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PURPOSE: This study aimed to evaluate the prognostic significance of changes in inflammatory markers in patients with Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) treated with first-line lenvatinib plus a programmed cell death protein 1 (PD-1) inhibitor. METHODS: This study retrospectively included 117 HBV-HCC patients treated with first-line lenvatinib in combination with a PD-1 inhibitor. Independent factors affecting progression-free survival (PFS) and overall survival (OS) were explored based on baseline indicators and inflammatory markers changes after one treatment cycle. RESULTS: Multivariate analysis revealed that an alpha-fetoprotein (AFP) level ⩾ 400 ng/mL [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.11-2.58; P = 0.01] was identified as an independent risk factor, platelet-to-neutrophil ratio (PNR) ⩽ 65.43 (HR 0.50; 95% CI 0.30-0.84; P < 0.01 ) and SII ⩽ 539.47 (HR 0.54; 95% CI 0.30-0.96; P = 0.03) were identified as independent protective factors for PFS. Additionally, multivariate analysis demonstrated that AFP ⩾ 400 ng/mL, HBV-HCC patients with diabetes mellitus (DM), and SII > 303.66 were independent risk factors of OS. The patients whose SII had increased after one cycle of treatment showed a poorer PFS (HR 1.61; 95 %CI 1.10-2.37; P = 0.015) and OS (HR 1.76; 95 % CI 1.15-2.70; P = 0.009) than patients whose SII had decreased. The objective response rate (ORR) was higher in the SII-decreased patients (47.5% vs 32.5%, P = 0.11). Mann-Whitney test found a significant difference in therapeutic response between the SII-increased patients and the SII-decreased patients (P = 0.04). CONCLUSION: SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.
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Histiocytic sarcoma (HS) is an extremely rare but aggressive hematopoietic malignancy, and the prognosis has been reported to be rather unfavorable with a median overall survival of merely 6 months. We presented a 58-year-old female patient complaining of abdominal pain and fever, who was admitted to our institution in September 2021. Fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) scan showed enlargement of generalized multiple lymph nodes. Subsequently, laparoscopic retroperitoneal lesion biopsy and bone marrow aspiration were performed. The pathological findings indicated the diagnosis of HS concurrent with follicular lymphoma. The immunohistochemistry (IHC) staining of the tumor lesion revealed a high expression of CD38 and PD-L1 proteins. Furthermore, KRAS gene mutation was identified by means of next-generation sequencing. The patient exhibited poor treatment response to both first- and second-line cytotoxic chemotherapies. Therefore, she underwent six cycles of Daratumumab (anti-CD38 monoclonal antibody), Pazopanib (multi-target receptor tyrosine kinases inhibitor) combined with third-line chemotherapy, followed by involved-site radiotherapy and maintenance therapy with the PD-1 inhibitor Tislelizumab. Long-term partial remission was finally achieved after multi-modality treatment. Duration of remission and overall survival reached 22 and 32 months, respectively. Our case indicated that immuno-targeted treatment coupled with chemotherapy and radiotherapy might constitute a potential therapeutic option for HS.
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Sarcoma Histiocítico , Linfoma Folicular , Humanos , Feminino , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/terapia , Linfoma Folicular/patologia , Pessoa de Meia-Idade , Sarcoma Histiocítico/tratamento farmacológico , Sarcoma Histiocítico/patologia , Sarcoma Histiocítico/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Indução de RemissãoRESUMO
PURPOSE: This study aimed to investigate challenges in speech-in-noise (SiN) processing faced by school-age children with autism spectrum conditions (ASCs) and their impact on listening effort. METHOD: Participants, including 23 Mandarin-speaking children with ASCs and 19 age-matched neurotypical (NT) peers, underwent sentence recognition tests in both quiet and noisy conditions, with a speech-shaped steady-state noise masker presented at 0-dB signal-to-noise ratio in the noisy condition. Recognition accuracy rates and task-evoked pupil responses were compared to assess behavioral performance and listening effort during auditory tasks. RESULTS: No main effect of group was found on accuracy rates. Instead, significant effects emerged for autistic trait scores, listening conditions, and their interaction, indicating that higher trait scores were associated with poorer performance in noise. Pupillometric data revealed significantly larger and earlier peak dilations, along with more varied pupillary dynamics in the ASC group relative to the NT group, especially under noisy conditions. Importantly, the ASC group's peak dilation in quiet mirrored that of the NT group in noise. However, the ASC group consistently exhibited reduced mean dilations than the NT group. CONCLUSIONS: Pupillary responses suggest a different resource allocation pattern in ASCs: An initial sharper and larger dilation may signal an intense, narrowed resource allocation, likely linked to heightened arousal, engagement, and cognitive load, whereas a subsequent faster tail-off may indicate a greater decrease in resource availability and engagement, or a quicker release of arousal and cognitive load. The presence of noise further accentuates this pattern. This highlights the unique SiN processing challenges children with ASCs may face, underscoring the importance of a nuanced, individual-centric approach for interventions and support.
