Roles of Anxiety and Depression in Predicting Cardiovascular Disease Among Patients With Type 2 Diabetes Mellitus: A Machine Learning Approach.

Cardiovascular disease (CVD) is a major complication of type 2 diabetes mellitus (T2DM). In addition to traditional risk factors, psychological determinants play an important role in CVD risk. This study applied Deep Neural Network (DNN) to develop a CVD risk prediction model and explored the bio-psycho-social contributors to the CVD risk among patients with T2DM. From 2017 to 2020, 834 patients with T2DM were recruited from the Department of Endocrinology, Affiliated Hospital of Harbin Medical University, China. In this cross-sectional study, the patients' bio-psycho-social information was collected through clinical examinations and questionnaires. The dataset was randomly split into a 75% train set and a 25% test set. DNN was implemented at the best performance on the train set and applied on the test set. The receiver operating characteristic curve (ROC) analysis was used to evaluate the model performance. Of participants, 272 (32.6%) were diagnosed with CVD. The developed ensemble model for CVD risk achieved an area under curve score of 0.91, accuracy of 87.50%, sensitivity of 88.06%, and specificity of 87.23%. Among patients with T2DM, the top five predictors in the CVD risk model were body mass index, anxiety, depression, total cholesterol, and systolic blood pressure. In summary, machine learning models can provide an automated identification mechanism for patients at CVD risk. Integrated treatment measures should be taken in health management, including clinical care, mental health improvement, and health behavior promotion.

The Impact of Transformational Leadership on Physicians' Performance in China: A Cross-Level Mediation Model.

Transformational leadership has been becoming increasingly vital to the provision of high-quality health care, particularly during major public health emergencies. The present study aims to investigate the impact of transformational leadership on physicians' performance and explore the cross-level underlying mechanisms with achievement motivations and coping styles among Chinese physicians. During 2017-2019, 1,527 physicians of 101 departments were recruited from six hospitals in China with a cluster random sampling method. Participants completed several questionnaires regarding their job performance, achievement motivations, coping styles, and transformational leadership. Multilevel mediation effects were tested using cross-level path analysis. The result of this study indicated that transformational leadership was applied well in Chinese medical settings with a score of 101.56 ± 6.42. The hierarchical linear model showed that transformational leadership had a cross-level direct positive effect on physicians' performance (ß = 1.524, p < 0.05). Furthermore, results of cross-level path analyses revealed that transformational leadership contributed to physicians' performance by sequentially influencing achievement motivations first and then coping styles. In addition, the path "transformational leadership → positive coping (PC) style → physicians' performance" showed the strongest cross-level indirect effect. In summary, public health leaders should enhance physicians' performance by promoting individual development, especially achievement motivation and PC style.

Social Support and Suicide Risk Among Chinese University Students: A Mental Health Perspective.

Background: World Health Organization recognizes suicide as a public health priority. This study aimed to investigate the risk life events which led university students to consider suicide and explore the protective mechanism of social support (including subjective support, objective support, and support utilization) on suicide risk. Methods: Three thousand nine hundred and seventy-two university students were recruited in Harbin, China. Social Support Rating Scale, Self-Rating Anxiety Scale, the Beck Depression Inventory, and the 25-item scale of suicide acceptability were used to collect participants' information. Descriptive statistics, Pearson's correlation, and mediation analysis were employed for statistical analysis. Results: "Drug addict," "infected with HIV," and "incurable illness" were the top three events that led university students to consider suicide. Social support played an important protective role against suicide risk. Subjective support and support utilization had total effects on suicide acceptability, including direct and indirect effects. Anxiety (indirect effect = -0.022, 95% CI = -0.037 ~ -0.009) and depressive symptoms (indirect effect = -0.197, 95% CI = -0.228 ~ -0.163) mediated the relationship between subjective support and suicide acceptability; meanwhile, the association between support utilization and suicide acceptability was mediated by anxiety (indirect effect = -0.054, 95% CI = -0.088 ~ -0.024) and depressive symptoms (indirect effect = -0.486, 95% CI = -0.558 ~ -0.422). However, the protective impact of objective support worked totally through decreasing anxiety (indirect effect = -0.018, 95% CI = -0.035 ~ -0.006) and depressive symptoms (indirect effect = -0.196, 95% CI = -0.246 ~ -0.143). Moreover, the mediation effects of depressive symptoms had stronger power than anxiety in the impact of social support on suicide risk. Conclusions: Among Chinese university students, suicide acceptability was elevated when there was a health scare. Social support effectively reduced suicide risk via decreasing anxiety and depressive symptoms. From the mental health perspective, families, peers, teachers, and communities should work together to establish a better social support system for university students, if necessary, help them to seek professional psychological services.

