Serum signature of antibodies to toxoplasma gondii, rubella virus, and cytomegalovirus in females with bipolar disorder: A cross-sectional study.

BACKGROUND AND AIM: Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and cytomegalovirus (CMV) shared clinical relevance with BD, remains controversial. This study aimed to investigate this association. METHODS: Antibody seropositivity of T gondii, rubella virus, CMV IgM, and IgG of females with BD and controls was extracted based on medical records (from January 2018 to January 2023). Family history, type of BD, onset age, and psychotic symptom history were also collected. RESULTS: 585 individuals with BD and 800 healthy controls were involved. Individuals with BD revealed a lower positive rate of T gondii IgG in the 10-20 aged group (OR = 0.10), and a higher positive rate of rubella IgG in the 10-20 (OR = 5.44) and 20-30 aged group (OR = 3.15). BD with family history preferred a higher positive rate of T gondii IgG (OR = 24.00). Type-I BD owned a decreased positive rate of rubella IgG (OR = 0.37) and an elevated positive rate of CMV IgG (OR = 2.12) compared to type-II BD, while BD with early onset showed contrast results compared to BD without early onset (Rubella IgG, OR = 2.54; CMV IgG, OR = 0.26). BD with psychotic symptom history displayed a lower positive rate of rubella IgG (OR = 0.50). LIMITATIONS: Absence of male evidence and control of socioeconomic status and environmental exposure. CONCLUSIONS: Differential antibody seropositive rates of T gondii, rubella, and cytomegalovirus in BD were observed.

Effect of antipsychotics and mood stabilisers on metabolism in bipolar disorder: a network meta-analysis of randomised-controlled trials.

Background: Antipsychotics and mood stabilisers are gathering attention for the disturbance of metabolism. This network meta-analysis aims to evaluate and rank the metabolic effects of the commonly used antipsychotics and mood stabilisers in treating bipolar disorder (BD). Methods: Registries including PubMed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar were searched before February 15th, 2024, for randomised controlled trials (RCTs) applying antipsychotics or mood stabilisers for BD treatment. The observed outcomes were twelve metabolic indicators. The data were extracted by two reviewers independently, and confirmed by another four reviewers and a corresponding author. The above six reviewers all participated in data analyses. Data extraction was based on PRISMA guidelines, and quality assessment was conducted according to the Cochrane Handbook. Use a random effects model for data pooling. The PROSPERO registration number is CRD42023466669. Findings: Together, 5421 records were identified, and 41 publications with 11,678 complete-trial participants were confirmed eligible. After eliminating possible sensitivity, risperidone ranked 1st in elevating fasting serum glucose (SUCRA = 90.7%) and serum insulin (SUCRA = 96.6%). Lurasidone was most likely to elevate HbA1c (SUCRA = 82.1%). Olanzapine ranked 1st in elevating serum TC (SUCRA = 93.3%), TG (SUCRA = 89.6%), and LDL (SUCRA = 94.7%). Lamotrigine ranked 1st in reducing HDL (SUCRA = 82.6%). Amisulpride ranked 1st in elevating body weight (SUCRA = 100.0%). For subgroup analyses, quetiapine is more likely to affect indicators of glucose metabolism among male adult patients with bipolar mania, while long-term lurasidone tended to affect glucose metabolism among female patients with bipolar depression. Among patients under 18, divalproex tended to affect glucose metabolism, with lithium affecting lipid metabolism. In addition, most observed antipsychotics performed higher response and remission rates than placebo, and displayed a similar dropout rate with placebo, while no between-group significance of rate was observed among mood stabilisers. Interpretation: Our findings suggest that overall, antipsychotics are effective in treating BD, while they are also more likely to disturb metabolism than mood stabilisers. Attention should be paid to individual applicability in clinical practice. The results put forward evidence-based information and clinical inspiration for drug compatibility and further research of the BD mechanism. Funding: The National Key Research and Development Program of China (2023YFC2506200), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (No. JNL-2023001B).