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Transtorno do Espectro Autista , Ruído , Pupila , Percepção da Fala , Humanos , Masculino , Percepção da Fala/fisiologia , Criança , Pupila/fisiologia , Feminino , Transtorno do Espectro Autista/psicologia , Transtorno do Espectro Autista/fisiopatologia , Mascaramento Perceptivo/fisiologiaRESUMO
INTRODUCTION: The histological transformation (HT) of follicular lymphoma (FL) is a crucial biological event. The study aimed to evaluate the incidence, clinicial characteristics, prognosis and impact of HT time on survival of FL transforming to diffuse large B-cell lymphoma in population-based large-scale cohorts. METHODS: A retrospective cohort study of FL with HT was performed in the Surveillance, Epidemiology, and End Results database. The Hematological Malignancy Research Network FL cohort and Aristotle study FL cohort were used to assess the external validity. RESULTS: Among 44,127 FL cases from the Surveillance, Epidemiology, and End Results database, 1311 cases were pathology-proven recorded to transform to diffuse large B-cell lymphoma. The cumulative rates of HT at 5, 10, and 15 years after FL diagnosis were estimated to be 1.19%, 2.93%, and 5.01%, respectively. Significantly worse overall survival and cancer-specific survival were exhibited in patients with HT than those without HT. Early HT (transformation of FL within 48 months after FL diagnosis [TOD48]) was an independent predictor for adverse overall survival of HT patients, regardless of treatment modalities before transformation. The adverse prognostic effect of TOD48 was validated in the Hematological Malignancy Research Network cohort and Aristotle study cohort. Older age (>75 years) and B symptoms within FL at diagnosis were the independent risk factors of TOD48. Furthermore, a novel prognostic model combining TOD48 with Follicular Lymphoma International Prognostic Index (TOD48-FLIPI) was constructed and validated for risk stratification. CONCLUSION: TOD48 was a risk indicator of HT, and the novel prognostic model "TOD48-FLIPI" for HT patients was proposed.
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As few studies have reported the impact of lower left ventricular ejection fraction (LVEF) on the prognosis of acute ischemic stroke (AIS) patients, we aimed to explore this through a retrospective cohort study and a meta-analysis. A total of 283 AIS patients receiving intravenous thrombolysis at the Third Affiliated Hospital of Wenzhou Medical University between 2016 and 2019 were enrolled and divided into three groups based on LVEF tertiles. The logistic regression model estimated the association between LVEF and the three-month AIS prognosis. After adjusting for confounding factors, patients in tertile 3 exhibited an increased risk of poor functional outcome and mortality [odds ratio (OR), 2.656 (95% CI: 1.443-4.889); OR, 7.586 (95% CI: 2.102-27.375)]. A systematic search of PubMed, EMBASE and Cochrane Library was performed. Our meta-analysis revealed that LVEF < 40% was significantly associated with poor functional outcome [OR 1.94 (95% CI: 1.08-3.50)], mortality [OR 3.69 (95% CI: 1.22-11.11)], as well as LVEF < 55% [OR 1.68 (95% CI: 1.22-2.32); 2.27 (95% CI: 1.30-3.96)], respectively. A decreased LVEF could predict an inferior prognosis for AIS; therefore, it could aid in clinical decision-making in this patient population.
