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BACKGROUND: Parkinson's disease (PD) is a neurodegenerative influenced by various clinical factors. The potential relationship between renal function and the risk of PD remains poorly understood. This study aims to explore the association between kidney function and the risk of developing PD. METHODS: A population-based cohort study was conducted using data from 400,571 UK Biobank participants. Renal function was assessed using the estimated glomerular filtration rate (eGFR), calculated from serum creatinine and cystatin C levels. The association between eGFR levels and PD risk was evaluated using univariate and multivariate Cox regression analyses, Restricted Cubic Spline (RCS) analysis, and Kaplan-Meier analysis. Additionally, a clinical prediction model was developed and its diagnostic accuracy was evaluated using ROC analysis. A heatmap was also constructed to examine the relationship between clinical factors and gray matter volume in various brain regions. RESULTS: Over a median observation period of 13.8 years, 2740 PD events were recorded. Cox regression and Kaplan-Meier analyses revealed a significant association between decreased eGFR and increased PD risk, particularly in participants with eGFR < 30 ml/min/1.73 m2. This association was confirmed across three adjusted models. RCS analysis demonstrated a nonlinear relationship between decreasing eGFR and increasing PD risk. Furthermore, changes in eGFR were correlated with alterations in subcortical gray matter volume in regions such as the frontal cortex, striatum, and cerebellum. The clinical prediction model showed high diagnostic accuracy with AUC values of 0.776, 0.780, and 0.824 for 4-, 8-, and 16-year predictions, respectively. CONCLUSION: Renal insufficiency is significantly associated with an increased risk of PD, highlighting the importance of maintaining good kidney function as a potential preventive measure against PD.
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Tasa de Filtración Glomerular , Enfermedad de Parkinson , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cistatina C/sangre , Tasa de Filtración Glomerular/fisiología , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Biobanco del Reino Unido , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Parkinson's disease (PD) demonstrates considerable heterogeneity in the manifestation of clinical symptoms and disease progression. Recently, six clinical milestones have been proposed to evaluate disease severity in PD. However, the identification of PD progression subtypes based on these milestone events has not yet been performed. METHODS: Latent class analysis (LCA) was employed to identify subtypes of PD progression based on the timing of the first occurrence of six milestones within a 6-year follow-up period in Parkinson's Progression Markers Initiative (PPMI) database. RESULTS: The study cohort consisted of 354 early PD patients, of whom 42.9% experienced at least one milestone within six years. LCA identified two distinct subtypes of PD progression: slow progression (83%) and rapid progression (17%). The total number of milestones over six years was significantly higher in the rapid progression subtype compared to the slow progression subtype (median: 3.00 vs. 0.00, p < 0.001). At baseline, the rapid progression subtype, compared to the slow progression subtype, was characterized by an older age at onset and more severe motor and non-motor symptoms. On biomarkers, the rapid progression subtype demonstrated elevated CSF p-tau and serum NFL, but decreased mean striatal DAT uptake. Five clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, and RBD) were selected to construct the predictive model. The original predictive model achieved an AUC of 0.82. In internal validation using bootstrap resampling, the model achieved an AUC of 0.82, with a 95%CI ranging from 0.76 to 0.87. The model's performance was acceptable regarding both calibration and clinical utility. CONCLUSION: Approximately 17% of early PD patients exhibited the rapid progression subtype, characterized by the occurrence of more and earlier-onset milestones. The nomogram predictive model, incorporating five baseline clinical variables (age, SDMT score, MDS-UPDRS I score, MDS-UPDRS II + III scores, RBD), serves as a valuable tool for prognostic counseling and patient selection in PD clinical trials.
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The intricate composition of wastewater impedes the recycling of agricultural and industrial effluents. This study aims to investigate the potential of sisal leaf wastewater (SLW), both water-treated (WTSLW) and alkali-treated (ATSLW), as a substitute for the alkali activator (NaOH solution) in the production of slag-powder- and fly-ash-based composites, with a focus on the effects of WTSLW substitution ratios and sisal leaf soaking durations. Initially, the fresh properties were assessed including electrical conductivity and fluidity. A further analysis was conducted on the influence of both WTSLW and ATSLW on drying shrinkage, density, and mechanical strength, including flexural and compressive measures. Microstructural features were characterized using SEM and CT imaging, while XRD patterns and FTIR spectra were employed to dissect the influence of WTSLW substitution on the composite's products. The results show that incorporating 14 wt% WTSLW into the composite enhances 90-day flexural and compressive strengths by 34.8% and 13.2%, respectively, while WTSLW curtails drying shrinkage. Conversely, ATSLW increases porosity and decreases density. Organic constituents in both WTSLW and ATSLW encapsulated in the alkaline matrix fail to modify the composites' chemical composition. These outcomes underscore the potential for sustainable construction materials through the integrated recycling of plant wastewater and solid by-products.
