KLF13 promotes VSMCs phenotypic dedifferentiation by directly binding to the SM22α promoter.

Krüppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.

Predictive role of neutrophil-to-platelet ratio in futile recanalization of patients after endovascular therapy.

Aim: To explore the association between the neutrophil-to-platelet ratio (NPR) and futile recanalization (FR) in patients with acute ischemic stroke due to large vascular occlusions after endovascular therapy (EVT). Methods: FR after EVT was defined as a poor 90-day prognosis (modified Rankin scale [mRS] score ≥3) despite successful reperfusion (modified thrombolysis in cerebral infarction grade 2b-3). Patients were divided into high NPR (>35; n = 115) and low NPR (≤35; n = 81) groups. Results: The FR rate was significantly higher in the high NPR group than low NPR group (81.74 vs 55.56%; p = 0.000). NPR was independently associated with FR (odds ratio: 2.107; 95% CI: 1.017-4.364; p = 0.045). Conclusion: High NPR was associated with the risk of FR in patients with acute ischemic stroke due to large vascular occlusions.

Polarization-Resolved Near-Infrared PdSe2 p-i-n Homojunction Photodetector.

Constructing high-quality homojunctions plays a pivotal role for the advancement of two-dimensional transition metal sulfide (TMDC) based optoelectronic devices. Here, a lateral PdSe2 p-i-n homojunction is constructed by electrostatic doping. Electrical measurements reveal that the homojunction diode exhibits a strong rectifying characteristic with a rectification ratio exceeding 104 and an ideality factor approaching 1. When functioning in photovoltaic mode, the device achieves a high responsivity of 1.1 A/W under 1064 nm illumination, with a specific detectivity of 1.3 × 1011 Jones and a high linearity of 45 dB. Benefiting from the lateral p-i-n structure, the junction capacitance is significantly reduced, and an ultrafast response (3/6 µs) is obtained. Additionally, the photodiode has the capability of polarization distinction due to the unique in-plane anisotropic structure of PdSe2, exhibiting a dichroic ratio of 1.6 at a 1064 nm wavelength. This high-performance polarization-sensitive near-infrared photodetector exhibits great potential in the next-generation optoelectronic applications.

Association of ultra-processed foods consumption with risk of cardio-cerebrovascular disease: A systematic review and meta-analysis of cohort studies.

AIMS: The epidemiological evidence regarding the impact of ultra-processed foods (UPFs) on the risk of cardio-cerebrovascular diseases (CCVDs) is controversial. The aim of this systematic review and meta-analysis is to examine the association between UPF consumption and the risk of CCVDs within cohort studies. DATA SYNTHESIS: A systematic literature search was conducted across multiple databases, including PubMed/Medline, Embase, Web of Science, Scopus, and the Cochrane Library databases, covering the inception of these databases up until January 1st, 2023. A total of 39 cohort studies involving 63,573,312 human participants were deemed eligible according to the inclusion criteria. Utilizing random-effects models, risk ratios (RRs) were estimated to determine the pooled results. Our findings indicate a significant association between a higher consumption of UPF and an increased likelihood of CCVDs (RR: 1.08, 95% CI: 1.01-1.16, I2 = 89%; p < 0.01) compared to individuals who either abstain from or consume lesser amounts of UPF. Nonlinear dose-response meta-analyses showed that a consistent high intake of UPFs was associated with an elevated risk of developing CCVDs (p non-linearity <0.001). Notably, the risk of CCVDs escalated by approximately 7% with an UPF intake of up to 1 serving per day. Subgroup analysis further revealed a significant augmentation in the risk of total CVD and hypertension with increased UPF consumption. CONCLUSIONS: A higher intake of UPF significantly increases the risk of developing CCVDs. Prospective studies controlling for confounding factors are needed to validate the relationship between UPF intake and the development of CCVDs.

Effects of aerobic exercise on depression-like behavior and TLR4/NLRP3 pathway in hippocampus CA1 region of CUMS-depressed mice.

