Disrupted phase behavior of FUS underlies poly-PR-induced DNA damage in amyotrophic lateral sclerosis.

GGGGCC (G4C2) hexanucleotide repeat expansion (HRE) in the first intron of the chromosome 9 open reading frame 72 (C9ORF72) gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Among the five dipeptide repeat proteins translated from G4C2 HRE, arginine-rich poly-PR (proline:arginine) is extremely toxic. However, the molecular mechanism responsible for poly-PR-induced cell toxicity remains incompletely understood. Here, we found that poly-PR overexpression triggers severe DNA damage in cultured cells, primary cortical neurons, and the motor cortex of a poly-PR transgenic mouse model. Interestingly, we identified a linkage between poly-PR and RNA-binding protein fused in sarcoma (FUS), another ALS-related gene product associated with DNA repair. Poly-PR interacts with FUS both in vitro and in vivo, phase separates with FUS in a poly-PR concentration-dependent manner, and impairs the fluidity of FUS droplets in vitro and in cells. Moreover, poly-PR impedes the recruitment of FUS and its downstream protein XRCC1 to DNA damage foci after microirradiation. Importantly, overexpression of FUS significantly decreased the level of DNA damage and dramatically reduced poly-PR-induced cell death. Our data suggest the severe DNA damage caused by poly-PR and highlight the interconnection between poly-PR and FUS, enlightening the potential therapeutic role of FUS in alleviating poly-PR-induced cell toxicity.

Two novel variants of the CAPN3 gene in Chinese patients with Limb-Girdle Muscular Dystrophy Recessive 1.

Introduction Recessive mutations in the CAPN3 gene can lead to Limb-girdle muscular dystrophy Recessive 1 (LGMD R1). Targeted next-generation sequencing facilitates the discovery of new mutations linked with disease, owing to its ability to selectively enrich specific genomic regions. Methods We performed targeted next-generation sequencing of all exons of the CAPN3 gene in four patients with sporadic LGMD and further analyzed the effects of the novel identified variant using various software tools. Results We found 5 variants in CAPN3 gene in four patients, c.82_83insC (insertion mutation) and c.1115+2T>C (splicing mutation) are reported for the first time in CAPN3 (NM_000070.2). The bioinformatics analysis indicated that these two novel variants affected CAPN3 transcription as well as translation. Discussion Our findings reveal previously unreported splicing mutation and insertion mutation in CAPN3 gene, further expanding the pathogenic gene profile of LGMD.

Au Nanozyme Driven Cascading Catalysis in Tollens' Reaction: An Insight of Glucose Oxidase-Like Mechanism.

Au nanoparticles (NPs) have been proven to be excellent glucose oxidase (GOx) mimics, which can catalyze the electrons transform pathway from glucose to oxygen. This study confirmed AuNPs can accelerate the reaction between [Ag(NH3 )2 ]+ and glucose under alkaline conditions, which is also known as the Tollens' reaction, and the possible mechanism was proposed. Here, [Ag(NH3 )2 ]+ instead of O2 acted directedly as an electron acceptor during glucose oxidation catalyzed by AuNPs, accompanied by hydrogen transfer. The as-synthesized Ag nanoparticles can also catalyze this process, similar to AuNPs, via a unique cascading catalysis mechanism in the Tollens' reaction. A simple and heatless glucose colorimetric assay can be established based on the plasmonic band of AgNPs with a liner range of 0.6-22.2 µM, and the limit of detection is 0.32 µM.

Assessment of Cerebral White Matter Involvement in Amyotrophic Lateral Sclerosis Patients With Disease Progression and Cognitive Impairment by Fixel-Based Analysis and Neurite Orientation Dispersion and Density Imaging.

