Exploring the differential effects of psychological resilience and social support in mitigating post-traumatic psychiatric symptoms: real-world network analysis of front-line rescuers.

BACKGROUND: Although both psychological resilience and social support are widely believed to be effective in alleviating post-traumatic psychiatric symptoms in individuals with traumatic events, there has been a lack of comparative analysis of their intervention effects on different post-traumatic psychiatric symptoms. Furthermore, previous studies have mostly failed to control for potential confounding effects caused by different traumatic events. AIMS: We used the novel network analysis approach to examine the differential moderating effects of psychological resilience and social support on post-traumatic psychiatric symptoms, controlling for the confounding effects of traumatic events. METHOD: We recruited 264 front-line rescuers who experienced the same traumatic event. Quantified edge weights and bridge expected influence (BEI) were applied to compare the alleviating effects of psychological resilience and social support. RESULTS: Our study revealed distinct correlations in a sample of front-line rescuers: social support negatively correlates more with psychosomatic symptoms, notably fatigue in depressive networks and sleep disturbance in post-traumatic stress disorder (PTSD) networks, whereas psychological resilience shows fewer such correlations. Quantitative analysis using BEI indicated that psychological resilience more effectively suppresses depressive and anxiety symptom networks, whereas social support more significantly inhibits PTSD symptom networks. CONCLUSIONS: The current study represents the first attempt to examine the differential effects of psychological resilience and social support on post-traumatic outcomes in real-world emergency rescuers, controlling for the confounding effect of traumatic events. Our results can act as the theoretical reference for future precise and efficient post-trauma psychological interventions.

Trajectories and comorbid symptom networks of posttraumatic stress symptoms in frontline rescuers: A longitudinal study.

BACKGROUND: Previous research has largely lacked studies that explore the trajectories of Posttraumatic stress symptoms (PTSS) and the structure of comorbid psychiatric symptom networks following traumatic event, while controlling for the severity of traumatic exposure. The present study aims to explore the characteristic trajectories of PTSS, in the context of ensuring controlled levels of traumatic exposure. Furthermore, the PTSS, depressive, and anxiety comorbid symptom networks of different PTSS trajectory subgroups are also investigated. METHODS: A total of 296 frontline rescue personnel were enrolled into our study. In an effort to control for variations in traumatic exposure severity, this study ensured that all participants had same responsibilities and cumulative operational duration at the post-disaster rescue circumstance. Growth mixture models (GMMs) were employed to scrutinize the trajectories of PTSS. Additionally, network analysis was used to examine the comorbid symptom network of PTSS, depression, and anxiety. RESULTS: Four distinct PTSS trajectories were identified, namely Persisting Symptom, Gradual Recovery, Gradual Aggravation, and Asymptomatic. Although both the Persisting Symptom and Gradual Aggravation groups belong to the high-risk subgroups for persistent PTSS, they exhibit differences in core symptoms within their respective networks. The core symptom for the Persisting Symptom Network is flashbacks, while for the Gradual Aggravation Network, it is sleep disturbances. CONCLUSION: To the best of our knowledge, the present study represents the first research endeavor to integrate longitudinal trajectory analysis of PTSS with longitudinal symptom network analysis, clarifying the evolving features of PTSS but also offering valuable insights for early screening and intervention strategies.

Dynamic risk factors of psychiatric readmission for major depressive disorder: A longitudinal study on patients treated with mono-antidepressant.

In this comprehensive study, we sought to unravel the risk factors for recurrence in Major Depressive Disorder (MDD), uniquely focusing on patients undergoing mono-antidepressant treatment. By considering psychiatric readmission as a direct indicator of MDD recurrence, we meticulously analyzed the records of 1,456 inpatients from a Chinese mental health center from 2012 to 2020. Our follow-up periods, spanning 90, 180, and 365 days post-discharge, allowed for a nuanced understanding of the recurrence dynamics. We identified four critical risk factors: thyroid function (FT3 and TSH), high-density lipoprotein (HDL) levels, and region of residence. Notably, the study revealed an increasing risk of readmission associated with decreased FT3 and HDL over time, while elevated TSH and residing in another province 's impact diminished. The antidepressant type did not significantly alter readmission risks, providing a unique perspective on MDD management. This research contributes to the field by offering a deeper understanding of how demographic and biochemical factors influence the likelihood of MDD recurrence, guiding more effective treatment approaches.