BACKGROUND AND PURPOSE: The paper observes regulation of the expression levels of NLRP3 and TLR4 in hippocampal CA1 neurons in CUMS mice by aerobic exercise with constructing CUMS depression mouse model, in order to explore the neuroprotective mechanism of aerobic exercise on the hippocampus of depressed mice. STUDY DESIGN AND METHOD: 24 healthy male 8-week-old C57BL/6 mice were randomly divided into CG, MG and ME. Thirteen stress-stimulating factors were randomly formulated into a CUMS stress-stimulating program. The mice were underwent 28 days of CUMS depression model, referenced clinical means for experimental research. The study was approved by the Ethics Committee of Yichun University (YCUEC IRB number LSK NO.2022.18). After model preparation, ME mice were subjected to moderate-intensity treadmill exercise training for 8 weeks. TST, FST and SPT were used to detect the depression-like behaviors of the mice in each group. Nissl staining was used to compare the cell morphology in the CA1 region of the mouse hippocampus. Immunohistochemical staining and western blot were used to detect the changes in the expression levels of NLRP3, TLR4 and other proteins in the CA1 region of the mouse hippocampus. RESULTS: The results of neurobehavioral assessment showed that, the immobility time of TST and FST were significantly increased, and SPT index was significantly decreased of MG mice. Compared with MG, ME mice significantly improved depression-like behaviors such as TST, FST and SPT index. Nissl staining showed that the morphology of neurons in CA1 region of hippocampus of MG mice were mostly vacuolar-like, with severe nuclear pyknosis. Abnormal morphological changes such as vacuolar-like and pyknotic pyknosis of neurons in the hippocampal CA1 region of ME mice were significantly reduced. Protein expression test showed that the number of NLRP3, TLR4, IL-1ß and IL-10 positive neurons in hippocampal CA1 region of MG mice increased significantly compared with CG, and the proportion of positive cells increased significantly, while NLRP3 and TLR4 positive neurons in the hippocampal CA1 region of ME mice were significantly reduced, the proportion of TLR4 positive cells was significantly reduced. CONCLUSION: Systematic moderate-intensity exercise can effectively improve the depression-like behavior of CUMS depressed mice through the expression of TLR4/NLRP3 inflammatory signaling pathway, and provide an effective experimental basis for the clinical rehabilitation treatment of depression.

Direct Thrombectomy versus Bridging Thrombectomy within 6 Hours of Stroke Onset: A Prospective Cohort Study on Cognitive and Physical Function Outcomes.

PURPOSE: To evaluate the physical and cognitive functions of patients with stroke who underwent either direct or bridging thrombectomy within 6 hours of stroke onset. MATERIALS AND METHODS: Patients with large vessel occlusion in anterior circulation treated with direct (direct group) or bridging thrombectomy (bridging group) were prospectively analyzed between June 2020 and February 2022. The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, the safety outcome was symptomatic intracranial hemorrhage (sICH), and cognitive function was assessed using the Clinical Dementia Rating (CDR) scale at 6 months after stroke. RESULTS: A total of 125 patients (direct group, n = 75; bridging group, n = 50) who had completed follow-up at 3 months by telephone call were included. No significant differences were observed between the direct and bridging groups in terms of an mRS score of 0-2 (25.3% vs 22.0%, respectively; P = .83), an mRS score of 0-3 (37.3% vs 44.0%, respectively; P = .58), sICH (17.3% vs 14.0%, respectively; P = .80), or 3-month all-cause mortality (36.3% vs 30.0%, respectively; P = .34). Sixty-nine patients (direct group, n = 38; bridging group, n = 31) completed the CDR assessment at 6 months after stroke. There was no significant difference in poststroke dementia, defined as a CDR score of ≥1 point between the direct group (42.1%) and bridging group (22.6%) (P = .12). Ordinal regression analyses showed that the CDR score at 6 months was not associated with treatment type (direct thrombectomy vs bridging thrombectomy). CONCLUSIONS: With regard to physical and cognitive functions at 3 and 6 months, direct thrombectomy was comparable with bridging thrombectomy in patients who were treated within 6 hours of stroke onset.

