Association between body mass index and medication-overuse headache among individuals with migraine: a cross-sectional study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; P = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤ 23.9 kg/m2), those with Q4 (BMI ≥ 28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; P = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Gra-CRC-miRTar: The pre-trained nucleotide-to-graph neural networks to identify potential miRNA targets in colorectal cancer.

Colorectal cancer (CRC) is the third most diagnosed cancer and the second deadliest cancer worldwide representing a major public health problem. In recent years, increasing evidence has shown that microRNA (miRNA) can control the expression of targeted human messenger RNA (mRNA) by reducing their abundance or translation, acting as oncogenes or tumor suppressors in various cancers, including CRC. Due to the significant up-regulation of oncogenic miRNAs in CRC, elucidating the underlying mechanism and identifying dysregulated miRNA targets may provide a basis for improving current therapeutic interventions. In this paper, we proposed Gra-CRC-miRTar, a pre-trained nucleotide-to-graph neural network framework, for identifying potential miRNA targets in CRC. Different from previous studies, we constructed two pre-trained models to encode RNA sequences and transformed them into de Bruijn graphs. We employed different graph neural networks to learn the latent representations. The embeddings generated from de Bruijn graphs were then fed into a Multilayer Perceptron (MLP) to perform the prediction tasks. Our extensive experiments show that Gra-CRC-miRTar achieves better performance than other deep learning algorithms and existing predictors. In addition, our analyses also successfully revealed 172 out of 201 functional interactions through experimentally validated miRNA-mRNA pairs in CRC. Collectively, our effort provides an accurate and efficient framework to identify potential miRNA targets in CRC, which can also be used to reveal miRNA target interactions in other malignancies, facilitating the development of novel therapeutics.

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.

Dynamics and concordance alterations of regional brain function indices in vestibular migraine: a resting-state fMRI study.

BACKGROUND: Prior MRI studies on vestibular migraine (VM) have revealed abnormalities in static regional intrinsic brain activity (iBA) and dynamic functional connectivity between brain regions or networks. However, the temporal variation and concordance of regional iBA measures remain to be explored. METHODS: 57 VM patients during the interictal period were compared to 88 healthy controls (HC) in this resting-state functional magnetic resonance imaging (fMRI) study. The dynamics and concordance of regional iBA indices, including amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo), were examined by utilizing sliding time-window analysis. Partial correlation analyses were performed between clinical parameters and resting-state fMRI indices in brain areas showing significant group differences. RESULTS: The VM group showed increased ALFF and ReHo dynamics, as well as increased temporal concordance between ALFF and ReHo in the bilateral paracentral lobule and supplementary motor area relative to the HC group. We also found decreased ReHo dynamics in the right temporal pole, and decreased ALFF dynamics in the right cerebellum posterior lobe, bilateral angular gyrus and middle occipital gyrus (MOG) in the VM group compared with the HC group. Moreover, a positive correlation was observed between ALFF dynamics in the left MOG and vertigo disease duration across all VM patients. CONCLUSION: Temporal dynamics and concordance of regional iBA indices were altered in the motor cortex, cerebellum, occipital and temporoparietal cortex, which may contribute to disrupted multisensory processing and vestibular control in patients with VM. ALFF dynamics in the left MOG may be useful biomarker for evaluating vertigo burden in this disorder.

Network analysis and experimental approach to investigate the potential therapeutic mechanism of zishen yutai pills on premature ovarian insufficiency.

