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Emerging studies reported that gut microbiota and fecal metabolites take part in major depressive disorder (MDD) pathogenesis. However, the conclusions based on a single depressive animal model seem inconsistent or even controversial.Multiple depression rat models, including chronic unpredictable mild stress, chronic restraint stress, social defeat, and learned helplessness, were used. Then, the 16S ribosomal RNA gene sequencing and liquid chromatography-mass spectrometry analysis determined the alteration of gut microbiota and fecal metabolites.The results of sucrose preference test and forced swimming test suggested that each model successfully established depression-like behavior. A total of 179 discriminative amplicon sequence variants (ASVs) were identified among four models. The overall discriminative ASVs mainly belonged to the family Lachnospiraceae, Muribaculaceae, and Oscillospiraceae. Moreover, the fecal metabolomic analysis identified 468 differential expressed metabolites. Among all the differential metabolites, 11 specific pathways significantly altered, which were mainly belonged to lipid and amino acid metabolism. Finally, co-occurrence network analysis suggested that target differential metabolites were associated with discriminative ASVs mainly assigned to family taxon Lachnospiraceae, Muribaculaceae, and Oscillospiraceae.The heterogeneity of MDD in humans cannot be totally imitated by animal models.In multiple depression models, the alterations of family Lachnospiraceae, Muribaculaceae, and Oscillospiraceae with the dysbiosis of lipid and amino acid metabolism were gut microbiota and fecal metabolome features. The findings of our research may help us to have a comprehensive understanding of gut microbiota and fecal metabolome in depression.

Most previous studies in the pathophysiology of major depressive disorder (MDD) focused on fecal samples, which limit the identification of the gut mucosal and luminal microbiome in depression. Here, we address this knowledge gap. Male cynomolgus macaques (Macaca fascicularis) were randomly assigned to a chronic unpredictable mild stress (CUMS) group, or to an unstressed control group. Behavioral tests were completed in both groups. At endpoint, microbe composition of paired mucosal and luminal samples from cecum, ascending, transverse, and descending colons were determined by 16S ribosomal RNA gene sequencing. The levels of 34 metabolites involved in carbohydrate or energy metabolism in luminal samples were measured by targeted metabolomics profiling. CUMS macaques demonstrated significantly more depressive-like behaviors than controls. We found differences in mucosal and luminal microbial composition between the two groups, which were characterized by Firmicutes and Bacteriodetes at the phylum level, as well as Prevotellaceae and Lachnospiraceae at the family level. The majority of discriminative microbes correlated with the depressive-like behavioral phenotype. In addition, we found 27 significantly different microbiome community functions between the two groups in mucosa, and one in lumen, which were mainly involved in carbohydrate and energy metabolism. A total of nine metabolites involved in these pathways were depleted in CUMS animals. Together, CUMS macaques with depressive-like behaviors associated with distinct alterations of covarying microbiota, carbohydrate and energy metabolism in mucosa and lumen. Further studies should focus on the mucosal and luminal microbiome to provide a deeper spatiotemporal perspective of microbial alterations in the pathogenesis of MDD.

The etiology in major depressive disorder (MDD) has not been fully understood. Accumulating evidence suggests an association between altered intestinal and blood-brain barrier (BBB) permeability and psychiatric disorders, while its changes in adolescent MDD populations have been received less attention. In this study, our aim was to explore the differences in plasma levels of intestinal and blood-brain barrier permeability markers in adolescents with MDD compared with healthy controls (HCs).We enrolled MDD (n = 50), and HCs (n = 40) with the age of 13-18 years old. The plasma level of zonulin, I-FABP, LPS, and claudin-5 were quantified. The Hamilton Depression Scale 17 items (HAMD-17) and Hamilton Anxiety Scale 14 items (HAMA-14) were used for symptom assessments.The plasma levels of zonulin, I-FABP, LPS, and claudin-5 in the MDD group were significantly higher than those in the HCs. Plasma I-FABP levels in MDD with moderate to severe anxiety were significantly higher than those in MDD without moderate to severe anxiety and HCs. In addition, these four biomarkers (alone or combined) can be used as diagnostic markers for MDD in adolescents.The key limitation of this study is the blood measurements at a single time point with a relatively small sample size.These findings advance our understanding of the pathophysiology of intestinal barrier injury, bacterial translocation, and blood-brain barrier injury involved in adolescents with MDD.