Negative emotions, self-care activities on glycemic control in adults with type 2 diabetes: a cross-sectional study.

Glycemic control has become a focus of concern among diabetic patients. However, only 26.71% of patients achieved better glycemic control in China. Given the complexity of glycemic control, it is worth investigating the potential mechanisms between negative emotions and glycemic control. A total of 428 participants were recruited from a tertiary hospital (the number of hospital beds>500). They completed questionnaires consisting of demographics, Zung Self-Assessed Anxiety Scale(SAS), Zung Self-Assessed Depression Scale(SDS), and the Summary of Diabetes Self-Care Activities (SDSCA). HbA1 c was used to measure glycemic control. Descriptive analysis, Pearson correlation analysis, and Bootstrap analysis were conducted to analyze data. A total of 428 questionnaires were distributed, with 28 invalid questionnaires (93.46% were valid). Depression and self-care activities (exercise, medication) were associated with glycemic control. At the same time, the Bootstrap analysis revealed that self-care activities (exercise: standardized coefficient ß = 0.0181, p < 0.05, medication: standardized coefficient ß = 0.0211, p < 0.05) mediated the relationship between depression and glycemic control.

Association Between FoxO1, A2M, and TGF-ß1, Environmental Factors, and Major Depressive Disorder.

INTRODUCTION: Investigations of gene-environment (G×E) interactions in major depressive disorder (MDD) have been limited to hypothesis testing of candidate genes while poly-gene-environmental causation has not been adequately address. To this end, the present study analyzed the association between three candidate genes, two environmental factors, and MDD using a hypothesis-free testing approach. METHODS: A logistic regression model was used to analyze interaction effects; a hierarchical regression model was used to evaluate the effects of different genotypes and the dose-response effects of the environment; genetic risk score (GRS) was used to estimate the cumulative contribution of genetic factors to MDD; and protein-protein interaction (PPI) analyses were carried out to evaluate the relationship between candidate genes and top MDD susceptibility genes. RESULTS: Allelic association analyses revealed significant effects of the interaction between the candidate genes Forkhead box (Fox)O1, α2-macroglobulin (A2M), and transforming growth factor (TGF)-ß1 genes and the environment on MDD. Gene-gene (G×G) and gene-gene-environment (G×G×E) interactions in MDD were also included in the model. Hierarchical regression analysis showed that the effect of environmental factors on MDD was greater in homozygous than in heterozygous mutant genotypes of the FoxO1 and TGF-ß1 genes; a dose-response effect between environment and MDD on genotypes was also included in this model. Haplotype analyses revealed significant global and individual effects of haplotypes on MDD in the whole sample as well as in subgroups. There was a significant association between GRS and MDD (P = 0.029) and a GRS and environment interaction effect on MDD (P = 0.009). Candidate and top susceptibility genes were connected in PPI networks. CONCLUSIONS: FoxO1, A2M, and TGF-ß1 interact with environmental factors and with each other in MDD. Multi-factorial G×E interactions may be responsible for a higher explained variance and may be associated with causal factors and mechanisms that could inform new diagnosis and therapeutic strategies, which can contribute to the personalized medicine of MDD.

