Network analysis of comorbid aggressive behavior and testosterone among bipolar disorder patients: a cross-sectional study.

Testosterone has complex effects on psychological traits and behavior; it is associated with social dominance and competition and is a potential human sex pheromone. This study aimed to investigate the associations between testosterone levels, aggressive behavior, and manic symptoms using a network analysis among bipolar disorder (BD) patients in psychiatric emergency departments (PED). Data from January 2021 and March 2022 BD patients in PED were analyzed. Manic symptoms were assessed using the Young Mania Rating Scale (YMRS). Aggression was assessed with subscale of the PANSS scale (PANSS-AG). The undirected network structures of testosterone levels, aggressive behavior, and manic symptoms were estimated, and centrality and bridge centrality indices were examined. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. We recruited a total of 898 BD patients, with the mean YMRS score as 13.30 ± 9.58. The prevalence of level II aggression was 35.6% (95%CI = 32.5%-38.7%), level III aggression was 29.5% (95%CI = 26.3%-32.6%), and level VI aggression was 7.0% (95%CI = 5.4%-8.8%). The male participants had a mean testosterone level of 391.71 (Standard Deviation (SD):223.39) compared to 36.90 (SD:30.50) for female participants in the whole sample. Through network analysis, "Increased motor activity-energy" emerged as the central symptom, with the highest centrality expected influence, followed by "Emotional Instability" and "Disruptive/aggression behavior". Notably, "Emotional Instability" appeared to be the bridge symptom linking manic symptoms to aggressive behavior. Within the flow network model, "Speech rate and amount" exhibited the strongest positive correlation with testosterone levels, followed closely by "Disruptive/aggression behavior". The constructed network model demonstrated robust stability, with gender showing no significant impact on the structure. In this study, "Increased motor activity-energy" stood out as the most influential symptom, and "Speech rate and amount" acted as the main bridge symptom linking testosterone levels, aggressive behavior, and manic symptoms. Targeting the central and bridge symptoms may improve the outcomes of aggression interventions implemented among BD patients in psychiatric emergency care.

EEG-based major depressive disorder recognition by neural oscillation and asymmetry.

Background: Major Depressive Disorder (MDD) is a pervasive mental health issue with significant diagnostic challenges. Electroencephalography (EEG) offers a non-invasive window into the neural dynamics associated with MDD, yet the diagnostic efficacy is contingent upon the appropriate selection of EEG features and brain regions. Methods: In this study, resting-state EEG signals from both eyes-closed and eyes-open conditions were analyzed. We examined band power across various brain regions, assessed the asymmetry of band power between the hemispheres, and integrated these features with clinical characteristics of MDD into a diagnostic regression model. Results: Regression analysis found significant predictors of MDD to be beta2 (16-24 Hz) power in the Prefrontal Cortex (PFC) with eyes open (B = 20.092, p = 0.011), beta3 (24-40 Hz) power in the Medial Occipital Cortex (MOC) (B = -12.050, p < 0.001), and beta2 power in the Right Medial Frontal Cortex (RMFC) with eyes closed (B = 24.227, p < 0.001). Asymmetries in beta1 (12-16 Hz) power with eyes open (B = 28.047, p = 0.018), and in alpha (8-12 Hz, B = 9.004, p = 0.013) and theta (4-8 Hz, B = -13.582, p = 0.008) with eyes closed were also significant predictors. Conclusion: The study confirms the potential of multi-region EEG analysis in improving the diagnostic precision for MDD. By including both neurophysiological and clinical data, we present a more robust approach to understanding and identifying this complex disorder. Limitations: The research is limited by the sample size and the inherent variability in EEG signal interpretation. Future studies with larger cohorts and advanced analytical techniques are warranted to validate and refine these findings.

Suicidality and its associated factors among mood disorder patients in emergency department in China: a comparative study using propensity score matching approach.

