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People tend to intervene in others' injustices by either punishing the transgressor or helping the victim. Injustice events often occur under stressful circumstances. However, how acute stress affects a third party's intervention in injustice events remains open. Here, we show a stress-induced shift in third parties' willingness to engage in help instead of punishment by acting on emotional salience and central-executive and theory-of-mind networks. Acute stress decreased the third party's willingness to punish the violator and the severity of the punishment and increased their willingness to help the victim. Computational modeling revealed a shift in preference of justice recovery from punishment the offender toward help the victim under stress. This finding is consistent with the increased dorsolateral prefrontal engagement observed with higher amygdala activity and greater connectivity with the ventromedial prefrontal cortex in the stress group. A brain connectivity theory-of-mind network predicted stress-induced justice recovery in punishment. Our findings suggest a neurocomputational mechanism of how acute stress reshapes third parties' decisions by reallocating neural resources in emotional, executive, and mentalizing networks to inhibit punishment bias and decrease punishment severity.
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Punição , Estresse Psicológico , Humanos , Punição/psicologia , Masculino , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Feminino , Adulto , Adulto Jovem , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/fisiopatologia , Emoções/fisiologia , Justiça Social , Encéfalo/fisiologia , Imageamento por Ressonância MagnéticaRESUMO
Gastric cancer is a malignant tumor associated with a high mortality rate. Recently, emerging evidence has shown that ferroptosis, a regulated form of cell death induced by iron (Fe)-dependent lipid peroxidation. Nuclear factor E2 related factor 2 (NRF2) is a key regulator of intracellular oxidation homeostasis that plays a pivotal role in controlling lipid peroxidation, which is closely related to the process of ferroptosis. However, the molecular mechanism of NRF2 on ferroptosis remains to be investigated in gastric cancer. In our study, NRF 2 was found to transcriptionally activate Aldo-keto reductase 1 member B1 (AKR1B1) expression in gastric cancer. AKR1B1 is involved in the regulation of lipid metabolism by removing the aldehyde group of glutathione. We found that AKR1B1 is highly expressed in gastric cancer and is associated with a poor prognosis of the patients. In vitro experiments found that AKR1B1 has the ability to promote the proliferation and invasion of gastric cancer cells. AKR1B1 inhibited RSL3-induced ferroptosis in gastric cancer by reducing reactive oxygen species accumulation and lipid peroxidation, as well as decreasing intracellular ferrous ion and malondialdehyde expression and increasing glutathione expression. Our study demonstrated that AKR1B1 resisted RSL3-induced ferroptosis by regulating GPX4, PTGS2 and ACSL4, which was further demonstrated in a xenograft nude mouse model. Our work reveals a critical role for the AKR1B1 in the resistance to RSL3-induced ferroptosis in gastric cancer.
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BACKGROUND: Parenting is a common and potent environmental factor influencing adolescent anxiety. Yet, the underlying neurobiological susceptibility signatures remain elusive. Here, we used a longitudinal twin neuroimaging study to investigate the brain network integration and its heritable relation to underpin the neural differential susceptibility of adolescent anxiety to parenting environments. METHODS: 216 twins from the Beijing Twin Study completed the parenting and anxiety assessments and fMRI scanning. We first identified the brain network integration involved in the influences of parenting at age 12 on anxiety symptoms at age 15. We then estimated to what extent heritable sensitive factors are responsible for the susceptibility of brain network integration. RESULTS: Consistent with the differential susceptibility theory, the results showed that hypo-connectivity within the central executive network amplified the impact of maternal hostility on anxiety symptoms. A high anti-correlation between the anterior salience and default mode networks played a similar modulatory role in the susceptibility of adolescent anxiety to paternal hostility. Genetic influences (21.18%) were observed for the connectivity pattern in the central executive network. CONCLUSIONS: Brain network integration served as a promising neurobiological signature of the differential susceptibility to adolescent anxiety. Our findings deepen the understanding of the neural sensitivity in the developing brain and can inform early identification and personalized interventions for adolescents at risk of anxiety disorders.