Factors influencing self-concept among adolescents infected with HIV: a cross-sectional survey in China.

OVERVIEW: The mental health problems of adolescents with human immunodeficiency virus (HIV) are important. It is of great significance to explore which factors can affect the self-evaluation and understanding of adolescents with HIV. OBJECTIVE: We found that adolescents with HIV have a lower level of self-concept than healthy adolescents. This study aimed to determine the factors influencing self-concept among adolescents with HIV in China. SETTING: A questionnaire was distributed among a total of 290 adolescents in Henan Province, China. One hundred and forty questionnaires were distributed in the case group (adolescents with HIV) and the control group (healthy adolescents) was issued 150 questionnaires.The Piers-Harris Children's Self-concept Scale, the Perceived Stress Scale, the Perceived Social Support Scale and the Simplified Coping Style Questionnaire were adapted for a Chinese population. Differences between the groups were tested for significance using Student's t-test, and analysis of variance was used to test continuous variables. The relationship between environmental personality factors and adolescent self-concept was examined by Pearson correlation analysis. Hierarchical linear regression analysis was used to model the effects of environmental personality factors on self-concept. RESULTS: The self-concept total score among adolescents with HIV was significantly lower than healthy adolescents (p<0.05). Hierarchical regression analysis indicated that age (ß=-0.19, t=-2.16, p=0.03), perceived stress (ß=-0.19, t=-2.22, p=0.03), perceived social support (ß=0.26, t=3.25, p=0.00), positive coping style (ß=0.50, t=5.75, p=0.00) and negative coping style (ß=-0.45, t=-5.33, p=0.00) were significantly associated with self-concept total scores. CONCLUSIONS: The self-concept of adolescents with HIV is related to perceived stress, perceived social support and coping style. These findings underline the significance of self-concept among adolescents infected with HIV.

Interactions Between Glycogen Synthase Kinase-3ß Gene Polymorphisms, Negative Life Events, and Susceptibility to Major Depressive Disorder in a Chinese Population.

Background: Recent studies suggest that glycogen synthase kinase (GSK)-3ß is involved in the development of major depressive disorder (MDD). The aim of this study was to investigate the interaction between GSK-3ß polymorphism (rs6438552, rs334558, and rs2199503) and negative life events in the pathogenesis of major depressive disorder (MDD). Methods: DNA genotyping was performed on peripheral blood leukocytes in 550 patients with MDD and 552 age- and gender-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A chi-square method was employed to assess the gene-environment interaction (G × E). Results: Differences in rs6438552, rs334558, and rs2199503 genotype distributions were observed between MDD patients and controls. Significant G × E interactions between allelic variation of rs6438552, rs334558, and rs2199503 and negative life events were observed. Individuals with negative life events and carrying genotypes of rs6438552 A+, rs334558 A+, and rs2199503G+ have increased the risk of depression. Conclusions: These results indicate that interactions between the GSK-3ß rs6438552, rs334558, and rs2199503 polymorphisms and environment increases the risk of developing MDD.

Epistatic Interaction Between 5-HT1A and Vascular Endothelial Growth Factor Gene Polymorphisms in the Northern Chinese Han Population With Major Depressive Disorder.

