Beijing Sanbo Brain Hospital

As the most common type of dementia, Alzheimer's disease (AD) often presents challenges in terms of early identification. In particular, there is a notable lack of reliable and accessible biomarkers. To measure the levels of amino acids and carnitine metabolites in the peripheral blood of AD patients to identify cognitive impairment-associated metabolites, two cohorts were recruited in this cross-sectional study from September 2018 to October 2023. Serum amino acid and carnitine levels were measured using liquid chromatography-mass spectrometry. The test cohort (normal cognition (NC), n = 70; amnesic mild cognitive impairment (aMCI), n = 41; dementia, n = 92) was used to analyze differences in serum amino acid and carnitine levels and to create a metabolite profile. The diagnostic performance of the metabolite profile was first assessed within the test cohort through receiver operating characteristic (ROC) curve analysis and machine learning approaches. Subsequent cognitive impairment subgroup analysis further confirmed its diagnostic efficacy. Finally, the validation cohort (NC, n = 10; aMCI, n = 10; dementia; n = 10; FDPV (FTD, DLB, PDD and VaD), n = 30) was used to determine the diagnostic and differential diagnostic capabilities of the metabolite profile. In the test cohort, serum levels of a total of 36 amino acids and carnitine metabolites were dysregulated. A profile of seven key metabolites successfully identified patients with NC, aMCI, and dementia. Cognitive subgroup (based on the Montreal Cognitive Assessment) analysis revealed that the profile was suitable for screening for mild, moderate, and severe cognitive impairment. The validation cohort further demonstrated the successful application of the metabolic profile for the discrimination of NC, aMCI, and dementia, as well as for the differential diagnosis of dementia and FDPV. In conclusion, extensive alterations in amino acid and carnitine metabolism levels were found in the peripheral blood of dementia patients, and a profile of seven amino acids and carnitine could be used as potential indicators for aMCI and dementia.

Scoliosis is a rare complication of intraspinal lesions. However, in patients with pre-existing scoliosis who have undergone lesion resection via laminoplasty, the subsequent progression of this deformity and its associated risk factors remain poorly understood. The objective of this study is to investigate the incidence of progressive scoliosis and identify risk factors contributing to its rapid progression in patients who underwent laminoplasty for resection of intraspinal lesions. This study retrospectively analyzed data from patients who underwent laminoplasty for resection of intraspinal lesions between January 2014 to December 2023. Multivariate logistic regression analysis was used to assess the statistical relationship between postoperative scoliosis progression and clinical, radiographic, and surgical-related variables. Fifty-two patients met the inclusion criteria for this study. During a follow-up of 28.5 (IQR,12-59.25) months, 32 patients (61.5%) exhibited scoliosis progression, with a mean progression of (16.3 ± 17.7) °. Notably, 16 patients (30.8%) demonstrated a progression exceeding 10° per annum. In the correlation analysis, variables such as age, Risser index, tumor location, scoliosis degree, the extent of laminoplasty, as well as postoperative syringomyelia, hypertonia and modified McCormick Scale (MMS) were associated with the rapid progression of scoliosis. However, multivariate analysis only identified three independent risk factors: preoperative curvature > 35°, laminoplasty involving ≥ 5 spinal segments, and postoperative hypertonia, which increased the odds of rapid progression by 5.2-, 4.8-, and 6.3-fold, respectively. In conclusion, after laminoplasty for resection of intraspinal lesions, 61.5% of patients with pre-existing scoliosis experienced progression of the deformity, and 30.8% of patients had rapid progression of scoliosis. A Cobb angle exceeding 35°, laminoplasty involving more than 5 vertebral segments, and postoperative hypertonia are all factors that increase the risk of rapid progression of scoliosis after surgery.

Photoplethysmography (PPG) detects hemodynamic changes during epileptic seizures. This study aim to investigate PPG signals changes during generalized tonic‒clonic seizures (GTCSs) and focal impaired awareness seizures (FIASs). 17 GTCS and 19 FIAS episodes were recorded from 18 patients. The 30 min preictal period was divided into three 10-minute intervals. PPG features analyzed were pulse upslope (PUS), maximal compliance (Kmax), and skewness. Features across 3 preictal intervals showed significant reductions compared to the baseline: PUS (F(3,64) = 11.870, p < 0.001), Kmax (F(3,64) = 7.419, p < 0.001) and skewness (F(3,64) = 2.852, p = 0.044) in the GTCS group. PUS (Kruskal–Wallis [K-W] = 22.600, p < 0.001) and Kmax (K-W = 28.110, p < 0.001) in the FIAS group. In the GTCS group, the largest difference was observed 30 min before seizure onset (PUS: p < 0.001, Cohen’s d = 1.843; Kmas: p < 0.001, Cohen’s d = 1.419; skewness: p = 0.043, Cohen’s d = 0.808), whereas this was not the case in the FIAS group. PPG signals showed earlier changes in the GTCS group than in the FIAS group, highlighting their differences and the potential of PPG-based monitoring for early seizure detection.

