An Artificial Intelligence-Driven Approach for Automatic Evaluation of Right-to-Left Shunt Grades in Saline-Contrasted Transthoracic Echocardiography.

BACKGROUND: Intracardiac or pulmonary right-to-left shunt (RLS) is a common cardiac anomaly associated with an increased risk of neurological disorders, specifically cryptogenic stroke. Saline-contrasted transthoracic echocardiography (scTTE) is often used for RLS diagnosis. However, the identification of saline microbubbles in the left heart can be challenging for novice residents, potentially leading to a delay in diagnosis and treatment. In this study, we proposed an artificial intelligence (AI)-based algorithm designed to automatically detect microbubbles in scTTE images and evaluate right-to-left shunt grades. This tool aims to support residency training and decrease the workload of cardiologists. METHODS: A dataset of 23,665 scTTE images obtained from 174 individuals was included in this study. This dataset was partitioned into a training set (n = 20,475) and an internal validation set (n = 3,190) on a patient-level basis. An additional cohort of 33 patients diagnosed with cryptogenic ischemic stroke was enrolled as an external validation set. The proposed algorithm for right-to-left shunt degree classification employed the EfficientNet-b4 model, and the model's performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity, and compared to the performance of residents. RESULTS: Our AI model demonstrated robust performance with an accuracy of 0.926, sensitivity of 0.827, and specificity of 0.951 on the internal testing dataset. In the external validation set, our AI model exhibited diagnostic accuracy, sensitivity, and specificity of 0.864, 0.818, and 0.909, respectively. In comparison, residents achieved values of 0.727, 0.636, and 0.818, respectively. CONCLUSION: Our AI model provides a swift, precise, and easily deployable methodology for grading the degree of right-to-left shunt in scTTE, carrying substantial implications for routine clinical practice. Residents can benefit from our artificial intelligence-based algorithm, enhancing both the accuracy and efficiency of RLS diagnosis.

Adaptive Dosage Strategy of Levetiracetam in Chinese Epileptic Patients: Focus on Pregnant Women.

There is presently no efficient dose individualization strategy for the use of antiseizure medications in epileptic pregnant patients. This study aimed to develop a population pharmacokinetics model for levetiracetam and propose a tailored adaptive individualized dosage strategy for epileptic pregnant patients. A total of 322 levetiracetam plasma concentrations from 238 patients with epilepsy were included, including 216 women with epilepsy (20.83% of whom were pregnant). The levetiracetam plasma concentration was measured using a validated ultra-performance liquid chromatography-tandem mass spectrometry assay, and the data were modeled using a nonlinear mixed-effects model. The resultant model served as the basis for simulating the dosage adjustment strategy. A one-compartment model with first-order elimination best described the pharmacokinetic data of levetiracetam. The apparent clearance (CL/F) was 3.43 L/h (95% CI 3.30-3.56) and the apparent volume of distribution was 43.7 L (95% CI 40.4-47.0) for a typical individual of 57.2 kg. Pregnancy and body weight were found to be significant covariates of CL/F of levetiracetam. The recommended regimen of levetiracetam could be predicted by the population pharmacokinetic model based on body weight, gestational age, and the daily dose of levetiracetam taken before pregnancy.

Identifying Genetic Factors of Polycystic Ovary Syndrome in Women with Epilepsy: A Whole-Genome Sequencing Study.

INTRODUCTION: Women with epilepsy (WWE) are more likely to develop reproductive endocrine disorders, especially polycystic ovary syndrome (PCOS). This study aimed to explore the genetic factors of PCOS in WWE in hope of improving individual precision diagnosis and treatment. METHODS: WWE registered at West China Hospital between January 2022 and October 2022 were enrolled in this study. Demographic and epilepsy-related characteristics were recorded, and blood samples were collected for hormones, glucose metabolism testing, and whole-genome sequencing. RESULTS: After sample sequencing, quality control, and variants selection, association analyses were performed. Pathway analysis was performed to identify involved biological pathways. The overall and PCOS "burden score" of each individual were calculated to count the deleterious variants. A total of 95 WWE were included in this study and 19 patients were diagnosed with PCOS. WWE with PCOS showed a significantly different hormone profiles and a tendency of impaired glucose metabolism. The most commonly associated genes were ZFYVE28, COL19A1, SIK3, ANKK1, PPIG, and REPIN1. The top 3 canonical pathways are adipogenesis pathway, epoxysqualene biosynthesis signaling, and glutamate degradation signaling. The most significant common variant was rs11914038 located in gene CELSR1 and rs651748 located in gene ZBTB16. In human gene connectome prioritizations, ITGA9, PNPLA2, and DAB2 are the top 3 genes having the shortest distance to known PCOS genes. CONCLUSION: Genetic factors involved in the abnormal regulation of glucose and insulin metabolism are likely to be associated with the comorbidity of PCOS in WWE. Interventions targeting these processes should be given more priority in clinical practice.