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Ansiedade , Encéfalo , Masculino , Humanos , Adolescente , Criança , Encéfalo/diagnóstico por imagem , Ansiedade/genética , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/genética , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Pai , Vias Neurais/diagnóstico por imagemRESUMO
Tightly connected clusters of nodes, called communities, interact in a time-dependent manner in brain functional connectivity networks (FCN) to support complex cognitive functions. However, little is known if and how different nodes synchronize their neural interactions to form functional communities ("modules") during visual processing and if and how this modularity changes postlesion (progression or recovery) following neuromodulation. Using the damaged optic nerve as a paradigm, we now studied brain FCN modularity dynamics to better understand module interactions and dynamic reconfigurations before and after neuromodulation with noninvasive repetitive transorbital alternating current stimulation (rtACS). We found that in both patients and controls, local intermodule interactions correlated with visual performance. However, patients' recovery of vision after treatment with rtACS was associated with improved interaction strength of pathways linked to the attention module, and it improved global modularity and increased the stability of FCN. Our results show that temporal coordination of multiple cortical modules and intermodule interaction are functionally relevant for visual processing. This modularity can be neuromodulated with tACS, which induces a more optimal balanced and stable multilayer modular structure for visual processing by enhancing the interaction of neural pathways with the attention network module.
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Doenças do Nervo Óptico , Traumatismos do Nervo Óptico , Humanos , Doenças do Nervo Óptico/complicações , Doenças do Nervo Óptico/terapia , Encéfalo , Nervo Óptico , Eletroencefalografia , Rede Nervosa/fisiologiaRESUMO
Human functional brain networks are dynamically organized to enable cognitive and behavioral flexibility to meet ever-changing environmental demands. Frontal-parietal network (FPN) and default mode network (DMN) are recognized to play an essential role in executive functions such as working memory. However, little is known about the developmental differences in the brain-state dynamics of these two networks involved in working memory from childhood to adulthood. Here, we implemented Bayesian switching dynamical systems approach to identify brain states of the FPN and DMN during working memory in 69 school-age children and 51 adults. We identified five brain states with rapid transitions, which are characterized by dynamic configurations among FPN and DMN nodes with active and inactive engagement in different task demands. Compared with adults, children exhibited less frequent brain states with the highest activity in FPN nodes dominant to high demand, and its occupancy rate increased with age. Children preferred to attain inactive brain states with low activity in both FPN and DMN nodes. Moreover, children exhibited lower transition probability from low-to-high demand states and such a transition was positively correlated with working memory performance. Notably, higher transition probability from low-to-high demand states was associated with a stronger structural connectivity across FPN and DMN, but with weaker structure-function coupling of these two networks. These findings extend our understanding of how FPN and DMN nodes are dynamically organized into a set of transient brain states to support moment-to-moment information updating during working memory and suggest immature organization of these functional brain networks in childhood, which is constrained by the structural connectivity.
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Mapeamento Encefálico , Memória de Curto Prazo , Adulto , Criança , Humanos , Adolescente , Adulto Jovem , Teorema de Bayes , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Vias Neurais/diagnóstico por imagemRESUMO
The default mode network (DMN) is a workspace for convergence of internal and external information. The frontal parietal network (FPN) is indispensable to executive functioning. Yet, how they interplay to support cognitive development remains elusive. Using longitudinal developmental fMRI with an n-back paradigm, we show a heterogeneity of maturational changes in multivoxel activity and network connectivity among DMN and FPN nodes in 528 children and 103 young adults. Compared with adults, children exhibited prominent longitudinal improvement but still inferior behavioral performance, which paired with less pronounced DMN deactivation and weaker FPN activation in children, but stronger DMN coupling with FPN regions. Children's DMN reached an adult-like level earlier than FPN at both multivoxel activity pattern and intranetwork connectivity levels. Intrinsic DMN-FPN internetwork coupling in children mediated the relationship between age and working memory-related functional coupling of these networks, with posterior cingulate cortex (PCC)-dorsolateral prefrontal cortex (DLPFC) coupling emerging as most prominent pathway. Coupling of PCC-DLPFC may further work together with task-invoked activity in PCC to account for longitudinal improvement in behavioral performance in children. Our findings suggest that the DMN provides a scaffolding effect in support of an immature FPN that is critical for the development of executive functions in children.
