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BACKGROUND: Coexistence of intracranial atherosclerotic stenosis (ICAS) and unruptured intracranial aneurysms (UIAs) is increasingly encountered in clinical practice. This study aims to determine the prevalence of ICAS in patients with UIAs and procedural ischemic risk associated with ICAS when treating UIAs. METHODS: Based on the CAIASA study (Coexistence of Atherosclerotic Intracranial Arterial Stenosis With Intracranial Aneurysms), we prospectively included patients undergoing treatment procedures for UIAs from October 2015 to December 2020 at Beijing Tiantan Hospital, China. We used computed tomography angiography or digital subtraction angiography to diagnose ICAS (stenosis≥50%). Multivariable logistic regression and propensity-score matching were performed to evaluate the risk of procedure-related ischemic stroke and unfavorable outcome associated with ICAS. The ICAS score was used to explore the association between different burden of ICAS and procedure-related ischemic risk. RESULTS: Among 3949 patients who underwent endovascular or open surgical procedures for UIAs, 245 (6.2%) had ICAS. After exclusion, 15.7% (32/204) of patients with ICAS experienced procedure-related ischemic stroke compared with 5.0% (141/2825) of patients without ICAS. From the unmatched and matched cohort, ICAS was significantly associated with increased risk of procedure-related ischemic stroke (unmatched: adjusted odds ratio=3.11 [1.89-5.11]; and matched: adjusted odds ratio=2.99 [1.38-6.48]). This association became more evident among patients not receiving antiplatelet therapy (Pinteraction=0.022). For patients undergoing different treatment modalities, similar increased risks were observed (clipping: adjusted odds ratio=3.43 [1.73-6.79]; and coiling: adjusted odds ratio=3.59 [1.94-6.65]). Higher ICAS score was correlated with higher procedural ischemic risk (Ptrend<0.001). CONCLUSIONS: The occurrence of ICAS is not infrequent in patients with UIAs. ICAS confers an ~2-fold increased procedural ischemic risk, irrespective of clipping or coiling. Previous antiplatelet therapy may decrease the risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02795078.
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Aneurisma Intracraniano , Arteriosclerose Intracraniana , AVC Isquêmico , Humanos , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/epidemiologia , Constrição Patológica/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Arteriosclerose Intracraniana/complicações , AVC Isquêmico/complicações , Inibidores da Agregação Plaquetária/uso terapêutico , Prevalência , Fatores de RiscoRESUMO
BMI1 Polycomb Ring Finger Proto-Oncogene (BMI1) is involved in the pathogenesis of different cancers, including acute myeloid leukemia (AML). However, the role of the circular RNA of BMI1 (circBMI1) has not been studied. Our study aimed to investigate the role and mechanism of circBMI1 in AML. circBMI1 was significantly decreased in bone marrow mononuclear cells aspirated from patients with AML. Receiver operating characteristic curve analysis showed that circBMI1 could distinguish patients with AML from controls. By overexpressing and knocking down circBMI1 in HL-60 cells, we found that circBMI1 inhibited cell proliferation, promoted apoptosis, and increased chemotherapeutic drug sensitivity in AML. Experiments using severe combined immune-deficient mice and circBMI1 transgenic mice showed that mice with circBMI1 overexpression had lower white blood cell counts, which suggested less severe AML invasion. RNA immunoprecipitation and dual-luciferase reporter assay revealed binding sites among circBMI1, miR-338-5p, and inhibitor of DNA binding 4 (ID4). Rescue experiments proved that circBMI1 inhibited AML progression by binding to miR-338-5p, which affected the expression of ID4. By coculturing exosomes extracted from circBMI1-HL-60 and small interfering circBMI1-HL-60 cells with HL-60 cells, we found that exosomes from circBMI1-HL-60 cells showed tumor suppressive effects, namely inhibiting HL-60 proliferation, promoting apoptosis, and increasing chemotherapeutic drug sensitivity. Exosomes from small interfering circBMI1-HL-60 cells showed the opposite effects. circBMI1 may act as an exosome-dependent tumor inhibitor. circBMI1, a potential biomarker for clinical diagnosis, acts as a tumor suppressor in AML by regulating miR-338-5p/ID4 and might affect the pathogenesis of AML by exosome secretion.