Suicidality in mood disorder patients is common, especially in emergency department (ED), but the patterns and associated factors of suicidality are not clear. This study compared biomarkers and mental health symptoms (i.e., depression, anxiety, and psychiatric symptoms) between mood disorder patients with and without the whole range of suicidality comprising suicidal ideation (SI), suicide plan (SP), and suicide attempt (SA). This cross-sectional, comparative, convenient-sampling study was conducted between January 2021 and March 2022, in emergency department of Beijing Anding Hospital, China. Patients with mood disorders at a psychiatric emergency department were assessed, with measurements of suicidality, biomarkers, depressive, anxiety, and psychiatric symptoms were assessed using the 24 items-Hamilton Depression Rating Scale (HAMD-24), Hamilton Anxiety Rating Scale (HAMA), Young Manic Rating Scale (YMRS) and Brief Psychiatric Rating Scale (BPRS), respectively. The propensity score matching (PSM) method was used to identify patients in mood disorder with and without SI, SP, and SA. A generalized linear model (GLM) was used to assess the differences in biomarkers, depressive, anxiety, and psychiatric symptoms between patients in mood disorder with and without SI, SP, and SA. In total, 898 participated in this survey and completed the assessment. Illness duration was significantly negatively associated with SA (OR = 0.969, 95%CI = 0.939-0.999, P = 0.046). HAMD-24 total score was significantly positively associated with the SI (OR = 1.167, 95%CI = 1.134-1.201, p < 0.001), SP (OR = 1.159, 95%CI = 1.126-1.192, p < 0.001) and SA (OR = 1.189, 95%CI = 1.144-1.235, p < 0.001) of the matched samptched sample. However, YMRS total score was significantly negatively associated with the SI (OR = 0.928, 95%CI = 0.905-0.951, p < 0.001), SP (OR = 0.920, 95%CI = 0.897-0.944, p < 0.001) and SA (OR = 0.914, 95%CI = 0.890-0.938, p < 0.001) of the matched sample after adjusting for age, gender, marital status, and occupation. The duration of illness, severity of depressive symptoms and severity of manic symptoms appeared to be more likely to influence suicidality. Considering the significant risk of suicide in mood disorders on psychiatric emergency care, timely treatment and effective management of suicidality in this population group need to be developed.

Artificial intelligence technology and ultrasound-guided nerve block for analgesia in total knee arthroplasty.

BACKGROUND: Knee diseases are more common in middle-aged and elderly people, so artificial knee replacement is also more used in middle-aged and elderly people. Although the patient's pain can be reduced through surgery, often accompanied by moderate pain after surgery and neutralization, which not only increases the psychological burden of the patient, but also greatly reduces the postoperative recovery effect, and may also lead to the occurrence of postoperative adverse events in severe cases. AIM: To investigate the analgesic effect of artificial intelligence (AI) and ultrasound-guided nerve block in total knee arthroplasty (TKA). METHODS: A total of 92 patients with TKA admitted to our hospital from January 2021 to January 2022 were opted and divided into two groups according to the treatment regimen. The control group received combined spinal-epidural anesthesia. The research group received AI technique combined with ultrasound-guided nerve block anesthesia. The sensory block time, motor block time, visual analogue scale (VAS) at different time points and complications were contrasted between the two groups. RESULTS: The time of sensory block onset and sensory block perfection in the research group was shorter than those in the control group, but the results had no significant difference (P > 0.05). Duration of sensory block in the research group was significantly longer than those in the control group (P < 0.05). The time of motor block onset and motor block perfection in the research group was shorter than those in the control group, but the results had no significant difference (P > 0.05). Duration of motor block in the research group was significantly longer than those in the control group. The VAS scales of the research group were significantly lower than that of the control group at different time points (P < 0.05). The postoperative hip flexion and abduction range of motion in the research group were significantly better than those in the control group at different time points (P < 0.05). The incidence of complications was significantly lower in the research group than in the control group (P = 0.049). CONCLUSION: In TKA, the combination of AI technology and ultrasound-guided nerve block has a significantly effect, with fewer postoperative complications and significantly analgesic effect, which is worthy of application.

OSGIN1 is a novel TUBB3 regulator that promotes tumor progression and gefitinib resistance in non-small cell lung cancer.