Background: As society continues to develop, women are more at risk of gonadotoxic substance exposure. Consequently, the incidence of premature ovarian insufficiency (POI) has increased significantly in the past decades. Hormone replacement therapy (HRT) is recommended as the standard treatment to relieve hypoestrogenic symptoms; however, its potential side effects and contraindications have drawn widespread controversy and concern. As such, the Chinese medicine Zishen Yutai Pill (ZSYTP) commonly used for treating miscarriage and menoxenia, is a highly promising alternative drug candidate against POI, however its therapeutic mechanism has not been completely elucidated. Objective: To systematically analyze the potential therapeutic targets of ZSYTP on POI, we combined network pharmacology analysis and molecular docking to predict critical target genes, with experimental validation on POI murine models. Methods: The active compounds of ZSYTP were collected from three online databases, and the candidate targets were predicted based on the chemical structure. The POI-related targets were obtained from four databases. A PPI network was constructed to find the key target genes between ZSYTP and POI, while GO and KEGG enrichment analyses were employed to study the mechanism of ZSYTP against POI. The binding capability of the key co-targets with active components was examined by molecular docking. We used a cyclophosphamide (CTX)-inducible POI mouse model to verify our predictions by histopathological observation, immunohistochemical staining (caspase-3, TUNEL assay), hormone determination (FSH, AMH) and ribonucleic acid sequencing (RNA Seq). Progynova was also used to study the difference between ZSYTP and HRT. Result: We identified 21 target genes as the hub between ZSYTP and POI. The GO and KEGG analyses revealed that the molecular mechanism of ZSYTP against POI were mainly based on the regulation of gene and protein expression. A variety of signaling pathways may be involved in the treatment of ZSYTP against POI, especially PI3K-AKT, HIF-1 and the AGE-RAGE cascades. Docking simulation showed that G1, C1, SR5, and F1 had relatively lower binding energy. In vivo, ZSYTP significantly reversed CTX-induced ovarian damage in follicle number, hormone level and apoptosis, with an overall improved therapeutic effect compared to Progynova. Results from RNA-Seq revealed that the PI3K-AKT, Hippo, AGE-RAGE, and Rap1 signaling pathways and regulation of inflammation, immune response, and lipid metabolism may mediate the protective effects of ZSYTP against POI, which is different than Progynova's mechanism of action. Conclusions: Collectively, this study indicates that ZSYTP could be a highly promising alternative as a non-HRT-based therapy for POI. Its mechanism involves multiple signaling pathways, alleviating ovarian apoptosis and recovering AMH and FSH level. However, the discrepancy between different research techniques highlight the necessity of further experimental verification from other aspects such as translation and posttranslational modification.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

Study on the thermal kinetics and microscopic characteristics of oxidized coal.

Revealing the characteristics of spontaneous combustion and re-combustion of oxidized coal is of great significance for the coal fire prevention and control. Synchronous Thermal Analyzer (STA) and Fourier Transform Infrared Spectrometer (FTIR) were used to measure the thermal kinetics and microscopic characteristics of coal samples with different oxidation degrees (unoxidized, 100 ℃, 200 ℃ and 300 ℃ oxidized coal). It is found that the characteristic temperatures decrease first and then increase with the increasing degree of oxidation. The ignition temperature of 100 ℃-O coal (oxidized at 100 ℃ for 6 h) is relatively the lowest at 334.1 ℃. Pyrolysis and gas-phase combustion reactions dominate the weight loss process, while solid-phase combustion reactions are relatively minor. The gas-phase combustion ratio of 100 ℃-O coal is the highest at 68.56%. With the deepening of coal oxidation degree, the relative content of aliphatic hydrocarbons and hydroxyl groups gradually decreases, while that of oxygen-containing functional groups (C-O, C = O, COOH, etc.) increases first and then decreases, reaching the highest value of 42.2% at 100 ℃. Moreover, the 100 ℃-O coal has the minimum temperature at the point of maximum exothermic power of 378.5 ℃, the highest exothermic power of -53.09 mW/mg and the maximum enthalpy of -18,579 J/g. All results show that 100 ℃-O coal has the highest risk of spontaneous combustion than the other three coal samples. This suggests that there is a maximum point of spontaneous combustion risk in the range of pre-oxidization temperatures of oxidized coal.

Maternal exposure to a glyphosate-based herbicide impairs placental development through endoplasmic reticulum stress in mice.

Glyphosate-based herbicides (GBHs) are the most widely used agrochemicals worldwide, increasing the risk of their occurrence in the environment. This study aimed to explore effects and mechanisms of GBH exposure on placental development in vivo during pregnancy in mice. Pregnant mice received GBH by gavage at 0, 5, and 50 mg⋅kg-1⋅day-1 doses from gestational day (GD) 1 to GD 13 and were sacrificed on GD 13 or GD19. Our data indicated that GBH administration significantly increased the number of resorbed fetuses, reduced the weight of fetuses and placentas, and inhibited placental growth, as evident from decreased placental total area and spongiotrophoblast area on GD 19. GBH treatment also inhibited proliferation and induced apoptosis of placenta via upregulation of Bax, cleaved caspase-3 and -12 expression, and downregulation of B cell lymphoma (Bcl)-2 expression. Further study showed that GBH exposure significantly increased expression levels of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) mRNAs and proteins and triggered oxidative stress in placenta on GD 13 and GD 19. In conclusion, our findings suggest that maternal exposure to GBH can impair placental development through the endoplasmic reticulum stress-mediated activation of GRP78/PERK/CHOP signaling pathway in mice.

