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AIM: To explore the neuro-ophthalmological characteristics of acute macular neuroretinopathy(AMN)after SARS-CoV-2 infection.METHODS: A total of 8 patients(14 eyes), including 6 females and 2 males, who were diagnosed with AMN in the neuro-ophthalmology department of Xi'an No.1 Hospital(The First Affiliated Hospital of Northwest University)from December 27, 2022 to February 1, 2023 were included in the study. All patients had a history of SARS-CoV-2 infection before the disease, and the results of best corrected visual acuity(BCVA), non-contact indirect intraocular pressure measurement, fundus color photography, near infrared(IR), spectral-domain optical coherence tomography(SD-OCT), OCT angiography(OCTA), fundus fluorescein angiography(FFA), indocyanine green angiography(ICGA), visual field, visual evoked potential(VEP), and electroretinogram(ERG)were collected. Furthermore, the neuro-opthalmology characteristics of the included patients were analyzed and summarized.RESULTS: The included 8 patients aged from 20 to 43, with an average age of(30±6.63)years old. The patients had a history of SARS-CoV-2 infection 3 to 11(mean 5±3.51)d before the disease, and 6 out of 8 patients developed visual symptoms within 5 d of infection with SARS-CoV-2, with manifestated with decreased vision or visual scotoma. The visual acuity varied from 0.08 to 1.0, with visual field defect characterized by central, paracentral or peripheral scotoma. VEP showed prolongation latency of P100 or P2, and ERG revealed impaired function of retinal photoreceptor cell. In the early stage of the disease, the size and shape of early visual acuity, visual field, and extraretinal lesions in patients with AMN associated with SARS-CoV-2 infection may not match, and the lower the visual acuity, the later the VEP peaks.CONCLUSION: The neuro-ophthalmic features of SARS-CoV-2 infection-associated AMN require the attention of clinicians. In addition to multi-mode fundus imaging, clinicians should use a variety of methods to comprehensively evaluate visual function and prognosis of patients.

目的 探讨动脉内溶栓（intra-arterial thrombolysis，IAT）治疗视网膜中央动脉阻塞（central retinal artery occlusion，CRAO）患者的临床特征及功能性视觉恢复情况。 方法 纳入2018年1月—2023年8月西北大学附属第一医院神经内科和神经眼科连续收治的非动脉炎性CRAO患者，根据入院后是否进行IAT治疗分为IAT组和非IAT组。功能性视觉定义为 视力≥20/100。比较分析两组患者的临床特征和不同时间段（入院、出院时和出院1个月时）功能性视觉恢复情况。 结果 共纳入131例（131只眼）非动脉炎性CRAO患者，男性93例（71.0%），平均年龄为（61.6±12.6）岁， 其中IAT组57例（43.5%），非IAT组74例（56.5%）。与非IAT组患者相比，IAT组患者年龄更低[（58.4±12.5）岁 vs.（64.1±12.2）岁，P=0.011]、合并卒中病史者比例更低[10（17.5%）vs. 25（33.8%）， P=0.037]、发病至就诊时间更短[10.0（6.0～24.0）h vs. 55.0（20.2～162.0）h，P＜0.001]、醒后发病者比例更高[26（45.6%）vs. 15（20.3%），P=0.002]和患侧颈内动脉血管状态更佳（无狭窄∶轻度狭窄∶中-重度狭窄∶闭塞=41∶7∶7∶2 vs. 32∶11∶21∶10，P=0.006）。IAT组患者出院1个月时功能性视觉比例较非IAT组患者更高[25（43.9%）vs. 18（24.3%），P=0.018]，而入院和出院时差异无统计学意义 （P＞0.05）。多因素logistic回归分析显示，IAT组患者出院1个月时的功能性视觉较非IAT组患者显著改善（OR 3.24，95%CI 1.08～9.69，P=0.036）。IAT组患者术中发生眼动脉痉挛2例（3.5%）、穿刺部位皮肤出血2例（3.5%）和新发脑栓塞（均为无症状性栓塞）事件4例（7.0%）。 结论 是否进行IAT治疗的CRAO患者部分临床特征存在差异，IAT治疗可显著提高CRAO患者出院1个月时的功能性视觉，且手术安全性较好。提示临床医师需重视CRAO患者的IAT治疗，以期改善患者的视觉功能。 Abstract: Objective To investigate the clinical characteristics and functional visual recovery of patients with central retinal artery occlusion (CRAO) treated with intra-arterial thrombolysis (IAT). Methods The non-arteriotic CRAO patients admitted to the Department of Neurology and Neuro-ophthalmology of the First Affiliated Hospital of Northwest University from January 2018 to August 2023 were included. They were divided into IAT group and non-IAT group according to whether IAT was performed after admission. Functional vision is defined as visual acuity≥20/100. The clinical features and functional visual recovery at different time periods (admission, discharge and 1 month after discharge) were compared and analyzed between the two groups. Results A total of 131 patients (131 eyes) with non-arteriotic CRAO were included, including 93 males (71.0%) with a mean age of (61.6±12.6) years. There were 57 patients (43.5%) in IAT group and 74 patients (56.5%) in non-IAT group. Compared with patients in non-IAT group, patients in IAT group had younger age [(58.4±12.5) years vs. (64.1±12.2) years, P=0.011], lower proportion of stroke history [10 (17.5%) vs. 25 (33.8%), P=0.037], shorter time from onset to visit [10.0 (6.0-24.0) h vs. 55.0 (20.2-162.0) h, P0.05). Multivariate logistic regression analysis showed that the functional vision of CRAO patients in the IAT group at 1 month after discharge was significantly improved compared with those in the non-IAT group (OR 3.24, 95%CI 1.08-9.69, P=0.036). In the IAT group, ophthalmic artery spasm occurred in 2 cases (3.5%), skin bleeding at the puncture site in 2 cases (3.5%), and new cerebral embolism (all asymptomatic embolism) occurred in 4 cases (7.0%). Conclusions Some clinical features of CRAO patients who were treated with or without IAT were different. IAT can significantly improve the functional vision of CRAO patients at 1 month after discharge, and the surgical safety is good. This suggests that clinicians should pay more attention to IAT in CRAO patients in order to improve their visual function.

