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BackgroundNeurological disorders are a major and increasing global health challenge, which accounts for a substantial portion of the disease burden worldwide. The aim of this systematic analysis is to present the most comprehensive and up-to-date estimates of disease burden, epidemiological trends, and attributable risk factors of neurological disorders at global, regional, and national levels.MethodsWe extracted data of 18 neurological disorders from the Global Burden of Disease 2019 study database. The burden of neurological disorders was measured using the incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and further described according to age, sex, year, geographical location and socio-demographic Index (SDI). All estimates were presented with corresponding 95% uncertainty intervals (UIs).FindingsGlobally, in 2019, there were nearly 10 million deaths and 349 million DALYs due to neurological disorders. Among the 18 neurological disorders, stroke was the biggest contributor to DALYs (143232.18 [95%UI 133095.81-153241.82] in thousands) and deaths (6552.72 [95%UI 5995.20-7015.14] in thousands), followed by neonatal encephalopathy due to birth asphyxia and trauma. From 1990 to 2019, the DALYs of neurological diseases belonging to the communicable, maternal, neonatal and nutritional categories showed a sharp decrease, while Alzheimer's disease and other dementias and Parkinson's disease showed a large increase. Neurological disorders exhibited different profiles in different regions and age groups. A significant correlation between the SDI and the age-standardized DALY rates was also found except for Alzheimer's disease and other dementias. In addition, risk factors such as high systolic blood pressure, low birth weight and short gestation period, and metabolic risk contribute significantly to neurological disorders.InterpretationThe overall burden of neurological disorders has increased from 1990 to 2019, especially for non-communicable neurological disorders. The substantial variations of burden across regions emphasize the need for region-specific interventional strategies and allocation of resources based on priorities.

Background and purposeAneurysmal subarachnoid hemorrhage (SAH) predisposes hippocampal injury, a major cause of follow-up cognitive impairment. Our previous study has revealed an abnormal resting-state brain network in patients after the rupture of anterior communicating artery (ACoA) aneurysm. However, the functional connectivity (FC) characteristics of the hippocampus and its relationship with cognitive performance in these patients remain unknown.MethodsThis study ultimately included 26 patients and 19 age- and sex-matched controls who completed quality control for resting-state functional magnetic resonance imaging (fMRI). The mean time series for each side of the hippocampus was extracted from individuals and then a seed-to-voxel analysis was performed. We compared the difference in FC strength between the two groups and subsequently analyzed the correlations between abnormal FC and their cognitive performance.ResultsThe results of bilateral hippocampus-based FC analysis were largely consistent. Compared with the healthy controls, patients after the rupture of ACoA aneurysm exhibited significantly decreased FC between the hippocampus and other brain structures within the Papez circuit, including bilateral anterior and middle cingulate cortex (MCC), bilateral medial superior frontal gyrus, and left inferior temporal gyrus (ITG). Instead, increased FC between the hippocampus and bilateral insula was observed. Correlation analyses showed that more subjective memory complaints or lower total cognitive scores were associated with decreased connectivity in the hippocampus and several brain regions such as left anterior cingulate cortex (ACC) and frontotemporal cortex.ConclusionThese results extend our previous findings and suggest that patients with ruptured ACoA aneurysm exist hypoconnectivity between the hippocampus and multiple brain regions within the Papez circuit. Deactivation of the Papez circuit may be a crucial neural mechanism related to cognitive deficits in patients after the rupture of ACoA aneurysm.

Based on the actor-partner interdependence model, this paper studied the relationship between marital commitment, sacrifice behavior and marital quality of military couples. A convenience sample of 171 Chinese military couples from Guangdong, Jiangsu and Sichuan province was used. All participants completed the self-report questionnaires independently including the Dimension of Commitment Inventory (DCI), the Couples Sacrifice Behavior Scale (CSBS) and the Evaluation and Nurturing Relationship Issues, Communication and Happiness (ENRICH). Results showed that the scores of marital commitment and marital quality of male soldiers were significantly higher than that of their spouses. Compared to their spouses, male soldiers reported higher frequency of sacrifice behaviors and perceiving sacrifice behaviors of spouses. Furthermore, the marital commitment of military couples had significant influence on their own marital quality and frequency of perceiving each other’s sacrifice behavior Military couples’ perception of the frequency of each other’s sacrifice behavior partially mediated the effect of marital commitment on their marital quality. Male soldiers’ perception of spouse’s sacrifice behavior frequency significantly predicted the marital quality of their spouses.