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OBJECTIVE: Nutritional screening tools based on laboratory examinations are relatively objective and available indicators. However, few studies have investigated whether malnutrition severity might be associated with adverse outcomes at the platform recovery period of 6 mo and differentiated in acute ischemic stroke patients with or without intravenous thrombolysis. Therefore, we assessed the association between malnutrition and 6-mo outcomes in both intravenous thrombolysis and non-intravenous thrombolysis patients. METHODS: We retrospectively recruited 138 acute ischemic stroke patients who received intravenous thrombolysis and 311 who did not. The Geriatric Nutritional Risk Index, prognostic nutritional index, and Controlling Nutritional Status were used to assess nutritional status. The concordance between the 3 malnutrition screening tools was investigated with the κ statistic. Subgroups analyses were conducted to assess the correlation between malnutrition and functional outcomes in intravenous thrombolysis and non-intravenous thrombolysis patients. RESULTS: A total of 17 (6.44%) patients were suffering from malnutrition, as indicated by the Geriatric Nutritional Risk Index, prognostic nutritional index, and Controlling Nutritional Status jointly. Moderate-severe malnutrition evaluated by the Geriatric Nutritional Risk Index was significantly associated with poor functional outcome (odds ratio = 4.074; P = 0.003). Patients in the good functional outcome group (modified Rankin scale scores = 0 to 2) had a higher proportion of intravenous thrombolysis treatment (32.79% versus 21.25%; P = 0.043). Furthermore, subgroup analyses found no significant interactions between malnourished levels and intravenous thrombolysis treatment (P interaction > 0.05). CONCLUSION: The Geriatric Nutritional Risk Index, over ≤24 h, compared with the prognostic nutritional index and Controlling Nutritional Status, provided timely signals to improve acute ischemic stroke patients' nutritional status. Also, nutritional status might not lead todifferent 6-mo outcomes, whether or not patients received intravenous thrombolysis treatment.
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Isquemia Encefálica , AVC Isquêmico , Desnutrição , Acidente Vascular Cerebral , Humanos , Idoso , Avaliação Nutricional , Acidente Vascular Cerebral/complicações , AVC Isquêmico/complicações , Estudos Retrospectivos , Estado Nutricional , Terapia Trombolítica , Desnutrição/etiologia , Desnutrição/complicações , Resultado do Tratamento , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológicoRESUMO
BACKGROUND: De novo donor-specific antibody (dnDSA) generation and acute rejection (AR) are the main factors affecting long-term graft survival. This study aims to investigate human leukocyte antigen (HLA) eplet mismatching (MM), delayed graft function (DGF), and tacrolimus (TAC) trough levels on the occurrence of dnDSA and AR in the early stages after kidney transplantation (KT). METHODS: This retrospective study included 526 cases of deceased donation KT. The effects of DGF, HLA eplet MM, and TAC trough levels on dnDSA and AR occurrence were analyzed with logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed the independent risk factor of dnDSA generation was HLA B eplet MM (OR: 1.201, 95% CI: 1.007-1.431, P = 0.041). The independent risk factors of AR occurrence include DGF (OR: 4.045, 95% CI: 1.047-15.626, P = 0.043), HLA B eplet MM (OR: 1.090, 95% CI: 1.000-1.187, P = 0.050), and TAC trough levels at 12 months (OR: 0.750, 95% CI: 565-0.997, P = 0.048). HLA B eplet MM combined with DGF and TAC trough levels at 12 months increased the predictive value of dnDSA (AUC 0.735) and AR (AUC 0.730) occurrence. HLA B eplet MM > 9 and TAC trough levels below 5.95 ng/mL at 12 months could increase the risk of early AR occurrence. CONCLUSIONS: HLA B eplet MM, DGF, and TAC trough levels at 12 months after KT could affect the occurrence of dnDSA and AR in the early stage of KT.
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Transplante de Rim , Humanos , Tacrolimo/uso terapêutico , Estudos Retrospectivos , Função Retardada do Enxerto , Rejeição de Enxerto , Anticorpos , Antígenos HLA , Antígenos de Histocompatibilidade Classe II , Antígenos HLA-B , Sobrevivência de Enxerto , Fatores de RiscoRESUMO
A rare subtype of diffuse large B-cell lymphoma (DLBCL) has been reported to be accompanied by elevated immunoglobulin M (IgM) paraprotein in the serum at diagnosis, called as IgMs-DLBCL. The monoclonal IgM paraprotein disappears soon after treatment in most of these patients. Here, we described a DLBCL patient with continuously elevated IgM following therapy. A 59-year-old male was diagnosed with DLBCL (GCB subtype per Hans algorithm, stage IA) with involvement of the right cervical lymph node. After six cycles of immuno-chemotherapy with the R-CHOP regimen, complete metabolic remission was achieved, but an elevated level of serum IgM persisted. To investigate the origin of elevated IgM, pathologic, immunophenotypic, and molecular analyses of lymph node and bone marrow (BM) samples were performed pre- and post-treatment. BM infiltration of lymphoplasmacytic cells, and a typical immunophenotypic profile by flow cytometry supported the diagnosis of Waldenström macroglobulinemia (WM). The MCD subtype of DLBCL was identified by next-generation sequencing of the lymph node at initial diagnosis characterized by co-occurring point mutations in MYD88 L265P and CD79B. Additionally, two different dominant clonotypes of the immunoglobulin heavy chain (IGH) were detected in the lymph node and BM by IGH sequencing, which was IGHV 3-11*06/IGHJ 3*02 and IGHV 3-11*06/IGHJ 6*02, respectively, speculating to be two independent clonal origins. This study will provide a panoramic understanding of the origin or biological characteristics of DLBCL co-occurring with WM.