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BACKGROUND: Neurotransmitter transport disorders may play a crucial role in Parkinson's Disease (PD), and Solute carrier family 6 member 12 (SLC6A12) encodes a neurotransmitter transporter. However, the relationship between SLC6A12 and PD remains largely unexplored. METHODS: We utilized the GEO database (107 samples) and clinical data (80 samples) to investigate the role of SLC6A12 in PD through differential expression analysis, ROC analysis, and RT-qPCR experiments. Subsequently, in vitro model, axon length measurement, CCK8 assay, flow cytometry, and JC-1 assays were conducted. Additionally, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, protein-protein interaction (PPI) network, gene set enrichment analysis (GSEA), and western blot experiments were assessed to explore the functional and mechanistic pathways of SLC6A12 in PD. Finally, CIBERSORT analysis was performed to investigate the correlation between SLC6A12 and immune cells in PD. RESULTS: The expression of SLC6A12 was significantly higher in individuals with PD compared to healthy controls. Inhibiting SLC6A12 expression in PD models enhanced neuronal growth and proliferation activity while reducing cell apoptosis. Furthermore, SLC6A12 was found to be involved in neuronal development, synaptic function, and neural protein transport processes in PD, potentially regulating the MAPK signaling pathway through the Ras/Raf/MEK/ERK axis, contributing to the pathological process of PD. Additionally, SLC6A12 was implicated in immune environment disturbances in PD, notably affecting CD4 T cell expression. CONCLUSION: This study documented the pathogenicity of SLC6A12 in PD for the first time, expanding the understanding of its molecular function and providing a potential target for precise treatment of PD.
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Sistema de Señalización de MAP Quinasas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Apoptosis , Proliferación Celular , Animales , Masculino , Mapas de Interacción de Proteínas , Femenino , Estudios de Casos y ControlesRESUMEN
Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. 18F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.
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JOURNAL/nrgr/04.03/01300535-202412000-00027/figure1/v/2024-04-08T165401Z/r/image-tiff Thalamic hemorrhage can lead to the development of central post-stroke pain. Changes in histone acetylation levels, which are regulated by histone deacetylases, affect the excitability of neurons surrounding the hemorrhagic area. However, the regulatory mechanism of histone deacetylases in central post-stroke pain remains unclear. Here, we show that iron overload leads to an increase in histone deacetylase 2 expression in damaged ventral posterolateral nucleus neurons. Inhibiting this increase restored histone H3 acetylation in the Kcna2 promoter region of the voltage-dependent potassium (Kv) channel subunit gene in a rat model of central post-stroke pain, thereby increasing Kcna2 expression and relieving central pain. However, in the absence of nerve injury, increasing histone deacetylase 2 expression decreased Kcna2 expression, decreased Kv current, increased the excitability of neurons in the ventral posterolateral nucleus area, and led to neuropathic pain symptoms. Moreover, treatment with the iron chelator deferiprone effectively reduced iron overload in the ventral posterolateral nucleus after intracerebral hemorrhage, reversed histone deacetylase 2 upregulation and Kv1.2 downregulation, and alleviated mechanical hypersensitivity in central post-stroke pain rats. These results suggest that histone deacetylase 2 upregulation and Kv1.2 downregulation, mediated by iron overload, are important factors in central post-stroke pain pathogenesis and could serve as new targets for central post-stroke pain treatment.