Abstract Background Temozolomide (TMZ) resistance limits its application in glioma. Exosome can carry circular RNAs (circRNAs) to regulate drug resistance via sponging microRNAs (miRNAs). miRNAs can control mRNA expression by regulate the interaction with 3’UTR and methylation. Nanog homeobox (NANOG) is an important biomarker for TMZ resistance. Hitherto, it is unknown about the role of exosomal hsa_circ_0072083 (circ_0072083) in TMZ resistance in glioma, and whether it is associated with NANOG via regulating miRNA sponge and methylation. Methods TMZ-resistant (n = 36) and sensitive (n = 33) patients were recruited. The sensitive cells and constructed resistant cells were cultured and exposed to TMZ. circ_0072083, miR-1252-5p, AlkB homolog H5 (ALKBH5) and NANOG levels were examined via quantitative reverse transcription polymerase chain reaction and western blot. The half maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, migration and invasion were analyzed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing and transwell assays. The in vivo function was assessed using xenograft model. The N6-methyladenosine (m6A) level was analyzed via methylated RNA immunoprecipitation (MeRIP). Target relationship was investigated via dual-luciferase reporter assay and RNA immunoprecipitation. Warburg effect was investigated via lactate production, glucose uptake and key enzymes expression. Exosome was isolated and confirmed via transmission electron microscopy and specific protein expression. Results circ_0072083 expression was increased in TMZ-resistant glioma tissues and cells. circ_0072083 knockdown restrained the resistance of resistant cells via decreasing IC50 of TMZ, proliferation, migration, invasion and xenograft tumor growth and increasing apoptosis. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. circ_0072083 could regulate NANOG and ALKBH5 via targeting miR-1252-5p to control TMZ resistance. Warburg effect promoted the release of exosomal circ_0072083 in resistant cells. Exosomal circ_0072083 from resistant cells increased the resistance of sensitive cells to TMZ in vitro and xenograft model. Exosomal circ_0072083 level was enhanced in resistant patients, and it had a diagnostic value and indicated a lower overall survival in glioma. Conclusion Exosomal circ_0072083 promoted TMZ resistance via increasing NANOG via regulating miR-1252-5p-mediated degradation and demethylation in glioma.

Abstract Background To present a surgical technique for the treatment of intradural extramedullary (IDEM) tumors by using endoscopically controlled surgery with open hemilaminectomy technique. Methods In this study, 20 patients with 22 IDEM tumors were enrolled. An endoscopically controlled surgery with open hemilaminectomy was employed to remove the tumors. Data related to clinical symptoms and medical images before and after surgery were collected for perioperative evaluation and follow-up analysis. Results All the tumors in 20 patients were well removed. The clinical symptoms were significantly reduced in all the patients as well. The short-term follow-up data showed that there was no tumor recurrence or spinal deformity. Conclusion The endoscopically controlled surgery with open hemilaminectomy technique provided favorable exposure and satisfactory resection to the IDEM tumors. It may be an effective surgical method for treating IDEM tumors. Larger samples and longer follow-up data are needed to verify its long-term effectiveness.

Purpose: To assess the correlation between admission body temperature and delayed cerebral infarction in elderly patients with ruptured intracranial aneurysm (IA).Methods: Patients with ruptured IA diagnosed between 2012 and 2020 were retrospectively analyzed. Patients were divided into a non-infarction and an infarction group based on the presence of cerebral infarction after treatment. The demographic and clinical information of the patients was gathered. Outcomes at the 3-month follow-up were assessed using the modified Rankin Scale. Correlation between admission body temperature and cerebral infarction was assessed using Spearman's rank correlation coefficient. A receiver operating characteristic (ROC) curve was used to assess the specificity and sensitivity of admission body temperature to predict cerebral infarction.Results: A total of 426 patients (142 men and 284 women) with ruptured IA were enrolled. Elderly patients with cerebral infarction (12.4%) had a lower body temperature at admission (p < 0.001), higher prevalence of hypertension and diabetes (p = 0.051 and p = 0.092, respectively), and higher rate of poor outcomes (p < 0.001). Admission body temperature was independently associated with cerebral infarction (odds ratio [OR] = 5.469, p < 0.001); however, hypertension (OR = 0.542, p = 0.056), diabetes (OR = 0.750, p = 0.465), and aneurysm size (OR = 0.959, p = 0.060) showed no association. An inverse correlation between admission body temperature and the incidence of cerebral infarction was observed (Spearman's r =−0.195, p < 0.001). An admission body temperature of 36.6°C was able to distinguish infarction and non-infarction patients. The area under the ROC curve was 0.669 (specificity, 64.15%; sensitivity, 81.50%; p < 0.001).Conclusions: Lower body temperature at admission (≤36.6°C) is an independent predictor of delayed cerebral infarction in elderly patients who have undergone treatment for ruptured IA. Therefore, it could be a risk factor for adverse outcomes of IA.

