RESUMO
BACKGROUND: People who undergo sphincter-preserving surgery have high rates of anorectal functional disturbances, known as low anterior resection syndrome (LARS). LARS negatively affects patients' quality of life (QoL) and increases their need for self-management behaviors. Therefore, approaches to enhance self-management behavior and QoL are vital. OBJECTIVE: This study aims to assess the effectiveness of a remote digital management intervention designed to enhance the QoL and self-management behavior of patients with LARS. METHODS: From July 2022 to May 2023, we conducted a single-blinded randomized controlled trial and recruited 120 patients with LARS in a tertiary hospital in Hefei, China. All patients were randomly assigned to the intervention group (using the "e-bowel safety" applet and monthly motivational interviewing) or the control group (usual care and an information booklet). Our team provided a 3-month intervention and followed up with all patients for an additional 3 months. The primary outcome was patient QoL measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. The secondary outcomes were evaluated using the Bowel Symptoms Self-Management Behaviors Questionnaire, LARS score, and Perceived Social Support Scale. Data collection occurred at study enrollment, the end of the 3-month intervention, and the 3-month follow-up. Generalized estimating equations were used to analyze changes in all outcome variables. RESULTS: In the end, 111 patients completed the study. In the intervention group, 5 patients withdrew; 4 patients withdrew in the control group. Patients in the intervention group had significantly larger improvements in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 total score (mean difference 11.51; 95% CI 10.68-12.35; Cohen d=1.73) and Bowel Symptoms Self-Management Behaviors Questionnaire total score (mean difference 8.80; 95% CI 8.28-9.32; Cohen d=1.94) than those in the control group. This improvement effect remained stable at 3-month follow-up (mean difference 14.47; 95% CI 13.65-15.30; Cohen d=1.58 and mean difference 8.85; 95% CI 8.25-9.42; Cohen d=2.23). The LARS score total score had significantly larger decreases after intervention (mean difference -3.28; 95% CI -4.03 to -2.54; Cohen d=-0.39) and at 3-month follow-up (mean difference -6.69; 95% CI -7.45 to -5.93; Cohen d=-0.69). The Perceived Social Support Scale total score had significantly larger improvements after intervention (mean difference 0.47; 95% CI 0.22-0.71; Cohen d=1.81). CONCLUSIONS: Our preliminary findings suggest that the mobile health-based remote interaction management intervention significantly enhanced the self-management behaviors and QoL of patients with LARS, and the effect was sustained. Mobile health-based remote interventions become an effective method to improve health outcomes for many patients with LARS. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200061317; https://tinyurl.com/tmmvpq3.
Assuntos
Qualidade de Vida , Autogestão , Telemedicina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Autogestão/métodos , Adulto , Método Simples-Cego , China , Idoso , Síndrome , Síndrome de Ressecção Anterior BaixaRESUMO
Cognitive dysfunction is not only a common symptom of major depressive disorder, but also a more common residual symptom after antidepressant treatment and a risk factor for chronic and recurrent disease. The disruption of hypocretin regulation is known to be associated with depression, however, their exact correlation is remains to be elucidated. Hypocretin-1 levels are increased in the plasma and hypothalamus from chronic unpredictable mild stress (CUMS) model mice. Excessive hypocretin-1 conducted with hypocretin receptor 1 (HCRTR1) reduced lactate production and brain-derived neurotrophic factor (BDNF) expression by hypoxia-inducible factor-1α (HIF-1α), thus impairing adult hippocampal neuroplasticity, and cognitive impairment in CUMS model. Subsequently, it is found that HCRTR1 antagonists can reverse these changes. The direct effect of hypocretin-1 on hippocampal lactate production and cognitive behavior is further confirmed by intraventricular injection of hypocretin-1 and microPET-CT in rats. In addition, these mechanisms are further validated in astrocytes and neurons in vitro. Moreover, these phenotypes and changes in molecules of lactate transport pathway can be duplicated by specifically knockdown of HCRTR1 in hippocampal astrocytes. In summary, the results provide molecular and functional insights for involvement of hypocretin-1-HCRTR1 in altered cognitive function in depression.