BackgroundAvailable evidence on the comparative efficacy and acceptability of psychotherapies for post-traumatic stress disorder (PTSD) in children and adolescents remains uncertain.ObjectiveWe aimed to compare and rank the different types and formats of psychotherapies for PTSD in children and adolescents.MethodsWe searched eight databases and other international registers up to 31 December 2020. The pairwise meta-analyses and frequentist network meta-analyses estimated pooled standardised mean differences (SMDs) and ORs with random-effects model. Efficacy at post-treatment and follow-up, acceptability, depressive and anxiety symptoms were measured.FindingsWe included 56 randomised controlled trials with 5327 patients comparing 14 different types of psychotherapies and 3 control conditions. For efficacy, cognitive processing therapy (CPT), behavioural therapy (BT), individual trauma-focused cognitive–behavioural therapy (TF-CBT), eye movement desensitisation and reprocessing, and group TF-CBT were significantly superior to all control conditions at post-treatment and follow-up (SMDs between −2.42 and −0.25). Moreover, CPT, BT and individual TF-CBT were more effective than supportive therapy (SMDs between −1.92 and −0.49). Results for depressive and anxiety symptoms were similar to the findings for the primary outcome. Most of the results were rated as ‘moderate’ to ‘very low’ in terms of confidence of evidence.ConclusionsCPT, BT and individual TF-CBT appear to be the best choices of psychotherapy for PTSD in young patients. Other types and different ways of delivering psychological treatment can be alternative options. Clinicians should consider the importance of each outcome and the patients’ preferences in real clinical practice.

Most previous studies in the pathophysiology of major depressive disorder (MDD) focused on fecal samples, which limit the identification of the gut mucosal and luminal microbiome in depression. Here, we address this knowledge gap. Male cynomolgus macaques (Macaca fascicularis) were randomly assigned to a chronic unpredictable mild stress (CUMS) group, or to an unstressed control group. Behavioral tests were completed in both groups. At endpoint, microbe composition of paired mucosal and luminal samples from cecum, ascending, transverse, and descending colons were determined by 16S ribosomal RNA gene sequencing. The levels of 34 metabolites involved in carbohydrate or energy metabolism in luminal samples were measured by targeted metabolomics profiling. CUMS macaques demonstrated significantly more depressive-like behaviors than controls. We found differences in mucosal and luminal microbial composition between the two groups, which were characterized by Firmicutes and Bacteriodetes at the phylum level, as well as Prevotellaceae and Lachnospiraceae at the family level. The majority of discriminative microbes correlated with the depressive-like behavioral phenotype. In addition, we found 27 significantly different microbiome community functions between the two groups in mucosa, and one in lumen, which were mainly involved in carbohydrate and energy metabolism. A total of nine metabolites involved in these pathways were depleted in CUMS animals. Together, CUMS macaques with depressive-like behaviors associated with distinct alterations of covarying microbiota, carbohydrate and energy metabolism in mucosa and lumen. Further studies should focus on the mucosal and luminal microbiome to provide a deeper spatiotemporal perspective of microbial alterations in the pathogenesis of MDD.

