Age-related changes in the susceptibility to clofibric acid,a hypolipidemic agent,of male rat liver

Age-related changes in the susceptibility to clofibric acid were investigated in male F344 rats of 8, 52, and 117 weeks old. Hepatomegaly, decrease of serum total cholesterol and triglyceride, increase of the total cytochrome P-450 contents, induction of the activities of microsomal ω-hydroxylation and peroxisomal β-oxidation, proliferation of smooth endoplasmic reticulum and peroxisomes were detected in 8- and 52-week-old rats. In 117-week-old rats clofibric acid treatment resulted in decrease of serum total cholesterol, elevation of the activities of microsomal and peroxisomal enzymes, and slight proliferation of peroxisomes. These results suggest that the susceptibility of the male F344 rat liver to clofibric acid decreases in 117-week-old rats, though the effect is still recognizable.     

高频重复经颅磁刺激联合舍曲林对青少年抑郁症患者自伤行为的疗效

目的 探讨重复经颅磁刺激（rTMS）联合舍曲林对青少年抑郁症（DD）患者自伤行为的疗效。方法 选取皖西卫生职业学院附属医院精神科在2018年1月至2021年12月期间收治的152例伴有自伤行为的青少年抑郁症患者为研究对象,根据随机数字表法随机分为观察组（高频rTMS+舍曲林,n=76）和对照组（舍曲林,n=76）。观察组在左侧前额叶背外侧皮质区（DLPFC）给予高频rTMS(10Hz)治疗,在相同刺激部位给予对照组假刺激治疗。rTMS每周治疗5次,持续治疗4周。记录治疗前、后两组患者汉密尔顿抑郁量表-24(HAMD-24)评分、自伤行为种类及频率、不良反应等情况。结果 组内比较,对照组和观察组治疗前后HAMD-24评分、自伤行为种类、自伤频率差异有统计学意义（P<0.05）,均改善;组间比较,对照组和观察组治疗前后的HAMD-24评分、自伤行为种类、自伤频率差值差异均有统计学意义（P<0.05）,观察组改善情况优于对照组。结论 舍曲林联合高频rTMS可显著改善患者抑郁症状和自伤行为。     

精神分裂症应用氯氮平228例初期血药浓度与临检指标水平的相关性

目的 研究精神分裂症病人使用氯氮平初期血药浓度与临检指标水平的相关性.方法 收集2018年1月至2019年1月在安徽医科大学附属心理医院住院治疗的精神分裂症病人228例氯氮平血药浓度及其人口学资料和实验室临检指标.采用Pearson相关检验和多元线性回归分析氯氮平血药浓度与实验室临检指标的关系.结果 Pearson相关...     

Electroconvulsive therapy modulates critical brain dynamics in major depressive disorder patients

BackgroundElectroconvulsive therapy (ECT) is widely considered as an effective and fast-acting option for treating patients with major depressive disorder (MDD). However, the neural basis underlying this powerful therapy remains uncertain. Recent studies have suggested that the healthy brain may operate near a critical state, which may reflect a balance between neuronal excitation and inhibition.ObjectiveIn the present study, we investigated whether there are any changes regarding criticality in MDD and, if so, whether ECT can reverse them. Critical dynamics analyses were performed on resting-state functional magnetic resonance imaging (rs-fMRI) data collected from 39 MDD patients and 38 healthy controls (HCs).ResultsWe found that compared with HCs, MDD patients, especially those who responded positively to ECT, tended to have smaller average avalanch sizes and lower branching ratios, suggesting a sub-critical state, at both the whole-brain and functional network levels. Importantly, ECT effectively corrected such anomalies, accompanied by enhanced degree centrality and functional connectivity of high-degree nodes located in the networks including the default-mode and the frontoparietal networks.ConclusionThese results indicate that ECT can modulate large-scale brain dynamics of MDD patients to be closer to criticality. Our study sheds new light on the pathology of MDD and the network mechanism by which ECT influences treatment.     

Clinical and preclinical evaluation of miR-144-5p as a key target for major depressive disorder

Background

Neuronal abnormalities are closely associated with major depressive disorder (MDD). Available evidence suggests a role for microRNAs (miRNAs) in regulating the expression of genes involved in MDD. Hence, miRNAs that can be potential therapeutic targets need to be identified.

Methods

A mouse model of chronic unpredictable stress (CUS) was used to evaluate the function of miRNAs in MDD. miR-144-5p was screened from the hippocampi of CUS mice based on sequencing results. Adenovirus-associated vectors were used to overexpress or knockdown miR-144-5p in mice. BpV(pic) and LY294002 were used to determine the relationship between miR-144-5p target genes PTEN and TLR4 in neuronal impairment caused by miR-144-5p deficiency. Western blotting, immunofluorescence, ELISA immunosorbent assay, and Golgi staining were used to detect neuronal abnormalities. Serum samples from healthy individuals and patients with MDD were used to detect miR-144-5p levels in the serum and serum exosomes using qRT-PCR.

Results

miR-144-5p expression was significantly decreased within the hippocampal dentate gyrus (DG) of CUS mice. Upregulation of miR-144-5p in the DG ameliorated depression-like behavior in CUS mice and attenuated neuronal abnormalities by directly targeting PTEN and TLR4 expression. Furthermore, miR-144-5p knockdown in normal mice led to depression-like behavior via inducing neuronal abnormalities, including abnormal neurogenesis, neuronal apoptosis, altered synaptic plasticity, and neuroinflammation. miR-144-5p deficiency-mediated neuronal impairment was mediated by PI3K/Akt/FoxO1 signaling. Furthermore, miR-144-5p levels were downregulated in the sera of patients with MDD and associated with depressive symptoms. Consistently, serum exosome-derived miR-144-5p levels were decreased in patients with MDD.

Conclusion

miR-144-5p plays a vital role in regulating neuronal abnormalities in depression. Our findings provide translational evidence that miR-144-5p is a new potential therapeutic target for MDD.