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RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare, highly malignant form of non-Hodgkin lymphoma categorized under the diffuse large B-cell type. It accounts for merely 1% of all non-Hodgkin lymphoma cases and comprises approximately 3% of all brain tumors. The involvement of the cerebellum is observed in only 9% of these cases. Recently, we came across an unusual instance: a young man presenting with multiple lesions located specifically within the cerebellum. PATIENT CONCERNS: A 26-year-old male was admitted to the hospital due to severe headaches. He has a medical history of sporadic headaches, accompanied by dizziness, nausea, and vomiting persisting for a month. Over the last 10 days, his headaches have intensified, coupled with decreased vision and protrusion of the eyeballs. Magnetic resonance imaging (MRI) revealed abnormal signals in both cerebellar hemispheres. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Diagnostic procedures included cerebellar biopsy, posterior fossa decompression, and lateral ventricle drainage. Histopathological examination identified diffuse large B-cell lymphoma (DLBCL) with high proliferative activity. To minimize neurotoxicity, chemotherapy involved intrathecal methotrexate (MTX) injections combined with the CHOP program. The patient has shown good tolerance to the treatment so far. LESSONS: While the definitive optimal treatment approach remains elusive, current chemotherapy centered on high-dose MTX stands as the standard induction therapy. Integrating surgery with radiotherapy and chemotherapy significantly extends patient survival.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Cerebelosas , Linfoma de Células B Grandes Difuso , Humanos , Masculino , Adulto , Linfoma de Células B Grandes Difuso/terapia , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Cerebelosas/terapia , Neoplasias Cerebelosas/patología , Ciclofosfamida/uso terapéutico , Ciclofosfamida/administración & dosificación , Vincristina/uso terapéutico , Doxorrubicina/uso terapéutico , Doxorrubicina/administración & dosificación , Metotrexato/uso terapéutico , Metotrexato/administración & dosificación , Prednisona/uso terapéutico , Prednisona/administración & dosificación , Terapia Combinada , Imagen por Resonancia Magnética , Cerebelo/patología , Cerebelo/diagnóstico por imagenRESUMEN
BACKGROUND: Lymphocyte antigen 96 (LY96) plays an important role in innate immunity and has been reported to be associated with various neurological diseases. However, its role in Parkinson's disease (PD) remains unclear. METHODS: Transcriptome data from a total of 49 patients with PD and 34 healthy controls were downloaded from the Gene Expression Omnibus (GEO) database to analyse the expression pattern of LY96 and its relationship with gene function and immune-related markers. In addition, peripheral blood samples were collected from clinical patients to validate LY96 mRNA expression levels. Finally, an in vitro cell model of PD based on highly differentiated SH-SY5Y cells was constructed, with small interfering RNA-silenced LY96 expression, and LY96 mRNA level, cell viability, flow cytometry, and mitochondrial membrane potential assays were performed. RESULTS: The results of the analyses of the GEO database and clinical samples revealed significantly abnormally high LY96 expression in patients with PD compared with healthy controls. The results of cell experiments showed that inhibiting LY96 expression alleviated adverse cellular effects by increasing cell viability, reducing apoptosis, and reducing oxidative stress. Gene set enrichment analysis showed that LY96 was positively correlated with T1 helper cells, T2 helper cells, neutrophils, natural killer T cells, myeloid-derived suppressor cells, macrophages, and activated CD4 cells, and may participate in PD through natural killer cell-mediated cytotoxicity pathways and extracellular matrix receptor interaction pathways. CONCLUSION: These findings suggested that LY96 might be a novel potential biomarker for PD, and offer insights into its immunoregulatory role.