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INTRODUCTION: Several studies have identified a relationship between functional brain network disturbance and cognitive decline in people with Parkinson's disease (PwP); however, few studies have explored whether cerebral small vessel disease (CSVD) burden modifies this relationship. This study aimed to investigate the potential moderating effect of CSVD on the relationship between functional brain network disturbance and cognitive decline in PwP. METHODS: We prospectively recruited 61 PwP from Beijing Tiantan Hospital between October 2021 to September 2022. The Montreal Cognitive Assessment (MoCA) score was used to assess cognition. CSVD imaging markers were evaluated following the STandards for ReportIng Vascular changes on nEuroimaging instructions, and the CSVD burden score was calculated. The functional connectivity indicator was obtained and calculated using quantitative electroencephalography examination. The moderating effect of CSVD burden on the relationship between functional brain network disturbance and cognitive decline was examined using hierarchical linear regression. RESULTS: Forty-six of 61 (75.4%) PwP had cognitive impairment. Higher global weighted phase lag index (wPLI) values in beta1 bands were significantly associated with lower adjusted MoCA scores. CSVD burden aggravated the effect of the global wPLI in beta1 bands on adjusted MoCA scores. This effect was reinforced by the high level of CSVD burden. CONCLUSIONS: Higher wPLI indicates a possible pathological activation of functional brain networks that are associated with cognitive decline in PwP, and the high level of CSVD burden aggravates this relationship.
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Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Doença de Parkinson , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/patologia , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Disfunção Cognitiva/diagnóstico , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagemRESUMO
Freezing of gait is a common and debilitating symptom in Parkinson's disease. Although high-frequency subthalamic deep brain stimulation is an effective treatment for Parkinson's disease, post-operative freezing of gait severity has been reported to alleviate, deteriorate or remain constant. We conducted this study to explore the optimal stimulation sites and related connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait in Parkinson's disease. A total of 76 Parkinson's disease patients with freezing of gait who underwent bilateral high-frequency subthalamic stimulation were retrospectively included. The volumes of tissue activated were estimated based on individual electrode reconstruction. The optimal and sour stimulation sites were calculated at coordinate/voxel/mapping level and mapped to anatomical space based on patient-specific images and stimulation settings. The structural and functional predictive connectivity networks for the change of the post-operative Freezing of Gait-Questionnaire were also identified based on normative connectomes derived from the Parkinson's Progression Marker Initiative database. Leave-one-out cross-validation model validated the above results, and the model remained significant after including covariates. The dorsolateral two-thirds of the subthalamic nucleus was identified as the optimal stimulation site, while the ventrocentral portion of the right subthalamic nucleus and internal capsule surrounding the left central subthalamic nucleus were considered as the sour stimulation sites. Modulation of the fibre tracts connecting to the supplementary motor area, pre-supplementary motor area and pedunculopontine nucleus accounted for the alleviation of freezing of gait, whereas tracts connecting to medial and ventrolateral prefrontal cortices contributed to the deterioration of freezing of gait. The optimal/sour stimulation sites and structural/functional predictive connectivity networks for high-frequency subthalamic deep brain stimulation treating freezing of gait are identified and validated through sizable Parkinson's disease patients in this study. With the growing understanding of stimulation sites and related networks, individualized deep brain stimulation treatment with directional leads will become an optimal choice for Parkinson's disease patients with freezing of gait in the future.
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BACKGROUND: Electrode reconstruction for postoperative deep brain simulation (DBS) can be achieved manually using a surgical planning system such as Surgiplan, or in a semi-automated manner using software such as the Lead-DBS toolbox. However, the accuracy of Lead-DBS has not been thoroughly addressed. METHODS: In our study, we compared the DBS reconstruction results of Lead-DBS and Surgiplan. We included 26 patients (21 with Parkinson's disease and 5 with dystonia) who underwent subthalamic nucleus (STN)-DBS, and reconstructed the DBS electrodes using the Lead-DBS toolbox and Surgiplan. The electrode contact coordinates were compared between Lead-DBS and Surgiplan with postoperative CT and MRI. The relative positions of the electrode and STN were also compared between the methods. Finally, the optimal contact during follow-up was mapped onto the Lead-DBS reconstruction results to check for overlap between the contacts and the STN. RESULTS: We found significant differences in all axes between Lead-DBS and Surgiplan with postoperative CT, with the mean variance for the X, Y, and Z coordinates being -0.13, -1.16, and 0.59 mm, respectively. Y and Z coordinates showed significant differences between Lead-DBS and Surgiplan with either postoperative CT or MRI. However, no significant difference in the relative distance of the electrode and the STN was found between the methods. All optimal contacts were located in the STN, with 70% of them located within the dorsolateral region of the STN in the Lead-DBS results. CONCLUSIONS: Although significant differences in electrode coordinates existed between Lead-DBS and Surgiplan, our results suggest that the coordinate difference was around 1 mm, and Lead-DBS can capture the relative distance between the electrode and the DBS target, suggesting it is reasonably accurate for postoperative DBS reconstruction.