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Cognição , Rede de Modo Padrão , Adulto Jovem , Criança , Humanos , Função Executiva/fisiologia , Memória de Curto Prazo/fisiologia , Lobo Frontal , Imageamento por Ressonância Magnética , Mapeamento Encefálico , Encéfalo/fisiologia , Rede Nervosa/fisiologiaRESUMO
BACKGROUND: Post coronavirus disease 2019 (COVID-19) pandemic, the widespread emergence and persistence of brain fog has led to a decline in people's productivity and quality of life. However, the clinical characteristics of COVID-19-associated brain fog are unclear, and standardized assessments are lacking. This study aims to develop a scale for brain fog assessment and support clinical practice and research. METHODS: The 17-item Brain Fog Assessment (BFA) scale was developed using a standardized methodology, including literature review, focus group discussions (FGDs), expert evaluation, and psychometric validation. Eighteen potential items were generated following the literature review. These items were subsequently refined during FGDs, which included input from patients, caregivers, and multidisciplinary experts in neurology, cognitive neuroscience, and psychology. After thorough deliberation and expert evaluation, the item pool was finalized into a 17-item scale. We recruited 1,325 patients recovered from COVID-19 from Chinese communities. Psychometric properties were assessed by reliability and validity analysis. RESULTS: Exploratory factor analysis of the BFA scale revealed a three-factor mode comprising 'cognitive decline' (nine items), 'confusion - disorientation' (five items), and 'fatigue' (three items). The internal consistency of each factor was strong (Cronbach's α: 0.82-0.92). Confirmatory factor analysis showed that the model fit, convergent validity, and discriminant validity of the scale were satisfactory. The test-retest reliability was strong (intraclass correlation coefficient = 0.84). Criterion-related validity analysis showed a strong correlation to the Wood Mental Fatigue Inventory (r = 0.70, p < 0.001). Individuals with a higher BFA score tended to score lower on the Montreal Cognitive Assessment (r = -0.23, p = 0.015). CONCLUSIONS: We established a novel BFA scale to quantify multiple clinical aspects of COVID-19-associated brain fog. Using the BFA scale, fatigue and declining performance in memory, attention, and thought were identified as the main symptoms of COVID-19-associated brain fog. This scale has potential implications for disease monitoring and therapy development for individuals with COVID-19-associated brain fog.
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Addiction is characterized by compulsive engagement despite adverse consequences. Psychobehavioural interventions targeting compulsivity in addictions are relatively rare, particularly for behavioural addictions like internet gaming disorder (IGD). Free from confounding drug-on-brain effects, IGD provides a promising model for understanding neuropsychological processes of addictions. IGD is a global concern in the setting of increasing internet use worldwide. Thus, developing interventions and understanding their mechanisms of action are important. Positive emotional association biases (EABs) towards addiction cues based on reward conditioning may underlie addiction-associated compulsivity. Here, we developed an EAB modification (EABM) protocol and examined whether modifying EABs via cognitive training would alter neurocognitive aspects of addiction-associated compulsivity in IGD. We recruited 90 IGD participants who were randomly assigned to receive EABM or sham training in a 1:1 ratio (clinicaltrials.gov identifier: NCT04068064). The EABM intervention involved six consecutive days of exposure to negative emotional terms linked to gaming stimuli and positive terms linked to non-gaming healthy-alternative stimuli. The sham training involved similar stimuli linked to neutral words. Participants underwent event-related functional MRI while performing a regulation-of-craving task and received several behavioural assessments pretraining and post-training. Primary efficacy measures were changes in gaming-related positive EABs, and compulsive gaming thoughts and behaviours. Behaviourally, EABM (versus sham) training decreased gaming-related positive EABs and compulsive gaming thoughts and behaviours. Neurally, EABM training involved decreased activation in the bilateral dorsal striatum in the regulation-of-craving task and altered left dorsal striatum-centric functional connectivity with ventral prefrontal cortical regions, which correlated with decreases in gaming-related EABs or compulsive gaming thoughts and behaviours. EABM training also implicated activation changes in the right medial frontal gyrus and posterior insula. EABM may reduce compulsive gaming thoughts and behaviours via reshaping functional organization of frontostriatal pathways and insular activity in IGD. The therapeutic potential of EABM should be examined in larger, longer-term studies, as should its application to other addictive disorders.