Enhancement of the anthocyanin contents of Caladium leaves and petioles via metabolic engineering with co-overexpression of AtPAP1 and ZmLc transcription factors.

Introduction: Metabolic engineering of anthocyanin synthesis is an active research area for pigment breeding and remains a research hotspot involving AtPAP1 and ZmLc transcription factors. Caladium bicolor is a desirable anthocyanin metabolic engineering receptor, with its abundant leaf color and stable genetic transformation system. Methods: We transformed C. bicolor with AtPAP1 and ZmLc and successfully obtained transgenic plants. We then used a combination of metabolome, transcriptome, WGCNA and PPI co-expression analyses to identify differentially expressed anthocyanin components and transcripts between wild-type and transgenic lines. Results: Cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and peonidin-3-O-rutinoside are the main components of anthocyanins in the leaves and petioles of C. bicolor. Exogenous introduction of AtPAP1 and ZmLc resulted in significant changes in pelargonidins, particularly pelargonidin-3-O-glucoside and pelargonidin-3-O-rutinoside in C. bicolor. Furthermore, 5 MYB-TFs, 9 structural genes, and 5 transporters were found to be closely associated with anthocyanin synthesis and transport in C. bicolor. Discussion: In this study, a network regulatory model of AtPAP1 and ZmLc in the regulation of anthocyanin biosynthesis and transport in C. bicolor was proposed, which provides insights into the color formation mechanisms of C. bicolor, and lays a foundation for the precise regulation of anthocyanin metabolism and biosynthesis for economic plant pigment breeding.

Case report: A choroidal fissure pial arteriovenous malformation inducing venous congestive edema of the medulla oblongata and cervicothoracic spinal cord presented with proximal arm predominant weakness.

Intracranial dural arteriovenous fistula (DAVF) can induce remote myelopathy via spinal perimedullary venous drainage. In the present study, we report a rare case of intracranial pial arteriovenous malformation (AVM)-related myelopathy. A 52-year-old man presented with progressive, predominantly proximal weakness and muscle atrophy in bilateral upper limbs, urinary retention, and hyperreflexia in bilateral upper and lower limbs. Brain and cervicothoracic MRI showed longitudinal myelopathy extending from the medulla oblongata to the T6 level, with perimedullary enlarged veins from the C1 to T12 level, and remarkable enhancement in bilateral anterior horns from the C2 to C7 level. Cerebral angiography revealed a choroidal fissure AVM, which was supplied by the left anterior choroidal artery and drained exclusively by an inferior ventricular vein descending toward the spinal perimedullary veins. After endovascular embolization of the feeding pedicle, nidus, and proximal segment of the draining vein, the patient's neurological deficits rapidly improved, and a significant recovery was achieved 3 months after the procedure. This rare case indicates that intracranial pial AVM can also cause extensive congestive myelopathy with similar mechanisms underlying intracranial and craniocervical DAVF cases, and gray matter in the spinal cord might be more susceptible to ischemia induced by intraspinal venous hypertension.

Diosgenin restores memory function via SPARC-driven axonal growth from the hippocampus to the PFC in Alzheimer's disease model mice.