BACKGROUND: Oxidative stress induced growth inhibitor 1 (OSGIN1) regulates cell death. The role and underlying molecular mechanism of OSGIN1 in non-small cell lung cancer (NSCLC) are uncharacterized. METHODS: OSGIN1 expression in NSCLC samples was detected using immunohistochemistry and Western blotting. Growth of NSCLC cells and gefitinib-resistant cells expressing OSGIN1 or TUBB3 knockdown was determined by MTT, soft agar, and foci formation assays. The effect of OSGIN1 knockdown on in vivo tumor growth was assessed using NSCLC patient-derived xenograft models and gefitinib-resistant patient-derived xenograft models. Potentially interacting protein partners of OSGIN1 were identified using IP-MS/MS, immunoprecipitation, PLA, and Western blotting assays. Microtubule dynamics were explored by tubulin polymerization assay and immunofluorescence. Differential expression of signaling molecules in OSGIN1 knockdown cells was investigated using phospho-proteomics, KEGG analysis, and Western blotting. RESULTS: We found that OSGIN1 is highly expressed in NSCLC tissues and is positively correlated with low survival rates and tumor size in lung cancer patients. OSGIN1 knockdown inhibited NSCLC cell growth and patient-derived NSCLC tumor growth in vivo. Knockdown of OSGIN1 strongly increased tubulin polymerization and re-established gefitinib sensitivity in vitro and in vivo. Additionally, knockdown of TUBB3 strongly inhibited NSCLC cell proliferation. Mechanistically, we found that OSGIN1 enhances DYRK1A-mediated TUBB3 phosphorylation, which is critical for inducing tubulin depolymerization. The results of phospho-proteomics and ontology analysis indicated that knockdown of OSGIN1 led to reduced propagation of the MKK3/6-p38 signaling axis. CONCLUSIONS: We propose that OSGIN1 modulates microtubule dynamics by enhancing DYRK1A-mediated phosphorylation of TUBB3 at serine 172. Moreover, elevated OSGIN1 expression promotes NSCLC tumor growth and gefitinib resistance through the MKK3/6-p38 signaling pathway. Our findings unveil a new mechanism of OSGIN1 and provide a promising therapeutic target for NSCLC treatment in the clinic.

Network analysis of comorbid depression, suicidality and biomarkers on HPA axis among mood disorder patients to psychiatric emergency services.

Rapid assessment and intervention of suicide risk are common and challenging in psychiatric emergency departments (PED). It is unclear whether distinct pathophysiological processes exist among depressive patients with suicidality. This study examined the network structures of biomarkers on Hypothalamic-Pituitary-Adrenal (HPA) axis, such as Adrenocorticotropic hormone (ACTH) and Corticosterone (Cort), as well as suicidality and depressive symptoms in mood disorder patients in PED. Mood disorder patients in PED were assessed with the measurements of suicidality and depressive symptoms, respectively. A network analysis was performed to identify central symptoms and bridge symptoms of this network and their links to ACTH and Cort. Network stability was examined using the case-dropping procedure. The Network Comparison Test (NCT) was conducted to evaluate whether network characteristics differed by gender. A total of 1815 mood disorder patients were recruited. The prevalence of SI was 31.2% (95% CI: 28.15-34.21%), SP was 30.4% (95% CI: 27.39-33.41%), SA was 30.62% (95% CI: 27.61-33.64%) among psychiatric outpatients. The mean score of HAMD-24 was 13.87 ± 8.02. Network analysis revealed that 'Somatic anxiety' had the highest expected centrality, followed by 'Hopelessness' and 'Suicide attempt'. 'Corticosterone' and 'Retardation' may be the main bridge symptoms between depressive symptoms and the suicidality community. The network model showed a high degree of stability. Gender did not significantly influence the network structure. The central symptoms and key bridge symptoms identified could be potential targets for interventions of the HPA axis, which is designed for regular screening of a range of suicidal activity. In the light of this, timely treatment should be provided for psychiatric emergency care.

Agomelatine in the treatment of anhedonia, somatic symptoms, and sexual dysfunction in major depressive disorder.