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Biomarcadores , Antígeno 96 de los Linfocitos , Enfermedad de Parkinson , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Apoptosis , Biomarcadores/sangre , Estudios de Casos y Controles , Supervivencia Celular , Inmunidad Innata , Potencial de la Membrana Mitocondrial , Estrés Oxidativo , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/genética , Transcriptoma , Antígeno 96 de los Linfocitos/sangre , Antígeno 96 de los Linfocitos/genéticaRESUMEN
BACKGROUND: Cognitive impairment is a serious nonmotor symptom in patients with Parkinson's disease (PD). Currently, there are few studies investigating the relationship of serum markers and retinal structural changes with cognitive function in PD. OBJECTIVE: To investigate the relationship between retinal structural changes, serum high mobility group box-1 (HMGB1) levels and cognitive function and motor symptoms in PD patients. METHODS: Eighty-nine participants, including 47 PD patients and 42 healthy subjects, were enrolled. PD patients were divided into Parkinson's disease with normal cognitive (PD-NC), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) groups. The motor and nonmotor symptoms of PD patients were evaluated with clinical scale. Serum HMGB1 levels were detected by enzyme-linked immunosorbent assay (ELISA), and ganglion cell-inner plexiform layer complex (GCIPL) thickness changes in the macula were quantitatively analyzed by swept source optical coherence tomography (SS-OCT) in all patients. RESULTS: Compared with the control group, the macular GCIPL (t = -2.308, P = 0.023) was thinner and serum HMGB1 (z = -2.285, P = 0.022) was increased in PD patients. Macular GCIPL thickness in patients with PD-MCI and PDD were significantly lower than that in PD-NC patients, but there were no significant difference between the PD-MCI and PDD groups. Serum HMGB1 levels in patients with PD-MCI and PDD were significantly higher than those in PD-NC patients, and serum HMGB1 levels in PDD patients were higher than those in PD-MCI patients. Correlation analysis showed that serum HMGB1 levels in PD patients were positively correlated with disease duration, HY stage, UPDRS-I score, UPDRS-III score, and UPDRS total score and negatively correlated with MOCA score. Macular GCIPL thickness was negatively correlated with HY stage and positively correlated with MOCA score, and macular GCIPL thickness was negatively correlated with serum HMGB1 level. Logistic regression analysis showed that elevated serum HMGB1 level, thinner macular GCIPL thickness, and higher HY stage were independent risk factors for Parkinson's disease with cognitive impairment (PD-CI). The areas under the receiver operating characteristic curve (AUC) for the serum HMGB1 level and macular GCIPL thickness-based diagnosis of PD-MCI, PDD and PD-CI based on in patients with PD were 0.786 and 0.825, 0.915 and 0.856, 0.852 and 0.841, respectively. The AUC for the diagnosis of PD-MCI, PDD and PD-CI with serum HMGB1 level and GCIPL thickness combined were 0.869, 0.967 and 0.916, respectively. CONCLUSION: The macular GCIPL thickness and serum HMGB1 level are potential markers of cognitive impairment in PD patients, and their combination can significantly improve the accuracy of the diagnosis of cognitive impairment in PD.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Proteína HMGB1 , Enfermedad de Parkinson , Humanos , Cognición , RetinaRESUMEN
BACKGROUND: Dopamine dysregulation syndrome (DDS) is a complication of Parkinson's disease (PD) that seriously affects the quality of life of PD patients. Currently, the risk factors for DDS are poorly known, and it is critical to identify them in the early stages of PD. OBJECTIVE: To explore the incidence of and risk factors for DDS in patients with early PD. METHODS: A retrospective cohort study was conducted on the general data, clinical features, and imaging data of patients with early PD in the PPMI database. Multivariate Cox regression analysis was performed to analyze the risk factors for the development of DDS in patients with early PD, and KaplanâMeier curves examined the frequency and predictors of incident DDS symptoms. RESULTS: At baseline, 2.2% (n = 6) of patients with early PD developed DDS, and the cumulative incidence rates of DDS during the 5-year follow-up period were 2.8%, 6.4%, 10.8%, 15.5%, and 18.7%, respectively. In the multivariate Cox regression model controlling for age, sex, and drug use, hypersexuality (HR = 3.088; 95% CI: 1.416~6.732; P = 0.005), compulsive eating (HR = 3.299; 95% CI: 1.665~6.534; P = 0.001), compulsive shopping (HR = 3.899; 95% CI: 1.769~8.593; P = 0.001), anxiety (HR = 4.018; 95% CI: 2.136~7.599; P < 0.01), and lower Hoehn-Yahr (H-Y) stage (HR = 0.278; 95% CI: 0.152~0.509; P < 0.01) were independent risk factors for DDS in patients with early PD. PD patients with DDS had lower DAT uptake values than those patients without DDS. CONCLUSION: Early PD patients with hypersexuality, compulsive eating, compulsive shopping, anxiety, and lower H-Y stage were at increased risk for DDS. The occurrence of DDS may be related to the decrease in the average DAT uptake of the caudate and putamen.
