Identification of Prostaglandin I2 Synthase Rare Variants in Patients With Williams Syndrome and Severe Peripheral Pulmonary Stenosis.

BACKGROUND: Peripheral pulmonary stenosis (PPS) is a condition characterized by the narrowing of the pulmonary arteries, which impairs blood flow to the lung. The mechanisms underlying PPS pathogenesis remain unclear. Thus, the aim of this study was to investigate the genetic background of patients with severe PPS to elucidate the pathogenesis of this condition. METHODS AND RESULTS: We performed genetic testing and functional analyses on a pediatric patient with PPS and Williams syndrome (WS), followed by genetic testing on 12 patients with WS and mild-to-severe PPS, 50 patients with WS but not PPS, and 21 patients with severe PPS but not WS. Whole-exome sequencing identified a rare PTGIS nonsense variant (p.E314X) in a patient with WS and severe PPS. Prostaglandin I2 synthase (PTGIS) expression was significantly downregulated and cell proliferation and migration rates were significantly increased in cells transfected with the PTGIS p.E314X variant-encoding construct when compared with that in cells transfected with the wild-type PTGIS-encoding construct. p.E314X reduced the tube formation ability in human pulmonary artery endothelial cells and caspase 3/7 activity in both human pulmonary artery endothelial cells and human pulmonary artery smooth muscle cells. Compared with healthy controls, patients with PPS exhibited downregulated pulmonary artery endothelial prostaglandin I2 synthase levels and urinary prostaglandin I metabolite levels. We identified another PTGIS rare splice-site variant (c.1358+2T>C) in another pediatric patient with WS and severe PPS. CONCLUSIONS: In total, 2 rare nonsense/splice-site PTGIS variants were identified in 2 pediatric patients with WS and severe PPS. PTGIS variants may be involved in PPS pathogenesis, and PTGIS represents an effective therapeutic target.

Functions and novel regulatory mechanisms of key glycolytic enzymes in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the pulmonary vasculature and elevated pulmonary arterial pressure, ultimately leading to right heart failure and death. Despite its clinical significance, the precise molecular mechanisms driving PAH pathogenesis warrant confirmation. Compelling evidence indicates that during the development of PAH, pulmonary vascular cells exhibit a preference for energy generation through aerobic glycolysis, known as the "Warburg effect", even in well-oxygenated conditions. This metabolic shift results in imbalanced metabolism, increased proliferation, and severe pulmonary vascular remodeling. Exploring the Warburg effect and its interplay with glycolytic enzymes in the context of PAH has yielded current insights into emerging drug candidates targeting enzymes and intermediates involved in glucose metabolism. This sheds light on both opportunities and challenges in the realm of antiglycolytic therapy for PAH.

Employing Bayesian analysis to establish a cut-off point and assess stigma prevalence in substance use disorder: a comprehensive study of the Chinese version of the Substance Use Stigma Mechanism Scale.

PURPOSE: In China, individuals with substance use disorders (SUD) face severe stigma, but reliable stigma assessment tool is lacking. Therefore, this study aimed to validate the Chinese version of the Substance Use Stigma Mechanism Scale (SU-SMS-C) and set its cut-off point. METHODS: We recruited 1005 individuals with SUDs from Chinese rehabilitation centers. These participants completed a battery of questionnaires that included the SU-SMS-C, The Multidimensional Scale of Perceived Social Support (MSPSS), Center for Epidemiologic Studies Depression Scale (CES-D), General Self-Efficacy Scale (GSES), and Perceived Devaluation and Discrimination (PDD). Confirmatory factor analysis was used to assess the construct validity of the scale. Additionally, the Naive Bayes classifier was used to establish the cut-off point for the SU-SMS-C. We additionally explored the correlation between patient demographic characteristics and stigma. RESULTS: A confirmatory factor analysis was utilized, revealing a second-order five-factor model. Based on the Naive Bayes classifier, the area under the receiver operating characteristic (AUCROC) of 0.746, the cut-off point for the SU-SMS-C was established at 44.5. The prevalence of stigma observed in the study population was 49.05%. Significant disparities were observed in the distribution of stigma across genders, with males experiencing more pronounced stigma than females. Moreover, patients consuming different primary substances reported diverse levels of stigma. Notably, those primarily using heroin endured a higher degree of stigma than users of other substances. CONCLUSION: The study is the first to identify a cut-off point for the SU-SMS-C by Naive Bayes classifier, bridging a major gap in stigma measurement research. SU-SMS-C may help treat and manage SUDs by reducing stigma.