Predicting the emergence of malignant brain oedema in acute ischaemic stroke: a prospective multicentre study with development and validation of predictive modelling.

Background: We aimed to develop and validate a prognostic model for predicting malignant brain oedema in patients with acute ischaemic stroke in a real-world setting of practice. Methods: A prospective multicentre study enrolled adult patients with acute ischaemic stroke with brain CT < 24 h of onset of symptoms admitted to nine tertiary-level hospitals in China between September 2017 and December 2019. Malignant brain oedema was defined as any patient who had decompressive craniectomy, discharge in coma, or in-hospital death attributed to symptomatic brain swelling. The derivation cohort was a consecutive cohort of patients from one centre and the validation cohort was non-consecutive patients from the other centres. Multivariable logistic regression was used to define independent predictors from baseline clinical characteristics, imaging features, complications, and management. A web-based nomogram and a risk score were developed based on the final model. Model performance was assessed for discrimination and calibration in both derivation and validation cohorts. The study is registered, NCT03222024. Findings: Based on the derivation cohort (n = 1627), the model was developed with seven variables including large infarct (adjusted odds ratio [OR] 40.90, 95% CI 20.20-82.80), National Institutes of Health Stroke Scale (NIHSS) score (OR 1.09, 1.06-1.12), thrombolysis (OR 2.11, 1.18-3.78), endovascular treatment (OR 2.87, 1.47-5.59), pneumonia (OR 2.47, 1.53-3.97), brain atrophy (OR 0.57, 0.37-0.86), and recanalisation (OR 0.36, 0.17-0.75). The classification threshold of a predicted probability ≥0.14 showed good discrimination and calibration in both derivation cohort (area under the receiver-operating curve [AUC] 0.90, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation cohort (n = 556, AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95). The risk score based on this model had a total point that ranged from -1 to 20, with an optimal score of ≥10 showing good discrimination and calibration in both derivation (AUC 0.89, 0.87-0.92; sensitivity 0.95, 0.92-0.98) and validation (AUC 0.88, 0.82-0.95; sensitivity 0.84, 0.73-0.95) cohorts. Interpretation: The INTEP-AR model (i.e. large Infarct, NIHSS score, Thrombolysis, Endovascular treatment, Pneumonia, brain Atrophy, and Recanalisation) incorporating multiple clinical and radiological characteristics has shown good prognostic value for predicting malignant brain oedema after acute ischaemic stroke. Funding: National Natural Science Foundation of China; Science and Technology Department of Sichuan Province; West China Hospital.

An Investigation of Compressive Creep Aging Behavior of Al-Cu-Li Alloy Pre-Treated by Compressive Plastic Deformation and Artificial Aging.

In this paper, the effects of compressive pre-deformation and successive pre-artificial aging on the compressive creep aging behavior and microstructure evolution of the Al-Cu-Li alloy have been studied. Severe hot deformation mainly occurs near the grain boundaries during the compressive creep initially, which steadily extends to the grain interior. After that, the T1 phases will obtain a low radius-thickness ratio. The secondary T1 phases in pre-deformed samples usually only nucleate on dislocation loops or Shockley incomplete dislocations induced by movable dislocations during creep, which are especially prevalent in low plastic pre-deformation. For all pre-deformed and pre-aged samples, two precipitation situations exist. When pre-deformation is low (3% and 6%), solute atoms (Cu and Li) can be consumed prematurely during pre-aging at 200 °C, with dispersed coherent Li-rich clusters in the matrix. Then, the pre-aged samples with low pre-deformation no longer have the ability to form secondary T1 phases in large quantities during subsequent creep. When dislocation entangles seriously to some extent, a large quantity of stacking faults, together with a "Suzuki atmosphere" containing Cu and Li, can provide the nucleation sites for the secondary T1 phase, even when pre-aged at 200 °C. The sample, pre-deformed by 9% and pre-aged at 200 °C, displays excellent dimensional stability during compressive creep because of the mutual reinforcement of entangled dislocations and pre-formed secondary T1 phases. In order to decrease the total creep strain, increasing the pre-deformation level is more effective than pre-aging.