Lsr2 acts as a cyclic di-GMP receptor that promotes keto-mycolic acid synthesis and biofilm formation in mycobacteria.

Cyclic di-GMP (c-di-GMP) is a second messenger that promotes biofilm formation in several bacterial species, but the mechanisms are often unclear. Here, we report that c-di-GMP promotes biofilm formation in mycobacteria in a manner dependent on the nucleoid-associated protein Lsr2. We show that c-di-GMP specifically binds to Lsr2 at a ratio of 1:1. Lsr2 upregulates the expression of HadD, a (3R)-hydroxyacyl-ACP dehydratase, thus promoting the synthesis of keto-mycolic acid and biofilm formation. Thus, Lsr2 acts as a c-di-GMP receptor that links the second messenger's function to lipid synthesis and biofilm formation in mycobacteria.

Integrative multiomics profiling of passion fruit reveals the genetic basis for fruit color and aroma.

Passion fruit (Passiflora edulis) possesses a complex aroma and is widely grown in tropical and subtropical areas. Here, we conducted the de novo assembly, annotation, and comparison of PPF (P. edulis Sims) and YPF (P. edulis f. flavicarpa) reference genomes using PacBio, Illumina, and Hi-C technologies. Notably, we discovered evidence of recent whole-genome duplication events in P. edulis genomes. Comparative analysis revealed 7.6∼8.1 million single nucleotide polymorphisms, 1 million insertions/deletions, and over 142 Mb presence/absence variations among different P. edulis genomes. During the ripening of yellow passion fruit, metabolites related to flavor, aroma, and color were substantially accumulated or changed. Through joint analysis of genomic variations, differentially expressed genes, and accumulated metabolites, we explored candidate genes associated with flavor, aroma, and color distinctions. Flavonoid biosynthesis pathways, anthocyanin biosynthesis pathways, and related metabolites are pivotal factors affecting the coloration of passion fruit, and terpenoid metabolites accumulated more in PPF. Finally, by heterologous expression in yeast (Saccharomyces cerevisiae), we functionally characterized 12 terpene synthases. Our findings revealed that certain TPS homologs in both YPF and PPF varieties produce identical terpene products, while others yield distinct compounds or even lose their functionality. These discoveries revealed the genetic and metabolic basis of unique characteristics in aroma and flavor between the 2 passion fruit varieties. This study provides resources for better understanding the genome architecture and accelerating genetic improvement of passion fruits.

The longitudinal change pattern of cognitive subtypes in medication-free patients with major depressive disorder: a cluster analysis.

This study aimed to investigate whether there are different cognitive subtypes in patients with major depressive disorder (MDD) and the change pattern of cognitive clusters across the course of MDD. A battery of comprehensive cognitive tests was used to assess the executive function, processing speed, attention, and memory of 153 medication-free patients and 142 healthy controls (HCs). After 6 months of treatment with antidepressants, 87 patients completed cognitive tests again. K-means cluster analysis was performed to determine the cognitive subtypes. A preserved cognition cluster and an impaired cognition cluster were identified in the acute episode phase and the 6-month follow-up phase. 80.5% of the patients remained in their original subgroup after 6 months of treatment. The impaired cognition cluster during the 6-month follow-up period could be predicted by impaired cognition during the episode phase, disease state (remission or non-remission), current illness duration, and education level. This study supporting the heterogeneity of cognitive performance across the course of disease in patients with MDD using cluster analysis. It was found that cognitive impairment during depressive episodes was predictive of poorer cognitive performance even after treatment with antidepressants. Therefore, interventions targeting cognitive function from the early stages of MDD is essential.

Post-traumatic stress disorder and traumatic events in China: a nationally representative cross-sectional epidemiological study.

