Development and validation of a novel nomogram for predicting good neoangiogenesis after encephaloduroarteriosynangiosis in patients with moyamoya disease and type 2 diabetes mellitus: a case-control study.

OBJECTIVE: Diabetes is often linked to poorer outcomes in patients with moyamoya disease (MMD). However, experience has shown that certain individuals with diabetes have favorable outcomes after encephaloduroarteriosynangiosis (EDAS). The authors aimed to develop a nomogram to predict good neoangiogenesis in patients with MMD and type 2 diabetes mellitus (T2DM) to aid neurosurgeons in the identification of suitable candidates for EDAS. METHODS: Adults with MMD and T2DM who underwent EDAS between June 2004 and December 2018 were included in the analysis. In total, 126 patients (213 hemispheres) with MMD and T2DM from the Fifth Medical Centre of the Chinese PLA General Hospital were included and randomly divided into training (152 hemispheres) and internal validation (61 hemispheres) cohorts at a ratio of 7:3. Univariate logistic and least absolute shrinkage and selection operator regression analyses were used to identify the significant factors associated with good neoangiogenesis, which were used to develop a nomogram. The discrimination, calibration, and clinical utility were assessed. RESULTS: A total of 213 hemispheres in 126 patients were reviewed, including 152 (71.36%) hemispheres with good postoperative collateral formation and 61 (28.64%) with poor postoperative collateral formation. The authors selected 4 predictors (FGD5 rs11128722, VEGFA rs9472135, Suzuki stage, and internal carotid artery [ICA] moyamoya vessels) for nomogram development. The C-indices of the nomogram in the training and internal validation cohorts were 0.873 and 0.841, respectively. The nomogram exhibited a sensitivity of 84.5% and specificity of 81.0%. The positive and negative predictive values were 92.1% and 66.7%, respectively. The calibration curves indicated high predictive accuracy, and receiver operating characteristic curve analysis showed the superiority of the nomogram. The decision-making analysis validated the fitness and clinical application value of this nomogram. Then a web-based calculator to facilitate clinical application was generated. CONCLUSIONS: The nomogram developed in this study accurately predicted neoangiogenesis in patients with MMD and T2DM after EDAS and may assist neurosurgeons in identifying suitable candidates for indirect revascularization surgery.

Development and validation of a novel nomogram for predicting long-term rebleeding risk among patients with hemorrhagic moyamoya disease: a 10-year multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to develop and validate a predictive nomogram model for long-term rebleeding events in patients with hemorrhagic moyamoya disease (HMMD). METHODS: In total, 554 patients with HMMD from the Fifth Medical Center of the Chinese PLA General Hospital (5-PLAGH cohort) were included and randomly divided into training (390 patients) and internal validation (164 patients) sets. An independent cohort from the First Medical Center and Eighth Medical Center of Chinese PLA General Hospital (the 1-PLAGH and 8-PLAGH cohort) was used for external validation (133 patients). Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) regression algorithm were used to identify significant factors associated with rebleeding, which were used to develop a nomogram for predicting 5- and 10-year rebleeding. RESULTS: Intraventricular hemorrhage was the most common type of cerebral hemorrhage (39.0% of patients in the 5-PLAGH cohort and 42.9% of the 1-PLAGH and 8-PLAGH cohort). During the mean ± SD follow-up period of 10.4 ± 2.9 years, 91 (16.4%) patients had rebleeding events in the 5-PLAGH cohort. The rebleeding rates were 12.3% (68 patients) at 5 years and 14.8% (82 patients) at 10 years. Rebleeding events were observed in 72 patients (14.3%) in the encephaloduroarteriosynangiosis (EDAS) surgery group, whereas 19 patients (37.3%) experienced rebleeding events in the conservative treatment group. This difference was statistically significant (p < 0.001). We selected 4 predictors (age at onset, number of episodes of bleeding, posterior circulation involvement, and EDAS surgery) for nomogram development. The concordance index (C-index) values of the nomograms of the training cohort, internal validation cohort, and the external validation cohort were 0.767 (95% CI 0.704-0.830), 0.814 (95% CI 0.694-0.934), and 0.718 (95% CI 0.661-0.775), respectively. The nomogram at 5 years exhibited a sensitivity of 48.1% and specificity of 87.5%. The positive and negative predictive values were 38.2% and 91.3%, respectively. The nomogram at 10 years exhibited a sensitivity of 47.1% and specificity of 89.1%. The positive and negative predictive values were 48.5% and 88.5%, respectively. CONCLUSIONS: EDAS may prevent rebleeding events and improve long-term clinical outcomes in patients with HMMD. The nomogram accurately predicted rebleeding events and assisted clinicians in identifying high-risk patients and devising individual treatments. Simultaneously, comprehensive and ongoing monitoring should be implemented for specific patients with HMMD throughout their entire lifespan.