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Comportamento Aditivo , Jogos de Vídeo , Humanos , Encéfalo , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Jogos de Vídeo/efeitos adversos , Jogos de Vídeo/psicologiaRESUMO
Sex differences in human emotion and related decision-making behaviors are recognized, which can be traced back early in development. However, our understanding of their underlying neurodevelopmental mechanisms remains elusive. Using developmental functional magnetic resonance imaging and computational approach, we investigated developmental sex differences in latent decision-making dynamics during negative emotion processing and related neurocognitive pathways in 243 school-aged children and 78 young adults. Behaviorally, girls exhibit higher response caution and more effective evidence accumulation, whereas boys show more impulsive response to negative facial expression stimuli. These effects parallel sex differences in emotion-related brain maturity linking to evidence accumulation, along with age-related decrease in emotional response in the basolateral amygdala and medial prefrontal cortex (MPFC) in girls and an increase in the centromedial amygdala (CMA) in boys. Moreover, girls exhibit age-related decreases in BLA-MPFC coupling linked to evidence accumulation, but boys exhibit increases in CMA-insula coupling associated with response caution. Our findings highlight the neurocomputational accounts for developmental sex differences in emotion and emotion-related behaviors and provide important implications into the neurodevelopmental mechanisms of sex differences in latent emotional decision-making dynamics. This informs the emergence of sex differences in typical and atypical neurodevelopment of children's emotion and related functions.
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Tonsila do Cerebelo , Caracteres Sexuais , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiologia , Criança , Emoções/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Adulto JovemRESUMO
The dynamical organization of brain networks is essential to support human cognition and emotion for rapid adaption to ever-changing environment. As the core nodes of emotion-related brain circuitry, the basolateral amygdala (BLA) and centromedial amygdala (CMA) as two major amygdalar nuclei, are recognized to play distinct roles in affective functions and internal states, via their unique connections with cortical and subcortical structures in rodents. However, little is known how the dynamical organization of emotion-related brain circuitry reflects internal autonomic responses in humans. Using resting-state functional magnetic resonance imaging (fMRI) with K-means clustering approach in a total of 79 young healthy individuals (cohort 1: 42; cohort 2: 37), we identified two distinct states of BLA- and CMA-based intrinsic connectivity patterns, with one state (integration) showing generally stronger BLA- and CMA-based intrinsic connectivity with multiple brain networks, while the other (segregation) exhibiting weaker yet dissociable connectivity patterns. In an independent cohort 2 of fMRI data with concurrent recording of skin conductance, we replicated two similar dynamic states and further found higher skin conductance level in the integration than segregation state. Moreover, machine learning-based Elastic-net regression analyses revealed that time-varying BLA and CMA intrinsic connectivity with distinct network configurations yield higher predictive values for spontaneous fluctuations of skin conductance level in the integration than segregation state. Our findings highlight dynamic functional organization of emotion-related amygdala nuclei circuits and networks and its links to spontaneous autonomic arousal in humans.