Phenylalanine (Phe) and its metabolite tyrosine (Tyr) have been shown to play an important role in the mechanisms and development of cardiovascular and cerebrovascular disease, and its ratio (Phe/Tyr) has been suggested to be an important indicator of inflammation. It was uncertain whether Phe/Tyr is associated with higher risk of MMD. Therefore, we conducted this study to evaluate the relationship between Phe/Tyr and the risk of MMD and its subtypes. A total of 360 adult MMD patients and 89 age-matched healthy controls (HCs) were consecutively recruited for this prospective study. We measured peripheral blood serum Phe and Tyr levels in all participants to analyze the association between Phe/Tyr and the risk of MMD and its subtypes. Serum Phe/Tyr was significantly higher in MMD patients and their subtypes than in HCs (p < 0.01). After adjusting for traditional risk factors, Phe/Tyr was positively associated with the risk of MMD (OR: 14.035, 95%CI: 2.784-70.748, p = 0.001). When Phe/Tyr was assessed in quartile subgroups, the third quartile (Q3) and fourth quartile (Q4) subgroups of Phe/Tyr had a significantly increased risk of MMD compared to the first quartile (Q3, OR: 2.019, 95%CI: 1.066-3.824, p = 0.031; Q4, OR: 2.887, 95%CI: 1.446-5.765, p = 0.003). The risk of MMD subtypes also increased with elevated Phe/Tyr level. Meanwhile, the addition of Phe/Tyr to conventional risk factors could significantly improve the risk prediction for MMD. In this study, the risk of MMD increased with elevated Phe/Tyr, suggesting that peripheral blood serum Phe/Tyr may be a valuable predictive biomarker of adult MMD.

BackgroundPsoriasis is a common chronic, recurrent, immune-mediated disease involved in the skin or joints or both. However, deeper insight into the genetic susceptibility of psoriasis is still unclear.MethodsHere we performed the largest multi-ancestry meta-analysis of genome-wide association study including 28,869 psoriasis cases and 443,950 healthy controls.ResultsWe identified 74 genome-wide significant loci for psoriasis. Of 74 loci, 32 were novel psoriasis risk loci. Across 74 loci, 801 likely causal genes are indicated and 164 causal genes are prioritized. SNP-based heritability analyses demonstrated that common variants explain 15% of genetic risk for psoriasis. Gene-set analyses and the genetic correlation revealed that psoriasis-related genes have the positive correlations with autoimmune diseases such as ulcerative colitis, inflammatory bowel diseases, and Crohn’s disease. Gene-drug interaction analysis suggested that psoriasis-associated genes overlapped with targets of current medications for psoriasis. Finally, we used the multi-ancestry meta-analysis to explore drug repurposing and the potential targets for psoriasis.ConclusionsWe identified 74 genome-wide significant loci for psoriasis. Based on 74 loci, we provided new biological insights to the etiology of psoriasis. Of clinical interest, we gave some hints for 76 potential targets and drug repurposing for psoriasis.

PurposeThis study aimed to describe the incidence, clinical and pathological features, and outcomes of H3 K27M- mutant Diffuse Midline Glioma (DMG) patients with leptomeningeal dissemination (LMD) and systematically investigate the predictive and prognostic factors to clarify the response to treatment after the onset of LMD.MethodsA total of 304 patients diagnosed with DMG from October 17, 2017, to October 17, 2023, were enrolled in this study, of which 32 patients were diagnosed with LMD. Logistic regression analyses were conducted to identify the predictors of LMD, including clinical, molecular, and imaging data. Univariable and multivariable cox regression analyses were used for overall survival (OS) and post-LMD survival (PLS) analysis.ResultsThe median OS and PLS were 12.5 and 8.0 months respectively. Tumor with contrast-enhanced lesions reaching ependyma (Ventricular contact type I) was the only independent risk factor for LMD. Male sex and ventricular contact type I were independent risk factors for primary LMD. In all LMD patients, Karnofsky Performance Status (KPS) of ≥ 90 and radiotherapy were statistically significantly associated with longer OS, and primary LMD was significantly associated with shorter OS. Supratentorial location and chemotherapy after LMD diagnosis were independent favorable prognostic factors on PLS. In primary LMD subgroup analysis, radiotherapy was the only independent favorable prognostic factor on OS.ConclusionsThe association between contrast-enhanced lesions and ventricular involvement is an independent predictive factor for LMD in DMG patients. Radiotherapy and preoperative KPS may contribute to improved overall survival in these patients. Chemotherapy is a potential treatment option following an LMD diagnosis.

BRG1 deficiency in patients with lung adenocarcinoma that has metastasized to the brain, termed BRG1-deficient brain metastasis lung adenocarcinoma, is an uncommon event. Prior to this study, these patients had not undergone extensive molecular and (epi)genetic analysis. We report a comprehensive clinical, histopathologic, and molecular assessment of 9 BRG1-deficient brain metastasis lung adenocarcinoma cohort (BRG1-deficient BM cohort) in comparison with a 16 BRG1-retained brain metastasis lung adenocarcinoma cohort (BRG1-retained BM cohort). Patients with BRG1-deficient BM exhibited a significantly increased risk of mortality. Molecular analysis revealed a high prevalence of mutations in SMARCA4 and TP53 genes within this group. DNA methylation molecular diagnostics showed a high rate of genomic instability and a markedly lower DNA methylation age in these patients. Functional enrichment analysis of differentially methylated genes suggested that hypomethylation genes were primarily associated with the negative regulation of neuron differentiation, G protein-coupled receptor signaling pathways, and cell differentiation. Conversely, hypermethylation was linked to the regulation of small GTPase mediated signal transduction, Rho protein signal transduction, DNA damage response, and apoptotic processes. This study investigated a rare subgroup of lung adenocarcinoma patients with brain metastasis characterized by BRG1 deficiency and a poor prognosis. Our study not only provides a comprehensive multi-omic data resource but also provides valuable biological insights into patients. The findings may serve as a valuable reference for the future pathological diagnosis of BRG1-deficient brain metastasis in lung adenocarcinoma patients.