RESUMO
AIM: This study aims to translate the English version of the 'caring ability of family caregivers of patients with cancer scale (CAFCPCS)' into Chinese and validate its psychometric properties in the family caregivers of elderly patients with cancer. DESIGN: A methodological study. METHODS: Based on the Brislin translation model, the original scale will be translated and back-translated, the Delphi expert consultation method will be adopted for cross-cultural adaptation, and the pilot will be carried out in 20-30 family caregivers of elderly patients with cancer. Then, a dual-centre prospective study will be conducted by recruiting 371-542 family caregivers of elderly patients with cancer to validate the psychometric properties of the Chinese version of CAFCPCS. RESULTS: The scale's content validity will be evaluated using the Delphi expert inquiry method, and the face validity will be evaluated using a pre-experiment. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) will be used to assess structural validity, while internal consistency reliability and split-half reliability will be used to assess reliability. PATIENT OR PUBLIC CONTRIBUTION: Public involvement is of great significance for this study. Participants will be used in a pre-test to give feedback on whether the contents of the clinical pilot version of CAFCPCS after expert consultation can reflect real problems and whether the sentences can be well understood. Based on their opinions, the research group will further refine the scale.
Assuntos
Cuidadores , Neoplasias , Psicometria , Humanos , Cuidadores/psicologia , Psicometria/instrumentação , Psicometria/normas , Neoplasias/psicologia , Neoplasias/enfermagem , Reprodutibilidade dos Testes , Inquéritos e Questionários/normas , Idoso , Estudos Prospectivos , Masculino , Feminino , China , Técnica Delphi , Tradução , Pessoa de Meia-Idade , TraduçõesRESUMO
Sepsis is characterized by a metabolic disorder of amino acid occurs in the early stage; however, the profile of serum amino acids and their alterations associated with the onset of sepsis remain unclear. Thus, our objective is to identify the specific kinds of amino acids as diagnostic biomarkers in pediatric patients with sepsis. Serum samples were collected from patients with sepsis admitted to the pediatric intensive care unit (PICU) between January 2019 and December 2019 on the 1st, 3rd and 7th day following admission. Demographic and laboratory variables were also retrieved from the medical records specified times. Serum amino acid concentrations were detected by UPLC-MS/MS system. PLS-DA (VIP > 1.0) and Kruskal-Wallis test (p < 0.05) were employed to identify potential biomarkers. Spearman's rank correlation analysis was conducted to find the potential association between amino acid levels and clinical features. The diagnostic utility for pediatric sepsis was assessed using receiver operating characteristic (ROC) curve analysis. Most of amino acid contents in serum were significantly decreased in patients with sepsis, but approached normal levels by the seventh day post-diagnosis. Threonine (THR), lysine (LYS), valine (VAL) and alanine (ALA) emerged as potential biomarkers related for sepsis occurrence, though they were not associated with PELOD/PELOD-2 scores. Moreover, alterations in serum THR, LYS and ALA were linked to complications of brain injury, and serum ALA levels were also related to sepsis-associated acute kidney injury. Further analysis revealed that ALA was significantly correlated with the Glasgow score, serum lactate and glucose levels, C-reactive protein (CRP), and other indicators for liver or kidney dysfunction. Notably, the area under the ROC curve (AUC) for ALA in distinguishing sepsis from healthy controls was 0.977 (95% CI: 0.925-1.000). The serum amino acid profile of children with sepsis is significantly altered compared to that of healthy controls. Notably, ALA shows promise as a potential biomarker for the early diagnosis in septic children.
Assuntos
Alanina , Biomarcadores , Unidades de Terapia Intensiva Pediátrica , Sepse , Humanos , Sepse/sangue , Sepse/diagnóstico , Biomarcadores/sangue , Masculino , Projetos Piloto , Feminino , Pré-Escolar , Alanina/sangue , Criança , Lactente , Curva ROC , Aminoácidos/sangue , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Impaired mitochondrial dynamics have been identified as a significant contributing factor to reduced neurogenesis under pathological conditions. However, the relationship among mitochondrial dynamics, neurogenesis, and spatial memory during normal development remains unclear. This study aims to elucidate the role of mitophagy in spatial memory mediated by neurogenesis during development. METHODS: Adolescent and adult male mice were used to assess spatial memory performance. Immunofluorescence staining was employed to evaluate levels of neurogenesis, and mitochondrial dynamics were assessed through western blotting and transmission electron microscopy. Pharmacological interventions further validated the causal relationship among mitophagy, neurogenesis, and behavioral performance during development. RESULTS: The study revealed differences in spatial memory between adolescent and adult mice. Diminished neurogenesis, accompanied by reduced mitophagy, was observed in the hippocampus of adult mice compared to adolescent subjects. Pharmacological induction of mitophagy in adult mice with UMI-77 resulted in enhanced neurogenesis and prolonged spatial memory retention. Conversely, inhibition of mitophagy with Mdivi-1 in adolescent mice led to reduced hippocampal neurogenesis and impaired spatial memory. CONCLUSION: The observed decline in spatial memory in adult mice is associated with decreased mitophagy, which affects neurogenesis in the dentate gyrus. This underscores the therapeutic potential of enhancing mitophagy to counteract age- or disease-related cognitive decline.
