Major depressive disorder (MDD) is widely accepted as having a heterogenous pathophysiology involving a complex mixture of systemic and CNS processes. A developmental etiology coupled to genetic and epigenetic risk factors as well as lifestyle and social process influences add further to the complexity. Consequently, antidepressant treatment is generally regarded as open to improvement, undoubtedly as a consequence of inappropriately targeted pathophysiological processes. This article reviews the diverse array of pathophysiological processes linked to MDD, and integrates these within a perspective that emphasizes alterations in mitochondrial function, both centrally and systemically. It is proposed that the long-standing association of MDD with suppressed serotonin availability is reflective of the role of serotonin as a precursor for the mitochondrial melatonergic pathway. Astrocytes, and the astrocyte mitochondrial melatonergic pathway, are highlighted as crucial hubs in the integration of the wide array of biological underpinnings of MDD, including gut dysbiosis and permeability, as well as developmental and social stressors, which can act to suppress the capacity of mitochondria to upregulate the melatonergic pathway, with consequences for oxidant-induced changes in patterned microRNAs and subsequent patterned gene responses. This is placed within a development context, including how social processes, such as discrimination, can physiologically regulate a susceptibility to MDD. Future research directions and treatment implications are derived from this.

https://www.mdpi.com/1422-0067/24/1/350/pdf?version=1672017302

Depression Pathophysiology: Astrocyte Mitochondrial Melatonergic Pathway as Crucial Hub

Pharmacokinetic evaluation of Sinisan containing vinegar-processed products in depressive rats, a comprehensive perspective of 'individual herb, herb-pair, and herbal formula'.

• SiNiSan exerts therapeutic effects on adolescent depression caused by stress in early life and adolescence. • SiNiSan downregulates N-methyl-D-aspartic acid (NMDA) receptor expression and regulates serotonergic/GABAergic neuron activity in the dorsal raphe nucleus region of the adolescent depression models. • SiNiSan regulates neuronal activity by downregulating NMDA receptors in the dorsal raphe nucleus of adolescent depression models. 

SiNiSan exerts antidepressant effects by modulating serotonergic/GABAergic neuron activity in the dorsal raphe nucleus region through NMDA receptor in the adolescent depression mouse model.

Digital healthcare systems in a federated learning perspective

"Decision Fatigue" (DF) describes the impaired ability to make decisions because of repeated acts of decision-making. 

Decision fatigue in hospital settings: A scoping review

Circadian rhythm disorder is a significant risk factor for mental diseases, and the recovery of circadian rhythm function has gradually become a signal of effective antidepressant therapy. Sini powder (SNP) is a classical, traditional Chinese formula for depression treatment. However, few clinical reports have been recorded. This randomized, double‐blinded, controlled trial (ChiCTR1900022700) aimed to explore the efficacy of SNP on depression via regulating circadian rhythm. In total, 36 patients with major depressive disorder (MDD) were enrolled for 4‐weeks medication and 6‐weeks follow‐up. HAMD‐24 score and circadian rhythm index, including dim light melatonin onset (DLMO) and phase angle difference (PAD), were included in the assessment. DLMO and PAD were statistically significant in the SNP group after 4 weeks of treatment (p < .05) and with greater improvement in DLMO (p = .03). In addition, DLMO and the HAMD‐24 score showed a positive correlation (p < .05); the HAMD‐24 score degree decreased significantly over time (p < .001). Similarly, interaction effects were shown significantly between group and time (p = .049). The duration of SNP supplementation was relatively short, and the sample size was relatively small. SNP granules combined with paroxetine tablets have definite efficacy in improving the circadian rhythms of MDD patients, reflecting the therapeutic advantages of traditional Chinese medicine as antidepressants.

Sini powder with paroxetine ameliorates major depressive disorder by modulating circadian rhythm: A randomized, double‐blind, placebo‐controlled trial

