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BACKGROUND: Acute pancreatitis (AP) is an unpredictable and potentially fatal disorder. A derailed or unbalanced immune response may be the root of the disease's severe course. Disorders of lipid metabolism are highly correlated with the occurrence and severity of AP. We aimed to characterize the contribution and immunological characteristics of lipid metabolism-related genes (LMRGs) in non-mild acute pancreatitis (NMAP) and identify a robust subtype and biomarker for NMAP. METHODS: The expression mode of LMRGs and immune characteristics in NMAP were examined. Then LMRG-derived subtypes were identified using consensus clustering. The weighted gene co-expression network analysis (WGCNA) was utilized to determine hub genes and perform functional enrichment analyses. Multiple machine learning methods were used to build the diagnostic model for NMAP patients. To validate the predictive effectiveness, nomograms, receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) were used. Using gene set variation analysis (GSVA) and single-cell analysis to study the biological roles of model genes. RESULTS: Dysregulated LMRGs and immunological responses were identified between NMAP and normal individuals. NMAP individuals were divided into two LMRG-related subtypes with significant differences in biological function. The cluster-specific genes are primarily engaged in the regulation of defense response, T cell activation, and positive regulation of cytokine production. Moreover, we constructed a two-gene prediction model with good performance. The expression of CARD16 and MSGT1 was significantly increased in NMAP samples and positively correlated with neutrophil and mast cell infiltration. GSVA results showed that they are mainly upregulated in the T cell receptor complex, immunoglobulin complex circulating, and some immune-related routes. Single-cell analysis indicated that CARD16 was mainly distributed in mixed immune cells and macrophages, and MGST1 was mainly distributed in exocrine glandular cells. CONCLUSIONS: This study presents a novel approach to categorizing NMAP into different clusters based on LMRGs and developing a reliable two-gene biomarker for NMAP.
Assuntos
Pancreatite , Humanos , Pancreatite/genética , Doença Aguda , Metabolismo dos Lipídeos , BiomarcadoresRESUMO
BACKGROUND: Ziprasidone mesylate injection is an atypical antipsychotic drug which is recently approved in China. In combination with its oral formulation, sequential therapy with ziprasidone brings new interventions to patients with agitation in the acute phase of schizophrenia. The purpose of this 7-day multicenter study conducted in China was to evaluate the efficacy and safety of ziprasidone sequential treatment through intramuscular/oral routes in agitated patients with schizophrenia. METHODS: A total of 95 patients were enrolled from three centers in this study. The study duration was 7 days. In the first 3 days, subjects were administered an intramuscular injection of ziprasidone 10-40 mg daily and started sequentially with oral ziprasidone 40-80 mg at dinner (or lunch) from the day of the last intramuscular injection. In the following 4 days, according to the severity of the symptoms and the drug response, 120-160 mg of ziprasidone was orally administered daily. In total, six visits were scheduled to assess the Positive and Negative Syndrome Scale (PANSS), the Behavioral Activity Rating Scale (BARS), the Clinical Global Impression of Severity (CGI-S), and Improvement (CGI-I) scores throughout the procedure. Lastly, adverse events were recorded during treatment. RESULTS: Out of the 95 patients that were enrolled, 83 cases were effectively completed. Visits 3, 4, 6, PANSS, and PANSS-excited component (PANSS-EC) subscale points, and Visit 2-Visit 6 viewpoints, BARS scale points, and baseline scores denote a progressive downward trend (P < 0.001). In this study, 62 adverse events were reported. The most common adverse events were extrapyramidal symptoms (EPS) (23 cases) and excessive sedation(10 cases), and 13 cases of prolonged QTc interval were reported. CONCLUSIONS: Ziprasidone IM demonstrated significant and rapid reduction in agitation, and sequential oral formulation keep stability and continuation of the treatment can further ensure efficacy. Ziprasidone sequential therapy may provide a new approach to acute agitation in schizophrenic patients. TRIAL REGISTRATION: The Chinese Clinical Trials Registry; URL: https://www.chictr.org.cn : ChiCTR-OIC-16007970.