Assuntos
Hipocampo , Mitofagia , Neurogênese , Memória Espacial , Animais , Neurogênese/fisiologia , Neurogênese/efeitos dos fármacos , Mitofagia/fisiologia , Mitofagia/efeitos dos fármacos , Memória Espacial/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial/fisiologia , QuinazolinonasRESUMO
As a versatile element for maintaining homeostasis, the chemokine system has been reported to be implicated in the pathogenesis of immune thrombocytopenia (ITP). However, research pertaining to chemokine receptors and related ligands in adult ITP is still limited. The states of several typical chemokine receptors and cognate ligands in the circulation were comparatively assessed through various methodologies. Multiple variable analyses of correlation matrixes were conducted to characterize the correlation signatures of various chemokine receptors or candidate ligands with platelet counts. Our data illustrated a significant decrease in relative CXCR3 expression and elevated plasma levels of CXCL4, 9-11, 13, and CCL3 chemokines in ITP patients with varied platelet counts. Flow cytometry assays revealed eminently diminished CXCR3 levels on T and B lymphocytes and increased CXCR5 on cytotoxic T cell (Tc) subsets in ITP patients with certain platelet counts. Meanwhile, circulating CX3CR1 levels were markedly higher on T cells with a concomitant increase in plasma CX3CL1 level in ITP patients, highlighting the importance of aberrant alterations of the CX3CR1-CX3CL1 axis in ITP pathogenesis. Spearman's correlation analyses revealed a strong positive association of peripheral CXCL4 mRNA level, and negative correlations of plasma CXCL4 concentration and certain chemokine receptors with platelet counts, which might serve as a potential biomarker of platelet destruction in ITP development. Overall, these results indicate that the differential expression patterns and distinct activation states of peripheral chemokine network, and the subsequent expansion of circulating CXCR5+ Tc cells and CX3CR1+ T cells, may be a hallmark during ITP progression, which ultimately contributes to thrombocytopenia in ITP patients.
Assuntos
Receptor 1 de Quimiocina CX3C , Púrpura Trombocitopênica Idiopática , Receptores CXCR3 , Receptores CXCR5 , Humanos , Receptores CXCR3/metabolismo , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/imunologia , Receptor 1 de Quimiocina CX3C/metabolismo , Masculino , Receptores CXCR5/metabolismo , Feminino , Adulto , Pessoa de Meia-Idade , Contagem de Plaquetas , Fator Plaquetário 4/sangue , Fator Plaquetário 4/metabolismo , Idoso , Linfócitos B/imunologia , Linfócitos B/metabolismoRESUMO
Biomass-derived materials can help develop efficient, environmentally friendly and cost-effective catalysts, thereby improving the sustainability of hydrogen production. Herein, we propose a simple method to produce nickel and molybdenum composites decorated spent coffee grounds (SCG) as an efficient catalyst, SCG(200)@NiMo, for electrocatalytic hydrogen production. The porous carbon supporter derived form SCG provided a larger surface, prevented aggregation during the high temperature pyrolysis, optimized the electronic structure by N and provided a reducing atmosphere for the oxides reduction to form heterojunctions. The sieved SCG showed obvious improvement of HER performance and enhanced conductivity and long-term durability. The obtained SCG(200)@NiMo exhibits the highest electrochemical performance for the hydrogen evolution reaction process, as evidenced by the overpotential of only 127â mV at a current density of ɳ10 and 97.7 % catalytic activity retention even after 12â h of operation. This work may stimulate further exploration of efficient electrocatalysts derived from biomass.
