Case report: Overlap syndrome of neuromyelitis optica spectrum disorder with anti-Argonaute antibodies.

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.

Potential actions of capsaicin for preventing vascular calcification of vascular smooth muscle cells in vitro and in vivo.

Vascular calcification (VC) is an accurate risk factor and predictor of adverse cardiovascular events; however, there is currently no effective therapy to specifically prevent VC progression. Capsaicin (Cap) is a bioactive alkaloid isolated from Capsicum annuum L., a traditional medicinal and edible plant that is beneficial for preventing cardiovascular diseases. However, the effect of Cap on VC remains unclear. This study aimed to explore the effects and related mechanisms of Cap on aortic calcification in a mouse and on Pi-induced calcification in vascular smooth muscle cells (VSMCs). First, we established a calcification mouse model with vitamin D3 and evaluated the effects of Cap on calcification mice using von Kossa staining, calcium content, and alkaline phosphatase activity tests. The results showed that Cap significantly improved calcification in mice. VSMCs were then cultured in 2.6 mM Na2HPO4 and 50 µg/mL ascorbic acid for 7 days to obtain a calcification model, and we investigated the effects and mechanisms of Cap on VSMCs calcification by assessing the changes of calcium deposition, calcium content, and subsequent VC biomarkers. These results showed that Cap alleviated VSMCs calcification by upregulating the expressions of TRPV1. Moreover, Cap reduced the expression of Wnt3a and ß-catenin, whereas DKK1 antagonised the inhibitory effect of Cap on VSMC calcification. This study is the first to offer direct evidence that Cap inhibits the Wnt/ß-catenin signaling pathway by upregulating the expression of the TRPV1 receptor, resulting in the decreased expression of Runx2 and BMP-2, thereby reducing VSMC calcification. Our study may provide novel strategies for preventing the progression of VC. This could serve as a theoretical basis for clinically treating VC with spicy foods.

Effects of CASZ1, WNT2B and PTPRG SNPs on stroke susceptibility in the Chinese Han population.

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.

A biosensor for S100B detection based on PSS-MA-GoldMag-LFIA in early clinical diagnosis of brain damage.

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.

Association of baseline fasting plasma glucose with 1-year mortality in non-diabetic patients with acute cerebral infarction: a multicentre observational cohort study.

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.

Association between Triglyceride-Glucose Index and 1-year Recurrent Stroke after Acute Ischemic Stroke: Results from the Xi'an Stroke Registry Study of China.

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 non-linear 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 non-linear 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.

Rituximab at lower dose for neuromyelitis optica spectrum disorder: a multicenter, open-label, self-controlled, prospective follow-up study.

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.

Elevated non-HDL-C/HDL-C ratio increases the 1-year risk of recurrent stroke in older patients with non-disabling ischemic cerebrovascular events: results from the Xi'an Stroke Registry Study of China.

BACKGROUND: Few studies have explored the prognostic role of nontraditional lipid-related indicators in non-disabling ischemic cerebrovascular events (NICE). In this study, we aimed to investigate the relationship between the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (non-HDL-C/HDL-C) and the1-year risk of recurrent stroke in patients with NICE. METHODS: Total cholesterol (TC), HDL-C, and patient information were collected at admission. Recurrent stroke events were followed up 3, 6, and 12 months after onset. Non-HDL-C levels were calculated by subtracting HDL-C from TC. The non-HDL-C/HDL-C ratio was treated as a continuous variable and in quartiles (Q1-Q4). Stratified multivariate Cox regression was used to investigate the relationship between the non-HDL-C/HDL-C ratio and the 1-year risk of recurrent stroke in patients with NICE. RESULTS: Overall, 1,659 patients with NICE were enrolled. For each unit increase in the non-HDL-C/HDL-C ratio, the 1-year risk of recurrent stroke in patients aged ≥ 65 years (older patients) with NICE increased by 64% in the adjusted model (hazard ratio [HR]: 1.64, 95%confidence interval [CI]:1.18-2.27, P = 0.003), and the HRs were 3.21 and 4.24 times higher in the Q3 and Q4 groups than that in the Q1 group, which was considered to be the reference (adjusted model Q3: HR: 3.21, 95%CI: 1.05-9.83, P = 0.041; adjusted model Q4: HR: 4.24, 95%CI: 1.30-13.85, P = 0.017). However, there was no significant difference in patients younger than 65 years. Both curve fitting and Kaplan-Meier cumulative risk analysis showed that an elevated non-HDL-C/HDL-C ratio significantly increased the 1-year risk of recurrent stroke in older patients with NICE. The optimal range for the non-HDL-C/HDL-C ratio should be no higher than the Q2 group (2.256-2.939). Stratified Cox regression analysis showed that these results tended to be stable for different comorbidities (all P for interaction > 0.05). CONCLUSIONS: Elevated non-HDL-C/HDL-C ratios significantly increased the 1-year risk of recurrent stroke in older patients with NICE. Therefore, clinicians need to pay more attention to this indicator when managing older patients with NICE.