Aims: Serotonin 1A receptor (5-HT1A) and vascular endothelial growth factor (VEGF) are widely expressed in the neurons of the hippocampus and have significant roles in the pathophysiological processes of major depressive disorders (MDDs). The present study was designed to examine 5-HT1A and VEGF gene polymorphisms and whether the gene-gene interaction of 5-HT1A and VEGF gene variants was associated with MDD. Methods: A total of 264 MDD patients and 264 healthy controls were included in the present genetic study. The rs6295, rs1364043, and rs878567 single-nucleotide polymorphisms (SNPs) in the 5-HT1A gene and the rs699947, rs833061, and rs2010963 SNPs in the VEGF gene were selected for genotypic analyses. The generalized multifactor dimensionality reduction method was employed to assess their interactions. Results: The genotype distributions of the two genes' respective SNPs were significantly different between patients and controls for 5-HT1A rs6295 (p = 0.041) and VEGF rs2010963 (p = 0.035); however, no significant allelic variation in 5-HT1A (rs6295, rs1364043, and rs878567) and VEGF (rs699947, rs833061, and rs2010963) was found. The interactions between 5-HT1A (rs6295, rs1364043, and rs878567) and VEGF (rs699947, rs833061, and rs2010963) had a cross-validation (CV) consistency of 10/10 and a p value of 0.0107, which was considered as the best generalized multifactor dimensionality reduction (GMDR) model. Conclusions: The interactions between 5-HT1A and VEGF gene polymorphisms may play a key role in the development of MDD in the Northern Chinese Han population.

Factors associated with depression among HIV/AIDS children in China.

BACKGROUND: Depression in HIV/AIDS children not only worsens the progression and outcome of illness, but also impacts their quality of life, having a negative influence on society. The present study was conducted from a psychosocial perspective, considering children's social desirability, cognitive emotion regulation, and perceived social support to identify the factors influencing depression in HIV-infected children in China. METHODS: Participants were 155 children aged 8-18 years who were eligible to participate in this study assessing depression and associated risk factors using the Children's Depression Inventory, Cognitive Emotion Regulation Questionnaire, Multidimensional Scale of Perceived Social Support, and Children's Social Desirability scale. Hierarchical linear regression analysis was conducted to model the effects of social desirability, perceived social support, and cognitive emotion regulation on depression in HIV/AIDS children. RESULTS: Statistically significant linear relationships were found among social desirability, perceived social support, partial dimensions of cognitive emotion regulation, and children's depression scores. Perceived social support, planning and positive reappraisal were negatively related to the depression. Conversely, social desirability, catastrophizing and other-blame were positively associated with the depression. Linear regression analysis indicated that children's social desirability, perceived social support, and one dimension of cognitive emotion regulation (catastrophizing) were found to significantly predict depression. CONCLUSIONS: Psychosocial factors have an important influence on the depression experienced by HIV-infected children. Interventions from personal subjective psychosocial to reduce depression in HIV-infected children in China are warranted.

CACNA1C rs1006737, Threatening Life Events, and Gene-Environment Interaction Predict Major Depressive Disorder.

INTRODUCTION: CACNA1C rs1006737 is a novel variant in discovery of replicable associations in major depressive disorder (MDD). However, there have been no specific studies considered effect of environmental pathogens to date examining its clinical significance. In this study we investigated the interaction effect between CACNA1C rs1006737 polymorphism and threatening life events (TLEs) in MDD and carried out a meta-analysis of published findings. METHODS: A total of 1,177 consecutive participants were genotyped. Information on exposure to TLEs, socio-demographic data, and history of psychological problems among first-degree relatives was collected. MDD was diagnosed according to the Chinese version of the 24-item Hamilton Rating Scale for Depression. RESULTS: There was a significant interaction effect between CACNA1C rs1006737 polymorphism and TLEs in MDD. A dose-response relationship was found between CACNA1C rs1006737 genotypes and TLEs in MDD. The results of the meta-analysis showed that CACNA1C rs1006737 genotypes interacted with TLEs in MDD. CONCLUSION: CACNA1C rs1006737 genotype and previous exposure to TLEs interact to influence the risk of developing MDD. We propose that CACNA1C rs1006737 may represent a target for novel pharmacological therapies to prevent or treat MDD.

BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction.