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Trastornos Disruptivos, del Control de Impulso y de la Conducta , Enfermedad de Parkinson , Humanos , Dopamina , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Estudios Retrospectivos , Calidad de Vida , SíndromeRESUMEN
Parkinson's disease (PD), the most common neurological motor system disorder, which characterised by the irreversible loss of dopaminergic neurones in the substantia nigra pars compacta, and leads to the deficiency of dopamine in the striatum. Deposited Lewy bodies (LBs) in diseased neurones and nerve terminals are the pathological hallmark of PD, and alpha-synuclein (α-Syn) is the most prominent protein in LBs. The tight association between α-Syn and the molecular pathology of PD has generatly increaed the interest in using the α-Syn species as biomarkers to diagnose early PD. α-Syn is not confined to the central nervous system, it is also present in the peripheral tissues, such as human skin. The assessment of skin α-Syn has the potential to be a diagnostic method that not only has excellent sensitivity, specificity, and reproducibility, but also convenient and acceptable to patients. In this review, we (i) integrate the biochemical, aggregation and structural features of α-Syn; (ii) map the distribution of the α-Syn species present in the brain, biological fluids, and peripheral tissues; and (iii) present a critical and comparative analysis of previous studies that have measured α-Syn in the skin. Finally, we provide an outlook on the future of skin biopsy as a diagnostic approach for PD, and highlight its potential implications for clinical trials, clinical decision-making, treatment strategies as well as the development of new therapies.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/tratamiento farmacológico , alfa-Sinucleína/metabolismo , Reproducibilidad de los Resultados , Cuerpos de Lewy/patología , BiomarcadoresRESUMEN
Background: Parkinson's disease (PD) is a heterogeneous movement disorder with patients manifesting with either tremor-dominant (TD) or postural instability and gait disturbance (PIGD) motor subtypes. Small nerve fiber damage occurs in patients with PD and may predict motor progression, but it is not known whether it differs between patients with different motor subtypes. Objective: The aim of this study was to explore whether there was an association between the extent of corneal nerve loss and different motor subtypes. Methods: Patients with PD classified as TD, PIGD, or mixed subtype underwent detailed clinical and neurological evaluation and corneal confocal microscopy (CCM). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were compared between groups, and the association between corneal nerve fiber loss and motor subtypes was investigated. Results: Of the 73 patients studied, 29 (40%) had TD, 34 (46%) had PIGD, and 10 (14%) had a mixed subtype. CNFD (no./mm2, 24.09 ± 4.58 versus 28.66 ± 4.27; p < 0.001), CNBD (no./mm2, 28.22 ± 11.11 versus 37.37 ± 12.76; p = 0.015), and CNFL (mm/mm2, 13.11 ± 2.79 versus 16.17 ± 2.37; p < 0.001) were significantly lower in the PIGD group compared with the TD group. Multivariate logistic regression showed that higher CNFD (OR = 1.265, p = 0.019) and CNFL (OR = 1.7060, p = 0.003) were significantly associated with the TD motor subtype. The receiver operating characteristic (ROC) analysis demonstrated that combined corneal nerve metrics showed excellent discrimination between TD and PIGD, with an area under the curve (AUC) of 0.832. Conclusion: Greater corneal nerve loss occurs in patients with PIGD compared with TD, and patients with a higher CNFD or CNFL were more likely to have the TD subtype. CCM may have clinical utility in differentiating different motor subtypes in PD.
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C-X-C chemokine receptor type 4 (CXCR4) is highly expressed in Parkinson's disease (PD) mice's brains and is related to astrocyte signaling and microglial activation. This makes CXCR4 related to neuroinflammation and also makes CXCR4 considered to be the PD development mechanism and possible therapeutic targets. Therefore, it is worth studying the effect of CXCR4 on neuropathological changes and its potential therapeutic value for PD. This study aimed to investigate the effect of CXCR4 knockout on neuropathological changes in the mouse model of PD and its mechanism. In this study, CXCR4-WT and CXCR4+/- C57BL mice were used to make Parkinson's model. Behavioral experiments, dopaminergic neuron markers, neuroinflammation, and blood-brain barrier damage were detected to verify the effect of CXCR4 knockout on neuropathological changes. CXCR4 knockout improved the behavioral results and tyrosine hydroxylase (TH) expression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice. In the substantia nigra (SN) area of the brain of PD mouse model, the number of Iba1-positive (p = 0.0004) and GFAP-positive cells (p = 0.0349) was significantly lower in CXCR4 knockout group than CXCR4-WT group. CXCR4 knockout reduced MPTP-induced infiltration of peripheral immune cells and the expression of pro-inflammatory cytokines. CXCR4 knockout also protected blood-brain barrier (BBB) from MPTP-induced damage. In conclusion, CXCR4 knockout inhibits the degeneration of dopamine neurons, microglial and astrocyte activation, neuroinflammation, and BBB damages in the MPTP-lesioned PD mice.
