Hao Deng

Parkinson’s disease (PD) involves not only the loss of dopaminergic neurons in the substantia nigra but also spinal cord degeneration. However, the molecular mechanisms of spinal cord degeneration remain unclear. This study investigated the spinal cord transcriptomic characteristics of MPTP-induced PD mice via transcriptome sequencing and weighted gene co-expression network analysis (WGCNA) to identify key gene modules and potential therapeutic targets. An MPTP-induced PD mouse model was established, and spinal cord transcriptome sequencing was conducted to screen differentially expressed genes (DEGs). Functional enrichment analysis, WGCNA for phenotype-correlated modules, and protein–protein interaction analysis were subsequently conducted to identify key genes. In total, 3473 DEGs were identified (1775 upregulated, 1698 downregulated). Downregulated genes were predominantly enriched in pathways related to oxidative phosphorylation and post-transcriptional regulation, whereas upregulated genes were associated with glutamatergic synapses, axonogenesis, and negative regulation of neurogenesis. Among the five co-expression modules, the brown and yellow modules were most strongly correlated with the PD phenotype, enriched in calcium signaling, inflammation, and spliceosome pathways. Key genes like Akt1, Nlrp3, Tgfb1, Lingo1, and Olig2 were upregulated, whereas Vps35 and Omg were downregulated. This study characterizes the spinal transcriptome of PD mice, suggesting that dysregulated post-transcriptional processes, abnormal oxidative phosphorylation, glutamatergic excitotoxicity, and neuroinflammation may be potential candidate mechanisms and vital involved factors in spinal cord degeneration. These findings provide novel insights into the pathological mechanisms of spinal cord degeneration in PD and lay a foundation for targeted therapy, deserving further investigation.

Background: Gamma Knife radiosurgery (GKS) is widely used for the management of intracranial disorders. Emerging evidence suggests that incorporating the biological effective dose (BED) into GKS planning may improve the prediction of treatment efficacy and toxicity. This review aims to evaluate the role of BED in GKS across multiple intracranial indications. Methods: A qualitative review of published clinical studies was performed to assess the application of BED models in GKS for pituitary adenomas, vestibular schwannomas, meningiomas, arteriovenous malformations (AVMs), trigeminal neuralgia, and other disorders. The relationships between BED, treatment outcomes, and adverse effects were compared across indications. Results: The association between BED and clinical outcomes was most consistent in AVMs, where higher BED correlated closely with obliteration rates. In other diseases, BED-based analyses showed promising but variable predictive value. Notably, BED-derived parameters demonstrated improved prediction of post-GKS hypopituitarism in pituitary adenomas and AVM obliteration compared with physical dose alone. However, most available evidence was derived from retrospective studies. Conclusions: BED may serve as a valuable complement to conventional physical dose metrics in GKS planning, but its ability to replace physical dose remains uncertain. Prospective studies and histology-specific radiobiological parameter validation are required to establish the routine clinical utility of BED.

Background: Hemorrhagic stroke (HS) accounts for approximately 30% of all stroke cases and has high mortality in the intensive care unit (ICU). The blood urea nitrogen-to-creatinine ratio (BUNCR) is a potential biomarker of catabolic stress in critically ill patients. Meanwhile, its dynamic prognostic value in ICU-admitted HS patients remains unclear. This study utilized Group-based Trajectory Modeling (GBTM) to investigate associations between early BUNCR patterns and mortality. Methods: This study was conducted using data from the MIMIC-IV (v2.2) database. HS cases were identified via ICD-9/10. BUNCR trajectories were assessed by applying GBTM during the first 7 days. Outcomes were all-cause mortality (ACM) on day 28, on day 90, and at 1 year, with ICU and in-hospital mortality also evaluated. Kaplan–Meier survival curves and log-rank test compared survival across groups. Multivariable Cox proportional models adjusted for confounders and subgroup analysis assessed robustness. Results: Among 2559 patients (52.48% male), mortality was 10.16% (ICU), 14.07% (in-hospital), 17.00% (28-day), 22.43% (90-day), and 36.97% (1-year). Three BUNCR trajectories were identified: Group 1 (upward–downward, n = 655), Group 2 (stable upward, n = 1270), and Group 3 (downward–upward, n = 634). Group 2 had the highest ACM risk at 28-day, 90-day, and 1-year (p < 0.01), and was identified as a significant risk factor in multivariate Cox regression. Subgroup revealed significant interactions of BUNCR trajectories with age and sepsis. Conclusions: Distinct BUNCR trajectories were significantly associated with ACM in critically ill HS patients. Persistently increasing BUNCR predicted the poorest outcomes, underscoring its potential as a dynamic biomarker for timely risk stratification and informed ICU decisions.

Obsessive–compulsive disorder (OCD) is a prevalent, chronic, and severe neuropsychiatric disorder that leads to illness-related disability. Despite the availability of several treatments, many OCD patients respond inadequately, because the underlying neural mechanisms remain unclear, necessitating the establishment of many animal models, particularly mouse models, to elucidate disease mechanisms and therapeutic strategies better. Although the development of animal models is ongoing, there remain many comprehensive summaries and updates in recent research, hampering efforts to develop novel treatments and enhance existing interventions. This review summarizes the phenotypes of several commonly used models and mechanistic insights from transgenic models of OCD, such as knockout mouse models. In addition, we present the advantages and limitations of these models and discuss their future in helping further understand the pathophysiology and advanced treatment. Here, we highlight current frontline treatment approaches for OCD, including neuromodulation and surgical interventions, and propose potential future directions. By studying gene mutations and observing phenotypes from available OCD animal models, researchers have classified the molecular signatures of each model reminiscent of changes in brain areas and neural pathways, with the hope of guiding the future selection of the most appropriate models for specific research in the OCD field.