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Antipsicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Antipsicóticos/efeitos adversos , Piperazinas/efeitos adversos , Tiazóis/efeitos adversos , Injeções Intramusculares , Resultado do Tratamento , Escalas de Graduação PsiquiátricaRESUMO
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is now the major contributor to chronic liver disease. Disorders of lipid metabolism are a major element in the emergence of NAFLD. This research intended to explore lipid metabolism-related clusters in NAFLD and establish a prediction biomarker. METHODS: The expression mode of lipid metabolism-related genes (LMRGs) and immune characteristics in NAFLD were examined. The "ConsensusClusterPlus" package was utilized to investigate the lipid metabolism-related subgroup. The WGCNA was utilized to determine hub genes and perform functional enrichment analysis. After that, a model was constructed by machine learning techniques. To validate the predictive effectiveness, receiver operating characteristic curves, nomograms, decision curve analysis (DCA), and test sets were used. Lastly, gene set variation analysis (GSVA) was utilized to investigate the biological role of biomarkers in NAFLD. RESULTS: Dysregulated LMRGs and immunological responses were identified between NAFLD and normal samples. Two LMRG-related clusters were identified in NAFLD. Immune infiltration analysis revealed that C2 had much more immune infiltration. GSVA also showed that these two subtypes have distinctly different biological features. Thirty cluster-specific genes were identified by two WGCNAs. Functional enrichment analysis indicated that cluster-specific genes are primarily engaged in adipogenesis, signalling by interleukins, and the JAK-STAT signalling pathway. Comparing several models, the random forest model exhibited good discrimination performance. Importantly, the final five-gene random forest model showed excellent predictive power in two test sets. In addition, the nomogram and DCA confirmed the precision of the model for NAFLD prediction. GSVA revealed that model genes were down-regulated in several immune and inflammatory-related routes. This suggests that these genes may inhibit the progression of NAFLD by inhibiting these pathways. CONCLUSIONS: This research thoroughly emphasized the complex relationship between LMRGs and NAFLD and established a five-gene biomarker to evaluate the risk of the lipid metabolism phenotype and the pathologic results of NAFLD.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/patologia , Metabolismo dos Lipídeos/genética , Biomarcadores/metabolismo , FenótipoRESUMO
BACKGROUND: Atherosclerosis is now the main cause of cardiac-cerebral vascular diseases around the world. Disturbances in lipid metabolism have an essential role in the development and progression of atherosclerosis. Thus, we aimed to investigate lipid metabolism-related molecular clusters and develop a diagnostic model for atherosclerosis. METHODS: First, we used the GSE100927 and GSE43292 datasets to screen differentially expressed lipid metabolism-related genes (LMRGs). Subsequent enrichment analysis of these key genes was performed using the Metascape database. Using 101 atherosclerosis samples, we investigated the LMRG-based molecular clusters and the corresponding immune cell infiltration. After that, a diagnostic model for atherosclerosis was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Finally, a series of bioinformatics techniques, including CIBERSORT, gene set variation analysis, and single-cell data analysis, were used to analyze the potential mechanisms of the model genes in atherosclerosis. RESULTS: A total of 29 LMRGs were found to be differentially expressed between atherosclerosis and normal samples. Functional and DisGeNET enrichment analyses indicated that 29 LMRGs are primarily engaged in cholesterol and lipid metabolism, the PPAR signaling pathway, and regulation of the inflammatory response and are also closely associated with atherosclerotic lesions. Two LMRG-related molecular clusters with significant biological functional differences are defined in atherosclerosis. A three-gene diagnostic model containing ADCY7, SCD, and CD36 was subsequently constructed. Receiver operating characteristic curves, decision curves, and an external validation dataset showed that our model exhibits good predictive performance. In addition, three model genes were found to be closely associated with immune cell infiltration, especially macrophage infiltration. CONCLUSIONS: Our study comprehensively highlighted the intricate association between lipid metabolism and atherosclerosis and created a three-gene model for future clinical diagnosis.
