Shaoqing Wu

Background Moyamoya disease (MMD), historically termed spontaneous occlusion of the circle of Willis, is a rare steno-occlusive cerebrovascular disease. Its etiology and pathogenesis remain incompletely understood, and lipid metabolism has recently attracted attention as a potential correlate of its clinical and biological heterogeneity. Methods This scoping review summarizes evidence on lipid metabolic abnormalities in MMD, including clinical associations, lipid-related markers, multi-omics findings, potential mechanisms, and therapeutic implications of lipid-modulating approaches. Results Epidemiological studies suggest that lipid abnormalities, including hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated lipoprotein(a), are common in MMD and are associated with disease phenotype, progression, stroke risk, and postoperative outcomes. Multi-omics studies reveal lipid metabolic alterations across peripheral blood, cerebrospinal fluid (CSF), and cerebrovascular tissue, suggesting a pattern of peripheral depletion, central enrichment, and tissue remodeling. Alterations in apolipoproteins such as APOE and lipid classes including sphingolipids, cardiolipins, and lysophosphatidylcholine may be associated with endothelial and vascular smooth muscle cell dysfunction, inflammatory responses, oxidative stress, and pathological vascular remodeling. Clinical studies suggest that statin use may be associated with improved collateral formation, although the underlying mechanisms remain uncertain. Conclusions This review maps emerging evidence linking lipid metabolism to MMD and highlights future directions for biomarker discovery, mechanistic validation, and therapeutic exploration.

Purpose: Surgical revascularization is the preferred treatment for most patients with Moyamoya disease (MMD). Nevertheless, a considerable number of eligible patients choose non-surgical management. This study aimed to identify factors influencing treatment decisions, with particular emphasis on asymptomatic MMD patients. Materials and Methods: We conducted a retrospective analysis of MMD patients without surgical contraindications treated at our center between 2010 and 2022. Baseline characteristics were compared using Wilcoxon rank-sum and chi-squared tests. Multivariable logistic regression was used to identify factors associated with treatment selection. Results: Among the 147 included patients, 62.6% underwent surgical treatment. Younger age (OR = 0.88, 95% CI: 0.88–0.94, p < 0.001), married status (OR = 653.3, 95% CI: 41.61–10,264.22, p < 0.001), and absence of hyperlipidemia (OR = 0.16, 95% CI: 0.03–0.85, p < 0.05) were significantly associated with choosing surgery. Asymptomatic patients underwent surgery at a higher rate than symptomatic patients (67.9% vs. 59.6%). Younger age was a significant predictor of surgical preference in both symptomatic and asymptomatic subgroups. Conclusion: Younger age is strongly associated with the choice of surgical treatment in MMD, including in asymptomatic cases.

Background: Mitochondrial D‐loop methylation leads to abnormal cerebral angiogenesis. This study examines its role in vascular phenotypes of moyamoya disease (MMD). Method: Blood samples from 96 intracranial artery stenosis/occlusion (ICASO) patients (35 MMD, 61 non‐MMD) and healthy controls underwent methylation analysis. D‐loop methylation levels were analyzed using chi‐square, T ‐test, and Wilcoxon tests. Propensity score matching (PSM) adjusted for age and gender disparities. Combine clinical information with methylation data to build a diagnostic model. Further studies included the methylation levels in MMD patients carrying the RNF213 p.R4810K mutation and the methylation levels and possible mechanisms of human brain microvascular endothelial cells (hCMEC/D3) with RNF213 knockdown. Results: Healthy controls showed higher D‐loop methylation than MMD ( p < 0.05). Post‐PSM, non‐MMD ICASO patients showed higher D‐loop methylation than MMD ( p < 0.05). The AUC of the prediction model was 0.891 (95% CI, 0.821–0.961) after combining clinical information with methylation data. MMD patients with the RNF213 mutation exhibited reduced methylation at most sites, though not statistically significant ( p > 0.05). RNF213 knockout in hCMEC/D3 enhanced proliferation, migration, and tube formation, while reducing apoptosis and DNMT1 expression, leading to decreased D‐loop methylation and ROS level, increased ATP production and mitochondrial membrane potential. Conclusion: There are differences in the methylation levels in the mitochondrial D‐loop region between MMD and non‐MMD ICASO. The methylation–metabolism–angiogenesis axis may represent a promising research direction for elucidating MMD pathogenesis.

