Search

IntroductionInsomnia, a common clinical disorder, significantly impacts the physical and mental well-being of patients. Currently, available hypnotic medications are unsatisfactory due to adverse reactions and dependency, necessitating the identification of new drug targets for the treatment of insomnia.MethodsIn this study, we utilized 734 plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis, with insomnia as the outcome variable, to identify potential drug targets for insomnia. Additionally, we validated our results externally using other datasets. Sensitivity analyses entailed reverse Mendelian randomization analysis, Bayesian co-localization analysis, and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets.ResultsMendelian randomization analysis indicated that elevated levels of TGFBI (OR = 1.01; 95% CI, 1.01–1.02) and PAM ((OR = 1.01; 95% CI, 1.01–1.02) in plasma are associated with an increased risk of insomnia, with external validation supporting these findings. Moreover, there was no evidence of reverse causality for these two proteins. Co-localization analysis confirmed that PAM (coloc.abf-PPH4 = 0.823) shared the same variant with insomnia, further substantiating its potential role as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of insomnia.ConclusionOverall, our findings suggested that elevated plasma levels of TGFBI and PAM are connected with an increased risk of insomnia and might be promising therapeutic targets, particularly PAM. However, further exploration is necessary to fully understand the underlying mechanisms involved.

BackgroundThe optimal type of anesthesia for acute vertebrobasilar artery occlusion (VBAO) remains controversial. We aimed to assess the influence of anesthetic management on the outcomes in VBAO patients received endovascular treatment (EVT).MethodsPatients underwent EVT for acute VBAO at 21 stroke centers in China were retrospectively enrolled and compared between the general anesthesia (GA) group and non-GA group. The primary outcome was the favorable outcome, defined as a modified Rankin Scale (mRS) score 0–3 at 90 days. Secondary outcomes included functional independence (90-day mRS score 0–2), and the rate of successful reperfusion. The safety outcomes included all-cause mortality at 90 days, the occurrence of any procedural complication, and the rate of symptomatic intracranial hemorrhage (sICH). In addition, we performed analyses of the outcomes in subgroups that were defined by Glasgow Coma Scale (GCS) score (≤8 or >8).ResultsIn the propensity score matched cohort, there were no difference in the primary outcome, secondary outcomes and safety outcomes between the two groups. Among patients with a GCS score of 8 or less, the proportion of successful reperfusion was significantly higher in the GA group than the non-GA group (aOR, 3.57, 95% CI 1.06–12.50, p = 0.04). In the inverse probability of treatment weighting-propensity score-adjusted cohort, similar results were found.ConclusionsPatients placed under GA during EVT for VBAO appear to be as effective and safe as non-GA. Furthermore, GA might yield better successful reperfusion for worse presenting GCS score (≤8).RegistrationURL: http://www.chictr.org.cn/; Unique identifier: ChiCTR2000033211.

BackgroundRestless Legs Syndrome (RLS) is a common neurological disorder. Growing evidence shows that dopaminergic dysfunction and iron deficiency are associated with the pathogenesis of RLS. Additionally, the dopaminergic system is linked with the hypothalamic-pituitary-thyroid (HPT) axis. Thus, the current study aimed to compare thyroid function between RLS patients and healthy subjects and investigate the associations with clinical characteristics of RLS.MethodsSerum levels of thyroid hormones were investigated in 102 first-episode drug-naïve RLS patients and 80 matched healthy controls (HCs). Baseline data and clinical characteristics were performed by professional personnel. In addition, multivariate regression was used to analyze the relationship between thyroid function and RLS.ResultsCompared with control group, RLS patients had significantly higher serum thyroid-stimulating hormone (TSH) levels (p < 0.001), and higher prevalence of subclinical hypothyroidism [Odds ratio (OR) 8.00; 95% confidence interval (CI) = 3.50–18.30; p < 0.001]. The Subclinical hypothyroidism rate (47.1 vs. 10%, p < 0.001) in RLS patients was higher than the HCs group. Regression analysis revealed that serum TSH (OR = 1.77; 95% CI = 1.41–2.23; p < 0.001) was independently associated with RLS. There was a statistically significant positive correlation between TSH and the Pittsburgh sleep quality index (PSQI) scores (r = 0.728, p < 0.001), and the International Restless Legs Scales (IRLS) points (r = 0.627, p < 0.001). Spearman correlation analysis showed that FT3 was positive correlated with HAMA14 score (r = 0.239, p = 0.015). In addition, compared with the good-sleeper group, poor-sleeper patients had significantly higher serum TSH levels (p < 0.001).ConclusionSerum levels of TSH and the prevalence of subclinical hypothyroidism were higher in RLS patients, indicating the imbalance between thyroid hormones (TH) and the dopaminergic system may contribute to the development of primary RLS. Additionally, the TH axis may influence the quality of sleep in RLS patients.