Objective: This study evaluated the treatment outcomes of agomelatine on anhedonic state, anxiety/somatic symptoms, and sexual function in Chinese patients with major depressive disorder (MDD). Method: In total, 93 adult patients with MDD were enrolled, and 68 of them were included in a prospective, open-label, multicenter clinical study. All patients received agomelatine monotherapy during a 9-week treatment phase. The effectiveness of the treatment was reflected by the improvement of anhedonia and somatic symptoms based on the 17-item Hamilton Depression Rating Scale (HAMD-17). In addition, the Arizona Sexual Dysfunction Scale (ASEX), Sheehan Disability Scale (SDS), and Short Form of Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF) were administered to all participants at baseline and at the 3-, 6-, and 9-week follow-ups. Results: After 9 weeks of treatment with agomelatine, the response and remission rates were 73.5% and 39.7%, respectively. Somatic symptoms significantly improved at week 9 (p < 0.001), and significant effects were also observed on the HAMD anhedonia items (p < 0.001). The patients exhibited lower levels of disease severity (the SDS score dropped from 15.52 ± 4.7 to 7.09 ± 5.62 at week 9; the ASEX score dropped from 21.89 ± 4.06 to 16.19 ± 4.79, p < 0.001) and higher levels of QOL (the Q-LES-Q-SF score dropped from 41.02 ± 5.99 to 50.49 ± 8.57, p < 0.001) during the follow-up. Furthermore, treatment with agomelatine improved depressive symptoms without causing serious adverse events. Conclusion: These analyses indicate that agomelatine is a treatment option for improving anhedonic status, anxiety/somatic symptoms, and sexual dysfunction in MDD patients.

The causal involvement of the BDNF-TrkB pathway in dentate gyrus in early-life stress-induced cognitive deficits in male mice.

Cognitive dysfunction is a significant, untreated clinical need in patients with psychiatric disorders, for which preclinical studies are needed to understand the underlying mechanisms and to identify potential therapeutic targets. Early-life stress (ELS) leads to long-lasting deficits of hippocampus-dependent learning and memory in adult mice, which may be associated with the hypofunction of the brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tropomyosin receptor kinase B (TrkB). In this study, we carried out eight experiments using male mice to examine the causal involvement of the BDNF-TrkB pathway in dentate gyrus (DG) and the therapeutic effects of the TrkB agonist (7,8-DHF) in ELS-induced cognitive deficits. Adopting the limited nesting and bedding material paradigm, we first demonstrated that ELS impaired spatial memory, suppressed BDNF expression and neurogenesis in the DG in adult mice. Downregulating BDNF expression (conditional BDNF knockdown) or inhibition of the TrkB receptor (using its antagonist ANA-12) in the DG mimicked the cognitive deficits of ELS. Acute upregulation of BDNF (exogenous human recombinant BDNF microinjection) levels or activation of TrkB receptor (using its agonist, 7,8-DHF) in the DG restored ELS-induced spatial memory loss. Finally, acute and subchronic systemic administration of 7,8-DHF successfully restored spatial memory loss in stressed mice. Subchronic 7,8-DHF treatment also reversed ELS-induced neurogenesis reduction. Our findings highlight BDNF-TrkB system as the molecular target of ELS-induced spatial memory deficits and provide translational evidence for the intervention at this system in the treatment of cognitive deficits in stress-related psychiatric disorders, such as major depressive disorder.

Heart failure and depression: A perspective from bibliometric analysis.

Background: Depression commonly occurs in heart failure patients, and negatively influences quality of life and disease prognosis. This study explored heart failure and depression-related research from a bibliometric perspective. Methods: Relevant publications were searched on June 24, 2022. The Bibliometrix package in R was used to conduct quantitative analyses including the trends in publications, and related countries, articles, authors and keywords. VOSviewer software was used to conduct the visualization map on co-word, co-author, and institution co-authorship analyses. CiteSpace software was used to illustrate the top keywords with citation burst. Results: A total of 8,221 publications in the heart failure and depression-related research field were published between 1983 and 2022. In this field, the United States had the most publications (N = 3,013; 36.65%) and highest total citation (N = 149, 376), followed by China, Germany, Italy and Japan. Author Moser and Duke University were the most productive author and institution, respectively. Circulation is the most influential journal. Apart from "heart failure" and "depression," "quality of life," "mortality" and "myocardial infarction" were the most frequently used keywords in this research area; whereas more recently, "self care" and "anxiety" have been used more frequently. Conclusion: This bibliometric analysis showed a rapid growth of research related to heart failure and depression from 1989 to 2021, which was mostly led by North America and Europe. Future directions in this research area include issues concerning self-care and anxiety about heart failure. As most of the existing literature were published in English, publications in other languages should be examined in the future.

Effects of K2TiF6 and Electrolyte Temperatures on Energy Consumption and Properties of MAO Coatings on 6063 Aluminum Alloy.