BACKGROUND: Previous studies using emerging diffusion MRI techniques have revealed damage to the white matter (WM) microstructure in amyotrophic lateral sclerosis (ALS), particularly the influence of crossed fibers, but there is a lack of subgroup analyses. PURPOSE: To detect WM microstructural changes in ALS patients using fixel-based analysis (FBA) and neurite orientation dispersion and density imaging (NODDI) MRI. STUDY TYPE: Prospective. POPULATION: Thirty-six ALS patients (aged 60.50 ± 9.5 years) and 25 healthy controls (HCs) (aged 58.90 ± 8.1 years). FIELD STRENGTH/SEQUENCE: 3 T; NODDI and FBA (b-values = 0, 1000, and 2500 seconds/mm2 ). ASSESSMENT: Subgroups were performed according to progression rate and cognition, including fast and slow progression (FP/SP), ALS with and without cognitive impairment (ALS-ci/ALS-nci). Fiber density (FD), fiber-bundle cross-section (FC), combined fiber density and cross-section (FDC), neurite density index (NDI), orientation dispersion index (ODI), isotropic volume fraction (ISO), and fractional anisotropy (FA) were calculated and their correlation with clinical variables examined. STATISTICAL TESTING: Chi-square test, Mann-Whitney U test, two-sample t test, partial correlation analysis, and false discovery rate (FDR) corrected. A P-value <0.05 was considered significant. RESULTS: ALS patients had lower FD and FDC values predominantly in the corticospinal tract (CST) and corpus callosum (CC) regions, as well as lower NDI value in the CC, radial crown, and internal capsule compared to HCs. Subgroup analysis based on progression rate and cognitive function showed significant differences in FBA results. The FC in the right CST region was significantly lower in the FP than SP, and the FD in the CC region was significantly lower in the ALS-ci than ALS-nci. Furthermore, a negative correlation was found between the mean FC value and the rate of progression in ALS patients (r = -0.408). DATA CONCLUSION: FBA is a powerful tool for detecting complex cerebral WM microstructural damage for evaluating ALS cognition and disease progression.

Novel Phenylethanoid Glycosides Improve Hippocampal Synaptic Plasticity via the Cyclic Adenosine Monophosphate-CREB-Brain-Derived Neurotrophic Growth Factor Pathway in APP/PS1 Transgenic Mice.

INTRODUCTION: Alzheimer's disease (AD) is a major public health concern worldwide, but there are still no drugs available that treat it effectively. Previous studies have shown that phenylethanoid glycosides have pharmacological effects, which include anti-AD properties, but the underlying mechanisms by which they ameliorate AD symptoms remain unknown. METHODS: In this study, we used an APP/PS1 AD mouse model to explore the function and mechanisms underlying savatiside A (SA) and torenoside B (TB) in the treatment of AD. SA or TB (100 mg·kg-1·d-1) was orally administered to 7-month-old APP/PS1 mice for 4 weeks. Cognitive and memory functions were measured using behavioral experiments (including the Morris water maze test and the Y-maze spontaneous alternation test). Molecular biology experiments (including Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays) were used to detect any corresponding changes in signaling pathways. RESULTS: The results showed that SA or TB treatment could significantly reduce cognitive impairment in APP/PS1 mice. We also showed that chronic treatment with SA/TB could prevent spine loss, synaptophysin immunoreactivity, and neuronal loss in mice, thereby improving synaptic plasticity and moderating learning and memory deficits. SA/TB administration also promoted the expression of synaptic proteins in APP/PS1 mouse brains and upregulated phosphorylation of proteins in the cyclic adenosine monophosphate (cAMP)/CREB/brain-derived neurotrophic growth factor (BDNF) pathway that are responsible for synaptic plasticity. Additionally, chronic SA/TB treatment increased the levels of BDNF and nerve growth factor (NGF) in the brains of APP/PS1 mice. Both astrocyte and microglia volumes, as well as the generation of amyloid ß, were also decreased in SA/TB-treated APP/PS1 mice compared to control APP/PS1 mice. CONCLUSION: In summary, SA/TB treatment was associated with activation of the cAMP/CREB/BDNF pathway and increased BDNF and NGF expression, indicating that SA/TB improves cognitive functioning via nerve regeneration. SA/TB is a promising candidate drug for the treatment of AD.

Elevated NT-proBNP levels are associated with CTP ischemic volume and 90-day functional outcomes in acute ischemic stroke: a retrospective cohort study.

