Development of a SERS aptasensor for the determination of L-theanine using a noble metal nanoparticle-magnetic nanospheres composite.

An ultrasensitive surface-enhanced Raman spectroscopy (SERS) aptamer sensor (aptasensor) using a noble metal nanoparticle-magnetic nanospheres composite was developed for L-theanine detection. It makes use of Fe3O4@Au MNPs and Au@Ag NPs embedded with the Raman reporter 4-mercaptobenzoic acid (4MBA). Au@4MBA@Ag NPs modified by aptamer and Fe3O4@Au MNPs modified by cDNA created the aptasensor with the strongest Raman signal of 4MBA through the specific binding of the aptamer. With the preferred binding of L-theanine aptamer to L-theanine, Au@4MBA@Ag NPs were released from Fe3O4@Au MNPs, causing a linear decrease in SERS intensity to achieve the SERS detection of the L-theanine. The SERS peak of 4MBA at 1078 cm-1 was used for quantitative determination. SERS intensity showed a good log-linear relationship within the range 10-10 to 10-6 M of L-theanine. The aptasensor has a high selectivity for L-theanine compared with other twelve tested analytes. Hence, this aptasensor is a promising analytical tool for L-theanine detection. The developed method was applied to the analysis of real samples, demonstrating excellent performance. The comparison with the standard liquid chromatography mass spectrometry method showed an error within 20%.

Realization of qualitative to semi-quantitative trace detection via SERS-ICA based on internal standard method.

Surface-enhanced Raman spectroscopy (SERS) can quickly identify molecular fingerprints and has been widely used in the field of rapid detection. However, the non-uniformity inherent in SERS substrate signals, coupled with the finite nature of the detection object, significantly hampers the advancement of SERS. Nowadays, the existing mature immunochromatographic assay (ICA) method is usually combined with SERS technology to address the defects of SERS detection. Nevertheless, the porous structure of the strip will also affect the signal uniformity during detection. Obviously, a method using SERS-ICA is needed to effectively solve signal fluctuations, improve detection accuracy, and has certain versatility. This paper introduces an internal standard method combining deep learning to predict and process Raman data. Based on the signal fluctuation of single-antigen SERS-ICA test strip, the double-antigen SERS-ICA test strip was constructed. The full spectrum Raman data of double-antigen SERS-ICA test strip was normalized by the sum of two characteristic peaks of internal standard molecules, and then processed by deep learning algorithm. The Relative Standard Deviation (RSD) of Raman data of bisphenol A was compared before and after internal standard normalization of double-antigen SERS-ICA test strip. The RSD processed by this method was increased by 3.8 times. After normalization, the prediction accuracy of Root Mean Square Error (RMSE) is improved by 2.66 times, and the prediction accuracy of R-square (R2) is increased from 0.961 to 0.994. The results showed that RMSE and R2 were used to comprehensively predict the collected data of double-antigen SERS-ICA test strip, which could effectively improve the prediction accuracy. The internal standard algorithm can effectively solve the challenges of uneven hot spots and poor signal reproducibility on the test strip to a certain extent, so as to improve the semi-quantitative accuracy.

The Association of Retinal Microvasculature With Gray Matter Changes and Structural Covariance Network: A Voxel-Based Morphometry Study.

Purpose: Increasing evidence suggests that retinal microvasculature may reflect global cerebral atrophy. However, little is known about the relation of retinal microvasculature with specific brain regions and brain networks. Therefore, we aimed to unravel the association of retinal microvasculature with gray matter changes and structural covariance network using a voxel-based morphometry (VBM) analysis. Methods: One hundred and forty-four volunteers without previously known neurological diseases were recruited from West China Hospital, Sichuan University between April 1, 2021, and December 31, 2021. Retinal microvasculature of superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP) were measured by optical coherence tomography angiography using an automatic segmentation. The VBM and structural covariance network analyses were applied to process brain magnetic resonance imaging (MRI) images. The associations of retinal microvasculature with voxel-wise gray matter volumes and structural covariance network were assessed by linear regression models. Results: In the study, 137 participants (mean age = 59.72 years, 37.2% men) were included for the final analysis. Reduced perfusion in SVP was significantly associated with reduced voxel-wise gray matter volumes of the brain regions including the insula, putamen, occipital, frontal, and temporal lobes, all of which were located in the anterior part of the brain supplied by internal carotid artery, except the occipital lobe. In addition, these regions were also involved in visual processing and cognitive impairment (such as left inferior occipital gyrus, left lingual gyrus, and right parahippocampal gyrus). In regard to the structural covariance, the perfusions in SVP were positively related to the structural covariance of the left lingual gyrus seed with the left middle occipital gyrus, the right middle occipital gyrus, and the left middle frontal gyrus. Conclusions: Poor perfusion in SVP was correlated with reduced voxel-wise gray matter volumes and structural covariance networks in regions related to visual processing and cognitive impairment. It suggests that retinal microvasculature may offer a window to identify aging related cerebral alterations.

