Profile of Chinese Cluster Headache Register Individual Study (CHRIS): Clinical characteristics, diagnosis and treatment status data of 816 patients in China.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

Effect of erenumab on the reversion from chronic migraine to episodic migraine in an Asian population: A post hoc analysis of the DRAGON study.

BACKGROUND: Erenumab is a fully human monoclonal antibody that selectively targets the calcitonin gene-related peptide receptor. It has been proven to be safe and efficacious in patients with episodic migraine (EM) and chronic migraine (CM) as demonstrated in phase 2 and 3 clinical trials including patients from Europe, Japan, and the United States. Reversion from CM to EM, as indicated by a reduction in the frequency of headache days, is an important indicator for efficacy outcome, though it has not been analyzed widely in patients with CM to date. OBJECTIVE: Primary results of the DRAGON study demonstrated the efficacy and safety of erenumab in patients with CM from China and other Asian countries. This post hoc analysis evaluated the rate of reversion from CM to EM in the overall population and in subgroups of patients defined by baseline demographic and clinical characteristics (age, body mass index, gender, prior preventive treatment failure, medication overuse status, and disease duration). METHODS: Reversion from CM to EM was defined as a reduction in headache frequency to < 45 headache days over the 12 weeks of the double-blind treatment period. In addition, migraine-related disability and disease impact on functional impairment were assessed within each treatment group in reverters and non-reverters using the Headache Impact Test-6 (HIT-6), Migraine Physical Function Impact Diary (MPFID), and modified Migraine Disability Assessment (mMIDAS). RESULTS: Overall, 557 patients with CM were randomized to monthly erenumab 70 mg (n = 279) or placebo (n = 278), of whom 52.3% (146 of 279) treated with erenumab reverted from CM to EM compared to 41.0% (114 of 278) in the placebo group (odds ratio [OR] 1.59, 95% confidence interval: 1.1-2.2; p = 0.007). Treatment with erenumab resulted in a greater mean change (standard error) from baseline in the HIT-6 total score for reverters versus non-reverters compared to placebo (erenumab: -9.5 [0.6] vs. -5.1 [0.5]; placebo: -8.9 [0.7] vs. -4.9 [0.5]). A similar pattern was observed for mMIDAS score in erenumab treatment groups versus placebo (erenumab: -22.1 [1.2] vs. -6.3 [1.8]; placebo: -19.9 [1.3] vs. -7.9 [1.6]). Substantial improvements were reported in MPFID-Physical Impairment (PI) and Everyday Activities (EA) scores in reverters versus non-reverters in erenumab treatment groups (MPFID-PI: -5.9 [0.3] vs. -1.9 [0.6]; MPFID-EA: -7.9 [0.4] vs. -3.4 [0.6]) and in placebo (MPFID-PI: -5.4 [0.4] vs. -1.0 [0.5]; MPFID-EA: -7.1 [0.5] vs. -3.2 [0.5]). CONCLUSIONS: This analysis demonstrated that a greater proportion of patients treated with erenumab reverted from CM to EM compared to patients treated with placebo. The reversion from CM to EM was reflected by the greater improvements in patient-reported outcomes in the erenumab group.

Serum uric acid predicts the development of atherosclerosis in women but not in men: A ten-year cohort study in China.

BACKGROUND AND AIM: Atherosclerosis is becoming a significant health burden. Serum uric acid (SUA) is the final enzymatic product of purine metabolism and can contribute to the development of atherosclerosis. The aim of this study was to explore the possible predictive value of SUA in the development of atherosclerosis in a healthy Chinese population. METHODS AND RESULTS: In this study, a total of 11,222 healthy subjects with no carotid plaque at baseline were enrolled and divided into sex-specific groups, and then the occurrence of carotid plaque during the follow-up time was documented. The association between carotid plaque and SUA levels was examined using Cox proportional-hazards regression models. The mean SUA level was 5.35 ± 1.41 mg/dL. A total of 2,911 individuals (25.94%) developed carotid plaque during the follow-up time, including 1,071 females and 1,840 males. After adjusting for potential confounding factors, the hazard ratio (HR) and 95% confidence interval (95% CI) in women for the occurrence of carotid plaque associated with SUA levels were 1.163 (1.017-1.330), but no significant correlation was found in men, as the HR was 1.050 (0.965-1.143). CONCLUSION: Our results indicate that SUA levels predict the development of carotid plaque independent of traditional risk factors only in women.

