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BACKGROUND: While new genetic analysis methods are widely used in the clinic, few researchers have focused on trigeminal neuralgia (TN) with familial clustering (≥ 2 TN patients in one kindred family). Previous literature suggests that familial trigeminal neuralgia (FTN) may be associated with inherited genetic factors. To date, few next-generation sequencing studies have been reported for FTN. This study investigated the pathogenic mechanism of FTN by using whole-exome sequencing (WES) technology, which may enhance our understanding of human TN pathophysiology. METHOD: We performed WES for 7 probands from families of FTN. Sanger sequencing was performed for two control groups (FTN family members group and nonfamilial TN subject group) to potentially identify new FTN-related gene mutations. In families where FTN probands carried potentially pathogenic gene mutations, the ribonucleic acid (RNA) of FTN probands and related family members, as well as nonfamilial TN patients were analysed by RNA sequencing (RNA-seq) to confirm differential gene expression. RESULTS: Seven probands were derived from 3 Chinese families. WES and Sanger sequencing identified MARS1 mutation c.2398C > A p.(Pro800Thr) in Family 1. MARS1 mutation was confirmed in 14/26 [53.8%] members of Family 1 in FTN family member group, while none of nonfamilial TN subjects had this MARS1 mutation. RNA-seq showed that 3 probands in Family 1 had higher expression of Fosl1 (Fos-like antigen 1) and NFE2 (Nuclear factor, erythroid 2) than 3 subjects in the nonfamilial TN subject group. Fosl1 and NFE2 are genes related to integrated stress response (ISR). CONCLUSION: MARS1 mutations may cause chronic activation of ISR, contribute to ISR pathophysiological changes in FTN, and cause/accelerate peripheral nerve degeneration. The findings of this study can enrich our knowledge of the role of molecular genetics in TN in humans.
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Metionina tRNA Ligase , Neuralgia do Trigêmeo , Humanos , Mutação , Linhagem , Neuralgia do Trigêmeo/genética , Metionina tRNA Ligase/genéticaRESUMO
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are now widely found in aquatic ecosystems, including sources of drinking water and portable water, due to their increasing prevalence. Among different PFAS treatment or separation technologies, nanofiltration (NF) and reverse osmosis (RO) both yield high rejection efficiencies (>95%) of diverse PFAS in water; however, both technologies are affected by many intrinsic and extrinsic factors. This study evaluated the rejection of PFAS of different carbon chain length (e.g., PFOA and PFBA) by two commercial RO and NF membranes under different operational conditions (e.g., applied pressure and initial PFAS concentration) and feed solution matrixes, such as pH (4-10), salinity (0- to 1000-mM NaCl), and organic matters (0-10 mM). We further performed principal component analysis (PCA) to demonstrate the interrelationships of molecular weight (213-499 g·mol-1 ), membrane characteristics (RO or NF), feed water matrices, and operational conditions on PFAS rejection. Our results confirmed that size exclusion is a primary mechanism of PFAS rejection by RO and NF, as well as the fact that electrostatic interactions are important when PFAS molecules have sizes less than the NF membrane pores. PRACTITIONER POINTS: Two commercial RO and NF membranes were both evaluated to remove 10 different PFAS. High transmembrane pressures facilitated permeate recovery and PFAS rejection by RO. Electrostatic repulsion and pore size exclusion are dominant rejection mechanisms for PFAS removal. pH, ionic strength, and organic matters affected PFAS rejection. Mechanisms of PFAS rejection with RO/NF membranes were explained by PCA analysis.
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Fluorocarbonos , Purificação da Água , Água , Ecossistema , Purificação da Água/métodos , Osmose , Membranas Artificiais , Filtração/métodosRESUMO
This study investigated the release of heavy metals from polluted soil under the pore water flow containing nanobubbles (NBs) to simulate natural ebullition. Three types of NBs (CH4, H2, and CO2) were generated in water and characterized, including bubble size, zeta potential, liquid density, and tension. The flow rate used in column tests was optimized to achieve proper soil fluidization and metal desorption or release. The leachate chemistries were monitored to assess the effect of NBs on conductivity, pH, oxidation-reduction potential (ORP), and dissolved oxygen (DO). The results showed that NBs in the pore water flow were significantly more effective in releasing Pb compared to DI water, with CO2 NB water being the most effective and H2 NB water being the least effective. CO2 NB water was also used to rinse column soil contaminated with four different metals (Pb, Cu, Zn, and Cr), which exhibited different leaching kinetics. Moreover, a convective-dispersion-deposition equation (CDDE) model accurately simulated the leaching kinetics and explained the effects of NBs on the key parameters, such as the deposition rate coefficient (Kd), that affect the released metal transport. The findings could provide new insights into soil pollutant release under ebullition and soil remediation using water wash containing NBs.