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Objectives: Low-beta oscillation (13-20 Hz) has rarely been studied in patients with early-onset Parkinson's disease (EOPD, age of onset ≤50 years). We aimed to explore the characteristics of low-beta oscillation in the subthalamic nucleus (STN) of patients with EOPD and investigate the differences between EOPD and late-onset Parkinson's disease (LOPD). Methods: We enrolled 31 EOPD and 31 LOPD patients, who were matched using propensity score matching. Patients underwent bilateral STN deep brain stimulation (DBS). Local field potentials were recorded using intraoperative microelectrode recording. We analyzed the low-beta band parameters, including aperiodic/periodic components, beta burst, and phase-amplitude coupling. We compared low-beta band activity between EOPD and LOPD. Correlation analyses were performed between the low-beta parameters and clinical assessment results for each group. Results: We found that the EOPD group had lower aperiodic parameters, including offset (p = 0.010) and exponent (p = 0.047). Low-beta burst analysis showed that EOPD patients had significantly higher average burst amplitude (p = 0.016) and longer average burst duration (p = 0.011). Furthermore, EOPD had higher proportion of long burst (500-650 ms, p = 0.008), while LOPD had higher proportion of short burst (200-350 ms, p = 0.007). There was a significant difference in phase-amplitude coupling values between low-beta phase and fast high frequency oscillation (300-460 Hz) amplitude (p = 0.019). Conclusion: We found that low-beta activity in the STN of patients with EOPD had characteristics that varied when compared with LOPD, and provided electrophysiological evidence for different pathological mechanisms between the two types of PD. These differences need to be considered when applying adaptive DBS on patients of different ages.
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Background: Freezing of gait (FOG) is a common disabling symptom in Parkinson's disease (PD). Cognitive impairment may contribute to FOG. Nevertheless, their correlations remain controversial. We aimed to investigate cognitive differences between PD patients with and without FOG (nFOG), explore correlations between FOG severity and cognitive performance and assess cognitive heterogeneity within the FOG patients. Methods: Seventy-four PD patients (41 FOG, 33 nFOG) and 32 healthy controls (HCs) were included. Comprehensive neuropsychological assessments testing cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function were performed. Cognitive performance was compared between groups using independent t-test and ANCOVA adjusting for age, sex, education, disease duration and motor symptoms. The k-means cluster analysis was used to explore cognitive heterogeneity within the FOG group. Correlation between FOG severity and cognition were analyzed using partial correlations. Results: FOG patients showed significantly poorer performance in global cognition (MoCA, p < 0.001), frontal lobe function (FAB, p = 0.015), attention and working memory (SDMT, p < 0.001) and executive function (SIE, p = 0.038) than nFOG patients. The FOG group was divided into two clusters using the cluster analysis, of which cluster 1 exhibited worse cognition, and with older age, lower improvement rate, higher FOGQ3 score, and higher proportion of levodopa-unresponsive FOG than cluster 2. Further, in the FOG group, cognition was significantly correlated with FOG severity in MoCA (r = -0.382, p = 0.021), Stroop-C (r = 0.362, p = 0.030) and SIE (r = 0.369, p = 0.027). Conclusions: This study demonstrated that the cognitive impairments of FOG were mainly reflected by global cognition, frontal lobe function, executive function, attention and working memory. There may be heterogeneity in the cognitive impairment of FOG patients. Additionally, executive function was significantly correlated with FOG severity.