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Aterosclerose , Metabolismo dos Lipídeos , Humanos , Metabolismo dos Lipídeos/genética , Aterosclerose/diagnóstico , Aterosclerose/genética , Biomarcadores , Antígenos CD36/genética , Biologia ComputacionalRESUMO
Unlike in randomized clinical trials (RCTs), confounding control is critical for estimating the causal effects from observational studies due to the lack of treatment randomization. Under the unconfoundedness assumption, matching methods are popular because they can be used to emulate an RCT that is hidden in the observational study. To ensure the key assumption hold, the effort is often made to collect a large number of possible confounders, rendering dimension reduction imperative in matching. Three matching schemes based on the propensity score (PSM), prognostic score (PGM), and double score (DSM, ie, the collection of the first two scores) have been proposed in the literature. However, a comprehensive comparison is lacking among the three matching schemes and has not made inroads into the best practices including variable selection, choice of caliper, and replacement. In this article, we explore the statistical and numerical properties of PSM, PGM, and DSM via extensive simulations. Our study supports that DSM performs favorably with, if not better than, the two single score matching in terms of bias and variance. In particular, DSM is doubly robust in the sense that the matching estimator is consistent requiring either the propensity score model or the prognostic score model is correctly specified. Variable selection on the propensity score model and matching with replacement is suggested for DSM, and we illustrate the recommendations with comprehensive simulation studies. An R package is available at https://github.com/Yunshu7/dsmatch.
Assuntos
Causalidade , Viés , Simulação por Computador , Humanos , Pontuação de PropensãoRESUMO
BACKGROUND: Overactivation of the salience network (SN) causes hyperarousal in insomnia patients and is associated with sleep-onset insomnia (SOI). Resting-state microstate 3 (RS-MS3) duration is closely related to SN overactivation. However, whether RS-MS3 duration is a biomarker for SOI has not yet been reported in the literature. In addition, SN activity is also associated with efficiency. However, it is not clear whether there are individual differences in the neural mechanisms of SOI in different efficiency groups. METHODS: Considering that RS-MS3 duration characterizes the stability and persistent activation of the SN in the resting state, the current study investigated the link between SOI measured by sleep latency of Pittsburg Sleep Quality Index (PSQI), efficiency measured by Kirton Adaption-Innovation Inventory (KAI), and RS-MS3 in a Chinese healthy (subclinical) student population, using electroencephalography (EEG) microstate analysis. RESULTS: We found that RS-MS3 duration was positively correlated with sleep latency and efficiency. The interaction between sleep latency and efficiency was significant. Simple slope analysis showed that high sleep latency was positively correlated with longer RS-MS3 duration in participants with higher efficiency scores. This correlation did not exist in participants with low efficiency scores. CONCLUSIONS: RS-MS3 duration may serve as a biomarker for SOI. There is heterogeneity in the relationship between SOI and RS-MS3 duration between individuals with high and low efficiency.
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Distúrbios do Início e da Manutenção do Sono , Eletroencefalografia , Humanos , Sono/fisiologia , Distúrbios do Início e da Manutenção do Sono/complicações , Fatores de TempoRESUMO
BACKGROUND: The apolipoprotein E (ApoE) gene polymorphisms are correlated with blood lipid levels and several neuropsychiatric symptoms. Therefore, this study aimed to examine whether the ApoE rs429358 affected the development and clinical symptoms of schizophrenia and to explore the relationship between apolipoproteins levels and clinical symptoms. METHODS: The ApoE rs429358 was genotyped using a case-control design. The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate the psychopathology of all patients. RESULTS: A total of 637 patients with schizophrenia and 467 healthy controls were recruited. We found no significant differences in the genotype and allele distribution between the patient and control groups. A significant correlation between PANSS negative symptoms and ApoA1 levels (p = 0.048) or ApoB levels (p = 0.001) was found in patients with schizophrenia, which was also confirmed by linear regression analyses (p = 0.048 vs. p = 0.001). Interestingly, only in the T homozygote group, ApoA1 and ApoB levels were predictors of the PANSS negative symptom score (p = 0.008 vs. p = 0.012), while in the C allele carrier group, no correlation was observed. CONCLUSIONS: This study found that the levels of ApoA1 and ApoB were negatively associated with negative symptoms of patients with schizophrenia. Furthermore, the association between ApoA1 or ApoB levels and psychopathology of schizophrenia was regulated by ApoE rs429358.
