Background: Neurological diseases share overlapping systemic and molecular features, but the specificity and interpretation of cross-disease metabolomic signatures remain uncertain. Methods: We analyzed summary-level Nightingale NMR metabolomic and genetic data from 274,241 UK Biobank participants across eight neurological endpoints. The disease rankings used here were derived from baseline plasma metabolites predicting future incident disease rather than from contemporaneous diagnostic case-control contrasts. Results: Among 57 priority metabolites with genome-wide significant instruments (2472 SNPs; mean F = 162.4), nine ranked in the top 30 for at least seven of the eight endpoints, defining a shared pre-diagnostic neurological signature confirmed as non-random cross-endpoint convergence by permutation testing (p < 0.0001). Because we did not perform a quantitative non-neurological disease control analysis, this signature should not be interpreted as neurologically specific and may partly reflect systemic morbidity, renal function, body composition, or frailty-related physiology. Forward Mendelian randomization across 45 metabolite-disease pairs found no Bonferroni-significant causal effects; three nominal protective associations are consistent with the number of false-positive findings expected under multiple testing and require replication. Conclusions: These results support a shared systemic, pre-diagnostic metabolic signature across the neurological disease spectrum, while the null MR findings and specificity limitations favor interpretation as a biomarker or prodromal downstream signal rather than a proven causal mechanism. External prospective validation is essential.

Parkinson’s disease (PD) represents a growing global health challenge, with prevalence doubling from 2.5 million cases in 1990 to 6.1 million in 2016, and projections suggesting it will exceed 12 million by 2040. This exponential growth has been termed the “Parkinson’s pandemic.” China and the United States, which together account for nearly half of the global PD population, have developed markedly different approaches to end-of-life (EOL) care, shaped by their distinct healthcare systems and cultural contexts. Understanding these differences is crucial for developing effective global strategies. This systematic review and meta-analysis comprehensively compares advanced-stage PD care between these two nations to quantify disparities and inform evidence-based policy interventions. We conducted a rigorous systematic review following PRISMA 2020 guidelines, searching six databases (PubMed, Embase, Scopus, Web of Science, CNKI, Wanfang) from January 2015 to October 2025. The timeframe was selected to capture contemporary care patterns following major healthcare reforms in both countries (Affordable Care Act implementation in the US; Healthy China 2030 initiative). Inclusion criteria encompassed peer-reviewed studies reporting on advanced PD (Hoehn-Yahr stage ≥ 3) with outcome measures including survival, quality of life (QoL), palliative care access, caregiver burden, rehabilitation utilization, or healthcare costs. The sample size threshold (n ≥ 100) balanced statistical power with inclusivity. Two independent reviewers screened 3,847 records with excellent agreement (Cohen’s κ = 0.82–0.89). Quality assessment employed the Newcastle-Ottawa Scale (NOS ≥ 8 indicating high quality) for observational studies and the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomized controlled trials, with GRADE criteria determining evidence certainty. Meta-analyses utilized random-effects models with comprehensive heterogeneity assessment (I² statistics, meta-regression) and publication bias evaluation (Egger’s test, trim-and-fill analysis). Sensitivity analyses included high-quality studies only and examined the influence of large database studies. Our analysis of 42 high-quality studies encompassing over 125,000 patients revealed profound and systematic cross-national disparities across multiple domains. In terms of care access, US patients demonstrated significantly higher hospice enrollment rates (28–35

The burden of traumatic brain injury (TBI) remains a challenge worldwide, and also in China. Since 2019, considerable changes in the epidemiology and characteristics of TBI have occurred, driven by social and economic factors, such as population ageing and the increasing use of mopeds for road transportation. Concurrently, substantial progress has been made in clinical research, including the implementation of high-quality studies on innovative treatments, such as long-term mild hypothermia for severe TBI, right median nerve stimulation for awakening patients in coma after a brain injury, and middle meningeal artery embolisation for chronic subdural haematoma. However, challenges remain, including in the establishment of training for neurosurgical residents, regional disparities in access to specialised healthcare, and low participation in international research networks. Clinical and other innovations provide opportunities for improving TBI care and research in China. Advances in China could offer guidance for the transition between TBI care in low-resource setting and highly specialised centres.

