The prognostic value of ASPECTS in specific regions following mechanical thrombectomy in patients with acute ischemic stroke from large-vessel occlusion.

Objective: The aim of this study is to investigate the relationship between the volume of specific regional infarction and the prognosis of patients who undergo mechanical thrombectomy (MT) for acute large vessel occlusion. Methods: In this study, we collected the clinical and imaging features of patients with unilateral acute anterior circulation ischemic stroke from January 2021 to June 2023 in the Second Affiliated Hospital of Nanchang University. All patients underwent CT perfusion and non-contrast CT scan before MT. The ASPECTS was assessed based on imaging data, and artificial intelligence was used to obtain the percentage of infarction in each of the 10 regions of ASPECTS. According to the modified Rankin Scale, the patients were divided into the good prognosis group and poor prognosis group at the 90-day follow-up. Various indicators in the two groups were compared. Multivariable logistic regression was used to assess the risk factors for poor prognosis. The relationship between core infarction volume and the probability of poor prognosis was plotted to analyze the trend of poor prognosis with changes in the proportion of infarction volume. Finally, a receiver operating characteristic curve was constructed to analyze the predictive ability on poor prognosis. Results: A total of 91 patients were included, with 58 patients having a good prognosis (mRS ≤ 2) and 33 patients having a poor prognosis (mRS ≥ 3). Multivariate analysis showed that NIHSS score and core infarction involving the internal capsule and M6 region were independent risk factors for poor prognosis. According to the linear correlation, a higher ratio of core infarction volume in the internal capsule or M6 region was linked to an increased risk of a poor prognosis. However, the non-linear analysis revealed that the prognostic impact of core infarction volume was significant when the ratio was greater than 69.7%. The ROC curve indicated that the combination of NIHSS score, infarct location, and the ratio of infarct volume has an AUC of 0.87, with a sensitivity of 84.8% and a specificity of 84.5%. Conclusion: It is important to examine the location and volume of the infarct in the internal capsule and M6 when deciding whether to do a MT.

Batoclimab vs Placebo for Generalized Myasthenia Gravis: A Randomized Clinical Trial.

Importance: Myasthenia gravis (MG) is caused by autoantibodies that disrupt the neuromuscular junction. The neonatal fragment crystallizable receptor (FcRn) antagonists, efgartigimod and rozanolixizumab, reduce immunoglobulin G (IgG) level in the circulation and alleviate symptoms in patients with generalized MG. Objective: To examine the efficacy and safety profile of batoclimab, a monoclonal IgG1 antibody, in patients with generalized MG. Design, Setting, and Participants: This was a multicenter randomized clinical trial conducted from September 15, 2021, to June 29, 2022, at 27 centers in China. Adult patients 18 years or older with generalized MG were screened, and those who were antibody positive were enrolled. Intervention: Eligible patients received batoclimab or matching placebo in addition to standard of care. Each treatment cycle consisted of 6 weekly subcutaneous injections of batoclimab, 680 mg, or matching placebo followed by 4 weeks of observation. A second treatment cycle was conducted in patients who required continuing treatment. Main Outcome and Measure: The primary outcome was sustained improvement, as defined by a 3-point or greater reduction in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline for 4 or more consecutive weeks in the first cycle in individuals who were positive for acetylcholine receptor or muscle-specific kinase antibodies. Results: A total of 178 adult patients with generalized MG were screened, 132 were randomly assigned, 131 tested positive for antibodies, and 1 tested negative for antibodies. A total of 132 patients (mean [SE] age, 43.8 [13.6] years; 88 women [67.2%]) were enrolled. The rate of sustained MG-ADL improvement in the first cycle in antibody-positive patients was 31.3% (20 of 64) in the placebo group vs 58.2% (39 of 67) in the batoclimab group (odds ratio, 3.45; 95% CI, 1.62-7.35; P = .001). The MG-ADL score diverged between the 2 groups as early as week 2. The mean (SE) maximum difference in MG-ADL score reduction occurred 1 week after the last dose (day 43, 1.7 [0.3] in the placebo group vs 3.6 [0.3] in the batoclimab group; group difference, -1.9; 95% CI, -2.8 to -1.0; nominal P < .001). The rates of treatment-related and severe treatment-emergent adverse events in patients were 36.9% (24 of 65) and 7.7% (5 of 65) in the placebo group vs 70.1% (47 of 67) and 3.0% (2 of 67) in the batoclimab group, respectively. Conclusions and Relevance: Batoclimab increased the rate of sustained MG-ADL improvement and was well tolerated in adult patients with generalized MG. Clinical effects and the extent of IgG reduction were similar to those previously reported for efgartigimod and rozanolixizumab. Future studies of large sample size are needed to further understand the safety profile of batoclimab. Trial Registration: ClinicalTrials.gov Identifier: NCT05039190.