Central nervous system axons have minimal capacity to regenerate in adult brains, hindering memory recovery in Alzheimer's disease (AD). Although recent studies have shown that damaged axons sprouted in adult and AD mouse brains, long-distance axonal re-innervation to their targets has not been achieved. We selectively visualized axon-growing neurons in the neural circuit for memory formation, from the hippocampus to the prefrontal cortex, and showed that damaged axons successfully extended to their native projecting area in mouse models of AD (5XFAD) by administration of an axonal regenerative agent, diosgenin. In vivo transcriptome analysis detected the expression profile of axon-growing neurons directly isolated from the hippocampus of 5XFAD mice. Secreted protein acidic and rich in cysteine (SPARC) was the most expressed gene in axon-growing neurons. Neuron-specific overexpression of SPARC via adeno-associated virus serotype 9 delivery in the hippocampus recovered memory deficits and axonal projection to the prefrontal cortex in 5XFAD mice. DREADDs (Designer receptors exclusively activated by designer drugs) analyses revealed that SPARC overexpression-induced axonal growth in the 5XFAD mouse brain directly contributes to memory recovery. Elevated levels of SPARC on axonal membranes interact with extracellular rail-like collagen type I to promote axonal remodeling along their original tracings in primary cultured hippocampal neurons. These findings suggest that SPARC-driven axonal growth in the brain may be a promising therapeutic strategy for AD and other neurodegenerative diseases.

Identifying risk factors for polycystic ovary syndrome in women with epilepsy: A comprehensive analysis of 248 patients.

To assess the risk factors for polycystic ovary syndrome (PCOS) in women with epilepsy (WWE) and develop a practical approach for PCOS screening based on clinical characteristic, blood indicator, and anti-seizure medication (ASM) profiles. This cross-sectional study was conducted with 248 WWE who were consecutively enrolled from the Epilepsy Center of West China Hospital between April 2021 and March 2022. The epilepsy characteristics, blood indicators, and use of ASMs were compared between WWE with and without PCOS. Multivariate logistic regression was used to identify the factors independently associated with PCOS. The differential analysis showed that younger age at onset of epilepsy (<13 years), a history of birth hypoxia, obesity (BMI ≥25 kg/m2 ), use of levetiracetam (LEV) (≥1 year), higher levels of cholesterol, luteinizing hormone (LH) and anti-Müllerian hormone (AMH), and lower levels of sex hormone-binding globulin were associated with PCOS (p < .05). Multivariate logistic regression identified that obesity (BMI ≥25 kg/m2 ), use of LEV (≥1 year), and higher levels of AMH and LH were independently associated with PCOS in WWE (p < .05). Obesity (BMI ≥25 kg/m2 ), LEV use (≥1 year), and elevated AMH and LH levels suggest an increased in the probability of occurrence of PCOS in WWE. The combination of these profiles provides a practical approach for screening PCOS in WWE.

Relationship between right-to-left shunt, hypoxia, and epilepsy.

OBJECTIVE: A right-to-left shunt (RLS) can mediate the hypoxic state, and hypoxemia is relevant for the development of drug-resistant epilepsy (DRE). The objective of this study was to identify the relationship between RLS and DRE and further investigate the contribution of RLS to the oxygenation state in patients with epilepsy (PWEs). METHODS: We performed a prospective observational clinical study of PWEs who underwent contrast medium transthoracic echocardiography (cTTE) between January 2018 and December 2021 at West China Hospital. The collected data included demographics, clinical features of epilepsy, antiseizure medications (ASMs), RLS identified by cTTE, electroencephalography (EEG), and magnetic resonance imaging (MRI). Arterial blood gas was also assessed in PWEs with or without RLS. The association between DRE and RLS was quantified using multiple logistic regression, and the parameters of oxygen levels were furtherly analyzed in PWEs with or without RLS. RESULTS: A total of 604 PWEs who completed cTTE were included in the analysis, of which 265 were diagnosed with RLS. The proportion of RLS was 47.2% in the group of DRE, and the proportion of RLS was 40.3% in the group of non-DRE. Having RLS was associated with DRE in multivariate logistic regression analysis (adjusted OR = 1.53, P = 0.045). In the analysis of blood gas, the partial oxygen pressure in PWEs with RLS was lower than those without RLS (88.74 mmHg versus 91.84 mmHg, P = 0.044). SIGNIFICANCE: Right-to-left shunt could be an independent risk factor of DRE, and low oxygenation might be a possible reason.

Axonal Regeneration Mediated by a Novel Axonal Guidance Pair, Galectin-1 and Secernin-1.