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How people recognize linguistic and emotional prosody in different listening conditions is essential for understanding the complex interplay between social context, cognition, and communication. The perception of both lexical tones and emotional prosody depends on prosodic features including pitch, intensity, duration, and voice quality. However, it is unclear which aspect of prosody is perceptually more salient and resistant to noise. This study aimed to investigate the relative perceptual salience of emotional prosody and lexical tone recognition in quiet and in the presence of multi-talker babble noise. Forty young adults randomly sampled from a pool of native Mandarin Chinese with normal hearing listened to monosyllables either with or without background babble noise and completed two identification tasks, one for emotion recognition and the other for lexical tone recognition. Accuracy and speed were recorded and analyzed using generalized linear mixed-effects models. Compared with emotional prosody, lexical tones were more perceptually salient in multi-talker babble noise. Native Mandarin Chinese participants identified lexical tones more accurately and quickly than vocal emotions at the same signal-to-noise ratio. Acoustic and cognitive dissimilarities between linguistic prosody and emotional prosody may have led to the phenomenon, which calls for further explorations into the underlying psychobiological and neurophysiological mechanisms.
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Aberrant activation of N-methyl-d-aspartate receptors (NMDAR) and the resulting neuronal nitric oxide synthase (nNOS) excessive activation play crucial pathogenic roles in neuronal damage caused by stroke. Disrupting postsynaptic density protein 95 (PSD95)-nNOS protein-protein interaction (PPI) has been proposed as a potential therapeutic strategy for ischemic stroke without incurring the unwanted side effects of direct NMDAR antagonism. Based on a specific PSD95-nNOS PPI inhibitor (SCR4026), we conducted a detailed study on structure-activity relationship (SAR) to discover a series of novel benzyloxy benzamide derivatives. Here, our efforts resulted in the best 29 (LY836) with improved neuroprotective activities in primary cortical neurons from glutamate-induced damage and drug-like properties. Whereafter, co-immunoprecipitation experiment demonstrated that 29 significantly blocked PSD95-nNOS association in cultured cortical neurons. Furthermore, 29 displayed good pharmacokinetic properties (T1/2 = 4.26 and 4.08 h after oral and intravenous administration, respectively) and exhibited powerful therapeutic effects in rats subjected to middle cerebral artery occlusion (MCAO) by reducing infarct size and neurological deficit score. These findings suggested that compound 29 may be a promising neuroprotection agent for the treatment of ischemic stroke.
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Isquemia Encefálica , AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Ratos , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , AVC Isquêmico/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana/metabolismo , Ratos Sprague-Dawley , Proteína 4 Homóloga a Disks-Large , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Óxido Nítrico Sintase Tipo I/metabolismo , Isquemia Encefálica/tratamento farmacológicoRESUMO
PURPOSE: Hearing assistive technology (HAT) has been shown to be a viable solution to the speech-in-noise perception (SPIN) issue in children with autism spectrum disorder (ASD); however, little is known about its efficacy in tonal language speakers. This study compared sentence-level SPIN performance between Chinese children with ASD and neurotypical (NT) children and evaluated HAT use in improving SPIN performance and easing SPIN difficulty. METHOD: Children with ASD (n = 26) and NT children (n = 19) aged 6-12 years performed two adaptive tests in steady-state noise and three fixed-level tests in quiet and steady-state noise with and without using HAT. Speech recognition thresholds (SRTs) and accuracy rates were assessed using adaptive and fixed-level tests, respectively. Parents or teachers of the ASD group completed a questionnaire regarding children's listening difficulty under six circumstances before and after a 10-day trial period of HAT use. RESULTS: Although the two groups of children had comparable SRTs, the ASD group showed a significantly lower SPIN accuracy rate than the NT group. Also, a significant impact of noise was found in the ASD group's accuracy rate but not in that of the NT group. There was a general improvement in the ASD group's SPIN performance with HAT and a decrease in their listening difficulty ratings across all conditions after the device trial. CONCLUSIONS: The findings indicated inadequate SPIN in the ASD group using a relatively sensitive measure to gauge SPIN performance among children. The markedly increased accuracy rate in noise during HAT-on sessions for the ASD group confirmed the feasibility of HAT for improving SPIN performance in controlled laboratory settings, and the reduced post-use ratings of listening difficulty further confirmed the benefits of HAT use in daily scenarios.