Crystallization Kinetics of Modified Nanocellulose/Monomer Casting Nylon Composites.

Polyisocyanate and caprolactone were used to chemically functionalize nanocellulose (CNF). Composites of CNF, caprolactone-modified nanocellulose (CNF-CL) and polyisocyanate-modified nanocellulose (CNF-JQ)/MC nylon were fabricated by anionic ring-opening polymerization. The effects of the crystal structure, crystal morphology and crystallization process of MC nylon composites have been characterized by wide-angle X-ray diffraction (WAXD), polarized optical microscopy(POM) and differential scanning calorimetry (DSC). Isothermal crystallization kinetics were analyzed using the Avrami equation, and the crystallization rate, half-time, and Avrami exponent were calculated. The results show that the nucleation effects of CNF-JQ/MC nylon composites is increased with the CNF-JQ increase, and it is best compared with MC nylon, CNF/MC nylon and CNF-CL/MC nylon composites, so CNF-JQ can play the role of effective nucleating agent in MC nylon. We also discussed the non-isothermal crystallization of the composites. Analysis of the Jeziorny and Mo model demonstrates that the Zc values of CNF, CNF-CL, CNF-JQ/MC nylon composites increase, and the F(T) values decrease in order. This indicates that CNF-JQ can better promote the crystallization rate of non-isothermal crystallization of MC nylon. The results of this work demonstrate that CNF-JQ can be an effective nucleation agent and increase the crystallization rate of MC nylon compared with CNF-CL. The activation energy of the composites was studied using the kissing method, and the results showed that CNF-CL decreased the activation energy of MC nylon, and CNF and CNF-JQ increased the activation energy of MC nylon.

Helicobacter pylori Infection Is Associated with Long-Term Cognitive Decline in Older Adults: A Two-Year Follow-Up Study.

BACKGROUND: Previous cross-sectional studies have identified a possible link between Helicobacter pylori (H. pylori) infection and dementia. However, the association of H. pylori infection with longitudinal cognitive decline has rarely been investigated. OBJECTIVE: This cohort study aims to demonstrate the effects of H. pylori infection on longitudinal cognitive decline. METHODS: This cohort study recruited 268 subjects with memory complaints. Among these subjects, 72 had a history of H. pylori infection, and the rest 196 subjects had no H. pylori infection. These subjects were followed up for 24 months and received cognitive assessment in fixed intervals of 12 months. RESULTS: At baseline, H. pylori infected, and uninfected participants had no difference in MMSE scores. At 2 years of follow-up, H. pylori infected participants had lower MMSE scores than uninfected participants. H. pylori infection was associated with an increased risk of longitudinal cognitive decline, as defined by a decrease of MMSE of 3 points or more during follow-up, adjusting for age, sex, education, APOEɛ4 genotype, hypertension, diabetes, hyperlipidemia, and smoking history (HR: 2.701; 95% CI: 1.392 to 5.242). H. pylori infection was associated with larger cognitive decline during follow-up, adjusting for the above covariates (standardized coefficient: 0.282, p < 0.001). Furthermore, H. pylori infected subjects had significantly higher speed of cognitive decline than uninfected subjects during follow-up, adjusting for the above covariates. CONCLUSION: H. pylori infection increases the risk of longitudinal cognitive decline in older subjects with memory complaints. This study is helpful for further understanding the association between infection and dementia.

Anti-CASPR2 encephalitis in a liver posttransplant patient receiving immune-suppression and lenvatinib: a case report and literature review.