Dysphagia affects up to 80% of people with Parkinson disease across the disease continuum and is a leading contributor to aspiration pneumonia–related mortality. Current risk stratification approaches prioritize discriminative accuracy over clinical transparency, limiting their utility for individualized decision-making at the point of care. Tools that combine predictive performance with auditable clinical reasoning remain unavailable for dysphagia risk assessment in this population. We aimed to develop and evaluate ClinicalSymbolic, a neuro-symbolic model that integrates a clinical multilayer perceptron (MLP) encoder with a differentiable symbolic reasoning layer of 40 clinically grounded rules, for interpretable dysphagia risk prediction in Parkinson disease. We used data from the Parkinson’s Progression Markers Initiative (PPMI), a multicenter longitudinal registry. The primary analysis cohort comprised 1,163 patients (375/1163, 32.2% high risk) with complete multimodal data. We extracted 47 clinical features from the Unified Parkinson’s Disease Rating Scale (UPDRS) parts I–III, demographic variables, and pharmacological data within a baseline window (months 0–12), with the outcome (self-reported swallowing difficulty, UPDRS-II item NP2SWAL ≥1) ascertained during months 13–60. ClinicalSymbolic was compared against logistic regression, random forest, MLP, and graph neural network (GNN) baselines using 5-fold stratified cross-validation. Platt scaling was applied uniformly to all models for probability calibration. A sensitivity analysis was conducted in a broader clinical cohort (N=3,224). ClinicalSymbolic achieved an out-of-fold area under the receiver operating characteristic curve (AUROC) of 0.743 (95% CI 0.712–0.772) with sensitivity of 0.907, compared with 0.832 (95% CI 0.807–0.856) for logistic regression—an 8.9 percentage-point deficit that we do not claim as equivalence. Following uniform Platt calibration, all models achieved comparable expected calibration error (ECE range 0.032–0.041), confirming that the primary differentiating advantage of ClinicalSymbolic is its 40-rule symbolic reasoning layer rather than calibration performance. The dysarthria composite rule (bimodal speech self-report and clinician-rating agreement) showed the strongest risk discrimination (Δ mean activation=+0.275; Mann–Whitney P<.001), with activation increasing markedly at Hoehn and Yahr stage 3 or higher versus stages 1–2 (Δ=+0.609; P<.001). Architecture ablation demonstrated that removing GNN message passing improved AUROC by 13.5 percentage points, indicating that graph-based methods degraded prediction in this registry setting. Differentiable symbolic reasoning enables clinically interpretable dysphagia risk stratification in Parkinson disease, yielding well-calibrated probability estimates comparable to standard approaches under uniform post-hoc calibration. Although ClinicalSymbolic does not match logistic regression in discriminative accuracy, its 40-rule symbolic layer provides an auditable, stage-sensitive decision pathway aligned with established bulbar assessment frameworks—a property that post-hoc explanation methods applied to opaque models cannot replicate. External validation with instrumentally confirmed swallowing outcomes is required before clinical deployment.

Objective This study examines how rapid changes in cerebral perfusion pressure (CPP) affect acute intraoperative brain herniation (AIBH) in patients with severe traumatic brain injury (sTBI). Materials and methods This single-institute retrospective study analyzed patients with sTBI (Glasgow Coma Scale (GCS) ≤ 8) who underwent surgical intervention from January 2017 to January 2019. An external ventricular drain (EVD)/intracranial pressure monitor (ICPm) was placed in all patients preoperatively. Intracranial pressures (ICPs) before the surgery at the time of both craniotomy and durotomy were recorded. CPP, calculated as mean arterial pressure (MAP) - ICP, was recorded as initial (CPPi), at the time of craniotomy (CPPc), and at the time of durotomy (CPPd). Changes in CPPc and CPPd were calculated as (CPPc - CPPi)/CPPi and (CPPd - CPPc)/CPPc, respectively. The effects of the change in CPP on AIBH were categorized into three groups according to the significance of the changes and were analyzed using SPSS version 22.0 (IBM Corp., Armonk, NY). Results A total of 98 cases were recruited, including 77 (78.57%) male patients and 21 (21.43%) female patients. Age ranged from 19 years old to 77 years old, with a mean/median of 49.01/50.50 years old. The changes in CPP at the time of both craniotomy and durotomy were all significantly related to AIBH. Changes in CPP were classified into three groups: (1) both were <50%, (2) at least one was ≥50% but <100%, and (3) at least one was ≥100%. The incidence rates of AIBH in the three groups were 27.1% (13/48), 61% (25/41), and 77.8% (7/9), respectively. Significant differences were also observed between each two groups (p<0.05). Conclusion Changes in CPP appear to be related to acute intraoperative brain herniation in patients with severe traumatic brain injury undergoing surgical intervention.