To decrease energy consumption and improve the performance of micro-arc oxidation (MAO) films on 6063 Al alloy, a policy of K2TiF6 additive and electrolyte temperature control was adapted. The specific energy consumption relied on the K2TiF6 additive and more particularly on the electrolyte temperatures. Scanning electron microscopy demonstrates that electrolytes with 5 g/L K2TiF6 can effectively seal the surface pores and increase the thickness of the compact inner layer. Spectral analysis shows that the surface oxide coating consists of γ-Al2O3 phase. Following 336 h of the total immersion process, the impedance modulus of the oxidation film, prepared at 25 °C (Ti5-25), remained 1.08 × 106 Ω·cm2. Moreover, Ti5-25 has the best performance/energy-consumption ratio with a compact inner layer (2.5 ± 0.3 µm). This research found that the time of the big arc stage increased with the temperature, resulting in producing more internal defects in the film. In this work, we employ a dual-track strategy of additive and temperature providing an avenue to reduce the energy consumption of MAO on alloys.

Cognitive reserve in patients with mood disorders: Validation study of the Chinese version of the cognitive reserve assessment scale in health.

BACKGROUND: Cognitive reserve (CR) is closely associated with cognitive and functional outcome, disease severity, progression and prognosis in psychiatric patients; however, it has not been extensively tested in mood disorders. This study examined the psychometric properties of the Cognitive Reserve Assessment Scale in Health (CRASH) in mood disorder patients. METHODS: Altogether 166 subjects were recruited, 44 with major depressive disorder (MDD), 64 with bipolar disorder (BD), and 58 healthy controls. CR was assessed using the CRASH and the Cognitive Reserve Questionnaire (CRQ). RESULTS: Internal consistency (Cronbach's alpha) was 0.779 for the CRASH. The Receiver Operating Characteristic (ROC) curve analysis revealed an area under the ROC curve (AUC) value of 0.73 (95 % CI: 0.647-0.809). The optimal cut-off score of 51 generated the best combination of sensitivity (0.78) and specificity (0.43) for discriminating between patients with mood disorders and healthy controls. The CRASH score was highly correlated with the CRQ score in both mood disorder patients (rs = 0.586, P < 0.001) and healthy controls (rs = 0.627, P < 0.001), indicating acceptable convergent validity for the CRASH. Within the mood disorder sample, the CRASH score was associated with functional outcomes (FAST: rs = -0.243, P = 0.011). CONCLUSIONS: The CRASH is a useful tool to measure CR in mood disorder with acceptable psychometric properties and could be used in both research and clinical practice.

Effect of Pre-Anodized Film on Micro-Arc Oxidation Process of 6063 Aluminum Alloy.

In the current investigation, micro-arc oxidation (MAO) ceramic coatings on aluminum are galvanostatically synthesized at various processing stages in an alkaline silicate system. The resultant coatings are systematically investigated in terms of the following respects: The working voltage and surface sparking evolution over the studied course of MAO are recorded by the signal acquisition system and the real-time imaging, respectively; the phase composition, the surface morphology, and the polished cross-section of the coatings are characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM) assisted with an energy-dispersive X-ray spectrometer (EDS), respectively. In particular, with the help of a low-rate increase in working voltage, the evolution of the sparks, the energy consumption, and the microstructure development of aluminum in alkaline silicate electrolyte by pre-anodizing are systematically investigated. The results show that the pre-anodized film can accelerate the evolution process of MAO spark and shorten the reaction process in the early stage of MAO reaction, reducing energy consumption and improving the corrosion resistance of the MAO coating. The γ-Al2O3 phase content after pre-anodized is significantly increased in MAO coatings. In particular, the thicker the pre-anodized film (beyond 8 µm) was broken down and fragmentation thinning in the early stage of the MAO process with the presence of micro discharges. This is due to the fact that the electron transition will be released by the emission of radiative recombination and reveals obvious galvanoluminescence (GL) behavior on the surface of the pre-anodized film. Further, based on the present MAO coating microstructure, a model of coating growth after pre-anodized that evolves over time is proposed.

Hippocalcin-like 1 is a key regulator of LDHA activation that promotes the growth of non-small cell lung carcinoma.