Feasibility of a clinical-radiomics combined model to predict the occurrence of stroke-associated pneumonia.

PURPOSE: To explore the predictive value of radiomics in predicting stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients and construct a prediction model based on clinical features and DWI-MRI radiomics features. METHODS: Univariate and multivariate logistic regression analyses were used to identify the independent clinical predictors for SAP. Pearson correlation analysis and the least absolute shrinkage and selection operator with ten-fold cross-validation were used to calculate the radiomics score for each feature and identify the predictive radiomics features for SAP. Multivariate logistic regression was used to combine the predictive radiomics features with the independent clinical predictors. The prediction performance of the SAP models was evaluated using receiver operating characteristics (ROC), calibration curves, decision curve analysis, and subgroup analyses. RESULTS: Triglycerides, the neutrophil-to-lymphocyte ratio, dysphagia, the National Institutes of Health Stroke Scale (NIHSS) score, and internal carotid artery stenosis were identified as clinically independent risk factors for SAP. The radiomics scores in patients with SAP were generally higher than in patients without SAP (P < 0. 05). There was a linear positive correlation between radiomics scores and NIHSS scores, as well as between radiomics scores and infarct volume. Infarct volume showed moderate performance in predicting the occurrence of SAP, with an AUC of 0.635. When compared with the other models, the combined prediction model achieved the best area under the ROC (AUC) in both training (AUC = 0.859, 95% CI 0.759-0.936) and validation (AUC = 0.830, 95% CI 0.758-0.896) cohorts (P < 0.05). The calibration curves and decision curve analysis further confirmed the clinical value of the nomogram. Subgroup analysis showed that this nomogram had potential generalization ability. CONCLUSION: The addition of the radiomics features to the clinical model improved the prediction of SAP in AIS patients, which verified its feasibility.

Wogonin alleviates NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/SIRT1.

Cerebral ischemia-reperfusion (IR) is the main pathophysiological process after stroke and can seriously impair neurological function. Wogonin, a natural flavonoid extracted from the roots of Scutellaria baicalensis, has potent anti-inflammatory properties. In this study, we investigated the protective mechanism of wogonin against middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) model-induced cerebral IR injury through adenosine 5'-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome axis. Our results showed that wogonin (20 mg/kg, intraperitoneal injection) effectively reduced infarct size, attenuated brain edema, improved neurological deficits, and alleviated histopathological damage. In addition, wogonin reduced microglial cell activation and inflammatory factors, including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, and IL-10, in brain tissue and serum after cerebral IR injury. Wogonin also effectively activated the AMPK/SIRT1 signaling pathway and inhibited NLPR3 inflammasome-related molecules upregulation in cerebral IR injury as well as in OGD/R-stimulated HT-22 cells. Furthermore, inhibition of the AMPK/SIRT1 signaling pathway by Compound C, an AMPK inhibitor, significantly reversed the protective effect of wogonin on OGD/R-induced NLRP3 inflammasome. Meanwhile, the protective effect of wogonin against brain IR injury was also reversed in the presence of compound C. These results suggest that wogonin ameliorates cerebral IR injruy-induced inflammation by inhibiting NLRP3 inflammasome through the AMPK/SIRT1 signaling pathway.

Prediction of recurrent ischaemic stroke using radiomics data and machine learning methods in patients with acute ischaemic stroke: protocol for a multicentre, large sample, prospective observational cohort study in China.