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For ordinal outcomes, the average treatment effect is often ill-defined and hard to interpret. Echoing Agresti and Kateri, we argue that the relative treatment effect can be a useful measure, especially for ordinal outcomes, which is defined as γ=pr{Yi(1)>Yi(0)}-pr{Yi(1)Assuntos
Modelos Estatísticos
, Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos
, Biometria
, Cárdia
, Causalidade
, Simulação por Computador
, Feminino
, Humanos
, Masculino
, Estudos Observacionais como Assunto/estatística & dados numéricos
, Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos
, Estupro/prevenção & controle
, Neoplasias Gástricas/mortalidade
, Neoplasias Gástricas/terapia
, Resultado do Tratamento
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BACKGROUND: Obstructive sleep apnea (OSA) is a probable risk factor with speculative roles in the induction or aggravation of acute ischemic stroke (AIS). METHODS: The association between OSA and AIS severity was retrospectively analyzed using clinical data of first-onset AIS patients, admitted to our hospital between January 2013 and September 2016. Eligible patients were categorized based on the presence of OSA prior to stroke. Stroke severity and functional outcomes were evaluated using the National Institute of Health Stroke Severity Scale (NIHSS) and the modified Rankin scale (mRS), respectively. RESULTS: No significant differences were observed among OSA and non-OSA groups for infarction volume, NIHSS at admission and discharge, or mRS at discharge and at the 3-month follow-up (all P > .05). OSA prior to stroke negatively correlated with infarction volume (Pâ¯=â¯.008), NIHSS at discharge (Pâ¯=â¯.006), and the 3-month mRS (Pâ¯=â¯.015). In addition to OSA, it was also found that infarction volume significantly correlated with large artery occlusion (LAO), anterior circulation involvement, neutrophil count, and fibrinogen level; NIHSS at discharge significantly correlated with LAO, transient ischemia attack (TIA), neutrophil count, and thrombolysis; and the 3-month mRS significantly correlated with LAO, TIA, age, neutrophil count, and thrombolysis. CONCLUSIONS: OSA before AIS does not increase the severity of stroke. The negative association between OSA and infarction volume, stroke severity, and clinical outcomes suggests an endogenous neuroprotective effect.
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Isquemia Encefálica/fisiopatologia , Encéfalo/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , China/epidemiologia , Avaliação da Deficiência , Feminino , Nível de Saúde , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Fatores de TempoRESUMO
Studies and findings regarding the impact of schizophrenia on quality of life (QOL) has been highly variable. This meta-analysis compared QOL between schizophrenia subjects and healthy controls with a focus on standardized measures. A systematic literature search was conducted through Pubmed, PsycINFO, EMBASE, Cochrane Library and Web of Science databases. Only studies using the World Health Organization Quality of Life (WHOQOL) or its brief version or the Short Form-36 Health Survey (SF-36) were included. Fifteen case-control studies with 2195 schizophrenia subjects and 1508 healthy controls were included in this meta-analysis. The WHOQOL/WHOQOL-BREF score was significantly lower in physical health (SMD = -1.80, 95% CI: -2.31 to -1.28, P < 0.001), psychological health (SMD = -1.28, 95% CI: -1.72 to -0.83, P < 0.001), social relationships (SMD = -1.60, 95% CI: -2.05 to -1.15, P < 0.001), and environment domains (SMD = -0.98, 95% CI: -1.38 to -0.59, P < 0.001) in schizophrenia subjects compared to controls. The SF-36 score was significantly lower in both physical (SMD = -1.09, 95% CI: -1.41 to -0.76, P < 0.001 and mental health domains (SMD = -2.08, 95% CI: -3.58 to -0.59, P = 0.006) in schizophrenia subjects than in controls. Subgroup and meta-regression analyses found that age, male gender, illness duration and income have significant moderating effects on QOL. The meta-analysis of studies with standardized measures confirmed that QOL in schizophrenia subjects is significantly lower than healthy controls. Effective interventions should be developed to improve QOL for this population.