BackgroundRestless Legs Syndrome (RLS) is a common sleep disorder. Polysomnographic (PSG) studies have been used to explore the night sleep characteristics of RLS, but their relationship with RLS has not been fully analyzed and researched.MethodsWe searched the Cochrane Library electronic literature, PubMed, and EMBASE databases to identify research literature comparing the differences in polysomnography between patients with RLS and healthy controls (HCs).ResultsThis review identified 26 studies for meta-analysis. Our research found that the rapid eye movement sleep (REM)%, sleep efficiency (SE)%, total sleep time (TST) min, and N2 were significantly decreased in patients with RLS compared with HCs, while sleep latency (SL) min, stage shifts (SS), awakenings number (AWN), wake time after sleep onset (WASO) min, N1%, rapid eye movement sleep latency (REML), and arousal index (AI) were significantly increased. Additionally, there was no significant difference among N3%, slow wave sleep (SWS)%, and apnea-hypopnea index (AHI).ConclusionOur findings demonstrated that architecture and sleep continuity had been disturbed in patients with RLS, which further illustrates the changes in sleep structure in patients with RLS. In addition, further attention to the underlying pathophysiological mechanisms of RLS and its association with neurodegenerative diseases is needed in future studies.

BackgroundThe study aims to investigate the role of serum albumin (ALB) and creatinine (CRE), bilirubin (BIL), and uric acid (UA) as major intravascular antioxidants in migraine.MethodsWe enrolled 148 patients with migraine and 150 age- and sex-matched healthy controls. The serum levels of ALB, TBIL, CRE, and UA were measured in patients with migraine of different subtypes. The risk of migraine was assessed by multiple stepwise logistic regression analysis.ResultsThe serum levels of ALB, total BIL (TBIL), CRE, and UA were significantly lower in the migraine group than in the HC group (p < 0.05). The ALB and UA levels were lower during migraine attack periods (p < 0.05). There were no statistically significant differences observed in serum ALB, TBIL, CRE, and UA levels between aura/without aura and episodic/chronic migraine subtypes (p > 0.05). The multiple stepwise logistic regression revealed that ALB [odds ratio (OR) 0.79, 95% confidence interval (CI) 0.69–0.89, p < 0.001], TBIL (OR 0.61, 95% CI 0.5–0.75, p < 0.001), and UA (OR 0.97, 95% CI 0.96–0.99, p = 0.014) were independently associated with migraine. In addition, the serum levels of ALB, TBIL, and UA were significantly lower in the migraine group when compared by sex.ConclusionThe serum levels of UA, TBIL, ALB, and CRE were lower in the patients with migraine, indicating a lower antioxidant status. In addition, ALB, TBIL, and UA were independently related to migraine. These results could provide insights into the possible role of oxidative stress in the pathogenesis of migraine.