Background Depression is a leading cause of disability worldwide. There is increasing evidence showing that depression is associated with the pathophysiology in amygdala; however, the underlying mechanism remains poorly understood. Method We established a rat model of chronic social defeat stress (CSDS) and conducted a series of behavior tests to observe behavioral changes. Then liquid chromatography mass spectrometry (LC–MS)-based metabolomics and isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics were employed to detect metabolomes and proteomes in the amygdala, respectively. Ingenuity pathway analysis (IPA) and other bioinformatic analyses were used to analyze differentially expressed metabolites and proteins. Results The significantly lower sucrose preference index in the sucrose preference test and longer immobile time in the forced swim test were observed in the CSDS rats compared with control rats. In the multi-omics analysis, thirty-seven significantly differentially expressed metabolites and 123 significant proteins were identified. Integrated analysis of differentially expressed metabolites and proteins by IPA revealed molecular changes mainly associated with synaptic plasticity, phospholipase c signaling, and glutamine degradation I. We compared the metabolites in the amygdala with those in the hippocampus and prefrontal cortex from our previous studies and found two common metabolites: arachidonic acid and N-acetyl- l -aspartic acid among these three brain regions. Conclusion Our study revealed the presence of depressive-like behaviors and molecular changes of amygdala in the CSDS rat model, which may provide further insights into the pathogenesis of depression, and help to identify potential targets for antidepressants.

Suicide is one of the leading causes of death and represents a significant public health problem worldwide; however, the underlying mechanism of suicide remains unclear, and there is no animal model with suicide-implicated endophenotypes for investigating the etiology, course and potential treatment targets of suicide. Thus, we generated a diathesis-stress rat model to simulate suicide-implicated endophenotypes. First, two hundred rats were screened in two rounds of learned helplessness (LH) tests and selected as learned helplessness-sensitive (LHS) rats (n = 37) and learned helplessness-resistant (LHR) rats (n = 39). Then, all LHS rats and half of the rats (randomly selected) in the LHR group were exposed to four weeks of social defeat stress (SDS) (LHS + SDS group, n = 37 and LHR + SDS group, n = 20, respectively). The remainder of the LHR rats were handled as controls (LHR + CON group, n = 19). The LHS + SDS group showed significantly more suicide-implicated endophenotypes than the LHR + CON group, including longer immobile times in the forced swim test (hopelessness), higher scores in the irritability test (irritability), shorter latencies to attack (impulsivity), longer total attack times in the resident-intruder test (aggression), and lower sucrose preference indices (anhedonia). Proteomic analyses revealed that the canonical pathways that were the most common between the LHS + SDS and LHR + CON groups were the PKA and GABA receptor pathways in the prefrontal cortex. A diathesis-stress paradigm would be a useful way to establish a rat model with suicide-implicated endophenotypes, providing novel perspectives for revealing the potential mechanism of suicide.

Major depressive disorder is a serious and complex mental illness, and multiple brain regions are involved in its pathogenesis. There is increasing evidence that the amygdala is involved in depression; however, the underlying molecular mechanisms remain unclear. In this study, we applied a combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomic and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic to study changes in the amygdala in a chronic unpredictable mild stress (CUMS) rat model of depression. Differential analysis identified 42 metabolites and 171 proteins that were differentially expressed in the CUMS and control groups. Integrated analyses revealed two major changes in the amygdala of CUMS rats: (1) perturbations in amino acids and carbohydrate metabolism, transport-/catabolism-related proteins activity, and metabolic enzyme activity; (2) abnormal expression of synaptogenesis and oxidative phosphorylation-associated proteins.