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Enfermedades del Sistema Nervioso , Enfermedad de Parkinson , Animales , Ratones , Enfermedad de Parkinson/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Enfermedades Neuroinflamatorias , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: The effect of three-dimensional (3D) printed bone-attached guide plate assisted cannulated screw fixation of pelvic fracture is reliable, but extensive soft tissue dissection is still required when installing the guide plate. This study aims to compare the efficacy of posterior pelvic ring fracture fixation with iliosacral screw insertion between the assistance of modified percutaneous patient specific 3D printed guide template and conventional fluoroscopy. METHODS: From May, 2019 and September 2021, 28 patients sustained posterior pelvic ring fractures were randomized into 2 groups: A guide template group, in which the iliosacral screw was inserted for fixation of the posterior pelvic ring fracture with the assistance of modified percutaneous patient specific 3D printed guide template, and a fluoroscopy group, in which the iliosacral screw was inserted under the guidance of conventional fluoroscopy. The operation time, fluoroscopic frequency, intraoperative blood loss, and incision length were recorded for each screw insertion. Fracture reduction was evaluated according to the Matta criteria. The screw position was evaluated according to the modified Gras classification, and the functional outcome was evaluated according to Majeed score. The parameters of both groups were compared, and statistical analysis was performed. RESULTS: All the 28 patients were followed up for 12-24 months. Of them, 15 iliosacral screws were inserted in 14 patients in the guide template group, and 14 iliosacral screws were inserted in 14 patients in the fluoroscopy group. The operation time, fluoroscopic frequency, screw deviation, incision length, and blood loss in the guide template group were 20-30(25.8±2.8) min, 9-15(12.2±1.9), 2-4(2.6±0.7) mm, 4-5(4.6±0.5) cm, and 5-10 (7.8±1.7) mL, respectively, whereas those in the fluoroscopy group were 30-60(48.1±7.5) min, 40-96(64.7±16.3), 3-6(4.2±0.9) mm, 0.8-1.2(1.0±0.1) cm, and 2-5(3.1±1.3) mL, respectively, and there were statistical significance (all P<0.001). Fracture reduction was evaluated according to the Matta criteria, and all the patients reached excellence and good (P=0.584) in the 2 groups. According to modified Gras classification, there were 12 Grade I screws, 3 Grade II screws, and 0 Grade III screws in the guide template group, and 10 Grade I screws, 3 Grade II screws, and 1 Grade III screw in the fluoroscopy group, with no statistical significance (P=0.334). The functional outcome was evaluated according to Majeed score at the last follow-up, without significant difference between the guide template group and the fluoroscopy group (P=0.908). CONCLUSIONS: Compared with the conventional fluoroscopy, it would cost less operation time, less fluoroscopic frequency and increase more accurate screw insertion to fixate the posterior pelvic ring fracture with the assistance of modified percutaneous patient specific 3D printed guide template.
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Fracturas Óseas , Hiperaldosteronismo , Herida Quirúrgica , Humanos , Fracturas Óseas/cirugía , Disección , Fluoroscopía , Impresión Tridimensional , Tornillos ÓseosRESUMEN
Autonomic dysregulation in Parkinson's disease (PD) can precede motor deficits and is associated with reduced quality of life, disease progression, and increased mortality. Objective markers of autonomic involvement in PD are limited. Corneal confocal microscopy (CCM) is a rapid ophthalmic technique that can quantify small nerve damage in a range of peripheral and autonomic neuropathies. Here we investigated whether CCM can be used to assess autonomic symptoms in PD. Based on the scale for outcomes in Parkinson's disease for autonomic symptoms (SCOPA-AUT), patients with PD were classified into those without autonomic symptoms (AutD-N), with single (AutD-S), and multiple (AutD-M) domain autonomic dysfunction. Corneal nerve fiber pathology was quantified using CCM, and the relationship with autonomic symptoms was explored. The study enrolled 71 PD patients and 30 control subjects. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and CNBD/CNFD ratio were lower in PD patients with autonomic symptoms compared to those without autonomic symptoms. Autonomic symptoms correlated positively with CNFD (r = -0.350, p = 0.004), and were not related to Levodopa equivalent daily dose (r = 0.042, p = 0.733) after adjusting for age, disease severity, disease duration or cognitive function. CCM parameters had high sensitivity and specificity in distinguishing patients with PD with and without autonomic symptoms. PD patients with autonomic symptoms have corneal nerve loss, and CCM could serve as an objective ophthalmic imaging technique to identify patients with PD and autonomic symptoms.