BACKGROUND:Hemiplegia is characterized by muscle weakness on one side of the body, often resulting from damage to the brain, spinal cord, or associated nerves. This condition commonly occurs due to strokes, traumatic brain injuries (TBI), or spinal cord injuries (SCI), which can damage corticospinal neurons (CSNs) and the corticospinal tract (CST). However, there is still a notable lack of comprehensive studies that systematically characterize the anatomical and behavioral aspects of these hemiplegic animal models. OBJECTIVE:This study aimed to validate and compare existing models of TBI, stroke, and SCI in order to identify the most suitable preclinical hemiplegia models for future research. METHOD:Using viral-based retrograde tracing, we first mapped the cortical distribution of CSNs responsible for hindlimb movement. Anterograde and retrograde viral tracing techniques were then employed to label and evaluate the damage to CSNs and the CST in three models: photothrombotic stroke, Feeney's weight-drop TBI, and T10 hemi-section SCI. We also conducted behavioral tests to assess spontaneous motor function recovery, including open field and rotarod tests for gross motor function, as well as beam walking and irregular ladder walking tasks for assessing skilled motor function. RESULTS:Our findings revealed that the CSNs controlling hindlimb movement are concentrated in the hindlimb region of the primary somatosensory cortex (S1HL). In the TBI and stroke models, there was complete destruction of ipsilateral CSNs in the S1HL and loss of CST fibers governing hindlimb movement. In the SCI model, ipsilateral CST fibers below T10 were also lost. After 8 weeks post-injury, all three groups of hemiplegic mice showed improvements in motor function, with gross motor function returning to normal levels; however, the recovery of skilled motor function was only modest. Notably, the degree of improvement in fine motor skills varied among the hemiplegia models, with mice subjected to brain injury (stroke and TBI) demonstrating significantly greater recovery in fine motor skills compared to those with SCI. CONCLUSION:We confirmed and validated previous hemiplegia models by damaging CSNs or CST controlling hindlimb movement. Post-injury, gross motor function gradually returned to normal levels across all groups, whereas recovery of skilled motor function was limited. Furthermore, there were significant differences in the recovery of skilled motor function between brain injury models and the SCI model. These hemiplegic mouse models are valuable tools for studying post-injury skilled motor functions. CLINICAL TRIAL NUMBER:Not applicable.

Supratentorial and infratentorial combined injuries is a rare but particularly type of severe traumatic brain injury (sTBI), characterized by high rates of morbidity and mortality. The injury spans the tentorium of cerebellum, involving key structures such as the supratentorial cerebral hemispheres, the infratentorial cerebellum and brain stem. Its pathophysiological mechanism is complex, progression is rapid, and diagnosis and treatment are extremely challenging. Currently, there is no unified clinical consensus established for its management, either domestically or internationally. This article systematically reviews recent research advances in the pathophysiological basis, injury characteristics, clinical manifestations, diagnostic evaluation, treatment strategies, and perioperative management of supratentorial and infratentorial combined injuries, aiming to provide a basis for clinical diagnosis and treatment.

Glioblastoma (GBM), the most aggressive primary brain tumor, is shaped by its integration into neural networks. While glutamatergic input is linked to tumor progression, the broader architecture and function of neuron-glioma connectomes remain unclear. Using monosynaptic rabies tracing, we map brain-wide neural input to patient-derived xenografts and reveal a consistent organizational logic: local inputs are primarily glutamatergic, while long-range connections exhibit diverse neurotransmitter profiles, with basal forebrain cholinergic projections emerging as a conserved input across sites. Functionally, presynaptic acetylcholine release promotes GBM progression through muscarinic receptor CHRM3 in a circuit-specific manner. Mechanistically, glutamatergic and cholinergic signals converge to enhance glioma calcium transients but diverge in temporal transcriptional control, with their dual blockade producing additive anti-tumor effects. Therapeutically, the anticholinergic drug scopolamine attenuates glioma growth, whereas the acetylcholinesterase inhibitor donepezil exacerbates disease. These findings reveal the complexity of neuron-glioma connectivity, highlighting long-range neuromodulatory pathways as promising therapeutic targets in GBM.