INTRODUCTION: Stroke is a leading cause of mortality and disability worldwide. Recurrent strokes result in prolonged hospitalisation and worsened functional outcomes compared with the initial stroke. Thus, it is critical to identify patients who are at high risk of stroke recurrence. This study is positioned to develop and validate a prediction model using radiomics data and machine learning methods to identify the risk of stroke recurrence in patients with acute ischaemic stroke (AIS). METHODS AND ANALYSIS: A total of 1957 patients with AIS will be needed. Enrolment at participating hospitals will continue until the required sample size is reached, and we will recruit as many participants as possible. Multiple indicators including basic clinical data, image data, laboratory data, CYP2C19 genotype and follow-up data will be assessed at various time points during the registry, including baseline, 24 hours, 7 days, 1 month, 3 months, 6 months, 9 months and 12 months. The primary outcome was stroke recurrence. The secondary outcomes were death events, prognosis scores and adverse events. Imaging images were processed using deep learning algorithms to construct a programme capable of automatically labelling the lesion area and extracting radiomics features. The machine learning algorithms will be applied to integrate cross-scale, multidimensional data for exploratory analysis. Then, an ischaemic stroke recurrence prediction model of the best performance for patients with AIS will be established. Calibration, receiver operating characteristic and decision curve analyses will be evaluated. ETHICS AND DISSEMINATION: This study has received ethical approval from the Medical Ethics Committee of the Second Affiliated Hospital of Nanchang University (medical research review No.34/2021), and informed consent will be obtained voluntarily. The research findings will be disseminated through publication in journals and presented at conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200055209.

Comparison of the Predictive Value of Inflammatory Biomarkers for the Risk of Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke.

Purpose: To investigate the predictive value of various inflammatory biomarkers in patients with acute ischemic stroke (AIS) and evaluate the relationship between stroke-associated pneumonia (SAP) and the best predictive index. Patients and Methods: We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), prognostic nutritional index (PNI), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS), and prognostic index (PI). Variables were selectively included in the logistic regression analysis to explore the associations of NLR, PLR, MLR, PNI, SIRI, SII, GPS, mGPS, and PI with SAP. We assessed the predictive performance of biomarkers by analyzing receiver operating characteristic (ROC) curves. We further used restricted cubic splines (RCS) to investigate the association. Next, we conducted subgroup analyses to investigate whether specific populations were more susceptible to NLR. Results: NLR, PLR, MLR, SIRI, SII, GPS, mGPS, and PI increased significantly in SAP patients, and PNI was significantly decreased. After adjustment for potential confounders, the association of inflammatory biomarkers with SAP persisted. NLR showed the most favorable discriminative performance and was an independent risk factor predicting SAP. The RCS showed an increasing nonlinear trend of SAP risk with increasing NLR. The AUC of the combined indicator of NLR and C-reactive protein (CRP) was significantly higher than those of NLR and CRP alone (DeLong test, P<0.001). Subgroup analyses suggested good generalizability of the predictive effect. Conclusion: NLR, PLR, MLR, PNI, SIRI, SII, GPS, mGPS, and PI can predict the occurrence of SAP. Among the indices, the NLR was the best predictor of SAP occurrence. It can therefore be used for the early identification of SAP.

Corrigendum to "Endovascular treatment of acute basilar artery occlusion caused by vertebral artery stump syndrome: A clinical analysis of 37 cases" [Heliyon 9 (4X), (March 2023) Article e14956].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e14956.].

Short-term efficacy and safety of personalized antiplatelet therapy for patients with acute ischaemic stroke or transient ischaemic attack: A randomized clinical trial.

AIMS: The aim of this study was to determine whether the testing strategy for clopidogrel and/or aspirin resistance using CYP2C19 genotyping or urinary 11-dhTxB2 testing has an impact on clinical outcomes. METHODS: A multicentre, randomized, controlled trial was conducted at 14 centres in China from 2019 to 2021. For the intervention group, a specific antiplatelet strategy was assigned based on the CYP2C19 genotype and 11-dhTxB2, a urinary metabolite of aspirin, and the control group received nonguided (ie, standard of care) treatment. 11-dhTXB2 is a thromboxane A2 metabolite that can help quantify the effects of resistance to aspirin in individuals after ingestion. The primary efficacy outcome was new stroke, the secondary efficacy outcome was a poor functional prognosis (a modified Rankin scale score ≥3), and the primary safety outcome was bleeding, all within the 90-day follow-up period. RESULTS: A total of 2815 patients were screened and 2663 patients were enrolled in the trial, with 1344 subjects assigned to the intervention group and 1319 subjects assigned to the control group. A total of 60.1% were carriers of the CYP2C19 loss-of-function allele (*2, *3) and 8.71% tested positive for urinary 11-dhTxB2- indicating aspirin resistance in the intervention group. The primary outcome was not different between the intervention and control groups (P = .842). A total of 200 patients (14.88%) in the intervention group and 240 patients (18.20%) in the control group had a poor functional prognosis (hazard ratio 0.77, 95% confidence interval [CI] 0.63 to 0.95, P = .012). Bleeding events occurred in 49 patients (3.65%) in the intervention group and 72 patients (5.46%) in the control group (hazard ratio 0.66, 95% CI 0.45 to 0.95, P = .025). CONCLUSIONS: Personalized antiplatelet therapy based on the CYP2C19 genotype and 11-dhTxB2 levels was associated with favourable neurological function and reduced bleeding risk in acute ischaemic stroke and transient ischaemic attack patients. The results may help support the role of CYP2C19 genotyping and urinary 11-dhTxB2 testing in the provision of precise clinical treatment.