It has been assumed that patients with strict immunosuppressive treatment after solid organ transplantation have only marginal risk in developing autoimmune encephalitis. We reported a woman in her late 40 s who presented with generalized convulsions and loss of consciousness. After detailed history review, neuropsychological tests, metagenomic next-generation sequencing of serum and cerebrospinal fluid (CSF), magnetic resonance imaging (MRI) brain, and electroencephalogram, she was diagnosed as anti-CASPR2 encephalitis based on the positive anti-CASPR2 auto-antibody in serum and CSF. The patient underwent liver transplantation and has taken lenvatinib for 2 months, in addition to tacrolimus, mycophenotale mofetil, and entecavir administered for half a year. This case was the first report of anti-CASPR2 encephalitis in post-organ transplantation patients. Together with the reports of other encephalitis cases in organ transplantation, it warns the possibility of developing immune-oriented encephalitis in patients undergoing immunosuppression, especially in combination with other treatments of immunomodulatory activity.

Cerebral blood volume index may be a predictor of independent outcome of thrombectomy in stroke patients with low ASPECTS.

INTRODUCTION: To evaluate the predictors for efficacy and safety of patients with acute ischemic stroke (AIS) and Alberta Stroke Program Early Computed Tomographic Score (ASPECTS) ＜6 undergoing endovascular therapy (EVT). METHODS: This study retrospectively analyzed consecutive patients presented between December 2020 and December 2021 with large vessel occlusions (LVO) within the anterior circulation and an ASPECTS ＜6, followed by EVT. The efficacy outcome was 90-day functional independence, defined as modified Rankin Scale (mRS) score 0-3. The primary safety outcome was symptomatic intracranial hemorrhage (sICH). Secondary safety outcomes included 90-day all-cause mortality and 24-hour any ICH. RESULTS: A total of 22 patients were included. The percentage of patients with mRS 0-3 at 90 days was 36.4% (8/22). The occurrence of sICH was 22.7% (5/22). The occurrence of any ICH was 45.5% (10/22). The 90-day all-cause mortality was 36.4% (8/22). Median (interquartile range, IQR) cerebral blood volume (CBV) index was 0.5 (0.4-0.7). CBV index in mRS 0-3 group (n = 8) was higher than mRS 4-5 group (n = 14) (P＜0.05). There was no significant difference of age, gender, comorbidities, baseline National Institutes of Health Stroke Scale (NIHSS) score, mismatch ratio, CBV index, interval between stroke onset and re-perfusion, good re-perfusion rate between sICH group (n = 5) and non-sICH group (n = 17). CONCLUSIONS: AIS patients with low ASPECTS can still benefit from EVT and gain good functional outcome, especial those had higher CBV index on pre-EVT computed tomography perfusion (CTP). Further studies with larger sample size are needed to validate our findings.

Association between Allium vegetables and the risk of non-digestive tract cancer: A systematic review and meta-analysis of cohort and case-control studies.

PURPOSE: To clarify the role of Allium vegetables in non-digestive tract cancer, we conducted this meta-analysis. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a meta-analysis of published studies assessing the associations between Allium vegetables and the risk of non-digestive tract cancer. We estimated the pooled odds ratio (OR) of non-digestive tract cancer for the highest and lowest Allium vegetable consumption using random-effects models. A dose-response regression model was used to evaluate the relationship between Allium vegetables and non-digestive tract cancer risk. RESULTS: In a pooled analysis of 25 studies (11 cohort and 14 case-control studies) on Allium vegetables, a total of 18,070 patients with non-digestive tract cancer were finally included. Integrated OR of non-digestive tract cancer was 0.86 [95% confidence interval (CI):0.80-0.93] for the highest versus the lowest Allium vegetable consumption for all studies, 0.78 (95% CI:0.69-0.90) for case-control studies and 0.94 (95%CI: 0.87-1.02) for cohort studies. Sensitivity analysis showed that the pooled effect was stable. No apparent publication bias was identified in this study; however, the cumulative meta-analysis suggested that studies conducted earlier (from 1994 to 1997) might be a source of heterogeneity. Dose-response regression model indicated that Allium vegetable consumption was associated with the risk of non-digestive tract cancer (P = 0.001 for non-linearity; P = 0.032 for linearity). CONCLUSION: Higher Allium vegetable consumption could reduce the risk of non-digestive tract cancers, demonstrating the protective role of Allium vegetables.