BACKGROUND:Craving is a key challenge in treating methamphetamine use disorder (MUD). The memory reconsolidation theory indicates that interference with MUD after drug memory retrieval helps to reduce craving. Previous studies have demonstrated the importance of the hippocampus in memory consolidation, but traditional non-invasive interventions cannot effectively locate and intervene in the hippocampus. Although tTIS can accurately intervene in deep brain regions, it is still unknown whether tTIS intervention on the MUD hippocampus is effective in reducing craving. METHOD:A total of 40 male participants with MUD were randomized to active or sham tTIS. Active tTIS delivered a 10 Hz electric field to the hippocampus for 20 min per day over 10 consecutive days, while sham stimulation lasted only 1 min per day during the same period. We also assessed its effects on craving, cognitive function and emotional symptoms at baseline, post intervention and one month follow-up. RESULTS:A two-way repeated-measures analysis of variances (ANOVAs) on drug cue-induced craving revealed a significant group × time interaction effect (F (2, 108) = 5.652, P = 0.005). Post hoc paired t-test indicated a significant decrease in craving in the active tTIS group (t = 5.04, P = 0.002) after the intervention and one month follow-up (t = 6.04, P < 0.001). In contrast, no significant changes were observed in the sham group. CONCLUSIONS:In this trial, 10 Hz tTIS was effective for METH craving reduction in MUD. Further trials are needed to explore neural mechanisms of tTIS.

BACKGROUND:Severe traumatic brain injury is the leading cause of death among young and middle-aged adults. Decompression is the primary surgical intervention but often is linked to poor outcomes. METHODS:This study evaluates the effects of controlled decompression surgery on postoperative cerebral microcirculation and long-term neurologic outcomes in patients with severe traumatic brain injury using a prospective, randomized controlled design. Patients were randomly assigned to either the control group (decompression) or the observation group (controlled decompression). Cerebral perfusion was assessed using computed tomography perfusion at various time points postsurgery. The mean blood flow velocity of the middle cerebral artery on the decompression side was monitored using transcranial Doppler. Follow-up was conducted at 6 and 12 months. RESULTS:A total of 245 patients were screened, with 148 ultimately included in the study: 71 in the control group and 77 in the observation group. Cerebral blood flow and cerebral blood volume increased significantly in the observation group at all time points, whereas mean transit time decreased over time with no significant difference between groups. The mean blood flow velocity was consistently lower in the observation group. On the basis of Glasgow Outcome Scale-Extended scores, the observation group showed better neurologic function at both 6 and 12 months. CONCLUSION:Controlled decompression significantly improves early postoperative cerebral microcirculation in patients with severe traumatic brain injury and leads to better long-term neurologic outcomes compared with standard decompression.

Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited. This limited plasticity serves as a primary barrier to functional recovery after brain injury. Neuromodulation technologies represent one of the fastest-growing fields in medicine. These techniques utilize electricity, magnetism, sound, and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury. Therefore, this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury. Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury. However, studies report negative findings, potentially due to variations in stimulation protocols, differences in observation periods, and the severity of functional impairments among participants across different clinical trials. Additionally, we observed that different neuromodulation techniques share remarkably similar mechanisms, including promoting neuroplasticity, enhancing neurotrophic factor release, improving cerebral blood flow, suppressing neuroinflammation, and providing neuroprotection. Finally, considering the advantages and disadvantages of various neuromodulation techniques, we propose that future development should focus on closed-loop neural circuit stimulation, personalized treatment, interdisciplinary collaboration, and precision stimulation.

