Structural changes in the retina and serum HMGB1 levels are associated with decreased cognitive function in patients with Parkinson's disease.

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.

Two new cases with the UBQLN2 gene mutation in Han Chinese.

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.

Association between kidney function and Parkinson's disease risk: a prospective study from the UK Biobank.

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.

Predictors of dopamine dysregulation syndrome in patients with early Parkinson's disease.

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 Kaplan‒Meier 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.

Efficacy comparison between iliosacral screw fixation of the posterior pelvic ring fracture with the assistance of modified percutaneous three-dimensional printing guide template and conventional fluoroscopy. / æ”¹è‰¯ç»çš®ä¸‰ç»´æ‰“å°å¯¼æ¿ä¸Žä¼ ç»Ÿé€è§†è¾ åŠ©éª¶é«‚èžºé’‰å›ºå®šéª¨ç›†åŽçŽ¯éª¨æŠ˜çš„ç–—æ•ˆæ¯”è¾ƒ.

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.

Long non-coding RNA CIR inhibits chondrogenic differentiation of mesenchymal stem cells by epigenetically suppressing ATOH8 via methyltransferase EZH2.

BACKGROUND: Osteoarthritis (OA) is the most common articular disorder, leading to joint malfunction and disability. Although the incidence of OA is increasing globally, the treatment of OA is very limited. LncRNA CIR has been implicated in OA through unclear mechanisms. Here, we investigated the role of lncRNA CIR in chondrogenic differentiation. METHODS: Human umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) were obtained from human umbilical cords. Flow cytometry was used to analyze the surface markers of hUC-MSCs. Various culture conditions and corresponding staining assays were employed to assess the differentiation abilities of hUC-MSC. qRT-PCR, western blot, and immunostaining were used to measure expression levels of related genes and proteins such as lncRNA CIR, ATOH8, EZH2, and H3K27me3. RNA immunoprecipitation assay, biotin pull-down, and chromatin immunoprecipitaion assay were performed to analyze the interactions of lncRNA CIR, EZH2, H3K27me3 and ATOH8 promoter. RESULTS: hUC-MSCs exhibited MSCs features and could differentiate into chondrocytes under specific conditions. LncRNA CIR was downregulated while ATOH8 was upregulated during the chondrogenic differentiation of hUC-MSCs. Knockdown lncRNA CIR or overexpression of ATOH8 promoted chondrogenic differentiation. Further, lncRNA CIR bound to EZH2 and repressed ATOH8 expression via EZH2-mediated H3K27me3, which promotes the methylation of ATOH8. Inhibition of ATOH8 reversed the effects of knockdown lncRNA CIR on chondrogenic differentiation. CONCLUSION: LncRNA CIR suppresses chondrogenic differentiation of hUC-MSCs. Mechanistically, lncRNA CIR could inhibit ATOH8 expression that functions to promote chondrogenic differentiation through EZH2-mediated epigenetic modifications.

[Research on regional distribution and industrial status analysis of genuine medicinal resources of flowers in Henan province].

Flower medicinal materials usually refer to Chinese medicinal materials with a complete flower,inflorescence,or part of a flower as the different medicinal parts,they have an important share in the Chinese herbal medicine market and appeared frequently in Chinese medicine prescriptions. Firstly,the species and regional distribution of the flower medicinal materials resources in China were briefly summarized. Secondly,the characteristics,yield,producing area and origin distribution of the main flower medicinal materials in Henan province were discussed. Finally,the present situation and the main problems of the flower medicinal materials industry in Henan province were comprehensively analyzed,and the corresponding industrial development countermeasures were put forward.This research was intended to provide decision-making demonstration and scientific basis for the rational exploitation and utilization of resources,breeding of new varieties,planting division,production layout and the healthy and sustainable development of the flower medicinal materials industry in Henan province.

Mailuoning for acute ischaemic stroke.

BACKGROUND: Mailuoning is widely used in the treatment of acute ischaemic stroke in China. Animal experimental studies and clinical pharmacological research indicate that mailuoning might improve blood circulation, prevent ischaemic injury, and protect heart and brain tissue. This review was last published in 2009. As new data have become available, it is necessary to reassess the evidence from randomised controlled trials. OBJECTIVES: To determine the effects and safety of mailuoning agents (injection or oral liquid) in the treatment of people with acute ischaemic stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL;2014, Issue 4), MEDLINE (1966 to May 2014), Embase (1980 to May 2014), AMED (1985 to May 2014), the Chinese Stroke Trials Register (June 2014), the China Biological Medicine Database (CBM-disc; 1979 to June 2014), China Science and Technology Journal database (CSTJ; 1979 to June 2014), Wanfang Data Chinese databases (1979 to June 2014), and the China National Knowledge Infrastructure (1979 to June 2014). We searched clinical trials and research registers, handsearched 10 Chinese journals including relevant conference proceedings, scanned reference lists, and contacted the pharmaceutical company that manufactures mailuoning. We also attempted to contact trial authors to obtain further data. SELECTION CRITERIA: Randomised controlled trials comparing mailuoning with placebo or mailuoning plus other treatment compared with that other treatment in people with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality, and extracted data. MAIN RESULTS: We included 21 trials, involving 1746 participants, in this update; six trials were new. The included trials did not report the numbers of dead and dependent participants at the end of at least three months' follow-up. Of the 12 trials that reported adverse events, five events occurred in two trials. There was no significant difference between the treatment group and the control group. We assessed 20 trials to be of a poor quality: When analysing these trials together, mailuoning was associated with a significant increase in the number of participants with an improved neurological deficit (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.23 to 0.42) and showed a significant improvement of neurological deficit with the European Stroke Scale (ESS) (mean difference (MD) (fixed) 8.29, 95% CI 3.44 to 13.15). One placebo-controlled trial, assessed to be of a better methodological quality, failed to show a significant improvement of neurological deficit at the end of three months' follow-up (MD (fixed) 2.49, 95% CI -1.45 to 6.43) or in quality of life. One trial, which reported cognitive function using the Montreal Cognitive Assessment as a continuous scale, showed a significant improvement of cognitive function (MD (fixed) 2.68, 95% CI 1.82 to 3.54). Two trials assessed activities of daily life: One trial showed a significant improvement, but the other did not. AUTHORS' CONCLUSIONS: This review did not provide sufficient evidence to support the routine use of mailuoning for the treatment of people with acute ischaemic stroke. High-quality large-scale randomised controlled trials are needed to confirm the efficacy of mailuoning.