Post-traumatic stress disorder (PTSD) is one of the most severe sequelae of trauma. But a nationally representative epidemiological data for PTSD and trauma events (TEs) was unavailable in China. This article firstly demonstrated detailed epidemiological information on PTSD, TEs, and related comorbidities in the national-wide community-based mental health survey in China. A total of 9,378 participants completed the PTSD-related interview of the CIDI 3.0. Lifetime prevalence and 12-month prevalence of PTSD in total respondents were 0.3% and 0.2%. while the conditional lifetime and 12-month prevalence of PTSD after trauma exposure were 1.8% and 1.1%. The prevalence of exposure to any type of TE was 17.2%. Among individuals with the exposed to TEs, younger, without regular work (being a homemaker or retried), and intimate relationship breakdown (separated/Widowed/Divorced), living rurally were associated with either the lifetime PTSD or the 12-month PTSD, while the count of a specific TE, the unexpected death of loved one, was related to both. Alcohol dependence was the most common comorbidity among male participants with PTSD but major depressive disorder (MDD) for female counterparts. Our study can provide a reliable reference for future identification and intervention for people with PTSD.

New Loss-of-Function Mutations in PCSK9 Reduce Plasma LDL Cholesterol.

BACKGROUND: Lower plasma levels of LDL (low-density lipoprotein) cholesterol (LDL-C) can reduce the risk of atherosclerotic cardiovascular disease. The loss-of-function mutations in PCSK9 (proprotein convertase subtilisin/kexin type 9) have been known to associate with low LDL-C in many human populations. PCSK9 genetic variants in Chinese Uyghurs who are at high risk of atherosclerotic cardiovascular disease due to their dietary habits have not been reported. METHODS: The study involved the whole-exome and target sequencing of college students from Uyghur and other ethnic groups in Xinjiang, China, for the association of PCSK9 loss-of-function mutations with low plasma levels of LDL-C. The mechanisms by which the identified mutations affect the function of PCSK9 were investigated in cultured cells using biochemical and cell assays. The causal effects of the identified PCSK9 mutations on LDL-C levels were verified in mice injected with adeno-associated virus expressing different forms of PCSK9 and fed a high-cholesterol diet. RESULTS: We identified 2 PCSK9 mutations-E144K and C378W-in Chinese Uyghurs with low plasma levels of LDL-C. The E144K and C378W mutations impaired the maturation and secretion of the PCSK9 protein, respectively. Adeno-associated virus-mediated expression of E144K and C378W mutants in Pcsk9 KO (knockout) mice fed a high-cholesterol diet also hampered PCSK9 secretion into the serum, resulting in elevated levels of LDL receptor in the liver and reduced levels of LDL-C in the serum. CONCLUSIONS: Our study shows that E144K and C378W are PCSK9 loss-of-function mutations causing low LDL-C levels in mice and probably in humans as well.

PatA Regulates Isoniazid Resistance by Mediating Mycolic Acid Synthesis and Controls Biofilm Formation by Affecting Lipid Synthesis in Mycobacteria.

