Aberrant Hippocampal Development in Early-onset Mental Disorders and Promising Interventions: Evidence from a Translational Study.

Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence. The methylazoxymethanol acetate (MAM) animal model, in which disruption in neurodevelopmental processes is induced, mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective. We conducted longitudinal structural magnetic resonance imaging (MRI) scans during childhood, adolescence, and adulthood in MAM rats to identify specific brain regions and critical windows for intervention. Then, the effect of repetitive transcranial magnetic stimulation (rTMS) intervention on the target brain region during the critical window was investigated. In addition, the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders (diagnosed with major depressive disorder or bipolar disorder) to evaluate its clinical translational potential. The results demonstrated that, compared to the control group, the MAM rats exhibited significantly lower striatal volume from childhood to adulthood (all P <0.001). In contrast, the volume of the hippocampus did not show significant differences during childhood (P >0.05) but was significantly lower than the control group from adolescence to adulthood (both P <0.001). Subsequently, rTMS was applied to the occipital cortex, which is anatomically connected to the hippocampus, in the MAM models during adolescence. The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group (P <0.01), while the volume of the striatum remained unchanged (P >0.05). In the clinical trial, adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline (P <0.01), and these volumetric changes were associated with improvement in depressive symptoms (r = - 0.524, P = 0.018). These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for early-onset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.

Colloidal antibiotic mimics: selective capture and killing of microorganisms by shape-anisotropic colloids.

The development of targeted and efficient antimicrobials for the selective killing of pathogenic bacteria is of great importance, yet remains challenging. Here, we propose a targeted approach to selectively capture and kill microorganisms with colloidal antibiotic mimics that are readily prepared by common chemical syntheses. The mimics are shape-anisotropic colloids, which can selectively capture shape-matching microorganisms due to lock-key depletion attractions. Furthermore, after being modified with gold nanoparticles (AuNPs) and irradiated with near-infrared light, the colloidal mimics can kill the selectively captured microorganisms due to the localized photothermal effect of the AuNPs. The work demonstrates the important ability of anisotropic colloids to selectively capture and precisely kill microorganisms, which holds considerable promise for safe and adaptive antibacterial therapies without the risk of antibiotic resistance.

Real-time 3D echocardiographic transilluminated imaging combined with artificially intelligent left atrial appendage measurement for atrial fibrillation interventional procedures.

Aims: This study investigated the feasibility and accuracy of real-time three-dimensional (3D) echocardiographic transilluminated imaging (TrueVue Glass) in left atrial appendage (LAA) anatomical morphology and artificial intelligence (AI)-assisted 3D automated LAA measurement (3D Auto LAA) software in the preoperative evaluation of LAA occlusion (LAAO) in patients with atrial fibrillation (AF). Method and results: Thirty-seven patients with AF were selected. Two-dimensional (2D) and real-time 3D transesophageal echocardiography (RT3D-TEE) were performed preoperatively, using conventional 3D, the new 3D TrueVue Glass mode, and cardiac computed tomography angiography (CCTA) to assess and type the morphology of LAA. Physiological parameters were measured using traditional 2D and 3D manual (3D Manual LAA), 3D Auto LAA, and CCTA. TrueVue Glass for LAA outer contour display was compared with CCTA. Comparisons were based on correlation and consistency in measuring the maximum diameter (LZ max), minimum diameter (LZ min), area (LZ area), and circumference (LZ cir) of LAA landing zone (LZ). Times and variabilities were compared. The concordance rate for external shape of LAA was 97.14% between TrueVue Glass and CCTA. 3D Auto LAA and 3D Manual LAA have a stronger correlation and higher consistency in all parameters. 3D Auto LAA showed higher intra- and interobserver reproducibility and allowed quicker analysis (p < 0.05). LAAO was performed in 35 patients (94.59%), and none of which had serious adverse events. Conclusion: TrueVue Glass is the first non-invasive and radiation-free visualization of the overall external contour of LAA and its adjacent structures. 3D Auto LAA simplifies the measurement, making the preoperative assessment more efficient and convenient while ensuring the accuracy and reproducibility. A combination of the two is feasible for accurate and rapid assessment of LAA anatomy and physiology in AF patients and has practical application in LAAO.

Identifying and validating subtypes within major psychiatric disorders based on frontal-posterior functional imbalance via deep learning.