Differences in intracranial atherosclerosis plaque between posterior circulation and anterior circulation on high-resolution magnetic resonance imaging: A systematic review and meta-analysis.

OBJECTIVE: The clinical characteristics and mechanisms of stroke caused by anterior circulation atherosclerotic plaques (ACAPs) and posterior circulation atherosclerotic plaques (PCAPs) are distinct. We aimed to compare the differences in vulnerability, morphology, and distribution between ACAPs and PCAPs based on hign-resolution magnetic resonance imaging (HR-MRI). MATERIALS AND METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang database were retrieved from inception through May 2023. Meta-analysis was performed by R 4.2.1 software. The quality of the literature was assessed by the Agency for Healthcare Research and Quality (AHRQ). Subgroup analysis was conducted to explore the heterogeneity of the pooled results. RESULTS: There were a total of 13 articles, including 1194 ACAPs and 1037 PCAPs. The pooled estimates demonstrated that the incidence of intraplaque hemorrhage in the PCAPs was higher (OR 1.72, 95%CI 1.35-2.18). The plaque length (SMD 0.23, 95%CI 0.06-0.39) and remodeling index (SMD 0.29, 95%CI 0.14-0.44) of PCAPs were larger than those in ACAPs. However, there were no evident differences in significant enhancement or stenosis degree between the two groups. CONCLUSION: There were more unstable features in PCAPs, highlighting an elevated risk of recurrent ischemic stroke in the posterior circulation. Furthermore, PCAPs were prone to developing penetrating artery disease due to their wider distribution. Nevertheless, posterior circulation arteries exhibited a greater propensity for outward remodeling, which may lead treatment team to miss the optimal intervention stage by being overlooked on angiographic detection.

Predictive value of transesophageal echocardiography combined with contrast transthoracic echocardiography for embolic stroke of undetermined source.

OBJECTIVE: In this study, we aimed to assess the predictive value of transesophageal echocardiography (TEE) combined with contrast transthoracic echocardiography (cTTE) for embolic stroke of undetermined source (ESUS). METHODS: A total of 52 patients with ESUS were examined by TEE and cTTE. The detection rate of patent foramen ovale (PFO) and right-to-left shunt (RLS) grade were compared in patients with ESUS between cTTE alone and cTTE combined with TEE. The Risk of Paradoxical Embolism (RoPE) score, PFO diameter, and PFO length of patients with PFO-associated ESUS and non-PFO-associated ESUS were compared by cTTE alone and cTTE combined with TEE. The receiver operating characteristic (ROC) curve was utilized to determine the effect of RoPE score and PFO diameter on patients with PFO-associated ESUS. RESULTS: The positive rate of PFO detected by cTTE alone (46.15%) was lower than that detected by cTTE combined with TEE (69.23%). The proportion of patients with RLS grade I + II + III detected by cTTE combined with TEE (69.23%) was higher than that detected by cTTE alone (46.15%). Both the RoPE score and PFO diameter were significantly greater in the patients with PFO-associated ESUS than in the patients with non-PFO-associated ESUS (p < .05). The combination of RoPE score and PFO diameter had the largest area under the ROC curve (AUC = 0.875), which was larger than the AUC alone of RoPE score (AUC = 0.819) and PFO diameter (AUC = 0.783) (p < .05). CONCLUSION: The combination of cTTE and TEE is helpful to the diagnosis of ESUS patients caused by PFO and to judge the degree of RLS.

Verification of a clinical decision support system for the diagnosis of headache disorders based on patient-computer interactions: a multi-center study.