Introduction: The triglyceride-glucose (TyG) index is reported to be related to poor functional outcomes and all-cause mortality post-stroke. However, the association between TyG index and recurrent stroke after acute ischemic stroke (AIS) has not been well described. We aimed to identify whether the TyG index was associated with 1-year recurrent stroke after AIS. Methods: Baseline patient information was collected at admission, and the TyG index was calculated. Recurrent stroke events were followed up at 1, 3, 6, and 12 months after diagnosis. We then examined the association between the TyG index and risk of 1-year recurrent stroke using multivariable Cox regression models and restricted cubic spline analyses. Results: Among 2,288 participants, the mean TyG index was 8.8 ± 0.7. Those in the fourth quartile (Q4) demonstrated higher recurrent stroke risk than those in Q1 (adjusted hazard ratio [HR] = 1.63; 95% confidence interval [CI], 0.98–2.72; p = 0.059). Subgroup analysis revealed a sex-specific association between TyG index and recurrent stroke (p for interaction = 0.022). Additionally, restricted cubic splines analyses showed a nonlinear association between the TyG index and 1-year recurrent stroke. In females, patients in the Q4 had a 2.95-fold increased recurrent stroke risk than did patients in the Q1 (adjusted HR = 2.95; 95% CI: 1.09–7.94; p = 0.032); the risk increased when the TyG index was >8.73. However, no significant correlation was observed in males. Conclusion: A nonlinear association was found between the TyG index and 1-year recurrent stroke risk. Subsequently, a high TyG index could predict an increased 1-year recurrent stroke risk in female AIS patients. [ABSTRACT FROM AUTHOR]

Background: Stroke is an important cause of death and disability worldwide, ranking second in the cause of death, and it is thought to be related to genetic factors. The purpose of our study is to investigate the association between CASZ1, WNT2B and PTPRG single nucleotide polymorphisms (SNPs) and stroke risk in the Chinese population. Methods: We recruited 1418 volunteers, comprised of 710 stroke cases and 708 controls in this study. We used MassARRAY iPLEX GOLD method to genotype the three SNPs on CASZ1, WNT2B and PTPRG. Logistic regression was used to analyse the association between these SNPs and stroke, and odds ratios (ORs) and 95% confidence intervals (CIs) were then calculated. What's more, the interactions among SNPs were predicted by multi‐factor dimensionality reduction (MDR) analysis. Results: This research demonstrated that CASZ1 rs880315 and PTPRG rs704341 were associated with reduced stroke susceptibility. More precisely, CASZ1 rs880315 was associated with reduced stroke susceptibility in people aged ≤64 years and women. PTPRG rs704341 was associated with reduced stroke susceptibility in people aged >64 years, women, non‐smokers and non‐drinkers. Conversely, WNT2B rs12037987 was related to elevated stroke susceptibility in people aged >64 years, women and non‐smokers. In addition, CASZ1 rs880315, WNT2B rs12037987 and PTPRG rs704341 had a strong redundancy relationship. Conclusion: Our study concludes that CASZ1 rs880315, WNT2B rs12037987 and PTPRG rs704341 are associated with stroke, and the study provides a basis for assessing genetic variants associated with stroke risk in the Han Chinese population. [ABSTRACT FROM AUTHOR]