Input-output specific orchestration of aversive valence in lateral habenula during stress dynamics. / åŽ‹åŠ›åŠ¨æ€è¿‡ç¨‹ä¸­è´Ÿæ€§æƒ ç»ªåœ¨å¤–ä¾§ç¼°æ ¸çš„"è¾“å ¥-输出"特异性整合.

Stress has been considered as a major risk factor for depressive disorders, triggering depression onset via inducing persistent dysfunctions in specialized brain regions and neural circuits. Among various regions across the brain, the lateral habenula (LHb) serves as a critical hub for processing aversive information during the dynamic process of stress accumulation, thus having been implicated in the pathogenesis of depression. LHb neurons integrate aversive valence conveyed by distinct upstream inputs, many of which selectively innervate the medial part (LHbM) or lateral part (LHbL) of LHb. LHb subregions also separately assign aversive valence via dissociable projections to the downstream targets in the midbrain which provides feedback loops. Despite these strides, the spatiotemporal dynamics of LHb-centric neural circuits remain elusive during the progression of depression-like state under stress. In this review, we attempt to describe a framework in which LHb orchestrates aversive valence via the input-output specific neuronal architecture. Notably, a physiological form of Hebbian plasticity in LHb under multiple stressors has been unveiled to incubate neuronal hyperactivity in an input-specific manner, which causally encodes chronic stress experience and drives depression onset. Collectively, the recent progress and future efforts in elucidating LHb circuits shed light on early interventions and circuit-specific antidepressant therapies.

Construction and Analysis of a New Resting-State Whole-Brain Network Model.

BACKGROUND: Mathematical modeling and computer simulation are important methods for understanding complex neural systems. The whole-brain network model can help people understand the neurophysiological mechanisms of brain cognition and functional diseases of the brain. METHODS: In this study, we constructed a resting-state whole-brain network model (WBNM) by using the Wendling neural mass model as the node and a real structural connectivity matrix as the edge of the network. By analyzing the correlation between the simulated functional connectivity matrix in the resting state and the empirical functional connectivity matrix, an optimal global coupling coefficient was obtained. Then, the waveforms and spectra of simulated EEG signals and four commonly used measures from graph theory and small-world network properties of simulated brain networks under different thresholds were analyzed. RESULTS: The results showed that the correlation coefficient of the functional connectivity matrix of the simulated WBNM and empirical brain networks could reach a maximum value of 0.676 when the global coupling coefficient was set to 20.3. The simulated EEG signals showed rich waveform and frequency-band characteristics. The commonly used graph-theoretical measures and small-world properties of the constructed WBNM were similar to those of empirical brain networks. When the threshold was set to 0.22, the maximum correlation between the simulated WBNM and empirical brain networks was 0.709. CONCLUSIONS: The constructed resting-state WBNM is similar to a real brain network to a certain extent and can be used to study the neurophysiological mechanisms of complex brain networks.

The distinct hepatic metabolic profile and relation with impaired liver function in congenital isolated growth hormone-deficient rats.

Objective: Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, the potential mechanism of how GHD influences liver function remains obscure. In the present study, we aim to perform hepatic metabolomics in Lewis dwarf rats, which were the standard congenital isolated GH-deficient rat, to evaluate the characterizations of hepatic metabolic profiles and explore their relations with liver functions. Methods: Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. Body lengths and weights, liver weights, serum alanine transaminase (ALT), and serum aspartate transaminase (AST) were measured. ELISA and RT-qPCR were used to assess IGF-1 levels in serum and liver, respectively. The non-targeted metabolomics was performed in the livers of dw/+ and dw/dw rats. Differential metabolites were selected according to the coefficient of variation (CV), variable importance in the projection (VIP) > 1, and P < 0.05. Hierarchical clustering of differential metabolites was conducted, and the KEGG database was used for metabolic pathway analysis. Results: The body weights, body lengths, liver weights, and IGF-1 levels in the serum and liver of dw/dw rats were significantly decreased compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 differential metabolites in positive ion mode, and 51 metabolites in negative ion mode were identified. Among them, lysophosphatidylcholine (LPC) 16:2, LPC 18:3, LPC 22:6, fatty acid esters of hydroxy fatty acids (FAHFA)18:1 were significantly decreased, while palmitoyl acid, dehydrocholic acid, and 7-ketolithocholic acid were significantly increased in dw/dw rats compared with dw/+ rats. These seven differential metabolites were significantly associated with phenotypes of rats. Finally, KEGG pathway analysis showed that the arginine and proline metabolism pathway and bile secretion pathway were mainly clustered. Conclusion: Lewis dw/dw rats with congenital isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with the distinctive hepatic metabolic profiles.