BACKGROUND: Although headache disorders are common, the current diagnostic approach is unsatisfactory. Previously, we designed a guideline-based clinical decision support system (CDSS 1.0) for diagnosing headache disorders. However, the system requires doctors to enter electronic information, which may limit widespread use. METHODS: In this study, we developed the updated CDSS 2.0, which handles clinical information acquisition via human-computer conversations conducted on personal mobile devices in an outpatient setting. We tested CDSS 2.0 at headache clinics in 16 hospitals in 14 provinces of China. RESULTS: Of the 653 patients recruited, 18.68% (122/652) were suspected by specialists to have secondary headaches. According to "red-flag" responses, all these participants were warned of potential secondary risks by CDSS 2.0. For the remaining 531 patients, we compared the diagnostic accuracy of assessments made using only electronic data firstly. In Comparison A, the system correctly recognized 115/129 (89.15%) cases of migraine without aura (MO), 32/32 (100%) cases of migraine with aura (MA), 10/10 (100%) cases of chronic migraine (CM), 77/95 (81.05%) cases of probable migraine (PM), 11/11 (100%) cases of infrequent episodic tension-type headache (iETTH), 36/45 (80.00%) cases of frequent episodic tension-type headache (fETTH), 23/25 (92.00%) cases of chronic tension-type headache (CTTH), 53/60 (88.33%) cases of probable tension-type headache (PTTH), 8/9 (88.89%) cases of cluster headache (CH), 5/5 (100%) cases of new daily persistent headache (NDPH), and 28/29 (96.55%) cases of medication overuse headache (MOH). In Comparison B, after combining outpatient medical records, the correct recognition rates of MO (76.03%), MA (96.15%), CM (90%), PM (75.29%), iETTH (88.89%), fETTH (72.73%), CTTH (95.65%), PTTH (79.66%), CH (77.78%), NDPH (80%), and MOH (84.85%) were still satisfactory. A patient satisfaction survey indicated that the conversational questionnaire was very well accepted, with high levels of satisfaction reported by 852 patients. CONCLUSIONS: The CDSS 2.0 achieved high diagnostic accuracy for most primary and some secondary headaches. Human-computer conversation data were well integrated into the diagnostic process, and the system was well accepted by patients. The follow-up process and doctor-client interactions will be future areas of research for the development of CDSS for headaches.

A phase 3, randomised, placebo-controlled study of erenumab for the prevention of chronic migraine in patients from Asia: the DRAGON study.

ABSTACT: BACKGROUND: DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. METHODS: DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18-65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. RESULTS: At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was - 8.2 days for erenumab and - 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: - 1.57 [95%CI: - 2.83, - 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (- 5.34 vs - 4.66) and mMIDAS scores (- 14.67 vs - 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). CONCLUSION: DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. TRIAL REGISTRATION: NCT03867201.

Use of the A2DS2 scale to predict morbidity in stroke-associated pneumonia: a systematic review and meta-analysis.

BACKGROUND: This review aims to evaluate the performance and clinical applicability of the A2DS2 scale via systematic review and meta-analysis. METHODS: The Medline, Embase, Cochrane Library, CBM, CNKI, and Wanfang databases were searched. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Funnel plots and Egger's test were used to evaluate publication bias. The bivariate random-effect model was used for calculating the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC). A Fagan nomogram was applied to evaluate the clinical applicability of the A2DS2 scale. RESULTS: A total of 29 full-text articles met the inclusion criteria, including 19,056 patients. Bivariate mixed-effects regression models yielded a mean sensitivity of 0.78 (95 % CI: 0.73-0.83), a specificity of 0.79 (95 % CI: 0.73-0.84), a positive likelihood ratio of 3.7 (95 % CI: 2.9-4.6), and a negative likelihood ratio of 0.27 (95 % CI: 0.23-0.33). The area under the receiver operating characteristic curve was 0.85 (95 % CI: 0.82-0.88). If given a pre-test probability of 50 %, the Fagan nomogram showed that when A2DS2 was positive, the post-test probability improved to 79 %. In contrast, when A2DS2 was negative, it decreased to 22 %. The results of the subgroup analysis showed no effect on the diagnostic accuracy of the A2DS2 scale in predicting stroke-associated pneumonia, except for the optimal cut-off value. CONCLUSIONS: The A2DS2 scale demonstrates high clinical applicability and could be a valid scale for the early prediction of stroke-associated pneumonia in stroke patients.

Role of liraglutide in brain repair promotion through Sirt1-mediated mitochondrial improvement in stroke.