Tracheostomy is frequently performed in severe ischemic stroke patients, yet the ideal timing for this procedure remains undefined. This study seeks to inform clinical decisions by evaluating the impact of early versus standard tracheostomy on clinical outcomes in this patient population. We retrospectively reviewed severe ischemic stroke patients who underwent tracheostomy at our hospital between January 2013 and November 2023. Patients were categorized into early tracheostomy (ET) and standard tracheostomy (ST) groups based on the interval from intubation to tracheostomy. Clinical outcomes were compared between the two groups. The logistic regression model was used to assess the correlation between the timing of tracheostomy and outcomes, and the Kaplan–Meier method was employed to analyze time-to-event results. The study encompassed 110 patients, with 57 in the ET group and 53 in the ST group. The results showed that the ET group had a longer interval from onset to intubation (P = 0.048), but there was no significant difference in the proportion of patients with severe disability after six months (OR 1.089 [95% CI 0.377–3.144], aOR 1.091 [95% CI 0.345–3.447]). The ET group demonstrated a shorter mechanical ventilation time (aOR 1.036 [95%CI 1.005–1.069]) and a decreased incidence of tracheostomy-related complications (aOR 5.378 [95%CI 1.065–27.144]). Early tracheostomy does not affect the long-term outcomes of patients with severe ischemic stroke, but it may offer potential benefits.

Moyamoya disease (MMD), most often diagnosed in children and adolescents, is a chronic cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Recently, many investigators show a great interest in MMD with pulmonary arterial hypertension (PAH). Ring finger protein 213 (RNF213) is a major susceptibility gene for MMD and also has strong correlations with PAH. Therefore, this review encapsulates current cases of MMD with PAH and discusses MMD with PAH in the aspects of epidemiology, pathology, possible pathogenesis, clinical manifestations, diagnosis, and treatment.

Background and purpose It remains inconclusive whether asymptomatic intracranial hemorrhage (aICH) after acute ischemic stroke is innocuous. We aimed to conduct a meta-analysis assessing the relationship between the aICH and poor neurological outcomes. Methods We searched PubMed, EMBASE and Web of Science from their inception to 30 November 2021 and performed a meta-analysis on the association between the aICH and neurological prognosis after acute ischemic stroke at 3 months, including poor outcomes (modified Rankin Scale [mRS] score ≥ 2 or mRS ≥ 3) and mortality. Results Fourteen studies were included in the analysis, reporting on a total of 10,915 participants after acute ischemic stroke. The risks of poor outcome (mRS ≥ 2 or mRS ≥ 3) in patients with aICH were significantly higher than patients without ICH (OR 1.70, 95% CI 1.33–2.18; OR 1.43, 95% CI 1.20–1.70, respectively), based on adjusted data. The difference between the two groups was not significant for mortality. The results of subgroup analysis showed aICH were associated with higher ratio of mild poor prognosis (mRS ≥ 2) (OR 1.59, 95% CI 1.11–2.27), but it had no association with functional dependence (mRS ≥ 3) after recanalization. No significant influence of aICH on poor outcome (mRS ≥ 3) was found in non-recanalization group. Further stratified analysis revealed that only aICH with patients receiving endovascular therapy (EVT) could increase the risk of mild poor prognosis (mRS ≥ 2) at 3 months. Conclusions Our results indicate that compared with patients without ICH, those who developed aICH during the acute stage of ischemic stroke had an increasing risk of worse outcome, especially in patients with endovascular therapy.