OBJECTIVE: To investigate the impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on CTP infarct core volume and poor 90-day functional outcomes in acute ischemic stroke (AIS). METHODS: A total of 403 hospitalized patients with AIS in the Stroke Center of the First Hospital Affiliated to Soochow University were enrolled from March 2018 to January 2021. The association between NT-proBNP and clinical outcomes in acute ischemic patients was assessed by logistic regression and adjusted for confounding factors. Also, subgroup analyses were conducted based on treatment decisions. RESULTS: NT-proBNP was positively correlated with CTP ischemic volume (p < 0.001), infarct core volume (p < 0.001), and ischemic penumbra volume (p < 0.001). Univariate analysis showed that the influence of NT-proBNP and functional outcomes were statistically significant in model 1 (p = 0.002). This phenomenon was persistent after adjusted for age, sex, and body mass index in model 2 (p = 0.011), adjusted for SBP, current smoking, family history of stroke, hypertension, and diabetes mellitus in model 3 (p < 0.001), and adjusted for TnI, D-dimer, PLT, Cr, TC, TG, HDL-C, treatment decisions, and NIHSS score in model 4 (p = 0.027). A high NT-proBNP was associated with a high 90-days mRS score among the total population, IV rt-PA, and standardized treatment groups, but not in IV rt-PA + EVT, EVT, and EVT/IV rt-PA + EVT groups. CONCLUSION: Elevated NT-proBNP levels reveal large CTP infarct core volume and poor 90-day functional outcome in AIS. NT-pro BNP is an independent risk factor for functional outcomes.

Effects of Virtual Reality Rehabilitation Training on Cognitive Function and Activities of Daily Living of Patients With Poststroke Cognitive Impairment: A Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the effects of virtual reality (VR) rehabilitation training on the cognitive function and activities of daily living (ADL) of patients with poststroke cognitive impairment (PSCI). DATA SOURCES: Four Chinese databases and 6 English databases were systematically searched for studies published until August 31, 2021, by using Medical Subject Headings of the National Library of Medicine terms such as virtual reality, cognition disorders, cognitive dysfunction, and stroke and free terms such as virtual environment, VR, cognition impairment, cerebrovascular accident, and PSCI. STUDY SELECTION: Randomized controlled trials treating PSCI with VR training were included. The control groups received conventional treatments such as conventional rehabilitation training and drug therapy; the experimental groups received VR rehabilitation training. The outcome measures were cognitive function and ADL. DATA EXTRACTION: Two researchers independently extracted key information from eligible studies. The methodological quality of the studies was evaluated using the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. Meta-analysis was performed using RevMan v5.4. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. DATA SYNTHESIS: Twenty-one studies (1149 participants) were included. Meta-analyses found that compared with the control group, VR rehabilitation training increased Mini-Mental State Examination, Montreal Cognitive Assessment, Loewenstein Occupational Therapy Cognitive Assessment, Rivermead Behavioral Memory Test Second Edition, Barthel Index, Modified Barthel Index, and FIM scores; event-related potential 300 (P300) amplitude; and the N-acetylaspartate/creatinine (Cr) ratio on proton magnetic resonance spectroscopy (1H-MRS) and reduced P300 latency; Trail Making Test scores; and the choline-containing compounds/Cr ratio on 1H-MRS (all P<.05). These results indicated that VR training improved cognitive function and ADL in PSCI. CONCLUSIONS: VR rehabilitation training promotes the rehabilitation of cognitive function and recovery of ADL in patients with PSCI and may be a good complementary approach to conventional cognitive interventions.

Fecal Microbiota Transplantation Alleviated Cerebral Ischemia Reperfusion Injury in Obese Rats.