Echocardiographic correlates of MRI imaging markers of cerebral small-vessel disease in patients with atrial-fibrillation-related ischemic stroke.

Background and objectives: Atrial fibrillation (AF) has been linked to dementia risk, partly explained by cerebral small vessel disease (CSVD). Since AF and cardiovascular comorbidities were associated with cardiac dysfunction, we aimed to determine the association between echocardiographic parameters and neuroimaging markers of CSVD in patients with AF-related ischemic stroke. Methods: This cross-sectional study enrolled patients with AF-related ischemic stroke from March 2013 to December 2019 who underwent transthoracic echocardiography and brain 3T MRI, including T1, T2, Flair, and SWI imaging sequences. We assessed the presence of lacunes and cerebellar microbleeds (CMBs), the severity of white matter hyperintensity (WMH) scored by the Fazekas scale (0-6), and the severity of enlarged perivascular spaces (EPVS) in basal ganglia (BG) and centrum semiovale (CSO) classified into three categories (0-10, 10-25, and >25). CSVD burden was rated on a 0-to-4 ordinal scale. Generalized linear regression analysis and post hoc comparisons with Bonferroni correction were performed to assess the association between various echocardiographic parameters and these lesions, adjusted for demographics and potential confounders. Results: 119 patients (68.38 ± 12.692 years; male 45.4 %) were included for analysis, of whom 55 (46.2%) had lacunes, 40 (33.6%) had CMBs, and median severity for WMH, BG-EPVS, CSO-EPVS, and CSVD burden were 2 (IQR: 1-3), 1 (IQR: 1-2), 1 (IQR: 0-1), and 1 (IQR: 1-2) respectively. In multivariable, fully adjusted models, left ventricular posterior wall thickness (LVPW) was associated with a higher risk of lacunes (RR 1.899, 95% CI: 1.342-2.686) and CSVD burden (RR = 2.081, 95%CI: 1.562-2.070). Right atrial diameter (RAD) was associated with greater CSO-EPVS (RR = 2.243, 95%CI: 1.234-4.075). No echocardiographic parameters were revealed to be associated with CMBs and WMH. Conclusion: In patients with AF-related ischemic stroke, LVPW is associated with a higher risk of lacunes and CSVD burden, while RAD was associated with greater CSO-EPVS. Larger studies are required to determine these associations and to elucidate if these associations can help facilitate cognitive evaluation and brain MRI screening.

CT-determined low skeletal muscle mass predicts worse overall survival of gastric cancer in patients with cachexia.

BACKGROUND: There were controversies for the association between computed tomography (CT)-determined low skeletal muscle mass (SMM) and overall survival (OS) in gastric cancer (GC). In this study, we investigated whether cachexia could be a potential confounding variable for this issue. METHODS: We retrospectively collected the patients of GC in our institution between July 2016 and January 2021. Preoperative SMM was determined by analyzing the skeletal muscle index of L3 with abdominal CT, and the cut-offs for low SMM were defined as <52.4 (men) and < 38.5 cm2 /m2 (women), respectively. Overall survival (OS) was the primary endpoint. RESULTS: Of the 255 included GC patients, 117 (46%) were classified as having low SMM. Those with low SMM were associated with a higher level of circulating interleukin 6 and C reactive protein but a lower level of albumin than those of normal SMM. The univariate analysis showed that low SMM, tumor-node-metastasis (TNM) stage, body mass index (BMI), postoperative chemotherapy, and cachexia were significantly associated with OS, while in the multivariate analysis, only low SMM and TNM stage were significantly associated with OS. Kaplan-Meier survival curves with log-rank tests indicated that low SMM significantly predicted worse OS of GC. After grouping by cachexia, the low SMM significantly predicted worse OS in patients with cachexia instead of those without cachexia. CONCLUSIONS: CT-determined low SMM predicts worse OS of GC in patients with cachexia instead of those without cachexia, and greater attention should be paid to such patients with synchronous low SMM and cachexia.