BACKGROUND: Depression is thought to be multifactorial in etiology, including genetic and environmental components. While a number of gene-environment interaction studies have been carried out, meta-analyses are scarce. The present meta-analysis aimed to quantify evidence on the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and stress in depression. METHODS: Included were 31 peer-reviewed with a pooled total of 21060 participants published before October 2016 and literature searches were conducted using PubMed, Wolters Kluwer, Web of Science, EBSCO, Elsevier Science Direct and Baidu Scholar databases. RESULTS: The results indicated that the Met allele of BDNF Val66Met polymorphism significantly moderated the relationship between stress and depression (Z=2.666, p = 0.003). The results of subgroup analysis concluded that stressful life events and childhood adversity separately interacted with the Met allele of BDNF Val66Met polymorphism in depression (Z = 2.552, p = 0.005; Z = 1.775, p = 0.03). LIMITATIONS: The results could be affected by errors or bias in primary studies which had small sample sizes with relatively lower statistic power. We could not estimate how strong the interaction effect between gene and environment was. CONCLUSIONS: We found evidence that supported the hypothesis that BDNF Val66Met polymorphism moderated the relationship between stress and depression, despite the fact that many included individual studies did not show this effect.

Meta-analysis of the interaction between serotonin transporter promoter variant, stress, and posttraumatic stress disorder.

Exposure to stress predicts the occurrence of posttraumatic stress disorder (PTSD) in individuals harboring the serotonin transporter promoter variant 5-HTTLPR. We carried out a meta-analysis of studies investigating the interaction between 5-HTTLPR, stress, and PTSD to clarify the interrelatedness of these factors. We reviewed all relevant studies published in English before May 2016. The Lipták-Stouffer z-score method for meta-analysis was applied to combined data. The z score was separately calculated for the stressful life events, childhood adversity, bi- and triallelic loci, and cross-sectional and longitudinal studies subgroups. A total of 14 studies with 15,883 subjects met our inclusion criteria. We found strong evidence that the presence of 5-HTTLPR influenced the relationship between stress and PTSD (P = 0.00003), with the strongest effects observed in the cross-sectional and longitudinal groups (P = 0.01 and 2.0 × 10-6, respectively). Stressful life events and childhood adversity separately interacted with 5-HTTLPR in PTSD (P = 2.0 × 10-8 and 0.003, respectively). When the studies were stratified by locus classification, the evidence was stronger for the triallelic (P = 4.0 × 10-8) than for the biallelic (P = 0.054) locus subgroup. There was strong evidence that 5-HTTLPR influences the relationship between stress and PTSD.

Independent Risk Factors Predicting Central Lymph Node Metastasis in Papillary Thyroid Microcarcinoma.

The incidence of papillary thyroid microcarcinoma (PTMC) has risen rapidly in recent years, and PTMC patients with central lymph node metastasis (CLNM) usually have poor prognosis. Independent risk factors predicting CLNM in PTMC have not been well understood. The aim of our study was to identify useful clinicopathological risk factors predicting CLNM in PTMC patients. This was a retrospective study of 917 patients with PTMC treated with surgery from January 2014 to December 2015 in our hospital. The relationship between clinicopathological factors and CLNM was analyzed to identify those factors predicting CLNM in PTMC. Univariate and multivariate logistic regression analyses were further performed. Of 917 PTMC patients, 344 (37.5%) were found to have CLNM confirmed by intraoperative frozen-section examination. Multivariate logistic regression analyses further found several independent factors predicting CLNM in PTMC patients, including male gender (OR=1.75, 95% CI 1.17-2.61; p=0.006), younger age (<45 years) (OR=1.69, 95%CI 1.20-2.38; p=0.002), positive CLNM on ultrasonography (OR=10.20, 95% CI 5.51-18.88; p<0.001), multifocality (OR=1.69, 95% CI 1.00-2.85; p=0.04), and larger tumor size (>5 mm) (OR=2.80, 95% CI 2.01-3.91; p<0.001). The findings of our study identified several useful and independent risk factors predicting CLNM in PTMC patients, such as male gender, younger age, multifocality, positive CLNM on ultrasonography, and larger tumor size. The CLNM is very common in PTMC patients, and routine prophylactic central neck dissection may be recommended in PTMC patients with those independent risk factors of CLNM.

