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.

Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study.

BACKGROUND: The phase 3 randomized PERSIST study demonstrated the efficacy and tolerability of galcanezumab, a humanized anti-calcitonin gene-related peptide (CGRP) monoclonal antibody for prevention of episodic migraines. We present findings from the open-label extension (OLE) of PERSIST, which evaluated the long-term efficacy and safety of galcanezumab in patients from China, India, and Russia. METHODS: Patients completing the 3-month double-blind period of PERSIST were eligible for the 3-month OLE. Patients previously randomized to galcanezumab (GMB/GMB group) continued to receive galcanezumab 120 mg at all three visits during the OLE whereas patients randomized to placebo received a 240 mg loading dose of galcanezumab and then two 120 mg doses (PBO/GMB group). The primary outcome was the mean change (from double-blind baseline) in the number of monthly migraine headache days (MHDs) to month 6. Other endpoints included percent reduction in monthly MHDs from double-blind baseline to month 6, functional outcomes, safety and tolerability. RESULTS: Overall, 99% of patients completing the double-blind period entered the OLE, and 96% completed through month 6. Patients in the GMB/GMB group achieved continued improvements in efficacy, with the reduction from baseline in the mean number of monthly MHDs, and slightly increasing from 4.01 days at the end of the double-blind period to 4.62 at the end of the OLE. Of patients who were ≥ 50% responders to galcanezumab at month 3, 66% maintained this response through to month 6. Patients in the PBO/GMB group experienced a rapid reduction in the number of monthly MHDs after initiation of galcanezumab, with a mean reduction from baseline of 4.56 days by month 6. The long-term benefits of galcanezumab were also supported by improvements in other efficacy and functional endpoints. All safety findings were consistent with the known long-term safety profile of galcanezumab; no patients experienced a treatment-related serious adverse event. CONCLUSIONS: Galcanezumab was efficacious and well-tolerated in patients with episodic migraine from China, India and Russia, for up to 6 months. TRIAL REGISTRATION: ClinicalTrisABSTRACT_pals.gov NCT03963232, registered May 24, 2019.

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.

A novel compound heterozygous EPM2A mutation in a Chinese boy with Lafora disease.

EPM2A has been certified as a causative gene in patients with Lafora disease (LD), which is a rare autosomal recessive and severe form of progressive myoclonus epilepsy. LD classically starts in adolescence, characterized by various types of seizure with myoclonic seizure as the main type. Typically within 10 years, intractable seizure attack, rapidly progressing dementia, and a vegetative state were present. LD is particularly frequently found in Mediterranean countries. Here, we report a Chinese family with a novel compound heterozygous mutation in the EPM2A gene, characterized by recurrent vomiting, intractable epilepsy, and progressive cognitive decline.

Transcriptional repressor Blimp1 regulates follicular regulatory T-cell homeostasis and function.

The B-lymphocyte-induced maturation protein 1 (Blimp1) regulates T-cell homeostasis and function. Loss of Blimp1 could double the proportion of follicular regulatory T (Tfr) cells. However, the effects that Blimp1 may have on the function of Tfr cells remain unknown. Here we document the function for Blimp1 in Tfr cells in vitro and in vivo. Data presented in this study demonstrate that Tfr cells indirectly inhibit the activation and differentiation of B cells by negatively regulating follicular helper T cells, so lowering the secretion of antibody. Lack of Blimp1 makes the immune suppression function of Tfr cells impaired in vitro. In the in vivo study, adoptive transfer of Tfr cells could reduce immune responses in germinal centres and relieve the muscle weakness symptoms of mice with experimental autoimmune myasthenia gravis. Blimp1 deficiency resulted in reduced suppressive ability of Tfr cells. This study identifies that Tfr cells are potent suppressors of immunity and are controlled by Blimp1.

Modulation of Synaptic Plasticity by Exercise Training as a Basis for Ischemic Stroke Rehabilitation.