Plasma lncRNA LIPCAR Expression Levels Associated with Neurological Impairment and Stroke Subtypes in Patients with Acute Cerebral Infarction: A Prospective Observational Study with a Control Group.

INTRODUCTION: This prospective observational study with a control group aimed to compare the plasma levels of long non-coding RNA (lncRNA) LIPCAR between patients with acute cerebral infarction (ACI) and healthy controls, and to assess the prognostic abilities of LIPCAR for adverse outcomes of patients with ACI at 1-year follow-up. METHODS: Eighty patients with ACI, of whom 40 had large artery atherosclerosis (LAA) and 40 had cardioembolism (CE) and who were hospitalized at Xi'an No. 1 Hospital from July 2019 to June 2020, were selected as the case group. Age- and sex-matched non-stroke patients from the same hospital throughout the same time period were chosen as the control group. Real-time quantitative reverse transcription polymerase chain reaction was used to measure the levels of plasma lncRNA LIPCAR. The correlations of LIPCAR expression among the LAA, CE, and control groups were assessed using Spearman's correlation analysis. Curve fitting and multivariate logistic regression were used to analyze the LIPCAR levels and 1-year adverse outcomes of patients with ACI and its subtypes. RESULTS: The expression of plasma LIPCAR in the case group was noticeably higher than that of the control group (2.42 ± 1.49 vs. 1.00 ± 0.47, p < 0.001). Patients with CE had considerably higher levels of LIPCAR expression than those with LAA. The National Institute of Health Stroke Scale score and modified Rankin scale score on admission were significantly positively correlated with LIPCAR expression in patients with CE and LAA. Furthermore, the correlation was stronger in patients with CE than in those with LAA, with correlation coefficients of 0.69 and 0.64, respectively. Curve fitting revealed a non-linear correlation between LIPCAR expression levels, 1-year recurrent stroke, all-cause mortalities, and poor prognoses, with a cut-off value of 2.2. CONCLUSION: The expression level of lncRNA LIPCAR may play a potential role in the identification of neurological impairment and CE subtype in patients with ACI. Increased 1-year risk of adverse outcomes may be associated with high levels of LIPCAR expression.

Acute cerebral infarction is the second-leading cause of death worldwide. Therefore, available diagnostic and prognostic tools are of the utmost importance. It is easy to acquire hematologic biomarkers and to provide direct information related to the severity of brain injury and the risk of stroke. However, it has been shown that the study of hematologic markers in aspects of both identifying stroke subtypes and predicting neurological impairment are still few and imperfect in clinical application of stroke prognosis. The long non-coding RNA LIPCAR plays an important role in the pathophysiology of cardiovascular disease. Nonetheless, to date, no exploration has been carried out on the correlation between lncRNA LIPCAR, severity on admission, and prognosis of stroke subtypes. Thus, this study aimed to investigate the plasma levels of lncRNA LIPCAR expression and their correlations in patients with acute cerebral infarction and its subtypes. Our results show that the plasma levels of LIPCAR expression of the patients with acute cerebral infarction were noticeably higher than those of the non-stroke control patients. Patients with cardioembolism subtype had considerably higher levels of LIPCAR expression than those with large artery atherosclerosis. The National Institute of Health Stroke Scale score and modified Rankin scale score on admission were significantly correlated with LIPCAR expression in patients with cardioembolism and large artery atherosclerosis; the correlation was stronger in patients with cardioembolism than in patients with large artery atherosclerosis, with correlation coefficients of 0.69 and 0.64, respectively. Furthermore, curve fitting revealed a non-linear correlation between LIPCAR expression levels and 1-year outcome events. The expression level of lncRNA LIPCAR may play a potential role in the identification of neurological impairment and cardioembolism subtype in patients with acute cerebral infarction.

Serum homocysteine level is an independent risk factor for 1-year stroke recurrence in patients with acute ischemic stroke and H-type hypertension: results from the Xi'an stroke registry study of China.

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.

CAN: Context-assisted full Attention Network for brain tissue segmentation.

Brain tissue segmentation is of great value in diagnosing brain disorders. Three-dimensional (3D) and two-dimensional (2D) segmentation methods for brain Magnetic Resonance Imaging (MRI) suffer from high time complexity and low segmentation accuracy, respectively. To address these two issues, we propose a Context-assisted full Attention Network (CAN) for brain MRI segmentation by integrating 2D and 3D data of MRI. Different from the fully symmetric structure U-Net, the CAN takes the current 2D slice, its 3D contextual skull slices and 3D contextual brain slices as the input, which are further encoded by the DenseNet and decoded by our constructed full attention network. We have validated the effectiveness of the CAN on our collected dataset PWML and two public datasets dHCP2017 and MALC2012. Our code is available at https://github.com/nwuAI/CAN.