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Qualidade de Vida/psicologia , Psicologia do Esquizofrênico , Adulto , Estudos de Casos e Controles , Feminino , Humanos , MasculinoRESUMO
In 2006, the "unlocking program" was implemented in Hebei province, China to promote the human rights for people with severe mental illness who were physically restrained at home. We assessed the long term outcomes of the "unlocking program" following the provision of hospital and community psychiatric care over 10 years and explored their associated factors. A total of 107 patients with severe mental illness who were "unlocked" in the program were included. Outcome measures were collected with standardized rating scales at 2 separate time points in August 2012 and November 2016. Poor outcome was defined either as being relocked, or missing to follow up or death. In 2012, 36 patients (33.6%) had poor outcomes. Poor outcome was positively associated with follow-up length and less caregiver burden at baseline. By 2016, 53 patients (49.5%) were found to have poor outcomes. There was only a trend of positive association between poor outcome and less caregiver burden at baseline. Poor long-term outcomes were common in patients with severe mental illness following the "unlocking program". Evidence-based treatment strategies and mental health services to improve the outcomes and protect the human rights of patients subjected to being locked in the community are urgently needed.
Assuntos
Transtornos Mentais , Saúde Mental , Direitos do Paciente , Psicoterapia/métodos , Adulto , China/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Transtornos Mentais/reabilitação , Serviços de Saúde Mental/estatística & dados numéricos , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Adulto JovemRESUMO
Objective To systematically evaluate the efficacy of clozapine combined with other antipsychotic drugs in the treatment of refractory schizophrenia. Methods We searched Medline, EMBASE, and China Biology Medicine databases in both English and Chinese for randomized controlled trials, quasi-randomization controlled trials, and clinical controlled trials concerning the combinations of clozapine with other antipsychotic drugs for refractory schizophrenia. Quality assessment and data extraction were conducted with the Cochrane collaboration's RevMan 5.3 software. Results Totally 47 trials met the inclusion criteria, in which clozapine was combined with risperidone, aripiprazole, sulpiride, ziprasidone, modified electroconvulsive therapy, valproate, or lithium carbonate, respectively. Analysis showed that most combination strategies were superior to clozapoine alone (P<0.05), except for the combination with lithium carbonate(8 weeks: RR=1.27, 95%CI=0.82-1.97,P=0.28; 12 weeks: RR=1.53, 95% CI=0.45-5.13, P=0.49). Conclusion Reasonable combination of clozapine with other drugs may improve the therapeutic effectiveness and reduce adverse reactions and thus can be effectively used for treating refractory schizophrenia.
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Antipsicóticos/uso terapêutico , Clozapina/uso terapêutico , Esquizofrenia/tratamento farmacológico , Benzodiazepinas , China , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Approximately 10% to 40% of patients with gastroesophageal reflux disease (GERD) exhibit poor response to proton pump inhibitors (PPIs), indicating refractory GERD (RGERD). Banxia Houpu Decoction is a traditional Chinese medicine formula used for treating GERD, particularly for atypical symptoms. This study aimed to investigate the improvement of different symptoms in RGERD patients treated with Banxia Houpu Decoction and identify relevant factors influencing its efficacy. From November 2021 to November 2022, a total of 89 RGERD patients voluntarily participated in this clinical study at our hospital. They were randomly assigned to 2 treatment groups: the Banxia Houpu Decoction group and the Western medicine group. The former received standard-dose Banxia Houpu Decoction, while the latter had a switch in PPI type with double-dose maintenance and the addition of magnesium aluminum carbonate as an acid suppressant. The improvement of different symptoms was compared between the 2 groups. Clinical data, including age, gender, gastric mucosal status, and esophagitis severity, were collected. Univariate analysis was performed to explore factors influencing the therapeutic effect of Banxia Houpu Decoction. Both treatment groups showed significant improvement in Frequency Scale for the Symptoms of GERD (FSSG) scores. The Banxia Houpu Decoction group exhibited the most significant efficacy in relieving throat burning sensation (Pâ =â .003) and frequent hiccups (Pâ =â .003). It also demonstrated improvement in swallowing difficulty (Pâ =â .048) and postprandial abdominal distension (Pâ =â .041), surpassing the Western medicine group. The Western medicine group had the most significant improvement in heartburn sensation (Pâ =â .008) and showed significant improvement in gastric burning sensation (Pâ =â .022), surpassing Banxia Houpu Decoction. Age (Pâ =â .025) and gastroesophageal flap valve (GEFV) grade (Pâ =â .014) were identified as factors influencing the efficacy of Banxia Houpu Decoction. Banxia Houpu Decoction exhibits superior efficacy compared to double-dose PPI combined with acid suppressants in relieving symptoms such as throat burning sensation, swallowing difficulty, and frequent hiccups. It shows significant efficacy in patients under 60 years of age and with GEFV grades I-II.