BACKGROUND: Hippocalcin-like 1 (HPCAL1), a neuronal calcium sensor protein family member, has been reported to regulate cancer growth. As yet, however, the biological functions of HPCAL1 and its molecular mechanisms have not been investigated in non-small cell lung carcinoma (NSCLC). METHODS: HPCAL1 expression in NSCLC samples was detected using immunohistochemistry, Western blotting and RT-PCR. The anticancer effects of HPCAL1 knockdown were determined by MTT, soft agar, cell cycle, oxygen consumption and reactive oxygen species assays. The effect of HPCAL1 knockdown on in vivo tumor growth was assessed using NSCLC cancer patient-derived xenograft models. Potentially interacting protein partners of HPCAL1 were identified using IP-MS/MS, immunoprecipitation and Western blotting assays. Metabolic alterations resulting from HPCAL1 knockdown were investigated using non-targeted metabolomics and RNA sequencing analyses. RESULTS: We found that HPCAL1 is highly expressed in NSCLC tissues and is positively correlated with low survival rates and AJCC clinical staging in lung cancer patients. Knockdown of HPCAL1 strongly increased oxygen consumption rates and the production of reactive oxygen species. HPCAL1 knockdown also inhibited NSCLC cell growth and patient-derived NSCLC tumor growth in vivo. Mechanistically, we found that HPCAL1 can directly bind to LDHA and enhance SRC-mediated phosphorylation of LDHA at tyrosine 10. The metabolomics and RNA sequencing analyses indicated that HPCAL1 knockdown reduces amino acid levels and induces fatty acid synthesis through regulating the expression of metabolism-related genes. Additionally, rescued cells expressing wild-type or mutant LDHA in HPCAL1 knockdown cells suggest that LDHA may serve as the main substrate of HPCAL1. CONCLUSIONS: Our data indicate that the effect of HPCAL1 knockdown on reducing SRC-mediated LDHA activity attenuates NSCLC growth. Our findings reveal novel biological functions and a mechanism underlying the role of HPCAL1 in NSCLC growth in vitro and in vivo.

Cyberbully victimization and its association with residual depressive symptoms among clinically stable adolescents with psychiatric disorders during the COVID-19 pandemic: A perspective from network analysis.

Objective: This study examined the prevalence of cyberbullying and its relationship with residual depressive symptoms in this patient population during the COVID-19 outbreak using network analysis. Methods: This was a multicenter, cross-sectional study. Adolescent patients attending maintenance treatment at outpatient departments of three major psychiatric hospitals were included. Experience of cyberbullying was measured with a standard question, while the severity of Internet addiction and depressive symptoms were measured using the Internet Addiction Test and the Patient Health Questionnaire-9, respectively. The network structure of depression and cyberbully were characterized and indices of "Expected Influence" was used to identify symptoms central to the network. To identify particular symptoms that were directly associated with cyberbully, the flow function was used. Results: Altogether 1,265 patients completed the assessments. The overall prevalence of cyberbullying was 92.3% (95% confidence interval (CI): 90.8-93.7%). Multiple logistic regression analysis revealed that male gender (p = 0.04, OR = 1.72, 95%CI: 1.04-2.85) was significantly associated with higher risk of cyberbullying, while a relapse of illness during the COVID-19 pandemic was significantly associated with a lower risk of cyberbullying (p = 0.03, OR = 0.50, 95%CI: 0.27-0.93). In the network of depression and cyberbully, "Sad mood," "Anhedonia" and "Energy" were the most central (influential) symptoms. Furthermore, "Suicidal ideation" had the strongest negative association with cyberbully followed by "Guilt". Conclusion: During the COVID-19 pandemic, the experience of cyberbullying was highly prevalent among clinically stable adolescent psychiatric patients, particularly male patients. This finding should raise awareness of this issue emphasizing the need for regular screening and interventions for adolescent patients. Central symptoms (e.g., "Sad mood," "Anhedonia" and "Energy") identified in this study should be targeted in interventions and preventive measures.

A comparison of aggression between patients with acute schizophrenia and mania presenting to psychiatric emergency services.