Harmine exerts anxiolytic effects by regulating neuroinflammation and neuronal plasticity in the basolateral amygdala.

Increasing evidence indicates that an altered immune system is closely linked to the pathophysiology of anxiety disorders, and inhibition of neuroinflammation may represent an effective therapeutic strategy to treat anxiety disorders. Harmine, a beta-carboline alkaloid in various medicinal plants, has been widely reported to display anti-inflammatory and potentially anxiolytic effects. However, the exact underlying mechanisms are not fully understood. Our recent study has demonstrated that dysregulation of neuroplasticity in the basolateral amygdala (BLA) contributes to the pathological processes of inflammation-related anxiety. In this study, using a mouse model of anxiety challenged with Escherichia coli lipopolysaccharide (LPS), we found that harmine alleviated LPS-induced anxiety-like behaviors in mice. Mechanistically, harmine significantly prevented LPS-induced neuroinflammation by suppressing the expression of pro-inflammatory cytokines including IL-1ß and TNF-α. Meanwhile, ex vivo whole-cell slice electrophysiology combined with optogenetics showed that LPS-induced increase of medial prefrontal cortex (mPFC)-driven excitatory but not inhibitory synaptic transmission onto BLA projection neurons, thereby alleviating LPS-induced shift of excitatory/inhibitory balance towards excitation. In addition, harmine attenuated the increased intrinsic neuronal excitability of BLA PNs by reducing the medium after-hyperpolarization. In conclusion, our findings provide new evidence that harmine may exert its anxiolytic effect by downregulating LPS-induced neuroinflammation and restoring the changes in neuronal plasticity in BLA PNs.

Prediction of recurrence of ischemic stroke within 1 year of discharge based on machine learning MRI radiomics.

Purpose: This study aimed to investigate the value of a machine learning-based magnetic resonance imaging (MRI) radiomics model in predicting the risk of recurrence within 1 year following an acute ischemic stroke (AIS). Methods: The MRI and clinical data of 612 patients diagnosed with AIS at the Second Affiliated Hospital of Nanchang University from March 1, 2019, to March 5, 2021, were obtained. The patients were divided into recurrence and non-recurrence groups according to whether they had a recurrent stroke within 1 year after discharge. Randomized splitting was used to divide the data into training and validation sets using a ratio of 7:3. Two radiologists used the 3D-slicer software to label the lesions on brain diffusion-weighted (DWI) MRI sequences. Radiomics features were extracted from the annotated images using the pyradiomics software package, and the features were filtered using the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Four machine learning algorithms, logistic regression (LR), Support Vector Classification (SVC), LightGBM, and Random forest (RF), were used to construct a recurrence prediction model. For each algorithm, three models were constructed based on the MRI radiomics features, clinical features, and combined MRI radiomics and clinical features. The sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC) were used to compare the predictive efficacy of the models. Results: Twenty features were selected from 1,037 radiomics features extracted from DWI images. The LightGBM model based on data with three different features achieved the best prediction accuracy from all 4 models in the validation set. The LightGBM model based solely on radiomics features achieved a sensitivity, specificity, and AUC of 0.65, 0.671, and 0.647, respectively, and the model based on clinical data achieved a sensitivity, specificity, and AUC of 0.7, 0.799, 0.735, respectively. The sensitivity, specificity, and AUC of the LightGBM model base on both radiomics and clinical features achieved the best performance with a sensitivity, specificity, and AUC of 0.85, 0.805, 0.789, respectively. Conclusion: The ischemic stroke recurrence prediction model based on LightGBM achieved the best prediction of recurrence within 1 year following an AIS. The combination of MRI radiomics features and clinical data improved the prediction performance of the model.

Endovascular treatment of acute basilar artery occlusion caused by vertebral artery stump syndrome: A clinical analysis of 37 cases.