Lipids are prominent components of the mycobacterial cell wall, and they play critical roles not only in maintaining biofilm formation but also in resisting environmental stress, including drug resistance. However, information regarding the mechanism mediating mycobacterial lipid synthesis remains limited. PatA is a membrane-associated acyltransferase and synthesizes phosphatidyl-myo-inositol mannosides (PIMs) in mycobacteria. Here, we found that PatA could regulate the synthesis of lipids (except mycolic acids) to maintain biofilm formation and environmental stress resistance in Mycolicibacterium smegmatis. Interestingly, the deletion of patA significantly enhanced isoniazid (INH) resistance in M. smegmatis, although it reduced bacterial biofilm formation. This might be due to the fact that the patA deletion promoted the synthesis of mycolic acids through an unknown synthesis pathway other than the reported fatty acid synthase (FAS) pathway, which could effectively counteract the inhibition by INH of mycolic acid synthesis in mycobacteria. Furthermore, the amino acid sequences and physiological functions of PatA were highly conserved in mycobacteria. Therefore, we found a mycolic acid synthesis pathway regulated by PatA in mycobacteria. In addition, PatA also affected biofilm formation and environmental stress resistance by regulating the synthesis of lipids (except mycolic acids) in mycobacteria. IMPORTANCE Tuberculosis, caused by Mycobacterium tuberculosis, leads to a large number of human deaths every year. This is so serious, which is due mainly to the drug resistance of mycobacteria. INH kills M. tuberculosis by inhibiting the synthesis of mycolic acids, which are synthesized by the FAS pathway. However, whether there is another mycolic acid synthesis pathway is unknown. In this study, we found a PatA-mediated mycolic acid synthesis pathway that led to INH resistance of in patA-deleted mutant. In addition, we first report the regulatory effect of PatA on mycobacterial biofilm formation, which could affect the bacterial response to environmental stress. Our findings represent a new model for regulating biofilm formation by mycobacteria. More importantly, the discovery of the PatA-mediated mycolic acid synthesis pathway indicates that the study of mycobacterial lipids has entered a new stage, and the enzymes might be new targets of antituberculosis drugs.

Post-traumatic stress disorder and depressive symptoms among firefighters: a network analysis.

Background: Firefighters, as first responders with a high risk of occupational exposure to traumatic events and heavy working stress, have a high prevalence of PTSD symptoms and depressive symptoms. But no previous studies analyzed the relationships and hierarchies of PTSD and depressive symptoms among firefighters. Network analysis is a novel and effective method for investigating the complex interactions of mental disorders at the symptom level and providing a new understanding of psychopathology. The current study was designed to characterize the PTSD and depressive symptoms network structure in the Chinese firefighters. Method: The Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) and the Self-Rating Depression Scale (SDS) were applied to assess PTSD and depressive symptoms, respectively. The network structure of PTSD and depressive symptoms was characterized using "expected influence (EI)" and "bridge EI" as centrality indices. The Walktrap algorithm was conducted to identify communities in the PTSD and depressive symptoms network. Finally, Network accuracy and stability were examined using the Bootstrapped test and the case-dropping procedure. Results: A total of 1,768 firefighters were enrolled in our research. Network analysis revealed that the relationship between PTSD symptoms, "Flashback" and "Avoidance," was the strongest. "Life emptiness" was the most central symptom with the highest EI in the PTSD and depression network model. Followed by "Fatigue" and "Interest loss." Bridge symptoms connecting PTSD and depressive symptoms in our study were "Numb," "High alertness," "Sad mood," and "Compunction and blame," successively. The data-driven community detection suggested the differences in PTSD symptoms in the clustering process. The reliability of the network was approved by both stability and accuracy tests. Conclusion: To the best of our knowledge, the current study first demonstrated the network structure of PTSD and depressive symptoms among Chinese firefighters, identifying the central and bridge symptoms. Targeting interventions to the symptoms mentioned above may effectively treat firefighters suffering from PTSD and depressive symptoms.

D-Xylose Blocks the Broad Negative Regulation of XylR on Lipid Metabolism and Affects Multiple Physiological Characteristics in Mycobacteria.

D-xylose is the most abundant fermentable pentose, which usually represents an architectural component of the bacterial cell wall. However, its regulatory function and the involved signaling pathway in bacteria remain largely unclear. Here, we show that D-xylose can act as a signaling molecule to regulate the lipid metabolism and affect multiple physiological characteristics in mycobacteria. D-xylose directly interacts with XylR and inhibits its DNA-binding ability, thus blocking XylR-mediated repression. The xylose inhibitor, XylR, plays a global regulatory role and affects the expression of 166 mycobacterial genes that are involved in lipid synthesis and metabolism. Furthermore, we show that the xylose-dependent gene regulation of XylR affects the multiple physiological characteristics of Mycobacterium smegmatis, including bacterial size, colony phenotype, biofilm formation, cell aggregation, and antibiotic resistance. Finally, we found that XylR inhibited the survival of Mycobacterium bovis BCG in the host. Our findings provide novel insights into the molecular mechanism of lipid metabolism regulation and its correlation with bacterial physiological phenotypes.