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During surgery for foci-related epilepsy, neurosurgeons face significant difficulties in identifying and resecting MRI-negative or deep-seated epileptic foci. Here, we present a neuro-robotic navigation system that is specifically designed for resection of MRI negative epileptic foci. We recruited 52 epileptic patients, and randomly assigned them to treatment group with either neuro-robotic navigation or conventional neuronavigation system. For each patient, in the neuro-robotic navigation group, we integrated multimodality imaging including MRI and PET-CT into the robotic workstation and marked the boundary of foci from the fused image. During surgery, this boundary was delineated by the robotic laser device with high accuracy, guiding resection for the surgeon. For deeply seated foci, we exploited the neuro-robotic navigation system to localize the deepest point with biopsy needle insertion and methylene dye application to locate the boundary of the foci. Our results show that, compared with the conventional neuronavigation, the neuro-robotic navigation system performs equally well in MRI positive epilepsy patients (ENGEL I ratio: 71.4% vs 100%, p = 0.255) systems and show better performance in patients with MRI-negative focal cortical dysplasia (ENGEL I ratio: 88.2% vs 50%, p = 0.0439). At present, there are no documented neurosurgery robots with similar function and application in the field of epilepsy. Our research highlights the added value of using neuro-robotic navigation systems in resection surgery for epilepsy, particularly in cases that involve MRI-negative or deep-seated epileptic foci.
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Epilepsia , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Imageamento por Ressonância Magnética/métodos , Neuronavegação/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
Narrow QRS tachycardia with atrial activation occurring before ventricular activation was induced in a 34-year-old woman with dilated cardiomyopathy. During tachycardia late ventricular extrastimulus delivered when His bundle was refractory failed to reset the tachycardia while early ventricular extrastimulus caused paradoxical delay of the subsequent atrial response and terminated the tachycardia with a QRS not being followed by an atrial response. This is a rare but specific sign for excluding atrial reentry as the mechanism of tachycardia when P wave or atrial activation is registered before QRS response.
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Fibrilação Atrial/diagnóstico , Eletrocardiografia/métodos , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , HumanosRESUMO
OBJECTIVE: Vagus nerve stimulation (VNS) has been used for adjunctive treatment in drug resistant epilepsy (DRE) for decades. Nevertheless, information is lacking on possible potential prognostic factors. Our study presents the efficacy and safety of VNS with a focus on prognostic factors in 45 patients with DRE. METHODS: We retrospectively evaluated the clinical outcome of 45 consecutive patients with DRE undergoing VNS implantation in The First Affiliated Hospital of Anhui Medical University between November 2016 and August 2021. Medical records were aggregated across all patient visits. Cox proportional hazards regression was used to estimate the prognostic factors. RESULTS: Significant decrease in seizure frequency was observed after intermittent stimulation of the vagus nerve. According to the modified McHugh classification, 11 patients (24.4%) were Class I, 11 patients (24.4%) were Class II, four patients (8.9%) were Class III, 10 patients (22.2%) were Class IV, and nine patients (20.0%) were Class V. Notably, 22 patients (48.9%) were responders and four patients (8.9%) were seizure-free at the final follow-up. No significant prognostic factors were found in this cohort. Furthermore, 37 patients reported improved quality of life. Of the patients, 22 (48.9%) experienced adverse events after surgery; hoarseness, discomfort at the surgical site, and coughing were the most common. CONCLUSION: The results confirmed the efficacy and safety of VNS. No prognostic factors were identified.
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Objective: In this study, we aimed to investigate the effects of STN-DBS on PD patients with different levels of depression and to identify predictors of the effects of STN-DBS on PD depression. Methods: We retrospectively collected data for 118 patients with PD depression who underwent STN-DBS at Beijing Tiantan Hospital. Neuropsychological, motor, and quality of life assessments were applied preoperatively and postoperatively. All patients were divided into two groups according to their HAM-D24 total scores (group I: mild depression; group â ¡: moderate depression). A mixed repeated-measure analysis of variance (ANOVA) was performed to investigate whether there were differences in depression scores before and after STN-DBS between the two groups. The changes in depression scores were also compared between groups using ANCOVA, adjusting for gender and preoperative HAMA scores. Logistic regression was performed to identify predictors of STN-DBS's effects on PD depression. Results: Both groups showed significant improvement in depression symptoms after STN-DBS. Compared with patients in group I, patients in group â ¡ showed greater reductions in their HAM-D24 total scores (p = 0.002) and in HAM-D24 subitems including cognitive disturbances (p = 0.026) and hopelessness symptoms (p = 0.018). Logistic regression indicated that gender (female) (p = 0.014) and preoperative moderate depression (p < 0.001) patients had greater improvements in depression after STN-DBS. Conclusions: Patients with moderate depression showed better improvement than patients with mild depression. Gender (female) and preoperative HAMA scores are predictors of STN-DBS's effects on PD depression.