Association between polymorphism in the MTHFR gene and encephaloduroarteriosynangiosis-induced collateral circulation formation.

OBJECTIVE: This study aimed to investigate whether high homocysteine (Hcy) levels associated with the MTHFR gene influence the formation of the collateral vascular network in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis (EDAS) by influencing the number of endothelial progenitor cells (EPCs) in peripheral blood. METHODS: A total of 118 Chinese patients with bilateral primary MMD were prospectively included. Blood samples were collected from the anterior cubital vein before surgery, and MTHFR rs9651118 was genotyped using high-throughput mass spectrometry to determine the genotype of the test specimen. Serum Hcy and EPC levels were measured, the latter with flow cytometry. Digital subtraction angiography was performed 6 months after EDAS, and the formation of collateral circulation was evaluated using the Matsushima grade system. The correlations between MTHFR rs9651118 genotype, Hcy and EPC levels, and Matsushima grade were compared. RESULTS: Among the 118 patients, 53 had the TT genotype (wild type) of MTHFR rs9651118, 33 TC genotype (heterozygous mutation), and 32 CC genotype (homozygous mutation). The mean ± SD Hcy level was 13.4 ± 9.5 µmol/L in TT patients, 9.8 ± 3.2 µmol/L in TC patients, and 8.9 ± 2.9 µmol/L in CC patients (p < 0.001). The level of EPCs in the venous blood of TT patients was 0.039% ± 0.016%, that of TC patients 0.088% ± 0.061%, and that of CC patients 0.103% ± 0.062% (p < 0.001). When the rs9651118 gene locus was mutated, Matsushima grade was better (p < 0.001) but there was no difference between heterozygous and homozygous mutations. CONCLUSIONS: The results suggest that the MTHFR rs9651118 polymorphism is a good biomarker for collateral vascular network formation after EDAS in MMD patients.

High Level of Serum Complement C3 Expression is Associated with Postoperative Vasculopathy Progression in Moyamoya Disease.

Background: The immune system plays an important role in the onset and development of moyamoya disease (MMD), but the specific mechanisms remain unclear. This study aimed to explore the relationship between the expression of complements and immunoglobulin in serum and progression of MMD. Methods: A total of 84 patients with MMD and 70 healthy individuals were enrolled. Serum immunoglobulin and complement C3 and C4 expression were compared between healthy individuals and MMD patients. Follow-up was performed at least 6 months post-operation. Univariate and multivariate analysis after adjusting different covariates were performed to explore predictive factors associated with vasculopathy progression. A nomogram basing on the results of multivariate analysis was established to predict vasculopathy progression. Results: Compared to healthy individuals, MMD patients had significantly lower expression of serum complements C3 (P = 0.003*). Among MMD patients, C3 was significantly lower in those with late-stage disease (P = 0.001*). Of 84 patients, 27/84 (32.1%) patients presented with vasculopathy progression within a median follow-up time of 13.0 months. Age (P=0.006*), diastolic blood pressure (P=0.004*) and serum complement C3 expression (P=0.015*) were associated with vasculopathy progression after adjusting different covariables. Conclusion: Complement C3 is downregulated in moyamoya disease and decreases even further in late-Suzuki stage disease. Age, diastolic blood pressure and serum complement C3 expression are associated with vasculopathy progression, suggesting that the complement might be involved in the development of moyamoya disease.

Isolated anterior cerebral artery occlusion: an atypical form of moyamoya disease.