Resolving heterogeneity in dynamics of synchronization stability within the salience network in autism spectrum disorder.

BACKGROUND: Heterogeneity in resting-state functional connectivity (FC) are one of the characteristics of autism spectrum disorder (ASD). Traditional resting-state FC primarily focuses on linear correlations, ignoring the nonlinear properties involved in synchronization between networks or brain regions. METHODS: In the present study, the cross-recurrence quantification analysis, a nonlinear method based on dynamical systems, was utilized to quantify the synchronization stability between brain regions within the salience network (SN) of ASD. Using the resting-state functional magnetic resonance imaging data of 207 children (ASD/typically-developing controls (TC): 105/102) in Autism Brain Imaging Data Exchange database, we analyzed the laminarity and trapping time differences of the synchronization stability between the ASD subtype derived by a K-means clustering analysis and the TC group, and examined the relationship between synchronization stability and the severity of clinical symptoms of the ASD subtypes. RESULTS: Based on the synchronization stability within the SN of ASD, we identified two subtypes that showed opposite changes in synchronization stability relative to the TC group. In addition, the synchronization stability of ASD subtypes 1 and 2 can predict the social interaction and communication impairments, respectively. CONCLUSIONS: These findings reveal that ASD subgroups with different patterns of synchronization stability within the SN appear distinct clinical symptoms, and highlight the importance of exploring the potential neural mechanism of ASD from a nonlinear perspective.

A Comparative Study on the Mechanism of Delayed-Type Hypersensitivity Mediated by the Recombinant Mycobacterium tuberculosis Fusion Protein ESAT6-CFP10 and Purified Protein Derivative.

While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette-Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.

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.

Summary of the application value of ultrasound imaging features in the clinical differential diagnosis of intramuscular capillary-type hemangioma and fibro-adipose vascular anomaly.

Objective: To investigate the value of ultrasonography as a diagnostic aid in differentiating intramuscular capillary-type hemangioma (ICTH) from fibro-adipose vascular anomaly (FAVA). Methods: A retrospective analysis was conducted of the clinical and ultrasound imaging data of 20 patients with ICTH and 45 patients with FAVA who were admitted to and pathologically confirmed in hospital between January 2013 and April 2023. The clinical and ultrasonographic appearances of the lesions in the two groups were compared and analyzed. A stepwise regression analysis was performed, and a joint diagnostic equation was constructed using the final variables selected. The receiver operating characteristic (ROC) curve and indicators, including sensitivity and specificity, were used to evaluate the efficacy of the joint diagnostic model. Results: The two groups of patients suffering from ICTH and FAVA presented a statistically significant difference (P< 0.05) in terms of 'age', 'lesion size', 'fascial tail sign', 'presence of a fatty-tissue-like hyperecho around the lesion', 'blood flow' and 'presence of straight blood capillaries within the lesion'. Finally, the variables 'fascial tail sign' and 'presence of straight blood capillaries within the lesion' were selected to construct the model. The constructed joint diagnostic model had a sensitivity value of 70.0% (95% CI: 59.00-81.00), a specificity value of 98.0% (95% CI: 94.70-100.00) and a ROC curve value of 0.908, indicating the high efficacy of the combined diagnosis method. Conclusions: Ultrasonography can be utilized to differentiate ICTH from FAVA, and the combined diagnosis method can further improve the technique's diagnostic efficacy.

Comparison of the Immune Responses to Different Formulations of BC02-Adjuvanted HPV Types 16 and 18 Bivalent Vaccines in Mice.