This study aimed to investigate whether fecal microbiota transplantation (FMT) provides protection for stroke injury in obese patients. Rats were fed high-fat diet (HFD) for 4 weeks and subjected to middle cerebral artery occlusion (MCAO). After FMT for 30 days, body weight, serum total cholesterol and triglyceride levels, neurological score, brain water content, and cerebral infarction volume were measured. Brain reactive oxygen species, superoxide dismutase and malondialdehyde were detected and the levels of Bcl-2, Bax and cleaved caspase-3 were examined. Rats fed with HFD had higher body weight and higher serum total cholesterol and triglyceride levels. Neurological score was lower, brain water content and cerebral infarction volume were higher in obese rats following MCAO, but FMT improved neurological deficit. Moreover, oxidative stress was enhanced in obese rats following MCAO, but FMT attenuated oxidative stress. Brain Bcl-2 level was lower while Bax and cleaved caspase-3 levels were higher in obese rats following MCAO, but FMT increased brain Bcl-2 level and decreased Bax and cleaved caspase-3 levels. In conclusion, FMT attenuated cerebral ischemic injury in obese rats and the beneficial effects of FMT may be mediated by the attenuation of oxidative stress and apoptosis in the brain.

Colorimetric assay of phosphate using a multicopper laccase-like nanozyme.

A new nanozyme (Cu-NADH) is reported composed of Cu-coordinated nicotinamide adenine dinucleotide (NADH) exhibiting laccase-like activity. The Cu-NADH nanozyme had higher heat tolerance and catalytic efficiency than natural laccase, and its catalytic activity can be enhanced by high concentration of Cl ions and it is intensely inhibited by phosphate. Therefore, a colorimetric method based on Cu-NADH and indigo carmine was successfully developed to detect phosphate in water. This method showed an excellent selectivity for phosphate, and it had a linear relationship in the phosphate concentration range 2-50 µM with a detection limit of 0.37 µM. We believe that this example of coordination between metal ions and biomolecules to mimic natural enzymes can inspire more effective and alternative strategies in nanozyme design and expand their use in sensing and determination.

The effects of computer-assisted cognitive rehabilitation on cognitive impairment after stroke: A systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of computer-assisted cognitive rehabilitation in improving cognitive function in patients with post-stroke cognitive impairment. BACKGROUND: In recent years, computer-assisted cognitive rehabilitation has been accepted as a good substitute or supplement for traditional cognitive rehabilitation. Some clinical randomised controlled trials have been carried out, but no relevant systematic evaluations have been performed. Therefore, we conducted a systematic review of studies involving computer-assisted cognitive rehabilitation to provide evidence-based data for its promotion and application. METHODS: Nine databases (Cochrane Library, PubMed, Web of Science, Embase, OVID, Wanfang Data, CNKI, VIP and SinoMed databases) were systematically searched. Randomised controlled trials that assessed computer-assisted cognitive rehabilitation for patients with post-stroke cognitive impairment were included. Two reviewers appraised the risks of bias through the Cochrane Collaboration's tool and performed the meta-analysis, including the assessment of heterogeneity. We follow the PRISMA 2020 guidelines. RESULTS: Thirty-two studies comprising 1837 participants were included. Compared with conventional therapy alone, the addition of computer-assisted cognitive rehabilitation significantly improved the global cognition of patients, evaluated using the Montreal cognitive assessment, mini-mental state examination and Loewenstein occupational therapy cognitive assessment (p < .01 for all tests). The therapy also significantly improved activities of daily living, assessed using the Barthel index, modified Barthel index and functional independence measure (p < .05 for all tests). CONCLUSION: Computer-assisted cognitive rehabilitation significantly improved the cognitive function and activities of daily living of patients with post-stroke cognitive impairment. RELEVANCE TO CLINICAL PRACTICE: Computer-assisted cognitive rehabilitation can be a valuable technique for cognitive rehabilitation after stroke. It is advantageous for improving patient cognition and restoring the overall functional state of patients. Moreover, the research findings can provide suggestions and inspiration for researchers to implement the proposal, which is conducive to the design of more rigorous and high-quality randomised controlled trials.

Systematic review and meta-analysis of randomized controlled trials assessing the impact of Baduanjin exercise on cognition and memory in patients with mild cognitive impairment.