S100B is an essential biomarker in the early diagnosis and treatment monitoring of brain injury. However, the traditional clinical diagnostic assay for S100B detection requires a complex operation or large equipment, which limits its application for rapid point-of-care tests (POCT). This study aimed to establish a lateral-flow immunoassay (LFIA) strip test system for S100B determination. PSS-MA-GoldMag nanoparticles were conjugated with anti-S100B antibodies as probes. Using this antibody-nanoparticle composite, an LFIA system based on magnetic quantification was established for S100B detection. For the evaluation of the performance of this LFIA system in clinical practice, 216 clinical samples were assayed using the LFIA test system and a commercial ECLI kit. Using the LFIA system, reliable results could be obtained in 30 min with a detection limit of 0.05 ng mL−1. The coefficient of variation (CV) was <13.8% and <14.03% for intra- and inter-assay precision, respectively. The recoveries were between 95.1 and 107.3%. The relative deviation of the interference experiments was <10%. In the analysis of clinical samples, the result indicated that the sera level of S100B in the detection group did not correlate with gender (p = 0.564 > 0.05) or age (p = 0.083 > 0.05). There is a good correlation between the novel method and the Elecsys®, with a determination coefficient of R2 0.9566, p > 0.05. The Bland–Altman analysis between the two ways shows that the 95% confidence bands between the two methods in measuring S100B were −0.27 ng mL−1 to +0.29 ng mL−1 with a mean difference of +0.006 ng mL−1. These results indicated that the novel LFIA system could be a simple, rapid, convenient, and accurate method for S100B determination. [ABSTRACT FROM AUTHOR]

A nine-year-old boy manifested with headache, progressive mild cognitive decline and hemiparesis, but without clinical epileptic seizures (with abnormal EEG waves). Brain magnetic resonance imaging (MRI) showed bilateral cortical lesions mainly on the right hemisphere, and new lesions developed in frontal, parietal, occipital and temporal lobes around the old lesions presenting as a lace-like or ring-like enhancement in T1 with contrast over a disease course of five years. A suspected diagnosis of primary angiitis of the central nervous system was initially considered. Treated with high-dose corticosteroids, intravenous immunoglobulins and monthly pulse cyclophosphamide, his symptoms worsened with the intracranial lesion progression. Brain biopsy of the right frontal lobe was performed nearly five years after onset; prominent neuronal loss, a microglial nodule, as well as parenchymal and perivascular lymphocytic infiltrate within the cortex were found, which coincided with RE pathology changes. Encouragingly, after a regimen of rituximab, lesions on the follow-up brain MRI tended to be stable. Apparently, it was immune-mediated, but did not strictly fit any known disease entity, although it was similar to RE. We summarize this unique case, including clinical characteristics, imaging and pathology findings. We also discuss the diagnosis and treatment, focusing on comparison to RE as well as other possible neurological diseases. [ABSTRACT FROM AUTHOR]

Psoralidin (PSO) is a natural phenolic coumarin extracted from the seeds of Psoralea corylifolia L. Growing preclinical evidence indicates that PSO has anti‐inflammatory, anti‐vitiligo, anti‐bacterial, and anti‐viral effects. Growth arrest‐specific gene 6 (GAS6) and its receptor, Axl, modulate cellular oxidative stress, apoptosis, survival, proliferation, migration, and mitogenesis. Notably, the neuroprotective role of the GAS6/Axl axis has been identified in previous studies. We hypothesize that PSO ameliorates cerebral hypoxia/reoxygenation (HR) injury via activating the GAS6/Axl signaling. We first confirmed that PSO was not toxic to the cells and upregulated GAS6 and Axl expression after HR injury. Moreover, PSO exerted a marked neuroprotective effect against HR injury, represented by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release, and reactive oxygen species (ROS) generation. Furthermore, PSO pretreatment also elevated the levels of nuclear factor‐related factor 2 (Nrf‐2), NAD(P)H dehydrogenase quinone‐1 (NQO1), heme oxygenase‐1 (HO‐1), silent information regulator 1 (SIRT1), peroxisome proliferator‐activated receptor coactivator 1α (PGC‐1α), nuclear respiratory factor 1 (NRF1), uncoupling protein 2 (UCP2), and B‐cell lymphoma 2 (BCl2) both in the condition of baseline and HR injury. However, GAS6 siRNA or Axl siRNA inhibited the neuroprotective effects of PSO. Our findings suggest that PSO pretreatment attenuated HR‐induced oxidative stress, apoptosis, and mitochondrial dysfunction in neuroblastoma cells through the activation of GAS6/Axl signaling. [ABSTRACT FROM AUTHOR]

Background: To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. Methods: In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2 years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. Results: In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non‐immunosuppression and immunosuppression groups, respectively. Relative to non‐immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable‐adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18–0.40; p < 0.001) and IPTW‐weighted Cox model (HR 0.28; 95% CI 0.19–0.42; p < 0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1‐month increase; 95% CI 0.87–0.92; p < 0.001; IPTW‐adjusted). Combination therapy with steroids and non‐steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07–0.26; p < 0.001). Conclusion: Immunosuppression significantly reduced the 2‐year risk of generalization in patients with OMG. [ABSTRACT FROM AUTHOR]