Converging evidence increasingly implicates shared etiologic and pathophysiological characteristics among major psychiatric disorders (MPDs), such as schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Examining the neurobiology of the psychotic-affective spectrum may greatly advance biological determination of psychiatric diagnosis, which is critical for the development of more effective treatments. In this study, ensemble clustering was developed to identify subtypes within a trans-diagnostic sample of MPDs. Whole brain amplitude of low-frequency fluctuations (ALFF) was used to extract the low-dimensional features for clustering in a total of 944 participants: 581 psychiatric patients (193 with SZ, 171 with BD, and 217 with MDD) and 363 healthy controls (HC). We identified two subtypes with differentiating patterns of functional imbalance between frontal and posterior brain regions, as compared to HC: (1) Archetypal MPDs (60% of MPDs) had increased frontal and decreased posterior ALFF, and decreased cortical thickness and white matter integrity in multiple brain regions that were associated with increased polygenic risk scores and enriched risk gene expression in brain tissues; (2) Atypical MPDs (40% of MPDs) had decreased frontal and increased posterior ALFF with no associated alterations in validity measures. Medicated Archetypal MPDs had lower symptom severity than their unmedicated counterparts; whereas medicated and unmedicated Atypical MPDs had no differences in symptom scores. Our findings suggest that frontal versus posterior functional imbalance as measured by ALFF is a novel putative trans-diagnostic biomarker differentiating subtypes of MPDs that could have implications for precision medicine.

Antipsychotic Effects on Cortical Morphology in Schizophrenia and Bipolar Disorders.

Background: Previous studies of atypical antipsychotic effects on cortical structures in schizophrenia (SZ) and bipolar disorder (BD) have findings that vary between the short and long term. In particular, there has not been a study exploring the effects of atypical antipsychotics on age-related cortical structural changes in SZ and BD. This study aimed to determine whether mid- to long-term atypical antipsychotic treatment (mean duration = 20 months) is associated with cortical structural changes and whether age-related cortical structural changes are affected by atypical antipsychotics. Methods: Structural magnetic resonance imaging images were obtained from 445 participants consisting of 88 medicated patients (67 with SZ, 21 with BD), 84 unmedicated patients (50 with SZ, 34 with BD), and 273 healthy controls (HC). Surface-based analyses were employed to detect differences in thickness and area among the three groups. We examined the age-related effects of atypical antipsychotics after excluding the potential effects of illness duration. Results: Significant differences in cortical thickness were observed in the frontal, temporal, parietal, and insular areas and the isthmus of the cingulate gyrus. The medicated group showed greater cortical thinning in these regions than the unmediated group and HC; furthermore, there were age-related differences in the effects of atypical antipsychotics, and these effects did not relate to illness duration. Moreover, cortical thinning was significantly correlated with lower symptom scores and Wisconsin Card Sorting Test (WCST) deficits in patients. After false discovery rate correction, cortical thinning in the right middle temporal gyrus in patients was significantly positively correlated with lower HAMD scores. The unmedicated group showed only greater frontotemporal thickness than the HC group. Conclusion: Mid- to long-term atypical antipsychotic use may adversely affect cortical thickness over the course of treatment and ageing and may also result in worsening cognitive function.

Comprehensive molecular characterization of circRNA-associated ceRNA network in constrictive pericarditis.

BACKGROUND: Aberrant gene expression occurs in almost all diseases including constrictive pericarditis (CP). However, the dysregulation of genes underlying the CP remains unclear. This study aims to investigate the potential molecular mechanisms underlying CP and screen hub genes critical for the pathogenesis of CP. METHODS: Differentially expressed mRNAs, miRNAs, lncRNAs and circRNAs in pericardial tissues were screened using RNA-seq in CP patients and controls. Furthermore, functional annotation analysis and protein-protein interaction (PPI) network were carried out to investigate the potential key pathways and identify hub genes in CP. Subsequently, a ceRNA network was established and the key circRNAs were determined by Gene Set Enrichment Analysis (GSEA). Finally, the corresponding RNA-seq results were confirmed and validated with a quantitative real time-PCR (qRT-PCR). RESULTS: Functional annotation analysis revealed that differentially expressed mRNAs (DEMs) mainly participated in inflammatory response related pathways and the 10 top genes with the highest degree in PPI network were considered as the hub genes. In addition, a total of 377 regulatory relationships among the differentially expressed genes (DEGs) could be constructed, from which a subsequent ceRNA network was also established, while the circRNAs were further validated with qRT-PCR and the key biological pathways were identified using GSEA as well. CONCLUSIONS: The genes determined to have altered expression levels in CP may participate in a number of biological signaling processes leading to inflammation and fibrosis frequently encountered in CP, and, therefore, our novel findings may provide an insight into the pathogenesis, molecular biomarkers, and potential therapeutic targets in CP.

Isolated metastasis of hepatocellular carcinoma in the right ventricle.