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Background: Ferroptosis is a type of iron-dependent programmed cell death. Ferroptosis has been shown to be a significant factor for the pathogenesis of Parkinson's disease (PD). However, the mechanism involved in ferroptosis has not been fully elucidated in PD. Methods: Repressor element-1 silencing transcription factor (REST) and specificity protein 1 (SP1) expressions were monitored by qRT-PCR. Cell viability, reactive oxygen species (ROS), and mitochondrial injury were validated by CCK-8, flow cytometry, and transmission electron microscope. The levels of neurons-related proteins and ferroptosis-associated proteins were identified by western blot and immunofluorescence assays. The interaction between miR-494-3p and REST or SP1 and ACSL4 was analyzed by luciferase, chromatin immunoprecipitation, or EMSA assay. Results: Erastin could dose-dependently induce neuron injury and ferroptosis of LUHMES cells. miR-494-3p overexpression induced ROS production, mitochondrial damage, ferroptosis, and neuron injury in erastin-induced LUHMES cells. Likewise, miR-494-3p inhibition had the opposite effects. We also showed that REST was a target gene of miR-494-3p and could repress erastin-induced ferroptosis, neuron injury, ROS, and mitochondrial injury via SP1 in LUHMES cells. Moreover, we demonstrated that SP1 could interact with ACSL4. We also confirmed that miR-494-3p could aggravate the pathological changes of substantia nigra and corpus striatum in the MPTP-induced PD mouse model. Conclusion: miR-494-3p significantly promotes ferroptosis by regulating the REST/SP1/ACSL4 axis in PD. Thus, our results open potential therapeutic targets for PD.
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Ferroptosis , MicroARNs , Enfermedad de Parkinson , Animales , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Enfermedad de Parkinson/genética , Piperazinas , Especies Reactivas de Oxígeno/metabolismo , Factores de TranscripciónRESUMEN
The current study investigated the physiological mechanisms by which extracellular vesicle (EV)-encapsulated miR-181a-2-3p derived from mesenchymal stem cells (MSCs) might mediate oxidative stress (OS) in Parkinson's disease (PD). First, 6-hydroxydopamine (6-OHDA)-induced PD cell and mouse models were established, after which miR-181a-2-3p, EGR1, and NOX4 expression patterns were determined in SH-SY5Y cells and substantia nigra (SN) of PD mice. Next, the binding affinity among miR-181a-2-3p, EGR1, and NOX4 was identified using multiple assays. Gain- or loss-of-function experiments were further adopted to detect SH-SY5Y cell proliferation and apoptosis and to measure the levels of SOD, MDA, and ROS. Finally, the effects of miR-181a-2-3p from MSC-derived EVs in PD mouse models were also explored. It was found that miR-181a-2-3p was poorly expressed in 6-OHDA-induced SH-SY5Y cells, whereas miR-181a-2-3p from MSCs could be transferred into SH-SY5Y cells via EVs. In addition, miR-181a-2-3p could target and inhibit EGR1, which promoted the expression of NOX4. The aforementioned miR-181a-2-3p shuttled by MSC-derived EVs facilitated SH-SY5Y proliferation and SOD levels, but suppressed apoptosis and MDA and ROS levels by regulating EGR1 via inhibition of NOX4/p38 MAPK, so as to repress OS of PD. Furthermore, in PD mice, miR-181a-2-3p was carried by EVs from MSCs to alleviate apoptosis of dopamine neurons and OS, accompanied by increased expressions of α-syn and decreased 4-HNE in SN tissues. Collectively, our findings revealed that MSC-derived EV-loaded miR-181a-2-3p downregulated EGR1 to inhibit OS via the NOX4/p38 MAPK axis in PD.