Galectin-1 (Gal-1), a member of the Galectin family, is expressed in various tissues and responsible for multiple biological activities. Previous studies reported that extracellular Gal-1 participated in axonal growth and repair, and Gal-1 knockout mice exhibited memory impairment. However, no study has demonstrated the direct contribution of intracellular Gal-1 upregulation in neurons to promoting axonal regeneration in the brain and recovering memory function. In the present study, we found that axonal growth is promoted by overexpression of Gal-1 via adeno-associated virus serotype 9 delivery in primary cultured hippocampal neurons. Moreover, Gal-1 was expressed on the membranes of growth cones in hippocampal neurons and interacted with a novel axonal guidance molecule, Secernin-1, which was secreted from prefrontal cortex (PFC) neurons. Gal-1-overexpression-driven axonal growth was enhanced when recombinant (extracellular) Secernin-1 was treated to the axonal site in a neuron device chamber. Direct binding of extracellular Secernin-1 with Gal-1 was detected through immunoprecipitation and immunocytochemistry, demonstrating that Gal-1 possibly works as an axonal guidance receptor for Secernin-1 in hippocampal neurons. In the PFC, the expression of Gal-1 in axonal shafts and terminals of hippocampal neurons was decreased in the 5XFAD mouse model of Alzheimer's disease (AD). Overexpression of Gal-1 in hippocampal neurons recovered memory deficits and induced axonal regeneration toward the PFC in 5XFAD mice. This study suggests that the enhanced interaction of Secernin-1 and Gal-1 can be harnessed as a therapeutic strategy for long-distance and direction-specific axonal regeneration in AD.

Optimizing DUS testing for Chimonanthus praecox using feature selection based on a genetic algorithm.

Chimonanthus praecox is a famous traditional flower in China with high ornamental value. It has numerous varieties, yet its classification is highly disorganized. The distinctness, uniformity, and stability (DUS) test enables the classification and nomenclature of various species; thus, it can be used to classify the Chimonanthus varieties. In this study, flower traits were quantified using an automatic system based on pattern recognition instead of traditional manual measurement to improve the efficiency of DUS testing. A total of 42 features were quantified, including 28 features in the DUS guidelines and 14 new features proposed in this study. Eight algorithms were used to classify wintersweet, and the random forest (RF) algorithm performed the best when all features were used. The classification accuracy of the outer perianth was the highest when the features of the different parts were used for classification. A genetic algorithm was used as the feature selection algorithm to select a set of 22 reduced core features and improve the accuracy and efficiency of the classification. Using the core feature set, the classification accuracy of the RF model improved to 99.13%. Finally, K-means was used to construct a pedigree cluster tree of 23 varieties of wintersweet; evidently, wintersweet was clustered into a single class, which can be the basis for further study of genetic relationships among varieties. This study provides a novel method for DUS detection, variety identification, and pedigree analysis.

Plaque characteristics after endovascular treatment in patients with intracranial atherosclerotic disease.

BACKGROUND: Endovascular treatment (EVT) is an alternative option for symptomatic intracranial atherosclerotic disease (ICAD). However, the effect of EVT treatment on ICAD plaques is still unclear. This study describes the ICAD plaque characteristics after EVT treatment and analyzes the effect of different EVT treatments on plaque characteristics. METHOD: From 2017 January to 2022 January, ICAD patients who underwent endovascular treatment and had follow-up high-resolution magnetic resonance image (HRMRI) were enrolled in the study. Multiple plaque characteristics, including plaque enhancement, plaque burden, were measured based on preoperative, and follow-up HRMRI. Plaque characteristics and postoperative plaque changes were analyzed between different treatment groups. RESULT: Finally, 50 intracranial atherosclerotic plaques in 45 patients were included. Including 28 male patients and 17 female, media age 63.0 years old. Among 50 plaques, 41 received percutaneous angioplasty (including 22 plain balloons and 19 drug-coated balloons (DCB)) and the other 9 underwent stenting. Stenosis rate, plaque burden and eccentricity index at the lesion site were significantly decreased after EVT compared with preoperative periods (p <0.001). And only the DCB group showed a significant reduction in plaque enhancement at follow-up (p < 0.001). No significant preoperative and postoperative changes in other plaque characteristics were found. CONCLUSION: EVT treatment could compromise the characteristics of intracranial periarterial atherosclerotic plaques, and DCB treatment may result in a reduction in plaque enhancement after treatment.