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Transtorno do Espectro Autista , Tecnologia Assistiva , Percepção da Fala , Humanos , Criança , População do Leste Asiático , Audição , IdiomaRESUMO
Phototherapy, which relies on light to trigger phototherapeutic agents (PAs) to generate cytotoxic reactive oxygen species or hyperthermia, has received much attention in cancer treatment. However, traditional PAs have shortcomings such as low water solubility, easy aggregation-induced fluorescence quenching and low target site accumulation efficiency, which severely limit clinical anticancer applications. Naturally derived polysaccharides have attracted great attention in the scientific community in nano-drug delivery systems (NDDS) due to their abundant resources, biocompatibility, targeting ability, bioactivity and so on, which is expected to assist PAs to play a synergistic effect. This article reviews the recent progress of polysaccharides in the field of cancer phototherapy, including the advantages of polysaccharides as nanocarrier materials to deliver PAs; the main mechanism for the preparation of PAs-loaded polysaccharides nanoformulation; construction of polysaccharides-based NDDS for delivery of PAs and its functional modification strategy, hoping to further improve the therapeutic effect of phototherapy against cancer.
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Fotoquimioterapia , Preparações de Ação Retardada , Polissacarídeos , Fototerapia , Portadores de FármacosRESUMO
BACKGROUND: Primary gastric T-cell lymphoma (PG-TCL) is a rare hematological malignancy with few data reported. The objective of this study is to investigate the epidemiology, clinical characteristics, and survivals of PG-TCL. METHODS: Totally, 164 patients with PG-TCL from 1975 to 2016 extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database were analyzed. Kaplan-Meier method was applied to plot overall survival (OS) and cancer-specific survival (CSS). The prognostic factors of OS and CSS were explored by Cox proportional hazard regression. Nomograms were constructed to predict survival possibilities. RESULTS: The age-adjusted incidence rate of PG-TCL was 0.0091 per 100,000 person-years and increased with age. The median age at onset was 65 years old with male predominance. The major histological type was peripheral T-cell lymphoma, NOS (63.4%). The 1-, 2-, and 5-year OS were 45.5%, 34.7%, and 23.5%, respectively while the 1-, 2-, and 5-year CSS were 47.4%, 37.3%, and 29.6%, respectively. Multivariate Cox analysis demonstrated that age at diagnosis, use of chemotherapy, and radiotherapy were the independent prognostic factors for OS. Chemotherapy combined with radiotherapy could significantly improve patients' OS compared with chemotherapy alone. Moreover, age at diagnosis and use of chemotherapy were also the independent prognostic factors for CSS. Nomograms for PG-TCL were developed to predict 1-, 2-, and 5-year OS possibilities. The predictability of nomograms was verified by high concordance index and good agreement with the predicted value in calibration plots. CONCLUSION: PG-TCL is a rare neoplasm with low incidence. Patients with PG-TCL generally exhibited poor prognosis. Use of chemotherapy plus radiotherapy was associated with favorable OS.