In 2020, the new type of coronal pneumonitis became a pandemic in the world, and has firstly been reported in Wuhan, China. Chest CT is a vital component in the diagnostic algorithm for patients with suspected or confirmed COVID-19 infection. Therefore, it is necessary to conduct automatic and accurate detection of COVID-19 by chest CT.The clinical classification of patients with COVID-19 pneumonia was predicted by Radiomics using chest CT.From the COVID-19 cases in our institution, 136 moderate patients and 83 severe patients were screened, and their clinical and laboratory data on admission were collected for statistical analysis. Initial CT Radiomics were modeled by automatic machine learning, and diagnostic performance was evaluated according to AUC, TPR, TNR, PPV and NPV of the subjects. At the same time, the initial CT main features of the two groups were analyzed semi-quantitatively, and the results were statistically analyzed.There was a statistical difference in age between the moderate group and the severe group. The model cohort showed TPR 96.9%, TNR 99.1%, PPV98.4%, NPV98.2%, and AUC 0.98. The test cohort showed TPR 94.4%, TNR100%, PPV100%, NPV96.2%, and AUC 0.97. There was statistical difference between the two groups with grade 1 score (P = .001), the AUC of grade 1 score, grade 2 score, grade 3 score and CT score were 0.619, 0.519, 0.478 and 0.548, respectively.Radiomics' Auto ML model was built by CT image of initial COVID -19 pneumonia, and it proved to be effectively used to predict the clinical classification of COVID-19 pneumonia. CT features have limited ability to predict the clinical typing of Covid-19 pneumonia.

Objective: To explore the possibility of predicting the clinical types of Corona-Virus-Disease-2019(COVID-19) pneumonia by analyzing the non-focus area of the lung in the first chest CT image of patients with COVID-19 by using automatic machine learning (Auto-ML).Methods: 136 moderate and 83 severe patients were selected from the patients with COVID-19 pneumonia. The clinical and laboratory data were collected for statistical analysis. The texture features of the Non-focus area of the first chest CT of patients with COVID-19 pneumonia were extracted, and then the classification model of the first chest CT of COVID-19 pneumonia was constructed by using these texture features based on the Auto-ML method of radiomics, The area under curve(AUC), true positive rate(TPR), true negative rate(TNR), positive predictive value(PPV) and negative predictive value(NPV) of the operating characteristic curve (ROC) were used to evaluate the accuracy of the first chest CT image classification model in patients with COVID-19 pneumonia.Result: The TPR, TNR, PPV, NPV and AUC of the training cohort and test cohort of the moderate group and the control group, the severe group and the control group, the moderate group and the severe group were all greater than 95% and 0.95 respectively. Conclusion: The non-focus area of the first CT image of COVID-19 pneumonia has obvious difference in different clinical types. The AUTO-ML classification model of Radiomics based on this difference can be used to predict the clinical types of COVID-19 pneumonia.

Since the outbreak of coronavirus disease (COVID-19) that was discovered in 2019 in Wuhan, China, no standard therapy guideline has been set despite the severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its high infectivity. The globally pandemic outbreak suggests that COVID-19 is highly infectious and difficult to control. A dual-combination of ribavirin and interferon-α has been the widely used regimen for the treatment of this disease in China. However, due to the varying results of treatment with these drugs, a novel antiviral combination therapy is urgently needed. This case reports the usage of lopinavir/ritonavir-based combination antiviral regimen for a patient with SARS-CoV-2 infection.

Purpose: To evaluate the vascular stenosis and collateral circulation in moyamoya disease using 4D CTA. Methods: Two neuroradiologists evaluated 4D CTA and DSA for 101 moyamoya patients. The performance of 4D CTA relative to DSA was determined using consistency checks (kappa values, 95% CI) and correlation analysis. Results: The kappa values were 0.714 (modified Suzuki score), 0.846 (Houkin score), 0.594 (basicranial moyamoya vessels), 0.435 (posterior circulation collaterals) and 0.591 (ECA collaterals). The correlation coefficients were 0.843, 0.872, 0.792, 0.635 and 0.797. Conclusions: 4D CTA showed strong consistency and correlation with DSA in the vascular stenosis score, but was insufficient in collateral circulation evaluation.