RESUMO
BACKGROUND AND AIM: Immunity alterations have been observed in bipolar disorder (BD). However, whether serum positivity of antibodies to Toxoplasma gondii (T gondii), rubella, and cytomegalovirus (CMV) shared clinical relevance with BD, remains controversial. This study aimed to investigate this association. METHODS: Antibody seropositivity of IgM and IgG to T gondii, rubella virus, and CMV of females with BD and controls was extracted based on medical records from January 2018 to January 2023. Family history, type of BD, onset age, and psychotic symptom history were also collected. RESULTS: 585 individuals with BD and 800 healthy controls were involved. Individuals with BD revealed a lower positive rate of T gondii IgG in the 10-20 aged group (OR = 0.10), and a higher positive rate of rubella IgG in the 10-20 (OR = 5.44) and 20-30 aged group (OR = 3.15). BD with family history preferred a higher positive rate of T gondii IgG (OR = 24.00). Type-I BD owned a decreased positive rate of rubella IgG (OR = 0.37) and an elevated positive rate of CMV IgG (OR = 2.12) compared to type-II BD, while BD with early onset showed contrast results compared to BD without early onset (Rubella IgG, OR = 2.54; CMV IgG, OR = 0.26). BD with psychotic symptom history displayed a lower positive rate of rubella IgG (OR = 0.50). LIMITATIONS: Absence of male evidence and control of socioeconomic status and environmental exposure. CONCLUSIONS: Differential antibody seropositive rates of T gondii, rubella, and cytomegalovirus in BD were observed.
Assuntos
Anticorpos Antiprotozoários , Anticorpos Antivirais , Transtorno Bipolar , Citomegalovirus , Imunoglobulina G , Imunoglobulina M , Vírus da Rubéola , Toxoplasma , Humanos , Transtorno Bipolar/imunologia , Transtorno Bipolar/sangue , Feminino , Toxoplasma/imunologia , Adulto , Vírus da Rubéola/imunologia , Citomegalovirus/imunologia , Estudos Transversais , Anticorpos Antivirais/sangue , Adulto Jovem , Imunoglobulina G/sangue , Anticorpos Antiprotozoários/sangue , Adolescente , Pessoa de Meia-Idade , Imunoglobulina M/sangue , Criança , Toxoplasmose/imunologia , Toxoplasmose/sangue , Rubéola (Sarampo Alemão)/imunologia , Infecções por Citomegalovirus/imunologiaRESUMO
Individuals with bipolar disorder (BD) have a greater suicide risk than the general population. In this study, we employed latent profile analysis (LPA) to explore whether Chinese individuals with different phases of BD differed at the levels of suicidal ideation. We recruited 517 patients. Depressive symptoms were measured using the 24-item Hamilton Depression Rating Scale (HAMD-24), and manic symptoms were evaluated using the Young Mania Rating Scale (YMRS). The extent of suicidal thoughts was determined through the Beck Scale for Suicide Ideation (BSSI). The scores of HAMD and YMRS were used to perform LPA. LPA categorized participants into three classes: one exhibiting severe depressive and mild manic symptomatology, another showing severe depressive and severe manic symptomatology, and the third one displaying severe depressive and intermediate manic symptomatology. Suicidal ideation levels were found to be remarkably elevated across all three classes. Additionally, the three classes showed no significant differences in terms of suicidal ideation. Our research confirms the link between depressive symptoms and suicide, independent of the manic symptoms. These findings carry meaning as they provide insight into the suicide risk profiles within different phases of BD.