Venous collaterals in acute ischemic stroke patients after endovascular treatments: a novel scoring system using 4D computed tomography angiography.

Background: To establish a novel cortical venous collateral score based on four-dimensional computed tomography angiography (4D CTA) and to assess the relationship between the score and clinical outcomes in patients with acute ischemic stroke (AIS) after endovascular treatments (EVTs). Methods: This was a retrospective case-control study designed to evaluate all consecutive patients with large vessel occlusion in unilateral anterior circulation who underwent EVTs at a single institution. Two independent neuroradiologists evaluated venous collaterals using different venous collateral scores: a cortical venous collateral score based on 4D CTA (4D-VCS), the prognostic evaluation based on cortical vein score difference in stroke (PRECISE) score, and the cortical vein opacification score (COVES). Spearman correlation analysis was used to analyze the correlation of different venous collateral scoring systems with final infarct volume (FIV), modified Rankin Scale (mRS) score, and artery collateral score. Multivariate logistic regression analysis was used to identify the prognostic value of each model. The areas under the curve (AUC) of the receiver operating characteristic (ROC) curve of the 6 models were compared by the DeLong test. Results: A total of 107 patients were enrolled in the study. The AUC of 4D-VCS was 0.92 [95% confidence interval (CI): 0.85 to 0.96; P<0.0001]. The 4D-VCS was highly correlated with FIV (r=-0.615; 95% CI: -0.737 to -0.473; P<0.001), mRS score (r=-0.706; 95% CI: -0.789 to -0.602; P<0.001), and arterial collateral score (r=0.769; 95% CI: 0.678 to 0.838; P<0.001). There were statistically significant differences between model 1 (AUC, 0.89; 95% CI: 0.81 to 0.94) and model 2 (AUC, 0.94; 95% CI: 0.88 to 0.98) (P=0.025), model 1 (AUC, 0.89; 95% CI: 0.81 to 0.94) and model 3 (AUC, 0.93; 95% CI: 0.87 to 0.97) (P=0.045), model 1 (AUC, 0.89; 95% CI: 0.81 to 0.94) and model 6 (AUC, 0.95; 95% CI: 0.89 to 0.98) (P=0.011), and model 2 (AUC, 0.94; 95% CI: 0.88 to 0.98) and model 5 (AUC, 0.89; 95% CI: 0.82 to 0.94) (P=0.032). Conclusions: The findings of this study suggested that 4D-VCS, a novel measurement of venous enhancement based on 4D CTA, may be accurately used to identify AIS patients with high risk of poor clinical outcome after EVTs.

Association between kinking of the cervical carotid or vertebral artery and ischemic stroke/TIA.

Introduction: Kinking of the cervical carotid or vertebral artery is a common structural abnormality in patients with cerebrovascular disease. However, there is no consensus about the relationship between kinking and ischemic stroke/TIA. We aim to determine the effect of arterial kinking on ischemic stroke/TIA. Methods: A retrospective study was performed on patients who underwent cerebral angiography with DSA between January 2014 and December 2018. Demographic information and comorbidities were recorded. Each anatomical circulation system was defined as an observation unit. Kinking and stenosis of each circulation unit were recorded. Ischemia stroke or TIA within 6 months and its location were assessed as an outcome. Logistic regression with a generalized estimating equation approach was used for the analysis. Results: A total of 1,062 patients (mean age 57.9 ± 14.5 years, 740 males and 322 females) were included in the study. Of the patients, 369 (35%) had kinking and 771 (73%) had ischemic stroke/TIA. There were 110 left anterior, 90 right anterior, and 308 posterior circulation units, among which 343 had mild, 160 had moderate, and 243 had severe kinking. Multivariate regression analysis showed that ischemic stroke/TIA was associated with severe kinking (OR 1.39, 95% CI 1.03-1.88, P = 0.03). Posterior circulation was more vulnerable to acute ischemia than left anterior and right anterior circulation (OR 3.58, 95% CI 2.81-4.56, P < 0.0001). Conclusion: Severe kinking of the cervical carotid or vertebral artery may be associated with a higher risk of ischemic stroke/TIA, especially when the kinking is located in the posterior circulation.

