Abstract At present, there is limited research on the mechanisms underlying moyamoya disease (MMD). Herein, we aimed to determine the role of glutamine in MMD pathogenesis, and 360 adult patients were prospectively enrolled. Human brain microvascular endothelial cells (HBMECs) were subjected to Integrin Subunit Beta 4 (ITGB4) overexpression or knockdown and atorvastatin. We assessed factors associated with various signaling pathways in the context of the endothelial‐to‐mesenchymal transition (EndMT), and the expression level of related proteins was validated in the superficial temporal arteries of patients. We found glutamine levels were positively associated with a greater risk of stroke (OR = 1.599, p = 0.022). After treatment with glutamine, HBMECs exhibited enhanced proliferation, migration, and EndMT, all reversed by ITGB4 knockdown. In ITGB4‐transfected HBMECs, the MAPK–ERK–TGF–β/BMP pathway was activated, with Smad4 knockdown reversing the EndMT. Furthermore, atorvastatin suppressed the EndMT by inhibiting Smad1/5 phosphorylation and promoting Smad4 ubiquitination in ITGB4‐transfected HBMECs. We also found the protein level of ITGB4 was upregulated in the superficial temporal arteries of patients with MMD. In conclusion, our study suggests that glutamine may be an independent risk factor for hemorrhage or infarction in patients with MMD and targeting ITGB4 could potentially be therapeutic approaches for MMD.
Abstract Background Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. Methods The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. Conclusions The MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.
Objective
To investigate the clinical value of C-reactive protein (CRP) combined with prothrombin time (PT) and partially activated thromboplastin time (APTT) in the diagnosis of neonatal late-onset sepsis.
Methods
From January 2013 to January 2018, 100 neonates with sepsis admitted to our department of neonatology in Lishui Maternal and Child Health-Care Center were collected.According to the
results
of blood culture, neonates with positive blood culture were classified as sepsis group A (53 cases), and neonates with negative blood culture were classified as sepsis group B (47 cases). Another 50 normal newborns born at the same period were included in the control group.The CRP, PT and APTT values of the three groups were detected and compared.The receiver-operating characteristic curves (ROC) were plotted to obtain the area under ROC curve (AUC) and the sensitivity, specificity, positive predictive value and negative predictive value.Another ROC curve was plotted to obtain the area under ROC curve (AUC) and the sensitivity, specificity, positive predictive value, and negative predictive value for a new variable, CPR+ PT+ APTT, which was established using a binomial logistic regression method.Results The results of CPR, PT and APTT in the control group, sepsis group A and sepsis group B all increased in turn (F=10.616, 6.155, 5.243, P=0.000, 0.000, 0.000). CPR+ PT+ APTT had the largest AUC (0.94), the highest sensitivity (93.42%), the highest specificity (91.66%), the highest positive predictive value (92.60%), and the highest negative predictive value (78.55%) in the four indicators.
Conclusion
When blood culture fails to diagnose late-onset neonatal sepsis, combined detection of CPR+ PT+ APTT can provide some clues for its early diagnosis, which is worthy of clinical attention.
Key words:
Sepsis, late-onset; C-reactive protein; Prothrombin time; Activated partial thrombin time; Neonatal; Sensitivity; Specificity; Positive predictive value; Negative predictive value
Growing evidence suggests that systemic immune and inflammatory responses may play a critical role in the formation and development of aneurysms. Exploring the differences between single intracranial aneurysm (SIA) and multiple IAs (MIAs) could provide insights for targeted therapies. However, there is a lack of comprehensive and detailed characterization of changes in circulating immune cells in MIAs. Peripheral blood mononuclear cell (PBMC) samples from patients with SIA (n = 16) or MIAs (n = 6) were analyzed using high-dimensional mass cytometry to evaluate the frequency and phenotype of immune cell subtypes. A total of 25 cell clusters were identified, revealing that the immune signature of MIAs included cluster changes. Compared to patients with SIA, patients with MIAs exhibited immune dysfunction and regulatory imbalance in T-cell clusters. They also had reduced numbers of CD8+ T cells and their subgroups CD8+ Te and CD8+ Tem cells, as well as reduced numbers of the CD4+ T-cell subgroup CD27-CD4+ Tem cells. Furthermore, compared to SIA, MIAs were associated with enhanced T-cell immune activation, with elevated expression levels of CD3, CD25, CD27, CCR7, GP130, and interleukin 10. This study provides insights into the circulating immune cell profiles in patients with MIAs, highlighting the similarities and differences between patients with SIA and those with MIAs. Furthermore, the study suggests that circulating immune dysfunction may contribute to development of MIAs.