BACKGROUND: The relationship between anterior cerebral artery (ACA) occlusion and moyamoya disease (MMD) has rarely been studied. In this study, we focused on a special type of MMD: isolated ACA-occlusive MMD. We investigated clinical attributes, genotypes and progression risk factors in patients with ACA-occlusive MMD, providing initial insights into the relationship between ACA occlusion and MMD. METHODS: We retrospectively analysed digital subtraction angiography (DSA) from 2486 patients and diagnosed 139 patients with ACA-occlusive MMD. RNF213 p.R4810K (rs112735431) mutation analysis was performed. Patients were categorised into progression and non-progression groups based on whether they progressed to typical MMD. Differences in clinical characteristics, neuropsychological assessment, radiological findings and genotypes were evaluated. Logistic regression analyses identified risk factors for ACA-occlusive MMD progression. RESULTS: The median age of patients with ACA-occlusive MMD was 36 years, and the primary symptom was transient ischaemic attack (TIA). 72.3% of ACA-occlusive MMD patients had cognitive decline. Of 116 patients who underwent RNF213 gene mutation analysis, 90 patients (77.6%) carried the RNF213 p.R4810K GG allele and 26 (22.4%) carried the GA allele. Of 102 patients with follow-up DSA data, 40 patients (39.2%) progressed. Kaplan-Meier curve estimates indicated a higher incidence of ischaemic stroke in the progression group during follow-up (p=0.035). Younger age (p=0.041), RNF213 p.R4810K GA genotype (p=0.037) and poor collateral compensation from the middle cerebral artery (MCA) to ACA (p<0.001) were risk factors of ACA-occlusive MMD progression to typical MMD. CONCLUSIONS: Cognitive decline and TIA might be the main manifestations of ACA-occlusive MMD. Isolated ACA occlusion may be an early signal of MMD. The initial lesion site of MMD is not strictly confined to the terminal portion of the internal carotid artery. Younger patients, patients with RNF213 p.R4810K GA genotype or those with inadequate MCA-to-ACA compensation are more likely to develop typical MMD.

Clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease: Longitudinal and Cross-Sectional Study.

Objective: This study aimed to explore the long-term outcome of unilateral moyamoya disease and predict the clinical and genetic factors associated with contralateral progression in unilateral moyamoya disease. Methods: We retrospectively recruited unilateral moyamoya disease patients with available genetic data who underwent encephaloduroarteriosynangiosis (EDAS) surgery at our institution from January 2009 to November 2017. Long-term follow-up data, including clinical outcomes, angiographic features, and genetic information, were analyzed. Results: A total of 83 unilateral moyamoya disease patients with available genetic data were enrolled in our study. The mean duration of clinical follow-up was 7.9 ± 2.0 years. Among all patients, 19 patients demonstrated contralateral progression to bilateral disease. Heterozygous Ring Finger Protein 213 p.R4810K mutations occurred significantly more frequently in unilateral moyamoya disease patients with contralateral progression. Furthermore, patients with contralateral progression typically demonstrated an earlier age of onset than those with non-progressing unilateral moyamoya disease. In the contralateral progression group, posterior circulation involvement was observed in 11 (11/19, 57.9%) patients compared to 12 (12/64, 18.8%) in the non-contralateral progression group (P = 0.001). The time to peak of cerebral perfusion and neurological status showed significant postoperative improvement. Conclusion: Long-term follow-up revealed that the EDAS procedure might provide benefits for unilateral moyamoya disease patients. Ring Finger Protein 213 p.R4810K mutations, younger age, and posterior circulation involvement might predict the contralateral progression of unilateral moyamoya disease.

Pentoxifylline protects against cerebral ischaemia-reperfusion injury through ferroptosis regulation via the Nrf2/SLC7A11/GPX4 signalling pathway.

OBJECTIVE: To investigate whether pentoxifylline (PTX) attenuates cerebral ischaemia-reperfusion injury (IRI) in rats by inhibiting ferroptosis and to explore the underlying molecular mechanisms. METHODS: Cerebral IRI was induced in male Sprague-Dawley (SD) rats using middle cerebral artery occlusion (MCAO). The effects of PTX on cerebral ischaemia-reperfusion brain samples were detected through neurological deficit score, staining and electron microscopy; levels of ferroptosis biomarkers from brain samples were detected using kits. Additionally, the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), transferrin receptor protein 1, divalent metal transporter 1, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) were determined by immunohistochemistry, real-time quantitative polymerase chain reaction and western blotting. RESULTS: Pre-treatment with PTX was found to improve neurological function, evidenced by reduced neurological deficit scores, decreased infarct volume and alleviated pathological features post-MCAO. This improvement was accompanied by reduced lipid peroxidation levels and mitigated mitochondrial damage. Notably, PTX's inhibitory effect on ferroptosis was characterised by enhanced Nrf2 nuclear translocation and regulation of ferroptosis-related proteins. Moreover, inhibition of Nrf2 using ML385 (an Nrf2-specific inhibitor) reversed PTX's neuroprotective effect on MCAO-induced ferroptosis via the SLC7A11/GPX4 signalling pathway. CONCLUSIONS: Ferroptosis is evident following cerebral ischaemia-reperfusion in rats. Pentoxifylline confers protection against IRI in rats by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signalling pathway.