Inheritance and QTL mapping of related root traits in soybean at the seedling stage.

KEY MESSAGE: This study provides a foundation for further research on root genetic regulation and molecular breeding with emphasis on correlations among root traits to ensure robust root growth and well-developed root systems. A set of 447 recombinant inbred lines (RILs) derived from a cross between Jingdou23 (cultivar, female parent) and ZDD2315 (semi-wild, male parent) were used to analyze inheritance and detect QTLs related to root traits at the seedling stage using major gene plus polygene mixed inheritance analysis and composite interval mapping. The results showed that maximum root length (MRL) was controlled by three equivalent major genes, lateral root number (LRN) was controlled by two overlapping major genes, root weight (RW) and volume (RV) were controlled by four equivalent major genes. Hypocotyl length (HL) was controlled by four additive main genes, and hypocotyl weight (HW) was controlled by four additive and additive × additive epistatic, major genes; however, polygene effects were not detected in these traits. Shoot weight (SW) was controlled by multi-gene effects, but major gene effects were not detected. Twenty-four QTLs for MRL, LRN, RW, RV, SW, HL, HW were mapped on LG A1 (chromosome 5), LG A2 (chromosome 8), LG B1 (chromosome 11), LG B2 (chromosome 14), LG C2 (chromosome 6), LG D1b (chromosome 2), LG F_1 (chromosome 13), LG G (chromosome 18), LG H_1 (chromosome 12), LG H_2 (chromosome 12), LG I (chromosome 20), LG K_2 (chromosome 9), LG L (chromosome 19), LG M (chromosome 7), LG N (chromosome 3), LG O (chromosome 10), separately. Root traits were shown to have complex genetic mechanisms at the seedling stage, SW was controlled by multi-gene effects, and the other six traits were controlled by major gene effects. It is concluded that correlations among root traits must be considered to improve the development of beneficial root traits.

Sustainable Alkali Activation: The Role of Water- and Alkali-Treated Sisal Leaf Wastewaters in Solid- Waste-Based Composite Synthesis.

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.

Disease progression subtypes of Parkinson's disease based on milestone events.

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.

Overexpression of solute carrier family 6 member 12 promotes cell injury in Parkinson's disease via MAPK signaling pathway.

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.

Lymphocyte antigen 96: A new potential biomarker and immune target in Parkinson's disease.

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.

Experience of multi-disciplinary treatment of multiple cerebellar diffuse large B-cell lymphoma: A case report.

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.

Repressing iron overload ameliorates central post-stroke pain via the Hdac2-Kv1.2 axis in a rat model of hemorrhagic stroke.

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.

Alpha-synuclein in skin as a high-quality biomarker for Parkinson's disease.

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.

CXCR4 knockout induces neuropathological changes in the MPTP-lesioned model of Parkinson's disease.

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.

The severity of corneal nerve loss differentiates motor subtypes in patients with Parkinson's disease.

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.

Neuroprotective effects of new protein kinase C activator TPPB against Aß25₋35 induced neurotoxicity in PC12 cells.

Alzheimer's disease (AD) is pathologically characterized by presence of senile plaques in the hippocampus, which are composed mainly of extracellular deposition of a polypeptide known as the beta amyloid, the Aß. It has been demonstrated on numerous occasions that it was the deposition and aggregation of this Aß peptide that cause neuronal dysfunction and even finally, the dementia. Lowering the deposition of Aß or decreasing its neurotoxicity has long been one of the purposes of AD therapy. In previous study, we reported that protein kinase C (PKC) activator TPPB could regulate APP processing by increasing α-secretase activity. In this study we further investigated the potential neuroprotective effect of TPPB against Aß(25-35)-induced neurotoxicity in PC12 cells. The results indicated that TPPB at concentration of 1 µM could antagonize Aß(25-35) induced cell damage as evidenced by MTT assays, LDH release and by morphological changes. Furthermore, the neuroprotection in cell viability can be blocked by inhibitors of PKC, Akt and MAPK. The experiment also indicated that TPPB could increase the phosphorylation of Akt, PKC, MARCKS and MAPK, which were inhibited by Aß(25-35) treatment. Finally, TPPB inhibited the activation of caspase-3 induced by Aß(25-35). Taken together, the experiment here implies that TPPB has a role against Aß(25-35)-induced neurotoxicity in PC12 cells and may suggest its therapeutic potential in AD.

Iliosacral screw fixation of pelvic ring disruption with tridimensional patient-specific template guidance.

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.