Abstract Background Circular RNA nuclear factor I X (circNFIX) has been reported to play an important role in glioma progression. However, the mechanism by which circNFIX participates in glioma progression remains poorly understood. Methods GERIA online were used to analyze the abnormally expressed genes in glioma tissues. The expression levels of circNFIX, microRNA (miR)-378e and Ribophorin-II (RPN2) were measured by quantitative real-time polymerase chain reaction or western blot. Cell cycle distribution, apoptosis, glycolysis, migration and invasion were determined by flow cytometry, special kit and trans-well assays, respectively. The target association between miR-378e and circNFIX or RPN2 was confirmed by luciferase reporter assay, RNA immunoprecipitation and pull-down. Xenograft model was established to investigate the role of circNFIX in vivo. Results The expression of circNFIX was enhanced in glioma tissues and cells compared with matched controls and high expression of circNFIX indicated poor outcomes of patients. Knockdown of circNFIX led to arrest of cell cycle, inhibition of glycolysis, migration and invasion and promotion of apoptosis in glioma cells. circNFIX was a sponge of miR-378e. miR-378e overexpression suppressed cell cycle process, glycolysis, migration and invasion but promoted apoptosis. miR-378e silence abated the suppressive role of circNFIX knockdown in glioma progression. RPN2 as a target of miR-378e was positively regulated via circNFIX by competitively sponging miR-378e. Silencing circNFIX decreased glioma xenograft tumor growth by regulating miR-378e/RPN2 axis. Conclusion Knockdown of circNFIX inhibits progression of glioma in vitro and in vivo by increasing miR-378e and decreasing RPN2, providing a novel mechanism for understanding the pathogenesis of glioma.

Introduction: We explored whether higher preoperative serum levels of lactate dehydrogenase (LDH) predicted outcome 3 months after surgery in patients with aneurysmal subarachnoid hemorrhage (aSAH) treated using microsurgical clipping in our institution.Methods: Patients with aSAH treated at our institution between 2010 and 2018 were enrolled. The following parameters were recorded: age, sex, smoking and drinking history, medical history, Hunt–Hess and Fisher grades, aneurysm location, aneurysm size, surgical treatment, delayed cerebral ischemia (DCI), intracranial infection, hydrocephalus, pneumonia, and preoperative serum LDH levels within 24 h of aSAH. We investigated whether preoperative serum LDH levels were associated with Hunt–Hess grade, Fisher grade, and functional neurological outcome.Results: In total, 2,054 patients with aSAH were enrolled, 874 of whom were treated using microsurgical clipping. The average serum LDH level (U/L) was significantly lower in the good outcome group (180.096 ± 50.237) than in the poor outcome group (227.554 ± 83.002; p < 0.001). After propensity score matching, the average serum LDH level (U/L) was still lower in the good outcome group (205.356 ± 76.785) than in the poor outcome group (227.119 ± 86.469; p = 0.029). The area under the receiver operating characteristic (ROC) curve was 0.702 (95% confidence interval [CI]: 0.650–0.754; p < 0.001). Based on the ROC curve, the optimal cutoff value for serum LDH levels as a predictor of poor 3-month outcome (modified Rankin Scale score > 2) was 201.5 U/L. The results revealed that Hunt–Hess grade, Fisher grade, DCI, pneumonia, and serum LDH (>201.5 U/L) were significantly associated with poor outcome. After propensity score matching, serum LDH levels > 201.5 U/L were still considered an independent risk factor for poor outcome (odds ratio: 2.426, 95% CI = 1.378–4.271, p = 0.002). Serum LDH levels were associated with Hunt–Hess and Fisher grades and were correlated with functional neurological outcomes (p < 0.001).Conclusions: Our findings showed that higher preoperative serum levels of LDH correlated with Hunt–Hess grade, Fisher grade, and neurological functional outcome, and predicted the outcome of aSAH treated by microsurgical clipping at 3 months, which was involved in the related mechanisms of early brain injury and showed its potential clinical significance in patients with aSAH.