The percentage of cognitive impairment in patients with major depressive disorder over the course of the depression: A longitudinal study.

BACKGROUND: Cognitive impairments (CI) are prevalent and persistent in patients with major depressive disorder (MDD). There is a lack of longitudinal studies exploring the changes of the percentage of CI among MDD patients before and after a long-term antidepressant treatment and the risk factors that predict the residual CI. METHODS: A neurocognitive battery was performed to assess four domains of cognitive function, including executive function, processing speed, attention, and memory. CI was set as cognitive performance scoring 1.5 SDs lower than the mean scores of healthy controls (HCs). Logistic regression models were conducted to examine the risk factors for the after-treatment residual CI. RESULTS: Over 50 % of patients showed at least one kind of CI. After the antidepressant treatment, the overall cognitive performance among remitted MDD patients was identical to HCs, however, there were still 24 % of the remitted MDD patients had at least one type of CI, especially in executive function and attention. Additionally, the percentage of CI among non-remitted MDD patients was still significantly different from HCs. Our regression analysis further identified that except for the non-remission of MDD, CI at baseline could also predict the residual CI in MDD patients. LIMITATIONS: A relatively high drop-out rate at follow-ups. CONCLUSIONS: Cognitive impairment in executive function and attention is persistent even in remitted patients with MDD, and baseline cognitive performance can predict the post-treatment cognitive performance. Our findings emphasize the integral role of early cognitive intervention in MDD treatment.

Psychosocial crisis intervention for coronavirus disease 2019 patients and healthcare workers. / æ–°åž‹å† çŠ¶ç— æ¯’è‚ºç‚Žæ‚£è€ å’ŒåŒ»åŠ¡äººå‘˜çš„å¿ƒç†ç¤¾ä¼šå±æœºå¹²é¢„ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Shelter hospital was an alternative way to provide large-scale medical isolation and treatment for people with mild coronavirus disease 2019 (COVID-19). Due to various reasons, patients admitted to the large shelter hospital was reported high level of psychological distress, so did the healthcare workers. This study aims to introduce a comprehensive and multifaceted psychosocial crisis intervention model. METHODS: The psychosocial crisis intervention model was provided to 200 patients and 240 healthcare workers in Wuhan Wuchang shelter hospital. Patient volunteers and organized peer support, client-centered culturally sensitive supportive care, timely delivery of scientific information about COVID-19 and its complications, mental health knowledge acquisition of non-psychiatric healthcare workers, group activities, counseling and education, virtualization of psychological intervention, consultation and liaison were exhibited respectively in the model. Pre-service survey was done in 38 patients and 49 healthcare workers using the Generalized Anxiety Disorder 7-item (GAD-7) scale, the Patient Health Questionnaire 2-item (PHQ-2) scale, and the Primary Care PTSD screen for the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (PC-PTSD-5). Forty-eight healthcare workers gave feedback after the intervention. RESULTS: The psychosocial crisis intervention model was successfully implemented by 10 mental health professionals and was well-accepted by both patients and healthcare workers in the shelter hospital. In pre-service survey, 15.8% of 38 patients were with anxiety, 55.3% were with stress, and 15.8% were with depression; 16.3% of 49 healthcare workers were with anxiety, 26.5% were with stress, and 22.4% were with depression. In post-service survey, 62.5% of 48 healthcare workers thought it was very practical, 37.5% thought more practical; 37.5% of them thought it was very helpful to relief anxiety and insomnia, and 27.1% thought much helpful; 37.5% of them thought it was very helpful to recognize patients with anxiety and insomnia, and 29.2% thought much helpful; 35.4% of them thought it was very helpful to deal with patients' anxiety and insomnia, and 37.5% thought much helpful. CONCLUSIONS: Psychological crisis intervention is feasible, acceptable, and associated with positive outcomes. Future tastings of this model in larger population and different settings are warranted.