Introduction: Acute basilar artery occlusion (ABAO) caused by vertebral artery stump syndrome (VASS) has a low incidence and is always underestimated. Due to the occlusion of the origin of the vertebral artery (VA), it is often combined with basilar artery (BA) endovascular diseases or non-dominant contralateral vertebral artery, making the endovascular treatment (EVT) challenging to implement. Objective: This article focuses on whether EVT and two interventional route options could bring clinical benefits to this group of patients: basilar artery thrombectomy through the occluded lateral vertebral artery and implementing revascularization of the occluded vertebral artery (dirty-road-path); thrombectomy through the non-occluded lateral vertebral artery (clean-road-path). Methods: We collected six cases of acute embolic basilar artery occlusion (ABAO) due to VASS from January 2020 to December 2021 at our hospital and retrospectively analyzed 31 patients previously reported in the literature and applied statistical analysis to investigate the treatment options and clinical prognosis of these patients. Results: The clean-road-path surgical protocol was applied in 4 of 37 patients, the dirty-road-path protocol was applied in 29 patients, and 4 patients did not recanalized the basilar artery. By statistical analysis we found that successful recanalization of the basilar artery was clinically significant in reducing the modified Rankin Scale (mRS) scores in these patients, the statistical difference in the benefit of the two surgical protocols was negative. There was a significant positive correlation between preoperative National Institute of Health Stroke Scale (NIHSS) and postoperative 90-day mRS scores. Conclusion: Endovascular treatment can benefit patients with ABAO due to VASS, and patients with higher preoperative NIHSS scores are more vulnerable to getting a poor prognosis. Comparison between the two endovascular options did not yield statistically significant results, but the dirty-road-path option may be superior to using the clean-road-path.

Exploring the relationship between brain white matter change and higher degree of invisible hand tremor with computer technology.

BACKGROUND: At present, the clinical diagnosis of white matter change (WMC) patients depends on cranial magnetic resonance imaging (MRI) technology. This diagnostic method is costly and does not allow for large-scale screening, leading to delays in the patient's condition due to inability to receive timely diagnosis. OBJECTIVE: To evaluate whether the burden of WMC is associated with the degree of invisible hand tremor in humans. METHODS: Previous studies have shown that tremor is associated with WMC, however, tremor does not always have imaging of WMC. Therefore, to confirm that the appearance of WMC causes tremor, which are sometimes invisible to the naked eye, we achieved an optical-based computer-aided diagnostic device by detecting the invisible hand tremor, and we proposed a calculation method of WMC volume by using the characteristics of MRI images. RESULTS: Statistical analysis results further clarified the relationship between WMC and tremor, and our devices are validated for the detection of tremors with WMC. CONCLUSIONS: The burden of WMC volume is positive factor for degree of invisible hand tremor in the participants without visible hand tremor. Detection technology provides a more convenient and low-cost evaluating method before MRI for tremor diseases.

High-risk screening of late-onset Pompe disease: A different early portrait in China.

Introduction: The lack of knowledge regarding the differences between Chinese and other ethnicities in the early manifestation of late-onset Pompe disease (LOPD) prohibits the development of an effective screening strategy. We conducted a multicenter screening study to determine LOPD prevalence in high-risk populations and define the early manifestation of LOPD in China. Methods: Between August 2020 and April 2021, the participants were prospectively identified through medical examination at 20 centers from inpatient departments and outpatient neuromuscular clinics in China. The inclusion criteria were as follows: (1) age ≥ 1 year and (2) either one of the following conditions: (a) persistent hyperCKemia, (b) muscle weakness of the axial and/or limb-girdle muscles, or (c) unexplained restrictive respiratory insufficiency (RI). Enzymatic activity of acid α-glucosidase (GAA) was measured in a dried blood spot (DBS) using a tandem mass spectrometry (MS/MS) assay. Next-generation sequencing (NGS) was used to evaluate all samples with decreased GAA activity, searching for GAA mutations and pseudodeficiency alleles. Results: Among the 492 cases, 26 positive samples (5.3%) were detected in the DBS test. Molecular studies confirmed a diagnosis of LOPD in eight cases (1.6%). Using MS/MS assay, GAA activities in individuals with pseudodeficiency could be distinguished from those in patients with LOPD. The median interval from the onset of symptoms to diagnosis was 5 years. All patients also showed RI, with a mean forced vital capacity (FVC) of 48%, in addition to axial/proximal muscle weakness. The creatine kinase (CK) level ranged from normal to no more than 5-fold the upper normal limit (UNL). LOPD with isolated hyperCKemia was not identified. Conclusion: Less frequent hyperCKemia and predominant RI depict a different early portrait of adult Chinese patients with LOPD. A modified high-risk screening strategy should be proposed for the early diagnosis of Chinese patients with LOPD.