In recent years, rehabilitation of ischemic stroke draws more and more attention in the world, and has been linked to changes of synaptic plasticity. Exercise training improves motor function of ischemia as well as cognition which is associated with formation of learning and memory. The molecular basis of learning and memory might be synaptic plasticity. Research has therefore been conducted in an attempt to relate effects of exercise training to neuroprotection and neurogenesis adjacent to the ischemic injury brain. The present paper reviews the current literature addressing this question and discusses the possible mechanisms involved in modulation of synaptic plasticity by exercise training. This review shows the pathological process of synaptic dysfunction in ischemic roughly and then discusses the effects of exercise training on scaffold proteins and regulatory protein expression. The expression of scaffold proteins generally increased after training, but the effects on regulatory proteins were mixed. Moreover, the compositions of postsynaptic receptors were changed and the strength of synaptic transmission was enhanced after training. Finally, the recovery of cognition is critically associated with synaptic remodeling in an injured brain, and the remodeling occurs through a number of local regulations including mRNA translation, remodeling of cytoskeleton, and receptor trafficking into and out of the synapse. We do provide a comprehensive knowledge of synaptic plasticity enhancement obtained by exercise training in this review.

Zhengtian Capsule versus flunarizine in patients with migraine: a multi-center, double-blind, double-dummy, randomized controlled, non-inferior clinical trial.

BACKGROUND: The primary objective of this study was to assess whether Zhengtian Capsule was non-inferior to flunarizine in efficacy and safety profile for prevention of migraine in adults. METHODS: This was a double-dummy, double-blind, multicenter, positive drug (flunarizine), parallel randomized controlled, non-inferior clinical trial. Patients (n = 360) were randomized in a 1:1 to receive either Zhengtian Capsule or flunarizine, including 12 weeks' intervention and 4 weeks' follow-up. The primary outcome measure was responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period). The secondary outcome measures included migraine attack frequency, the number of migraine days, pain evaluated by visual analogue scale (VAS) score, duration of migraine attacks, the times of using analgesics, patient-reported outcome (PRO) measure of migraine and the scores of short-form 36 Health Survey Scale (SF-36). Weight variation in both groups was also evaluated. Adverse events were monitored throughout the trial. RESULTS: Zhengtian Capsule was non-inferior to flunarizine in responder rate at week 12 and follow-up period (P = 0.002, P < 0.001). There was fewer migraine days in Zhengtian Capsule group at follow-up period compared with flunarizine (P = 0.001). For the total duration of migraine attacks, there was significant group difference at week 4 which favored the control group (P = 0.009). For the total score of PRO scale, there was statistical difference between the two groups at follow-up period (P = 0.021). There were also group differences between the two groups in the dimensions of somatization symptoms at week 4 (P = 0.022) and functional status at week 12 and follow-up period (P < 0.001, P < 0.001). However, there were no significant differences between the two groups in migraine attack frequency, VAS scores reduction, consumption of acute pain drugs and the dimension scores of SF-36 at any time interval of the treatment period (P > 0.05). No severe adverse events occurred in the trial. Flunarizine was found associated with a weight gain. CONCLUSION: Zhengtian Capsule was non-inferior to flunarizine with regard to the primary endpoint. In addition, it could reduce migraine days and improve the functional status and somatization symptoms of migraine patients with good safety profile. TRIAL REGISTRATION: This trial was registered at Chinese Clinical Trial Register (ChiCTR), ChiCTR-TRC-13004412.

Elevated blood pressure and headache disorders in China--associations, under-treatment and implications for public health.

BACKGROUND: Both hypertension (HTN) and headache disorders are highly prevalent worldwide. Our purpose, in a nationwide study of the Chinese general population, was to evaluate any association between primary headache disorders and elevated blood pressure (eBP). We could not collect data on antihypertensive therapy, but took the view that, whatever such therapy might be taken, eBP was a sign that it was failing to meet treatment needs. Therefore, as a secondary purpose, important from the public-health perspective, we would present the prevalence of eBP (treated or not) as indicative of unmet health-care need in China. METHODS: This was a questionnaire-based nationwide cross-sectional door-to-door survey using cluster random-sampling, selecting one adult (18-65 years) per household. Headache was diagnosed by ICHD-II criteria and eBP as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg. Chi-squared test and multivariate logistic regression analysis were used to assess the strength and significance of associations. We set significance at P ≤ 0.05. RESULTS: Of 5,041 survey participants (participation rate 94.1 %), 154 were excluded because of missing BP data, leaving 4,987 for analysis [mean age: 43.6 ± 12.8 years; male 2,532 (mean age: 43.4 ± 12.9 years); female 2,455 (mean age 43.9 ± 12.8 years)]. There were 466 participants with migraine, 535 with tension type headache (TTH) and 48 with all causes of headache on ≥15 days/month. The prevalence of eBP was 22.1 % (males 22.9 %, females 21.3 %). No associations of eBP with any of the headache disorders survived multivariate adjusted analysis. The demographic and anthropometric variables most strongly associated with eBP were higher age (AOR 3.7) and being overweight (AOR 2.4), seen in both genders. Less strong were male gender, lower educational level and urban habitation. CONCLUSIONS: We found no clear-cut associations between eBP and any headache disorder. The associations with demographic and anthropometric variables may have acted as confounders in past reports to the contrary. We did find an alarmingly high prevalence of eBP, recognizing that this signals substantial under-treatment in China of a serious condition, and therefore a major public-health concern.