Altered spontaneous neurological activity in methamphetamine use disorders and its association with cognitive function.

BACKGROUND: Methamphetamine (MA) is a widely used and detrimental drug, yet the precise mechanisms by which MA affects cognitive function remain unclear. This study aims to investigate the relationship between cognitive function and brain functional imaging in individuals with MA use disorder (MUD). METHODS: This study involved 45 patients diagnosed with MUD and 43 healthy controls (HC). Cognitive function assessment utilized the MATRICS Consensus Cognitive Battery, and functional data were acquired using a 3.0 Tesla magnetic resonance imaging scanner. RESULTS: The MUD group exhibited lower regional homogeneity (ReHo) values in the bilateral postcentral, the left superior temporal, and the left lingual regions compared to the HC group. Additionally, the MUD group displayed higher amplitude of low-frequency fluctuation (ALFF) values in the bilateral fusiform and the left putamen compared to the HC group, along with lower ALFF values in the bilateral postcentral cortices and the left middle cingulate cortex compared to the HC group (all p < 0.05, with false discovery rate corrected). Linear regression analysis revealed a positive correlation between the ReHo value in the right postcentral cortex and the neuropsychology assessment battery-mazes test (p = 0.014). Furthermore, the ALFF value in the left putamen showed negative correlations with the scores of the digit-symbol coding test (p = 0.027), continuous performance test (p = 0.037), and battery-mazes test (p = 0.024). CONCLUSION: Patients with MUD exhibit altered brain spontaneous neurological activities, and the intensity of spontaneous neurological activity in the left putamen is strongly associated with cognitive function.

Inter-relationships of insomnia and psychiatric symptoms with suicidal ideation among patients with chronic schizophrenia: A network perspective.

BACKGROUND: Insomnia is common in patients with schizophrenia, which contributes to worsening psychiatric symptoms and suicidality. We aimed to assess the inter-relationships of insomnia and psychopathology with suicidal ideation (SI) among 1407 Chinese patients with chronic schizophrenia via the network approach. METHOD: We used Positive and Negative Syndrome Scale, Insomnia Severity Index, and Beck Scale for Suicidal Ideation to assess psychiatric symptoms, insomnia, and SI, respectively. Lifetime suicidal attempts (SA) were collected. RESULTS: (1) The incidence of insomnia, lifetime SI, lifetime SA, and current SI was 13.5% (n = 190), 22.8% (n = 321), 13.5% (n = 190), and 9.7% (n = 136), respectively. (2) Patients with insomnia had worse clinical symptoms and higher suicidal risk. (3) Daytime dysfunction, sleep-related distress, conceptual disorganization, delusions, anxiety, and poor rapport were the core symptoms, while late sleep onset and sleep dissatisfaction emerged as bridge symptoms connecting insomnia and psychopathology. (4) Depressive mood, hallucinations, poor impulse control, guilty feelings, insomnia-related impaired quality of life, and sleep dissatisfaction were directly associated with SI. CONCLUSION: Our findings called for formal assessment of insomnia in patients with schizophrenia, which should cover both nocturnal and daytime insomnia symptoms. Targeted interventions for key symptoms may help reduce insomnia, psychiatric symptoms, and SI in patients with schizophrenia.

The Mediating Effects of Perceived Family Support in the Relationship Between Anxiety and Problematic Smartphone Use: A Cross-Cultural Validation.