The ring finger protein 213 gene (RNF213) rs112735431 was significantly associated with intracranial artery stenosis/occlusion disease (ICASO) in Japan and Korea and to a lesser degree in China. We conducted a case–control study to examine the prevalence and correlates of the RNF213 rare variants in Chinese patients with symptomatic ICASO. A total of 503 cases including 390 ischemic stroke patients (ICASO-IS), 113 intracranial hemorrhage patients (ICASO-ICH) and 227 control subjects were recruited. The snapshot technique was used for RNF213 rare variants analysis, including rs112735431, rs148731719, rs37144111 and rs138130613. Moreover, a meta-analysis was performed to explore the relationship between RNF213 variants and ICASO in Asian. In our case–control study, we found that the rs138130613 variant was significantly associated with ICASO-IS (OR = 9.92, 95% CI 1.24–79.19, p = 0.03). The mean age of first ischemic stroke onset of variant carriers was earlier than the noncarriers (51.3 ± 18.0 versus 66.0 ± 12.9 years old, p = 0.02), but the conventional atherosclerotic risk factors and the characteristics of artery stenosis did not differ between them. In addition, the meta-analysis showed significant association between the rs112735431 polymorphism and the ICASO or ICASO-IS, and this variant was found more often in women and young-onset patients in Asia. This study suggests that the RNF213 rs112735431 and rs138130613 are genetic risk variants for ischemic stroke with intracranial artery stenosis/occlusion in China and rs112735431 is also associated with the high risk of ICASO in Asia. Further large-scale investigation of the RNF213 gene will provide new insights into pathogenetic mechanisms of symptomatic ICASO.

Background: Hypoxic preconditioning alters the biological properties of mesenchymal stem cells (MSCs). It is not known whether this process has an effect on circular RNAs (circRNAs) in MSCs.Methods: Human placental chorionic plate‐derived MSCs (hpcpMSCs) isolated from the same placentae were classed into two groups: hypoxic pretreated (hypoxia) group and normally cultured (normoxia) group. The comparative circRNA microarray analysis was used to determine circRNAs expression and verified by quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR) in the two groups.Results: One hundred and two differentially expressed circRNAs in the hypoxia group were found compared to that in the normoxia group (fold change >1.5‐fold and P < 0.05). The expression levels of circRNAs by qRT‐PCR were consistent with those evaluated by microarray analysis. Gene ontology (GO) analysis showed that the putative function of their target genes for those differentially expressed circRNAs was primarily involved in cell development and its differentiation and regulation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that transcriptional misregulation in cancer and mitogen‐activated protein kinase (MAPK) signaling pathway were the most significant. MAPK signaling pathway was found to be the core regulatory pathway triggered by hypoxia.Conclusions: The results indicate that the altered expression of specific circRNAs in MSCs is associated with hypoxic preconditioning. This finding provides further exploration of underlying mechanisms of the characteristic changes of MSCs with hypoxic preconditioning.

Inhibitors of cyclin-dependent kinases (Cdks) have been reported to have activities in many types of cancer cells by inhibiting Cdk7 and Cdk9, which control transcription. SNS-032 is a potent and selective inhibitor of Cdk2, Cdk7 and Cdk9 and has emerged in clinical trials. Here, we examined the viability of MCF-7 and MDA-MB-435 breast cancer cells in the presence of SNS-032 and observed a dose-dependent inhibition of cellular proliferation in both cell lines. SNS-032 had a direct apoptosis-inducing effect through both the extrinsic and intrinsic apoptotic pathways in breast cancer cells as shown by a dose-dependent increase in Annexin V-positive cells and terminal deoxynucleotidyl transferase-mediated dUTP nick?end labeling (TUNEL)-positive cells, as well as activation of caspase-8, -9 and poly(ADP-ribose) polymerase (PARP). At the molecular level, SNS-032 induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and blocked RNA synthesis. Consistent with the inherently rapid turnover rates of their transcripts and proteins, the anti-apoptotic proteins Mcl-1 and X-linked inhibitor of apoptosis protein (XIAP) were rapidly reduced on exposure to SNS-032. Our results also indicated that SNS-032 suppressed the growth of breast cancer xenografts in mice. These data demonstrate that the use of SNS-032 may be a rational and novel therapeutic strategy for human breast cancer and warrants further clinical investigation.