Circular RNA circPRDX3 mediates neuronal survival apoptosis in ischemic stroke by targeting miR-641 and NPR3.

OBJECTIVE: circPRDX3 is a circular RNA (circRNA) that has received little attention yet. The purpose of this research is to elucidate circPRDX3 expression pattern and its underlying network in ischemic stroke (IS). METHODS: Oxygen-glucose deprivation on/reoxygenation (OGD/R) and mice model of middle cerebral artery occlusion (MCAO) were used to generate IS model in N2a cells or mice, respectively. Expression levels of circPRDX3, miR-641, Natriuretic Peptide Receptor 3 (NPR3), and members of the mitogen-activated protein kinases (MAPK) pathway were determined using real-time quantitative PCR (qRT-PCR) and western blot. Cell viability was assessed by CCK-8 assay and apoptosis was evaluated using TUNEL staining and flow cytometry. Molecule-molecule interactions were verified by dual luciferase and RNA immunoprecipitation (RIP) assays. The infarcted area was depicted by Triphenyl tetrazolium chloride (TTC) staining and the level of neurological function was measured using National Institute of Health stroke scale (NIHSS). RESULTS: CircPRDX3 and NPR3 were shown to be considerably downregulated in IS samples, as well as OGD/R cells or MCAO mice, while miR-641 was found to be significantly upregulated. A circPRDX3/miR-641/NPR3 mechinary was verified using luciferase and RIP assays. Overexpression of circPRDX3 dramatically reduced miR-641 expression and increased NPR3 expression, boosting cell survival and lowering apoptosis in an OGD/R model, either with inactivated MAPK signaling pathways. Moreover, overexpression of circPRDX3 lowered infarct volume and enhanced neurobehavioral outcomes in mice after MCAO, and these protective effects were dramatically abrogated by depletion of NPR3. CONCLUSION: Altogether, circPRDX3 inhibited the development of IS by sponging miR-641, hence increasing NPR3 expression and inactivating MAPK pathway. These results may aid in the search of potential therapy targets for IS.

Threshold effect of plasma total homocysteine levels on cognitive function among hypertensive patients in China: A cross-sectional study.

Background: Increased plasma total homocysteine (tHcy) is an influencing factor of cognitive impairment in the general population. However, studies on the relationship between the risk of cognitive impairment and plasma tHcy levels in patients with hypertension are limited. This study aimed to explore the association between plasma tHcy levels and cognitive function assessed by MMSE scores among hypertensive patients in China. Methods: A total of 9,527 subjects from the Chinese Hypertension Registry Study participated in this study. Plasma tHcy levels were quantified by high-performance liquid chromatography using a fluorescence detector. Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Linear regression models, two piecewise linear regression models, and smoothing curve fitting were applied to determine the relationship between plasma tHcy levels and cognitive function. Results: This analysis included 9,527 Chinese hypertensive adults. Based on the results of linear regression models, a negative relationship was identified between plasma tHcy levels and MMSE scores [beta coefficient (ß) per standard deviation (SD) increase: -0.26, 95% confidence interval (CI) -0.35, -0.16, P < 0.001]. The fully adjusted smooth curve fitting presented a nonlinear between plasma tHcy levels and MMSE scores. The threshold effect analysis showed that the inflection point of tHcy was about 27.1 µmol/L. The effect size [ß (95% CI)] per SD increase in plasma tHcy concentrations on MMSE scores was -0.93 (-1.24, -0.6) on the left side and -0.07 (-0.24, 0.10) on the right side of the inflection point (P-value for log-likelihood ratio (LLR) test was <0.001). Moreover, subgroup analyses revealed that sex could influence the negative association between plasma tHcy levels and MMSE scores up to a specific threshold (P-value for interaction <0.001). Linear regression models indicated that there was an enhanced inverse association between tHcy levels and MMSE scores in female patients with tHcy concentrations less than 26.9 µmol/L compared to male patients with tHcy concentrations less than 32.0 µmol/L. Conclusions: Plasma tHcy levels had a threshold effect on MMSE scores among hypertensive patients in China. Increased plasma tHcy levels were independently inversely associated with cognitive decline among hypertensive patients with tHcy concentrations <27.1 µmol/L.

Association of marital status with cognitive function in Chinese hypertensive patients: a cross-sectional study.