BACKGROUND: Hepatocellular carcinoma (HCC) with right ventricle metastasis without inferior vena cava and right atrium involvement is very rare and the prognosis of HCC with RV metastasis is generally poor. The mass in the cardiac chamber may lead to lethal instability of hemodynamics, however, the initial symptom is probably non-specific, which means that diagnosis timely becomes even harder. CASE PRESENTATION: We present a 63-year-old male with isolated metastasis of HCC in the right ventricle which caused inflow obstruction. Moreover, we reviewed a series of studies of isolated metastasis of hepatocellular carcinoma between 1980 and 2018, and summarized the relative outcomes. CONCLUSIONS: Isolated metastasis of hepatocellular carcinoma in the right ventricle is extraordinarily rare. It may damage cardiac structure and broke hemodynamic balance. Multimodality imaging plays an important in accurate pre-operation assessment. Nowadays, palliative treatments could relieve fatal symptoms to some degree, however, standard treatment has not been well established.

Criss-cross heart with double-outlet right ventricle, subpulmonary ventricular septal defect, and bicuspid pulmonary valve.

Criss-cross heart (CCH) is an extremely rare complex congenital heart malformation. It accounts for less than 0.1% of congenital heart diseases. Here, we describe a unique case of CCH with double-outlet right ventricle, huge subpulmonary ventricular septal defect, bicuspid pulmonary valve, and right-hand aortic arch. The anatomic features were observed with echocardiography, and the diagnosis was confirmed at surgery. Many variations of CCH have been described. The present case expands the spectrum of this entity and may provide new insight into this complex anatomy.

Age-Related Alterations of White Matter Integrity in Adolescents and Young Adults With Bipolar Disorder.

BACKGROUND: Alterations of white matter integrity during adolescence/young adulthood may contribute to the neurodevelopmental pathophysiology of bipolar disorder (BD), but it remains unknown how white matter integrity changes in BD patients during this critical period of brain development. In the present study, we aimed to identify possible age-associated alterations of white matter integrity in adolescents and young adults with BD across the age range of 13-30 years. METHODS: We divided the participants into two groups by age as follows: adolescent group involving individuals of 13-21 years old (39 patients with BD and 39 healthy controls) and young adult group involving individuals of 22-30 years old (47 patients with BD and 47 healthy controls). Diffusion tensor imaging (DTI) was performed in all participants to assess white matter integrity. RESULTS: In the adolescent group, compared to those of healthy controls, fractional anisotropy (FA) values were significantly lower in BD patients in the left inferior longitudinal fasciculus, splenium of the corpus callosum and posterior thalamic radiation. In the young adult group, BD patients showed significantly decreased FA values in the bilateral uncinate fasciculus, genu of the corpus callosum, right anterior limb of internal capsule and fornix compared to healthy controls. White matter impairments changed from the posterior brain to the anterior brain representing a back-to-front spatiotemporal directionality in an age-related pattern. CONCLUSIONS: Our findings provide neuroimaging evidence supporting a back-to-front spatiotemporal directionality of the altered development of white matter integrity associated with age in BD patients during adolescence/young adulthood.

[Relationship among the Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Mouse Bone Marrow Hematopoietic Stem Cells].

OBJECTIVE: To investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation. METHODS: The detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them. RESULTS: The oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower. CONCLUSION: The ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

[Effect of different oxygen concentrations on biological properties of bone marrow hematopoietic stem cells of mice].

This study purposed to investigate the effects of different oxygen concentrations and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and their possible mechanisms through simulating oxygen environment to which the peripheral blood HSC are subjected in peripheral blood HSCT. The proliferation ability, cell cycle, directed differentiation ability, ROS level and hematopoietic reconstitution ability of Lin(-)c-kit(+)Sca-1(+) BMHSC were detected by using in vitro amplification test, directional differentiation test, cell cycle analysis, ROS assay and transplantation of Lin(-)c-kit(+)Sca-1(+) HSC from sublethally irradiated mice respectively. The results showed that oxygen concentrations lower than normal oxygen concentration, especially in hypoxic oxygen environment, could reduce ROS generation and amplify more primitive CD34(+)AC133(+) HSC and active CD34(+) HSC, and maintain more stem cells in the G(0)/G(1) phase, which is more helpful to the growth of CFU-S and viability of mice. At the same time, BMHSC exposed to normal oxygen level or inconstant and greatly changed oxygen concentrations could produce a high level of ROS, and the above-mentioned features and functional indicators are relatively low. It is concluded that ROS levels of HSC in BMHSCT are closely related with the oxygen concentration surrounding the cells and its stability. Low oxygen concentration and antioxidant intervention are helpful to transplantation of BMHSC.