Xinmin Ding

The proteome is a key source of therapeutic targets. We conducted a comprehensive Mendelian randomization analysis across the proteome to identify potential causal relationships between proteins and the development of intracranial aneurysms (IAs). We conducted a Mendelian randomization study to explore potential therapeutic targets for IAs, using genetic data from the International Stroke Genetics Consortium. Genetic instruments for 734 plasma proteins and 154 cerebrospinal fluid (CSF) proteins were derived from recent genome-wide association studies. Independent validation was performed using datasets from FinnGen, deCODE, and the UK Biobank. We identified six proteins genetically associated with IAs risk. Among them, plasma RELT and CSF PDGF Rb passed false discovery rate (FDR) correction and were consistently validated in external cohorts. RELT was associated with a reduced risk of unruptured intracranial aneurysms, while PDGF Rb was linked to an increased risk of subarachnoid hemorrhage. Additionally, CSF levels of sFRP-3, IL-1 sRII, IL-1 R4, and LY86 showed initial associations with SAH risk; however, these associations were not confirmed in external validation. All findings were supported by sensitivity analyses. Our integrative analysis identifies RELT and PDGF Rb as robust, genetically supported protein candidates potentially involved in the pathogenesis of intracranial aneurysms and subarachnoid hemorrhage. These findings provide a foundation for future functional validation and clinical studies aimed at biomarker discovery or therapeutic targeting.

Traumatic Brain Injury (TBI) is a major cause of mortality and morbidity, with acute kidney injury (AKI) as a common complication. This study aimed to investigate the potential of serum Klotho protein levels as a diagnostic and prognostic marker for AKI in TBI patients.The results showed that serum Klotho level 177.3 (165.43,195.07) (pg/ml) was elevated in patients with traumatic brain injury as compared to normal group 134.8(125.6,138.9) (pg/ml) . We conducted univariate analyses of all potential factors, resulting in four variables for inclusion in the multivariate analysis. Among them, the HR value of Klotho protein was 2.076. Comparing the predictive efficacy of serum creatinine and Klotho protein, the ROC value of Klotho protein was 0.832 (95% CI: 0.709–0.898), suggesting higher predictive ability than serum creatinine. Modestly elevated serum Klotho protein levels were associated with a higher risk of AKI and a poor long-term prognosis.These findings suggested that serum Klotho protein levels may serve as an early diagnostic indicator and predictor of outcomes in TBI patients with AKI, providing insights for potential therapeutic interventions. Further research is needed to validate these findings and explore the clinical utility of targeting the Klotho pathway in TBI-associated AKI.

Despite advancements in diagnostic and therapeutic strategies, early detection and improved prognosis of gliomas remain challenging. A deeper understanding of glioma pathogenesis and the identification of reliable biomarkers are crucial for early diagnosis and the reduction of healthcare costs. Mitochondrial ribosomal protein S33 (MRPS33), a key component of mitochondrial protein synthesis, has not been well-characterized in terms of its expression profile, prognostic significance, and immunological relevance in glioma. This study aims to elucidate these aspects through bioinformatics analyses utilizing data from The Cancer Genome Atlas, Genotype-Tissue Expression Project, and Tumor Immune Estimation Resource databases through the Sangerbox platform. Our results indicate a pronounced upregulation of MRPS33 in glioma tissues, which is significantly associated with poor prognosis, heightened immune cell infiltration, and differential drug sensitivities. Furthermore, functional enrichment analyses suggest that MRPS33 is intricately involved in several key biological processes, thereby underscoring its potential role in glioma pathophysiology. In conclusion, our findings support the potential of MRPS33 as a prognostic biomarker and therapeutic target in glioma, providing insights that may advance our understanding of disease mechanisms and inform future clinical strategies.

Background: Data regarding the association between anthropometric factors and meningioma risk are inconsistent. Our aim was to investigate the association of body mass index (BMI), height, waist to hip ratio (WHR), waist circumference, and meningioma risk through a comprehensive meta-analysis. Methods: An extensive review of literature was conducted in PubMed and Embase databases. Random-effects models were used to pool the study-specific relative risk estimates (RRs) and 95% confidence intervals (CIs). Moreover, we employed a dose-response meta-analysis with a one-stage robust error meta-regression (REMR) model. Results: We included nine prospective studies for four anthropometric factors listed above and meningioma risk. Compared with normal weight, both overweight (RR:1.11, 95% CI: 1.04, 1.19; P = 0.003, I² = 0.0%) and obesity (RR: 1.38, 95% CI:1.16, 1.64; P < 0.001, I² = 54.7%) were statistically significantly associated with meningioma risk. Dose-response analysis showed a nonlinear relationship between BMI and meningioma risk (P = 0.038). For height, a positive association was identified for men (RR:1.30, 95% CI:1.08, 1.56; P = 0.005, I² = 0.0%) but not women (RR:1.13, 95% CI: 0.94,1.36; P = 0.186, I² = 49.8%). Highest vs. lowest levels analyses also showed a positive association between meningioma risk and waist circumference (RR:1.89, 95% CI:1.34, 2.66; P < 0.001, I² = 0.0%) and WHR (RR:1.40, 95% CI:1.00, 1.94; P = 0.048, I² = 0.0%). Conclusion: Our meta-analysis indicates greater height (in men) and excess weight and body fat mass were associated with an increased risk of meningioma. Further prospective studies with particular attention to sex disparity and dose-response analysis are warranted to confirm our observation.