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Nível de Alerta/fisiologia , Complexo Nuclear Basolateral da Amígdala/fisiologia , Mapeamento Encefálico/métodos , Núcleo Central da Amígdala/fisiologia , Imageamento por Ressonância Magnética/métodos , Adulto , Complexo Nuclear Basolateral da Amígdala/diagnóstico por imagem , Núcleo Central da Amígdala/diagnóstico por imagem , Conectoma/métodos , Emoções/fisiologia , Feminino , Resposta Galvânica da Pele , Humanos , Processamento de Imagem Assistida por Computador , Aprendizado de Máquina , Masculino , Descanso/fisiologia , Adulto JovemRESUMO
BACKGROUND: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) may reduce substance use and other addictive behaviours. However, the cognitive mechanisms that underpin such effects remain unclear. Impaired inhibitory control linked to hypoactivation of the prefrontal cortex may allow craving-related motivations to lead to compulsive addictive behaviours. However, very few studies have examined whether increasing the activation of the dlPFC via anodal tDCS could enhance inhibitory control over addiction-related distractors. The current study aimed to enrich empirical evidence related to this issue. METHODS: Thirty-three males with Internet gaming disorder underwent active (1.5 mA for 20 minutes) and sham tDCS 1 week apart, in randomized order. We assessed inhibitory control over gaming-related distractors and craving pre- and post-stimulation. RESULTS: Relative to sham treatment, active tDCS reduced interference from gaming-related (versus non-gaming) distractors and attenuated background craving, but did not affect cue-induced craving. LIMITATIONS: This study was limited by its relatively small sample size and the fact that it lacked assessments of tDCS effects on addictive behaviour. Future tDCS studies with multiple sessions in larger samples are warranted to examine the effects on addictive behaviours of alterations in addiction-related inhibitory control. CONCLUSION: These findings demonstrate that stimulation of the dlPFC influences inhibitory control over addiction-related cues and addiction-related motivation. This is the first empirical study to suggest that enhanced inhibitory control may be a cognitive mechanism underlying the effects of tDCS on addictions like Internet gaming disorder. Our finding of attenuated background craving replicated previous tDCS studies. Intriguingly, our finding of distinct tDCS effects on 2 forms of craving suggests that they may have disparate underlying mechanisms or differential sensitivity to tDCS. CLINICAL TRIALS #: NCT03352973.
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Fissura , Função Executiva , Inibição Psicológica , Transtorno de Adição à Internet/fisiopatologia , Transtorno de Adição à Internet/terapia , Córtex Pré-Frontal , Estimulação Transcraniana por Corrente Contínua , Adolescente , Adulto , Fissura/fisiologia , Função Executiva/fisiologia , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde , Córtex Pré-Frontal/fisiopatologia , Adulto JovemRESUMO
Creative thought relies on the reorganization of existing knowledge to generate novel and useful concepts. However, how these new concepts are formed, especially through the processing of novelty and usefulness (which are usually regarded as the key properties of creativity), is not clear. Taking familiar and useful (FU) objects/designs as the starting point or fundamental baseline, we modified them into novel and useless (NS) objects/designs or novel and useful (NU) ones (i.e., truly creative ones) to investigate how the features of novelty and usefulness are processed (processing of novelty: NU minus FU; processing of usefulness: NU minus NS). Specifically, we predicted that the creative integration of novelty and usefulness entails not only the formation of new associations, which could be critically mediated by the hippocampus and adjacent medial temporal lobe (MTL) areas, but also the formation of new concepts or categories, which is supported by the middle temporal gyrus (MTG). We found that both the MTL and the MTG were involved in the processing of novelty and usefulness. The MTG showed distinctive patterns of information processing, reflected by strengthened functional connectivity with the hippocampus to construct new concepts and strengthened functional connectivity with the executive control system to break the boundaries of old concepts. Additionally, participants' subjective evaluations of concept distance showed that the distance between the familiar concept (FU) and the successfully constructed concept (NU) was larger than that between the FU and the unsuccessfully constructed concept (NS), and this pattern was found to correspond to the patterns of their neural representations in the MTG. These findings demonstrate the critical mechanism by which new associations and concepts are formed during novelty and usefulness processing in creative design; this mechanism may be critically mediated by the hippocampus-MTG connection.