Brain repair, especially axonal sprouting, is critical to restore motor function in disabled stroke patients. Liraglutide (LG) is a new kind of long-acting analogue of glucagon-like peptide-1 (GLP-1) and has potential protective effects in stroke. The mitochondria participate in brain repair after cerebral injury. However, the mechanism of the effect of LG on brain repair and its potential influence on mitochondria in stroke remains obscure. Here, in focal cerebral cortical ischemic mice model, LG improved the motor functional recovery and promoted axonal sprouting by restoring the activities of isocitrate dehydrogenase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Moreover, LG remarkably increased the cell survival rate and revived the NeuN and GAP-43 levels in cortical neurons under hydrogen peroxide (H2 O2 ) exposure. It was also observed that LG reduced the generation of reactive oxygen species, stabilized the mitochondrial membrane potential, enhanced the levels of adenosine triphosphate, enhanced activities of mitochondrial complex-I, and decreased protein expression levels of fission-1 in H2 O2 -injured cortical neurons. Additionally, LG suppressed the expressions of sirtuin 1 (Sirt1) in cortical neurons exposed to H2 O2 . Furthermore, knockdown of Sirt1 by short interfering RNA facilitated the LG-mediated mitochondrial protection in cortical neurons under H2 O2 . Collectively, this data from the present study illustrated that LG exerted a promoting influence on brain repair, after cerebral ischemic injury, through Sirt1-mediated mitochondrial improvement.

Liraglutide Protects Neurite Outgrowth of Cortical Neurons Under Oxidative Stress though Activating the Wnt Pathway.

BACKGROUND: Neurogenesis including neurite outgrowth is important for brain plasticity under physiological conditions and in brain repair after injury. Liraglutide has been found to have neuroprotective action in the risk of central nervous system disease. However, the effect and the potential mechanism of liraglutide-induced neurite outgrowth in primary cortical neurons under oxidative stress remain poorly documented. METHODS: In the text, H2O2 was used to mimic ischemia injury in primary cortical neurons. The viability and apoptosis of cell was assessed by Cell Counting Kit-8 and Hoechst 33342. Immunofluorescence method was used to examine the effect of liraglutide on neurite outgrowth in cortical neuron under H2O2 condition. Then, the potential mechanisms involving the Wnt pathway were investigated. The expression of ß-catenin, c-myc, and cyclin D1 was determined using quantitative real-time polymerase chain reaction and Western blot. RESULTS: Liraglutide significantly increased the viability and alleviated the apoptosis rate of cortical neurons induced by H2O2. Next, liraglutide promoted neurite outgrowth, which could be partially inhibited by the Wnt pathway inhibitor Xav939. Besides, liraglutide induced an increase of ß-catenin, c-myc, and cyclin D1 levels, which could also be blocked in the presence of Xav939. CONCLUSIONS: These results illustrate that liraglutide exerts neurotrophin-like activity in cortical neurons under oxidative stress condition, partly through activating the Wnt pathway.

Cognitive Function and Prognosis of Multimodal Neuroimage-Guided Thrombectomy on Mild to Moderate Anterior Circulation Infarction Patients with Broadened Therapeutic Window: A Prospective Study.

BACKGROUND AND OBJECTIVES: Endovascular mechanical thrombectomy is an important approach for acute ischemic stroke (AIS) treatment. Multimodal neuroimaging methods ideally provide the exact localization, extent, and metabolic activity of target tissues. Post-stroke cognitive impairment has recently been realized to be another major concern except for neurological function impairment. The aim of our study was to carry out a prospective study to compare neurological and cognitive functions after thrombectomy in mild to moderate anterior circulation infarction patients selected by multimodal neuroimaging. METHODS: Ninety patients were recruited from January 2016 to March 2017 consecutively. Neurological function was assessed by NIHSS before thrombectomy, and 6 h, 24 h, 7 days, 90 days after mechanical thrombectomy. Cognitive functions were evaluated by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Hachinski Ischemic Scale. RESULTS: Patients who received mechanical thrombectomy had significantly better neurological functions at 6 h (p < 0.001), 24 h (p < 0.001), 7 days (p < 0.001), and 90 days (p < 0.001), as well as cognitive functions evaluated by MoCA (26.23 ± 3.85 vs. 24.62 ± 2.25, p = 0.022, n = 85) and MMSE (26.65 ± 2.77 vs. 25.10 ± 2.36, p = 0.023, n = 85) compared to the standard therapy group. CONCLUSIONS: The current prospective study demonstrated that mechanical thrombectomy can significantly improve neurological and cognitive functions in patients with mild to moderate AIS at broadened therapeutic window under multimodal CT and multimodal MRI imaging.