Assuntos
Medicamentos de Ervas Chinesas , Refluxo Gastroesofágico , Inibidores da Bomba de Prótons , Humanos , Refluxo Gastroesofágico/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Resultado do Tratamento , IdosoRESUMO
Purpose: Depressive disorder is a mental health disorder with complicated etiopathogenesis. Environmental stress and neurodevelopment combined with other factors contribute to the occurrence of depression. Especially for the depressive disorder with chronic negative stress, it has characteristics of recurrence and poor curative effect because of unclear mechanism. Here, we investigated the hippocampal structures and functional connectivity (FC) according to resting-state functional magnetic resonance imaging in patients with depression who underwent chronic negative stress. Patients and Methods: A total of 65 patients with depression (34 underwent chronic negative stress and 31 non-underwent chronic negative stress) and 30 healthy controls who did not undergo chronic negative stress were included in the study. The volumes of hippocampal subfields, seed-based FCs between hippocampus and the whole brain voxels, and ROI-wise-based FC between hippocampal subfields were compared among the three groups. Results: In the patients with depression who underwent chronic negative stress, the volumes of right_GC-ML-DG-head, right_CA4-head and right_CA3-head increased, FCs between Temporal_Mid_R, Precuneus_R, Frontal_Sup_R, Temporal_Sup_R, Angular_L, Frontal_Inf_Tri_R, Supp_Motor_Area_R, Precentral_L and hippocampus increased, and FCs between parasubiculum and CA3, and presubiculum and CA1 decreased. When compared to the patients who did not undergo chronic negative stress, the patients who underwent chronic negative stress had larger volumes of right_GC-ML-DG-head and right_CA3-head, higher FCs between Frontal_Sup_R, Frontal_Inf_Tri_R and hippocampus, and lower FCs between presubiculum and CA1. Conclusion: The depression underwent chronic negative stress may experience disrupted hippocampal structures and functional connectivity. It may be one of potential depressive disorder subtypes.
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Pancreatic cancer (PC) is one of the most common malignant tumors of the digestive tract and has a very high mortality rate worldwide. Different PC patients may respond differently to therapy and develop therapeutic resistance due to the complexity and variety of the tumor microenvironment. The Eph/ephrin signaling pathway is extensively involved in tumor-related biological functions. However, the key function of the Eph/ephrin signaling pathway in PC has not been fully elucidated. We first explored a pan-cancer overview of Eph/ephrin signaling pathway genes (EPGs). Then we grouped the PC patients into 3 subgroups based on EPG expression levels. Significantly different prognoses and tumor immune microenvironments between different subtypes further validate Eph/ephrin's important role in the pathophysiology of PC. Additionally, we estimated the IC50 values for several commonly used molecularly targeted drugs used to treat PC in the three clusters, which could help patients receive a more personalized treatment plan. Following a progressive screening of optimal genes, we established a prognostic signature and validated it in internal and external test sets. The receiver operating characteristic (ROC) curves of our model exhibited great predictive performance. Meanwhile, we further validated the results through qRT-PCR and immunohistochemistry. Overall, this research provides fresh clues on the prognosis and therapy of PC as well as the theoretical groundwork for future Eph/ephrin signaling pathway research.
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Biologia Computacional , Efrinas , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas , Receptores da Família Eph , Transdução de Sinais , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Efrinas/metabolismo , Efrinas/genética , Biologia Computacional/métodos , Prognóstico , Receptores da Família Eph/metabolismo , Receptores da Família Eph/genética , Microambiente Tumoral/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Perfilação da Expressão GênicaRESUMO
In clinical practice, accurately identifying self-injurious behavior among adolescents with major depressive disorder (MDD) is crucial for individualized treatment. This study aimed to examine the differences in prefrontal cortex activation using the functional near-infrared spectroscopy (fNIRS) during the verbal fluency task (VFT) assessment of adolescents with MDD and self-harm (SH) compared with those without SH. A total of 60 eligible patients were included for final analysis, with the SH group containing 36 participants, and the Non-SH group containing 24 participants. We found that right middle frontal gyrus (rMFG) was more activated in the SH group than that in the Non-SH group during the VFT assessments (z = -3.591, p = 0.004, FDR correction). The z-scores of beta values of rMFG exhibited a good discriminatory power with the area under the curve (AUC) in distinguishing the two groups (AUC = 0.775, p < 0.001). These findings reveal that the fNIRS-VFT paradigm may be a useful tool for discovering neurobiological differences among adolescents with MDD.