OBJECTIVE: To determine the effectiveness of Baduanjin exercise in improving cognition and memory in patients with mild cognitive impairment. DATA SOURCES: Relevant English- and Chinese-language studies published until 15th September 2020 were retrieved from the PubMed, Web of Science, Cochrane Library, Embase, EBSCOhost, OVID, National Knowledge Infrastructure, WANFANG DATA, VIP Information, and SinoMed databases. REVIEW METHODS: Randomized controlled trials assessing Baduanjin exercise in patients with mild cognitive impairment were included. Two researchers independently identified eligible studies and extracted data. Risk-of-bias assessment was performed using the Cochrane Risk of Bias Tool. RESULTS: This study included 16 randomized controlled trials (1054 participants) from China that used Chinese versions of standardized tests. Most studies had no significant bias, and only one study had a high risk of bias in the random allocation category. Compared with conventional therapy alone, Baduanjin plus conventional therapy significantly improved the Montreal Cognitive Assessment and Mini-Mental State Examination scores after 6 months of treatment (P < 0.00001 for both), significantly decreased the tau/Aß1-42 ratio in the cerebrospinal fluid (P < 0.00001), and significantly improved some dimensional scores on the Wechsler Memory Scale and the auditory verbal learning test scores at 6 months (P < 0.05 for all). CONCLUSION: Compared with conventional therapy, Baduanjin plus conventional therapy significantly improved cognitive and memory function in patients with mild cognitive impairment.

A Chinese CADASIL Family with a Novel Mutation on Exon 10 of Notch3 Gene.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is caused by the Notch3 gene mutation, has its unique clinical and imaging characteristics. Here we present a Chinese family with a novel mutation on exon 10 of Notch3 gene. METHODS: Clinical and MRI data of the three patients in the family during the 7-year follow-up were collected. The CADASIL Scale Score was calculated to evaluate the disease risk of the three patients at their first admission or clinic visit. Five family members underwent genetic test. RESULTS: Genetic test confirmed the diagnosis of CADASIL in this family. A novel mutation of p.C533S on exon 10 of Notch3 gene was detected. The CADASIL score of the proband and her sister was both 17 and that of her brother was 14. CONCLUSIONS: Our report not only expands the mutation spectrum of Notch3 gene in CADASIL, but also shows the distinct heterogeneity of CADASIL patients in the same family with the same mutation.

Comparison of regional and local anesthesia for arteriovenous fistula creation in end-stage renal disease: a systematic review and meta-analysis.

BACKGROUND: Arteriovenous fistulae (AVF) are the hemodialysis access modality of choice for patients with end-stage renal disease. However, they have a high early failure rate. Good vascular access is essential to manage long-term hemodialytic treatment, but some anesthesia techniques directly affect venous diameter as well as intra- and post-operative blood flow. The main purpose of this meta-analysis was to compare the results of regional and local anesthesia (RA and LA) for arteriovenous fistula creation in end-stage renal disease. METHODS: We conducted a systematic review and meta-analysis to synthesize evidence from 7 randomized controlled trials (565 patients) and 1 observational study (408 patients) with the aim of evaluating the safety and efficacy of RA versus LA in surgical construction of AVF. RESULTS: Pooled data showed that RA was associated with higher primary patency rates than LA (odds ratio [OR], 1.88; 95% confidence interval [CI]: 1.24-2.84; P = 0.003; I2 = 31%). Additionally, brachial artery diameter was significantly increased in the RA versus LA group (mean difference [MD], 0.83; 95% CI: 0.75-0.92; P < 0.001; I2 = 97%) and the need for intra- as well as post-operative pain killers was significantly less (RA, P = 0.0363; LA, P = 0.0318). Moreover, operation duration was significantly reduced using RA versus LA (MD, - 29.63; 95% CI: - 32.78 - -26.48; P < 0.001; I2 = 100%). CONCLUSIONS: This meta-analysis suggests that RA is preferable to LA in patients with end-stage renal disease in guaranteeing AVF patency and increasing brachial artery diameter.

Tunable optical microwave generation using self-injection locked monolithic dual-wavelength amplified feedback laser.