Real-World Treatment Patterns and Outcomes Among Patients with Episodic Migraine in China: Results from the Adelphi Migraine Disease Specific Programme™.

Objective: This study assessed treatment patterns, disease burden, outcomes, and unmet needs among patients with episodic migraine (EM) in China using Adelphi Migraine Disease Specific Programme™ (DSP) real-world data. Background: Migraine is a prevalent and debilitating neurological disorder which presents a major public health burden globally. Research on characteristics, disease burden, and treatment patterns in EM patients in China is limited. Methods: Data were drawn from an existing data set Adelphi Migraine DSP, a point-in-time survey conducted in China (January-June 2014). Internists/neurologists completed patient record forms for the next 9 patients who consulted them in clinical practice; these same patients completed the 'patient self-completion questionnaires'. Descriptive analyses were used to assess key variables: patient demographics, treatment patterns (current acute and preventive medication [AM/PM]), effectiveness, issues with existing treatment, Migraine Disability Assessment (MIDAS) scores, and Work Productivity and Activity Impairment scores. Results: Total of 125 internists/neurologists provided data on 1113 patients with EM (headache days/month <15). Mean (standard deviation [SD]) age was 43.8 (13.1) years; mean (SD) number of migraine days/month was 3.2 (1.7). AM was prescribed in 86.1% of patients (non-steroid anti-inflammatory drugs [NSAIDs]: 62.7%; triptans: 7.7%), PM in 38.5%, and both in 24.9% of patients. Approximately 55% of patients experienced ≥1 issue with their current AM or PM. Migraine-related symptoms (including nausea, photophobia, and phonophobia) were fully controlled in <50% of patients receiving NSAIDs (21.7-38.4%) or triptans (32.4-43.5%). Insufficient response to current AM (migraine headache fully resolved within 2 hours in ≤3/5 attacks) was reported by 42.5% of patients. Mild-to-severe disability was reported by 36.8% of patients with a mean (SD) MIDAS score of 5.8 (7.3). Overall, 58.0% of work time was impaired (including time missed and impairment while working). Conclusion: This analysis suggests, despite existing treatment options, disease burden and unmet medical needs remain substantial in Chinese patients with EM.

The prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache: The survey of fibromyalgia comorbid with headache.

OBJECTIVE: The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache. BACKGROUND: Studies done in non-Chinese populations suggest that around one-third of patients with primary headache have fibromyalgia, but data from mainland China are limited. Investigations into the prevalence and clinical features of fibromyalgia in Chinese patients with primary headache would improve our understanding of these two complex disease areas and help guide future clinical practice. METHODS: This cross-sectional study included adults with primary headache treated at 23 Chinese hospitals from September 2020 to May 2021. Fibromyalgia was diagnosed using the modified 2010 American College of Rheumatology criteria. Mood and insomnia were evaluated employing the Hospital Anxiety and Depression Scale and the Insomnia Severity Index. RESULTS: A total of 2782 participants were analyzed. The fibromyalgia prevalence was 6.0% (166/2782; 95% confidence interval: 5.1%, 6.8%). Compared to primary headache patients without combined fibromyalgia, patients with primary headache combined with fibromyalgia were more likely to be older (47.8 vs. 41.7 years), women (83.7% [139/166] vs. 72.8% [1904/2616]), less educated (65.1% [108/166] vs. 45.2% [1183/2616]), and with longer-duration headache (10.0 vs. 8.0 years). Such patients were more likely to exhibit comorbid depression (34.3% [57/166] vs. 9.9% [260/2616]), anxiety (16.3% [27/166] vs. 2.7% [70/2612]), and insomnia (58.4% [97/166] vs. 17.1% [447/2616]). Fibromyalgia was more prevalent in those with chronic (rather than episodic) migraine (11.1% [46/414] vs. 4.4% [72/1653], p < 0.001) and chronic (rather than episodic) tension-type headache (11.5% [27/235] vs. 4.6% [19/409], p = 0.001). Most fibromyalgia pain was in the shoulders, neck, and upper back. CONCLUSIONS: The prevalence of fibromyalgia in mainland Chinese patients with primary headache was 6.0%. Fibromyalgia was more common in those with chronic rather than episodic headache. The most common sites of fibromyalgia pain were the neck, shoulders, and back.