Effects of diabetes mellitus complicated by admission hyperglycemia on clot histological composition and ultrastructure in patients with acute ischemic stroke.

BACKGROUND: Type 2 diabetes mellitus (T2DM) affects the occurrence and prognosis of acute ischemic stroke (AIS). However, the impact of diabetes on thrombus characteristics is unclear. The relationship between the composition and ultrastructure of clots and DM with admission hyperglycemia was investigated. METHODS: Consecutive patients with AIS who underwent endovascular thrombus retrieval between June 2017 and May 2021 were recruited. The thrombus composition and ultrastructure were evaluated using Martius scarlet blue stain and scanning electron microscopy. Clot perviousness was evaluated via thrombus attenuation increase on computed tomography angiography (CTA) versus non-contrast CT. Patients with admission hyperglycemia DM (ahDM) and those without DM (nonDM) were compared in terms of thrombus composition, ultrastructure, and perviousness. RESULTS: On admission, higher NIHSS scores (17 vs. 12, respectively, p = 0.015) was evident in ahDM patients. After the 90-day follow-up, the rates of excellent outcomes (mRS 0-1) were lower in patients with ahDM (16.6%, p = 0.038), but functional independence (mRS 0-2) and handicapped (mRS 3-5) were comparable between patients with ahDM and nonDM. The outcome of mortality was higher in patients with ahDM (33.3%, p = 0.046) than in nonDM patients. Clots in patients with ahDM had more fibrin (39.4% vs. 25.0%, respectively, p = 0.007), fewer erythrocyte components (21.2% vs. 41.5%, respectively, p = 0.043), equivalent platelet fraction (27.7% vs. 24.6%, respectively, p = 0.587), and higher WBC counts (4.6% vs. 3.3%, respectively, p = 0.004) than in nonDM patients. The percentage of polyhedral erythrocytes in thrombi was significantly higher in ahDM patients than in nonDM patients (68.9% vs. 45.6%, respectively, p = 0.007). The proportion of pervious clots was higher in patients nonDM than in patients with ahDM (82.61% vs. 40%, respectively, p = 0.026). CONCLUSION: Patients with ahDM presented with greater stroke severity on admission and poorer functional outcomes after 3 months. Clots in patients with ahDM had more fibrin, leucocytes, and fewer erythrocyte components than in patients nonDM. The content of polyhedral erythrocytes and impervious clots proportion were significantly higher in thrombi of patients with AIS and ahDM. Further research is required to validate these findings.

A single-center pilot randomized controlled trial of atorvastatin loading for preventing ischemic brain damage after carotid artery stenting.

Objective: Carotid artery stenting (CAS) performed perioperatively with high-dose atorvastatin may reduce the incidence of new ischemic brain lesions, but more high-level evidence is needed. Furthermore, the optimal dose and course of perioperative statin therapy remain uncertain. Methods: A single-center, prospective, parallel controlled, pilot randomized clinical trial was conducted at Beijing Hospital. The study includes a total of 130 patients with CAS. The patients were randomly assigned to receive a high-dose of 80 mg/day atorvastatin (n = 65) or a standard-dose of 20 mg/day atorvastatin (n = 65) 3 days before and 3 days after planned CAS. The primary endpoint event was the cumulative incidence of silent new ischemic cerebral lesions (sNICL) on post-CAS cerebral diffusion-weighted magnetic resonance imaging (DW-MRI), transient ischemic attack (TIA), or ischemic stroke within 30 days after CAS. Results: Among the 130 patients, 123 completed the study, of which 63 were in the high-dose group and 60 were in the standard-dose group. The incidence of major endpoint events was 69.8% (44 cases) and 78.3% (46 cases) in the high-dose and standard-dose groups, respectively. There was no significant difference between the two groups (HR, 0.705; 95% CI, 0.315-1.576; p = 0.393). According to the stratified analysis results, the sNICL incidence was significantly different between the two groups in the symptomatic patients (HR, 0.263; 95% CI, 0.70-0.984; p = 0.04). Conclusion: Among patients with CAS, a periprocedural high-dose of atorvastatin did not reduce the rate of periprocedural ischemic brain damage. However, high-dose statins can reduce the incidence of sNICL after CAS in patients with symptomatic carotid stenosis. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT03079115.

Histologic differences between in situ and embolized carotid web thrombi: a case report.