Mental condition and function of resilience among families of frontline medical workers during COVID-19: Potential influencing factors and mediating effect.

BACKGROUND: Studying the role of psychological resilience in self-perceived stress and mental disorders among family members of medical workers can help us understand its importance in mental health care and guide us to develop psychological intervention strategies for family members of medical workers. METHODS: A total of 671 family members of medical workers were enrolled. Self-perceived stress, resilience, depression symptoms, anxiety symptoms, and post-traumatic stress disorder (PTSD) symptoms were measured in our research. RESULTS: The prevalence of anxiety, depression, and PTSD symptoms among relatives of medical workers were 49.0 %, 12.2 %, and 20.3 % respectively during the COVID-19 epidemic. According to the Multivariate regression model, compared with family members of doctor, family members of nurse and medical technologists were more likely to report anxiety symptoms. Female members of medical staff were more likely to have PTSD symptoms than male counterparts; and family members of medical technologist appeared to less likely have PTSD symptoms than family members of either doctor or nurse. The mediation analysis confirmed that mental resilience mediated the relationship between self-perceived stress and anxiety symptoms. LIMITATIONS: Single cross-sectional study design without the follow-up comparative analysis, only self-reported measurements were adopted, and inadequate pre-set demographic variables. CONCLUSIONS: To the best of our knowledge, our study firstly demonstrated the risk of psychological distress present in the family members of medical providers during the COVID-19 epidemic. Meanwhile, our findings highlighted the importance of mental resilience in family members of frontline medical workers as it mediated the relationship between self-perceived stress and anxiety symptoms.

Relationship between childhood maltreatment and cognitive function in medication-free patients with major depressive disorder.

This study aimed to elucidate the contribution of childhood maltreatment (CM) and the disease of major depressive disorder (MDD) on cognitive function in medication-free patients in a current depressive episode, and to examine the effect of CM on the improvement of cognitive function after treatment with antidepressants. One hundred and fifty-three unmedicated patients with MDD and 142 healthy controls (HCs) underwent clinical interviews. CM assessment was performed using the Childhood Trauma Questionnaire (CTQ), and a battery of comprehensive neurocognitive tests was used to assess the participants' executive function, processing speed, attention, and memory. After 6 months of treatment with antidepressants, the neurocognitive tests were reperformed in patients with MDD and HCs. There was a significant main effect of MDD on all four cognitive domains, while the main effect of CM was only significant on memory. No significant interactive effect was found between MDD and CM on any of the cognitive domains. In the MDD group, higher CTQ total score was predictive of poorer memory performance. After treatment, significant main effects of treatment and MDD were found on all four cognitive domains in remitted patients with MDD. No significant main effect of CM or three-way interaction effect of treatment × MDD × CM was found on any of the cognitive domains. The disease of MDD contributed to impairments in all four cognitive domains. CM independently contributed to memory impairment in patients in a current depressive episode, with higher severity of CM predictive of poorer memory performance.

Altered Effective Connectivity Among the Cerebellum and Cerebrum in Patients with Major Depressive Disorder Using Multisite Resting-State fMRI.

Major depressive disorder (MDD) is a serious and widespread psychiatric disorder. Previous studies mainly focused on cerebrum functional connectivity, and the sample size was relatively small. However, functional connectivity is undirected. And, there is increasing evidence that the cerebellum is also involved in emotion and cognitive processing and makes outstanding contributions to the symptomology and pathology of depression. Therefore, we used a large sample size of resting-state functional magnetic resonance imaging (rs-fMRI) data to investigate the altered effective connectivity (EC) among the cerebellum and other cerebral cortex in patients with MDD. Here, from the perspective of data-driven analysis, we used two different atlases to divide the whole brain into different regions and analyzed the alterations of EC and EC networks in the MDD group compared with healthy controls group (HCs). The results showed that compared with HCs, there were significantly altered EC in the cerebellum-neocortex and cerebellum-basal ganglia circuits in MDD patients, which implied that the cerebellum may be a potential biomarker of depressive disorders. And, the alterations of EC brain networks in MDD patients may provide new insights into the pathophysiological mechanisms of depression.