ABSTRACT: Problematic smartphone use (PSU) is frequently considered a public health issue, especially in East Asia and Europe. Yet, there is a paucity of research focusing on cultural and familial determinants of PSU. This cross-cultural study aimed to investigate smartphone usage patterns and possible mediating effects of perceived family support (PFS) from a stress-coping perspective. Convenience samples of 790 Chinese and 439 Belgian undergraduates completed an online survey that focused on sociodemographics and psychological variables ( i.e. , anxiety, depression, PFS, and PSU). In both samples, PSU was positively associated with anxiety and depression, and negatively associated with PFS. However, after controlling for sex and age in structural equation models, the consistent mediating effects of PFS were only found between anxiety and PSU in both cultural settings. These findings suggest that psychological interventions that take into account familial factors could be helpful for young people presenting with anxiety and PSU.

Association of subclinical hypothyroidism with metabolic syndrome and its components among outpatients with first-episode drug-naïve major depressive disorder: a large-scale cross-sectional study.

Both metabolic syndrome (MetS) and subclinical hypothyroidism (SCH) are prevalent in major depressive disorder (MDD) patients. However, their relationship in this population remains unknown. The study assessed the association between SCH and MetS in 1706 first-episode drug-naïve (FEDN) MDD patients. We also compared the relationship between MetS and clinical symptoms in patients with and without comorbid SCH. The Positive and Negative Syndrome Scale positive subscale, the Hamilton Anxiety Rating Scale, and the Hamilton Depression Rating Scale were used to detect clinical symptoms. Serum levels of free triiodothyronine, free thyroxine, thyroid stimulating hormone (TSH), anti-thyroglobulin, thyroid peroxidases antibody, cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and fasting glucose were measured. The Area Under the Curve (AUC) was used to test the performance of serum TSH in identifying MetS patients. The prevalence of MetS and SCH was 34.5% (n = 585) and 61% (n = 1034), respectively. The presence of SCH increased the risk of MetS, hyperglycemia, hypertension, obesity, and low HDL-C by 4.91, 3.51, 3.54, 2.02, and 2.34 times, respectively. Serum TSH had a nice ability to distinguish MetS patients from non-MetS patients (AUC value = 0.77). MetS and its components exhibited a positive association with clinical profiles only in SCH patients, but not in non-SCH patients. Taken together, our study suggested SCH was closely related to MetS and might play a vital role in the relationship between MetS and clinical symptoms. Regular thyroid function checks might help early detect MetS.

Workplace violence inflicted by patients or their family members/visitors and its relationship with suicidal ideation among undergraduate medical students during clinical training in China.

BACKGROUND: Workplace violence in healthcare settings is a significant public concern that profoundly impacts healthcare workers. However, there is a dearth of knowledge regarding the prevalence of workplace violence and its correlation with suicidal ideation among undergraduate medical students in China during their clinical training. The objective of this study was to evaluate the prevalence of workplace violence inflicted by patients or their family members/visitors and to assess its association with suicidal ideation among undergraduate medical students. METHOD: The snowballing sampling technique was used to recruit Chinese medical students. A question designed by the research team was used to ask medical students about their encounters with workplace violence. Students' basic demographic information and mental distresses (learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence, excessive daytime sleepiness and history of mental disorders) were also assessed. As appropriate, the data were analysed using descriptive statistics, chi-square tests, independent-sample t-tests and multiple logistic regression. RESULTS: Out of the 1402 undergraduate medical students who participated, 493 (35.2%) reported having experienced workplace violence inflicted by patients or their family members/visitors, of which 394 (28.1%) were verbal abuse, 14 (1.0%) were physical aggression, and 85 (6.1%) were suffered from both verbal abuse and physical aggression. Furthermore, students exposed to workplace violence were more likely to report suicidal ideation and had a higher prevalence of learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence and excessive daytime sleepiness. Depression symptoms, history of mental disorders, learning burnout and having a partner were significantly associated with suicidal ideation in this population. CONCLUSION: The prevalence of workplace violence inflicted by patients or their family members/visitors was high among undergraduate medical students in China. This may be associated with their mental distress and suicidal ideation. Consequently, it is crucial to strengthen workplace safety measures and promptly implement interventions to mitigate the potentially serious consequences.

Workplace violence was common among Chinese undergraduate medical students during clinical training and may be associated with suicidal ideation, learning burnout, depression symptoms, anxiety symptoms, alcohol abuse/dependence and excessive daytime sleepiness.Depression symptoms, history of mental disorders, learning burnout and having a partner were significantly associated with suicidal ideation among undergraduate medical students exposed to workplace violence.