BACKGROUND: The significance of carotid webs (CaWs) in ischemic stroke is becoming acknowledged. Histological features of clot composition in situ and secondary cerebrovascular embolized thrombi caused by CaW have not been described concurrently. Understanding clots' histological composition is essential for understanding the pathophysiology of clot formation in CaW. CASE PRESENTATION: A 50-year-old male patient with acute ischemic stroke, which was believed to be caused by ipsilateral CaW, was admitted to the hospital. Mechanical thrombectomy was used to retrieve thromboemboli from the middle cerebral artery. One month thereafter, the patient underwent carotid endarterectomy, and in situ CaW thrombi were retrieved. Histological analysis by hematoxylin and eosin staining revealed that histopathologic embolized thrombi appeared as typical mixed thrombi, 46.03% fibrin/platelet ratio, 48.12% RBCs, and 5.85% white blood cells. In situ thrombi had a higher fibrin/platelet ratio (68.0%), fewer RBCs (17.2%), and 14.8% white blood cells. CONCLUSION: The histopathology of large vessel occlusion stroke embolized thrombi by CaW is similar to that of other stroke etiologies. However, the clot composition of embolized thrombi significantly differs from that of in situ thrombi. CaW's in situ thrombi showed predominantly fibrin, and embolized thrombi had equivalent contents of red blood cells and fibrin/platelets. Histopathological differences between in situ and embolized thrombi suggest new research directions for the etiology of embolization. Further studies are required to confirm these results.

Carotenoid Cleavage Dioxygenase Genes of Chimonanthus praecox, CpCCD7 and CpCCD8, Regulate Shoot Branching in Arabidopsis.

Strigolactones (SLs) regulate plant shoot development by inhibiting axillary bud growth and branching. However, the role of SLs in wintersweet (Chimonanthus praecox) shoot branching remains unknown. Here, we identified and isolated two wintersweet genes, CCD7 and CCD8, involved in the SL biosynthetic pathway. Quantitative real-time PCR revealed that CpCCD7 and CpCCD8 were down-regulated in wintersweet during branching. When new shoots were formed, expression levels of CpCCD7 and CpCCD8 were almost the same as the control (un-decapitation). CpCCD7 was expressed in all tissues, with the highest expression in shoot tips and roots, while CpCCD8 showed the highest expression in roots. Both CpCCD7 and CpCCD8 localized to chloroplasts in Arabidopsis. CpCCD7 and CpCCD8 overexpression restored the phenotypes of branching mutant max3-9 and max4-1, respectively. CpCCD7 overexpression reduced the rosette branch number, whereas CpCCD8 overexpression lines showed no phenotypic differences compared with wild-type plants. Additionally, the expression of AtBRC1 was significantly up-regulated in transgenic lines, indicating that two CpCCD genes functioned similarly to the homologous genes of the Arabidopsis. Overall, our study demonstrates that CpCCD7 and CpCCD8 exhibit conserved functions in the CCD pathway, which controls shoot development in wintersweet. This research provides a molecular and theoretical basis for further understanding branch development in wintersweet.

A Novel Heptapeptide, GPPGPAG Transfers to the Brain, and Ameliorates Memory Dysfunction and Dendritic Atrophy in Alzheimer's Disease Model Mice.

We investigated the effects of a heptapeptide, GPPGPAG, on memory improvement and neuritic regeneration in Alzheimer's disease models to evaluate its potency as a new anti-Alzheimer's disease (AD) therapy. The anti-AD effects of GPPGPAG were evaluated in Aß-treated cortical neurons and 5XFAD, a mouse model of AD. Exposure of cortical neurons to Aß25-35 for 3 days resulted in atrophy of axons and dendrites. Treatment with GPPGPAG improved the dendritic atrophy of Aß-treated cortical neurons, but not axonal atrophy. Postsynaptic and presynaptic densities under Aß1-42 exposure were increased by GPPGPAG post treatment. Oral administration of GPPGPAG to 5XFAD mice for 15 days improved significantly object recognition memory and dendritic density. Direct infusion of GPPGPAG into the lateral ventricle of 5XFAD mice for 28 days improved object recognition memory. Following oral administration of GPPGPAG in mice, the undigested heptapeptide was detected in the plasma and cerebral cortex. Analysis of target protein of GPPGPAG in neurons by DARTS method identified 14-3-3ε as a bound protein. The protective effect of GPPGPAG on Aß1-42-induced dendritic atrophy was canceled by knockdown of 14-3-3ε. Taken together, these results suggest that GPPGPAG is orally available, transfers to the brain, and ameliorates memory dysfunction in AD brain, which is possibly mediated by 14-3-3ε-related dendritic restoration.