Altered functional connectivity within and between resting-state networks in patients with vestibular migraine.

PURPOSE: Previous functional magnetic resonance imaging studies have substantiated changes in multiple brain regions of functional activity in patients with vestibular migraine. However, few studies have assessed functional connectivity within and between specific brain networks in vestibular migraine. METHODS: Our study subjects included 37 patients with vestibular migraine and 35 healthy controls, and the quality of magnetic resonance images of all subjects met the requirements. Independent component analysis was performed to identify resting-state networks, and we investigated changes in functional connectivity patterns within and between brain networks. We also used Pearson correlation analysis to assess the relationship between changes in functional connectivity and the clinical features of patients with vestibular migraine. RESULTS: A total of 14 independent components were identified. Compared to healthy controls, patients with vestibular migraine exhibited decreased intra-network functional connectivity in the executive control network and weakened functional connectivity between the anterior default mode network and the ventral attention network, between the anterior default mode network and the salience network, and between the right frontoparietal network and the auditory network. Moreover, the functional connectivity between the salience network and the dorsal attention network was increased. However, the functional connectivity of networks and clinical characteristics of vestibular migraine patients did not demonstrate any significant correlation. CONCLUSION: In conclusion, our study suggested that patients with vestibular migraine also have abnormal multisensory integration during the interictal period and that the attention network is involved. Changing within- and between-network functional connectivity may indicate that vestibular cortex areas are in a sensitive state.

Elevated Serum Ninjurin-1 Is Associated with a High Risk of Large Artery Atherosclerotic Acute Ischemic Stroke.

Ninjurin-1 is a novel adhesion molecule which is involved in many inflammatory diseases. Functional blockage of Ninjurin-1 has exerted an atheroprotective effect. The aim of the study is to explore the association between serum Ninjurin-1 and the risk of large artery atherosclerotic acute ischemic stroke. From August 2020 through December 2021, patients with large artery atherosclerotic acute ischemic stroke (LAA-AIS) admitted to the First Hospital Affiliated to Soochow University, and age- and sex-matched controls free of ischemic stroke were recruited. Serum Ninj1 was measured with an enzyme-linked immunosorbent assay. Multivariable logistic regression models were used to calculate the odds ratios and 95% confidence intervals of LAA-AIS associated with serum Ninj1 levels, and receiver operating characteristic (ROC) curves were performed to assess the improvement value of Ninj1 for the prediction of LAA-AIS after adding Ninj1 to established risk factors. Of the 110 patients and 110 age- and sex-matched controls free of ischemic stroke enrolled, serum Ninj1 levels in LAA-AIS patients were significantly higher than that in control group (142.70 ng/ml [IQR: 110.41-163.44] vs 101.62 ng/ml [IQR: 86.63-120.86], p < 0.001). In multivariable analysis, Ninj1 levels were expressed as continuous variable and ordinal variable (tertiles), and it turned out that Ninj1 levels were positively associated with increased risk of LAA-AIS, especially in tertile3 compared with tertile1 (adjusted OR = 12.567, 95%CI: 5.148-30.678, p < 0.001), and the adjusted odds OR per 10 ng/ml increment was 1.541, 95%CI: 1.348-1.763, p < 0.001. Furthermore, adding Ninj1 to a multivariate logistic model including conventional risk factors associated LAA-AIS improved the area under ROC curves from 0.787 to 0.874. Elevated circulating levels of Ninj1 were associated with increased risk of LAA-AIS, indicating that serum Ninj1 may act as a predictor independent of established conventional risk factors.

Temperate Lianas Have More Acquisitive Strategies than Host Trees in Leaf and Stem Traits, but Not Root Traits.

