BackgroundExposure to high-altitude hypoxia is associated with an increased risk of impaired brain structure and function, with oxidative stress and neuroinflammation widely recognized as key mechanisms involved. In this context, hyperbaric oxygen therapy is considered a potential intervention; however, the mechanism by which it affects cerebral function changes caused by high-altitude exposure remains to be further elucidated.ObjectiveThis study aims to explore and compare the therapeutic effects of normobaric oxygen (NBO) and hyperbaric oxygen (HBO) on high-altitude cerebral injury (HACI), and to elucidate the molecular mechanisms underlying their neuroprotective effects using transcriptomic profiling and targeted validation.MethodsA mouse model of high-altitude cerebral injury was established using a hypobaric hypoxia chamber. Mice were exposed to a simulated altitude of 7,000 m (approximately 9.8% O₂ at 0.47 ATA) for 3 consecutive days to induce severe hypoxia. Animals were divided into four groups: Control (Con), High-Altitude exposure (HH), post-HH treated with normobaric oxygen (NBO; 100% O₂ at 1.0 ATA for 1 h daily for 3 days), and post-HH treated with hyperbaric oxygen (HBO; 100% O₂ at 2.0 ATA for 1 h daily for 3 days). Brain tissues were analyzed using H&E staining, RNA sequencing (RNA-seq), Western blotting for key pathway proteins, immunofluorescence for glial cell activation, and ELISA for inflammatory cytokines. Oxidative stress markers (SOD, MDA, GSH, NO) were also assessed.ResultsHistopathological analysis confirmed cerebral damage in the HH group, which was significantly ameliorated by both HBO and NBO treatments. RNA-seq revealed widespread disruption of the cerebral transcriptome following high-altitude exposure. Oxygen therapy was associated with partial restoration of global gene expression patterns. KEGG pathway analysis highlighted significant enrichment in pathways related to NF-κB signaling, cytokine–cytokine receptor interaction, IL-17 signaling, and PI3K–AKT signaling. Subsequent targeted validation demonstrated that oxygen treatment reduced oxidative stress (increased SOD and GSH; decreased MDA and NO) and modulated the PI3K–AKT signaling pathway (increased p-AKT/AKT). Concurrently, oxygen therapy attenuated neuroinflammatory responses, inhibiting microglial and astrocytic activation, reducing pro-inflammatory cytokine levels (IL-1β, IL-6, TNF-α), and modulating the TLR4–NF-κB signaling axis (decreased TLR4 and p-p65/p65). HBO treatment was associated with broader modulation of several molecular pathways involved in oxidative stress and inflammation.ConclusionExisting evidence suggests that HBO may exert protective effects against altitude-related brain injury. This mechanism likely involves activating the PI3K–AKT/Nrf2 axis to alleviate oxidative stress and inhibiting the TLR4–NF-κB pathway to reduce neuroinflammation, thereby partially restoring transcriptional homeostasis. However, the causal relationships between these pathways and their interactions require further validation and refinement.
From peripheral initiation to central integration: a narrative review of the antihypertensive mechanisms of acupuncture in regulating autonomic nervous system homeostasis
Essential Hypertension (EH) is one of the most prevalent chronic cardiovascular diseases, imposing a significant burden on healthcare systems worldwide due to its high rates of disability and mortality. Long-term elevation of blood pressure leads to multi-organ damage in the heart, brain, and kidneys, resulting in severe complications such as coronary heart disease, stroke, and chronic kidney disease. Current treatment for hypertension primarily relies on pharmacological interventions. Although antihypertensive drugs have achieved notable success in controlling blood pressure, challenges remain, including poor long-term medication adherence, side effects, and inadequate blood pressure control in some patients with resistant hypertension. In parallel, acupuncture, a key modality of traditional Chinese medicine, has demonstrated unique advantages in hypertension management in recent years. Characterized by its holistic regulatory effects and minimal side effects, acupuncture is recognized by the World Health Organization as a recommended complementary and alternative therapy for hypertension, although its precise mechanisms remain incompletely understood. This review aims to summarize the “peripheral-central synergy” antihypertensive mechanism of acupuncture in regulating autonomic nervous system (ANS) homeostasis. Studies indicate that acupuncture primarily modulates autonomic homeostasis through the following pathways: (1) activating peripheral nerve fibers to convert physical stimulation into complex bioelectrical signals; (2) regulating synaptic neurotransmitter release and the expression of related membrane receptors; (3) modulating the synaptic microenvironment; (4) regulating the NTS-CVLM-RVLM neural circuit; and (5) modulating the HPA axis neuro-endocrine circuit. Through in-depth analysis, this review elucidates the multi-level and multi-dimensional impact of acupuncture therapy on primary hypertension, providing stronger evidence and a theoretical foundation for its clinical application.