Gender differences in alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period (October 20, 2020-April 5, 2021) in China.

BACKGROUND: This study aimed to assess the prevalence and the gender-specific risk factors of alcohol abuse/dependence among medical undergraduates during the post-COVID­19 pandemic period in China. METHOD: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) was used to identify respondents with alcohol abuse/dependence. A questionnaire on basic demographics and mental distresses (learning burnout, depression symptoms, anxiety symptoms, excessive daytime sleepiness, and history of mental disorders) was used. The logistic regression model was used to explore the associations between the above characteristics and alcohol abuse/dependence. RESULTS: A total of 3,412 medical undergraduates were included in the analysis. Males showed a higher prevalence of alcohol abuse/dependence than females (16.6% vs 7.4%, p < 0.001). Alcohol abuse/dependence was associated with learning burnout (OR: 2.168, p < 0.001) and having a partner (OR: 1.788 p = 0.001) among female medical undergraduates. Among male medical undergraduates, excessive daytime sleepiness (OR: 1.788 p = 0.001) and older age (OR: 1.788, p = 0.001) were independently associated with alcohol abuse/dependence. CONCLUSION: Alcohol abuse/dependence was common among medical undergraduates during the post-COVID­19 pandemic period. Substantial gender differences in the prevalence and risk factors of alcohol abuse/dependence were found among medical undergraduates in this study, which highlighted the need for timely gender-specific screening and interventions. However, the cross-sectional design adopted in this study has limited the examination of causality, thus further longitudinal studies are warranted.

Effects of Multiple High-Dose Methamphetamine Administration on Enteric Dopaminergic Neurons and Intestinal Motility in the Rat Model.

Several studies have identified the effects of methamphetamine (MA) on central dopaminergic neurons, but its effects on enteric dopaminergic neurons (EDNs) are unclear. The aim of this study was to investigate the effects of MA on EDNs and intestinal motility. Male Sprague-Dawley rats were randomly divided into MA group and saline group. The MA group received the multiple high-dose MA treatment paradigm, while the controls received the same saline treatment. After enteric motility was assessed, different intestinal segments (i.e., duodenum, jejunum, ileum, and colon) were taken for histopathological, molecular biological, and immunological analysis. The EDNs were assessed by measuring the expression of two dopaminergic neuronal markers, dopamine transporter (DAT) and tyrosine hydroxylase (TH), at the transcriptional and protein levels. We also used c-Fos protein, a marker of neural activity, to detect the activation of EDNs. MA resulted in a significant reduction in TH and DAT mRNA expression as well as in the number of EDNs in the duodenum and jejunum (p < 0.05). MA caused a dramatic increase in c-Fos expression of EDNs in the ileum (p < 0.001). The positional variability of MA effects on EDNs paralleled the positional variability of its effect on intestinal motility, as evidenced by the marked inhibitory effect of MA on small intestinal motility (p < 0.0001). This study found significant effects of MA on EDNs with locational variability, which might be relevant to locational variability in the potential effects of MA on intestinal functions, such as motility.

Stigmatizing attitudes toward mental illness among caregivers of patients with mental disorders in China.

Objective: This study aimed to investigate stigmatizing attitudes toward depression, schizophrenia, and general anxiety disorder (GAD) among caregivers of patients with mental disorders in China. Methods: A cross-sectional study was conducted among 607 caregivers in China, using vignettes that described three mental illnesses. Data on the caregivers' attitudes and other people's attitudes toward individuals with mental disorders and their willingness to come in contact with people with mental disorders were collected. Results: In the three vignettes, caregivers agreed that positive outcomes outnumbered negative outcomes. The top two statements endorsing the stigma were "the person could snap out of the problem" and "people with this problem are dangerous." In the section for perceived stigma, caregivers in the GAD vignette agreed that most people believed this problem is not a real medical illness, compared to schizophrenia. The rates of the statement endorsing unpredictability were significantly different in the schizophrenia (57.2%) and depression (45.5%) vignette, in comparison to the GAD (45.6%) vignette. For personal stigma, the caregivers tended to avoid people described in the depression vignette more often than in the GAD vignette. The caregivers were most unwilling to let the person described in the vignettes marry into their family, especially in the schizophrenia vignette. Conclusion: Despite the stigma and desire for social distance associated with schizophrenia, depression, and GAD, caregivers often expect positive outcomes. Actions should be taken to improve caregivers' knowledge about mental health and reduce the stigma.