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.

Headache yesterday in China: a new approach to estimating the burden of headache, applied in a general-population survey in China.

BACKGROUND: In order to minimize recall bias in burden estimation, questions about headache yesterday were included in a population-based survey initiated by LIFTING THE BURDEN : The Global Campaign against Headache. METHODS: Throughout China, nonrelated respondents aged 18-65 years were randomly sampled from the general population by a door-to-door survey. A validated structured questionnaire included inquiry into occurrence and burden of headache on the preceding day ("headache yesterday"). RESULTS: The participation rate was 94.1%. Of 5041 participants, 286 (5.7%) (male 3.6%, female 7.9%) reported headache yesterday. Age-weighted prevalence of headache yesterday was 4.8% (male 3.0%, female 6.6%). Headache yesterday lasted all day in 36.8%, <1 hour in 14.3% and for a mean of 3.7 ± 3.3 hours in 48.9%. Headache yesterday was moderate to severe in 79.9%; disability such that they could do less than half of what they had expected was reported by 19.9% and such that they could do nothing by a further 7.5% (total 27.4%). Almost three-quarters (71.5%) with headache yesterday took medication to treat it. CONCLUSIONS: Of the adult Chinese population, 1.8% have headache at any one time that is of moderate to severe intensity in 1.4%, and 1.3% lose the equivalent of a whole day to headache-attributed disability every day. In China this means 12.3 million people.

Health-care utilization for primary headache disorders in China: a population-based door-to-door survey.

BACKGROUND: In order to know the status quo of health care for primary headache disorders in China, questions about headache consultation and diagnosis were included in a nationwide population-based survey initiated by Lifting The Burden: the Global Campaign against Headache. METHODS: Throughout China, 5,041 unrelated respondents aged 18-65 years were randomly sampled from the general population and visited unannounced at their homes. After basic sociodemographic and headache diagnostic questions, respondents with headache answered further questions about health-care utilization in the previous year. RESULTS: Significantly higher proportions of respondents with migraine (239/452; 52.9%) or headache on ≥15 days per month (23/48; 47.9%) had consulted a physician for headache than of those with tension-type headache (TTH) (218/531; 41.1%; P < 0.05). Multivariate analysis showed associations between disability and probability of consultation in those with migraine (mild vs. minimal: AOR 3.4, 95% CI: 1.6-7.4; moderate vs. minimal: 2.5, 1.2-5.4; severe vs. minimal: 3.9, 1.9-8.1) and between rural habitation and probability of consulting in those with TTH (AOR: 3.5; 95% CI: 1.9-6.3, P < 0.001). Married respondents with TTH were less likely than unmarried to have consulted (AOR: 0.26; 95% CI: 0.07-0.93; P = 0.038). About half of consultations (47.8-56.5%) for each of the headache disorders were at clinic level in the health system. Consultations in level-3 hospitals were relatively few for migraine (5.9%) but more likely for headache on ≥15 days/month (8.7%) and, surprisingly, for TTH (13.3%). Under-diagnosis and misdiagnosis were common in consulters. More than half with migraine (52.7%) or headache on ≥15 days/month (51.2%), and almost two thirds (63.7%) with TTH, reported no previous diagnosis. Consulters with migraine were as likely (13.8%) to have been diagnosed with "nervous headache" as with migraine. "Nervous headache" (9.8%) and "vascular headache" (7.6%) were the most likely diagnoses in those with TTH, of whom only 5.6% had previously been correctly diagnosed. These were also the most likely diagnoses (14.0% each) in consulters with headache on ≥15 days/month. CONCLUSIONS: This picture of the status quo shows limited reach of headache services in China, and high rates of under-diagnosis and misdiagnosis in those who achieve access to them. This is not a picture of an efficient or cost-effective response to major causes of public ill-health and disability.