The prevalence of primary headache disorders and their associated factors among nursing staff in North China.

BACKGROUND: Epidemiological data on the prevalence of headache in nursing staff in Mainland China are lacking. We therefore performed a study to assess the prevalence of headache, and factors associated with headaches, in nursing staff in three hospitals in North China. METHODS: Stratified random cluster sampling was used to select 1102 nurses from various departments in three hospitals. A structured questionnaire was used to collect epidemiological data, headache characteristics and associated factors. RESULTS: The response rate was 93.0%. Among nursing staff, the 1-year prevalence of primary headache disorders was 45.3%, of migraine 14.8% (migraine with aura 3.4%, migraine without aura 11.4%), of tension-type headache (TTH) 26.2%, of chronic daily headache (CDH) 2.7%. Multivariate analysis showed that seniority (≥5 years) was a risk factor for migraine (OR 2.280), obesity (BMI ≥ 25) was a risk factor for TTH and CDH (OR 1.684 and 3.184), and age (≥40 years) was a risk factor for CDH (OR 8.455). Nurses working in internal medicine were more likely to suffer CDH than those in other departments. Working a greater number of night shifts was also associated with increased prevalence of headache. CONCLUSION: The prevalence of primary headache disorders in nurses is higher than that in the general population in China, and occupational factors may play an important role. Therefore, the prevalence of headache in nurses should be a focus of attention, and coping strategies should be provided. Such measures could contribute to improving patient care.

Comorbidity of poor sleep and primary headaches among nursing staff in north China.

BACKGROUND: Sleep disorders and primary headaches are both more prevalent among nursing staff than in the general population. However, there have been no reports about the comorbidity of poor sleep and primary headaches among nursing staff. METHODS: Stratified random cluster sampling was used to select 1102 nurses from various departments in three hospitals in north China. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI). The diagnosis of primary headaches including migraine, tension-type headache (TTH), and chronic daily headache (CDH) was based on the International Classification of Headache Disorders, 3rd edition (beta version) (ICHD-3-beta). RESULTS: The response rate was 93 %. Among 1023 nurses, the prevalence of poor sleep was 56.7 %. Of these, 315 nurses (34.13 %) had poor sleep comorbid with primary headaches. The prevalence of poor sleep in the groups with CDH (82.1 %), migraine (78.9 %), and TTH (59.0 %) was significantly higher than that in the group without headaches (47.3 %) (all P < 0.05). Multivariate logistic regression revealed that rotating shifts and suffering headache were independent risk factors for poor sleep. Also, the 1-year prevalence of the three types of primary headache was significantly increased in the poor sleep group (migraine: 21.2 % vs. 7.2 %; TTH: 27.9 % vs. 24.9 %; CDH: 4.1 % vs. 1.1 %; P < 0.05). Compared with normal sleepers, nurses with poor sleep were 1.72 times more likely to have severe headache (OR: 1.72, 95 % CI: 1.14-2.57). CONCLUSION: Comorbidity of poor sleep and primary headaches among nursing staff is common. Therefore, sleep quality should be carefully evaluated in nurses with primary headaches.

Telomere length exhibits inverse association with migraine among Americans aged 20-50 years, without implications beyond age 50: a cross-sectional study.

