Age-Associated UBE2O Reduction Promotes Neuronal Death in Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease leading to dementia in the elderly. Ubiquitin proteasome system (UPS) is critical for protein homeostasis, while the functional decline of UPS with age contributes to the pathogenesis of AD. Ubiquitin-conjugating enzyme E2O (UBE2O), an E2-E3 hybrid enzyme, is a major component of UPS. However, its role in AD pathogenesis has not been fully defined. OBJECTIVE: We aimed to identify the age-associated expression of UBE2O and its role AD pathogenesis. METHODS: Western blot analysis were used to assess expression of UBE2O in organs/tissues and cell lines. Immunofluorescence staining was performed to examine the cellular distribution of UBE2O. Neuronal death was determined by the activity of lactate dehydrogenase. RESULTS: UBE2O is highly expressed in the cortex and hippocampus. It is predominantly expressed in neurons but not in glial cells. The peak expression of UBE2O is at postnatal day 17 and 14 in the cortex and hippocampus, respectively. Moreover its expression is gradually reduced with age. Importantly, UBE2O is significantly reduced in both cortex and hippocampus of AD mice. Consistently, overexpression of amyloid-ß protein precursor (AßPP) with a pathogenic mutation (AßPPswe) for AD reduces the expression of UBE2O and promotes neuronal death, while increased expression of UBE2O rescues AßPPswe-induced neuronal death. CONCLUSION: Our study indicates that age-associated reduction of UBE2O may facilitates neuronal death in AD, while increasing UBE2O expression or activity may be a potential approach for AD treatment by inhibiting neuronal death.

Perceived parenting styles and incidence of major depressive disorder: results from a 6985 freshmen cohort study.

BACKGROUND: Even though a fair amount of studies focus on depression among college students, the effect of perceived parenting styles on the incidence of major depressive disorder (MDD) among representative freshmen in Chinese context is scarcely studied. The aim of this study is to investigate the effect of parenting styles on MDD in Chinese freshmen. METHODS: A total of 9,928 Chinese freshmen were recruited in 2018. 6985 valid questionnaires were collected at one-year follow-up. Composite International Diagnostic Interview 3.0 (CIDI-3.0) was used for the diagnosis of MDD. Egna Minnen Beträffande Uppfostran (EMBU) questionnaire and Beck Depression Inventory-II (BDI-II) were used to assess parenting styles and baseline depressive symptoms, respectively. The associations between parenting styles and MDD incidence was analyzed with logistic regression. RESULTS: The incidence of MDD in freshmen was 2.23% (95%CI: 1.91-2.60%). Maternal overprotection (OR = 1.03, 95%CI: 1.01-1.05) and disharmony relationship between parents (OR = 2.35, 95% CI: 1.42-3.89) increased the risk of new-onset MDD in freshmen, respectively. Mild depressive symptoms (OR = 2.06, 95%CI: 1.06-4.02), moderate (OR = 4.64, 95%CI: 2.55-8.44) and severe depressive symptoms (OR = 7.46, 95%CI: 2.71-20.52) at baseline increased the risk of new-onset MDD. CONCLUSIONS: Maternal overprotection, disharmony relationship between parents and baseline depressive symptoms are risk factors for new-onset MDD in Chinese freshmen.

Negative life events increase the risk of suicidal ideation in 6653 Chinese freshmen: From a 1-year longitudinal study.

BACKGROUND: Suicide is one of the leading causes of juvenile death. Suicidal ideation (SI) is a strong predictor of suicide, while negative life events are associated with SI in adolescents. The aim of this study was to investigate the effect of negative life events on SI in a sample of Chinese freshmen. METHODS: The current study employed a cluster sampling method with 7118 freshmen at baseline and 6653 at follow-up. Negative life events were assessed by using the Adolescent Self-Rating Life Events Check List (ASLEC), and SI was assessed by a separate question for self-report. The PHQ-9 was used to measure depression at baseline. RESULTS: The incidence of suicidal ideation was 1.52% (95% CI: 1.22%-1.81%). Two dimensions of negative life events, interpersonal relationship and others were risk factors for SI, while female students were more susceptible to them. Consistently, interpersonal relationship and others were risk factors for SI in participants without depression and with mild depression. However, health & adaptation was found to be the only dimension of negative life events contributing to the risk of SI in participants with moderate, severe and extremely severe depression. LIMITATIONS: There may be recall bias in this study. CONCLUSIONS: Negative life events increase the risk of SI in college students. Female students are more susceptible to negative life events. The effect of different dimensions of negative life events on SI varies in participants with and without depression.