Neural activity changes in first-episode, drug-naïve patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study.

Introduction: Major depressive disorder (MDD) is a disease with prominent individual, medical, and economic impacts. Drug therapy and other treatment methods (such as Electroconvulsive therapy) may induce treatment-resistance and have associated side effects including loss of memory, decrease of reaction time, and residual symptoms. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel and non-invasive treatment approach which stimulates brain structures with no side-effects. However, it remains little understood whether and how the neural activation is modulated by taVNS in MDD patients. Herein, we used the regional homogeneity (ReHo) to investigate the brain activity in first-episode, drug-naïve MDD patients after taVNS treatment. Materials and methods: Twenty-two first-episode, drug-naïve MDD patients were enrolled in the study. These patients received the first taVNS treatment at the baseline time, and underwent resting-state MRI scanning twice, before and after taVNS. All the patients then received taVNS treatments for 4 weeks. The severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD) at the baseline time and after 4-week's treatment. Pearson analysis was used to assess the correlation between alterations of ReHo and changes of the HAMD scores. Two patients were excluded due to excessive head movement, two patients lack clinical data in the fourth week, thus, imaging analysis was performed in 20 patients, while correlation analysis between clinical and imaging data was performed in only 18 patients. Results: There were significant differences in the ReHo values in first-episode, drug-naïve MDD patients between pre- or post- taVNS. The primary finding is that the patients exhibited a significantly lower ReHo in the left/right median cingulate cortex, the left precentral gyrus, the left postcentral gyrus, the right calcarine cortex, the left supplementary motor area, the left paracentral lobule, and the right lingual gyrus. Pearson analysis revealed a positive correlation between changes of ReHo in the right median cingulate cortex/the left supplementary motor area and changes of HAMD scores after taVNS. Conclusion: The decreased ReHo were found after taVNS. The sensorimotor, limbic and visual-related brain regions may play an important role in understanding the underlying neural mechanisms and be the target brain regions in the further therapy.

Factors related to the length of stay for major depressive disorder patients in China: A real-world retrospective study.

Background: As numerous patients with depression have to be hospitalized because of various reasons, the demand far exceeds the limited bed count in the psychiatry department. Controlling the length of stay (LOS) of the patient is gradually being considered an effective method to alleviate this problem. Given the lack of statistical evidence of the LOS of patients with major depressive disorder (MDD) in China and the strain on the limited psychiatric resources, the purpose of our study was to investigate the LOS of patients with MDD among in-patient samples and to analyze related factors of the LOS in China by building a regression model. Method: The data were exported from the electronic medical record system. A total of three categories of independent variables were enrolled in our study, namely, demographic, clinical, and biochemical. Univariate analysis and binominal regression analysis were applied comprehensively to find the factors related to the LOS among MDD samples. The discrimination accuracy of the model was evaluated by the receiver operating characteristic (ROC) analysis. ROC analysis indicated that the discrimination accuracy of our model was acceptable (AUC = 0.790, 95% CI = 0.714-0.865, P < 0.001). Result: A total of 254 patients were finally brought into analysis after filtering. Regression analysis indicated that abnormal LDL was the only risk factor of long LOS (OR = 3.352, 95% CI = 1.087-10.337, P = 0.035) among all the kinds of variables. Notably, in the statistically irrelevant factors of the LOS, the category of anti-depressant drugs [serotonin-norepinephrine reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRI)] prescribed to patients with MDD was not associated statistically with the LOS, which was against our initial hypothesis that the LOS of patients with MDD treated with SNRI would vary from that of the patients treated with SSRI. Conclusion: Up to our knowledge, our research is the first study to show the potential factors related to the LOS from various domains, especially biochemical indexes, and the effect of drugs, among clinical patients with MDD in China. Our results could provide a theoretical reference for efficient psychiatry hospitalization management and prioritization of allocating medical resources. Future studies are required for updating independent variables which are potentially related to the LOS and verifying existing results in a larger sample.