OBJECTIVE: Aggression is common and challenging in psychiatric emergency departments (PED). However, the prevalence of aggression and its correlates in PED patients are not well documented. This study compared the prevalence of aggression between patients with acute schizophrenia and manic episodes. METHODS: In this cross-sectional study, patients at a psychiatric emergency department were assessed with measurements of aggression, psychotic and manic symptoms. RESULTS: A total of 4,172 patients were included. The prevalence of aggression was 54.8% (95%CI=53.3%-65.2%) in the whole sample, with 48.0% (95%CI=45.8%-50.1%) in patients with an acute schizophrenia episode, and 61.8% (95%CI=59.8%-63.9%) in patients with a manic episode. Multiple logistic regression analysis revealed that, within the acute schizophrenia episode group, male gender (OR=1.47, P<0.01), involuntary admission (OR=3.61, P<0.01) and more severe manic symptoms (OR=1.30, P<0.01) were significantly associated with aggression. Within the manic episode group, living in Beijing (OR=1.51, P<0.01), unemployment (OR=1.34, P=0.03), involuntary admission (OR=7.93, P<0.01), lower education (OR=0.95, P=0.01) and more severe psychotic symptoms (OR=1.05, P<0.01) were significantly associated with aggression. CONCLUSION: In this study, aggression appeared to be more common among patients with a manic episode than those with an acute schizophrenia episode. Considering the significant risk of aggression on psychiatric emergency care, appropriate and effective management of aggression in this population group need to be developed.

Prevalence of Suicidality in Major Depressive Disorder: A Systematic Review and Meta-Analysis of Comparative Studies.

Background: Suicidality is common in major depressive disorder (MDD), but there has been no systematic review published about all aspects of suicidality. This meta-analysis and systematic review compared the prevalence of the whole range of suicidality comprising suicidal ideation (SI), suicide plan (SP), suicide attempt (SA), and completed suicide (CS), between patients with MDD and non-MDD controls. Methods: Major international (PubMed, PsycINFO, Web of Science, EMBASE) and Chinese (Chinese Nation Knowledge Infrastructure and WANFANG) databases were systematically and independently searched from their inception until January 12, 2021. Results: Fifteen studies covering 85,768 patients (12,668 in the MDD group and 73,100 in the non-MDD group) were included in the analyses. Compared to non-MDD controls, the odds ratios (ORs) for lifetime, past month, past year, and 2-week prevalence of SI in MDD were 2.88 [95% confidence interval (CI) = 0.30-27.22, p = 0.36], 49.88 (95% CI = 2-8.63, p < 0.001), 13.97 (95% CI = 12.67-15.41, p < 0.001), and 24.81 (95% CI = 15.70-39.22, p < 0.001), respectively. Compared to non-MDD controls, the OR for lifetime SP in MDD was 9.51 (95% CI = 7.62-11.88, p < 0.001). Compared to non-MDD controls, the ORs of lifetime and past-year prevalence of SA were 3.45 (95% CI = 1.58-7.52, p = 0.002), and 7.34 (95% CI = 2.14-25.16, p = 0.002), respectively, in MDD patients. No difference in the prevalence of CS between MDD and controls was found (OR = 0.69, 95% CI = 0.23-2.02, p = 0.50). Conclusions: MDD patients are at a higher risk of suicidality, compared to non-MDD controls. Routine screening for a range of suicidality should be included in the management of MDD, followed by timely treatment for suicidal patients. Systematic Review Registration: Identifier [INPLASY202120078].

Harmaline isolated from Peganum harmala suppresses growth of esophageal squamous cell carcinoma through targeting mTOR.

Harmaline is a naturally occurring ß-carboline alkaloid that is isolated from Peganum harmala. It has shown efficacy in treating Parkinson's disease and has been reported to exhibit antimicrobial and anticancer properties. However, the molecular mechanism of harmaline in the context of esophageal squamous cell carcinoma (ESCC) has not been characterized. Here, we report that harmaline attenuates ESCC growth by directly targeting the mammalian target of rapamycin (mTOR). Harmaline strongly reduced cell proliferation and anchorage-independent cell growth. Additionally, harmaline treatment induced G2/M phase cell-cycle arrest through upregulation of p27. The results of in vitro and cell-based assays showed that harmaline directly inhibited the activity of mTOR kinase and the phosphorylation of its downstream pathway components. Depletion of mTOR using an shRNA-mediated strategy in ESCC cell lines indicated that reduced mTOR protein expression levels are correlated with decreased cell proliferation. Additionally, we observed that the inhibitory effect of harmaline was dependent upon mTOR expression. Notably, oral administration of harmaline suppressed ESCC patient-derived tumor growth in vivo. Taken together, harmaline is a potential mTOR inhibitor that might be used for therapeutically treating ESCC.