[Expression of cation-chloride cotransporters KCC2 and NKCC1 in brainstem of para- chlorophenylalanine-induced acute insomnia rats].

OBJECTIVE: To explore the possible roles of KCC2 and NKCC1 in the pathological mechanism of acute insomnia in rats. METHODS: A total of 18 Sprague-Dawley rats were randomly selected into model, interference and normal control groups.The expressions of KCC2 and NKCC1 in brainstem were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.The concentration of intracellular Cl(-) ([Cl(-)]i) in brainstem was detected by fluorescence probe MQAE with laser confocal microscopy. RESULTS: (1) Comparing with the control group, both KCC2 mRNA and protein expression were down-regulated in the model and interference groups (mRNA:0.196 ± 0.021 vs 0.939 ± 0.109, P < 0.05; 0.485 ± 0.026 vs 0.939 ± 0.109, P < 0.05; protein expression:0.363 ± 0.058 vs 0.967 ± 0.155, P < 0.05; 0.663 ± 0.106 vs 0.967 ± 0.155, P < 0.05).However they became up-regulated in the interference group versus the model group (mRNA: 0.485 ± 0.026 vs 0.196 ± 0.021, P < 0.05; protein expression:0.663 ± 0.106 vs 0.363 ± 0.058, P < 0.05). (2) Comparing with the control group, both NKCC1 mRNA and protein expression in the model group were slightly up-regulated.But statistical difference was insignificant (mRNA: 0.344 ± 0.026 vs 0.320 ± 0.019, P > 0.05; protein expression:0.244 ± 0.010 vs 0.230 ± 0.021, P > 0.05).There was down-regulation in the interference group versus the model and control groups (mRNA: 0.066 ± 0.031 vs 0.320 ± 0.019, P < 0.05; 0.066 ± 0.031 vs 0.344 ± 0.026, P < 0.05; protein expression:0.131 ± 0.012 vs 0.230 ± 0.021, P < 0.05; 0.131 ± 0.012 vs 0.244 ± 0.010, P < 0.05). (3) Comparing with the control group, [Cl(-)]i became up-regulated in the model group (0.0315 ± 0.0039 vs 0.0164 ± 0.0019, P < 0.05).It was down-regulated in the interference group versus the model group (0.0182 ± 0.0013 vs 0.0315 ± 0.0039, P < 0.05), but higher than control group without statistical difference (0.0182 ± 0.0013 vs 0.0164 ± 0.0019, P > 0.05). CONCLUSION: The down-regulation of KCC2 and rise of [Cl(-)]i in brainstem may participate in the pathological mechanism of acute insomnia in rats. And the mechanism of sedative-hypnotic diazepam may be operate through an up-regulation of KCC2, a down-regulation of NKCC1 and decreased [Cl(-)]i.

[Neuroprotective mechanism of hydrogen sulfide after cerebral ischemia-reperfusion in rats].

OBJECTIVE: To explore the neuroprotective mechanism of exogenous hydrogen sulfide after cerebral ischemia-reperfusion (I/R) in rats. METHODS: A total of 240 male Sprague-Dawley rats were randomly divided into 4 groups of sham-operation group (I), I/R model group (II), low-dose sodium hydrosulfide (NaHS) group (III) and high-dose NaHS group (IV) (n = 60 each). Reversible middle cerebral artery occlusion (MCAO) model was established by intraluminal suture. However, the rats of group I were operated without a blockage of middle cerebral artery. The occlusions in other groups were removed after 2 h. And at 20 min pre-removal, normal saline, 50 µmol/kg NaHS, and 100 µmol/kg NaHS were injected into the abdomens of rats in groups II, III and IV respectively. At 6 h, 24 h, 48 h and 7 d post-reperfusion, behavioral test was performed to evaluate the neurological deficiency. And triphenyltetrazolium chloride (TTC) staining was used to observe the volume of cerebral infarction. In addition, the protein expressions of tumor necrosis factor-alpha (TNF-α) and heat shock protein 20 (HSP20) in ischemic cortex were measured by immunohistochemistry and Western blot. RESULTS: Compared with I/R group, the neurological deficiency scores and volume of cerebral infarction of groups III and IV significantly decreased. Furthermore, the protein expression of HSP20 was markedly up-regulated in the groups III and IV while there was a marked down-regulation of TNF-α after reperfusion. CONCLUSION: NaHS may exert anti-necrotic and anti-inflammatory function by inducing the expression of HSP20, inhibiting the expression of TNF-α and reducing the size of cerebral infarction so as to protect neurons after I/R injury.