To achieve maximum efficacy, vaccines, such as subunit, recombinant, and conjugate vaccines, necessitate the incorporation of immunostimulators/adjuvants. Adjuvants play a vital role in bolstering and extending the strength of the immune response while also influencing its type. As antigen and adjuvant formulations become more intricate, it becomes imperative to establish a well-characterized and robust formulation to ensure consistent and reproducible outcomes in preclinical and clinical studies. In the present study, an HPV bivalent vaccine was developed using a BC02 adjuvant in conjunction with HPV 16 and 18 L1 VLP antigens produced from an E. coli expression system. The study involved evaluating the adjuvant formulation and in vivo immunogenicity in mice. Remarkably, a medium-dose of BCG-CpG-DNA combined with a low-dose of aluminum hydroxide substantially enhanced the immunogenicity of HPV16 and 18 VLPs, resulting in improved cellular and humoral immune responses.

Pushing the Frontiers: Optogenetics for Illuminating the Neural Pathophysiology of Bipolar Disorder.

Bipolar disorder (BD), a disabling mental disorder, is featured by the oscillation between episodes of depression and mania, along with disturbance in the biological rhythms. It is on an urgent demand to identify the intricate mechanisms of BD pathophysiology. Based on the continuous progression of neural science techniques, the dysfunction of circuits in the central nervous system was currently thought to be tightly associated with BD development. Yet, challenge exists since it depends on techniques that can manipulate spatiotemporal dynamics of neuron activity. Notably, the emergence of optogenetics has empowered researchers with precise timing and local manipulation, providing a possible approach for deciphering the pathological underpinnings of mental disorders. Although the application of optogenetics in BD research remains preliminary due to the scarcity of valid animal models, this technique will advance the psychiatric research at neural circuit level. In this review, we summarized the crucial aberrant brain activity and function pertaining to emotion and rhythm abnormities, thereby elucidating the underlying neural substrates of BD, and highlighted the importance of optogenetics in the pursuit of BD research.

Heterogeneity of dynamic synergetic configurations of salience network in children with autism spectrum disorder.

Atypical functional connectivity (FC) patterns have been identified in autism spectrum disorders (ASD), especially within salience network (SN) and between SN and default mode network (DMN) and central executive network (CEN). But whether the dynamic configuration of intra-SN and inter-SN (SN with DMN and CEN) FC in ASD is also heterogeneous remains unknown. Based on the resting-state functional magnetic resonance imaging data from 105 ASD and 102 typically-developing controls (TC), we calculated the time-varying FC of intra-SN and inter-SN (SN with DMN and CEN). Then, the joint recurrence features for the time-varying FC were calculated to assess how the SN dynamically recruits different configurations of network segregation and integration in ASD, that is, synergies, from the dynamical systems perspective. We analyzed the differences in synergetic patterns between ASD subtypes obtained by k-means clustering algorithm based on the synergy of SN and TC, and investigated the relationships between synergy of SN and severity of clinical symptoms of ASD for ASD subtypes. Two ASD subtypes were revealed, where the synergy of SN in ASD subtype 1 has lower stability and periodicity compared to the TC, and ASD subtype 2 exhibits the opposite alteration. Synergy of SN for ASD subtype 1 and 2 was found to predict the severity of communication impairments and restricted and repetitive behaviors in ASD, respectively. These results suggest the existence of subtypes with distinct patterns of the synergy of SN in ASD, and provide insight into the complex pathophysiological mechanism of clinical manifestations of ASD.

Decreased functional concordance in male children with autism spectrum disorder.