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OBJECTIVE: To explore the expression of δ subunit-containing γ-aminobutyric acid(A) (GABA)(A) receptors in insular electrical kindled rats and analyze the significance of the findings. METHODS: A total of 48 male Sprague-Dawley rats were divided randomly into 3 groups: kindled, sham-operated and control. Kindled group: chronic insular electrical kindled models of rats established by electrical stimulation. Sham-operated group: the same method of the kindled group without electrical stimulation. CONTROL GROUP: without surgery. The number of hippocampal neurons of rat epilepsy, sham-operated and control groups were detected by Nissl staining. The hippocampal expressions of δ subunit of these groups were tested by immunohistochemistry. The mRNA of δ subunit of hippocampus of these groups was detected by quantitative-polymerase chain reaction (q-PCR). RESULTS: The findings of Nissl staining showed that there was no significant difference of the number of hippocampal neurons between epileptic and normal rats (P > 0.05). The findings of q-PCR showed that mRNA of δ subunit of the hippocampus of sham-operated and control groups represented much more than that of kindled group at Day 7 post-kindling (P < 0.01). The findings of immunohistochemistry showed that the hippocampal expression of δ subunit of sham-operated and control groups represented much more than that of kindled group at Day 7 post-kindling (P < 0.01). CONCLUSION: The hippocampal expression of δ subunit-containing GABA(A) receptors decreases in insular epilepsy. It may play an important role in the occurrence and development of insular epilepsy.
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Hipocampo/metabolismo , Excitação Neurológica/metabolismo , Receptores de GABA-A/metabolismo , Animais , Modelos Animais de Doenças , Epilepsia/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Deep Sylvian meningiomas are rare and difficult to diagnose when small tumours lead to various symptoms. The difficulty associated with surgery is underestimated. Our case involved a mass (11 mm × 12 mm × 12 mm in size) in the right Sylvian fissure. It is the smallest deep Sylvian meningioma known and might be more easily misdiagnosed than previous examples. CASE SUMMARY: A well-enhanced mass in the right Sylvian fissure of a 26-year-old male with a three-month history of seizure was identified via magnetic resonance imaging. The patient underwent operations twice for seizure control. During the first operation, the tumour was surrounded by the second segment of the middle cerebral artery and its numerous perforators. Partial resection had to be selected due to mild arterial damage. After the first operation, the patient presented with simple partial seizure. During reoperation, we isolated the anatomical structure near the tumour and the tumour over and removed it from its dorsal side by piecemeal resection. CONCLUSION: This case reported the smallest deep Sylvian meningioma according to a literature review. Preoperative diagnosis is a crucial step due to deep Sylvian meningioma firmly adhering to the middle cerebral artery and its perforators. Adequate preparation is crucial to ensure the success of surgery.
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Deep brain stimulation (DBS) is an effective treatment for dyskinesia in patients with Parkinson's disease (PD), among which the therapeutic targets commonly used include the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Levodopa-induced dyskinesia (LID) is one of the common motor complications arising in PD patients on chronic treatment with levodopa. In this article, we retrospectively evaluated the outcomes of LID with the Unified Dyskinesia Rating Scale (UDysRS) in patients who underwent DBS in multiple centers with a GPi or an STN target. Meanwhile, the Med off MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-â ¢) and the levodopa equivalent daily dose (LEDD) were also observed as secondary indicators. PD patients with a GPi target showed a more significant improvement in the UDysRS compared with an STN target (92.9 ± 16.7% vs. 66.0 ± 33.6%, p < 0.0001). Both the GPi and the STN showed similar improvement in Med off UPDRS-III scores (49.8 ± 22.6% vs. 52.3 ± 29.5%, p = 0.5458). However, the LEDD was obviously reduced with the STN target compared with the GPi target (44.6 ± 28.1% vs. 12.2 ± 45.8%, p = 0.006).
