated) of immune cells and their functions during inflammation processes following ICH. Specifically, the temporal dynamics, polarization, and function of microglia/macrophages, neutrophils, lymphocytes, and astrocytes in ICH are summarized in a cell-specific manner. In addition, we also discuss key challenges and unanswered questions that need to be addressed in the future. A thorough understanding of the functions of different immune cells in ICH will provide a strong foundation for future studies and lead to the identification of novel cellular/molecular targets for therapeutic development.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 2","pages":"Pages 86-94"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No association of brain CT blend sign with functional outcomes in patients with spontaneous supratentorial intracerebral hemorrhage after craniotomy","authors":"Li Luo ,&nbsp;Jinhua Yang ,&nbsp;Lian He ,&nbsp;Shiqi Lin ,&nbsp;Desislava Doycheva ,&nbsp;Siying Ren ,&nbsp;Likun Wang","doi":"10.1016/j.hest.2024.08.001","DOIUrl":"10.1016/j.hest.2024.08.001","url":null,"abstract":"<div><h3>Objective</h3><div>This study retrospectively analyzed the association of blend sign with long-term outcomes in patients who underwent craniotomy following spontaneous supratentorial intracerebral hemorrhage.</div></div><div><h3>Methods</h3><div>A retrospective analysis was conducted on a cohort comprising 259 patients. Initially, patients were stratified into two groups: the blend sign group and the non-blend sign group. Subsequently, the neurological status of these patients was assessed using the NIHSS, GCS, and mRS following craniotomy. Furthermore, at six months post-craniotomy, patients were categorized into either the “good outcome group” or the “poor outcome group”. A multivariate regression analysis was applied to ascertain the independent correlation between the CT blend sign and prognosis.</div></div><div><h3>Results</h3><div>No statistically significant disparities were observed in the proportion of patients experiencing favorable outcomes during the follow-up period between the two groups. Nevertheless, it is noteworthy that the incidence of the blend sign was higher among patients in the good outcome group compared to those in the poor outcome group. Multivariate regression analysis disclosed that poor outcomes following craniotomy was not associated with the blend sign.</div></div><div><h3>Conclusions</h3><div>The presence of the blend sign may not serve as a reliable predictor of functional outcomes in patients undergoing craniotomy for spontaneous supratentorial ICH.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 2","pages":"Pages 69-75"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing neuroimaging visualization technology to enhance standardized neurosurgical training for Traditional Chinese Medicine residents: A neuroanatomical education study","authors":"Rongjun Zhang ,&nbsp;Zhigang Gong ,&nbsp;Wenbing Jiang ,&nbsp;Zhaofeng Su","doi":"10.1016/j.hest.2024.07.005","DOIUrl":"10.1016/j.hest.2024.07.005","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to address the difficulties encountered by Traditional Chinese Medicine (TCM) students in learning neuroanatomy during clinical training by utilizing neuroimaging visualization technology.</div></div><div><h3>Methods</h3><div>81 students were divided into a control group (40 students) and an observation group (41 students). The control group followed traditional teaching methods as prescribed by the curriculum, while the observation group received additional training with the neuroimaging visualization software DSI Studio. This included whole-brain neural fiber reconstruction and cortical spinal tract evaluation in the context of stroke. Upon completion of the training, both groups were assessed on neuroanatomical theory, case analysis, neurological examination, and clinical skills. The teaching effectiveness was compared based on assessment results and feedback from questionnaires administered to the observation group.</div></div><div><h3>Results</h3><div>The observation group significantly outperformed the control group in theoretical knowledge, case analysis, and physical examination (P &lt; 0.05). Over 90 % of students in the observation group reported via questionnaire that the integration of neuroimaging visualization technology significantly enhanced their understanding of neuroanatomy and clinical reasoning skills.</div></div><div><h3>Conclusion</h3><div>The clinical teaching approach augmented with neuroimaging visualization technology significantly improves the standardized training outcomes for TCM neurosurgical residents.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 2","pages":"Pages 81-85"},"PeriodicalIF":1.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune System Perspective in Intracerebral Hemorrhage Research: A Focus on Monocytes and Macrophages","authors":"Hang Hang ,&nbsp;Lei Huang ,&nbsp;Yuanhong Mao ,&nbsp;Guofeng Wu","doi":"10.1016/j.hest.2024.07.004","DOIUrl":"10.1016/j.hest.2024.07.004","url":null,"abstract":"<div><div>Monocytes and macrophages are crucial elements of the immune system, having various roles in tissue balance, inflammation, and conditions like stroke. They exhibit significant functional diversity, particularly evident in the M1 and M2 phenotypes and their marker characteristics. The functions of monocytes and macrophages are crucial in stroke studies, notably those related to intracerebral hemorrhage (ICH). ICH is the most severe type of stroke, characterized by inflammation, oxidative stress, and neuronal death, significantly increasing patient mortality and morbidity. Monocytes and macrophages play key roles in the inflammatory processes following ICH, participating in hematoma clearance and tissue repair. Despite their potential dual roles in the pathophysiology of ICH, involving both harmful and protective effects, the specific mechanisms remain to be further elucidated. This review summarizes the latest research progress on monocyte and macrophage subsets, with a particular focus on their contributions to ICH. It covers the relationships and differences between monocytes and macrophages, the functional diversity of macrophages, cell phenotypes and functions, regulatory mediators, gene expression and transcriptome analysis, and the clinical prognosis associated with blood monocyte counts. These research advancements aim to provide new insights for improving the diagnosis and treatment strategies for ICH.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 1","pages":"Pages 30-37"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141705721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leakage sign based on contrast-enhanced CT is a predictive marker for hematoma expansion and poor prognosis in primary brainstem hemorrhage","authors":"Motohisa Koga,&nbsp;Yu Hasegawa,&nbsp;Jin Kikuchi,&nbsp;Aya Hashimoto,&nbsp;Keiichiro Furuta,&nbsp;Takehiro Makizono,&nbsp;Hidenobu Yoshitake,&nbsp;Kimihiko Orito,&nbsp;Motohiro Morioka","doi":"10.1016/j.hest.2024.10.003","DOIUrl":"10.1016/j.hest.2024.10.003","url":null,"abstract":"<div><h3>Objective</h3><div>Although hematoma expansion is a poor prognostic factor in patients with intracerebral hemorrhage (ICH), its effect on primary brainstem hemorrhage (PBSH) remains unclear. Since we previously observed the “leakage sign” (LS) on computed tomography (CT) to be a significant predictor for hematoma expansion, we herein investigated the effect of LS in PBSH.</div></div><div><h3>Methods</h3><div>Between January 2013 and August 2023, 515 patients with ICH were admitted to our institute. Thirty-six patients with PBSHs met the inclusion criteria, who were then divided into LS-positive (LS+) and LS-negative (LS-) groups based on the presence of LS. We evaluated hematoma expansion and prognosis at discharge.</div></div><div><h3>Results</h3><div>Patients in the LS+ group had larger baseline hematoma volume and lower Glasgow Coma Scale scores on admission and significantly poor prognosis at discharge. Subgroup analysis revealed that LS was frequently observed within 100 min after the onset of symptoms in patients with a hematoma size of &gt;10 mm³ on CT; additionally, patients in the LS+ group more frequently experienced hematoma expansion and had poor prognosis at discharge.</div></div><div><h3>Conclusions</h3><div>LS is a significant predictive marker for disease severity at admission, hematoma expansion, and poor prognosis at discharge.</div></div>","PeriodicalId":33969,"journal":{"name":"Brain Hemorrhages","volume":"6 1","pages":"Pages 19-23"},"PeriodicalIF":1.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143529505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}