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INTRODUCTION: Posterior pelvic ring disruption includes sacral fractures, sacroiliac joint fracture dislocations and ilium fractures. Percutaneous iliosacral screw fixation of sacral fractures and sacraoiliac joint fracture dislocations have been prevailing, it has the advantages of minimal invasiveness, less blood loss and low wound infection rate. HYPOTHESIS: This study was to evaluate the application of three-dimensional (3D) printed patient-specific guide template in closed reduction and iliosacral screw fixation of posterior pelvic ring disruption. MATERIAL AND METHODS: The data of patients, who were treated with closed reduction and iliosacral screw fixation of posterior pelvic ring disruption with the assistance of 3D printed guide template from December 2014 to September 2018, were collected. The screw placement time, fluoroscopy time, intraoperative blood loss, fracture reduction, screw position, and functional assessment were recorded. RESULTS: There were 17 cases of unstable pelvic fractures,and 20 screws were inserted for fixation of sacral fractures or sacroiliac joint dislocations, with bilateral screw placement in 3 cases. The average time for each screw placement was 45.9±8.6min (30-60min). The average fluoroscopy time for each screw insertion was 50.3±19.7s (24-96 s). The mean blood loss for each screw placement was 32.0±11.1ml (20-50ml). According to Matta scale, the fracture reduction was graded as excellent in all the 17 cases. According to the modified Gras classification, the 3D CT reconstruction of the pelvis demonstrated Grade 1 for 18 screws and Grade 2 for 2 screw. Functional outcome 1 year postoperatively was rated as 15 excellent and 2 good, according to the Majeed functional scale. DISCUSSION: It is feasible and safe to stabilize the posterior pelvic ring disruption using iliosacral screw fixation under assistance of the 3D printed guide template. It could reduce fluoroscopy time, screw placement time and intraoperative blood loss and achieve good postoperative recovery. LEVEL OF PROOF: IV; Retrospective study.
Asunto(s)
Fractura-Luxación , Fracturas Óseas , Luxaciones Articulares , Huesos Pélvicos , Fracturas de la Columna Vertebral , Pérdida de Sangre Quirúrgica , Tornillos Óseos/efectos adversos , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/etiología , Fracturas Óseas/cirugía , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/etiología , Luxaciones Articulares/cirugía , Huesos Pélvicos/diagnóstico por imagen , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Pelvis , Estudios Retrospectivos , Sacro/diagnóstico por imagen , Sacro/lesiones , Sacro/cirugía , Fracturas de la Columna Vertebral/etiologíaRESUMEN
Parkinson's disease is a neurodegenerative disorder while secondary-parkinsonism can be caused by infectious, inflammatory, traumatic, vascular, hereditary, paraneoplastic, or even induced by drug/metal poisoning. Here we report an uncommon subacute parkinsonism who presented with micrographia and mild cognitive impairment. The CSF examination showed inflammatory profile and positive anti-NMDAR antibody. The patient showed no improvement with levodopa/benserazide administration but satisfactory response to immunotherapy with methylprednisolone. This case indicated that autoimmune etiology should also be considered in parkinsonism to exclude a treatable condition.
Asunto(s)
Encefalitis Antirreceptor N-Metil-D-Aspartato/complicaciones , Autoanticuerpos/líquido cefalorraquídeo , Disfunción Cognitiva/etiología , Escritura Manual , Inmunoterapia , Enfermedad de Parkinson Secundaria/inmunología , Adulto , Encefalitis Antirreceptor N-Metil-D-Aspartato/tratamiento farmacológico , Encefalitis Antirreceptor N-Metil-D-Aspartato/inmunología , Antiparkinsonianos/uso terapéutico , Benserazida/uso terapéutico , Combinación de Medicamentos , Fiebre de Origen Desconocido/etiología , Humanos , Inmunosupresores/uso terapéutico , Levodopa/uso terapéutico , Masculino , Metilprednisolona/uso terapéutico , Pruebas Neuropsicológicas , Enfermedad de Parkinson Secundaria/diagnóstico , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Enfermedad de Parkinson Secundaria/psicología , Temblor/etiologíaRESUMEN
Cognitive impairment in Parkinson's disease (PD) adversely influences quality of life. There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (P < 0.05). CNBD and CNBD/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (r = 0.683, P < 0.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (r = -0.481, P < 0.001) and total UPDRS scores (r = -0.401, P = 0.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (r = 0.176, P = 0.161). CNFD, CNBD, CNFL, and CNBD/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.