Acute Cerebral Microinfarcts in Acute Ischemic Stroke: Imaging and Clinical Significance.

BACKGROUND: Limited data exist on the significance of acute cerebral microinfarcts (A-CMIs) in the context of acute ischemic stroke (AIS). We aimed to determine the profile and prognostic significance of A-CMIs on magnetic resonance imaging (MRI) in patients presenting with AIS. METHODS: A prospective single-center series of patients with AIS who had 3T MRIs between March 2013 and December 2019. The presence, number, and location of A-CMIs on diffusion-weighted imaging, and markers of cerebral small vessel disease (CSVD), macroinfarcts features, and etiology were classified as cardioembolism (CE) or large artery atherosclerosis (LAA) or none. RESULTS: Among 273 patients, A-CMIs were detected in 130 patients (47.6%), of whom cortical A-CMIs were found in 95 (73.0%) patients. Patients with A-CMIs were significantly older, less likely to have diabetes mellitus, and more likely to have atrial fibrillation and an embolic source (CE or LAA) compared to other patients. Patients with A-CMI had a higher frequency of macroinfarcts (diameter >20 mm), more often multiple and distributed in single or multiple vessel territories than other patients. An embolic source (LAA or CE) was independently associated with cortical A-CMIs (LAA adjusted odds ratio [aOR] 4.0 95% confidence interval [CI] 1.6-9.5; CE aOR 2.5, 95% CI 1.1-5.6), whereas lacunes were independently related to subcortical A-CMIs (aOR 2.6, 95% CI 1.2-5.8). CONCLUSIONS: We have shown A-CMIs occur in cortical and subcortical regions in nearly half of AIS patients, where microembolism and CSVD are, respectively, the key presumed etiological mechanism.

Development of cognition decline in non-acute symptomatic patients with cerebral small vessel disease: Non-Acute Symptomatic Cerebral Ischemia Registration study (NASCIR)-rationale and protocol for a prospective multicentre observational study.

INTRODUCTION: Headaches, dizziness and memory loss of unspecific causes are the most common non-acute ischemia symptoms in the ageing population, which are often associated with cerebral small vessel disease (CSVD) imaging markers; however, there is insufficient evidence concerning their association with the development of cognitive decline. This study aims to investigate risk factors, clinical course, cerebral and retinal imaging changes, proteomics features of non-symptomatic ischaemia symptomatic patients with cognitive decline. METHODS AND ANALYSIS: The Non-Acute Symptomatic Cerebral Ischemia Registration study is a multicentre, registry-based, prospective observational study, is designed to investigate the cognitive decline in non-acute ischaemia symptomatic patients. We will recruit 500 non-acute ischaemia symptomatic patients from four tertiary hospitals in China. For this study, non-acute ischaemia symptoms will be defined as headaches, dizziness and memory loss. Patients with headaches, dizziness or memory loss over 50 years of age will be included. Clinical features, cognitive assessment, cerebral and retinal imaging data, and a blood sample will be collected after recruitment. Patients will be followed up by structured telephone interviews at 1, 2, 3, 4, 5 years after recruitment. This study will improve our knowledge of the development of cognitive decline in non-acute ischaemia symptomatic patients and factors affecting the cognitive outcomes, which will eventually elucidate underlying pathways and mechanisms of cognitive decline in these patients and facilitate the optimisation of individualised interventions for its prevention and treatment. ETHICS AND DISSEMINATION: Ethics approval is obtained from The Biomedical Research Ethics Committee of West China Hospital, Sichuan University (Reference No. 2016 (335)). We will present our findings at national and international conferences and peer-reviewed journals in stroke and neurology. TRIAL REGISTRATION NUMBER: ChiCTR-COC-17013056.