Migraine, common in individuals under 50 years, is linked to oxidative stress. The association between telomere length shortening and migraine, along with potential age-related influences, has not been comprehensively studied. This cross-sectional study included data from 6169 participants in the National Health and Nutrition Survey (NHANES) from 1999 to 2002, encompassing information on peripheral blood leukocyte telomere length, severe headache or migraine, and potential confounders. Stratifying by age (20-50 years, > 50 years), we employed multivariable logistic regression, restricted cubic splines and interaction test to investigate age-influenced telomere length in relation to migraine. In participants aged 20-50 years, the odds ratio (OR) for migraine in the shortest telomere length group T1 (0.39-0.89) was 1.35 (95% confidence interval [95% CI] 1.01, 1.79) compared to the longest group T3 (1.10-9.42), whereas in those aged > 50 years, the OR of T1 was 0.93 (95% CI 0.60, 1.43). Additionally, telomere length and age interacted in the development of migraine (p for interaction: 0.010). In individuals aged 20-50, an L-shaped relationship was found between telomere length and migraine, with an inflection point at 1.02T/S ratio. The OR was 9.34 (95% CI 1.56, 55.99) for telomere lengths < 1.02T/S ratio. These findings suggest age influences the association between telomere length and migraine in U.S. adults.

Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.

Endothelial cell (EC) dysfunction is associated with atherosclerosis. Circular RNAs (circRNAs) are covalently closed loops formed by back-splicing, are highly expressed in a tissue-specific or cell-specific manner, and regulate ECs mainly through miRNAs (mircoRNAs) or protein sponges. This review describes the regulatory mechanisms and physiological functions of circRNAs, as well as the differential expression of circRNAs in aberrant ECs. This review focuses on their roles in inflammation, proliferation, migration, angiogenesis, apoptosis, senescence, and autophagy in ECs from the perspective of signaling pathways, such as nuclear factor κB (NF-κB), nucleotide-binding domain, leucine-rich-repeat family, pyrin-domain-containing 3 (NLRP3)/caspase-1, Janus kinase/signal transducer and activator of transcription (JAK/STAT), and phosphoinositide-3 kinase/protein kinase B (PI3K/Akt). Finally, we address the issues and recent advances in circRNAs as well as circRNA-mediated regulation of ECs to improve our understanding of the molecular mechanisms underlying the progression of atherosclerosis and provide a reference for studies on circRNAs that regulate EC dysfunction and thus affect atherosclerosis.

ß-hydroxybutyrate and ischemic stroke: roles and mechanisms.

Stroke is a significant global burden, causing extensive morbidity and mortality. In metabolic states where glucose is limited, ketone bodies, predominantly ß-hydroxybutyrate (BHB), act as alternative fuel sources. Elevated levels of BHB have been found in the ischemic hemispheres of animal models of stroke, supporting its role in the pathophysiology of cerebral ischemia. Clinically, higher serum and urinary BHB concentrations have been associated with adverse outcomes in ischemic stroke, highlighting its potential utility as a prognostic biomarker. In both animal and cellular models, exogenous BHB administration has exhibited neuroprotective effects, reduction of infarct size, and improvement of neurological outcomes. In this review, we focus on the role of BHB before and after ischemic stroke, with an emphasis on the therapeutic potential and mechanisms of ketone administration after ischemic stroke.

Association between Oxidative Balance Score and Severe Headache or Migraine among American Adults A Cross-Section Study.

BACKGROUND: Migraine is implicated in oxidative stress. The oxidative balance score (OBS) assesses the combined impact of diet and lifestyle on oxidative and antioxidant balance in diseases. However, the association between OBS and migraine remains underexplored. OBJECTIVE: We aimed to examine the relationship between OBS and severe headaches or migraines among American adults. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, defining severe headaches or migraine via self-reports and calculating OBS from 16 diaries and 4 lifestyle factors. Multivariable weighted logistic regression models were used to explore the OBS-migraine relationship, with stratified analysis for result validation. RESULTS: The study included 6,653 participants (average age 45.6, 52.1% male), and 19.1% reported severe headaches or migraines. There was a significant inverse association between OBS and severe headache or migraine, with an adjusted odds ratio (OR) of 0.97 (95% [confidence interval] CI: 0.96, 0.98, p < 0.001). The highest OBS tertile had an adjusted OR of 0.58 (95% CI: 0.47, 0.73) compared to the lowest. This pattern was consistent across sexes, with an adjusted OR of 0.98 (0.95, 1.00) in males and 0.97 (0.95, 1.00) in females. The adjusted OR for migraine was 0.61 (0.44, 0.87) and 0.54 (0.37, 0.79) in the highest tertile for males and females, respectively. CONCLUSION: The study highlights a significant association between OBS and severe headaches or migraines, suggesting the potential role of oxidative stress in these conditions. The findings emphasize the importance of a balanced, antioxidant-rich diet and lifestyle in managing severe headaches or migraine.