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BACKGROUND: Aberrant DNA methylation plays a crucial role in the progression of myeloid neoplasms. Previously, our literature reported that slit guidance ligand 2 (SLIT2) promoter methylation was associated with disease progression and indicated a poor prognosis in patients with myelodysplastic syndrome. Herein, we further investigated the clinical implications and role of SLIT2 promoter methylation in patients with chronic myeloid leukemia (CML). METHODS: The level of SLIT2 promoter methylation was determined in 104 CML patients, and its clinical significance was analyzed. Moreover, demethylation studies were performed in K562 cells to determine the epigenetic mechanism by which SLIT2 promoter methylation is regulated in CML. RESULTS: The level of SLIT2 promoter methylation was similar between CML patients and controls. However, deeper analysis revealed that the SLIT2 promoter methylation level in the accelerated phase (AP) and blast crisis (BC) was markedly higher than that in the chronic phase (CP) and controls. Additionally, a marked difference was identified between the SLIT2 promoter hypermethylated and non-hypermethylated groups among CML patients grouped by clinical stage. The frequency of SLIT2 hypermethylation was markedly increased with the progression of clinical stage, that is, it was the lowest in CP samples (12/80, 15%), higher in AP samples (4/8, 50%) and the highest in BC samples (11/16, 69%). Importantly, the level/density of SLIT2 promoter methylation was significantly higher in the advanced stage than in the early stage among the 6 tested paired CML patients. Epigenetically, the expression of the SLIT2-embedded non-coding genes SLIT2-IT1 and miR-218 expression was decreased in patients with CML. SLIT2 promoter hypermethylated cases had a markedly lower SLIT2-IT1 expression level than SLIT2 promoter non-hypermethylated cases. Moreover, SLIT2-IT1 and miR-218 expression was remarkably upregulated in a dose-dependent manner after demethylation treatment of K562 cells. CONCLUSIONS: Hypermethylation of the SLIT2 promoter is correlated with disease progression in CML. Furthermore, SLIT2 promoter methylation may function by regulating the expression of the SLIT2-embedded non-coding genes SLIT2-IT1 and miR-218 during CML progression.
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Peptídeos e Proteínas de Sinalização Intercelular , Leucemia Mielogênica Crônica BCR-ABL Positiva , MicroRNAs , Proteínas do Tecido Nervoso , Humanos , Progressão da Doença , Metilação de DNA/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Regiões Promotoras Genéticas/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/metabolismoRESUMO
Background: Deep brain stimulation (DBS) improves motor and non-motor symptoms in patients with Parkinson's disease (PD). Researchers mainly investigated the motor networks to reveal DBS mechanisms, with few studies extending to other networks. This study aimed to investigate multi-network modulation patterns using DBS in patients with PD. Methods: Twenty-four patients with PD underwent 1.5 T functional MRI (fMRI) scans in both DBS-on and DBS-off states, with twenty-seven age-matched healthy controls (HCs). Default mode, sensorimotor, salience, and left and right frontoparietal networks were identified by using the independent component analysis. Power spectra and functional connectivity of these networks were calculated. In addition, multiregional connectivity was established from 15 selected regions extracted from the abovementioned networks. Comparisons were made among groups. Finally, correlation analyses were performed between the connectivity changes and symptom improvements. Results: Compared with HCs, PD-off showed abnormal power spectra and functional connectivity both within and among these networks. Some of the abovementioned abnormalities could be corrected by DBS, including increasing the power spectra in the sensorimotor network and modulating the parts of the ipsilateral functional connectivity in different regions centered in the frontoparietal network. Moreover, the DBS-induced functional connectivity changes were correlated with motor and depression improvements in patients with PD. Conclusion: DBS modulated the abnormalities in multi-networks. The functional connectivity alterations were associated with motor and psychiatric improvements in PD. This study lays the foundation for large-scale brain network research on multi-network DBS modulation.