Gender Difference in Associations Between Telomere Length and Risk Factors in Patients With Stroke.

Multiple risk factors of stroke are associated with telomere length shortening. Although leukocyte telomere length (LTL) is shorter in patients with stroke, the heterogeneity is high. Risk factors may be differentially associated with LTL in male and female patients contributing to the heterogeneity. However, the gender difference in associations between LTL and risk factors in stroke patients has not been investigated. In this study, we investigated the gender difference in associations between LTL and risk factors in 312 stroke patients. Real-time quantitative PCR was used to determine relative LTL, and multiple linear regression analysis was applied for association analyses. We found that LTL was negatively associated with triglyceride (TG) in all patients [ß(95% CI) = -0.69 (-1.26, -0.11), P < 0.05] after adjusting confounders. Importantly, LTL was negatively associated with lack of exercise [ß(95% CI) = -1.80 (-3.12, -0.49), P < 0.05] and LDL levels [ß(95% CI) = -3.22 (-6.05, -0.390), P < 0.05] in male patients, while LTL was negatively associated with dyssomnia [ß(95%CI) = -2.00 (-3.96, -0.07), P < 0.05] and diabetes [ß(95%CI) = -2.13 (-4.10, -0.27), P < 0.01] in female patients. Our study showed that LTL is differently associated with risk factors in male and female patients with stroke, indicating that gender difference should be considered when LTL is potentially applied as an index of risk and prognosis for stroke. Our study also provides an insight into that gender differences should be considered when developing intervention strategies for stroke prevention and treatment.

The Profile of Microbiological Pathogens in Diabetic Foot Ulcers.

Diabetic foot, a main complication of diabetes mellitus, renders the foot susceptible to infection, and may eventually lead to non-traumatic limb amputation due to the deterioration of diabetic foot ulcers (DFUs). Characterizing the pathogen spectrum and antibiotic susceptibility is critical for the effective treatment of DFUs. In the current study, the characteristics and antibiotic susceptibility of the pathogen spectrum were analyzed. Secretions from the DFUs of 102 patients were cultured, and dominant pathogens were identified by using test cards. Antibiotic susceptibility of dominant pathogens was assayed by the Kirby-Bauer assay. We found that the dominant pathogens varied with age, duration of diabetes, blood sugar control, and the initial cause of ulcers. Moreover, the dominant pathogens were susceptible to at least one antibiotic. However, the antibacterial efficacy of several commonly used antibiotics decreased from 2016 to 2019. Our study indicates that the identification of dominant pathogens and antibiotic susceptibility testing is essential for the treatment of DFUs with effective antibiotics, while the abuse of antibiotics should be strictly restrained to reduce the generation of antibiotic-resistant strains.

[Effects of continuous blood purification on hemodynamics and oxygenation in patients with acute respiratory distress syndrome].

OBJECTIVE: To evaluate the effects of continuous blood purification on the hemodynamics and oxygenation in patients with acute respiratory distress syndrome (ARDS). METHODS: Twenty-one patients with ARDS were treated with continuous veno-venous hemofiltration (CVVH) combined with plasma exchange. Hemodynamics and oxygenation were measured or calculated at scheduled intervals using Swan-Ganz catheters. RESULTS: The mean arterial pressure, partial pressure of arterial oxygen, oxygen delivery, oxygen consumption increased, heart rate, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, blood lactate concentration all decreased significantly after the treatment, and the oxygen extraction ratio underwent no obvious changes. CONCLUSIONS: Continuous blood purification can increase blood and oxygen supply but has no significant effects on oxygen extraction ratio in ARDS patients.