Neuronal intranuclear inclusion disease (NIID) is a rare and slowly progressive neurodegenerative disease characterized by the presence of eosinophilic neuronal intranuclear inclusions. The clinical manifestations of NIID are diverse, and the most common initial feature in cases of sporadic NIID is dementia. Herein, we report an adult female with keratitis as the initial presentation with subsequent bilateral limb tremor, gait disturbances, overemotional behavior, sweating and constipation. Diffusion-weighted imaging (DWI) showed hyperintensity in the bilateral fronto-parieto-occipital corticomedullary junction. Skin biopsy specimens revealed eosinophilic hyaline intranuclear inclusions in fibroblast cells, sweat gland cells and adipose cells. In vivo confocal microscopy of the cornea indicated the absence of corneal nerves in both affected eyes. The patient's diagnosis of NIID was based on the presence of intranuclear inclusions in biopsied skin and the characteristic high-intensity signal in the corticomedullary junction obtained with DWI. This case report emphasizes that the clinical heterogeneity of NIID and an examination of the corneal nerves may offer valuable clues to its early diagnosis in some patients. [ABSTRACT FROM AUTHOR]

Background: The relationship between baseline fasting blood glucose (FBG) levels and 1-year stroke recurrence in non-diabetic patients with acute cerebral infarction (ACI) is unclear. We aimed to clarify this relationship in non-diabetic patients with ACI. Methods: Baseline FBG levels and related information of the patients were collected at admission and the events of stroke recurrence were followed up 1, 3, 6, and 12 months after the patients were discharged. Baseline FBG levels were analyzed as continuous variables and quartiles (Q1–Q4). Multivariate Cox regression models and a two-piecewise linear regression model were used to investigate the relationship and determine the threshold effect between baseline FBG levels and 1-year stroke recurrence in non-diabetic patients with ACI. Results: Overall, 1,634 non-diabetic patients with ACI were enrolled. After adjusting for potential confounding factors, the hazard is 2.24-fold higher in Q4 than those in Q2, being considered the reference in non-diabetic patients with ACI [hazard ratio (HR) = 2.24, 95%CI: 1.08–4.65, P = 0.031]. Plotting hazard ratios over baseline FBG levels suggested a J-shaped relationship for 1-year stroke recurrence. Further analysis revealed that the nadir value of baseline FBG levels is 4.6 mmol/L. The relationship was more significant in patients with atrial fibrillation than in those without (P for interaction = 0.009). Conclusion: Lower and higher baseline FBG levels may lead to an increased risk of 1-year stroke recurrence in non-diabetic patients with ACI as shown by a J-shaped curve with a nadir value of 4.6 mmol/L. [ABSTRACT FROM AUTHOR]

Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS. [ABSTRACT FROM AUTHOR]

Abstract Background There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients. Methods/Design In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period. Discussion The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy. Trial Registration ClinicalTrials.gov: NCT01201642

Gold magnetic nanoparticles (GoldMag) have attracted great attention due to their unique physical and chemical performances combining those of individual FeO and Au nanoparticles. Coating GoldMag with polymers not only increases the stability of the composite particles suspended in buffer but also plays a key role for establishing point-of-care optical tests for clinically relevant biomolecules. In the present paper, poly(4-styrenesulfonic acid-co-maleic acid) (PSS-MA), a negatively charged polyelectrolyte with both sulfonate and carboxylate anionic groups, was used to coat the positively charged GoldMag (30 nm) surface. The PSS-MA-coated GoldMag complex has a stable plasmon resonance adsorption peak at 544 nm. A pair of anti-D-dimer antibodies has been coupled on this GoldMag composite nanoparticle surface, and a target protein, D-dimer was detected, in the range of 0.3-6 μg/mL. The shift of the characteristic peak, caused by the assembly of GoldMag due to the formation of D-dimer-antibody sandwich bridges, allowed the detection. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function–normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1‐year outcomes in patients with acute ischemic stroke (AIS).This is a prospective, multicenter observational study. Renal function–normalized SUA levels were determined by calculating the ratio of SUA to SCr. One‐year outcomes included stroke recurrence, all‐cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1‐year stroke outcomes.Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one‐unit increase in SUA/SCr corresponded to a 19% decrease in 1‐year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1–Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1‐year stroke recurrence risks. The trend test indicated significant differences in the 1‐year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all‐cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1‐year stroke recurrence.In patients with AIS, low SUA/SCr may be an independent risk factor for 1‐year stroke recurrence. Changes in SUA/SCr had no significant impact on 1‐year poor prognosis and all‐cause mortality. [ABSTRACT FROM AUTHOR]

Background: Dorsolateral medullary infarction (Wallenberg syndrome) is rare in clinical practice; however, the subsequent corneal lesions are more uncommon. To our knowledge, only one such case was previously reported. We report a similar case with successful treatment and recovery, and analyse both cases to address the clinical features and outcomes of such syndrome.Case Presentation: A 43-year-old male presented with neurotrophic keratopathy one month after sustaining dorsolateral medullary infarction. The patient underwent amniotic membrane transplantation twice. Two-year follow-up observation revealed changes in nerve fibers and epithelial cells of corneal by laser confocal microscopy.Conclusion: By studying both cases, we confirm that neurotrophic keratopathy could be as a delayed-onset complication of Wallenberg syndrome. The recognition that neurotrophic keratopathy can follow dorsolateral medullary infarction could prevent the clinical misdiagnosis. [ABSTRACT FROM AUTHOR]