RESUMO
BACKGROUND: Sepsis-associated encephalopathy (SAE) presents a significant clinical challenge, associated with increased mortality and healthcare expenses. Hyperbaric oxygen therapy (HBOT), involving inhaling pure or highly concentrated oxygen under pressures exceeding one atmosphere, has demonstrated neuroprotective effects in various conditions. However, the precise mechanisms underlying its protective actions against sepsis-associated brain injury remain unclear. This study aimed to determine whether HBOT protects against SAE and to elucidate the impact of the hypoxia-inducible factor-1α (HIF-1α) signaling pathway on SAE. METHODS: The experiment consisted of two parts. In the first part, C57BL/6 J male mice were divided into five groups using a random number table method: control group, sham surgery group, sepsis group, HBOT + sepsis group, and HBOT + sham surgery group. In the subsequent part, C57BL/6 J male mice were divided into four groups: sepsis group, HBOT + sepsis group, HIF-1α + HBOT + sepsis group, and HIF-1α + sepsis group. Sepsis was induced via cecal ligation and puncture (CLP). Hyperbaric oxygen therapy was administered at 1 h and 4 h post-CLP. After 24 h, blood and hippocampal tissue were collected for cytokine measurements. HIF-1α, TNF-α, IL-1ß, and IL-6 expression were assessed via ELISA and western blotting. Microglial expression was determined by immunofluorescence. Blood-brain barrier permeability was quantified using Evans Blue. Barnes maze and fear conditioning were conducted 14 days post-CLP to evaluate learning and memory. RESULTS: Our findings reveal that CLP-induced hippocampus-dependent cognitive deficits coincided with elevated HIF-1α and increased TNF-α, IL-1ß, and IL-6 levels in both blood and hippocampus. Observable activation of microglial cells in the hippocampus and increased blood-brain barrier (BBB) permeability were also evident. HBOT mitigated HIF-1α, TNF-α, IL-1ß, and IL-6 levels, attenuated microglial activation in the hippocampus, and significantly improved learning and memory deficits in CLP-exposed mice. Additionally, these outcomes were corroborated by injecting a lentivirus that overexpressed HIF-1α into the hippocampal region of the mice. CONCLUSION: HIF-1α escalation induced peripheral and central inflammatory factors, promoting microglial activation, BBB impairment, and cognitive dysfunction. However, HBOT ameliorated these effects by reducing HIF-1α levels in Sepsis-Associated Encephalopathy.
Assuntos
Modelos Animais de Doenças , Oxigenoterapia Hiperbárica , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias , Encefalopatia Associada a Sepse , Transdução de Sinais , Animais , Oxigenoterapia Hiperbárica/métodos , Masculino , Camundongos , Encefalopatia Associada a Sepse/metabolismo , Encefalopatia Associada a Sepse/terapia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais/fisiologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/terapia , Sepse/complicações , Sepse/terapia , Sepse/metabolismoRESUMO
OBJECTIVES: This study aims to evaluate the safety and efficacy of escitalopram and sertraline in post-stroke depression (PSD) patients, to provide more reliable therapeutics for cardiovascular and psychiatric clinical practice. METHODS: We recruited 60 patients (aged 40-89 years old) with an ICD-10 diagnosis of PSD, who were then randomly assigned to two groups and treated with flexible doses of escitalopram (10 to 20 mg/day, n = 30) or sertraline (50 to 200 mg/day, n = 30) for consecutive 8 weeks, respectively. The 24-item Hamilton Depression Rating Scale (HAMD-24), the 14-item Hamilton Anxiety Rating Scale (HAMA-14), the Treatment Emergent Symptom Scale (TESS), the Montreal Cognitive Assessment Scale (MOCA), and the Activity of Daily Living scale (ADL) were used to assess patients before, during, and after treatment for depression, anxiety, adverse effects, cognitive function, and daily living activities. Repeated measures ANOVA, the Mann-Whitney U test, the chi-square test (χ2), or Fisher's exact test was employed to assess baseline demographics, response rate, adverse effects rate, and changes in other clinical variables. RESULTS: Significant reduction in HAMD-24 and HAMA-14 scores was evaluated at baseline, as well as 1, 3, 4, 6, and 8 weeks of drug intervention (p < 0.01). There was a significant group difference in post-treatment HAMD-24 scores (p < 0.05), but no difference was observed in HAMA-14 scores (p > 0.05). Further analysis showed a significant variance in the HAMD-24 scores between the two groups at the end of the first week (p < 0.01). The incidence of adverse effects in both patient groups was mild, but there was a statistically significant difference between the two groups (p < 0.05). The improvement in cognitive function and the recovery of daily living abilities were comparable between both groups (p > 0.05). CONCLUSION: Escitalopram and sertraline showed comparable efficacy for anxiety symptoms, cognitive function, and daily living abilities in PSD patients. In addition, escitalopram was more appropriate for alleviating depressive symptoms. To validate the conclusion, trials with a larger sample size are in demand in the future. The registration number is ChiCTR1800017373.