A tunable optical microwave generation scheme using self-injection locked monolithic dual-wavelength amplified feedback laser (AFL) is proposed and experimentally demonstrated. By using a dual-loop feedback scheme, the 3-dB linewidth of the optical microwave output resulting from mode beating is reduced from MHz to kHz scale. Optical microwave generation tunable from 30 to 38 GHz with 3-dB linewidth below 2 kHz is experimentally demonstrated.

Au nanozyme-based colorimetric sensor array integrates machine learning to identify and discriminate monosaccharides.

As different monosaccharides exhibit different redox characteristics, this paper presented a novel colorimetric sensor array based on the glucose oxidase-like (GOx-like) activity of Au nanoparticles (NPs) for monosaccharides identification. AuNPs can use O2, ABTS+•, or [Ag(NH3)2]+ as an electron acceptor to catalyze the oxidation of monosaccharides in different velocity, resulting in cross-responsive signals. The current sensor array can distinguish between different monosaccharides or their mixtures through linear discriminant analysis (LDA) and hierarchical clustering analysis (HCA). Moreover, the glucose and fructose concentrations can be estimated simultaneously using a neural network regression model based on the sensor array. This method shows potential for monosaccharide detection in industrial, medical, and biological applications.

Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II.

Glutaric aciduria type II (GA II) is an autosomal recessive metabolic disorder of fatty acid, amino acid, and choline metabolism. The late-onset form of this disorder is caused by a defect in the mitochondrial electron transfer flavoprotein dehydrogenase or the electron transfer flavoprotein dehydrogenase (ETFDH) gene. Thus far, the high clinical heterogeneity of late-onset GA II has brought a great challenge for its diagnosis. In this study, we reported a 21-year-old Chinese man with muscle weakness, vomiting, and severe pain. Muscle biopsy revealed myopathological patterns of lipid storage myopathy, and urine organic acid analyses showed a slight increase in glycolic acid. All the aforementioned results were consistent with GA II. Whole-exome sequencing (WES), followed by bioinformatics and structural analyses, revealed two compound heterozygous missense mutations: c.1034A > G (p.H345R) on exon 9 and c.1448C>A (p.P483Q) on exon 11, which were classified as "likely pathogenic" according to American College of Medical Genetics and Genomics (ACMG). In conclusion, this study described the phenotype and genotype of a patient with late-onset GA II. The two novel mutations in ETFDH were found in this case, which further expands the list of mutations found in patients with GA II. Because of the treatability of this disease, GA II should be considered in all patients with muscular symptoms and acute metabolism decompensation such as hypoglycemia and acidosis.

Astaxanthin Ameliorates Worsened Muscle Dysfunction of MDX Mice Fed with a High-Fat Diet through Reducing Lipotoxicity and Regulating Gut Microbiota.

Duchenne muscular dystrophy (DMD), a severe X-linked inherited neuromuscular disease, has a high prevalence of obesity. Obesity exacerbates muscle damage and results in adverse clinical outcomes. Preventing obesity helps DMD patients delay disease progression and improve quality of life. Astaxanthin (AX) is a kind of carotenoid which has antioxidant and anti-adipogenesis effects. In this study, male C57BL/10ScSnDmdmdx/J mice were fed with a normal diet, a high-fat diet (HFD), and an HFD containing AX for 16 weeks, respectively. The results showed that AX significantly increased gastrocnemius fiber cross-section area and grip strength, improved treadmill endurance test and mitochondrial morphology, and reduced muscle triglyceride and malonaldehyde levels compared to the HFD. Lipidomic analysis revealed that AX decreased high levels of triglyceride, diglyceride, ceramides, and wax ester induced by HFD. Gut microbiota analysis indicated that AX supplementation failed to alleviate abnormal microbiota diversity, but increased the relative abundances of Akkermansia, Bifidobacterium, Butyricicoccus, and Staphylococcus. In conclusion, AX was expected to alleviate disease progression associated with obesity in DMD patients by reducing lipotoxicity and increasing the abundance of beneficial bacteria.