Assuntos
Transtorno Depressivo Maior , Córtex Pré-Frontal , Comportamento Autodestrutivo , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Masculino , Feminino , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Adolescente , Comportamento Autodestrutivo/fisiopatologia , Comportamento Autodestrutivo/diagnóstico por imagem , CriançaRESUMO
BACKGROUND: Glycans constitute the primary components of proteins that regulate key carcinogenic processes in cancer progression. This study investigated the significance of O-glycan synthesis in the pathogenesis, outcome, and therapy of pancreatic cancer (PC). METHODS: Transcriptomic data and clinical prognostic information of PC were acquired via TCGA and GEO databases. CSA database was used to obtain single-cell data of PC. The O-glycan biosynthesis signaling pathway and its related genes were acquired via the MSigDB platform. The nonnegative matrix factorization (NMF) clustering was utilized to construct the O-glycan biosynthesis-associated molecular subtypes in PC. The LASSO and Cox regression were utilized to build the prognostic prediction model. We utilized real-time quantitative PCR (qRT-PCR) to verify the expressed levels of model genes. Single-cell analysis was utilized to investigate the levels of target genes and O-glycan biosynthesis signaling pathway in the PC tumour microenvironment. RESULTS: : We obtained 30 genes related to O-glycan biosynthesis, among which 15 were associated with the prognosis of PC. All PC samples were grouped into two distinct molecular subtypes associated with O-glycan biosynthesis: OGRGcluster C1 and OGRGcluster C2, and compared to OGRGcluster C1. PCs in OGRGcluster C2 had a more advanced clinical stage and pathological grade, worse prognosis, and more active O-glycan biosynthesis function. Immune analysis indicated that naïve B cell, CD8+ T cell, memory-activated CD4+ T cell, and monocytes displayed remarkably higher infiltration levels in OGRGcluster C1 while resting NK cell, macrophages M0, resting dendritic cell, activated dendritic cell, and neutrophils exhibited markedly higher infiltration levels in OGRGcluster C2. OGRGcluster C1 exhibited higher sensitivities to drugs, such as cisplatin, irinotecan, KRAS(G12C) inhibitor-12, oxaliplatin, paclitaxel, and sorafenib. Besides, we built the O-glycan biosynthesis-related prognostic model (including SPRR1B, COL17A1, and ECT2) with a good prediction performance. SPRR1B, COL17A1, and ECT2 were remarkably highly expressed in PC tissues and linked to a poor outcome. Single-cell analysis revealed that O-glycan biosynthesis was observed only in PC, and consistent with this, the target genes were significantly enriched in PC. CONCLUSION: We first constructed molecular subtypes and prognostic models related to O-glycan biosynthesis in PC. It is clear that O-glycan biosynthesis is related to the development, prognosis, immune microenvironment, and treatment of PC. This provides new strategies for stratification, diagnosis, and treatment of PC patients.
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BACKGROUND: Research in functional asymmetry of Major Depressive Disorder (MDD) under different tasks is crucial for clinical diagnose. METHODS: Fifty individuals with MDD and twenty healthy controls (HCS) were recruited for hemodynamic data collection under four fNIRS tasks (Emotional picture, Verbal fluency, Fingering and Negative emotional picture description task). Integral values and functional connectivity strength were employed to probe neural activation and functional connectivity in frontal and temporal lobes in MDD. Following, asymmetry characteristic of the frontal cortex between MDD and HCS under four tasks were carefully analyzed and compared. RESULTS: Individuals with MDD demonstrated heightened connectivity between the frontal and right temporal lobes and reduced connectivity between the frontal and left temporal lobes compared to HCS in all tasks. Additionally, MDD exhibited attenuated activation in the left frontal lobes and exaggerated activation in the right frontal lobes, diverging from HCS. Furthermore, the disparities in left-right asymmetry characteristic of frontal cortex activation between MDD and HCS were more pronounced during the combined task. LIMITATIONS: Further research is required to grasp the neurophysiological mechanisms governing left-right asymmetry across various tasks and the influence of task-induced brain fatigue on cerebral cortex hemodynamics in MDD. CONCLUSION: The left-right asymmetry feature provides valuable neurophysiological insights for diagnosing MDD clinically. Variations in activation patterns and functional connectivity features between MDD and HCS are closely tied to the task chosen. Thus, in clinical practice, carefully selecting appropriate fNIRS tasks and relevant features can significantly improve the diagnostic accuracy of MDD.