ABSTRACT Background Creatine is essential for energy storage and transfer within and outside cells. However, its relationship with cerebrovascular disease has not been fully explored. This study examined the association between serum creatine levels and postoperative cerebrovascular events, including transient ischemic attack (TIA), ischemic stroke, and hemorrhagic stroke, in patients with moyamoya disease (MMD). Methods Serum creatine and disodium creatine phosphate levels were quantified in 352 patients with MMD using liquid chromatography–tandem mass spectrometry. Kaplan–Meier (KM) curves were used to analyze the impact of serum creatine levels on cerebrovascular event risk, whereas univariate and multivariate Cox regression analyses were used to identify predictors of postoperative outcomes. A prognostic nomogram was developed to predict stroke‐free survival at 12, 24, and 36 months postoperatively. Results In patients with MMD, serum creatine showed a negative correlation with creatinine ( r = −0.22; p < 0.001) and homocysteine ( r = −0.10; p < 0.05) but not with disodium creatine phosphate ( r = −0.08; p = 0.15). When patients were divided into high and low groups based on the median serum creatine concentration, KM curve analysis revealed that patients in the high concentration group had a lower relative risk of cerebrovascular events than those in the low concentration group (hazard ratio: 0.55; 95% confidence interval, 0.33–0.94; p = 0.026). Furthermore, when patients were categorized into three levels based on creatine concentration, the overall KM curve analysis showed a significant difference ( p = 0.038), such that the highest creatine concentration group (third tertile) showed a significantly reduced risk compared with the lowest concentration group (first tertile; p = 0.04). Conclusion Lower preoperative serum creatine levels were associated with a higher risk of postoperative cerebrovascular events in patients with MMD. Therefore, creatine supplementation may be an effective means of preventing adverse outcomes in patients with MMD.
One of the most common birth defects is cleft palate only (CPO) of which non-syndromic cleft palate only (NSCPO) accounts for 50%. NSCPO is a complex disease where multiple genes and environmental factors contribute to its risk. Unlike non-syndromic cleft lip with or without cleft palate (NSCL/P), previous genome-wide association studies only identified a few common genetic variations achieving genome-wide significance. This review summarizes the recent findings on genetic epidemiology of NSCPO. According to the current evidence, the candidate genes are divided into three categories: candidate genes with strong evidence, candidate genes with suggestive evidence, and candidate genes with inadequate evidence. The findings of epigenetic studies, the next generation sequencing studies, interaction analysis on NSCPO are also reviewed.单纯腭裂是一种较为常见的出生缺陷，其中非综合征型单纯腭裂（NSCPO）占50%。NSCPO是受遗传和环境共同作用的复杂疾病，与非综合征型唇裂伴或不伴腭裂（NSCL/P）不同，通过全基因组关联研究发现的与NSCPO相关的常见遗传变异相对较少。本文对NSCPO的遗传流行病学研究进展进行综述。根据现有研究证据将已发现的NSCPO候选基因分为研究证据比较充分的候选基因、具备一定研究证据的候选基因和现有研究证据较少的候选基因三类，展望了表观遗传学研究、新一代测序技术、交互作用分析在NSCPO病因探索中的应用，为进一步开展病因学研究提供线索。.
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