The Dilator-Dotter technique can successfully treat tandem lesions of posterior circulation.

In this study, we applied the Dilator-Dotter technique, a catheter-based angioplasty, to cross through severely stenotic or occluded vertebral arteries during mechanical thrombectomy, and we explored its efficacy and safety in treating tandem lesions of posterior circulation. We performed a retrospective analysis of patients with acute stroke caused by tandem lesions of posterior circulation treated with the Dilator-Dotter technique and thrombectomy between July 2017 and December 2021. In addition to collecting clinical, radiographic, and procedural data from patient records, we also collected information about surgical complications and outcome. We enrolled 9 patients for this study. In all cases, the vertebral artery (VA) on the affected side was crossed through via the Dilator-Dotter technique, and mechanical thrombectomy was successfully performed. The average time from groin puncture to revascularization (TICI 2B-3) was 26 minutes (range 16-50 minutes). Eight patients (89%) achieved complete recanalization with TICI 3, and only 1 patient suffered from thrombus escape to the posterior cerebral artery. Eight patients underwent VA stenting, while the remaining patient was excluded from this procedure because a postoperative brain CT scan recorded obvious staining of the contrast medium within the infarcted area. Five patients had modified Rankin Scale scores ≤ 3 at the 3-month follow-up examination, and 2 patients died due to postoperative cerebral hemorrhage and severe ischemia. The Dilator-Dotter technique may represent a safe and effective treatment for tandem lesions of posterior circulation. Using this method, the lesions can be rapidly recanalized and treated.

PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.

RATIONALE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored. AIM AND HYPOTHESIS: To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone. SAMPLE SIZE ESTIMATES: With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden. METHODS AND DESIGN: This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone. STUDY OUTCOMES: The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period. DISCUSSION: This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data. TRIAL REGISTRATION NUMBER: ChiCTR2300068868; https://www.chictr.org.cn/.

High-throughput Sequencing and Bioinformatics Analysis Reveals the Neurogenesis Key Targets of Curcumin Action in Mouse Brain with MCAO.

BACKGROUND: Experimental studies have shown that curcumin exerts neuroprotective effects in animal models with middle cerebral artery occlusion (MCAO). However, the mechanisms of protective effects of curcumin in MCAO are not fully understood. OBJECTIVE: This study aims to investigate the key neurogenesis targets of curcumin action in mouse brain with MCAO. METHODS: The MCAO models were established in mice. High-throughput sequencing was used to identify differentially expressed mRNA, lncRNA, and circRNA. The reverse expressed mRNAs, lncRNA, and circRNA in sham vs. MCAO and MCAO vs. curcumin were identified. Biological functions were determined by gene ontology (GO) analyses. The protein-protein interaction (PPI) network of neurogenesis-related genes was constructed. Next, neurogenesis-related lncRNA/ circRNA-miRNA-mRNA ceRNA networks were constructed. RESULTS: The total of reverse expressed 1215 mRNAs, 32 lncRNAs, and 43 circRNAs were filtered based on the 2 series (sham vs. MCAO and MCAO vs. Curcumin). The functional enrichment analysis of 1215 reverse expressed mRNAs found that they were involved in neurogenesis, neuron generation, neurogenesis regulation, and others. The PPI network of neurogenesis-related genes consisted of 115 nodes, including 27 down-regulated genes and 36 up-regulated genes. Furthermore, the neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNAs networks were constructed, and 5 lncRNA ceRNA networks and 3 circRNA ceRNA networks were explored. CONCLUSION: Our study revealed that curcumin exerts neuroprotective effects by regulating neurogenesis. The neurogenesis-related lncRNA/circRNA-miRNA-mRNA ceRNA networks are potential therapeutic targets of curcumin in MCAO. This study provided a theoretical basis for curcumin exerting neuroprotective effects in MCAO.