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Objective: Suicidal behavior is strongly correlated with depressive symptoms and the degree of suicidal ideation. Cognitive impairment may have varying degrees of influence on suicidal ideation (SI) and suicidal attempts (SA). The aim of this study was to identify the cognitive biomarkers that distinguish suicidal ideation from suicidal attempts in adolescents. Methods: The cross-sectional sample comprised 54 adolescents with major depressive disorder (MDD) and 32 healthy controls (HC). The THINC-it was utilized to assess cognitive function of all the samples. Suicidal ideation was examined by the Positive and Negative Suicide Ideation Scale (PANSI). Based on the type of data, one-way ANOVA or Kruskal-Wallis was performed to investigate group differences. Bonferroni post-hoc analysis was employed for regulating type I error for pairwise comparisons. Network analysis was used to compare the networks associated with suicidal ideation, depression symptoms, and cognitive function between SA and SI. Results: The depression symptoms (HAMD-17) (F=72.515, P<0.001) and suicidal ideation (PANSI) (F=267.952, P<0.001) in the SA were higher than those in the SI. Analysis of between-group differences showed SA performed worse in THINC-it, especially in "Spotter (SP)" (P=0.033), "Objective cognition score (OS)" (P=0.027) and "Composite score (CS)" (P=0.017). Compared with SI, network analysis revealed that SA had a unique network of cognitive function, depressive symptoms, and suicidal ideation. Nevertheless, both networks exhibit comparable performance concerning the node strength of cognitive function. Within their separate networks, the aspects of CS, OS, and SP have emerged as the three most crucial elements. Conclusion: Adolescents with SI or SA exhibit a broad spectrum of cognitive impairments. Attention impairment can be beneficial in discerning between SI and SA. Future interventions for adolescent suicide can center on attention and the comprehensive cognitive ability that it represents.
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BACKGROUND: Qing-Yi Recipe, a classic traditional Chinese medicine (TCM), is widely used for treating acute diseases of the abdomen, especially pancreatitis, the efficacy of which has been demonstrated in more than thirty clinical trials. However, the in-vivo pharmacodynamic material basis for this formula remains unclear. METHODS: A sensitive and accurate method for quantifying twenty-two potential bioactive constituents of Qing-Yi Recipe in biological samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and this method was fully validated. Then, the integrated pharmacokinetic properties of Qing-Yi Recipe and its major metabolites in rats were investigated using the post-listed granules at both dosages. Subsequently, tissue distributions of those constituents in nine organs (especially the pancreas) were determined, and the overall parameters between the two formulations were compared. RESULTS: Though the chemical profiles of the formulas varied across formulations, the overall exposure level was very similar, and baicalin, wogonoside, geniposide, rhein, costunolide, and paeoniflorin were the top six bioactive compounds in the circulation. All twenty-two natural products reached their first peak within 2 h, and several of them exhibited bimodal or multimodal patterns under the complicated transformation of metabolic enzymes, and the parameters of these products markedly changed compared with those of monomers. Diverse metabolites of emodin and baicalin/baicalein were detected in circulation and tissues, augmenting the in vivo forms of these compounds. Finally, the enrichment of tetrahydropalmatine and corydaline in the pancreas were observed and most compounds remained in the gastrointestinal system, providing a foundation basis for their potential regulatory effects on the gut microbiota as well as the intestinal functions. CONCLUSION: Herein, the pharmacokinetic properties and tissue distribution of multiple potential active constituents in Qing-Yi Recipe were investigated at two dosages, providing a pharmacodynamic material basis of Qing-Yi Recipe for the first time. This investigation is expected to provide a new perspective and reference for future studies on the physiological disposition and potential pharmacodynamic basis of traditional Chinese medicine to treat acute abdomen diseases.