Autism spectrum disorder (ASD) is an early-onset neurodevelopmental condition with altered function of the brain. At present, a variety of functional metrics from neuroimaging techniques have been used to explore ASD neurological mechanisms. However, the concordance of these functional metrics in ASD is still unclear. This study used resting-state functional magnetic resonance imaging data, which were obtained from the open-access Autism Brain Imaging Data Exchange database, including 105 children with ASD and 102 demographically matched typically developing (TD) children. Both voxel-wise and volume-wise functional concordance were calculated by combining the dynamic amplitude of low-frequency fluctuations, dynamic regional homogeneity, and dynamic global signal correlation. Furthermore, a two-sample t-test was performed to compare the functional concordance between ASD and TD groups. Finally, the relationship between voxel-wise functional concordance and Autism Diagnostic Observation Schedule subscores was analyzed using the multivariate support vector regression in the ASD group. Compared with the TD group, we found that ASD showed decreased voxel-wise functional concordance in the left superior temporal pole (STGp), right amygdala, and left opercular part of the inferior frontal gyrus (IFGoper). Moreover, decreased functional concordance was associated with restricted and repetitive behaviors in ASD. Our results found altered brain function in the left STGp, right amygdala, and left IFGoper in ASD by functional concordance, indicating that functional concordance may provide new insights into the neurological mechanisms of ASD.

Principle on Selecting the Coordination Ligands of Palladium Precursors Encapsulated by Zeolite for an Efficient Purification of Formaldehyde at Ambient Temperature.

High-performance zeolite-supported noble metal catalysts with low loading and high dispersion of active components are the most promising materials for achieving the complete oxidation of formaldehyde (HCHO) at room temperature. In this work, palladium nanoparticles (Pd NPs) with different sizes were successfully encapsulated inside the silicalite-1 (S-1) zeolite framework by using diverse stabling ligands via the one-pot method. Thereafter, the rule on selecting the coordinative ligands for palladium was clarified: more N atoms, a short carbon chain, a smaller branch chain, and bidentate coordination are characteristics of an ideal ligand. Accordingly, the best-performing 0.2Pd@S-1(Ethylenediamine) catalyst exhibited outstanding performance for HCHO oxidation, achieving 100% conversion even at room temperature. High-resolution high-angle annular dark-field scanning transmission electron microscopy (HR HAADF-STEM) and density functional theory (DFT) calculations indicate that the chelate is formed by complexation of Pd2+ ions with ethylenediamine, displaying the smallest spatial site resistance simultaneously with the zeolite synthesis, resulting in Pd located mostly within the 5-membered ring (5-MR) channels of S-1 after calcination, thus limiting the growth of Pd clusters and promoting their dispersion.

Intragastric Safflower Yellow Alleviates HFD Induced Metabolic Dysfunction-Associated Fatty Liver Disease in Mice through Regulating Gut Microbiota and Liver Endoplasmic Reticulum Stress.

The gut microbiota was reported to play a significant role in the progression of the metabolic associated fatty liver disease (MAFLD). Our recent study suggested that gastrointestinal tract and liver were important targets mediating the anti-obesity effects of intragastric safflower yellow (SY). Therefore, our present study aims to investigate the effect of intragastric SY on MAFLD and possible mechanism. DIO mice were treated with 125 mg/kg/d SY for 12 weeks by gavage. We found intragastric SY significantly slowed weight gain of body, reduced the food intake and liver weight, improved hepatic steatosis, liver function and glucose metabolism in DIO mice. The comparison between OGTT and IPGTT illustrated OGTT produced a better improvement of glucose tolerance after SY treatment. We also found intragastric SY significantly increased the energy expenditure and locomotor activity of DIO mice. SY obviously decreased the expression of lipogenesis-associated and ERS-related genes in liver of DIO mice and PA-induced MAFLD hepatocyte model. Gut microbiota analysis demonstrated intragastric SY apparently changed the diversity and composition of gut microbiota of DIO mice. Further function prediction analysis indicated that gut microbiotas in SY-treated mice was positively related with energy metabolism, lipid metabolism and endocrine system. Intragastric SY has a significant therapeutic effect on MAFLD, which is mediated partly by modulating gut microbiota and improving liver ERS.

Dysregulated dynamic time-varying triple-network segregation in children with autism spectrum disorder.