Increasingly, tropical studies based on aboveground traits have suggested that lianas have a more acquisitive strategy than trees, thereby possibly explaining the increase in lianas relative to trees in many tropical forests under global change. However, few studies have tested whether this pattern can be extended to root traits and temperate forests. In this study, we sampled 61 temperate liana-host tree pairs and quantified 11 commonly studied functional traits representative of plant economics in roots, stems, and leaves; we aimed to determine whether root, stem and leaf traits are coordinated across lifeforms, and whether temperate lianas are also characterized by more fast and acquisitive traits than trees. Our results showed that leaf and stem traits were coordinated across lifeforms but not with root traits, suggesting that aboveground plant economics is not always correlated with belowground economics, and leaf and stem economic spectra cannot be expanded to the root directly. Compared with host trees, lianas had more acquisitive leaf and stem traits, such as higher specific leaf area and lower leaf dry matter content, leaf carbon content, leaf mass per area, and wood density, suggesting that lianas have a more acquisitive strategy than host trees in the temperate forest. The differences between lianas and trees in plant strategy may drive their contrasting responses to the changing temperate forest environment under global change.

Identification of immune-related features involved in Duchenne muscular dystrophy: A bidirectional transcriptome and proteome-driven analysis.

Background: We aimed to investigate the biological mechanism and feature genes of Duchenne muscular dystrophy (DMD) by multi-omics and experimental verification strategy. Methods: We integrated the transcriptomic and proteomic methods to find the differentially expressed mRNAs (DEMs) and proteins (DEPs) between DMD and Control groups. Weighted gene co-expression network analysis (WGCNA) was then used to identify modules of highly correlated genes and hub genes. In the following steps, the immune and stromal cells infiltrations were accomplished by xCELL algorithm. Furthermore, TF and miRNA prediction were performed with Networkanalyst. ELISA, western blot and external datasets were performed to verify the key proteins/mRNAs in DMD patient and mouse. Finally, a nomogram model was established based on the potential biomarkers. Results: 4515 DEMs and 56 DEPs were obtained from the transcriptomic and proteomic study respectively. 14 common genes were identified, which is enriched in muscle contraction and inflammation-related pathways. Meanwhile, we observed 33 significant differences in the infiltration of cells in DMD. Afterwards, a total of 22 miRNAs and 23 TF genes interacted with the common genes, including TFAP2C, MAX, MYC, NFKB1, RELA, hsa-miR-1255a, hsa-miR-130a, hsa-miR-130b, hsa-miR-152, and hsa-miR-17. In addition, three genes (ATP6AP2, CTSS, and VIM) showed excellent diagnostic performance on discriminating DMD in GSE1004, GSE3307, GSE6011 and GSE38417 datasets (all AUC > 0.8), which is validated in patients (10 DMD vs. 10 controls), DMD with exon 55 mutations, mdx mouse, and nomogram model. Conclusion: Taken together, ATP6AP2, CTSS, and VIM play important roles in the inflammatory response in DMD, which may serve as diagnostic biomarkers and therapeutic targets.

Propagation Structure of Intrinsic Brain Activity in Migraine without Aura.

Previous studies have revealed highly reproducible patterns of temporally lagged brain activity in healthy human adults. However, it is unknown whether temporal organization of intrinsic activity is altered in migraines or if it relates to migraine chronification. In this resting-state functional magnetic resonance imaging study, temporal features of intrinsic activity were investigated using resting-state lag analysis, and 39 episodic migraine patients, 17 chronic migraine patients, and 35 healthy controls were assessed. Temporally earlier intrinsic activity in the hippocampal complex was revealed in the chronic migraine group relative to the other two groups. We also found earlier intrinsic activity in the medial prefrontal cortex in chronic compared with episodic migraines. Both migraine groups showed earlier intrinsic activity in the lateral temporal cortex and sensorimotor cortex compared with the healthy control group. Across all patients, headache frequency negatively correlated with temporal lag of the medial prefrontal cortex and hippocampal complex. Disrupted propagation of intrinsic activity in regions involved in sensory, cognitive and affective processing of pain may contribute to abnormal brain function during migraines. Decreased time latency in the lateral temporal cortex and sensorimotor cortex may be common manifestations in episodic and chronic migraines. The temporal features of the medial prefrontal cortex and hippocampal complex were associated with migraine chronification.