Subarachnoid hemorrhage (SAH), a severe cerebrovascular disorder, is principally instigated by the rupture of an aneurysm. Early brain injury (EBI), which gives rise to neuronal demise, microcirculation impairments, disruption of the blood-brain barrier, cerebral edema, and the activation of oxidative cascades, has been established as the predominant cause of mortality among patients with SAH. These pathophysiological processes hinge on the activation of inflammasomes, specifically the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)and absent in melanoma 2 (AIM2) inflammasomes. These inflammasomes assume a crucial role in downstream intracellular signaling pathways and hold particular significance within the nervous system. The activation of inflammasomes can be modulated, either by independently regulating these two entities or by influencing their engagement at specific target loci within the pathway, thereby attenuating EBI subsequent to SAH. Although certain clinical instances lend credence to this perspective, more in-depth investigations are essential to ascertain the optimal treatment regimen, encompassing dosage, timing, administration route, and frequency. Consequently, targeting the ensuing early brain injury following SAH represents a potentially efficacious therapeutic approach.

To compare the safety and efficacy of clipping and coiling in patients with ruptured anterior circulation aneurysms. A systematic search of four databases (PubMed, Web of Science, Cochrane Library, and Embase) was conducted to identify comparative articles on endovascular coiling and surgical clipping in patients with ruptured anterior circulation aneurysms. Meta-analyses were conducted using random-effects models. Nineteen studies, including 1983 patients, were included. The meta-analysis showed that neurosurgical clipping was associated with a lower incidence of retreatment (OR:0.28, 95% CI (0.11, 0.70), P = 0.006) than endovascular coiling, which seemed to be a result of incomplete occlusion (OR:0.22, 95% CI (0.11, 0.45), P < 0.001). Neurosurgical clipping was associated with lower mortality (OR:0.45, 95% CI (0.25, 0.82), P = 0.009) at short-term follow-up than endovascular coiling. However, neurosurgical clipping showed a higher incidence of ischemic infarction (OR:2.28, 95% CI (1.44, 3.63), P < 0.001) and a longer length of stay (LOS) (WMD:6.12, 95% CI (4.19, 8.04), P < 0.001) after surgery than endovascular coiling. Furthermore, the pooled results showed no statistically significant differences between the two groups regarding poor outcome, long-term mortality, rebleeding, vasospasm, and hydrocephalus. Evidence from this systematic review illustrates that neurosurgical clipping may be superior to endovascular coiling for ruptured anterior circulation aneurysms. Large-scale RCTs should be conducted to verify these outcomes and provide results according to patient status.

Purpose: To demonstrate that occipital artery (OA)-p1 posterior inferior cerebellar artery (PICA) bypass can be an alternative for complex posterior circulation aneurysms. Methods: A far-lateral approach to craniotomy was performed on 20 cadaveric specimens, and the OA was obtained 'in-line.' Its length, diameter, and the number of p1/p2 and p3 segmental perforators were determined, and the relationship between the caudal loop and cerebellar tonsil position was also assessed. The distance between the PICA’s origin and the cranial nerve XI (CN XI), the buffer length above the CN XI after dissection, the OA length required to complete the OA-p1/p3 PICA bypass, and the p1 and p3 segment diameters were all measured. A bypass training practical scale (TSIO) was used to evaluate the quality of the anastomosis. Results: All specimens underwent OA-p1 PICA end-to-end bypass and had favorable results for the TSIO score, 15 sides underwent OA-p3 PICA end-to-side bypass, and the other bypass protocols were less common. The buffer length above the CN XI after dissection, the distance between the PICA’s origin and the CN XI, and the first perforator were all of sufficient length. The direct length of the OA needed to complete the OA-p1 PICA end-to-end bypass was significantly less than the available length and the OA-p3 PICA end-to-side bypass, with the OA matching the p1 segment diameter. The number of p1 perforators was less than that of p3, and the OA diameter was equal to that of the p1 segment. Conclusion: OA-p1 PICA end-to-end bypass is a feasible alternative in cases in which p3 segment has high caudal loops or anatomic anomalies.