Objective: In this study, we assessed the correlation between the lactate dehydrogenase (LDH) to phosphate ratio and the prognosis of microsurgical clippings for ruptured intracranial aneurysm (rIA) to test the hypothesis that the serum LDH to phosphate ratio could be a predictor of the outcome of microsurgical clipping for rIA. Methods: Records of rIA patients between 2012 and 2018 were retrospectively collected. Age, sex, Hunt-Hess grade, Fisher grade, medical history, aneurysm location, hydrocephalus, laboratory data including serum LDH, phosphate, and LDH to phosphate ratio, related complications, and the outcomes in 3 months were recorded. Results: A total of 1608 rIA patients in our institution were collected, and 856 patients treated by microsurgical clipping were enrolled. On admission, a significantly higher LDH-phosphate ratio was observed in patients with poor outcomes at 3 months (median ± SD, 200.175 ± 107.290 for mRS 0–2 vs. 323.826 ± 219.075 for mRS score 3–6; p = 0.000). An LDH to phosphate ratio of 226.25 in the receiver operating characteristic (ROC) curve was the optimal cutoff value to discriminate between good and poor outcomes at 3 months. The LDH to phosphate ratio ≥ 226.25 on admission was independently correlated with poor outcomes in rIA patients. In addition, Hunt and Hess grade, Fisher grade, pneumonia, and DIND were also independently correlated with poor outcomes. After removing the bias in essential clinical variables between patients with LDH to phosphate, ratio ≥ 226.25 versus p = 0.005). Conclusions: The LDH to phosphate ratio was a potential biomarker and could predict the unfavorable outcome of microsurgical clipping for rIA in 3 months, related to neuronal damage, cerebral hypoxia, and early brain injury after aneurysm ruptures.

PurposeThe aim of this study was to explore the correlation and clinical significance of preoperative fibrinogen and neutrophil-lymphocyte ratio (F-NLR) scoring system with 3-year progression-free survival (PFS) of patients with atypical meningioma.Materials and MethodsClinical, pathological, radiological, and laboratory variables were collected to analyze their correlation with 3-year PFS in the training set with 163 patients. Patients were classified by different F-NLR scores (0, 1, or 2). External validation for the predictive value of F-NLR scoring system was performed in the validation set with 105 patients.ResultsOverall, 37.3% (100 of 268) of the enrolled patients were male. The scoring system showed good performance in predicting 3-year PFS (AUC = 0.872, 95%CI = 0.811–0.919, sensitivity = 66.1%, specificity = 93.3%, and Youden index = 0.594). DeLong’s test indicated that the AUC of F-NLR scoring system was significantly greater than that of fibrinogen level and NLR (Z = 2.929, P = 0.003; Z = 3.376, P < 0.001). Multivariate Cox analysis revealed that tumor size (HR = 1.39, 95%CI = 1.10–1.76, P = 0.007), tumor location (HR = 3.11, 95%CI = 1.60–6.95, P = 0.001), and F-NLR score (score of 1: HR = 12.78, 95%CI = 3.78–43.08, P < 0.001; score of 2: HR = 44.58, 95%CI = 13.02–152.65, P < 0.001) remained significantly associated with 3-year PFS. The good predictive performance of F-NLR scoring system was also demonstrated in the validation set (AUC = 0.824, 95%CI = 0.738–0.891, sensitivity = 62.5%, specificity = 87.9%, and Youden index = 0.504).ConclusionOur study confirmed the correlation and clinical significance of preoperative F-NLR scoring system with 3-year PFS of patients with atypical meningioma. A prospective and large-scale study is required to validate our findings.