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Criatividade , Hipocampo/fisiologia , Lobo Temporal/fisiologia , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: RA is a systemic auto-immune inflammatory disease that can lead to local bone erosions and generalized osteoporosis (OP). The aim of this study was to investigate the relationship between systemic osteoporosis and local bone erosion with RA patients in the Chinese population. METHODS: In total, 1235 patients with RA and 158 normal subjects were enrolled in this study. Clinical and laboratory features were recorded in detail. Information about functional class and physical activity was collected using specific questionnaires. Dual-energy X-ray absorptiometry was used to measure BMD. The MECALL castor-50-hf model X-ray scanner was used for two-hand (including wrist) photographs. RESULTS: The median Sharp scores differed significantly between the normal bone mass group, osteopenia group and OP group (P < 0.001). There was a modest negative linear correlation between Sharp and HAQ scores and longer disease duration (P < 0.001). There was a clear increasing trend in Sharp score, incidence of OP and HAQ score in the different DAS in 28 joints (DAS28) activity groups (P < 0.001). Spearman's correlation test showed that Sharp and HAQ scores were negatively correlated with BMD at all measured sites (femoral neck, total hip and L1-4) (P < 0.001). Logistic regression indicated that age, female gender, and Sharp and HAQ scores were independent risk factors in the occurrence of OP in RA patients. The use of DMARDs and BMI were protective factors for OP. CONCLUSION: These results suggest that BMD is associated with local bone erosion among Chinese patients with RA. Local bone erosion is closely related to clinical symptoms and BMD in patients with RA.
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CONTEXT: Metabolic syndrome (MS) refers to the clustering of metabolic derangements that include hyperglycemia, dyslipidemia, hypertension, and chronic kidney impairment. Those conditions are well known as being synergistically responsible for morbidity from cardiovascular disease as well as for driving the global epidemic of type 2 diabetes. It is still unknown whether an exact unifying pathogenesis of MS exists. OBJECTIVE: The meta-analysis intended to analyze the use of Chinese medicine (CM) as a therapeutic tool to explore indirectly the unifying pathogenesis of MS. METHODS: PubMed, the Chinese National Knowledge Infrastructure (CNKI), and the Wanfang databases were systematically searched from inception to November 2013 for randomized, controlled trials (RCTs) that compared treatment efficacy for MS patients using the Wen Dan decoction (WDD), a CM formula, versus Western conventional therapeutics. OUTCOME MEASURES: Measurements included tests of the overall therapeutic efficacy of WDD for hyperglycemia, hypertension, dyslipidemia, and renal functions, and the study also analyzed adverse events. Data were expressed as weighted mean differences (WMDs), with 95% confidence intervals (95% CIs) and the odds ratio (OR). RESULTS: A total of 31 RCTs were included for meta-analysis, involving 2512 patients and including 1282 participants in the intervention groups. The pooled data favored WDD over the control treatments as follows: (1) hyperglycemia, with a WMD of -0.95 mmol/L (95% CI: -1.19 to -0.71); (2) hypertension, with a WMD of -7.40 mm Hg (95% CI: -9.86 to -4.93); (3) dyslipidemia: (a) total cholesterol (TC), with a WMD of -0.62 mmol/L (95% CI: -0.90 to -0.33); (b) triglycerides (TGs), with a WMD of -0.32 mmol/L (95% CI: -0.52 to -0.13); (c) low-density lipoproteins (LDPs), with a WMD of -0.22 mmol/L (95% CI: -0.41 to -0.02); and (d) high-density lipoproteins (HDPs), with a WMD of 0.10 mmol/L (95% CI: 0.03 to 0.17); and (4) of renal functions: (a) urea, with a WMD of -3.41 mmol/L (95% CI: -5.50 to -1.32) and (b) creatinine, with a WMD of -68.81 µmol/L (95% CI: -132.63 to -4.98). No statistical significance was documented in creatinine clearance between the 2 treatments with a WMD of 15.47 mL/min (95% CI: -7.71 to 38.64). The overall efficacy rate was 91.4% for WDD and 66.9% for the control treatments (OR: 5.33; 95% CI: 4.06 to 6.99). Adverse events were rare and minor. CONCLUSIONS: The consistent improvements found in metabolic profiles by use of the single herbal formula may indirectly imply a common pathogenesis in MS.