BACKGROUND:Neuromodulatory techniques have been proven to enhance functional recovery after stroke in patients and animals, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). However, the success and feasibility of these approaches were often variable, largely due to a lack of target specificity.OBJECTIVE:We explored the effects of specific chemogenetic stimulation of intact corticospinal tract during rehabilitative training on functional recovery after stroke in mice.METHODS:We developed a viral-based intersectional targeting approach that allows specific chemogentic activation of contralateral hindlimb corticospinal neurons (CSNs) in a photothrombotic stroke model.RESULTS:We demonstrated that specific chemogenetic activation of CSNs, when combined with daily rehabilitation training, leads to significant skilled motor functional recovery via promoting corticospinal tract (CST) axons midline crossing sprouting from intact to the denervated spinal hemicord, and rewiring new functional circuits by new synapse formation. Mechanistically, we revealed that combined chemogenetic stimulation of CSNs and daily rehabilitation training significantly enhanced the mTOR activity of CSNs.CONCLUSIONS:Our findings highlight the great potential of specific neural activation protocols in combination with motor training for the recovery of skilled motor functions after stroke.

It is difficult to predict the surgical effect and outcome of severe traumatic brain injury (TBI) before surgery. This study aims to approve an evaluation method of computed tomography angiography (CTA) to predict the effect of surgery and outcome in severe TBI. Between January 2010 and January 2020, we retrospectively reviewed 358 severe TBI patients who underwent CTA at admission and reexamination. CTA data were evaluated for the presence of cerebrovascular changes, including cerebrovascular shift (CS), cerebral vasospasm (CVS), large artery occlusion (LAO), and deep venous system occlusion (DVSO). Medical records were reviewed for baseline clinical characteristics and the relationship between CTA changes and outcomes. Cerebrovascular changes were identified in 247 (69.0%) of 358 severe TBI patients; only 25 (10.12%) of them had poor outcomes, and 162 (65.6%) patients had a good recovery. Eighty-three (23.18%) patients were diagnosed with CVS, 10 (12.05%) had a good outcome, 57 (68.67%) had severe disability and 16 (19.28%) had a poor outcome. There were twenty-six (7.3%) patients who had LAO and thirty-one (8.7%) patients who had DVSO; no patients had good recovery regardless of whether they had the operation or not. Cerebrovascular injuries and changes are frequent after severe TBI and correlate closely with prognosis. CTA is an important tool in evaluating the severity, predicting the operation effect and prognosis, and guiding therapy for severe TBI. Well-designed, multicenter, randomized controlled trials are needed to evaluate the value of CTA for severe TBI in the future.

The mitochondrial permeability transition pore is a nonspecific transmembrane channel. Inhibition of mitochondrial permeability transition pore opening has been shown to alleviate mitochondrial swelling, calcium overload, and axonal degeneration. Cyclophilin D is an important component of the mitochondrial permeability transition pore. Whether cyclophilin D participates in mitochondrial impairment and axonal injury after intracerebral hemorrhage is not clear. In this study, we established mouse models of intracerebral hemorrhage in vivo by injection of autologous blood and oxyhemoglobin into the striatum in Thy1-YFP mice, in which pyramidal neurons and axons express yellow fluorescent protein. We also simulated intracerebral hemorrhage in vitro in PC12 cells using oxyhemoglobin. We found that axonal degeneration in the early stage of intracerebral hemorrhage depended on mitochondrial swelling induced by cyclophilin D activation and mitochondrial permeability transition pore opening. We further investigated the mechanism underlying the role of cyclophilin D in mouse models and PC12 cell models of intracerebral hemorrhage. We found that both cyclosporin A inhibition and short hairpin RNA interference of cyclophilin D reduced mitochondrial permeability transition pore opening and mitochondrial injury. In addition, inhibition of cyclophilin D and mitochondrial permeability transition pore opening protected corticospinal tract integrity and alleviated motor dysfunction caused by intracerebral hemorrhage. Our findings suggest that cyclophilin D is used as a key mediator of axonal degeneration after intracerebral hemorrhage; inhibition of cyclophilin D expression can protect mitochondrial structure and function and further alleviate corticospinal tract injury and motor dysfunction after intracerebral hemorrhage. Our findings provide a therapeutic target for preventing axonal degeneration of white matter injury and subsequent functional impairment in central nervous diseases.