One of the remarkable characteristics of autism spectrum disorder (ASD) is the dysregulation of functional connectivity of the triple-network, which includes the salience network (SN), default mode network (DMN), and central executive network (CEN). However, there is little known about the segregation of the triple-network dynamics in ASD. This study used resting-state functional magnetic resonance imaging data including 105 ASD and 102 demographically-matched typical developing control (TC) children. We compared the dynamic time-varying triple-network segregation and triple-network functional connectivity states between ASD and TC groups, and examined the relationship between dynamic triple-network segregation alterations and clinical symptoms of ASD. The average dynamic network segregation value of the DMN with SN and the DMN with CEN in ASD was lower but the coefficient of variation (CV) of dynamic network segregation of the DMN with CEN was higher in ASD. Furthermore, partially reduced triple-network segregation associated with the DMN was found in connectivity states analysis of ASD. These abnormal average values and CV of dynamic network segregation predicted social communication deficits and restricted and repetitive behaviors in ASD. Our findings indicate abnormal dynamic time-varying triple-network segregation of ASD and highlight the crucial role of the triple-network in the neural mechanisms underlying ASD.

Serum metabolomics profiling of improved metabolic syndrome is characterized by decreased pro-inflammatory biomarkers: A longitudinal study in Chinese male adults.

Metabolic syndrome (MetS) is a serious global health concern. The objective of this study is to dynamically investigate the changes of metabolic profiles and metabolites in Chinese male MetS subjects after an 18 months diet and exercise intervention. Fifty male MetS patients defined according to International Diabetes Federation 2005 guidelines were subjected to diet and exercise counseling for 18 months. Serum samples were taken at baseline, 12 months, and 18 months, respectively, for clinical evaluation and metabolomics analyses. Diet and exercise intervention for 18 months achieved significant improvements in the metabolic profiles of all participants. Nineteen subjects (38.0%) exhibited MetS remission at the end of the study. A total of 812 relative features were characterized and 61 were successfully identified. Furthermore, 17 differential metabolites were of significance at both time points (baseline-12 months, baseline-18 months) and presented nonlinear trends through time. Eight metabolites (47.1%) were predominantly converged to inflammation and oxidative stress. Pro-inflammatory biomarkers were remarkably decreased after 18 months of intervention, and prostaglandin E2, neuroprotectin D1, and taxiphyllin in combination were firstly found to demonstrate a fair discriminative power (area under curve = 0.911) to predict the improvement of MetS undergone diet and exercise intervention. The significant shift of metabolomic profiling after 18 months of lifestyle counseling provide a novel insight and reveal that earlier inflammation control may be of potential benefit in MetS management.

Increased Serum EphrinA1 Is Associated with Parenchymal Hematoma after Ischemic Stroke.

INTRODUCTION: Previous preclinical studies reported that the level of serum EphrinA1 was associated with blood-brain barrier disruption; however, its role in predicting parenchymal hematoma (PH) after ischemic stroke is underexplored. We aimed to explore the association between the level of serum EphrinA1 and PH in patients with ischemic stroke. METHODS: Patients with ischemic stroke after onset from West China Hospital, Sichuan University, were prospectively enrolled between January 2017 and December 2019. The level of serum EphrinA1 at baseline was measured after admission. PH was diagnosed as hematoma within the infarct territory detected on the brain CT/MRI scans within 7 days after onset but not on the initial scan according to European Cooperative Acute Stroke Study (ECASS) III criteria. The association between the level of serum EphrinA1 and PH after ischemic stroke was assessed by multiple logistic regression analysis. RESULTS: A total of 667 patients were included in the final analysis. The mean age was 67.20 ± 14.31 years, and 57.87% (368/667) were males. Of the 667 patients, 65 (9.75%) patients had PH. The median of EphrinA1 on admission was 82.83 ng/mL (IQR, 70.11-93.75 ng/mL). Compared with patients without PH, those with PH had a higher level of serum EphrinA1 (p = 0.024). Patients were divided into 3 categories based on EphrinA1 tertiles (T1, <79.11 ng/mL, n = 223; T2, 79.11-93.75 ng/mL, n = 222; and T3, >93.75 ng/mL, n = 222). After adjusting for age, sex, atrial fibrillation, smoking, statins, antiplatelets, Trail of Org 10172 in Acute Stroke Treatment (TOAST) classification and National Institutes of Health Stroke Scale (NIHSS) score ≥15, patients in the second and third EphrinA1 tertiles showed a significant increase in PH compared with those in the lowest tertile (OR 2.44, 95% CI: 1.10-5.40, p = 0.028; OR 2.61, 95% CI: 1.19-5.74, p = 0.017, respectively). Additionally, adjusting for reperfusion therapy (thrombolysis and/or endovascular therapy), only patients in the highest group (tertile 3) had a significantly higher risk of PH compared to the lowest group (OR 2.30, 95% CI: 1.03-5.13, p = 0.042). CONCLUSION: Higher serum EphrinA1 is independently associated with a higher risk of PH after ischemic stroke. Future studies with larger sample sizes are needed to validate our findings and elucidate the potential role of EphrinA1 in PH.