The associations of systemic inflammation and insulin resistance-related indicators with psychopathology and BDNF in patients with chronic schizophrenia
BackgroundThe triglyceride-glucose (TyG) index and C-reactive protein-triglyceride-glucose index (CTI) are innovative indicators for assessing insulin resistance (IR) and inflammation, yet research on them in patients with schizophrenia remains limited. This study aimed to explore TyG index and CTI levels and their associations with psychopathology and brain-derived neurotrophic factor (BDNF) in patients with chronic schizophrenia (CS).MethodsThis cross-sectional study was conducted across one general hospital and two psychiatric hospitals in Anhui Province, China. Socio-demographic information and hematological parameters were collected from participants, and their psychiatric and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS), respectively.ResultsA total of 324 patients with CS and 150 healthy controls (HCs) were enrolled in the study. Compared with HCs, patients had higher TyG index and CTI levels (all P < 0.001). Binary logistic regression analyses revealed that among patients, a high TyG index level was significantly associated with higher BDNF levels and lower negative factor scores of the PANSS, while a high CTI level was significantly associated with higher depression-hopelessness factor scores of the CDSS and lower negative factor scores of the PANSS (all P < 0.05).ConclusionPatients with CS had higher levels of TyG index and CTI, which were significantly associated with the severity of negative and depressive symptoms, as well as BDNF levels. It is suggested that the integration of the TyG index and CTI into clinical monitoring for patients with CS is necessary.
Effect of transcranial magnetic stimulation on prognosis in patients with postherpetic neuralgia and comorbid depression undergoing interventional neuromodulation therapy: protocol for a randomized double-blind placebo-controlled trial
BackgroundPostherpetic neuralgia (PHN) is often accompanied by depression, creating a vicious cycle that exacerbates symptoms and contributes to suboptimal treatment outcomes, even with interventional therapies. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in alleviating both pain and mood disturbances. However, its efficacy in enhancing prognosis when used alongside interventional neuromodulation therapy for PHN accompanied by depression remains inadequately explored and requires further investigation.ObjectiveThis study aims to generate preliminary evidence on the efficacy and safety of rTMS in enhancing prognosis and alleviating pain in patients with PHN and mild to moderate depression undergoing interventional neuromodulation therapy.MethodsThis study is a single-center, randomized, double-blind, placebo-controlled trial involving 174 adult patients with PHN. Participants will be randomly assigned, stratified by interventional neuromodulation therapy, to either the rTMS group (n=87) or the control group (n=87). Both groups will undergo either 10 Hz rTMS or sham stimulation for five consecutive days. The primary outcome is the incidence of poor prognosis at 3 months post-discharge. Secondary outcomes include the incidence of poor prognosis at 6 months post-discharge; Visual Analog Scale (VAS) sleep scores; short-form McGill Pain Questionnaire (SF-MPQ) scores; Self-Rating Depression Scale (SDS) scores; patient satisfaction; Pain Disability Index (PDI) scores; Multidimensional Fatigue Inventory-20 (MFI-20) scores; pregabalin oral doses; and the need for tramadol or antidepressants. Safety outcomes will include assessments of headache, pain at the stimulation site, neck pain, insomnia, muscle soreness, dizziness, nausea, tinnitus, irritability, tachycardia (heart rate > 100 bpm), and epilepsy. Data will be analyzed using a modified intention-to-treat approach.DiscussionThis study aims to provide preliminary evidence on the efficacy and safety of 10 Hz rTMS in improving prognosis and alleviating pain in PHN patients with mild to moderate depression undergoing interventional pain management.Trial registrationhttps://www.chictr.org.cn/bin/project/edit?pid=261070, identifier ChiCTR2500096978.
From work-related trauma to suicidal ideation: a serial mediation model of posttraumatic stress and depression in rescue workers
ObjectivesRescue workers face frequent occupational trauma, increasing their risk for posttraumatic stress symptoms (PTSS), depression, and suicidal ideation. However, pathways linking trauma to suicidality remain poorly understood. This study investigated these mechanisms by testing a serial mediation model.MethodsFrom a larger survey of Swiss rescue workers, participants reporting suicidal ideation (n = 44) were matched by age, sex, and profession with a control group without suicidal ideation (n = 44). Symptomatology was assessed using validated questionnaires such as the Posttraumatic Stress Scale-10 (PTSS-10) for posttraumatic stress and the Brief Symptom Inventory (BSI) for depressive symptoms. Structural Equation Modeling (SEM) was employed to test a serial two-mediator model: Trauma Exposure – PTSS – Depressive Symptoms – Suicidal Ideation.ResultsParticipants with suicidal ideation had significantly higher levels of trauma, PTSS, and depressive symptoms. SEM confirmed an excellent model fit (χ² = 1.925, CFI = 1.000, RMSEA <.001) and a full mediation effect: trauma exposure was associated with PTSS, which in turn related to depressive symptoms, which were subsequently linked to suicidal ideation. The specific serial indirect pathway was significant (B = 0.143, p = .011), while the direct path from trauma to suicidal ideation was non-significant. The model explained 69.4% of the variance in suicidal ideation.ConclusionThe findings suggest a developmental pathway in which trauma exposure is associated with suicidal ideation through the sequential roles of PTSS and depressive symptoms. Consequently, suicide prevention for rescue workers should prioritize the management of post-traumatic and depressive symptoms to potentially disrupt this symptomatic progression.