Effects of Cistanche tubulosa Wight Extract on Locomotive Syndrome: A Placebo-Controlled, Randomized, Double-Blind Study.

In an aging society, preventing dysfunction and restoring function of the locomotive organs are necessary for long-term quality of life. Few interventional studies have investigated supplementation for locomotive syndrome. Additionally, very few interventional clinical studies on locomotive syndrome have been performed as placebo-controlled, randomized, double-blind studies. We previously found that the administration of 30% ethanolic extract of Cistanche tubulosa improved walking ability in a cast-immobilized skeletal muscle atrophy mouse model. Therefore, we conducted a clinical study to evaluate the effects of C. tubulosa (CT) extract on the locomotive syndrome. Twenty-six subjects with pre-symptomatic or mild locomotive syndrome completed all tests and were analyzed in the study. Analyses of muscle mass and physical activity were performed based on the full analysis set. Intake of CT extract for 12 weeks increased step width (two-step test) and gait speed (5 m walking test) in patients over 60 years old compared with those in a placebo control (p = 0.046). In contrast, the skeletal muscle mass of the body trunk and limbs was unchanged following administration of CT extract. Adverse effects were evaluated by blood tests; no obvious adverse events were observed following the intake of CT extract. In conclusion, this placebo-controlled, randomized, double-blind study demonstrated that treatment with CT extract significantly prevented a decline in walking ability without any notable adverse effects in patients with locomotive syndrome.

High-Resolution MR for Follow-Up of Intracranial Steno-Occlusive Disease Treated by Endovascular Treatment.

Background and Purpose: An endovascular recanalization is an alternative option for symptomatic intracranial atherosclerotic steno-occlusive disease (ICAD). Accurate non-invasive alternatives to digital subtraction angiography (DSA) for follow-up imaging after endovascular treatment are desirable. We aimed to evaluate the image quality and diagnostic performance of high-resolution magnetic imaging in follow-up using DSA as a reference. Materials and Methods: From January 2017 to June 2021, data from 35 patients with 40 intracranial steno-occlusive lesions who underwent endovascular recanalization and received high-resolution magnetic resonance (HR-MR) follow-up were retrospectively collected in our prospective database. Studies were evaluated for the quality of visualization of the vessel lumen, restenosis rate, and accuracy of high-resolution magnetic resonance (HR-MR) with DSA used as the reference standard. Intraclass correlation coefficient (ICC) analyses were performed to assess the agreement between the two different readers. Results: In total, 40 intracranial steno-occlusive lesions in 35 patients, with 34 lesions undergoing balloon angioplasty [including 16 drug-coated balloons (DCBs)] and 8 lesions undergoing stenting were enrolled. The median age was 63.6 years (IQR 58.5-70.0 years), and the mean imaging follow-up time was 9.5 months (IQR 4.8-12.5 months). The median degrees of preprocedural and residual stenosis were 85.0% (IQR 75.0-99.0%) and 32.8% (IQR 15.0-50.0%), respectively. Intracranial periprocedural complications occurred in 1 (3.6%) patient. In the case of a stainless-steel stent (n = 1), there was a signal drop at the level of the vessel, which did not allow evaluation of the vessel lumen. However, this was visible in the case of nitinol stents (n = 7) and angioplasty (n = 34). The overall restenosis rate was 25.8% (n = 9). The DCB subgroup showed a lower rate of restenosis than the percutaneous transluminal angioplasty (PTA) subgroup [5.3% (2/13) vs. 35.7% (5/14)]. Conclusion: High-resolution magnetic resonance may be a reliable non-invasive method for demonstrating the vessel lumen and diagnostic follow-up after endovascular recanalization for ICAD. Compared with MR angiography (MRA), HR-MR showed a higher inter-reader agreement and could provide more information after endovascular recanalization, such as enhancement of the vessel wall.