Fibroadipose vascular anomaly: a clinicopathological study of 75 cases.

AIMS: Fibroadipose vascular anomaly (FAVA) is a complex vascular malformation that is likely to be under-recognised. In this study we aimed to report the pathological features and somatic PIK3CA mutations associated with the most common clinicopathological features. METHODS AND RESULTS: Cases were identified by reviewing the lesions resected from patients with FAVA registered at our Haemangioma Surgery Centre and unusual intramuscular vascular anomalies in our pathology database. There were 23 males and 52 females, who ranged in age from 1 to 51 years. Most cases occurred in the lower extremities (n = 62). The majority of the lesions were intramuscular, with a few disrupting the overlying fascia and involving subcutaneous fat (19 of 75), and a minority of the cases had cutaneous vascular stains (13 of 75). Histopathologically, the lesion was composed of anomalous vascular components that were intertwined with mature adipocytic and dense fibrous tissues and vascular components with: (a) clusters of thin-walled channels, some with blood-filled nodules and others with thin walls resembling pulmonary alveoli; (b) numerous small vessels (arteries, veins and indeterminate channels) - proliferative small blood vessels were often mixed with adipose tissue; (c) larger abnormal venous channels usually irregularly and sometimes excessively muscularised; (d) lymphoid aggregates or lymphoplasmacytic aggregates were usually observed; and (e) lymphatic malformations were sometimes seen as minor elements. All patients had their lessons subjected to PCR, and 53 patients had somatic PIK3CA mutations (53 of 75). CONCLUSIONS: FAVA is a slow-flow vascular malformation with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for targeted therapy.

Safflower yellow and its main component hydroxysafflor yellow A alleviate hyperleptinemia in diet-induced obesity mice through a dual inhibition of the GIP-GIPR signaling axis.

Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone secreted by K cells in the small intestine and is considered an obesity-promoting factor. In this study, we systematically investigated the anti-obesity effects of intragastric safflower yellow (SY)/hydroxysafflor yellow A (HSYA) and the underlying mechanism for the first time. Our results showed that intragastric SY/HSYA, rather than an intraperitoneal injection, notably decreased serum GIP levels and GIP staining in the small intestine in diet-induced obese (DIO) mice. Moreover, intragastric SY/HSYA was also first found to significantly suppress GIP receptor (GIPR) signaling in both the hypothalamus and subcutaneous White adipose tissue. Our study is the first to show that intragastric SY/HSYA obviously reduced food intake and body weight gain in leptin sensitivity experiments and decreased serum leptin levels in DIO mice. Further experiments demonstrated that SY treatment also significantly reduced leptin levels, whereas the inhibitory effect of SY on leptin levels was reversed by activating GIPR in 3 T3-L1 adipocytes. In addition, intragastric SY/HSYA had already significantly reduced serum GIP levels and GIPR expression before the serum leptin levels were notably changed in high-fat-diet-fed mice. These findings suggested that intragastric SY/HSYA may alleviate diet-induced obesity in mice by ameliorating hyperleptinemia via dual inhibition of the GIP-GIPR axis.