AIM:To establish, and validate a practical nomogram to predict recurrence of chronic subdural hematoma (CSDH) in patients after initial burr-hole surgery.MATERIAL AND METHODS:The prediction model was developed from a training set of 272 patients with CSDH who had undergone standard burr hole with irrigation surgery. A separate external validation cohort comprising 112 patients who underwent the same operation was also included. Least absolute shrinkage and selection operator (LASSO) regression was adopted to minimize the high dimension of data and predictor selection. Binary logistic regression was used to develop the present model. Subsequently, a nomogram was established as the ultimate representation of the prediction model. Area under the curve (AUC) was used to identify the discrimination of the designed predictive nomogram. The calibration plot was used to verify the goodness-of-fit of the nomogram. Finally, Decision curve analysis (DCA) was employed to appraise the clinical applicability of the present nomogram.RESULTS:A total of 3 independent variables were filtered by LASSO analysis from the 22 candidate factors. The AUC of the training and validation sets were 0.833 (95%CI: 0.774-0.894) and 0.817 (95%CI: 0.711-0.922), respectively, which indicated a good discrimination ability. The calibration charts showed that the prediction probability and the actual probability fitted well. The DCA of the prediction model indicated an excellent clinical efficacy.CONCLUSION:The proposed nomogram can quantitatively and conveniently predict the recurrence rate of CSDH after burr hole with irrigation surgery. Besides it can facilitate customized treatment adjustment and follow-up of patients who are at a high-risk of recurrence.

Decompressive craniectomy (DC) is a major form of surgery that is used to reduce intracranial hypertension (IH), the most frequent cause of death and disability following severe traumatic brain injury (sTBI) and stroke. Our previous research showed that controlled decompression (CDC) was more effective than rapid decompression (RDC) with regard to reducing the incidence of complications and improving outcomes after sTBI; however, the specific mechanisms involved have yet to be elucidated. In the present study, we investigated the effects of CDC in regulating inflammation after IH and attempted to identify the mechanisms involved. Analysis showed that CDC was more effective than RDC in alleviating motor dysfunction and neuronal death in a rat model of traumatic intracranial hypertension (TIH) created by epidural balloon pressurization. Moreover, RDC induced M1 microglia polarization and the release of pro-inflammatory cytokines. However, CDC treatment resulted in microglia primarily polarizing into the M2 phenotype and induced the significant release of anti-inflammatory cytokines. Mechanistically, the establishment of the TIH model led to the increased expression of hypoxia-inducible factor-1α (HIF-1α); CDC ameliorated cerebral hypoxia and reduced the expression of HIF-1α. In addition, 2-methoxyestradiol (2-ME2), a specific inhibitor of HIF-1α, significantly attenuated RDC-induced inflammation and improved motor function by promoting M1 to M2 phenotype transformation in microglial and enhancing the release of anti-inflammatory cytokines. However, dimethyloxaloylglycine (DMOG), an agonist of HIF-1α, abrogated the protective effects of CDC treatment by suppressing M2 microglia polarization and the release of anti-inflammatory cytokines. Collectively, our results indicated that CDC effectively alleviated IH-induced inflammation, neuronal death, and motor dysfunction by regulating HIF-1α-mediated microglial phenotype polarization. Our findings provide a better understanding of the mechanisms that underlie the protective effects of CDC and promote clinical translational research for HIF-1α in IH.

BACKGROUND:Venous thromboembolism (VTE) is a common neurosurgical complication after brain tumor resection, and its prophylaxis has been widely studied. There are no effective drugs in the clinical management of venous thromboembolism, and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.AIM:To explore whether ulinastatin (UTI) can prevent VTE after brain tumor resection.METHODS:The present research included patients who underwent brain tumor resection. Patients received UTIs (400,000 IU) or placebos utilizing computer-based random sequencing (in a 1:1 ratio). The primary outcome measures were the incidence of VTE, coagulation function, pulmonary emboli, liver function, renal function, and drug-related adverse effects.RESULTS:A total of 405 patients were evaluated between January 2019 and December 2021, and 361 of these were initially enrolled in the study to form intention-to-treat, which was given UTI (n = 180) or placebo (n = 181) treatment in a random manner. There were no statistically significant differences in baseline clinical data between the two groups. The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group. UTI can improve coagulation dysfunction, pulmonary emboli, liver function, and renal function. No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea, vomiting, hospital stays, or hospitalization costs. The incidence of allergies was higher in the UTI group than in the placebo group.CONCLUSION:The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.