Different Doses of Intravenous Tissue-Type Plasminogen Activator for Acute Ischemic Stroke: A Network Meta-Analysis.

Background: This study aims to assess the efficacy and safety of different doses of intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) by adopting a network meta-analysis (NMA). Methods: Studies comparing different doses of tPA in AIS were identified by retrieving electronic databases. NMAs of outcome measures included favorable functional outcome with a modified Rankin scale score (mRS) of 0 or 1 at 3 months after treatment (3M-FF), the functional independence with a mRS of 0, 1, or 2 at 3 months (3M-FI), symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M). Symptomatic intracranial hemorrhage (sICH) and 3-month all-cause mortality (3M-M) were assessed. Probability-based ranking and surface under cumulative ranking (SUCRA) were performed to identify the best dose of tPA. Inconsistency was evaluated by node-splitting analysis and a loop-specific approach. Publication bias was analyzed by funnel plots. Results: A total of 14 studies were included in the quantitative synthesis. The NMA results revealed no difference among low (<0.7 mg/kg), moderate (0.8 mg/kg), and standard (0.9 mg/kg) doses of tPA with regard to efficacy and safety. The SUCRAs of 3M-FF and 3M-FI showed that the standard dose ranked first, the moderate dose ranked second, and the low dose ranked third. The SUCRA of sICH showed that the standard dose ranked first (78.1%), the low dose ranked second (61.0%), and the moderate dose ranked third (11.0%). The SUCRAs of 3-month mortality showed that the standard dose ranked first (73.2%), the moderate dose ranked second (40.8%), and the low dose ranked third (36.1%). No significant inconsistency was shown by node-splitting analysis and no publication bias was shown in funnel plots. Conclusion: Lower dose tPA was comparable to the standard dose with regard to efficacy and safety. Based on the SUCRA results and American Heart Association/American Stroke Association (AHA/ASA) guidelines, the standard dose was still the optimal selection for AIS.

A Prospective, Multicenter, Single-Group Target-Value Clinical Trial to Evaluate the Safety and Efficacy of a Large Bore Aspiration Catheter System for the Endovascular Treatment of Acute Ischemic Stroke.

Objective: This study was conducted to determine the safety and efficacy of the Esperance® Distal Access Catheter (0.071"), a novel large bore aspiration catheter in treating acute ischemic stroke (AIS) with large vessel occlusion (LVO). Methods: A prospective multicenter clinical trial involving 15 stroke centers was performed. Baseline characteristics, procedural data, and angiographic and clinical outcomes of all acute stroke procedures (from May 2020 to March 2021) using the novel large bore aspiration catheter were analyzed. Results: During the study period, 160 consecutive patients were recruited. The mean age and median baseline NIHSS were 65.4 years and 16, respectively. Successful reperfusion was achieved in 147 (91.9%) cases [at least modified Thrombolysis in Cerebral Infarction (mTICI) 2b] with aspiration alone, with complete reperfusion (mTICI 3) in 94 (58.8%) cases. Successful/complete first pass reperfusion was achieved in 104 (64.60%) cases, including mTICI 2b in 34 (21.1%) cases and mTICI 3 in 70 (43.5%) cases. The time from groin puncture to successful reperfusion was 44 (33, 62) min. There were 16 (9.9%) cases requiring rescue therapy using stent-retriever. Procedure-related complications included 2 (1.3%) cases of arterial perforation, 2 (1.3%) cases of arterial dissection, 12 (7.5%) cases of distal embolization, and 1(0.6%) case of puncture site infection. The rate of symptomatic intracranial hemorrhage (sICH) was 3.8% and mortality rate was 13.8%. A total of 99 (62.3%) cases had a favorable outcome (mRS 0-2) at 90 days. Conclusions: In current practice, the first-line aspiration approach with the Esperance® Distal Access Catheter is safe and efficacious. This device may achieve high reperfusion rates with lower instances of rescue stent retriever therapy.