Semi-supervised medical image segmentation via cross-guidance and feature-level consistency dual regularization schemes.

BACKGROUND: Semi-supervised learning is becoming an effective solution for medical image segmentation because of the lack of a large amount of labeled data. PURPOSE: Consistency-based strategy is widely used in semi-supervised learning. However, it is still a challenging problem because of the coupling of CNN-based isomorphic models. In this study, we propose a new semi-supervised medical image segmentation network (DRS-Net) based on a dual-regularization scheme to address this challenge. METHODS: The proposed model consists of a CNN and a multidecoder hybrid Transformer, which adopts two regularization schemes to extract more generalized representations for unlabeled data. Considering the difference in learning paradigm, we introduce the cross-guidance between CNN and hybrid Transformer, which uses the pseudo label output from one model to supervise the other model better to excavate valid representations from unlabeled data. In addition, we use feature-level consistency regularization to effectively improve the feature extraction performance. We apply different perturbations to the feature maps output from the hybrid Transformer encoder and keep an invariance of the predictions to enhance the encoder's representations. RESULTS: We have extensively evaluated our approach on three typical medical image datasets, including CT slices from Spleen, MRI slices from the Heart, and FM Nuclei. We compare DRS-Net with state-of-the-art methods, and experiment results show that DRS-Net performs better on the Spleen dataset, where the dice similarity coefficient increased by about 3.5%. The experimental results on the Heart and Nuclei datasets show that DRS-Net also improves the segmentation effect of the two datasets. CONCLUSIONS: The proposed DRS-Net enhances the segmentation performance of the datasets with three different medical modalities, where the dual-regularization scheme extracts more generalized representations and solves the overfitting problem.

The prevalence and burden of primary headaches in China: a population-based door-to-door survey.

OBJECTIVES: In the absence of reliable data on the prevalence and burden of primary headache disorders in the mainland of China, a population-based survey was initiated by Lifting The Burden: the Global Campaign against Headache. METHODS: Throughout all regions of China, 5041 non-related adult respondents aged 18-65 years were randomly sampled from the general population according to the expanded programme on immunization method established by World Health Organization. They were visited by door-to-door calling and surveyed using the structured questionnaire developed by Lifting The Burden, translated into Chinese and adapted to Chinese culture after a pilot study. RESULTS: The responder rate was 94.1%.The estimated 1-year prevalence of primary headache disorders was 23.8% (95%confidence interval 22.6-25.0%), of migraine 9.3% (95% confidence interval 8.5-10.1%), of tension-type headache (TTH) 10.8%(9.9-11.6%), and of chronic daily headache (CDH) 1.0% (0.7-1.2%). Of respondents with migraine, TTH, and CDH, moderate or severe impact and therefore high need for effective medical care were reported by 38.0%, 23.1%, and 47.9%, respectively.The World Health Organization quality of life-8 questionnaire showed that all 3 types of headache reduced life quality. The total estimated annual cost of primary headache disorders, including migraine,TTH, and CDH was CNY 672.7 billion, accounting for 2.24% of gross domestic product (GDP) (direct cost: CNY 108.8 billion, 0.36% of GDP; indirect cost: CNY 563.9 billion, 1.88%of GDP). CONCLUSION: The prevalence of primary headaches is high in China and not dissimilar from the world average. These headaches cause disability, impair work, study and daily activities, decrease life quality, and bring about a heavy and hitherto unrecognized socioeconomic burden.

Body mass index and migraine: a survey of the Chinese adult population.

The objective of this study is to evaluate the association between body mass index (BMI) and migraine in general population Chinese cohort. This was a cross-sectional secondary analysis from a general population Chinese cohort of men and women of reproductive and post-reproductive age ranging between 18 and 65 years. Migraine was defined utilizing ICHD criteria. Body mass indices were calculated using measured height and weight and categorized based on the World Health Organizations criteria. The 1-year period prevalence of migraine was 9.3 %. No association was identified between migraine and those with a BMI < 30.0. Compared to those with normal BMI (18.5-23.0), those with BMI ≥ 30 (morbid obesity) had a greater prevalence of migraine (8.6 vs. 13.8 %, p = 0.000). Multivariate-adjusted odds ratio demonstrated that those with morbid obesity had a greater than twofold increased odds of migraine [OR 2.10 (1.39-3.12)] as compared to those with a BMI between 18.5 and 23.0. No association was found between obesity and migraine severity, frequency, or disability. Morbid obesity was associated with twofold increased odds of migraine in this Chinese men and women cohort of predominantly reproductive age.