ObjectiveThis study aimed to investigate whether thyroid function profiles are associated with post-stroke depression (PSD) and evaluate the mediation effect of cerebral small vessel disease (cSVD) on the association of thyroid function profiles and PSD in patients with acute ischemic lacunar stroke.MethodsIn this study, 372 patients with confirmed acute ischemic lacunar stroke within 3 days of onset were consecutively recruited. Serum levels of thyroid hormones and thyroid antibodies were detected on admission. Lacunar infarcts, white matter lesions, cerebral microbleeds, and enlarged perivascular spaces were rated using validated scales. The severity of depression was scored with the 24-item Hamilton Depression Scale in the hospital after a week of stroke onset. Multivariate regression was utilized to analyze the association of thyroid function profiles and PSD. Mediation analysis was employed to evaluate the effect of cSVD on the association of thyroid function profiles and PSD.ResultsA total of 87 (23.4%) participants were diagnosed with depression after stroke. Serum thyroid-stimulating hormone (TSH) levels were significantly higher in patients with PSD than in those without PSD, while free triiodothyronine (FT3) and free thyroxine (FT4) were not significantly different between the two groups. After adjusting for potential confounders, serum TSH levels were positively associated with the risk of PSD (OR = 1.228; 95% CI: 1.053–1.431, p = 0.009). A similar association was also found between the total cSVD burden score and PSD (OR = 2.137; 95% CI: 1.634–2.793, p < 0.001). Further mediation analysis indicated that 26.37% of the association between TSH and PSD was mediated by cSVD.ConclusionsSerum TSH levels on admission can probably predict depression after acute ischemic lacunar stroke.

BackgroundPoststroke fatigue (PSF) is a dynamic process over time. Current evidence for interventions for PSF is limited. Our study investigated the effects of selective serotonin reuptake inhibitors (SSRIs) on the time course of PSF.MethodsThe patients with acute ischaemic stroke were enrolled in this study. All patients were scored with the Fatigue Severity Scale (FSS) at baseline and 6, 12, and 24 months after the index stroke. The time course of PSF was classified as non-PSF, incident PSF, recovered PSF and persistent PSF according to the PSF status at baseline and the 24-month follow-up. Multivariate logistic regression analysis and generalized mixed model were applied to explore the relationships between SSRIs and the time course of PSF.ResultsEight hundred forty-seven patients were analyzed in this study. No significant association between SSRIs and the time course of PSF was observed in all patients (p = 0.076). The subgroup analyses indicated that SSRI antidepressants reduced the risk of incident PSF [Odds Ratio (OR) 0.23; 95% confidence interval (CI) 0.05–0.96, p = 0.044] and persistent PSF (OR 0.28; 95% CI 0.09–0.90, p = 0.033) in the PSD subgroup, but not in the non-PSD group. In the longitudinal analysis, generalized logistical mixed-effect models indicated that early administration of SSRIs reduced the risk (OR 0.955; 95% CI 0.928–0.984, p = 0.002) and severity (β = −0.018, p = 0.041) of PSF in the PSD subgroup.ConclusionNo relationship was identified between the use of SSRIs and the time course of PSF in all patients. However, these drugs might be effective in PSF patients with depression.

Objective: The objective of this study was to evaluate the effect of blood pressure (BP) management with transcranial Doppler (TCD) guidance in patients with large-vessel occlusion in the anterior circulation after endovascular thrombectomy (EVT) on the long-term prognosis.Methods: This was a prospective study; 232 patients were nonrandomized assigned to TCD-guided BP management (TBM) group or non-TCD-guided BP management (NBM) group. In the TBM group, BP was controlled according to TCD showing cerebral blood flow fluctuation. In the NBM group, BP was controlled according to the guidelines. The primary endpoint was a modified Rankin scale (mRS) score of 2 or lower at 90 days. The safety outcomes were the rates of symptomatic or any intracerebral hemorrhage (ICH) and mortality at 90 days.Results: One hundred sixty-three patients were assigned to the TBM group, and 69 were assigned to the NBM group. In the propensity score-matched cohort (65 matches in both groups), there was significant difference in the proportion of participants with mRS 0–2 at 90 days according to BP management (adjusted odds ratio 3.34, 95% CI 1.36 to 8.22). There was no difference in the rates of symptomatic or any ICH and mortality between two groups. In inverse probability-weighted regression adjustment analysis, mortality decreased significantly in the TBM group than in the NBM group (adjusted odds ratio 0.86, 95% CI 0.76–0.99, p = 0.03).Conclusion: In patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation, BP management under TCD was superior to NBM in improving the clinical outcomes at 90 days.Clinical Trial Registration: (URL: https://www.chictr.org.cn/showproj.aspx?proj=55484; Identifier: ChiCTR2000034443.