Association Between Plasma Apolipoprotein M With Alzheimer's Disease: A Cross-Sectional Pilot Study From China.

Background: Recent evidence of genetics and metabonomics indicated a potential role of apolipoprotein M (ApoM) in the pathogenesis of Alzheimer's disease (AD). Here, we aimed to investigate the association between plasma ApoM with AD. Methods: A multicenter, cross-sectional study recruited patients with AD (n = 67), age- and sex-matched cognitively normal (CN) controls (n = 73). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, we examined and compared the plasma levels of ApoM, tau phosphorylated at threonine 217 (p-tau217) and neurofilament light (NfL). Multivariate logistic regression analysis was applied to determine the association of plasma ApoM with the presence of AD. The correlation analysis was used to explore the correlations between plasma ApoM with cognitive function [Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA)], activities of daily living (ADL), and the representative blood-based biomarkers (plasma p-tau217 and NfL). Receiver operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma ApoM. Results: Plasma ApoM and its derived indicators (ratios of ApoM/TC, ApoM/TG, ApoM/HDL-C, and ApoM/LDL-C) were significantly higher in AD group than those in CN group (each p < 0.0001). After adjusted for the risk factors of AD, the plasma ApoM and its derived indicators were significantly associated with the presence of AD, respectively. ApoM (OR = 1.058, 95% CI: 1.027-1.090, p < 0.0001), ApoM/TC ratio (OR = 1.239, 95% CI: 1.120-1.372, p < 0.0001), ApoM/TG ratio (OR = 1.064, 95% CI: 1.035-1.095, p < 0.0001), ApoM/HDL-C ratio (OR = 1.069, 95% CI: 1.037-1.102, p < 0.0001), and ApoM/LDL-C ratio (OR = 1.064, 95% CI:1.023-1.106, p = 0.002). In total participants, plasma ApoM was significantly positively correlated with plasma p-tau217, plasma NfL, and ADL (each p < 0.0001) and significantly negatively correlated with MMSE and MoCA (each p < 0.0001), respectively. In further subgroup analyses, these associations remained in different APOEϵ 4 status participants and sex subgroups. ApoM/TC ratio (ΔAUC = 0.056, p = 0.044) and ApoM/TG ratio (ΔAUC = 0.097, p = 0.011) had a statistically remarkably larger AUC than ApoM, respectively. The independent addition of ApoM and its derived indicators to the basic model [combining age, sex, APOEϵ 4, and body mass index (BMI)] led to the significant improvement in diagnostic power, respectively (each p < 0.05). Conclusion: All the findings preliminarily uncovered the association between plasma ApoM and AD and provided more evidence of the potential of ApoM as a candidate biomarker of AD.

The potential pharmacological mechanisms of ß-hydroxybutyrate for improving cognitive functions.

ß-Hydroxybutyl acid (ßOHB), the most prevalent type of ketone in the human body, is involved in the pathogenesis of cognitive disorders, especially Alzheimer's dementia (AD), through a variety of mechanisms, such as enhancing mitochondrial metabolism, regulating signaling molecule, increasing histone acetylation, affecting the metabolism of Aß and Tau proteins, inhibiting inflammation and lipid metabolism, and regulating intestinal microbes. Based on the above findings, clinical drug development in AD has begun to focus on ßOHB.

Association Between Serum C1q Tumor Necrosis Factor-Related Protein 9 and the Clinical Characteristics and Prognosis of Ischemic Stroke.