Long-term outcomes after conservative and EDAS treatment for 111 elderly patients with moyamoya disease: longitudinal and cross-sectional study.

OBJECTIVE: This study aimed to explore the clinical features of moyamoya disease (MMD) and the efficacy of encephaloduroarteriosynangiosis (EDAS) in elderly patients with MMD and to identify the risk factors for long-term stroke events. METHODS: Clinical data were retrospectively collected on elderly patients with MMD (age ≥ 60 years) who had been treated at the authors' center from May 2007 to December 2017. Clinical features, angiographic findings, and long-term outcomes (> 5-year follow-up) were analyzed. Cox regression analysis was performed to determine the risk factors for postoperative stroke events. Long-term stroke events were analyzed using Kaplan-Meier curves. RESULTS: The mean age at symptom onset was 62.9 ± 3.0 years among 111 elderly patients with MMD. Vascular comorbidities were present in 80 (72.1%) patients. The ratio of female to male patients was 1:1.2. Familial MMD was found in 7 (6.3%) patients. Cerebral ischemia was the most common clinical manifestation observed in 82 (73.9%) patients. Most patients (59.5%) presented with Suzuki stages 5 and 6 MMD, and 29 (26.1%) patients presented with stenosis or occlusion of the posterior circulation. Unilateral MMD was present in 17 (15.3%) patients. Among the 58 (52.3%) patients who underwent EDAS, 28 (48.3%) and 30 (51.7%) underwent bilateral and unilateral surgeries, respectively. Overall, 53 (47.7%) patients were treated conservatively using internal medicine. After a median follow-up duration of 8.2 years, stroke incidence in the EDAS and conservative treatment groups was respectively 17.2% (7 and 3 cases of cerebral infarction and hemorrhage, respectively) and 49.1% (22 and 4 cases of cerebral infarction and hemorrhage, respectively). The stroke incidence rate was higher in the conservative group than in the EDAS group, with a statistically significant difference (p = 0.001) according to results of the Kaplan-Meier analysis. The identified predictor of postoperative stroke events was initial hemorrhage in the EDAS group and advanced age, aneurysm, and initial ischemia in the conservative treatment group. CONCLUSIONS: The postoperative long-term stroke rate among elderly patients with MMD was lower in the EDAS group than in the conservative treatment group. Long-term stroke events were associated with advanced age, aneurysm, and initial ischemia after conservative treatment and only initial hemorrhage after EDAS.

[Microbial Community Composition and Diversity in Metal Sulfide Mine Water Systems].

To understand the characteristics of heavy metal pollution and physicochemical properties caused by mining activities in mine water systems and the response of the microbial community to habitats with different contamination levels, this study selected different types of water (mining area wastewater, spoil heap area wastewater, dressing area wastewater, mine seepage water, and pond water) as the variables related to the mining activities in the water system of the Shizishan mining area in Tongling, Anhui Province. The pollution characteristics and physicochemical properties were compared, and the relationship between environmental factors and the microbial communities were analyzed. The results showed that the content of heavy metals, the physicochemical properties, and the structure and diversity of the microbial community of different types of water were significantly different in different mine areas, among which the most seriously polluted areas were the mining area, the spoil heap area, and the dressing area. There were significant differences in microbial community structure among different functional types of wastewaters, and the diversity and abundance of the microbial community in DW with the heaviest heavy metal pollution were weaker than those in the other four regions. PcoA analysis showed that samples of similar water types had similar clustering. Spearman correlation heat map analysis and canonical correlation analysis (CCA) indicated that heavy metal pollution, pH, electrical conductivity (EC), SO2-4, and chemical oxygen demand (COD) had the greatest effect on the microbial communities in the mine water systems. Moreover, this study found that Proteobacteria, Euryarchaeota, and Bacteroidetes dominated in mine water systems, and their potential use could be explored in the future. Our results provide a better understanding of the different types of water pollution characteristics in mine water systems and the key factors that determine the microbial community structure.