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AIMS: Previous studies have confirmed that BMI1 is elevated in esophageal cancer, which is a potential therapeutic target for esophageal cancer. However, the clinical significance of circular RNA BMI1 (circ-BMI1) in esophageal cancer is not yet clear. Herein, we revealed the clinical implication of circ-BMI1 in esophageal cancer, and provided a theoretical basis for molecular diagnosis and potential targeted therapy of esophageal cancer. METHODS: Firstly, 10 fresh paired esophageal cancer tissues and paracancer tissues, 49 esophageal cancer serum samples and 28 healthy control serum samples were involved in our study. Differential expression and clinical significance of circ-BMI1 in esophageal cancer patients and healthy controls were evaluated by quantitative Real-time RT-PCR (RT-qPCR). Secondly, effects of circ-BMI1 differential expression on biological function of esophageal cancer cell line Eca109 were analyzed. Effects of circ-BMI1 on cell proliferation, migration and colony forming ability were evaluated by CCK-8, wound healing, and colony-forming assay. Cell apoptosis, drug sensitivity tests were also be conducted. Finally, influence of Eca109 cells differentially expressed by circ-BMI1 on tumorigenicity in nude mice was studied. RESULTS: Expression of circ-BMI1 in serum and tissues of esophageal cancer patients was significantly decreased compared to controls (P < 0.001 and P = 0.003, respectively). Area under the receiver operating characteristic curve (ROC) was 0.726. Cell proliferation, migration and colony forming ability of circBMI1-Eca109 cells were obviously decreased than that of NC-Eca109 cells (P < 0.05). circBMI1-Eca109 cells were more sensitive to 5-fluorouracil and cisplatin, and tumor volume of nude mice in circBMI1-Eca109 group was smaller (P < 0.05). CONCLUSIONS: The study indicated that expression of circ-BMI1 was significantly down-regulated in esophageal cancer. Overexpression of circ-BMI1 inhibited proliferation, migration, colony formation of Eca109 cells, and tumor growth of Eca109 cells in nude mice. circ-BMI1 may be a potential target for diagnosis and treatment in esophageal cancer.
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Biomarcadores Tumorais , Neoplasias Esofágicas/genética , Complexo Repressor Polycomb 1/genética , RNA Circular , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose/genética , Linhagem Celular Tumoral , Modelos Animais de Doenças , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Curva ROCRESUMO
BACKGROUND: Recent clinical and preclinical studies have suggested that deep brain stimulation (DBS) can be used as a tool to enhance cognitive functions. The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit, including the anterior nucleus of thalamus (ANT), the entorhinal cortex (EC), and the fornix (FX), on cognitive behaviors in an Alzheimer's disease (AD) rat model. METHODS: Forty-eight rats were subjected to an intrahippocampal injection of amyloid peptides 1-42 to induce an AD model. Rats were divided into six groups: DBS and sham DBS groups of ANT, EC, and FX. Spatial learning and memory were assessed by the Morris water maze (MWM). Recognition memory was investigated by the novel object recognition memory test (NORM). Locomotor and anxiety-related behaviors were detected by the open field test (OF). By using two-way analysis of variance (ANOVA), behavior differences between the six groups were analyzed. RESULTS: In the MWM, the ANT, EC, and FX DBS groups performed differently in terms of the time spent in the platform zone (F(2,23) = 6.04, P < 0.01), the frequency of platform crossing (F(2,23) = 11.53, P < 0.001), and the percent time spent within the platform quadrant (F(2,23) = 6.29, P < 0.01). In the NORM, the EC and FX DBS groups spent more time with the novel object, although the ANT DBS group did not (F(2,23) = 10.03, P < 0.001). In the OF, all of the groups showed a similar total distance moved (F (1,42) = 1.14, P = 0.29) and relative time spent in the center (F(2,42) = 0.56, P = 0.58). CONCLUSIONS: Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently than ANT DBS. In addition, hippocampus-independent recognition memory was enhanced by EC and FX DBS. None of the targets showed side-effects of anxiety or locomotor behaviors.