Nomogram for Predicting Long-term Outcomes of Encephaloduroarteriosynangiosis in Toddlers with Moyamoya Disease: a Longitudinal and Cross-sectional Study.

We investigated the long-term outcomes of encephaloduroarteriosynangiosis (EDAS) for stroke prevention in toddlers with moyamoya disease (MMD) using nomogram. Between January 2005 and December 2018, 74 toddlers with MMD underwent surgery in the Fifth Medical Centre, Chinese PLA General Hospital, 69 were < 4 years of age and included in the analysis. The modified Rankin scale (mRS) during follow-up evaluated clinical outcomes. To measure the effectiveness of EDAS, the annual risk of symptomatic infarction within the operated brain hemispheres was calculated. The event-free survival rate was determined using Kaplan-Meier curves. A nomogram generated using multivariate logistic regression analysis identified potential predictors associated with unfavorable outcomes. Additionally, discrimination, calibration, and clinical utility were assessed. A favorable clinical outcome was observed in 81.2% of the patients. The operated hemispheres showed an annual risk of 0.87% of symptomatic infarction and 0.23% of hemorrhage. Moreover, the 10-year event-free survival rates were 92.8% and 97.0% for symptomatic infarction and hemorrhage. Multivariate logistic analysis indicated that onset with infarction, initial mRS ≥ 3, and perioperative adverse events had significant and independent associations with unfavorable outcomes. However, an age at diagnosis of ≥ 2 years showed an association with favorable outcomes. Using these four factors, our model attained a concordance index of 0.912 (95% confidence interval, 0.842-0.982), well-fitted calibration curve, and cutoff value of 0.212 for predicting unfavorable outcomes. EDAS may prevent recurrent stroke and improve overall long-term clinical outcomes in toddlers with MMD. The developed nomogram accurately predicted unfavorable outcomes and assisted surgeons in patient evaluation.

The Potential Mechanism Behind Native and Therapeutic Collaterals in Moyamoya.

Background and Purpose: To explore the genetic basis and molecular mechanism of native arteriogenesis and therapeutic synangiosis in moyamoya disease (MMD). Methods: An angiography-based study using patients from a prospective trial of encephaloduroarteriosynangiosis (EDAS) surgery was performed. The spontaneous collaterals grades were evaluated according to the system described by a new grading system. Blood samples were collected from all the recruited patients before EDAS and during the second hospitalization 3 months post-EDAS. We performed Boolean analysis using a combination of specific cell surface markers of CD34briCD133+CD45dimKDR+. Genotyping of p.R4810K was also performed. The correlation of age, sex, initial symptoms at diagnosis, collateral grade, Suzuki stages, the RNF213 genotype, time to peak (TTP), and endothelial progenitor cell (EPC) count with good collateral circulation was evaluated. Results: Eighty-five patients with MMD were included in this study. The mutation rate of RNF213 p.R4810K in our study was 25.9% (22/85). The heterozygous mutations were occurred significantly more frequently in the cases that were presented with infarction, worse neurological status, severe posterior cerebral artery (PCA) stenosis, and longer TTP delay. Further, the heterozygous mutations occurred significantly more frequently in the poor collateral stage group. Lower grades were significantly correlated with severe ischemia symptoms, worse neurological status, and a longer TTP delay. The post-operative angiographic findings showed that a good Matsushima grade was correlated with heterozygous mutations, a lower collateral stage, and a longer TTP delay. The CD34briCD133+CD45dimKDR+ cell count in patients 3 months post-EDAS was significantly higher as compared to the count before EDAS in the good Matsushima grade group. However, this change was not observed in the poor Matsushima grade group. Conclusions: These data imply that mutations of RNF213 p.R4810K affect the establishment of spontaneous collateral circulation, and EPCs are involved in the process of formation of new EDAS collaterals.

Lycium barbarum Polysaccharides Promotes Mitochondrial Biogenesis and Energy Balance in a NAFLD Cell Model.

OBJECTIVE: To explore the protective effect and underlying mechanism of Lycium barbarum polysaccharides (LBP) in a non-alcoholic fatty liver disease (NAFLD) cell model. METHODS: Normal human hepatocyte LO2 cells were treated with 1 mmol/L free fatty acids (FFA) mixture for 24 h to induce NAFLD cell model. Cells were divided into 5 groups, including control, model, low-, medium- and high dose LBP (30,100 and 300 µg/mL) groups. The monosaccharide components of LBP were analyzed with high performance liquid chromatography. Effects of LBP on cell viability and intracellular lipid accumulation were assessed by cell counting Kit-8 assay and oil red O staining, respectively. Triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), adenosine triphosphate (ATP) and oxidative stress indicators were evaluated. Energy balance and mitochondrial biogenesis related mRNA and proteins were determined by quantitative real-time polymerase chain reaction and Western blot, respectively. RESULTS: Heteropolysaccharides with mannose and glucose are the main components of LBP. LBP treatment significantly decreased intracellular lipid accumulation as well as TG, ALT, AST and malondialdehyde levels (P<0.05 or P<0.01), increased the levels of superoxide dismutase, phospholipid hydroperoxide glutathione peroxidase, catalase, and ATP in NAFLD cell model (P<0.05). Meanwhile, the expression of uncoupling protein 2 was down-regulated and peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A pathway was up-regulated (P<0.05). CONCLUSION: LBP promotes mitochondrial biogenesis and improves energy balance in NAFLD cell model.