Resident neural precursor cells (NPCs) activation is a promising therapeutic strategy for brain repair. This strategy involves stimulating multiple stages of NPCs development, including proliferation, self-renewal, migration, and differentiation. Metformin, an FDA-approved diabetes drug, has been shown to promote the proliferation and differentiation of NPCs. However, it is still unclear whether metformin promotes the migration of NPCs. EVOS living cell imaging system was used for observing the migration for primary NPCs dynamically in vitro after metformin treatment. For in vivo study, a mouse model of ischemic stroke was established through middle cerebral artery occlusion (MCAO). To label the proliferating cell in subventricular zone, BrdU was injected intraperitoneally into the mice. After co-staining with BrdU and doublecortin (DCX), a marker for NPCs, the migration of Brdu and DCX double positive NPCs was detected along the rostral migratory stream (RMS) and around the infarct area using frozen brain sections. Finally, the rotarod test, corner test and beam walking were performed to evaluate the motor functions of the mice after stroke in different groups. The results showed that metformin enhanced NPCs migration in vivo and in vitro by promoting F-actin assembly and lamellipodia formation. What's more, metformin treatment also significantly reduced the infarct volume and alleviated functional dysfunction after stroke. Mechanistically, metformin promoted NPCs migration via up-regulating the CDC42 expression. Taken together, metformin represents an optimal candidate agent for neural repair that is capable of not only expanding the adult NPC population but also subsequently driving them toward the destination for neuronal differentiation.

Dysfunction of ionotropic glutamate receptors (iGluRs) is a key molecular mechanism of excitotoxic neuronal injury following traumatic brain injury (TBI). Edonerpic maleate is a low molecular-weight compound that was screened as a candidate neuroprotective agent. In this study, we investigated its effects on TBI and GluRs signaling. Traumatic neuronal injury (TNI) induced by scratch followed by glutamate treatment was performed to mimic TBI in vitro. Edonerpic maleate at 1 and 10 μM exerted protective activity when it was added within 2 h following injury. The protective activities were also confirmed by the reduction of lipid peroxidation and oxidative stress. In addition, edonerpic maleate inhibited the expression of surface NR2B, total GluR1, and surface GluR1, and mitigated the intracellular Ca2+ responses following injury in vitro. Western blot analysis showed that edonerpic maleate reduced the cleavage of collapsing response mediator protein 2 (CRMP2), but increased the expression of postsynaptic protein Arc. By using gene overexpression and silencing technologies, CRMP2 was overexpressed and Arc was knockdown in cortical neurons. The results showed that the effect of edonerpic maleate on NMDA receptor expression was mediated by CRMP2, whereas the edonerpic maleate-induced AMPA receptor regulation was dependent on Arc activation. In in vivo TBI model, 30 mg/kg edonerpic maleate alleviated the TBI-induced brain edema, neuronal loss, and microglial activation, with no effect on locomotor function at 24 h. However, edonerpic maleate improves long-term neurological function after TBI. Furthermore, edonerpic maleate inhibited CRMP2 cleavage but increased Arc activation in vivo. In summary, our results identify edonerpic maleate as a clinically potent small compound with which to attenuate TBI-related brain damage through regulating GluRs signaling.

We proposed a novel deep learning–based radiomics (DLR) model to diagnose Parkinson’s disease (PD) based on [18F]fluorodeoxyglucose (FDG) PET images. In this two-center study, 255 normal controls (NCs) and 103 PD patients were enrolled from Huashan Hospital, China; 26 NCs and 22 PD patients were enrolled as a separate test group from Wuxi 904 Hospital, China. The proposed DLR model consisted of a convolutional neural network–based feature encoder and a support vector machine (SVM) model–based classifier. The DLR model was trained and validated in the Huashan cohort and tested in the Wuxi cohort, and accuracy, sensitivity, specificity and receiver operator characteristic (ROC) curve graphs were used to describe the model’s performance. Comparative experiments were performed based on four other models including the scale model, radiomics model, standard uptake value ratio (SUVR) model and DLR model. The DLR model demonstrated superiority in differentiating PD patients and NCs in comparison to other models, with an accuracy of 95.17