Differences in clinical features and gut microbiota between individuals with methamphetamine casual use and methamphetamine use disorder.

Background: The transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge gap if gut microbiota (GM) play a role in differing MCU from MA use disorder (MUD). We aimed to investigate the clinical features and GM differences between individuals with MCU and MUD. Method: We recruited two groups of MA users -MCU and MUD - and matched them according to age and body mass index (n=21 in each group). Participants were accessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, and their fecal samples were undergone 16S ribosomal DNA sequencing. We compared the hosts' clinical features and GM diversity, composition, and structure (represented by enterotypes) between the two groups. We have identified differential microbes between the two groups and performed network analyses connecting GM and the clinical traits. Result: Compared with the casual users, individuals with MUD had higher incidences of MA-induced neuropsychiatric symptoms (e.g., paranoia, depression) and withdrawal symptoms (e.g., fatigue, drowsiness, and increased appetite), as well as stronger cravings for and intentions to use MA, and increased MA tolerance. The GM diversity showed no significant differences between the two groups, but four genera (Halomonas, Clostridium, Devosia, and Dorea) were enriched in the individuals with MUD (p<0.05). Three distinct enterotypes were identified in all MA users, and Ruminococcus-driven enterotype 2 was dominant in individuals with MUD compared to the MCU (61.90% vs. 28.60%, p=0.03). Network analysis shows that Devosia is the hub genus (hub index = 0.75), which is not only related to the counts of the MUD diagnostic criteria (ρ=0.40; p=0.01) but also to the clinical features of MA users such as reduced social activities (ρ=0.54; p<0.01). Devosia is also associated with the increased intention to use MA (ρ=0.48; p<0.01), increased MA tolerance (ρ=0.38; p=0.01), craving for MA (ρ=0.37; p=0.01), and MA-induced withdrawal symptoms (p<0.05). Conclusion: Our findings suggest that Ruminococcus-driven enterotype 2 and the genera Devosia might be two influential factors that differentiate MA casual use from MUD, but further studies are warranted.

Association between thyroid hormones and comorbid psychotic symptoms in patients with first-episode and drug-naïve major depressive disorder.

Thyroid dysfunction is common in major depressive disorder (MDD) patients; however, its relationship with psychotic depression (PD) remains unclear. We aimed to assess thyroid hormones in 1718 first episode drug naïve (FEND) MDD patients and to determine their association with PD. The positive subscale of the Positive and Negative Symptom Scale (PANSS-P), Hamilton Anxiety Rating Scale (HAMA), and Hamilton Depression Rating Scale (HAMD) were used to detect clinical symptoms. The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroglobulin (TgAb), and thyroid peroxidases antibody (TPOAb) were assessed. The logistic regression model was conducted to determine risk factors for PD, and the Area Under the Curve (AUC) was used to test the performance of this model. 171 (10%) patients were identified as having PD. Serum levels of TSH, TgAb, and TPOAb displayed small-to-moderate associations with PANSS-P. HAMA score, HAMD score, and TSH levels were independently associated with PD. The regression model had excellent power to distinguish PD patients from non-PD patients with an AUC value of 0.93. Our study suggests TSH levels and severity of depression and anxiety symptoms were independent risk factors for PD. Regular thyroid function tests may help early detect PD.

The prevalence and clinical correlates of anxiety in Chinese patients with first-episode and drug-naïve major depressive disorder at different ages of onset.