Factors Influencing Collateral Circulation Formation After Indirect Revascularization for Moyamoya Disease: a Narrative Review.

Indirect revascularization is one of the main techniques for the treatment of Moyamoya disease. The formation of good collateral circulation is a key measure to improve cerebral blood perfusion and reduce the risk of secondary stroke, and is the main method for evaluating the effect of indirect revascularization. Therefore, how to predict and promote the formation of collateral circulation before and after surgery is important for improving the success rate of indirect revascularization in Moyamoya disease. Previous studies have shown that vascular endothelial growth factor, endothelial progenitor cells, Caveolin-1, and other factors observed in patients with Moyamoya disease may play a key role in the generation of collateral vessels after indirect revascularization through endothelial hyperplasia and smooth muscle migration. In addition, mutations in the genetic factor RNF213 have also been associated with this process. This study summarizes the factors and mechanisms influencing collateral circulation formation after indirect revascularization in Moyamoya disease.

Xue-Jie-San prevents the early development of colitis-associated intestinal fibrosis by blocking Notch1 and FGL1 signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Xue-Jie-San (XJS), as a traditional Chinese herb prescription, has satisfactory effects on improving clinical symptoms and facilitating the healing of intestinal ulcers in patients with Crohn's disease (CD). This motivates the application of XJS on CD-associated complications. AIM OF THE STUDY: Intestinal fibrosis is a debilitating complication of CD. Currently, there is no effective medication available for preventing or reversing CD-related intestinal fibrosis. This study aimed to assess the efficacy and underlying mechanisms of XJS in the treatment of colitis-associated intestinal fibrosis. MATERIALS AND METHODS: A rat model of CD-related intestinal fibrosis was induced by 2,4,6-trinitrobenzene sulfonic acid administration and treated with XJS. The pathological changes of intestinal fibrosis were evaluated using Masson staining. Collagen deposition and epithelial-to-mesenchymal transition (EMT) were verified by immunohistochemical staining and Western blot analysis. Endothelial-to-mesenchymal transition (EndoMT) was assessed with immunofluorescence and immunohistochemical staining as well as Western blot analysis. Transmission electron microscopy was utilized to observe autophagosomes. The levels of autophagy-related proteins were detected via immunofluorescence staining and Western blot. Finally, the mTOR/ULK1 signaling pathway regulated by Notch1 or FGL1 was analyzed by Western blot. RESULTS: The results found that XJS ameliorated intestinal fibrosis through reducing the deposition of collagens such as Collagen 1 and Collagen 3. XJS inhibited the EMT process by increasing E-cadherin levels and decreasing the expressions of N-cadherin, Vimentin and Snail, which played a crucial role in collagen secretion and intestinal fibrosis. In addition, XJS also repressed the EndoMT process as reflected by the upregulation of CD31 and VE-cadherin levels and the downregulation of FSP1 and α-SMA expressions. Autophagy was activated following XJS treatment via suppression of the mTOR/ULK1 signaling pathway. Furthermore, XJS acted as an inhibitor of Notch1 and FGL1 signals, both of which regulated the mTOR signaling. CONCLUSIONS: Our findings validated that XJS prevented the early development of CD-related intestinal fibrosis by blocking the Notch1 and FGL1 signaling pathways to activate autophagy and thereby inhibit EMT and EndoMT.

To explore the effectiveness of atorvastatin in the postoperative formation of collateral blood vessels after encephaloduroarteriosynangiosis in patients with moyamoya disease: a prospective double-blind randomized controlled study.