Elevated Serum Ninjurin-1 Is Associated with a High Risk of Large Artery Atherosclerotic Acute Ischemic Stroke.

Ninjurin-1 is a novel adhesion molecule which is involved in many inflammatory diseases. Functional blockage of Ninjurin-1 has exerted an atheroprotective effect. The aim of the study is to explore the association between serum Ninjurin-1 and the risk of large artery atherosclerotic acute ischemic stroke. From August 2020 through December 2021, patients with large artery atherosclerotic acute ischemic stroke (LAA-AIS) admitted to the First Hospital Affiliated to Soochow University, and age- and sex-matched controls free of ischemic stroke were recruited. Serum Ninj1 was measured with an enzyme-linked immunosorbent assay. Multivariable logistic regression models were used to calculate the odds ratios and 95% confidence intervals of LAA-AIS associated with serum Ninj1 levels, and receiver operating characteristic (ROC) curves were performed to assess the improvement value of Ninj1 for the prediction of LAA-AIS after adding Ninj1 to established risk factors. Of the 110 patients and 110 age- and sex-matched controls free of ischemic stroke enrolled, serum Ninj1 levels in LAA-AIS patients were significantly higher than that in control group (142.70 ng/ml [IQR: 110.41-163.44] vs 101.62 ng/ml [IQR: 86.63-120.86], p < 0.001). In multivariable analysis, Ninj1 levels were expressed as continuous variable and ordinal variable (tertiles), and it turned out that Ninj1 levels were positively associated with increased risk of LAA-AIS, especially in tertile3 compared with tertile1 (adjusted OR = 12.567, 95%CI: 5.148-30.678, p < 0.001), and the adjusted odds OR per 10 ng/ml increment was 1.541, 95%CI: 1.348-1.763, p < 0.001. Furthermore, adding Ninj1 to a multivariate logistic model including conventional risk factors associated LAA-AIS improved the area under ROC curves from 0.787 to 0.874. Elevated circulating levels of Ninj1 were associated with increased risk of LAA-AIS, indicating that serum Ninj1 may act as a predictor independent of established conventional risk factors.

NT-proBNP Levels and Collateral Circulation Status in Patients with Acute Ischemic Stroke.

Methods: In this study, 326 hospitalized patients with acute anterior circulation ischemic stroke (AACIS) were included. A comparison of the clinical characteristics of those with and without AF was conducted. The Spearman rank correlation was used for the correlation analysis of plasma NT-proBNP level, regional leptomeningeal collateral (rLMC) score, and computed tomography perfusion (CTP) status in the AF and non-AF groups. An analysis of multivariate linear regression was used to determine how plasma NT-proBNP level, rLMC score, and CTP status influenced the score on the NIHSS. Results: There was a greater plasma NT-proBNP level in the AF group compared with the non-AF group, an increased CTP volume (including CTP ischemic volume, CTP infarct core volume, and CTP ischemic penumbra volume (P = 0.002)), higher NIHSS score on admission, and lower rLMC score (P < 0.001 for the remaining parameters). A negative correlation exists between plasma NT-proBNP level and rLMC score (r = -0.156, P = 0.022), but a positive correlation exists between plasma NT-proBNP level and both CTP ischemic volume and CTP infarct core volume (r = 0.148, P = 0.003) in the AF group, but not in the non-AF group. Multivariate linear regression analysis demonstrated that NT-proBNP, CTP ischemic penumbra volume, and rLMC score were associated with NIHSS score, and NT-proBNP was positively associated with NIHSS scores (95% confidence interval (CI), 0.000-0.002; P = 0.004) in the AF group, whatever in the unadjusted model or adjusted models, but not in the nonlarge artery atherosclerosis (LAA) group. Conclusion: In AACIS patients with AF, NT-proBNP level negatively correlated with collateral status, positively with CTP ischemic volume, and positively with NIHSS score.

Effect of sacubitril/valsartan on brain natriuretic peptide level and prognosis of acute cerebral infarction.

BACKGROUND AND PURPOSE: Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI. METHODS: In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge). RESULTS: We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05). CONCLUSIONS: Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.