Assuntos
Atividades Cotidianas , Escitalopram , Sertralina , Acidente Vascular Cerebral , Humanos , Sertralina/uso terapêutico , Sertralina/efeitos adversos , Masculino , Idoso , Feminino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso de 80 Anos ou mais , Escitalopram/uso terapêutico , Escitalopram/efeitos adversos , Depressão/tratamento farmacológico , Depressão/etiologia , Resultado do Tratamento , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Escalas de Graduação Psiquiátrica , Antidepressivos/uso terapêutico , Antidepressivos/efeitos adversos , Citalopram/uso terapêutico , Citalopram/efeitos adversosRESUMO
Background: Antipsychotics and mood stabilisers are gathering attention for the disturbance of metabolism. This network meta-analysis aims to evaluate and rank the metabolic effects of the commonly used antipsychotics and mood stabilisers in treating bipolar disorder (BD). Methods: Registries including PubMed, Embase, Cochrane Library, Web of Science, Ovid, and Google Scholar were searched before February 15th, 2024, for randomised controlled trials (RCTs) applying antipsychotics or mood stabilisers for BD treatment. The observed outcomes were twelve metabolic indicators. The data were extracted by two reviewers independently, and confirmed by another four reviewers and a corresponding author. The above six reviewers all participated in data analyses. Data extraction was based on PRISMA guidelines, and quality assessment was conducted according to the Cochrane Handbook. Use a random effects model for data pooling. The PROSPERO registration number is CRD42023466669. Findings: Together, 5421 records were identified, and 41 publications with 11,678 complete-trial participants were confirmed eligible. After eliminating possible sensitivity, risperidone ranked 1st in elevating fasting serum glucose (SUCRA = 90.7%) and serum insulin (SUCRA = 96.6%). Lurasidone was most likely to elevate HbA1c (SUCRA = 82.1%). Olanzapine ranked 1st in elevating serum TC (SUCRA = 93.3%), TG (SUCRA = 89.6%), and LDL (SUCRA = 94.7%). Lamotrigine ranked 1st in reducing HDL (SUCRA = 82.6%). Amisulpride ranked 1st in elevating body weight (SUCRA = 100.0%). For subgroup analyses, quetiapine is more likely to affect indicators of glucose metabolism among male adult patients with bipolar mania, while long-term lurasidone tended to affect glucose metabolism among female patients with bipolar depression. Among patients under 18, divalproex tended to affect glucose metabolism, with lithium affecting lipid metabolism. In addition, most observed antipsychotics performed higher response and remission rates than placebo, and displayed a similar dropout rate with placebo, while no between-group significance of rate was observed among mood stabilisers. Interpretation: Our findings suggest that overall, antipsychotics are effective in treating BD, while they are also more likely to disturb metabolism than mood stabilisers. Attention should be paid to individual applicability in clinical practice. The results put forward evidence-based information and clinical inspiration for drug compatibility and further research of the BD mechanism. Funding: The National Key Research and Development Program of China (2023YFC2506200), and the Research Project of Jinan Microecological Biomedicine Shandong Laboratory (No. JNL-2023001B).
RESUMO
Objectives: This clinical trial primarily aimed to investigate the effects of blonanserin on social functioning in patients with first-episode schizophrenia. Methods: In this prospective, multi-centre, single-arm clinical trial study, blonanserin (flexible oral dose ranging from 8mg to 24mg per day) was given 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. The primary endpoint was social function improvement evaluated by PSP scale at the end of blonanserin treatment. And the secondary endpoint was to validate the efficacy and neurocognitive effects of blonanserin. Adverse drug reactions (ADRs) were also recorded and analysed. Results: A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Fifty-one participants (53.1%) completed the PSP scale measurements at baseline and week 26. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase up to 68.1% ± 103.7% at the end of the treatment (46.6 ± 14.6 at baseline, 69.4 ± 17.4 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Conclusion: Blonanserin treatment exhibited favourable effects on social functioning in individuals with first-episode schizophrenia. The results suggest that blonanserin was effective treatment options for patients with schizophrenia encountering functional impairments.