Introduction: The aim of this large, prospective, double-blind randomized controlled trial is to investigate the effect of atorvastatin on the formation of collateral blood vessels in patients after encephaloduroarteriosynangiosis (EDAS) and to provide a theoretical basis for clinical drug intervention. Specifically, we will determine whether atorvastatin has an effect on the development of collateral vascularization and on cerebral blood perfusion after revasculoplasty in patients with moyamoya disease (MMD). Methods and analysis: Overall, 180 patients with moyamoya disease will be recruited and randomly assigned to the atorvastatin treatment group or the placebo control group in a 1:1 ratio. Before revascularization surgery, magnetic resonance imaging (MRI) scanning and digital subangiography (DSA) examination will be routinely performed on the enrolled patients. All patients will receive intervention via EDAS. According to the randomization results, patients in the experimental group will be treated with atorvastatin (20 mg/day, once a day, for 8 weeks) and patients in the control group will be treated with placebo (20 mg/day, once a day, for 8 weeks). All participants will return to the hospital for MRI scan and DSA examination 6 months after EDAS surgery. The primary outcome of this trial will be the difference in the formation of collateral blood vessels revealed by DSA examination at 6 months after EDAS surgery between the two groups. The secondary outcome will be an improvement in the dynamic susceptibility contrast sequence cerebral perfusion on MRI at 6 months after EDAS, compared to the preoperative baseline. Ethics and dissemination: This study was approved by the Ethics Committee of the First Medical Center of the PLA General Hospital. All participates will voluntary provide written informed consent before participating in the trial. Clinical trial registration: ClinicalTrials.gov, ChiCTR2200064976.

Surgical outcomes following encephaloduroarteriosynangiosis in moyamoya disease associated with hyperhomocysteinemia.

INTRODUCTION: This study investigated the effect of indirect revascularization surgery in adult patients with moyamoya disease (MMD) complicated with hyperhomocysteinemia (HHcy), and the effect of HHcy on the progression of adult MMD. METHODS: A retrospective case-control study was conducted in patients with MMD, with or without HHcy (n = 123). Postoperative collateral angiogenesis was evaluated using the Matsushima grading system and disease progression using the Suzuki staging system. Cerebral blood flow was evaluated before and after surgery using dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) and neurological function prognosis using the improved Rankin score (mRS). Univariate and multivariate logistic regression analyses were performed to determine risk factors for the clinical outcomes. RESULTS: There was no significant difference in the Suzuki stage composition ratios between the HHcy group and the non-HHcy group before and after surgery. Non-HHcy patients were more likely to grow new collateral circulating vessels after encephaloduroarteriosynangiosis (EDAS). Moreover, postoperative DSC-MRI indicated that the time to peak significantly improved. CONCLUSIONS: HHcy level may be a specific predictor of adverse clinical outcomes after EDAS in patients with MMD and a risk factor for poor collateral circulation and poor prognosis. Patients with MMD complicated with HHcy need to strictly control homocysteine levels before EDAS surgery.

In this retrospective study, we found that patients with MMD complicated by HHcy had poor collateral angiogenesis after EDAS, faster disease progression, and worse clinical outcomes.

Butylphthalide protects against ischemia-reperfusion injury in rats via reducing neuron ferroptosis and oxidative stress.

Local ischemia in the cerebra leads to vascular injury and necrosis. Ferroptosis is involved in the pathophysiological process of many diseases and widely exists when ischemia-reperfusion injury occurs in many organs. The aim of this study was to evaluate the effect of Butylphthalide (NBP) on middle cerebral artery occlusion (MCAO) rats model-caused neuron injury. Sprague Dawley Rats were randomly allocated to receive sham and MCAO operation. NBP low-dose (40 mg/kg b.w), and high-dose (80 mg/kg b.w) were administrated in MACO rats. Results showed NBP improves infarct volume, attenuates neuronal apoptosis in the brain tissue of MCAO rats. The tumor necrosis factor (TNF-α), IL-6, and malondialdehyde (MDA) levels decreased after NBP administration, while the activity of superoxide dismutase (SOD) and the ratio of GSH/GSSG in MACO rats increased. MACO caused non-heme iron accumulation in the brain tissue and Perl's staining confirmed NBP attenuates ferroptosis in MACO rats. The protein expressions of SCL7A11 and glutathione peroxidase 4 (GPX4) decreased following MCAO, and NBP treatment subsequently increased the expression of SCL7A11 and GPX4. In vitro analysis in cortical neuron cells indicated that the GPX4 inhibitor reverses the inhibition of ferroptosis by NBP, which suggested that the SCL7A11/GPX4 pathway majorly contributed to the NBP ferroptosis protection effect.