Ipriflavone Suppresses Growth of Esophageal Squamous Cell Carcinoma Through Inhibiting mTOR In Vitro and In Vivo.

Ipriflavone, a synthetic isoflavone that inhibits osteoclastic bone resorption, has been used clinically for the treatment of osteoporosis. However, the anticancer activity of Ipriflavone and its molecular mechanisms in the context of esophageal squamous cell carcinoma (ESCC) have not been investigated. In this study, we report that Ipriflavone is a novel mammalian target of rapamycin (mTOR) inhibitor that suppresses cell proliferation and induces cell apoptosis in ESCC cells. Ipriflavone inhibited anchorage-dependent and -independent growth of ESCC cells. Ipriflavone induced G1 phase cell cycle arrest and intrinsic cell apoptosis by activating caspase 3 and increasing the expression of cytochrome c. Based on the results of in vitro screening and cell-based assays, Ipriflavone inhibited mTOR signaling pathway through directly targeting mTOR. Knockdown of mTOR strongly inhibited the growth of ESCC cells, and the cell growth inhibitory effect exerted by Ipriflavone was found to be dependent upon mTOR signaling pathway. Remarkably, Ipriflavone strongly inhibited ESCC patient-derived xenograft tumor growth in an in vivo mouse model. Our findings suggest that Ipriflavone is an mTOR inhibitor that could be potentially useful for treating ESCC.

Prevalence of depression and its impact on quality of life in frontline otorhinolaryngology nurses during the COVID-19 pandemic in China.

OBJECTIVE: Exposure to the coronavirus disease 2019 (COVID-19) was associated with high risk of mental health problems among frontline nurses. This study examined the prevalence of depressive symptoms (depression hereafter) and its impact on quality of life (QOL) in otorhinolaryngology (ENT) nurses during the COVID-19 pandemic in China. METHODS: An online study was conducted between March 15 and March 20, 2020. Depression and QOL were assessed using standardized instruments. RESULTS: A total of 1,757 participants were recruited. The prevalence of depression was 33.75% (95% CI: 31.59%-35.97%). Results emerging from multiple logistic regression analysis showed that direct care of COVID-19 patients (OR: 1.441, 95% CI: 1.031-2.013, P = 0.032), and current smoking (OR: 2.880, 95% CI: 1.018-8.979, P = 0.048) were significantly associated with depression. After controlling for covariates, ENT nurses with depression had a lower overall QOL compared to those without depression (F(1, 1757)= 536.80, P < 0.001). CONCLUSIONS: Depression was common among ENT nurses during the COVID-19 pandemic in China. Considering the negative impact of depression on QOL and care quality, regular screening for depression should be conducted in ENT nurses and treatment should be provided.

2,6-DMBQ suppresses cell proliferation and migration via inhibiting mTOR/AKT and p38 MAPK signaling pathways in NSCLC cells.

2,6-Dimethoxy-1,4-benzoquinone (2,6-DMBQ) is the major bioactive compound found in fermented wheat germ extract. Although fermented wheat germ extract has been reported to show anti-proliferative and anti-metabolic effects in various cancers, the anticancer potential and molecular mechanisms exerted by 2,6-DMBQ have not been investigated in non-small cell lung cancer (NSCLC) cells. Here, we report that 2,6-DMBQ suppresses NSCLC cell growth and migration through inhibiting activation of AKT and p38 MAPK. 2,6-DMBQ significantly suppressed anchorage-dependent and independent cell growth. Additionally, 2,6-DMBQ induced G2 phase cell cycle arrest through inhibiting the expression and phosphorylation of cyclin B1 and CDC2, respectively. Furthermore, 2,6-DMBQ strongly suppressed NSCLC cell migration through induction of E-cadherin expression. To determine the molecular mechanism(s) exerted by 2,6-DMBQ upon NSCLC cell lines, various signaling kinases were screened; the results indicate that 2,6-DMBQ strongly inhibits the phosphorylation of AKT and p38 MAPK. Additionally, the growth kinetics of cells treated with an AKT or p38 MAPK inhibitor in combination with 2,6-DMBQ indicate that 2,6-DMBQ suppresses NSCLC cell growth and migration through inhibition of AKT and p38 MAPK. Taken together, our results suggest that 2,6-DMBQ is a potential anticancer reagent against NSCLC cells and could be useful for treating lung cancer patients.