Non-Linear Association Between Serum Alkaline Phosphatase and 3-Month Outcomes in Patients With Acute Stroke: Results From the Xi'an Stroke Registry Study of China.

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.

Development and Validation of a Nomogram for Predicting Generalization in Patients With Ocular Myasthenia Gravis.

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.

Relationship between serum alkaline phosphatase and poor 3-month prognosis in acute ischemic stroke patients with preserved renal function: results from Xi'an Stroke Registry Study of China.

BACKGROUND: In recent years, alkaline phosphatase (ALP) has been considered as one of the independent risk factors of acute ischemic stroke (AIS) and leads to worse clinical outcomes in patients with renal failure. In this study, we aim to investigate whether serum ALP level is associated with poor early-term prognosis in relationship of AIS patients with preserved renal function. METHODS: A prospectively collected database of AIS patients hospitalized in the Xi'an district of China from January to December, 2015 was analyzed. The demographics, serum ALP levels and stroke outcomes of all patients at 3 months were reviewed. Patients were routinely followed-up for 3 months. Serum ALP level was analyzed as a continuous variable and quintiles (Q1-Q5). Multivariate logistic regression model and a two-piecewise linear regression model were used to investigate the relationship and to determine the threshold effect regarding serum ALP levels and poor 3-month prognosis of AIS patients with preserved renal function. RESULTS: Overall, 1922 AIS patients were enrolled with 62.3% of them being men. The risk of having a poor 3-month prognosis was significantly increased in Q1, Q2, Q3 and Q5, when compared to that in Q4 being as the reference. The highest risk was noted in Q5 (odds ratio 2.21, 95% confidence interval: 1.32-3.73, P = 0.003) after being adjusted for confounders. Further analysis revealed a J-shaped curvilinear relationship between ALP levels and a poor 3-month prognosis of strokes (optimal threshold ALP level = 90 U/L). The relationship between both parameters was not significantly affected by age, sex, drinking, hypertension and leukocyte count (stratified by 10 × 109/L) (P for interaction > 0.05). CONCLUSIONS: Serum ALP was noted as an independent risk factor for a poor 3-month prognosis of AIS patients with preserved renal function. ALP levels higher than 90 U/L could cause an increased risk of a poor 3-month prognosis.

Neuronal Intranuclear Inclusion Disease-Related Neurotrophic Keratitis: A Case Report.

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.

Psoralidin protects against cerebral hypoxia/reoxygenation injury: Role of GAS6/Axl signaling.

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.

Association of immunosuppression treatment with generalization among patients with ocular myasthenia gravis: A propensity score analysis.

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.

Risk Factors for Generalization in Patients with Ocular Myasthenia Gravis: A Multicenter Retrospective Cohort Study.

INTRODUCTION: Many patients with ocular myasthenia gravis (OMG) progress to generalized disease within the first 2 years of the onset of ocular symptoms. Several retrospective studies have identified risk factors associated with generalization, however these studies included patients on immunosuppression therapy or those undergoing thymectomy, which may reduce the generalization risk. In this study we explored the risk factors for generalization in non-immunosuppressed and non-thymectomized patients with OMG. METHODS: Data from patients with OMG treated at seven tertiary hospitals in China were retrospectively reviewed. Clinical characteristics, including sex, age at onset, symptoms at onset, comorbid autoimmune diseases, neostigmine test response, repetitive nerve stimulation (RNS) findings, presence of serum anti-acetylcholine receptor antibody (AChR-Ab), and thymic status based on radiological and pathological studies, were collected. The main outcome measure was disease generalization. The follow-up period was defined as the date of ocular symptom onset to the date of confirmation of generalization or immunotherapy initiation, or last follow-up (defined as 60 months). The Cox proportional hazards model was used to assess the risk factors for generalization. RESULTS: Overall, 572 patients (269 women) were eligible for inclusion in the analysis, of whom 144 developed generalization. The mean (standard deviation) onset age was 45.5 (19.8) years, and the median (interquartile range) follow-up period was 14.5 (7.0-47.3) months. Multivariable Cox regression analysis demonstrated that both early-onset (adjusted hazard ratio [aHR] 5.34; 95% confidence interval [CI] 1.64-17.36; p = 0.005) and late-onset (aHR 7.18; 95% CI 2.22-23.27; p = 0.001) in adulthood, abnormal RNS findings (aHR 3.01; 95% CI 1.97-4.61; p < 0.001), seropositivity for AChR-Ab (aHR 2.58; 95% CI 1.26-5.26; p = 0.01), and thymoma (aHR 1.62; 95% CI 1.05-2.49; p = 0.03) were independently associated with increased risk of generalization. CONCLUSION: The risk of generalization increased significantly in patients with adult-onset OMG, abnormal RNS findings, seropositivity for AChR-Ab, and thymoma, suggesting that these risk factors may predict OMG generalization.