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BACKGROUND AND STUDY AIMS: Primary intraspinal primitive neuroectodermal tumors (PNETs) account for â¼0.4% of all intraspinal tumors, but information about these tumors in the medical literature is limited to single case reports. We report four cases of primary intraspinal PNETs and present a systematic literature review of the reported cases. MATERIALS AND METHODS: We retrospectively reviewed and analyzed the clinical data of 4 patients with primary intraspinal PNETs who underwent neurosurgical treatment at our clinic between January 2013 and January 2020, and of 32 cases reported in the literature. RESULTS: The female-to-male ratio was 2.6:1. The mean patient age was 21.42 ± 15.76 years (range: 1-60 years), and patients <36 years of age accounted for 83.30% of the study cohort. Progressive limb weakness and numbness were the chief symptoms (accounting for â¼55.6%). The mean complaint duration was 0.89 ± 0.66 months for males and 2.72 ± 3.82 months for females (p = 0.028). Epidural (41.7%) was the most common site, and thoracic (47.3%) was the most frequent location. Most PNETs were peripheral, and magnetic resonance imaging (MRI) appearance was isointense or mildly hypointense on T1-weighted images and hyperintense on T2-weighted images. Homogeneous contrast enhancement was observed. The 1-year survival rate of patients who underwent chemoradiation after total or subtotal lesion resection was better compared with patients who did not undergo chemotherapy, radiotherapy, or total or subtotal resection. The modality of treatment was associated with survival time (p = 0.007). CONCLUSION: Primary intraspinal PNETs mainly occur in young people with a female preponderance. In patients with a rapid loss of lower limb muscle strength and large intraspinal lesions on MRI, PNETs should be considered. Surgical resection and adjuvant radio chemotherapy are key prognostic factors.
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Tumores Neuroectodérmicos Primitivos , Neoplasias da Coluna Vertebral , Adolescente , Adulto , Criança , Pré-Escolar , Espaço Epidural , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tumores Neuroectodérmicos Primitivos/diagnóstico por imagem , Tumores Neuroectodérmicos Primitivos/cirurgia , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Adulto JovemRESUMO
BACKGROUND: Gliomas are prevalent primary intracerebral malignant tumors. Increasing evidence indicates an association between the immune signature and Grade II/III glioma prognosis. Thus, we aimed to develop an immune-related gene pair (IRGP) signature that can be used as a prognostic tool in Grade II/III glioma. METHODS: The gene expression levels and clinical information of Grade II/III glioma patients were collected from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The TCGA data were randomly divided into a training cohort (n = 249) and a validation cohort (n = 162), and a CGGA dataset served as an external validation group (n = 605). IRGPs significantly associated with prognosis were selected by Cox regression. Gene set enrichment analysis and filtration were performed with the IRGPs. RESULTS: Within a set of 1991 immune genes, 8 IRGPs including 15 unique genes that significantly affect survival constituted a gene signature. In the validation datasets, the IRGP signature significantly stratified patients with Grade II/III glioma into low- and high-risk groups (P < 0.001), and the IRGP index was found to be an independent prognostic factor through univariate and multivariate analyses (P < 0.05). Additionally, 26 functional pathways were identified through the intersection of Gene Set Enrichment Analysis (GSEA) and Gene Ontology (GO) enrichment analysis. CONCLUSION: The IRGP signature demonstrated good prognostic value for Grade II/III gliomas, which may provide new insights into individual treatment for glioma patients. The IRGPs might function through the identified 26 functional pathways.
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PURPOSE: To explore the value of F-NLR-AGR score based on preoperative fibrinogen, neutrophil to lymphocyte ratio (NLR), and albumin to globulin ratio (AGR) in predicting the prognosis in patients with glioma. PATIENTS AND METHODS: 203 glioma patients were retrospectively analyzed. Receiver-operating characteristic (ROC) curve analysis was used to determine the optimal cut-off values for NLR, AGR, and fibrinogen. According to these cut-off values, patients with high NLR (>1.90), low AGR (<1.54), and elevated fibrinogen (>2.61 g/L) were defined as a score of 3, if none of the patients' three parameters met these standards they were given a score of 0, if any two or one parameter met these standards they were scored as 2 or 1, respectively. The correlation between F-NLR-AGR score and glioma grade was also evaluated. RESULTS: The three-year overall survival (OS) rate and the mean overall survival in patients with F-NLR-AGR=3 were lower than those of patients with F-NLR-AGR = 2, 1 or 0 [17.6% vs 35.2%, 66.9% or 83.7% (26.0 vs 39.0, 64.0 or 81.0 months), P<0.001]. Multivariate analysis revealed that age (HR=2.071; 95% CI=1.195-3.588; P=0.009), WHO grade (P<0.001), and F-NLR-AGR score (P<0.001) were independent prognostic factors for OS. Spearman's rank correlation analysis revealed that F-NLR-AGR score was positively correlated with glioma grade (r=0.278, P<0.01). CONCLUSION: Preoperative F-NLR-AGR score was correlated with glioma grading, high F-NLR-AGR score was an independent predictor of poor prognosis in glioma. Therefore, the scoring system may be applied in clinical practice to identify high-risk patients.