Association Between Tumor Necrosis Factor-α and Diabetic Peripheral Neuropathy in Patients with Type 2 Diabetes: a Meta-Analysis.

Tumor necrosis factor-α (TNF-α) is a cell signaling protein involved in systemic inflammation, and is also an important cytokine in the acute phase reaction. Several studies suggested a possible association between TNF-α and diabetic peripheral neuropathy (DPN) in type 2 diabetic patients, but no accurate conclusion was available. A systematic review and meta-analysis of observational studies was performed to comprehensively assess the association between serum TNF-α levels and DPN in type 2 diabetic patients. We searched Pubmed, Web of Science, Embase, and China Biology Medicine (CMB) databases for eligible studies. Study-specific data were combined using meta-analysis. Fourteen studies were finally included into the meta-analysis, which involved a total of 2650 participants. Meta-analysis showed that there were obviously increased serum TNF-α levels in DPN patients compared with type 2 diabetic patients without DPN (standard mean difference [SMD] = 1.203, 95 % CI 0.795-1.611, P < 0.001). There were also obviously increased levels of serum TNF-α in diabetic patients with DPN when compared with healthy controls (SMD = 2.364, 95 % CI 1.333-3.394, P < 0.001). In addition, there were increased serum TNF-α levels in painful DPN patients compared with painless DPN patients (SMD = 0.964, 95 % CI 0.237-1.690, P = 0.009). High level of serum TNF-α was significantly associated with increased risk of DPN in patients with type 2 diabetes (odds ratio [OR] = 2.594, 95 % CI 1.182-5.500, P = 0.017). Increased serum levels of TNF-α was not associated with increased risk of painful DPN in patients with type 2 diabetes (OR = 2.486, 95 % CI 0.672-9.193, P = 0.172). Sensitivity analysis showed that there was no obvious change in the pooled estimates when omitting single study by turns. Type 2 diabetic patients with peripheral neuropathy have obviously increased serum TNF-α levels than type 2 diabetic patients without peripheral neuropathy and healthy controls, and high level of serum TNF-α may be associated with increased risk of peripheral neuropathy independently. Further prospective cohort studies are needed to assess the association between TNF-α and DPN.

Inverse Association Between Serum Uric Acid Levels and Alzheimer's Disease Risk.

The association between Alzheimer's disease and uric acid levels had gained great interest in recent years, but there was still lack of definite evidence. A systematic review and meta-analysis of relevant studies was performed to comprehensively estimate the association. Relevant studies published before October 26, 2014, were searched in PubMed, Embase, and China Biology Medicine (CBM) databases. Study-specific data were combined using random-effects or fixed-effects models of meta-analysis according to between-study heterogeneity. Twenty-four studies (21 case-control and 3 cohort studies) were finally included into the meta-analysis. Those 21 case-control studies included a total of 1128 cases of Alzheimer's disease and 2498 controls without Alzheimer's disease. Those 3 cohort studies included a total of 7327 participants. Meta-analysis showed that patients with Alzheimer's disease had lower levels of uric acid than healthy controls (weighted mean difference (WMD) = -0.77 mg/dl, 95% CI -2.28 to -0.36, P = 0.0002). High serum uric acid levels were significantly associated with decreased risk of Alzheimer's disease (risk ratio (RR) = 0.66, 95% CI 0.52-0.85, P = 0.001). There was low risk of publication bias in the meta-analysis. There is an inverse association between serum uric acid levels and Alzheimer's disease. High serum uric acid level is a protective factor of Alzheimer's disease.

Association of LEPR Gln223Arg polymorphism with T2DM: A meta-analysis.

A meta-analysis was conducted to evaluate the association of LEPR Gln223Arg polymorphism with type 2diabetes (T2DM). Sixteen individual studies with 7827 subjects were included into the meta-analysis. Current studies suggest that LEPR Gln223Arg polymorphism may not affect the susceptibility with type 2diabetes (T2DM).