BACKGROUND: Major depressive disorder (MDD) with comorbid anxiety is very common and is associated with worse clinical outcomes. MDD patients at different ages of onset may have different clinical features and associated factors. The aim of this study was to investigate the prevalence of anxiety and related factors in MDD patients at different ages of onset. METHODS: A total of 1718 first-episode and drug-naïve (FEDN) MDD patients were recruited. The cutoff point for early-adulthood onset (EAO) and mid-adulthood onset (MAO) was the first depressive episode before or after age 45 years. Clinical features (depressive, anxiety and psychiatric symptoms) and some metabolic parameters were collected. RESULTS: There was no significant difference in the prevalence of anxiety between EAO patients (50.7 %) and MAO patients (55.7 %). For EAO patients, regression analysis showed that TSH levels, TgAb levels, and TC levels were significantly associated with anxiety. For MAO patients, regression analysis showed that anxiety was associated with HDL-c levels and impaired glucose metabolism. Furthermore, suicide attempts, psychotic symptoms, and depression severity were correlated with anxiety in both groups. LIMITATIONS: Our cross-sectional study cannot explain the causal relationship between anxiety and related factors in MDD patients at different ages of onset. CONCLUSIONS: This study revealed that the clinical characteristics and factors associated with anxiety in MDD patients differed according to age of onset, and therefore age of onset needs to be considered while treating anxiety.

Association between white matter microstructure and cognitive function in patients with methamphetamine use disorder.

Methamphetamine use disorder (MUD) has been associated with broad neurocognitive impairments. While the cognitive impairments of MUD have been demonstrated, the neuropathological underpinnings remain inadequately understood. To date, the published human diffusion tensor imaging (DTI) studies involving the correlation between diffusion parameters and neurocognitive function in MUD are limited. Hence, the present study aimed to examine the association between cognitive performance and white matter microstructure in patients with MUD. Forty-five patients with MUD and 43 healthy controls (HCs) completed their demographic information collection, cognitive assessments, and DTI imaging. DTI images were preprocessed to extract fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of various fiber tracts. Univariate tests were used to examine group differences in cognitive assessments and DTI metrics. Linear regression was used to examine the relationship between these two metrics. The results revealed that patients with MUD had lower subset scores of the MATRICS Consensus Cognitive Battery (MCCB), which reflects five cognitive domains: processing speed, attention, verbal learning, visual learning, problem-solving. Patients with MUD also had significantly higher AD, MD, and RD values of the left superior longitudinal fasciculus than HCs. Furthermore, the RD value of the left superior longitudinal fasciculus was a significant predictor of processing speed and problem-solving ability, as shown by the digit-symbol coding test and NAB-Mazes scores, respectively. Findings extended our understanding of white matter microstructure that is related to neurocognitive deficits in MUD and provided potential targets for the prevention and treatment of this chronic disorder.

The prevalence and risk factors of mental problems in medical students during COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the global prevalence and risk factors of mental problems (i.e., depression, anxiety, stress, sleep disorder, posttraumatic stress disorder (PTSD), burnout, psychological distress, and suicidal ideation) among medical students during the COVID-19 pandemic. METHOD: We searched PubMed, Embase, Web of Science, psycARTICLES, PsycINFO, CNKI, and Wan Fang for studies on the prevalence of mental problems among medical students from January 1, 2020, to April 1, 2022. The pooled prevalence was calculated by random-effect models. We performed a narrative review to identify the risk factors. RESULTS: The meta-analysis included 201 studies (N = 198,000). The prevalence of depression (41 %, 95 % CI, 37-45 %,), anxiety (38 %,95 % CI, 34 %-42 %), stress (34 %, 95 % CI, 27 %-42 %), sleep disorder (52 %, 95 % CI, 44 %-60 %), psychological distress (58 %, 95 % CI, 51 %-65 %), PTSD (34 %, 95 % CI, 22 %-46 %), suicidal ideation (15 %, 95 % CI, 11 %-18 %) and burnout (38 %, 95 % CI, 25 %-50 %) was high. The major risk factors were being female, being junior or preclinical students, exposure to COVID-19, academic stress, psychiatric or physical disorders history, economic trouble, fear of education impairment, online learning trouble, fear of infection, loneliness, low physical activity, low social support, problematic internet or smartphone use, and young age. LIMITATIONS: Most studies were cross-sectional. Few studies provided a reasonable response rate, suggesting potential selection bias. CONCLUSIONS: The study demonstrated a high prevalence and risk factors for mental problems during COVID-19, calling for mental health services. Our findings are valuable for college and health authorities to identify high-risk students and provide targeted intervention.