A long-term study of posterior circulation changes after revascularization in patients with moyamoya disease.

OBJECTIVE: This study aimed to explore the long-term course of posterior circulation changes and predictors in patients with moyamoya disease (MMD). METHODS: The authors retrospectively enrolled patients who were diagnosed with MMD and underwent encephaloduroarteriosynangiosis (EDAS) surgery at the authors' department from December 2002 to September 2011. A comparative study between short-term (6-12 months) and long-term (≥ 9 years) follow-up angiography was conducted. The progression of lesions was defined from lower to higher stages of the posterior cerebral artery (PCA). RESULTS: Eighty-eight patients who received indirect EDAS were enrolled in the study. The mean age at first surgery was 28.1 ± 15.0 years. Among these 88 patients with MMD, 39 (44.3%) exhibited transient ischemic attack and 27 (30.7%) exhibited infarction, comprising 5 with occipital lobe infarction, 14 (15.9%) with hemorrhagic symptoms, and 8 (9.1%) with atypical symptoms as the initial symptoms. Heterozygous mutations occurred significantly more frequently in the cases that presented with PCA involvement. During follow-up, stage progression of PCA was observed in 21 patients (28 hemispheres). At short-term follow-up, 21/176 (11.9%) hemispheres had progression of steno-occlusive lesions in the PCA. At long-term follow-up, 7 (4.0%) hemispheres had progression of steno-occlusive lesions in the PCA. At short-term follow-up, the progression of steno-occlusive lesions in the PCA was associated with progression of the internal carotid artery. Stage progression of PCA occurred significantly more frequently in the cases with PCA involvement on preoperative angiography. Nine strokes (10.2%) occurred in 88 patients during long-term follow-up. Four patients (4.5%) presented with ischemic stroke, including 2 with occipital lobe infarctions. CONCLUSIONS: Progression of PCA stenosis is common in patients with MMD, even if the PCA is normal initially. Mutations of RNF213 p.R4810K may predict PCA involvement or progression. Follow-up of the PCA in MMD patients should be conducted, and timely surgical revascularization is needed.

The impacts of bronze age in the gene pool of Chinese: Insights from phylogeographics of Y-chromosomal haplogroup N1a2a-F1101.

Objectives: Previous studies of archaeology and history suggested that the rise and prosperity of Bronze Age culture in East Asia had made essential contribution to the formation of early state and civilization in this region. However, the impacts in perspective of genetics remain ambiguous. Previous genetic researches indicated the Y-chromosome Q1a1a-M120 and N1a2a-F1101 may be the two most important paternal lineages among the Bronze Age people in ancient northwest China. Here, we investigated the 9,000-years history of haplogroup N1a2a-F1101 with revised phylogenetic tree and spatial autocorrelation analysis. Materials and Methods: In this study, 229 sequences of N1a2a-F1101 were analyzed. We developed a highly-revised phylogenetic tree with age estimates for N1a2a-F1101. In addition, we also explored the geographical distribution of sub-lineages of N1a2a-F1101, and spatial autocorrelation analysis was conducted for each sub-branch. Results: The initial differentiation location of N1a2a-F1101 and its most closely related branch, N1a2b-P43, a major lineage of Uralic-speaking populations in northern Eurasia, is likely the west part of northeast China. After ~4 thousand years of bottleneck effect period, haplgroup N1a2a-F1101 experienced continuous expansion during the Chalcolithic age (~ 4.5 kya to 4 kya) and Bronze age (~ 4 kya to 2.5 kya) in northern China. Ancient DNA evidence supported that this haplogroup is the lineage of ruling family of Zhou Dynasty (~ 3 kya-2.2 kya) of ancient China. Discussion: In general, we proposed that the Bronze Age people in the border area between the eastern Eurasian steppe and northern China not only played a key role in promoting the early state and civilization of China, but also left significant traces in the gene pool of Chinese people.

Lignin-based covalent organic polymers with improved crystallinity for non-targeted analysis of chemical hazards in food samples.