Ischemia reperfusion injury (IRI) is associated with poor prognoses in the setting of ischemic brain diseases. Silence information regulator 1 (SIRT1) is a member of the third class of nicotinamide adenine dinucleotide (NAD+)-dependent sirtuins. Recently, the role of SIRT1/peroxisome proliferators-activated receptor-γ coactivator 1α (PGC-1α) pathway in organ (especially the brain) protection under various pathological conditions has been widely investigated. Mangiferin (MGF), a natural C-glucosyl xanthone polyhydroxy polyphenol, has been shown to be beneficial to several nervous system diseases and the protective effects of MGF can be achieved through the regulation of SIRT1 signaling. This study is designed to investigate the protective effects of MGF treatment in the setting of cerebral IRI and to elucidate the potential mechanisms. We first evaluated the toxicity of MGF and chose the safe concentrations for the following experiments. MGF exerted obvious neuroprotection against hypoxia/reoxygenation (HR)-induced injury, indicated by restored cell viability and cell morphology, decreased lactate dehydrogenase (LDH) release and reactive oxygen species generation. MGF also restored the protein expressions of SIRT1, PGC-1α, Nrf2, NQO1, HO-1, NRF1, UCP2, and Bcl2 down-regulated by HR treatment. However, SIRT1 siRNA could reverse MGF-induced neuroprotection and decrease the expressions of molecules mentioned above. Taken together, our findings suggest that MGF treatment exerts neuroprotection against HR injury via activating SIRT1/PGC-1α signaling. These findings may provide a theoretical basis for the exploitation of MGF as a potential neuroprotective drug candidate, which may be beneficial for the ischemic stroke patients in clinic. [ABSTRACT FROM AUTHOR]

Background: Central retinal artery occlusion (CRAO) is a medical condition characterized by sudden blockage of the central retinal artery, which leads to a significant and often irreversible loss of vision. Observational studies have indicated that diabetes mellitus is a risk factor for CRAO; however, there is no research on the causal relationship between diabetes mellitus, particularly type 2 diabetes, and CRAO. This study aimed to perform Mendelian randomization (MR) analysis to clarify the causal relationship between type 2 diabetes and CRAO., Methods: Genetic variants associated with type 2 diabetes were selected from two different datasets. A recent genome-wide association study of CRAO conducted using the FinnGen database was used as the outcome data. A two-sample MR was performed to evaluate the causal relationship between type 2 diabetes and CRAO. Inverse variance weighting was the primary method, and MR-Egger, maximum likelihood, and median weighting were used as complementary methods. A multivariate MR (MVMR) analysis was performed to further evaluate the robustness of the results. Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test were used for the sensitivity analyses., Results: Genetically predicted type 2 diabetes was causally associated with CRAO(odds ratio [OR] =2.108, 95% confidence interval [CI]: 1.221-3.638, P=7.423×10 -3 ), which was consistent with the results from the validation dataset (OR=1.398, 95%CI: 1.015-1.925, P=0.040). The MVMR analysis suggested that type 2 diabetes may be an independent risk factor for CRAO (adjusted OR=1.696; 95%CI=1.150-2.500; P=7.655×10 -3 ), which was assumed by the validation dataset (adjusted OR=1.356; 95%CI=1.015-1.812; P=0.039)., Conclusion: Our results show that genetically predicted type 2 diabetes may be causally associated with CRAO in European populations. This suggests that preventing and controlling type 2 diabetes may reduce the risk of CRAO., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Lu, Liu, Lin, Peng, Lu, Guo, Liu, Zhang and Wu.)

Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute antibodies (AGO-Abs) present as potential biomarkers of the overlap syndrome between NMOSD and other autoimmune diseases. In this paper, we present the case of an adult woman with numbness, tingling, and burning sensations in her arms and subsequent bilateral internuclear ophthalmoplegia. Brain-cervical-thoracic magnetic resonance imaging (MRI) showed T2 hyperintensities in the dorsal brainstem and around the midbrain aqueduct and longitudinally transverse myelitis with homogeneous enhancement on gadolinium-enhanced MRI. The contemporaneous detection of AQP4- and AGO-Abs led to a definite diagnosis of overlap syndrome of NMOSD with AGO-Abs. The patient was treated with immunosuppressive agents, including corticosteroids and immunoglobulins, and achieved remission. This case highlights a novel phenotype of NMOSD with AGO-Abs overlap syndrome, which presents with relapsing brainstem syndrome and longitudinally extensive myelitis with acute severe neurological involvement. The promising prognosis of the disease could serve as a distinct clinical profile. Broad screening for antibodies against central nervous system autoimmune antigens is recommended in suspected patients with limited or atypical clinical manifestations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Lin and Wu.)