Relationships between cerebral small vessel diseases markers and cognitive performance in stroke-free patients with atrial fibrillation.

Background: Atrial fibrillation (AF) is related to an increased risk of cognitive dysfunction. Besides clinically overt stroke, AF can damage the brain via several pathophysiological mechanisms. We aimed to assess the potential mediating role of cerebral small vessel disease (SVD) and cognitive performance in individuals with AF. Methods: Stroke-free individuals with AF from the cardiological outpatient clinic at West China Hospital of Sichuan University were recruited. Extensive neuropsychological testing tools were assessed including global function, domains of attention, executive functions, learning, and memory. 3 T magnetic resonance imaging (MRI) was used for SVD markers assessment of white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). The correlation between SVD markers and cognitive measures was analyzed by multivariate linear regression models. Results: We finally enrolled 158 participants, of whom 95 (60.1%) were males. In multivariate models, the presence of lacunes independently associated with Montreal Cognitive Assessment (Model 1: ß = 0.52, Model 2: ß = 0.55), Rey Auditory Verbal Learning Test-immediate and delayed recall (Model 1: ß = 0.49; ß = 0.69; Model 2: ß = 0.53; ß = 0.73) as well as Stroop-Acorrect (Model 1: ß = 0.12; Model 2: ß = 0.13), while total WMH severity independently associated with Strooptime-A (Model 1: ß = 0.24; Model 3: ß = 0.27), Strooptime-B (Model 1: ß = 0.17; Model 3: ß = 0.17), Strooptime-C (Model 1: ß = 0.22; Model 3: ß = 0.21) and Shape Trail Test-A (Model 1: ß = 0.17; Model 3: ß = 0.16). Conclusion: In our cohort of stroke-free individuals with AF, lacunes, and WMHs were independently associated with cognitive decline while EPVS and CMBs did not show significance. Assessment of SVD MRI markers might be valuable for cognition risk stratification and facilitate optimal management of patients with AF.

Association between admission blood fibrinogen-to-albumin ratio and clinical outcomes after acute lacunar stroke.

Aim: We aimed to investigate the influence of admission fibrinogen-to-albumin ratio (FAR) on 3-month outcomes after acute lacunar stroke. Materials & methods: Consecutive patients with acute lacunar stroke were included and classified into two groups according to an optimized FAR cut-off value determined by receiver operating characteristic curve analysis. Results: Compared with those with low FAR (<0.077), patients from the high FAR group (≥0.077) had significantly higher risk for 3-month disability and the composite outcome of death/disability. After logistic regression adjustment, high FAR was still significantly associated with 3-month disability and death/disability. Conclusion: FAR ≥0.077 on admission might be an independent predictor of disability and death/disability at 3 months after lacunar stroke, which needs to be verified in future studies.

Radiomics-based prediction of hemorrhage expansion among patients with thrombolysis/thrombectomy related-hemorrhagic transformation using machine learning.

INTRODUCTION: Patients with hemorrhagic transformation (HT) were reported to have hemorrhage expansion. However, identification these patients with high risk of hemorrhage expansion has not been well studied. OBJECTIVES: We aimed to develop a radiomic score to predict hemorrhage expansion after HT among patients treated with thrombolysis/thrombectomy during acute phase of ischemic stroke. METHODS: A total of 104 patients with HT after reperfusion treatment from the West China hospital, Sichuan University, were retrospectively included in this study between 1 January 2012 and 31 December 2020. The preprocessed initial non-contrast-enhanced computed tomography (NECT) imaging brain images were used for radiomic feature extraction. A synthetic minority oversampling technique (SMOTE) was applied to the original data set. The after-SMOTE data set was randomly split into training and testing cohorts with an 8:2 ratio by a stratified random sampling method. The least absolute shrinkage and selection operator (LASSO) regression were applied to identify candidate radiomic features and construct the radiomic score. The performance of the score was evaluated by receiver operating characteristic (ROC) analysis and a calibration curve. Decision curve analysis (DCA) was performed to evaluate the clinical value of the model. RESULTS: Among the 104 patients, 17 patients were identified with hemorrhage expansion after HT detection. A total of 154 candidate predictors were extracted from NECT images and five optimal features were ultimately included in the development of the radiomic score by using logistic regression machine-learning approach. The radiomic score showed good performance with high area under the curves in both the training data set (0.91, sensitivity: 0.83; specificity: 0.89), test data set (0.87, sensitivity: 0.60; specificity: 0.85), and original data set (0.82, sensitivity: 0.77; specificity: 0.78). The calibration curve and DCA also indicated that there was a high accuracy and clinical usefulness of the radiomic score for hemorrhage expansion prediction after HT. CONCLUSIONS: The currently established NECT-based radiomic score is valuable in predicting hemorrhage expansion after HT among patients treated with reperfusion treatment after ischemic stroke, which may aid clinicians in determining patients with HT who are most likely to benefit from anti-expansion treatment.