Galcanezumab in episodic migraine: the phase 3, randomized, double-blind, placebo-controlled PERSIST study.

BACKGROUND: Galcanezumab, a humanized monoclonal antibody that binds calcitonin gene-related peptide, has demonstrated efficacy and good tolerability in patients with episodic migraine in previous phase 3 trials. We report results from the PERSIST study, which was designed to assess the efficacy and safety of galcanezumab in patients with episodic migraine from China, India, and Russia. METHODS: This phase 3 study was conducted at 40 centers in China (n = 26), India (n = 10), and Russia (n = 4). Eligible adult patients with episodic migraine were randomized in a 1:1 ratio to receive monthly galcanezumab 120 mg (with 240 mg loading dose) or placebo during a double-blind, 3-month treatment period. The primary endpoint was the overall mean change from baseline in monthly migraine headache days (MHDs). Key secondary endpoints were the mean proportion of patients with ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs and mean change in the Migraine-Specific Quality of Life Questionnaire (MSQ) Role Function-Restrictive domain score. RESULTS: In total, 520 patients were randomized and received at least one dose of galcanezumab (N = 261) or placebo (N = 259). The least squares (LS) mean reduction from baseline in monthly MHDs over 3 months was significantly greater with galcanezumab compared with placebo (-3.81 days vs. -1.99 days; p < 0.0001). Significantly greater mean proportions of patients with galcanezumab versus placebo had ≥ 50%, ≥ 75%, and 100% reductions from baseline in MHDs (all p < 0.0001). The overall mean improvement from baseline in MSQ Role Function-Restrictive score over 3 months was significantly greater with galcanezumab versus placebo (p < 0.0001). There were no clinically meaningful differences between the galcanezumab and placebo group on any safety parameters except for a higher incidence of injection site pruritus (5.0% vs. 0.0%), injection site reaction (3.8% vs. 0.4%), and injection site discomfort (2.3% vs. 0.0%). TEAEs related to injection sites were mild in severity, except in 1 patient who had a moderate injection site reaction. Six serious adverse events were reported by 6 patients (2 galcanezumab, 4 placebo). CONCLUSIONS: Galcanezumab 120 mg once monthly was effective and well tolerated in patients with episodic migraine from China, India, and Russia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03963232 (PERSIST), registered May 24, 2019.

High-sensitivity C-reactive protein as a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy.

BACKGROUND: C-reactive protein (CRP) is an important biomarker of inflammation and plays a pivotal role in predicting the clinical prognosis of cardiovascular and cerebrovascular diseases. However, the mechanism of inflammation influencing the outcome of patients with ischemic stroke are unknown. AIMS: We aim to investigate the association between hsCRP and mRS in 194 eligible patients by therapy-stratified analyses. METHODS: The modification effects of antiplatelet therapy on the association between mRS and different exposure variables were analyzed. The retained variables were analyzed in the receiver operating characteristic (ROC) curve to discriminate patients with poor outcome. RESULTS: hsCRP was positively correlated with mRS in therapy-stratified analyses. There was a statistical modification effect of antiplatelet therapy on the association of hsCRP and mRS (P for interaction = 0.0101). The discriminative effect of poor outcome was further verified by ROC curve analyses (AUCwith from 0.758 to 0.872, AUCwithout from 0.709 to 0.713). CONCLUSIONS: hsCRP is correlated with the clinical outcome of patients treated with IVrt-PA, and may be a better predictor of post-thrombolytic functional outcome in patients with previous antiplatelet therapy than in non-used patients.

Efficacy and Safety of Lasmiditan as a Novel Acute Treatment in Chinese Patients with Migraine: A Subpopulation Analysis of the Randomized Controlled Phase 3 CENTURION Trial.