INTRODUCTION: C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS). Here, we aimed to study the relationship between serum CTRP9 and the etiology, severity, and prognosis of IS patients. METHODS: A total of 302 patients with IS and 173 non-stroke controls were selected from the same hospital, and all patients with IS were followed up 12 months after stroke onset. Stroke etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment classification. Symptomatic severity was determined using the National Institutes of Health Stroke Scale score. The lesion volume of acute cerebral ischemia was measured using magnetic resonance imaging (MRI). The unfavorable functional outcome was a combination of death or major disability 12 months after stroke onset. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in the statistical analysis. RESULTS: We found that serum CTRP9 levels and the ratios of CTRP9/total cholesterol (TC), CTRP9/triglyceride (TG), CTRP9/low-density lipoprotein cholesterol (LDL-C), and CTRP9/high-density lipoprotein cholesterol (HDL-C) were associated with the presence of IS. Moreover, the serum CTRP9 concentration was positively associated with the severity of IS. Incorporation of CTRP9/LDL-C levels into a fully adjusted model for IS-cardioembolic (CE) improved discrimination and calibration, and significantly improved reclassification. In addition, CTRP9 was a predictor of unfavorable functional outcomes. CONCLUSIONS: All the findings indicated that serum CTRP9 could be a promising blood-derived biomarker for the early evaluation and prognosis assessment of IS. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020330.

Serum glial fibrillary acidic protein and S100 calcium-binding protein B correlates cerebral vessel reactivity following carotid artery stenting.

Using detection markers in serum has the advantages of simplicity, repeatability and the capability. This study combined the use of serum glial fibrillary acidic protein (GFAP) and S100B protein (S100B) with imaging tools to confirm the role of serum biomarkers in evaluating the cerebral vessel reactivity after carotid artery stenting (CAS). After CAS, the serum concentrations of GFAP and S100B increased to the peak at 24 h after operation, and then gradually decreased. The mean flow velocity (MFV) (pre-operation, post-operation, 30 days follow-up: 47.65 ± 17.24 cm/s, 62.37 ± 18.25 cm/s, 70.29 ± 16.89 cm/s; P < 0.05) and pulsatility index (PI) (pre-operation, post-operation, 30 days follow-up: 0.78 ± 0.21, 0.98 ± 0.19, 1.02 ± 0.20; P < 0.05) increased significantly in the ipsilateral middle cerebral artery after CAS. At the 30-day follow-up, the cerebrovascular reserve (CVR) (post-operation, 30 days follow-up: 27.47 ± 12.13 cm/s, 31.92 ± 10.94 cm/s; P < 0.05) improved significantly. In patients with different degrees of stenosis, the more severe the stenosis in the carotid artery, the more obvious the improvement of CVR at the 30 days of follow-up (CVR changes: 11.08 ± 7.95 cm/s, Kendall's tau-b = 0.645, P < 0.001). And the serum concentrations of GFAP (r = - 0.629, P < 0.0001) and S100B (r = - 0.604, P < 0.0001) correlated negatively with CVR at 30 days after CAS. Therefore, we recommend using the biomarkers GFAP and S100B associated with imaging tools such as transcranial Doppler (TCD) and Magnetic resonance imaging (MRI) to evaluate the cerebral vessel reactivity following CAS.

Circulating Neurofilament Light Predicts Cognitive Decline in Patients With Post-stroke Subjective Cognitive Impairment.

BACKGROUND: Subjective cognitive impairment (SCI) is common after acute ischemic stroke and adversely affects the quality of life. SCI is associated with an increased risk of developing mild cognitive impairment and dementia. Identifying biomarkers which could predict long-term cognitive outcomes of post-stroke SCI is of importance for early intervention. This study aims to investigate the association between circulating neurofilament light (NfL) and long-term cognitive function in patients with post-stroke SCI. METHODS: This longitudinal study recruited 304 patients with post-stroke SCI, and serum NfL levels were determined at baseline. These patients were followed up for 12 months for the observation of cognitive change. Cognitive performances were assessed by a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) scale. RESULTS: The patients were divided into a progression group (as determined by decreased TICS-40 scores) and a stable group (as determined by increased or unchanged TICS-40 scores). The progression group had significantly higher serum NfL levels than the stable group at baseline. Serum NfL levels were predictive for longitudinal cognitive decline during follow-up. CONCLUSION: These findings imply that circulating NfL could predict the long-term cognitive change of patients with post-stroke SCI.