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Medicamentos de Ervas Chinesas/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Crizotinib, an oral first-generation tyrosine kinase inhibitor (TKI), is superior to systemic chemotherapy for the treatment of non-small cell lung cancer (NSCLC) with positive rearrangement of anaplastic lymphoma kinase (ALK). However, an increased incidence of renal and hepatic cysts has been reported in the patients on crizotinib treatment. CASE PRESENTATION: Here, we describe a case of a 71-year-old Chinese women developed multiple cystic lesions in kidney and liver during crizotinib treatment for the primary and metastatic NSCLC. The renal and hepatic cysts were noted by CT scan 3 months after crizotinib treatment, which were spontaneously and significantly regressed after stopping crizotinib. CONCLUSIONS: Based on literature review and our experience in this case report, we concluded that crizotinib-associated renal cyst (CARCs) has features of malignancy and abscess in radiographic imaging, and thus, pathological confirmation is necessary to avoid inappropriate treatment decision. In addition, to benefit the patients with progress-free survival (PFS), switching from crizotinib to alectinib is recommended for the treatment of NSCLC patients who developed CARCs.
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Carcinoma Pulmonar de Células não Pequenas , Cistos , Doenças Renais Císticas , Neoplasias Pulmonares , Humanos , Feminino , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Crizotinibe/efeitos adversos , Quinase do Linfoma Anaplásico/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Doenças Renais Císticas/induzido quimicamente , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Cistos/induzido quimicamenteRESUMO
Magnetic resonance imaging (MRI)-based deep neural networks (DNN) have been widely developed to perform prostate cancer (PCa) classification. However, in real-world clinical situations, prostate MRIs can be easily impacted by rectal artifacts, which have been found to lead to incorrect PCa classification. Existing DNN-based methods typically do not consider the interference of rectal artifacts on PCa classification, and do not design specific strategy to address this problem. In this study, we proposed a novel Targeted adversarial training with Proprietary Adversarial Samples (TPAS) strategy to defend the PCa classification model against the influence of rectal artifacts. Specifically, based on clinical prior knowledge, we generated proprietary adversarial samples with rectal artifact-pattern adversarial noise, which can severely mislead PCa classification models optimized by the ordinary training strategy. We then jointly exploited the generated proprietary adversarial samples and original samples to train the models. To demonstrate the effectiveness of our strategy, we conducted analytical experiments on multiple PCa classification models. Compared with ordinary training strategy, TPAS can effectively improve the single- and multi-parametric PCa classification at patient, slice and lesion level, and bring substantial gains to recent advanced models. In conclusion, TPAS strategy can be identified as a valuable way to mitigate the influence of rectal artifacts on deep learning models for PCa classification.
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Artefatos , Imageamento por Ressonância Magnética , Neoplasias da Próstata , Reto , Humanos , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Reto/diagnóstico por imagem , Redes Neurais de Computação , Interpretação de Imagem Assistida por Computador/métodos , Aprendizado ProfundoRESUMO
The consolidation of discrete experiences into a coherent narrative shapes the cognitive map, providing structured mental representations of our experiences. In this process, past memories are reactivated and replayed in sequence, fostering hippocampal-cortical dialogue. However, brain-wide engagement coinciding with sequential reactivation (or replay) of memories remains largely unexplored. In this study, employing simultaneous EEG-fMRI, we capture both the spatial and temporal dynamics of memory replay. We find that during mental simulation, past memories are replayed in fast sequences as detected via EEG. These transient replay events are associated with heightened fMRI activity in the hippocampus and medial prefrontal cortex. Replay occurrence strengthens functional connectivity between the hippocampus and the default mode network, a set of brain regions key to representing the cognitive map. On the other hand, when subjects are at rest following learning, memory reactivation of task-related items is stronger than that of pre-learning rest, and is also associated with heightened hippocampal activation and augmented hippocampal connectivity to the entorhinal cortex. Together, our findings highlight a distributed, brain-wide engagement associated with transient memory reactivation and its sequential replay.