The alterations of brain functional connectivity networks in major depressive disorder detected by machine learning through multisite rs-fMRI data.

BACKGROUND: The current diagnosis of major depressive disorder (MDD) is mainly based on the patient's self-report and clinical symptoms. Machine learning methods are used to identify MDD using resting-state functional magnetic resonance imaging (rs-fMRI) data. However, due to large site differences in multisite rs-fMRI data and the difficulty of sample collection, most of the current machine learning studies use small sample sizes of rs-fMRI datasets to detect the alterations of functional connectivity (FC) or network attribute (NA), which may affect the reliability of the experimental results. METHODS: Multisite rs-fMRI data were used to increase the size of the sample, and then we extracted the functional connectivity (FC) and network attribute (NA) features from 1611 rs-fMRI data (832 patients with MDD (MDDs) and 779 healthy controls (HCs)). ComBat algorithm was used to harmonize the data variances caused by the multisite effect, and multivariate linear regression was used to remove age and sex covariates. Two-sample t-test and wrapper-based feature selection methods (support vector machine recursive feature elimination with cross-validation (SVM-RFECV) and LightGBM's "feature_importances_" function) were used to select important features. The Shapley additive explanations (SHAP) method was used to assign the contribution of features to the best classification effect model. RESULTS: The best result was obtained from the LinearSVM model trained with the 136 important features selected by SVMRFE-CV. In the nested five-fold cross-validation (consisting of an outer and an inner loop of five-fold cross-validation) of 1611 data, the model achieved the accuracy, sensitivity, and specificity of 68.90 %, 71.75 %, and 65.84 %, respectively. The 136 important features were tested in a small dataset and obtained excellent classification results after balancing the ratio between patients with depression and HCs. CONCLUSIONS: The combined use of FC and NA features is effective for classifying MDDs and HCs. The important FC and NA features extracted from the large sample dataset have some generalization performance and may be used as a reference for the altered brain functional connectivity networks in MDD.

Rapid recovery of male cats with postrenal acute kidney injury by treating with allogeneic adipose mesenchymal stem cell-derived extracellular vesicles.

BACKGROUND: Acute kidney injury (AKI) is a complex disease and can be generally divided into prerenal, intrarenal, and postrenal AKI (PR-AKI). Previous studies have shown that mesenchymal stem cells (MSCs)-derived extracellular vesicles have protective function on prerenal and intrarenal AKI treatment, but whether they have therapeutic efficacy on PR-AKI remains unclear. In this study, we investigated the therapeutic efficacy of allogeneic adipose mesenchymal stem cell-derived extracellular vesicles (ADMSCEVs) on cat models of PR-AKI. METHODS: The cat models of PR-AKI were established by using artificial urinary occlusion and then treated with ADMSCEVs. Histopathological section analysis, blood routine analysis, plasma biochemical test, imaging analysis, and plasma ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) were performed to evaluate the therapeutic efficacy of ADMSCEVs. RESULTS: Physiological and biochemical test showed that the ADMSCEVs could recover creatinine, urea nitrogen and plasma phosphorus to homeostasis efficiently. Blood routine analysis showed that leukocytes in PR-AKI cats with ADMSCEVs treatment returned to normal physiological range more quickly than that of control. UHPLC-MS/MS analysis revealed that the plasma metabolome profile of PR-AKI cats treated with ADMSCEVs was highly similar to that of normal cats. Furthermore, UHPLC-MS/MS analysis also revealed six metabolites (carnitine, melibiose, D-Glucosamine, cytidine, dihydroorotic acid, stachyose) in plasma were highly correlated with the dynamic process of PR-AKI on cats. CONCLUSIONS: We demonstrate the efficacy of ADMSCEVs in the treatment of PR-AKI on cats. Our study also suggests six metabolites to be novel PR-AKI markers and to be potential targets for ADMSCEVs therapy. Our findings will be useful to improve clinical treatment of both animal and human PR-AKI patients with ADMSCEVs in the future.