Objectives: Evidence on the association between fasting blood glucose and mortality in non-diabetic patients who had a stroke is limited. We aimed to investigate the association of baseline fasting plasma glucose (FPG) with 1 year all-cause mortality in non-diabetic patients with acute cerebral infarction (ACI)., Design: A multicentre prospective cohort study., Setting: Four grade A tertiary hospitals in the Xi'an district of China., Participants: A total of 1496 non-diabetic patients within 7 days of ACI were included., Main Outcome Measures: The outcome was 1 year all-cause mortality. Baseline FPG was analysed as a continuous variable and was divided into four quartiles (group Q1-group Q4). We used multivariable Cox regression analyses, curve fitting and Kaplan-Meier (K-M) analyses to explore the association of baseline FPG with 1 year all-cause mortality in non-diabetic patients with ACI., Results: After controlling for confounders, multivariable Cox regression analyses indicated a 17% increase in 1 year all-cause mortality for every 1 mmol/L of baseline FPG increase (HR=1.17, 95% CI 1.02 to 1.35, p=0.030). Patients from the Q4 group had 2.08 times increased hazard of 1 year all-cause mortality compared with the Q1 group (HR=2.08, 95% CI 1.13 to 3.82, p=0.019), while the survival rate of patients in group Q4 was decreased compared with that in other groups (p<0.001). The curve fitting revealed a positive but non-linear association of baseline FPG with 1-year all-cause mortality in non-diabetic patients with ACI., Conclusion: In non-diabetic patients with ACI, elevated baseline FPG is an independent risk factor for 1-year all-cause mortality, and the two are positively and non-linearly associated. These results suggest that high FPG should be seen as a concern in non-diabetic patients with ACI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To address a novel lower-dose rituximab (RTX) therapy strategy based on our clinical experience and assess its efficacy and safety in neuromyelitis optica spectrum disorder (NMOSD)., Methods: A multicenter, open-label, self-controlled, prospective follow-up study. Totally, 108 NMOSD patients were enrolled and a lower-dose RTX strategy was applied including 100 mg weekly for 3 weeks and then reinfusions every 6 months. Annualized relapse rate (ARR), the expanded disability status scale (EDSS) score and length of spinal cord lesions were included to evaluate the efficacy. Side effects were recorded to assess the safety profile., Results: Of 108 patients, 80 (74.1%) initiated low-dose RTX therapy immediately after acute attack treatment and 33 (30.6%) initiated it after the first attack. During a median treatment period of 35.5 (22.0-48.8) months, significant decreases were observed in median ARR (1.1 [0.8-2.0] versus 0 [0-0.2], p < 0.001), EDSS score (3.5 [2.5-4.0] versus 2.0 [1.0-3.0], p < 0.001) and spinal cord lesion segments (5.0 [4.0-8.0] versus 3.0 [1.0-6.0], p < 0.001). The cumulative risk of relapses significantly decreased during the post- versus pre-RTX period (HR 0.238, 95%CI 0.160-0.356, p < 0.001) and on early therapy initiated within 24 months after disease onset versus delayed therapy (HR 0.506, 95%CI 0.258-0.994, p = 0.041). No serious side effects were recorded and all the subjects did not discontinue treatment due to RTX-related side effects., Conclusion: Our research provided evidence supporting the lower-dose RTX strategy in treating NMOSD and reopened the issues of optimal dosage and therapy initiation timing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Ren, Lu, Liu, Li, Wu, Xu, Wu, Lei, Ma, Zhao, Bai, Li and Guo.)

Background: H-type hypertension has a high prevalence in China. However, the association of serum homocysteine levels with 1-year stroke recurrence in patients with acute ischemic stroke (AIS) and H-type hypertension has not been studied., Methods: A prospective cohort study of patients with AIS admitted to hospitals between January and December 2015 in Xi'an, China, was conducted. Serum homocysteine levels, demographic data, and other relevant information were collected from all patients upon admission. Stroke recurrences were routinely tracked at 1, 3, 6, and 12 months after discharge. The blood homocysteine level was studied as a continuous variable and tertiles (T1-T3). A multivariable Cox proportional hazard model and a two-piecewise linear regression model were utilized to evaluate the association and ascertain the threshold effect regarding the serum homocysteine level and 1-year stroke recurrence in patients with AIS and H-type hypertension., Results: Overall, 951 patients with AIS and H-type hypertension were enrolled, of whom 61.1% were male. After adjusting for confounders, patients in T3 had a significantly increased risk of recurrent stroke within 1 year, compared with those in T1 as the reference (hazard ratio = 2.24, 95% confidence interval: 1.01-4.97, p = 0.047). Curve fitting showed that serum homocysteine levels were positively curvilinearly correlated with 1-year stroke recurrence. Threshold effect analysis showed that an optimal threshold of serum homocysteine level <25 μmol/L was effective in reducing the risk of 1-year stroke recurrence in patients with AIS and H-type hypertension. Elevated homocysteine levels in patients with severe neurological deficits on admission significantly increased the risk of 1-year stroke recurrence ( p for interaction = 0.041)., Conclusions: In patients with AIS and H-type hypertension, the serum homocysteine level was an independent risk factor for 1-year stroke recurrence. A serum homocysteine level of ≥25 μmol/L significantly increased the risk of 1-year stroke recurrence. These findings can inform the creation of a more precise homocysteine reference range for the prevention and treatment of 1-year stroke recurrence in patients with AIS and H-type hypertension and provide a theoretical foundation for the individualized prevention and treatment of stroke recurrence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Liu, Guo, Lu, Zhang, Lei, Liu, Huang, Wang, Chang, Lin, Wang and Wu.)