INTRODUCTION: Over the last two decades, there has been no novel acute treatment for migraine to address the large unmet medical need in Chinese patients. Lasmiditan, a novel selective serotonin 1F receptor agonist (ditan), is anticipated to bring clinical benefit in Chinese patients with migraine. The CENTURION study is a multi-country, placebo-controlled phase 3 study designed to assess the first attack efficacy and the consistency of response of lasmiditan in acute treatment of migraine. This subpopulation analysis pooled Chinese patients' data from the primary cohort and additional extended enrollment cohort which was not published previously. This is the first analysis focusing on lasmiditan's efficacy and safety in Chinese patients with migraine and aims to provide relevant evidence for Chinese physicians. METHODS: Patients were randomized 1:1:1 to one of the three treatment groups for four attacks: (a) lasmiditan 100 mg; (b) lasmiditan 200 mg; or (c) control group. Primary endpoints were pain freedom at 2 h (first attack) and pain freedom at 2 h in at least two out of three attacks. Secondary endpoints included pain relief, sustained pain freedom, and disability freedom. RESULTS: In total, 281 Chinese patients (lasmiditan 100 mg, 95; lasmiditan 200 mg, 92; control, 94) were treated for at least one migraine attack. Both doses of lasmiditan showed improvement versus placebo for pain freedom at 2 h after first attack, with lasmiditan 200 mg showing nominal significance. An early onset of effect was observed with lasmiditan versus placebo. Both doses of lasmiditan showed better results for all key secondary endpoints versus placebo. The most commonly reported treatment-emergent adverse event across all groups was dizziness. CONCLUSION: In the Chinese population, lasmiditan was better than placebo for both primary endpoints and key secondary endpoints with an acceptable safety profile. No new safety signals were detected in the Chinese population. These findings are generally consistent with those observed in the CENTURION study published data and the established product profile. TRIAL REGISTRATION NUMBER: NCT03670810.

Artesunate restores mitochondrial fusion-fission dynamics and alleviates neuronal injury in Alzheimer's disease models.

Alzheimer's disease (AD) remains a leading cause of dementia and no therapy that reverses underlying neurodegeneration is available. Recent studies suggest the protective role of artemisinin, an antimalarial drug, in neurological disorders. In this study, we investigated the therapeutic potential of artesunate, a water-soluble derivative of artemisinin, on amyloid-beta (Aß)-treated challenged microglial BV-2, neuronal N2a cells, and the amyloid precursor protein/presenilin (APP/PS1) mice model. We found that Aß significantly induced multiple AD-related phenotypes, including increased expression/production of pro-inflammatory cytokines from microglial cells, enhanced cellular and mitochondrial production of reactive oxygen species, promoted mitochondrial fission, inhibited mitochondrial fusion, suppressed mitophagy or biogenesis in both cell types, stimulated apoptosis of neuronal cells, and microglia-induced killing of neurons. All these in vitro phenotypes were attenuated by artesunate. In addition, the over-expression of the mitochondrial fission protein Drp-1, or down-regulation of the mitochondrial fusion protein OPA-1 both reduced the therapeutic benefits of artesunate. Artesunate also alleviated AD phenotypes in APP/PS1 mice, reducing Aß deposition, and reversing deficits in memory and learning. Artesunate protects neuronal and microglial cells from AD pathology, both in vitro and in vivo. Maintaining mitochondrial dynamics and simultaneously targeting multiple AD pathogenic mechanisms are associated with the protective effects of artesunate. Consequently, artesunate may become a promising therapeutic for AD.

Rhino-Orbital Cerebral Mucormycosis in a Patient With Diabetic Ketoacidosis: A Case Report and Literature Review.

Background: Rhino-orbital cerebral mucormycosis (ROCM) is a rare, invasive, and fatal fungal disease. Due to the lack of specific clinical manifestations and adequate auxiliary examinations, patients are easily misdiagnosed in the early stage. Early diagnosis and timely therapy are essential for successful treatment. Case Report: We report a 68-year-old man with diabetic ketoacidosis, presented with orbital apex syndrome (OAS), fever, and pansinusitis, which progressively worsened to death only 4 days after admission. It was finally confirmed as a fungal Rhizopus arrhizus infection by metagenomics cell-free DNA next-generation sequencing (mNGS) testing. Conclusion: Orbital apex syndrome could be the initial presentation for mucormycosis. Thus, it is necessary to evaluate the presence of mucormycosis in patients with OAS, especially in diabetic or immunosuppressed hosts, and mNGS testing and timely antifungal therapy should be strongly recommended in highly suspected cases.