Background: Studies investigating the change in distance between the bilateral internal carotid arteries (ICAs) in acromegalic patients have provided ambiguous results. The influencing factors of these changes have not been well-identified.Objective: To further investigate the change in distance between bilateral ICAs in acromegaly patients and identify the influencing factors of the change.Method: Patients diagnosed as acromegaly from Jan 2016 to Sep 2019 in the Department of Neurosurgery of the First Affiliated Hospital of Fujian Medical University, were included in this study. Computed tomography angiography (CTA) or magnetic resonance angiography (MRA) data were obtained for all patients for three-dimensional reconstruction of the ICAs. Distance between bilateral ICAs was measured and recorded for assessment.Result: 172 patients including 86 cases with acromegaly in the study group and 86 cases with non-functional pituitary adenoma in the control group were enrolled in this study. The difference of adenoma sizes between two groups was not statistically significant. Patients in acromegaly group had significantly larger maximum distances between bilateral siphon carotid ectasias (25.5 ± 4.1 vs. 23.4 ± 3.5 mm, P = 0.001) and between bilateral lacerum segments (26.2 ± 3.2 vs. 24.1 ± 4.3 mm, P < 0.001) compared with those of patients with non-functional pituitary adenomas. Multivariate analysis showed that the increased bilateral ICAs distance was associated with disease duration (odds ratio = 1.01, 95% confidence interval = 1.01–1.02, P = 0.005) and refractory pituitary adenoma (odds ratio = 9.8, 95% confidence interval = 1.1–88.7, P = 0.043) but not with level of growth hormone (GH), insulin-like growth factor-1 (IGF-1) and adenoma size in acromegaly.Conclusion: Our study showed significant change in distance between the bilateral ICAs in acromegalic patients, comparing to patients with non-functional pituitary adenomas. The increased intercarotid artery distance is associated with disease duration but not with preoperative level of GH and IGF-1. Refractory pituitary adenoma and longer disease duration are the both risk factors of the increased ICAs distance in patient with acromegly.

Abstract Background The neuroglobin (Ngb) is well recognized as a potential biomarker for the hypoxic‐ischemic brain injury. However, connection between Ngb and delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is still unclear. Objective To investigate the relationship between early stage Ngb level of aSAH patient and the occurrence of DCI. Methods We evaluated 126 aSAH patients who were enrolled into a prospective observational cohort study. Serum Ngb level on days 1, 2, 3, 5, and 7 after aSAH were determined using a commercial enzyme‐linked immunosorbent assay kit. The relationship between Ngb level and DCI was analyzed. Results Forty‐six (36.5%) aSAH patients experienced DCI. Patients with DCI had significantly higher Ngb levels than those without (p 8.4 ng/ml has a significantly worse DCI survival rate than those having day 3 Ngb level

Abstract Background The pineal region tumors are surrounded by important structures. Neuroendoscopy has been increasingly used at home and abroad. This study is to simulate pure neuroendoscopic infratentorial supracerebellar approach for resection of pineal region tumor from the cadaveric head, and discuss the advantages and safety through this corridor. Methods The anatomical structure for resection of pineal region tumor was visualized through pure neuroendoscopic infratentorial supracerebellar approach in three cadaveric heads. Three cases with pineal region tumors were retrospectively analyzed and summarized between June 2017 and December 2017. All cases were operated through pure neuroendoscopic infratentorial supracerebellar approach in the first affiliated hospital of Fujian medical university. Results The anatomical structures of pineal region can be completely visualized by pure neuroendoscopic infratentorial supracerebellar corridor in the cadaveric head. Among the three cases, the first case was total resection, the second case was subtotal resection and the last case was partial resection. The postoperative pathology revealed cavernous hemangioma, germinoma and yolk sac tumor, respectively. The patients were followed-up for 1–6 months and had normal life.The KPS (karnofsky performance status) score was 100. Conclusion The anatomical structure of the pineal region can be completely visualized and the tumor can be safely removed through pure neuroendoscopic infratentorial supracerebellar approach.

Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH (P<0.05) and peaked at 48 hours after SAH (P<0.05). However, they were greatly reduced after treatment with necrostatin-1 (P<0.05). Concurrently, neurologic outcomes were significantly improved after necrostatin-1 treatment (P<0.05). Furthermore, brain edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation were also greatly inhibited after necrostatin-1 treatment. These results indicate that necroptosis is an important mechanism of cell death involved in the early brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a promising neuroprotective agent for SAH treatment. [ABSTRACT FROM AUTHOR]

The article describes a study on the recovery level from an injured spinal cord after venous transplantation of bone marrow mesenchymal cells (BMSCs) with consecutive injections of brain-derived neurotrophic factor (BDNF). Stem cell transplantation effects using BMSCs have not been favorable since they do not secrete BDNF. The study results revealed that 3 to 5 weeks after transplantation, transplanted BMSCs differentiated into neuron-like cells as well as neurological function and pathological damage improved following treatment.