Association of serum uric acid to serum creatinine ratio with 1-year stroke outcomes in patients with acute ischemic stroke: A multicenter observational cohort study.

BACKGROUND AND PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of age on clinical characteristics and 1-year outcomes of non-disabling ischemic cerebrovascular events: A multicenter prospective cohort study.

BACKGROUND: The exploration of age-related clinical features and adverse outcomes of non-disabling ischemic cerebrovascular disease (NICE) has been largely unaddressed in current research. This study aimed to analyze the differences in clinical characteristics and prognostic outcomes of NICE across various age groups, utilizing data from the Xi'an Stroke Registry Study in China. METHODS: The age distribution of NICE was categorized into four groups: age ≤ 54 years, age 55-64 years, age 65-74 years, and age ≥ 75 years. Multivariate Cox logistic regression analysis was employed to evaluate the 1-year risk of outcome events in each age group of patients with NICE. A subgroup analysis was conducted to explore interaction factors influencing age-dependent outcomes in patients with NICE. RESULTS: This study included 1,121 patients with NICE aged between 23 and 96 years, with an average age of 63.7 ± 12.2 years. Patients aged ≥ 75 years had a higher proportion of women, lower education levels, and a greater likelihood of having urban employee medical insurance. Those aged < 55 years had a higher prevalence of smoking, while individuals aged > 65 years showed a higher prevalence of comorbidities. Furthermore, there was a significant decrease in body mass index among patients aged ≥ 75 years. Laboratory tests indicated well-controlled blood lipids, liver function, and inflammation across all age groups, but renal function was notably reduced in patients with NICE aged ≥ 75 years. Adjusting for potential confounding factors revealed a significant increase in the one-year risk of all-cause mortality and poor prognosis among patients aged ≥ 75 years compared to those aged < 55 years, with no significant gender difference observed. Subgroup analysis indicated that patients with NICE who consumed alcohol were more prone to experience all-cause mortality with advancing age. CONCLUSIONS: Age significantly influences the clinical characteristics and prognostic outcomes of NICE patients. Clinicians should consider age-specific characteristics when diagnosing, treating, and developing prevention strategies. Tailored prevention and treatment strategies for different age groups can enhance prognosis and reduce adverse outcomes in NICE patients.

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.

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.

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.

Dorsolateral medullary infarction registry: a study protocol for a prospective, multicentric registry.

BACKGROUND: Dorsolateral medullary infarction is a typical cerebral infarction which is characterized by Wallenberg's syndrome. Neurotrophic keratopathy is an uncommon consequence of dorsolateral medullary infarction. At present, the protocol is aimed to study the dynamic changes in corneal innervation and the ocular surface environment after dorsolateral medullary infarction. METHODS: This study will involve consecutive data from all medical records of patients within 7 days of acute dorsolateral medullary infarction onset at the Departments of Neurology from 10 collaborating stroke centers. Eligible patients will mainly be characterized based on detailed physical examinations, multimodal imaging, and corneal related examinations and patients will be followed-up for 2 years. Neurotrophic keratopathy after dorsolateral medullary infarction is the primary endpoint. The dynamic histological corneal innervation and ocular surface environment after dorsolateral medullary infarction will be observed during the follow-up period. DISCUSSION: This multicentric, prospective registry is the first to identify and characterize the dynamic changes of corneal innervation and the ocular surface environment after acute dorsolateral medullary infarction. The significance of the study is to emphasize that the curative effect is based on the doctors' identification of the disease in the earliest stage before irreversible damage occurs to the cornea. TRIAL REGISTRATION: The registry was registered ( ChiCTR-OPC-17,011,625 ) on June 11, 2017.

Risk factors affecting the 1-year outcomes of minor ischemic stroke: results from Xi'an stroke registry study of China.

BACKGROUND: The prevalence of stroke recurrence, disability, and all-cause mortality of patients with minor ischemic stroke (MIS) remains problematic. The aim of the present study was to identify risk factors associated with adverse outcomes at 1 year after MIS in the Xi'an region of China. METHODS: This prospective cohort study included MIS patients above 18 years old with National Institutes of Health Stroke Scale (NIHSS) score ≤ 3 who were treated in any of four hospitals in Xi'an region of China between January and December 2015. The 1-year prevalence of stroke recurrence, disability, and all-cause mortality were evaluated, respectively. Multivariate logistic regression analysis was performed to assess the association between the identified risk factors and clinical outcomes. RESULTS: In this study, 131(10.5%, 131/1252) patients were lost to follow-up at 1 year. A total of 1121 patients were included for analysis, the prevalence of stroke recurrence, disability, and all-cause mortality at 1 year after MIS were 3.4% (38/1121), 9.3% (104/1121), and 3.3% (37/1121), respectively. Multivariate logistic regression analysis identified age, current smoking, and pneumonia as independent risk factors for stroke recurrence. Age, pneumonia, and alkaline phosphatase were independent risk factors for all-cause mortality. Independent risk factors for disability were age, pneumonia, NIHSS score on admission, and leukocyte count. CONCLUSIONS: The 1-year outcomes of MIS in Xi'an region of China were not optimistic, especially with a high prevalence of disability. The present study indicated that age and pneumonia were the common independent risk factors affecting the 1-year outcomes of MIS in Xi'an region of China.

Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways.

Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 µM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways.

Expression of nerve growth factor and hypoxia inducible factor-1α and its correlation with angiogenesis in non-small cell lung cancer.

In order to investigate the expression of nerve growth factor (NGF) and hypoxia inducible factor-1α (HIF-1α) and its correlation with angiogenesis in non-small cell lung cancer (NSCLC), paraffin-embedded tissue blocks from 20 patients with NSCLC were examined. Twenty corresponding para-cancerous lung tissue specimens were obtained to serve as a control. The expression of NGF, HIF-1α, and vascular endothelial growth factor (VEGF) in the NSCLC tissues was detected by using immunohistochemistry. The microvascular density (MVD) was determined by CD31 staining. The results showed that the expression levels of NGF, HIF-1α and VEGF in the NSCLC tissues were remarkably higher than those in the para-cancerous lung tissues (P<0.05). There was significant difference in the MVD between the NSCLC tissues (9.19±1.43) and para-cancerous lung tissues (2.23±1.19) (P<0.05). There were positive correlations between NGF and VEGF, between HIF-1α and VEGF, and between NGF and HIF-1α in NSCLC tissues, with the spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In NSCLC tissues, the MVD had a positive correlation with the three factors (P<0.05). Theses results suggest that NGF and HIF-1α are synergically involved in the angiogenesis of NSCLC.

Causal association of type 2 diabetes with central retinal artery occlusion: a Mendelian randomization study.

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.

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.

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.

A Special Case of Relapsing-Remitting Bilateral Encephalitis: Without Epilepsy, but Responding to Rituximab and with a Brain Biopsy Coinciding with Rasmussen Encephalitis.

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.

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.

p75NTR/proBDNF Modulates Basal Cell Carcinoma (BCC) Immune Microenvironment via Necroptosis Signaling Pathway.

Basal cell carcinoma (BCC) is the most common skin cancer. While most of the basal cell carcinomas were localized lesion and can be easily managed, the treatment options to the advanced basal cell carcinomas are still remarkably limited. In recent years, proBDNF and its receptor p75NTR have been reported to play important roles in various diseases, including cancers and psychotic disorders. However, the role of p75NTR/proBDNF signaling in basal cell carcinoma remains unclear. Here, we found that the expression level of p75NTR/proBDNF was decreased in basal cell carcinoma patient samples and cell lines. In vitro study showed overexpression of p75NTR/proBDNF could significantly facilitate tumor cell death, including inflammatory-silent apoptosis and lytic inflammatory activated necroptosis. In vivo study showed overexpression of p75NTR/proBDNF dramatically promotes tumor-associated macrophage (M1) and T cell recruitment in a syngeneic mouse model of BCC. These results show a crucial role for p75NTR/proBDNF signaling in basal cell carcinoma immune microenvironment.

A J-Shaped Curve Relationship Between Baseline Fasting Blood Glucose and 1-Year Stroke Recurrence in Non-diabetic Patients With Acute Cerebral Infarction in Xi'an, China: A Multicenter Observational Cohort Study.

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.

5-HT receptor agonist Valerenic Acid enhances the innate immunity signal and suppresses glioblastoma cell growth and invasion.

Glioblastoma multiform (GBM) continues to threaten people's lives due to the limited therapeutic strategies. As a new drug, Valerenic Acid suppresses the progression of GBM, however, the mechanism is largely unknown. Here, we found that Valerenic Acid can inhibit cell proliferation, migration and invasion of GBM cells by increasing innate immune signals such as enhancing ROS levels and activating the AMPK pathway. Inhibition of ROS by N-acetylcysteine (NAC) or attenuation of AMPK by Compound C could block Valerenic Acid-induced cell death. Additionally, the xenograft mouse model also confirmed that Valerenic Acid had anti-tumor effect. Together, our results provide compelling rational to develop Valerenic Acid as an anti-tumor agent against GBM patients.

RNA-binding protein IGF2BP1 maintains leukemia stem cell properties by regulating HOXB4, MYB, and ALDH1A1.

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an oncofetal protein expressed in various cancers including leukemia. In this study, we assessed the role of IGF2BP1 in orchestrating leukemia stem cell properties. Tumor-initiating potential, sensitivity to chemotherapeutic agents, and expression of cancer stem cell markers were assessed in a panel of myeloid, B-, and T-cell leukemia cell lines using gain- and loss-of-function systems, cross-linking immunoprecipitation (CLIP), and photoactivatable ribonucleoside-enhanced cross-linking and immunoprecipitation (PAR-CLIP) techniques. Here, we report that genetic or chemical inhibition of IGF2BP1 decreases leukemia cells' tumorigenicity, promotes myeloid differentiation, increases leukemia cell death, and sensitizes leukemia cells to chemotherapeutic drugs. IGF2BP1 affects proliferation and tumorigenic potential of leukemia cells through critical regulators of self-renewal HOXB4 and MYB and through regulation of expression of the aldehyde dehydrogenase, ALDH1A1. Our data indicate that IGF2BP1 maintains leukemia stem cell properties by regulating multiple pathways of stemness through transcriptional and metabolic factors.