PURPOSE: The aim of this study was to evaluate the association of marital status with cognitive function and to examine the potential effect modifiers in Chinese hypertensive populations. METHODS: A total of 9,525 adult Chinese hypertensive patients were enrolled in this cross-sectional study. Cognitive function, as the dependent variable in our study, was assessed by the Chinese version of the Mini-Mental State Examination (MMSE). We adjusted for potential confounding factors in multiple linear regression models to examine the relationship of marital status with cognitive function. In addition, we divided the population according to sex to explore whether there were sex-specific differences. RESULTS: Among the 9,525 study participants, the mean (SD) age for men was 63.5 (10.3) years, and the mean MMSE score was 24.9 ± 5.0, whereas for women, the mean (SD) age was 63.8 (9.3) years, and the mean MMSE score was 19.4 ± 6.4. Unmarried persons had lower scores on the MMSE and lower subscores in each of the cognitive domains. A stronger correlation between marital status and a lower MMSE score was statistically significant in men (unmarried men: ß = -1.55; 95% CI: -1.89, -1.21) but not women (unmarried women: ß = -0.22; 95% CI: -0.56, 0.12; p interaction = 0.006). Compared to men who were widowed or divorced, never married men were more likely to have lower MMSE scores (ß = -2.30, 95% CI -3.10,-1.50; p < 0.001). CONCLUSIONS: Our study demonstrated that being unmarried is an extremely important but neglected social risk factor for cognitive function. Sex was a strong effect modifier: being unmarried was correlated with a higher risk of cognitive decline than being married in Chinese hypertensive men, especially among older men, but this correlation was not observed among women. Moreover, never married men showed poorer cognitive function than those who were divorced or widowed.

Sex Modified the Association between Sleep Duration and worse Cognitive Performance in Chinese Hypertensive Population: Insight from the China H-Type Hypertension Registry Study.

Objectives: Cognitive decline could be seen as the sign of preclinical phase of dementia, which was found to be sex differentiated. Previous studies had discovered that there might be some link between abnormal sleep duration and cognitive performance. Additionally, hypertension was found to be one of the important risk factors for cognitive decline and abnormal sleep duration was also a significant risk factor for hypertension. Therefore, the purpose of this study was to investigate sex differences in the association of sleep duration with cognitive performance and to further explore potential effect modifiers that may exist. Methods: Data analyzed in this study was from the China H-type Hypertension Registry Study. Sleep duration was assessed with a sleep questionnaire and categorized as <5 hours, 5-8 hours, and ≥8 hours. Cognitive performance was evaluated with the Mini-Mental State Examination (MMSE). Result: A total of 9527 subjects were included. The average age was 63.7 ± 9.8 years. Linear regression analyses showed that the association between long sleep duration (≥8 h) and MMSE score adjusting for pertinent covariables was stronger in female (ß = -0.95, 95% CI: -1.23 to -0.68, P < 0.001) than in male (ß = -0.29, 95% CI: -0.53 to -0.06, P = 0.013). Furthermore, there was a significant interaction between sleep duration and age on cognitive performance only in female. Conclusion: In summary, this study found that long sleep duration (≥8 h) was associated with poorer cognitive performance. Furthermore, this association was more pronounced in female than in male, especially in older female.

Personalized antiplatelet therapy based on clopidogrel/aspirin resistance tests in acute ischemic stroke and transient ischemic attack: Study protocol of a multi-center, single-blinded and randomized controlled trial.

BACKGROUND: Clopidogrel and aspirin are key intervention for acute ischemic stroke (AIS) and transient ischemic attack (TIA). However, with increased clinical application, many patients have shown clopidogrel resistance (CR) and/or aspirin resistance (AR) that affect antiplatelet therapy on AIS/TIA. At present, there is no research reported on personalized antiplatelet therapy guidelines for patients with CR and/or AR. Our study aims to assess the effect of personalized antiplatelet therapy based on CYP2C19 genotype and urine 11-dhTxB2 tests in patients with AIS or TIA. METHODS: This is a multi-center randomized controlled trial. Eligible patients with AIS/TIA from 14 comprehensive hospitals in Jiangxi province will be recruited after obtaining informed consent. Participants will be randomly divided into the intervention group and the control group at a ratio of 1:1. personalized antiplatelet therapy based on the CYP2C19 genotype/urine11-dhTxB2 tests will be given to the intervention group. Demographics, disease history, laboratory investigations, therapys, physiological tests, imaging reports and other clinical features will be collected. Clinical outcomes including stroke recurrence, Modified Rankin Scale (mRS) score, bleeding events and all-cause mortality will be assessed at the 1st, 3rd, 6th, and 12th-month post-discharge. DISCUSSION: Our study will conduct free antiplatelet resistance tests and personalized antiplatelet therapy for AIS/TIA patients with CR/AR, ultimately evaluating personalized therapy effectiveness through one-year follow-up. The research results will help to assess the impact of personalized antiplatelet therapy on the prognosis of stroke, thus providing reference for precise clinical treatment.