Peer Mentor Training and Supervision for a Digital Adolescent Depression Treatment in South Africa and Uganda: Mixed Methods Evaluation
Background: Blended digital mental health interventions combining technology with human support are more effective than stand-alone treatments. However, limited research has examined how to train and supervise personnel delivering human support components. The Kuamsha app, a gamified digital intervention for adolescent depression based on behavioral activation, was designed to be paired with low-intensity telephone-based peer support. A structured training and supervision program for peer supporters was codeveloped through workshops with mental health professionals and youth with lived experience of mental health challenges in South Africa and Uganda. To the best of our knowledge, this is the first study to evaluate a structured peer mentor model within a digital mental health intervention in low- and middle-income countries. Objective: This study assessed the feasibility, acceptability, and fidelity of a training and supervision program for peer supporters delivering a digital mental health intervention in South Africa and Uganda. Methods: We conducted a mixed methods evaluation of the peer mentor program. Quantitative metrics assessed the feasibility of recruitment, retention, and attendance among peer mentors (n=13, South Africa; n=4, Uganda), as well as training acceptability. Fidelity, adherence, and competence were scored at the session level and converted to percentages of the maximum possible score. Linear mixed-effects regression models with a random intercept for provider and site estimated adjusted marginal means (95% CI). In-depth interviews and focus group discussions explored program acceptability and implementation factors. Results: The peer mentor training and supervision program was feasible and acceptable in both settings, with high recruitment (South Africa: n=13/19, 68%; Uganda: 4/4, 100%), retention (South Africa: 9/13, 69%; Uganda: 4/4, 100%), and training attendance rates (89%‐92% in South Africa and 100% in Uganda), alongside qualitative reports of high satisfaction. All peer mentors met a minimum posttraining competency threshold (≥50%), with median competency scores of 70.7% (IQR 45.8%‐78.2%) in South Africa and 75.4% (IQR 73.8%‐77.3%) in Uganda. Independent ratings of recorded calls indicated high overall fidelity in South Africa (84.7%, 95% CI 80.3%‐89.0%) and Uganda (87.7%, 95% CI 83.4%‐92.1%). Adherence was higher in Uganda than South Africa (adjusted mean difference [AMD] 13.30 percentage points, 95% CI 8.99‐17.61; <.001), as was competence (AMD 4.88 percentage points, 95% CI 1.23‐8.53; =.009). The AMD in overall fidelity (3.06 percentage points, 95% CI −0.98 to 7.10) was not statistically significant (=.14). The qualitative findings emphasized the value of ongoing supervision and capacity development, interactive training approaches, and blended delivery models. Conclusions: Locally adapted training and supervision models can strengthen peer mentor capabilities to support digital interventions. Adequate supervisory capacity and incentive structures are critical to sustain engagement, retention, and fidelity. In settings with frequent network disruptions, periodic in-person contact between peer mentors and supervisors may enhance fidelity. Future research should examine how peer mentor fidelity influences user engagement and mental health outcomes. Trial Registration: Pan African Clinical Trials Registry PACTR202206574814636; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=23792 International Registered Report Identifier (IRRID): RR2-10.1136/bmjopen-2022-065977
Targeting the microbiota-gut-brain axis in post-stroke insomnia: a phase-dependent therapeutic framework
Post-stroke insomnia (PSI) is a critical biological barrier to neurorehabilitation afflicting over half of all stroke survivors. Traditional sedatives often force clinicians into a therapeutic dilemma between sleep efficacy and cognitive suppression. The microbiota-gut-brain (MGB) axis has recently emerged as a transformative target to resolve this impasse. Acute stroke triggers profound autonomic dysfunction, causing immediate intestinal barrier collapse. This “leaky gut” facilitates the systemic translocation of lipopolysaccharides (LPS) and activates the NLRP3 inflammasome. The resulting inflammatory storm hijacks central tryptophan metabolism via the indoleamine 2,3-dioxygenase (IDO) enzyme. This “tryptophan steal” diverts serotonin precursors toward neurotoxic kynurenine pathways, driving severe cortical hyperarousal. Sleep fragmentation then prevents the glymphatic system from clearing metabolic waste, further exacerbating neuroinflammation. To break this vicious cycle of neurotoxicity, we propose a phase-dependent therapeutic framework. During the highly vulnerable acute phase, interventions must prioritize gut barrier protection using postbiotics to mitigate infection risks under CNS injury-induced immunodepression (CIDS), often discussed as stroke-induced immunosuppression. As patients enter the chronic phase, therapy shifts toward metabolic restoration using live therapeutics, such as washed microbiota transplantation (WMT) and next-generation psychobiotics like Akkermansia muciniphila. Targeting the MGB axis offers a mechanism-based strategy to achieve precision sleep medicine, restoring the biological foundation necessary for optimal neuroplasticity and recovery.
<![CDATA[BPL-003 phase 2a part 2 results show reductions in depression symptoms.]]>
<![CDATA[Explore glutamate-based depression treatments—esketamine and dextromethorphan-bupropion—boost synaptogenesis and deliver fast relief when monoamines fail.]]>
<![CDATA[Why settle for “less bad”? Clinicians urge aggressive depression care aimed at true remission, balancing side effects and patient priorities.]]>