[Clinical and imaging features of adult anoxic-ischemic encephalopathy after cardiopulmonary resuscitation].

OBJECTIVE: To explore the clinical and imaging features of anoxic-ischemic encephalopathy (AIE) patients after cardiopulmonary resuscitation. METHODS: A total of 28 qualified AIE patients during the last decade from Xiangya Hospital, Central South University were recruited and analyzed retrospectively. RESULTS: The symptoms of status epilepticus, acute posthypoxic myoclonus, Lance-Adams syndrome, subarachnoid hemorrhage and cognitive deficits were observed. The abnormal findings of magnetic resonance imaging (MRI) or computed tomography (CT), involving neocortex, basal ganglia and para-ventricular white matter, were also recorded. During the early phase of disease, swollen cortex was present on MRI/CT. However, encephalatrophy appeared during the late phase. The more severe symptoms were observed, the more foci were present on MRI/CT. CONCLUSION: The etiologies of AIE patients are heterogeneous after cardiopulmonary resuscitation. The clinical symptoms and imaging studies are of prognostic significance.

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.

Safety Findings in Lasmiditan as a Novel Acute Treatment of Migraine in Chinese Patients: A Post Hoc Analysis of the Randomized Controlled Phase 3 CENTURION Trial.

INTRODUCTION: Lasmiditan is the first 5-HT1F receptor agonist with potential to address the huge unmet medical needs for the treatment of migraine in China. The CENTURION study was the first phase 3 study of lasmiditan in Caucasian and Chinese patients with migraine. This post hoc analysis further demonstrates the safety profile of lasmiditan in the Chinese population and was urgently needed. METHODS: Patients were randomized 1:1:1 to lasmiditan 200 mg lasmiditan 100 mg, or a control group. The incidence of treatment-emergent adverse events (TEAEs), their severity, and incidence by treated attacks for frequently reported TEAEs (≥ 5%) were evaluated. The duration, onset, and relationship of efficacy with very common TEAEs (≥ 10%) was analyzed. RESULTS: A total of 281 Chinese patients were included in this post hoc analysis. No deaths and no study drug-related treatment emergent serious adverse events (TESAEs) were reported. The incidence of at least one TEAE was higher in patients receiving lasmiditan 200 mg (73.9%) and 100 mg (66.3%) versus placebo (26.6%). TEAEs were generally mild or moderate in severity, and the incidence of frequently reported TEAEs was generally highest during the first attack. Very common TEAEs with lasmiditan included dizziness, asthenia, somnolence, muscular weakness, fatigue, and nausea. The duration of dizziness was longest during the first attack. There were no cardio-cerebrovascular ischemic events and serotonin syndrome. The presence of very common TEAEs (except nausea), and severe dizziness, did not appear to have a negative influence on the efficacy. CONCLUSION: In the Chinese population of the CENTURION study, most of the TEAEs were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort, while the overall safety profile of lasmiditan in the Chinese population was generally consistent with the CENTURION primary cohort. No new safety concerns were observed in the Chinese population. TRIAL REGISTRATION: NCT03670810.

Although there is significant unmet medical need among patients with migraine, there has been no novel compound for treatment of migraine over past two decades in China. These unmet medical needs persist because the current available medications for the acute treatment of migraine are reported to have safety and tolerability issues. Lasmiditan is a new class of acute migraine medication (5-HT receptor agonist with high selectivity for the 5-HT_1F receptor) with a proven efficacy and safety in phase 2 and 3 studies. Owing to some differences in clinical practice between China and western countries, there is need to get additional evidence on safety of lasmiditan in the Chinese population to support its usage in clinical practice.This post hoc analysis was conducted to present the detailed safety profile of lasmiditan in the Chinese population using data from the CENTURION study. Approximately half of the analyzed population was not covered in the published primary cohort.The results show that in the Chinese population of the study, most of the treatment-emergent adverse events (TEAEs) were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort with no new safety concerns observed in the Chinese population. The overall safety profile of lasmiditan in the Chinese population was generally consistent with the primary cohort. The results provide additional evidence and emphasize that lasmiditan may be considered as a useful acute treatment option with acceptable safety profile for patients with migraine in China.