Lignin, the most abundant source of renewable aromatic compounds derived from natural lignocellulosic biomass, has great potential for various applications as green materials due to its abundant active groups. However, it is still challenging to quickly construct green polymers with a certain crystallinity by utilizing lignin as a building block. Herein, new green lignin-based covalent organic polymers (LIGOPD-COPs) were one-pot fabricated with water as the reaction solvent and natural lignin as the raw material. Furthermore, by using paraformaldehyde as a protector and modulator, the LIGOPD-COPs prepared under optimized conditions displayed better crystallinity than reported lignin-based polymers, demonstrating the feasibility of preparing lignin-based polymers with improved crystallinity. The improved crystallinity confers LIGOPD-COPs with enhanced application performance, which was demonstrated by their excellent performances in sample treatment of non-targeted food safety analysis. Under optimized conditions, phytochromes, the main interfering matrices, were almost completely removed from different phytochromes-rich vegetables by LIGOPD-COPs, accompanied by "full recovery" of 90 chemical hazards. Green, low-cost, and reusable properties, together with improved crystallinity, will accelerate the industrialization and marketization of lignin-based COPs, and promote their applications in many fields.

Wavelet Analysis of Cerebral Oxygenation Signal Measured by Near-Infrared Spectroscopy in Moyamoya Disease.

BACKGROUND: Spontaneous low-frequency oscillations (LFOs) have been widely studied in cerebrovascular disease, but little is known about their role in moyamoya disease (MMD). The objective of this study was to assess the value of spontaneous LFOs in MMD based on wavelet analysis of near-infrared spectroscopy signals. METHODS: Sixty-four consecutive idiopathic adult patients were prospectively enrolled. The regional tissue oxygenation index (TOI) obtained from continuous near-infrared spectroscopy signals. Five frequency intervals of spontaneous LFOs (I, 0.0095-0.02 Hz; II, 0.02-0.06 Hz; III, 0.06-0.15 Hz; IV, 0.15-0.40 Hz; and V, 0.40-2.00 Hz) were extracted based on wavelet analysis. The data were compared between the patients and healthy control groups. Clinical features, cognitive function, and disease progression of MMD were analyzed using TOI and frequency interval data. RESULTS: Compared with the healthy control group, patients with MMD had a higher cerebral TOI in both hemispheres. Based on wavelet analysis, the spontaneous LFO of TOI was found to be significantly lower for patients with MMD in frequency intervals II to IV than that for the controls. The spontaneous LFO of TOI is also related to the Suzuki stages in intervals II to IV, stroke in interval III, and cognitive impairment in intervals III to Ⅳ. CONCLUSIONS: There were significant differences in spontaneous LFO between patients with MMD and healthy controls. The change in spontaneous LFO in MMD is related to Suzuki stage, cerebral infarction, and cognitive impairment. This might be an effective method for evaluating the severity and monitoring the progression of MMD.

Effect of Rabeprazole and Rebamipide in the Treatment of Upper Gastrointestinal Hemorrhage Associated with Dual Antiplatelet Therapy in Elderly Patients with Coronary Heart Disease.

To investigate the therapeutic effect of rabeprazole and rebamipide on patient age over 60 with dual antiplatelet therapy (DAPT)-related upper gastrointestinal hemorrhage following percutaneous coronary intervention (PCI). A total of 360 patients age over 60 undergoing PCI were recruited for antiplatelet therapy involving a combined treatment of aspirin (100 mg/d) and clopidogrel (75 mg/d). The enrolled patients were divided into 4 groups: the control group, the rabeprazole group, the rebamipide group, and the rabeprazole + rebamipide group. The incidence and severity of any upper gastrointestinal hemorrhage and the incidence of major adverse cardiac events (MACEs) were observed 6 months after the operation. The incidence of upper gastrointestinal hemorrhage in the 4 groups was 11.1%, 3.3%, 8.9%, and 1.1%, respectively, and the differences were statistically significant (P < 0.05). On comparing the groups, the differences between the control group and the rabeprazole group, those between the control group and the rabeprazole + rebamipide group, and those between the rebamipide group and the rabeprazole + rebamipide group were found to be statistically significant (P < 0.05). The severity of the upper gastrointestinal hemorrhage in the rabeprazole group and the rabeprazole + rebamipide group was significantly lower than that in the control group. The 4 groups exhibited no significant differences in the incidence of MACEs (P > 0.05). For patients age over 60 receiving DAPT following PCI in our study population, treatment with rabeprazole or a combination of rabeprazole and rebamipide could reduce the risk of upper gastrointestinal hemorrhage, as well as reduce its severity.