The mechanism underlying atherosclerotic ischemic events within the middle cerebral artery (MCA) is unclear. High structural stress induced by blood pressure might be a potential aetiology as plaque rupture occurs when such mechanical loading exceeds its material strength. To perform reliable analyses quantifying the mechanical loading within a plaque, the local blood pressure is needed. However, data on MCA blood pressure is currently lacking. In this study, the arterial pressure proximal to the stenotic site in the MCA was measured in 15 patients scheduled for intervention. The relationships between these local measurements and pre-intervention and intra-intervention non-invasive arm measurements were assessed. The impact of luminal stenosis on the local blood pressure was quantified. Compared with the pre-intervention arm measurement, the intra-intervention arm pressure decreased significantly by 23.9 ± 11.8 and 9.3 ± 14.7 % at diastole and systole, respectively. The pressure proximal to the stenosis was much lower than the pre-intervention arm measurement (diastole: 65.3 ± 15.7 vs 82.0 ± 9.7, p < 0.01; systole: 81.1 ± 15.9 vs 133.9 ± 18.7, p < 0.01; unit: mmHg). The systolic pressure in the MCA in patients with stenosis

Background and aimsRecent development of high resolution MRI techniques have enabled imaging of intracranial atherosclerotic plaque invivo. However, identifying plaque composition remains challenging given the small size and the lack of histological validation. This study aims to quantify the relaxation times of intracranial plaque components exvivo at 3T and to determine whether multi-contrast MRI could classify intracranial plaque according to the American Heart Association classification with histological validation.MethodsA total of 53 intracranial arteries with atherosclerotic plaques from 20 cadavers (11 male, age 73.8±10.9) were excised. Quantitative T1/T2/T2* mapping sequences and multi-contrast fast-spin echo sequences (T1, T2, proton-density weighted and short time inversion recovery) were acquired. Plaque components including: fibrous cap, lipid core, fibrous tissue, calcification, and healthy wall were segmented on histology, and their relaxation times were derived from quantitative images. Two radiologists independently classified plaque type blinded to the histology results.ResultsRelaxation times of plaque components are distinct and different. T2 and T2* values of lipid core are lower than fibrous cap (p=0.026 & p&nbsp

Purpose To evaluate the intra- and inter-observer variability of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) criteria for the evaluation of middle cerebral artery (MCA) stenosis using digital subtraction angiography (DSA). Materials and Methods DSA images of 114 cases with 131 stenotic MCAs were retrospectively analyzed. Two radiologists and a researcher measured the degree of MCA stenosis independently using both NASCET and WASID methods. To determine intra-observer agreement, all the observers reevaluated the degree of MCA stenosis 4 weeks later. The linear relation and coefficient of variation (CV) between the measurements made by the two methods were assessed by correlation coefficient and multi-factor analysis of variance (ANOVA), respectively. Intra- and inter-observer variability of the two methods was evaluated by intraclass correlation coefficient (ICC), Spearman’s R value, Pearson correlation coefficient and Bland-Altman plots. Results Despite the fact that the degree of MCA stenosis measured by NASCET was lower than measured using the WASID method, there was good linear correlation between the measurements made by the two methods (for the mean measurements of the 3 observers, NASCET% = 0.891 × WASID% - 1.89%; ICC, Spearman’s R value and Pearson correlation were 0.874, 0.855, and 0.874, respectively). The CVs of both intra- and inter-observer measurements of MCA stenosis using WASID were significantly lower than that using NASCET confirmed by the multi-factor ANOVA results, which showed only the measurement methods of MCA stenosis had significant effects on the CVs both in intra- and inter-observer measurements (both P values < 0.001). Intra-observer measurements showed good or excellent agreement with respect to WASID and NASCET evaluation (ICC, 0.656 to 0.817 and 0.635 to 0.761, respectively). Good agreement for the WASID evaluation (ICC, 0.592 to 0.628) and for the NASCET evaluation (ICC, 0.529 to 0.568) was observed for inter-observer measurements. Bland-Altman plots demonstrated that the WASID method had better reproducibility and intra-observer agreement than NASCET method for evaluating MCA stenosis. Conclusion Both NASCET and WASID methods have an acceptable level of agreement; however, the WASID method had better reproducibility for the evaluation of MCA stenosis, and thus the WASID method may serve as a standard for measuring the degree of MCA stenosis.