[Magnetic Resonance Imaging Tissue Feature Tracking for Cardiac Amyloidosis].

OBJECTIVE: To detect cardiac amyloidosis (CA) using cardiac magnetic resonance feature tracking(CMR-FT). METHODS: Forty-three CA patients and 24 healthy volunteers underwent steady-state free precession cine sequence on 3.0T MRI after injection of Magnevist. Software cvi 42 was used for analyzing the left ventricular function including left ventricular mass (diastole) (LVMD), left ventricular mass (systole) (LVMS), left ventricle end-diastolic volume (LVEDV), left ventricle end-systolic volume (LVESV), left ventricle stroke volume (LVSV), and left ventricular ejection fraction (LVEF), as well as myocardial strains including 3D global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS), and 2D endocardial and epicardial longitudinal strain, circumferential strain, and radial strain (ENDO-LS, EPI-LS, ENDO-CS, EPI-CS, ENDO-RS, and EPI-RS). The global and layer-specific strains were compared between the CA patients with LVEF >50%, the CA patients with LVEF ≤50%, and the healthy controls. RESULTS: For the left ventricular function, the CA patients had greater myocardial mass than the healthy controls (P < 0.05); the CA patients with LVEF ≤50% had greater LVESV and lower LVSV than those with LVEF >50% (P < 0.05). For the global strains, significant differences also appeared in GLS and GCS among the three groups (all P < 0.05). The CA patients had lower GRS than the healthy controls (P < 0.05), while no significant difference was found in GRS between the CA patients with LVEF >50% and those with LVEF ≤50% (P>0.05). For the layer-specific strains, significant differences in ENDO-LS, EPI-LS, ENDO-CS, EPI-CS, ENDO-RS, and EPI-RS were found among the three groups (all P < 0.05). There were significant correlations between GLS and LVEF (r=-0.404, P=0.016), and between GCS and LVEF (r=-0.602, P < 0.001) in the CA patients. CONCLUSION: CMR-FT can assess not only global strains but also layer-specific strains for the myocardial function of CA patients.

[Establishment of Bone Metastasis Model of Prostate Cancer in Mice with Monitoring of 18F-NaF PET-CT].

OBJECTIVES: To establish a mouse model bearing human prostate cancer xenograft with bone metastasis by the monitoring with X-Ray, Micro CT, and ¹8F-NaF PET/CT. METHODS: Sixteen male Balb/c nude mice were allocated into control (6 mice) and experimental group (10 mice). In experimental group, the mice were subjected to percutaneous injection of 2×105PC-3 cells into tibial plateau, bone defects were assessed after 21 d by X-ray, Micro-CT and ¹8F-NaF PET/CT, and bone damages were evaluated by HE staining. In control group, equal volume of saline was injected into the mice. RESULTS: At 21 d post modeling, the significant radioactive ¹8F--NaF signals were found in the tibial intramedullary cavity of all 10 mice in experimental group. The ROI value evaluation showed that SUVmaxin control group was 0.62±0.14, but SUVmaxin tumor group was 2.10±0.13, which indicated abnormal bone metabolism. The serum alkaline phosphate level and HE staining results also confirmed that tumor mediated bone destruction and osteogenesis. However, X-ray and Micro-CT did not indicate precise diagnostic bone defect. CONCLUSION: Bone metastasis model of prostate PC-3 cancer cells were successfully established by intratibial injection. ¹8F-NaF PET/CT could detect tumor invasion and bone osteogenesis in the early stage of modeling.