Background: Alkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China., Methods: We enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1-Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3-6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes., Results: Overall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19-3.96; P = 0.011] and patients in Q3 (76.8-92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14-0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0-76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes ( P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia ( P > 0.05) for all outcomes., Conclusion: Non-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guo, Liu, Lu, Liu, Lin, Wang, Wang, Chang, Wang and Wu.)

Background: This study aims to develop and validate a nomogram for predicting 1- and 2-year generalization probabilities in patients with ocular myasthenia gravis (OMG)., Methods: In total, 501 eligible patients with OMG treated at seven tertiary hospitals in China between January 2015 and May 2019 were included. The primary outcome measure was disease generalization. A nomogram for predicting 1- and 2-year generalization probabilities was constructed using a stepwise Cox regression model. Nomogram performance was quantified using C-indexes and calibration curves. Two-year cumulative generalization rates were analyzed using the Kaplan-Meier method for distinct nomogram-stratified risk groups. The clinical usefulness of the nomogram was evaluated using decision curve analysis (DCA)., Result: The eligible patients were randomly divided into a development cohort (n=351, 70%) and a validation cohort (n=150, 30%). The final model included five variables: sex, onset age, repetitive nerve stimulation findings, acetylcholine receptor antibody test results, and thymic status. The model demonstrated good discrimination (C-indexes of 0.733 and 0.788 in the development and validation cohorts, respectively) and calibration, with good agreement between actual and nomogram-estimated generalization probabilities. Kaplan-Meier curves revealed higher 2-year cumulative generalization rates in the high-risk group than that in the low-risk group. DCA demonstrated a higher net benefit of nomogram-assisted decisions compared to treatment of all patients or none., Conclusion: The nomogram model can predict 1- and 2-year generalization probabilities in patients with OMG and stratified these patients into distinct generalization risk groups. The nomogram has potential to aid neurologists in selecting suitable patients for initiating immunotherapy and for enrolment in clinical trials of risk-modifying treatments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruan, Sun, Lang, Gao, Guo, Xu, Yu, Wu, Lei, Liu, Zhang, Li, Tang, Gao, Gao, Lu, Li and Chang.)

Background and Purpose: Stroke is the second leading cause of death worldwide and the leading cause of mortality and long-term disability in China, but its underlying risk genes and pathways are far from being comprehensively understood. We here describe the design and methods of whole genome sequencing (WGS) for 10 914 patients with acute ischaemic stroke or transient ischaemic attack from the Third China National Stroke Registry (CNSR-III)., Methods: Baseline clinical characteristics of the included patients in this study were reported. DNA was extracted from white blood cells of participants. Libraries are constructed using qualified DNA, and WGS is conducted on BGISEQ-500 platform. The average depth is intended to be greater than 30× for each subject. Afterwards, Sentieon software is applied to process the sequencing data under the Genome Analysis Toolkit best practice guidance to call genotypes of single nucleotide variants (SNVs) and insertion-deletions. For each included subject, 21 fingerprint SNVs are genotyped by MassARRAY assays to verify that DNA sample and sequencing data originate from the same individual. The copy number variations and structural variations are also called for each patient. All of the genetic variants are annotated and predicted by bioinformatics software or by reviewing public databases., Results: The average age of the included 10 914 patients was 62.2±11.3 years, and 31.4% patients were women. Most of the baseline clinical characteristics of the 10 914 and the excluded patients were balanced., Conclusions: The WGS data together with abundant clinical and imaging data of CNSR-III could provide opportunity to elucidate the molecular mechanisms and discover novel therapeutic targets for stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High plasma levels of trimethylamine N-oxide (TMAO) and its precursor choline have been linked to stroke; however, their association with cerebral small vessel disease remains unclear. Here we evaluated the association of plasma levels of TMAO and choline with imaging markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and cerebral microbleeds. Methods: We performed a baseline cross-sectional analysis of a multicenter hospital-based cohort study from 2015 to 2018. The data were collected from 30 hospitals in China and included 1,098 patients with ischemic stroke/transient ischemic attack aged ≥18 years. White matter hyperintensities, lacunes, and cerebral microbleeds were evaluated with the patients' demographic, clinical, and laboratory information removed. White matter hyperintensities were rated using the Fazekas visual grading scale, while the degree of severity of the lacunes and cerebral microbleeds was defined by the number of lesions. Results: Increased TMAO levels were associated with severe white matter hyperintensities [adjusted odds ratio (aOR) for the highest vs. lowest quartile, 1.5; 95% confidence interval (CI), 1.0-2.1, p = 0.04]. High TMAO levels were more strongly associated with severe periventricular white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.6; 95% CI, 1.1-2.3, p = 0.009) than deep white matter hyperintensities (aOR for the highest vs. lowest quartile, 1.3; 95% CI, 0.9-1.9, p = 0.16). No significant association was observed between TMAO and lacunes or cerebral microbleeds. Choline showed trends similar to that of TMAO in the association with cerebral small vessel disease. Conclusions: In patients with ischemic stroke or transient ischemic attack, TMAO and choline appear to be associated with white matter hyperintensities, but not with lacunes or cerebral microbleeds; TMAO and choline were associated with increased risk of a greater periventricular, rather than deep, white matter hyperintensities burden., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Xu, Pan, Yan, Jing, Yang, Wang, Wan, Gao, Han, Zhong, Liu, Pi, Li, Luo, Wang, Zhao, Wang, Lin, Meng, Zhao, Liu, Li, Jiang, Li, Zhang, Yang, Ji, Wang, Li, Wang, Zheng, Ji, Cai, Wu, Han, Wang and Wang.)