RESUMO
We employed a Bayesian network meta-analysis for comparison of the efficacy and tolerability of US Food and Drug Administration (FDA)-approved atypical antipsychotics (AAPs) for the treatment of bipolar patients with depressive episodes. Sixteen randomized controlled trials with 7234 patients treated by one of the five AAPs (cariprazine, lumateperone, lurasidone, olanzapine, and quetiapine) were included. For the response rate (defined as an improvement of ≥50% from baseline on the Montgomery-Åsberg Depression Rating Scale [MADRS]), all AAPs were more efficacious than placebo. For the remission rate (defined as the endpoint of MADRS ≤12 or ≤ 10), cariprazine, lurasidone, olanzapine, and quetiapine had higher remission rates than placebo. In terms of tolerability, olanzapine was unexpectedly associated with lower odds of all-cause discontinuation in comparison with placebo, whereas quetiapine was associated with higher odds of discontinuation due to adverse events than placebo. Compared with placebo, lumateperone, olanzapine, and quetiapine showed higher odds of somnolence. Lumateperone had a lower rate of ≥ weight gain of 7% than placebo and other treatments. Olanzapine was associated with a significant increase from baseline in total cholesterol and triglycerides than placebo. These findings inform individualized prescriptions of AAPs for treating bipolar depression in clinical practice.
Assuntos
Antipsicóticos , Transtorno Bipolar , Metanálise em Rede , Humanos , Transtorno Bipolar/tratamento farmacológico , Antipsicóticos/uso terapêutico , Antipsicóticos/efeitos adversos , Estados Unidos , United States Food and Drug Administration , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Fumarato de Quetiapina/uso terapêutico , Fumarato de Quetiapina/efeitos adversos , Olanzapina/uso terapêutico , Olanzapina/efeitos adversosRESUMO
Hypocretin is synthesized exclusively in the hypothalamus and distributes inputs to several areas of the brain, which may play an important role in depression. Our previous study showed that hypocretin-1 was increased in the lateral hypothalamus in female patients with depression compared to female controls. Estrogen acts through estrogen receptor (ER)α and ERß. We studied the possibility of a direct action of estrogen receptors on the expression of human hypocretin. We found that hypocretin-1 plasma levels were significantly higher in female patients with depression than in female controls. Female depression estrogen receptors and hypocretin are colocalized in the human lateral hypothalamus, PC12, and SK-N-SH cells. The estrogen receptor response elements (ERE) that exist in the hypocretin promoter region may directly regulate the gene expression of hypocretin. The synchronicity of change of hypocretin and estradiol both in hypothalamus and plasma was verified in female rats. In the presence of estradiol, specific binding occurs between the recombinant human ER and hypocretin-ERE. Expression of ER combined with estradiol repressed hypocretin promoter activity via the ERE. In conclusion, we found that estradiol may directly affect hypocretin neurons in the human hypothalamus via ER binding to the hypocretin-ERE, which may lead to the sex-specific pathogenesis of depression.
Assuntos
Estrogênios , Receptores de Estrogênio , Masculino , Humanos , Ratos , Feminino , Animais , Orexinas/genética , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estradiol/metabolismo , Receptor beta de Estrogênio/metabolismoRESUMO
Purpose: Venous thromboembolism (VTE) poses a significant threat to individuals' health, yet its correlation with mental disorders remains underappreciated. Here, we conducted a retrospective analysis to explore the characteristics of psychiatric patients presenting with VTE. Methods: We retrospectively analyzed psychiatric inpatients with elevated plasma D-dimer levels at the Mental Health Center, First Affiliated Hospital, Zhejiang University School of Medicine, from January 2014 to January 2022. The inclusion criteria comprised comprehensive demographic and clinical profiles, including laboratory and imaging findings. Results: A cohort of 33 eligible patients was included, with plasma D-dimer levels ranging from 880 to 10,700 µg/L FEU. Significantly higher D-dimer levels were observed in patients diagnosed with severe mental disorders (SMD), such as schizophrenia and bipolar disorder, compared to those with mild mental disorders (MMD), including depression and anxiety disorders (p = 0.007). Furthermore, individuals receiving antipsychotic medications for less than one year exhibited elevated D-dimer levels compared to those on treatment for over one year (p = 0.005). However, normalization of D-dimer levels did not demonstrate a significant association with psychiatric diagnosis or treatment duration (p > 0.05). Conclusion: Our findings suggest that patients diagnosed with SMD or those undergoing antipsychotic treatment for less than one year may have elevated D-dimer levels, indicating a potential predisposition to VTE severity. This underscores the importance of recognizing VTE risk in individuals with severe mental disorders and warrants further investigation into the impact of antipsychotic treatment duration on thrombotic risk.
