Moyamoya disease (MMD) is an idiopathic disease associated with recurrent stroke. However, the pathogenesis of MMD remains unknown. Therefore, we performed long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in blood samples from MMD patients (N = 15) and healthy controls (N = 10). A total of 880 differentially expressed lncRNAs (3649 probes) and 2624 differentially expressed mRNAs (2880 probes) were obtained from the microarrays of MMD patients and healthy controls (P < 0.05; Fold Change >2.0). Gene ontology (GO) and pathway analyses showed that upregulated mRNAs were enriched for inflammatory response, Toll-like receptor signaling pathway, chemokine signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway among others, while the downregulated mRNAs were enriched for neurological system process, digestion, drug metabolism, retinol metabolism and others. Our results showed that the integrated analysis of lncRNA-mRNA co-expression networks were linked to inflammatory response, Toll-like signaling pathway, cytokine-cytokine receptor interaction and MAPK signaling pathway. These findings may elucidate the pathogenesis of MMD, and the differentially expressed genes could provide clues to find key components in the MMD pathway.

Ischemic stroke impacts glymphatic function, but its role in prognosis remains unclear. This study evaluated glymphatic function in 146 participants, including non-stroke (healthy controls, n = 48; nonvascular cognitive impairment patients, n = 47) and ischemic stroke cohorts (n = 51). The bilateral diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index, choroid plexus (CP), and perivascular space (PVS) volume ratio, which represent the glymphatic system, were compared across two cohorts and between pre-rehabilitation (Time 1) and 30 days post-rehabilitation (Time 2). Post-stroke cognitive impairment (PSCI) was characterized as enduring cognitive deficits persisting six months after a stroke. Stroke patients exhibited significantly lower bilateral DTI-ALPS index compared with the non-stroke population (P < 0.05), while the infarct side showed post-rehabilitation improvement (P < 0.05). The DTI-ALPS index of infarct side at Time 1 did not predict poor outcome but was correlated with 6-month PSCI (P < 0.05). These results indicate that ischemic stroke diminishes glymphatic function, partially recovering post-rehabilitation, and suggest that the DTI-ALPS index could serve as a predictor for cognitive impairment following ischemic stroke.

Background and Objective: The combined effect of insulin resistance (IR) and total plasma homocysteine (tHcy) levels on the risk of mortality in nondiabetic populations has rarely been studied. We aimed to examine the association of tHcy levels and IR with the risk of mortality in nondiabetic populations. Methods: This observational cohort study was based on data from the Third National Health and Nutrition Examination Survey (NHANES III) database (1999–2002). A generalized additive model based on the Cox proportional hazards models was applied to estimate the relationship of tHcy levels with all-cause and cardiovascular disease (CVD) mortality. Smooth curve fitting was used to analyze their dose-dependent relationship. Results: During 5.7 years of follow-up, a total of 146 (5.8%) deaths occurred, including 65 deaths from CVD among 2053 individuals aged 40–80 years. In the multivariable adjusted model, every 1-μM increment of the tHcy level was associated with a 15% increase in risk of all-cause mortality and 20% increase in risk of CVD mortality among participants with IR (adjusted HR [95% CI]: 1.15 [1.06–1.24] and 1.20 [1.04–1.38]). However, among participants without IR, an increase of 1 μM in the tHcy level was associated with a 6% increase in risk of all-cause mortality and 3% increase in risk of CVD mortality (adjusted HR [95% CI]: 1.06 [1.00–1.13] and 1.03 [0.92–1.16]). Conclusions: Homocysteine levels were associated with higher risk of all-cause and CVD mortality among individuals with IR than among those without IR in a nondiabetic population aged 40–80 years.

Background: This study aims to identify ocular fundus blood flow biomarkers, using swept-source optical coherence tomography angiography (SS-OCTA), that reflect choroid plexus (CP) changes in patients with white matter hyperintensities (WMHs). Design: This is a retrospective analysis based on prospective data. Methods: The study was an analysis of collected data from patients with WHMs who underwent multimodal magnetic resonance imaging (MRI) and SS-OCTA (FRESH-CSVD study, NCT06431711). Automatic segmentation was used to calculate the volumes of CP and WMHs. The bilateral CP asymmetry index was defined as the value of the difference in volume between the right and left CP, divided by the volume of the left CP. The association between SS-OCTA parameters, CP volume and its asymmetry index, and WMH volume (WMH-V) was analyzed using a LASSO-derived logistic regression model, with mediation analysis to explore their connections. Results: The study included 240 eyes from 137 patients. A significant correlation was found between the bilateral CP asymmetry index and WMH-V (β = −6.03, 95% CI: −11.36 to −0.70, p = 0.027). WMH-V was correlated with the optic nerve head choriocapillaris perfusion area (ONH CC PA) (β = −2.95, 95% CI: −5.62 to −0.28, p = 0.031). The bilateral CP asymmetry index was also related to ONH CC PA (β = 0.07, 95% CI: 0.01 to 0.13, p = 0.027). Mediation analysis showed that WMH-V mediated 15.11% of the association between the bilateral CP asymmetry index and ONH CC PA ( p = 0.036), but this mediation effect disappeared after adjusting for age. Conclusion: These findings suggest that the morphological changes of the CP have a significant impact on the ONH blood flow in patients with WMHs. The ONH CC PA shows potential as a biomarker for detecting morphological changes of CP among WMHs patients.

Hyperhomocysteinaemia (HHcy) is associated with all-cause mortality in some disease states. However, the correlation between HHcy and the risk of mortality in the general population has rarely been researched. We aimed to evaluate the association between HHcy and all-cause and cause-specific mortality among adults in the USA. This study analysed data from the National Health and Nutrition Examination Survey database (1999–2002 survey cycle). A multivariable Cox regression model was built to evaluate the correlation between HHcy and all-cause and cause-specific mortality. Smooth curve fitting was used to analyse their dose-dependent relationship. A total of 8442 adults aged 18–70 years were included in this study. After a median follow-up period of 14·7 years, 1007 (11·9 %) deaths occurred including 197 CVD-related deaths, 255 cancer-related deaths and fifty-eight respiratory disease deaths. The participants with HHcy had a 93 % increased risk of all-cause mortality (hazard ratio (HR) 1·93; 95 % CI (1·48, 2·51)), 160 % increased risk of CVD mortality (HR 2·60; 95 % CI (1·52, 4·45)) and 82 % increased risk of cancer mortality (HR 1·82; 95 % CI (1·03, 3·21)) compared with those without HHcy. For unmeasured confounding, E-value analysis proved to be robust. In conclusion, HHcy was associated with high risk of all-cause and cause-specific (CVD, cancer) mortality among adults aged below 70 years.