Background and Purpose: Stroke is the leading cause of mortality and disability in China. Precise aetiological classification, imaging and biological markers may predict the prognosis of stroke. The Third China National Stroke Registry (CNSR-III), a nationwide registry of ischaemic stroke or transient ischaemic attack (TIA) in China based on aetiology, imaging and biology markers, will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke., Methods: Between August 2015 and March 2018, the CNSR-III recruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China. Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews. Patients were followed for clinical outcomes at 3 months, 6 months and 1-5 year annually. Brain imaging, including brain MRI and CT, were completed at baseline. Blood samples were collected and biomarkers were tested at baseline., Results: A total of 15 166 stroke patients were enrolled, among which 31.7% patients were women with the average age of 62.2±11.3 years. Ischaemic stroke was predominant (93.3%, n=14 146) and 1020 (6.7%) TIAs were enrolled., Conclusions: CNSR-III is a large scale nationwide registry in China. Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To evaluate the relationship between cyclin D1 overexpression and bladder cancer prognosis., Methods: A systematic literature search up to July 27, 2013 was carried out in PubMed and Wanfang databases, and the references of retrieved articles were screened. The hazard ratios (HRs) and their 95% CIs were used to combine the data. Heterogeneity and publication bias were also evaluated., Results: A total of 15 studies containing 2,591 cases were included. We found that increased cyclin D1 levels were significantly correlated with progression-free survival with a pooled HR estimate of 0.54 (95% CI: 0.32-0.92). There was a significant degree of heterogeneity (I² = 93.8%, P <0.001). Moreover, subgroup analysis indicated that elevated cyclin D1 levels were significantly associated with overall survival in muscle-invasive bladder patients (HR: 0.95, 95% CI: 0.91-0.99), without a significant heterogeneity in the data (I² = 0.0%, P = 0.456)., Conclusions: Increased cyclin D1 expression level detected by immunohistochemistry is associated with good progression-free survival for bladder cancer. Because of the limited number of studies, further well-designed prospective studies are warranted to confirm the findings from our study.

Background: There are a variety of treatment options for Bell's palsy. Evidence from randomized controlled trials indicates corticosteroids can be used as a proven therapy for Bell's palsy. Acupuncture is one of the most commonly used methods to treat Bell's palsy in China. Recent studies suggest that staging treatment is more suitable for Bell's palsy, according to different path-stages of this disease. The aim of this study is to compare the effects of prednisolone and staging acupuncture in the recovery of the affected facial nerve, and to verify whether prednisolone in combination with staging acupuncture is more effective than prednisolone alone for Bell's palsy in a large number of patients., Methods/design: In this article, we report the design and protocol of a large sample multi-center randomized controlled trial to treat Bell's palsy with prednisolone and/or acupuncture. In total, 1200 patients aged 18 to 75 years within 72 h of onset of acute, unilateral, peripheral facial palsy will be assessed. There are six treatment groups, with four treated according to different path-stages and two not. These patients are randomly assigned to be in one of the following six treatment groups, i.e. 1) placebo prednisolone group, 2) prednisolone group, 3) placebo prednisolone plus acute stage acupuncture group, 4) prednisolone plus acute stage acupuncture group, 5) placebo prednisolone plus resting stage acupuncture group, 6) prednisolone plus resting stage acupuncture group. The primary outcome is the time to complete recovery of facial function, assessed by Sunnybrook system and House-Brackmann scale. The secondary outcomes include the incidence of ipsilateral pain in the early stage of palsy (and the duration of this pain), the proportion of patients with severe pain, the occurrence of synkinesis, facial spasm or contracture, and the severity of residual facial symptoms during the study period., Discussion: The result of this trial will assess the efficacy of using prednisolone and staging acupuncture to treat Bell's palsy, and to determine a best combination therapy with prednisolone and acupuncture for treating Bell's palsy., Trial Registration: ClinicalTrials.gov: NCT01201642.