RESUMO
In this paper, we propose a feed-forward equalizer (FFE)-assisted simplified soft-output MLSE (sMLSE) by collaborating the maximum likelihood sequence estimation (MLSE) with soft-decision low-density-parity-check (LDPC) decoding. The simplified sMLSE results in undetermined log-likelihood ratio (LLR) magnitudes when the reserved level is less than or equal to the half of modulation order. This severely degrades the performance of soft-decision forward error correction (SD-FEC) decoding. In the FFE-assisted simplified sMLSE, we use the LLRs calculated from pre-set FFE to replace these undetermined LLRs of simplified sMLSE. Thus, the proposed method eliminates the SD-FEC decoding performance degradation resulted from simplification. We conduct experiments to transmit 184-Gb/s PAM-4 or 255-Gb/s PAM-8 signal in IM-DD system at C-band to evaluate the performance of the proposed sMLSE. The results show that the proposed sMLSE can effectively compensate for the degradation of LLR quality. For 255-Gb/s PAM-8 signal transmissions, the FFE-assisted simplified sMLSE achieves almost the same SD-FEC decoding performance as the conventional sMLSE but with 85% complexity reduction.
RESUMO
Background: Schizophrenia (SCZ) is a heritable disorder with a polygenic architecture, and the gut microbiota seems to be involved in its development and outcome. In this study, we investigate the interplay between genetic risk and gut microbial markers. Methods: We included 159 first-episode, drug-naïve SCZ patients and 86 healthy controls. The microbial composition of feces was characterized using the 16S rRNA sequencing platform, and five microbial α-diversity indices were estimated [Shannon, Simpson, Chao1, the Abundance-based Eoverage Estimator (ACE), and a phylogenetic diversity-based estimate (PD)]. Polygenic risk scores (PRS) for SCZ were constructed using data from large-scale genome-wide association studies. Effects of microbial α-diversity, microbial abundance, and PRS on SCZ were evaluated via generalized linear models. Results: We confirmed that PRS was associated with SCZ (OR = 2.08, p = 1.22×10-5) and that scores on the Shannon (OR = 0.29, p = 1.15×10-8) and Simpson (OR = 0.29, p = 1.25×10-8) indices were inversely associated with SCZ risk. We found significant interactions (p < 0.05) between PRS and α-diversity indices (Shannon, Simpson, and PD), with the effects of PRS being larger in those exhibiting higher diversity compared to those with lower diversity. Moreover, the PRS effects were larger in individuals with a high abundance of the genera Romboutsia, Streptococcus, and Anaerostipes than in those with low abundance (p < 0.05). All three of these genera showed protective effects against SCZ. Conclusion: The current findings suggest an interplay between the gut microbiota and polygenic risk of SCZ that warrants replication in independent samples. Experimental studies are needed to determine the underpinning mechanisms.
RESUMO
Early detection of bipolar depression (BPD) and major depressive disorder (MDD) has been challenging due to the lack of reliable and easily measurable biological markers. This study aimed to investigate the accuracy of discriminating patients with mood disorders from healthy controls based on task state skin potential characteristics and their correlation with individual indicators of oxidative stress. A total of 77 patients with BPD, 53 patients with MDD, and 79 healthy controls were recruited. A custom-made device, previously shown to be sufficiently accurate, was used to collect skin potential data during six emotion-inducing tasks involving video, pictorial, or textual stimuli. Blood indicators reflecting individual levels of oxidative stress were collected. A discriminant model based on the support vector machine (SVM) algorithm was constructed for discriminant analysis. MDD and BPD patients were found to have abnormal skin potential characteristics on most tasks. The accuracy of the SVM model built with SP features to discriminate MDD patients from healthy controls was 78% (sensitivity 78%, specificity 82%). The SVM model gave an accuracy of 59% (sensitivity 59%, specificity 79%) in classifying BPD patients, MDD patients, and healthy controls into three groups. Significant correlations were also found between oxidative stress indicators in the blood of patients and certain SP features. Patients with depression and bipolar depression have abnormalities in task-state skin potential that partially reflect the pathological mechanism of the illness, and the abnormalities are potential biological markers of affective disorders.