ABSTRACT Vital signs have been widely used to assess the disease severity of patients, but there is still a lack of research on their circadian rhythms. The objective is to explore the circadian rhythms of vital signs in critically ill patients and establish an in-hospital mortality prediction model. Study patients from the recorded eICU Collaborative Research Database were included in the present analyses. The circadian rhythms of vital signs are analyzed in critically ill patients using the cosinor method. Logistic regression was used to screen independent predictors and establish a prediction model for in-hospital mortality by multivariate logistic regression analysis and to show in the nomogram. Internal validation is used to evaluate the prediction model by bootstrapping with 1000 resamples. A total of 29,448 patients were included in the current analyses. The Mesor, Amplitude, and Peak time of vital signs, such as heart rate (HR), temperature, respiration rate (RR), pulse oximetry-derived oxygen saturation (SpO2), and blood pressure (BP), were significant differences between survivors and non-survivors . Logistic regression analysis showed that Mesor, Amplitude, and Peak time of HR, RR, and SpO2 were independent predictors for in-hospital mortality in critically ill patients. The area under the curve (AUC) and c-index of the prediction model for the Medical intensive care unit (MICU) and Surgical intensive care unit (SICU) were 0.807 and 0.801, respectively. The Hosmer-Lemeshow test P-values were 0.076 and 0.085, respectively, demonstrating a good fit for the prediction model. The calibration curve and decision curve analysis (DCA) also demonstrated its accuracy and applicability. Internal validation assesses the consistency of the results. There were significant differences in the circadian rhythms of vital signs between survivors and non-survivors in critically ill patients. The prediction model established by the Mesor, Amplitude, and Peak time of HR, RR, and SpO2 combined with the Acute Physiology and Chronic Health Evaluation (APACHE) IV score has good predictive performance for in-hospital mortality and may eventually support clinical decision-making. Abbreviations: ICU: Intensive care unit; MICU: Medical intensive care unit; SICU: Surgical intensive care unit; HR: Heart rate; RR: Respiration rate; SpO2: Pulse oximetry-derived oxygen saturation; BP: Blood pressure; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; APACHE: Acute Physiology and Chronic Health Evaluation; bpm: beats per min; BMI: Body mass index; OR: Odd ratio; CI: Confidential interval; IQR: Interquartile range; SD: Standard deviation; ROC: Receiver operating characteristic; AUC: area under the curve; DCA: Decision curve analysis; IRB: Institutional review board.

/pdf/circadian-rhythms-of-vital-signs-are-associated-with-in-18pejxdx.pdf

Circadian rhythms of vital signs are associated with in-hospital mortality in critically ill patients: A retrospective observational study

: In order to explore the therapeutic targets and molecular mechanisms of resveratrol in amyotrophic lateral sclerosis based on network pharmacology and molecular docking techniques. In this study, we obtained the active compounds of resveratrol from TCMSP Chinese Medicine System Pharmacology database and used the Swiss Target Prediction platform to predict the potential targets of the active compounds. The effective targets of amyotrophic lateral sclerosis were obtained from GeneCards database, and the intersection was taken with the potential targets of resveratrol. Protein interaction networks were performed using the STRING database, and further network topology analysis was performed using Cytoscape 3.9.1 software. Meanwhile, gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersecting targets by Metascape database; finally, molecular docking validation was carried out by Pubchem and PDB databases as well as by Pymol and Autodocktools software. Resultly, forty-nine potential targets of resveratrol and 1599 potential targets of amyotrophic lateral sclerosis were obtained. The enrichment analysis showed that resveratrol could have therapeutic effects on amyotrophic lateral sclerosis through multi-targets and multi-pathways. The molecular docking results showed that the core components could bind to the core targets better. Resveratrol mainly acts on Pathways in cancer pathway, Proteoglycans in cancer proteoglycans, Relaxin signaling pathway, Lipid and atherosclerosis lipids and atherosclerosis pathway through the core targets such as EGFR, PTGS2, SRC, MMP9, IGF1R and so on. In conclusion, this study obtained the potential targets and molecular mechanisms of resveratrol for the treatment of amyotrophic lateral sclerosis, which provides a theoretical basis for promoting the development and clinical application of targeted drugs.

Therapeutic Targets and Molecular Mechanisms of Resveratrol in Amyotrophic Lateral Sclerosis: A Systematic Study of Network Pharmacology Incorporating Molecular Docking

: The timing and effectiveness of anticoagulant therapy (AT) are controversial in patients with hemorrhagic stroke (HS). We aim to evaluate the potential impact of AT on in-hospital mortality in HS, and how this impact is influenced by the Acute Physiological and Chronic Health Evaluation (APACHE) IV score. We identified individuals with hemorrhagic stroke as the primary diagnosis (n=1654) using individual patient data from a national multicenter cohort study (eICU database; n=200859). With in-hospital mortality as the primary outcome, hemorrhagic stroke patients were split into the anticoagulant therapy group and the other treatment (OT) group. First, univariate and multivariate logistic regression analyses were conducted to identify independent predictors of in-hospital mortality in patients receiving different forms of treatment. Next, the independent predictor's interaction with the AT status was evaluated.Resultly, 8.3%(n=137) of patients were in AT group. The survival rate in the AT group was significantly higher than that in the OT group (87.6% vs. 78.8%; P < 0.05). AT was an independent predictor of in-hospital mortality risk in the entire cohort [OR= 0.

The impact of anticoagulant therapy on patients with hemorrhagic stroke: a retrospective observational study from eICU database

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Sini powder with paroxetine ameliorates major depressive disorder by modulating circadian rhythm: A randomized, double‐blind, placebo‐controlled trial

Circadian rhythms of vital signs are associated with in-hospital mortality in critically ill patients: A retrospective observational study

Therapeutic Targets and Molecular Mechanisms of Resveratrol in Amyotrophic Lateral Sclerosis: A Systematic Study of Network Pharmacology Incorporating Molecular Docking

The impact of anticoagulant therapy on patients with hemorrhagic stroke: a retrospective observational study from eICU database