LncRNA TUG1 Demethylated by TET2 Promotes NLRP3 Expression, Contributes to Cerebral Ischemia/Reperfusion Inflammatory Injury.

LncRNA TUG1 has not yet been reported in cerebral ischemia/reperfusion (I/R) injury. Methylcytosine dioxygenase TET2 is involved in ischemic damage. This study aimed to investigate the effects of TUG1 demethylated by TET2 on I/R-induced inflammatory response and identified its possible mechanisms.We found that TUG1 expression was significantly upregulated in oxygen-glucose deprivation and reoxygenation (OGD/R)-induced SH-SY5Y and SK-N-SH cells. Using the middle cerebral artery occlusion (MCAO) mice, we observed a similar effect. We also found that I/R injury could downregulate miR-200a-3p and upregulate NLRP3 and TET2. The knockdown of TUG1 could alleviate OGD/R-induced inflammatory response through upregulating miR-200a-3p and downregulating NLRP3 and other pro-inflammatory molecules. miR-200a-3p inhibition can partially reverse the effects of TUG1 silencing. Further experiments confirmed that TUG1 sponged miR-200a-3p to diminish miR-200a-3p and promote NLRP3 dependent inflammatory responses. Mechanically, knockdown of TET2 induced low levels of TUG1 and high levels of miR-200a-3p in both SK-N-SH and SH-SY5Y cells. IL-18, IL-1ß, NLRP3, Caspase-1, and GSDMD-N were highly downregulated in OGD/R-induced SK-N-SH and SH-SY5Y cells after TET2 knockdown. TUG1 overexpression could reverse this effect. All the data indicated that TET2 could demethylate TUG1 and contribute to the inflammatory response. In additional experiments using the MCAO mice model, we confirmed knockdown of TET2 attenuated I/R-induced inflammatory response and brain injuries via decreasing TUG1 and increasing miR-200a-3p to inhibit NLRP3 expression. The demethylation of TUG1 by TET2 might aggravate I/R-induced inflammatory injury via modulating NLRP3 by miR-200a-3p. Our data confirmed that TET2 contributed to I/R-induced inflammatory response via the demethylation of TUG1 and regulated TUG1/miR-200a-3p/NLRP3 pathway.

High Estimated Glomerular Filtration Rate Is Associated With Worse Cognitive Performance in the Hypertensive Population: Results From the China H-Type Hypertension Registry Study.

BACKGROUND: Increasing studies have focused on the predictive value of high estimated glomerular filtration rate (eGFR) on cardiovascular diseases and mortality; however, the association between high eGFR with cognitive function is still not established. Thus, this study aimed to determine the co-relationship between high eGFR and cognitive performance in the hypertensive population. METHODS: We conducted a baseline cross-sectional study using data from the China H-type Hypertension Registry study. Mini-Mental State Examination (MMSE) assessment was performed to evaluate the cognitive function scale, and serum creatinine was collected to estimate eGFR level. Different MMSE cutoff values were applied in participants with the various educational background to define dementia: <24 in participants with secondary school and above education setting, <20 in those with primary school, and <17 in illiterate participants. RESULTS: A total of 9,527 hypertensive adults with mean age 63.7 ± 9.8 years and 67% female gender were analyzed. The eGFR cutoff value of 71.52 ml/min/1.73 m2 was found after adjusting for potential covariates in a threshold effect analysis. The MMSE increased significantly with the increment of eGFR (ß, 0.27; 95% CI: 0.12-0.41) in participants with eGFR < 71.52 ml/min/1.73 m2 and decreased (ß, -0.28; 95% CI: -0.39 to -0.17) in participants with eGFR ≥ 71.52 ml/min/1.73 m2. Individuals with eGFR ≥ 85 ml/min/1.73 m2 have an elevated risk of cognitive impairment than those with eGFR of 65-75 ml/min/1.73 m2. Subgroup analysis showed that a greater reduction degree of MMSE was observed in female individuals and those who had body mass index (BMI) ≥ 24 kg/m2 among participants with eGFR ≥ 71.52 ml/min/1.73 m2. CONCLUSION: Our findings observed an inverted U-shaped relationship between eGFR and cognitive function. Both the low and high levels of eGFR were independently associated with worse cognitive assessment in the hypertensive population.