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Encéfalo , Eletroencefalografia , Hipocampo , Imageamento por Ressonância Magnética , Humanos , Masculino , Hipocampo/fisiologia , Hipocampo/diagnóstico por imagem , Feminino , Adulto , Adulto Jovem , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/diagnóstico por imagem , Mapeamento Encefálico , Aprendizagem/fisiologia , Memória/fisiologia , Córtex Entorrinal/fisiologia , Córtex Entorrinal/diagnóstico por imagemRESUMO
Despite the critical role of self-disturbance in psychiatric diagnosis and treatment, its diverse behavioral manifestations remain poorly understood. This investigation aimed to elucidate unique patterns of self-referential processing in affective disorders and first-episode schizophrenia. A total of 156 participants (41 first-episode schizophrenia [SZ], 33 bipolar disorder [BD], 44 major depressive disorder [MDD], and 38 healthy controls [HC]) engaged in a self-referential effect (SRE) task, assessing trait adjectives for self-descriptiveness, applicability to mother, or others, followed by an unexpected recognition test. All groups displayed preferential self- and mother-referential processing with no significant differences in recognition scores. However, MDD patients showed significantly enhanced self-referential recognition scores and increased bias compared to HC, first-episode SZ, and BD. The present study provides empirical evidence for increased self-focus in MDD and demonstrates that first-episode SZ and BD patients maintain intact self-referential processing abilities. These findings refine our understanding of self-referential processing impairments across psychiatric conditions, suggesting that it could serve as a supplementary measure for assessing treatment response in first-episode SZ and potentially function as a discriminative diagnostic criterion between MDD and BD.
Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Esquizofrenia , Psicologia do Esquizofrênico , Autoimagem , Humanos , Feminino , Masculino , Adulto , Esquizofrenia/fisiopatologia , Transtorno Bipolar/psicologia , Transtorno Bipolar/fisiopatologia , Transtorno Depressivo Maior/psicologia , Adulto Jovem , Estudos de Casos e Controles , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Adolescents raised in families with different maternal and paternal parenting combinations exhibit variations in neurocognition and psychopathology; however, whether neural differences exist remains unexplored. This study used a longitudinal twin sample to delineate how different parenting combinations influence adolescent brain structure and to elucidate the genetic contribution. METHODS: A cohort of 216 twins participated in parenting assessments during early adolescence and underwent MRI scanning during middle adolescence. We utilized latent profile analysis to distinguish between various maternal and paternal parenting profiles and subsequently investigated their influences on brain anatomy. Biometric analysis was applied to assess the genetic influences on brain structure, and associations with internalizing symptoms were explored. RESULTS: In early adolescence, four parenting profiles emerged characterized by levels of harshness and hostility in one or both parents. Compared to adolescents in "catparent" families (low harshness/hostility in both parents), those raised in "tigermom" families (harsh/hostile mother only) exhibited smaller nucleus accumbens volume and larger temporal cortex surface area; those in "tigerdad" families demonstrated larger thalamus volumes; those in "tigerparent" families displayed smaller volumes in the mid-anterior corpus callosum. Genetic risk factors contributed significantly to the observed brain structural heterogeneity and internalizing symptoms. However, the influences of parenting profiles and brain structure on internalizing symptoms were not significant. CONCLUSIONS: The findings underscore distinct brain structural features linked to maternal and paternal parenting combinations, particularly in terms of subcortical volume and cortical surface area. This study suggests an interdependent role of maternal and paternal parenting in shaping adolescent neurodevelopment.