α5 integrin regulates hepatic tight junctions through SRC-TET1-mediated DNA hydroxymethylation.

The functional tight junctions' integrity plays an important role in liver physiology. A variety of liver diseases have been associated with the perturbation of tight junctions. Herein, we showed that the lower expression of α5 integrin in hepatocytes in patients with liver cirrhosis is associated with matrix deposition in the space of Disse. Selective silencing of α5 integrin in hepatocytes compromised the ultrastructure of tight junctions by downregulating claudin 1 in an SRC (proto-oncogene, non-receptor tyrosine kinase) signaling-dependent manner. α5 integrin signaling induced SRC-TET-mediated changes in 5-hydroxymethylcytosine and 5-methylcytosine levels in hepatocytes in vitro and in vivo. hMeDIP sequencing showed intergenic hypohydroxymethylation of the claudin 1 gene in hepatocytes after α5 integrin silencing in mice. Therefore, understanding the mechanisms regulating hepatic tight junction integrity in which α5 integrin-SRC signaling and epigenetic modifications cooperate might help advance the development of useful diagnostics and therapeutic approaches for liver disease.

A network analysis of anxiety and depression symptoms among Chinese nurses in the late stage of the COVID-19 pandemic.

Background: Nurses are at high risk for depression and anxiety symptoms after the outbreak of the COVID-19 pandemic. We aimed to assess the network structure of anxiety and depression symptoms among Chinese nurses in the late stage of this pandemic. Method: A total of 6,183 nurses were recruited across China from Oct 2020 to Apr 2021 through snowball sampling. We used Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder scale-7 (GAD-7) to assess depression and anxiety, respectively. We used the Ising model to estimate the network. The index "expected influence" and "bridge expected influence" were applied to determine the central symptoms and bridge symptoms of the anxiety-depression network. We tested the stability and accuracy of the network via the case-dropping procedure and non-parametric bootstrapping procedure. Result: The network had excellent stability and accuracy. Central symptoms included "restlessness", "trouble relaxing", "sad mood", and "uncontrollable worry". "Restlessness", "nervous", and "suicidal thoughts" served as bridge symptoms. Conclusion: Restlessness emerged as the strongest central and bridge symptom in the anxiety-depression network of nurses. Intervention on depression and anxiety symptoms in nurses should prioritize this symptom.

A brainnetome atlas-based methamphetamine dependence identification using neighborhood component analysis and machine learning on functional MRI data.

Addiction to methamphetamine (MA) is a major public health concern. Developing a predictive model that can classify and characterize the brain-based biomarkers predicting MA addicts may directly lead to improved treatment outcomes. In the current study, we applied the support vector machine (SVM)-based classification method to resting-state functional magnetic resonance imaging (rs-fMRI) data obtained from individuals with methamphetamine use disorder (MUD) and healthy controls (HCs) to identify brain-based features predictive of MUD. Brain connectivity analyses were conducted for 36 individuals with MUD as well as 37 HCs based on the brainnetome atlas, and the neighborhood component analysis was applied for feature selection. Eighteen most relevant features were screened out and fed into the SVM to classify the data. The classifier was able to differentiate individuals with MUD from HCs with a high prediction accuracy, sensitivity, specificity, and AUC of 88.00, 86.84, 89.19, and 0.94, respectively. The top six discriminative features associated with changes in the functional activity of key nodes in the default mode network (DMN), all the remaining discriminative features are related to the thalamic connections within the cortico-striato-thalamo-cortical (CSTC) loop. In addition, the functional connectivity (FC) between the bilateral inferior parietal lobule (IPL) and right cingulate gyrus (CG) was significantly correlated with the duration of methamphetamine use. The results of this study not only indicated that MUD-related FC alterations were predictive of group membership, but also suggested that machine learning techniques could be used for the identification of MUD-related imaging biomarkers.