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Linfoma de Células T , Nomogramas , Humanos , Masculino , Idoso , Feminino , Estadiamento de Neoplasias , Programa de SEER , PrognósticoRESUMO
BACKGROUND: Citrus grandis 'Tomentosa,' a fruit epicarp of C. grandis 'Tomentosa' or C. grandis (L.) Osbeck is widely used in health food and medicine. Based on our survey results, there are also rich essential oils with bioactivities in leaves, but the chemical compounds in this part and relevant pharmacological activities have never been studied systematically. Therefore, this study was to preliminarily decipher the pharmacological activities and mechanisms of the essential oil in leaves of C. grandis 'Tomentosa' by an integrated network pharmacology approach. METHODS: Essential oil compositions from leaves ofC. grandis 'Tomentosa' were identified using GC-MS/MS. And then, the targets of these oil compositions were predicted and screened from TCMSP, SwissTargetPrediction, STITCH and SEA databases. STRING database was used to construct the protein-protein interaction networks, and the eligible protein targets were input into WebGestalt 2019 to carry out GO enrichment and KEGG pathway enrichment analysis. Based on the potential targets, disease enrichment information was obtained by TTD databases. Cytoscape software was used to construct the component-target-disease network diagrams. RESULTS: Finally, 61 essential oil chemical components were identified by GC-MS/MS, which correspond to 679 potential targets. Biological function analysis showed 12, 19, and 12 GO entries related to biological processes, cell components and molecular functions, respectively. 43 KEGG pathways were identified, of which the most significant categories were terpenoid backbone biosynthesis, TNF signaling pathway and leishmaniasis. The component-target-disease network diagram revealed that the essential oil compositions in leaves of C. grandis 'Tomentosa' could treat tumors, immune diseases, neurodegenerative diseases and respiratory diseases, which were highly related to CHRM1, PTGS2, CASP3, MAP2K1 and CDC25B. CONCLUSION: This study may provide new insight into C. grandis 'Tomentosa' or C. grandis (L.) Osbeck and may provide useful information for future utilization and development.
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Medicamentos de Ervas Chinesas , Óleos Voláteis , Espectrometria de Massas em Tandem , Óleos Voláteis/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Farmacologia em Rede , Folhas de Planta/química , Medicamentos de Ervas Chinesas/análise , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: Tumor necrosis factor alpha-induced protein 2 (TNFAIP2), a TNFα-inducible gene, appears to participate in inflammation, immune response, hematopoiesis, and carcinogenesis. However, the potential role of TNFAIP2 in the development of acute myeloid leukemia (AML) remains unknow yet. Therefore, we aimed to study the biological role of TNFAIP2 in leukemogenesis. METHODS: TNFAIP2 mRNA level, prognostic value, co-expressed genes, differentially expressed genes, DNA methylation, and functional enrichment analysis in AML patients were explored via multiple public databases, including UALCAN, GTEx portal, Timer 2.0, LinkedOmics, SMART, MethSurv, Metascape, GSEA and String databases. Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Beat AML database were used to determine the associations between TNFAIP2 expression and various clinical or genetic parameters of AML patients. Moreover, the biological functions of TNFAIP2 in AML were investigated through in vitro experiments. RESULTS: By large-scale data mining, our study indicated that TNFAIP2 was differentially expressed across different normal and tumor tissues. TNFAIP2 expression was significantly increased in AML, particularly in French-American-British (FAB) classification M4/M5 patients, compared with corresponding control tissues. Overexpression of TNFAIP2 was an independent poor prognostic factor of overall survival (OS) and was associated with unfavorable cytogenetic risk and gene mutations in AML patients. DNA hypermethylation of TNFAIP2 at gene body linked to upregulation of TNFAIP2 and inferior OS in AML. Functional enrichment analysis indicated immunomodulation function and inflammation response of TNFAIP2 in leukemogenesis. Finally, the suppression of TNFAIP resulted in inhibition of proliferation by altering cell-cycle progression and increase of cell death by promoting early and late apoptosis in THP-1 and U937AML cells. CONCLUSION: Collectively, the oncogenic TNFAIP2 can function as a novel biomarker and prognostic factor in AML patients. The immunoregulation function of TNFAIP2 warrants further validation in AML.
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Leucemia Mieloide Aguda , Fator de Necrose Tumoral alfa , Biomarcadores Tumorais/genética , Carcinogênese , Citocinas , DNA , Humanos , Inflamação , Leucemia Mieloide Aguda/patologia , Prognóstico , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Inconsistent results have been reported about the affective prosody recognition (APR) ability in patients with bipolar (BD) and depressive (DD) disorders. We aimed to (i) evaluate the magnitude of APR dysfunction in BD and DD patients, (ii) identify moderators for heterogeneous results, and (iii) highlight research trends in this field. METHODS: A computerized literature search was conducted in five electronic databases from the inception to May 9th, 2022 to identify behavioural experiments that studied APR in BD or DD patients. Effect sizes were calculated using a random-effect model and recalculated after removing outliers and adjusting publication bias. RESULTS: Twelve eligible articles totalling 16 studies were included in the meta-analysis, aggregating 612 patients and 809 healthy controls. Individual r2 ranged from 0.008 to 0.355, six of which reached a medium-to-large association strength. A medium-to-large pooled effect size (Hedges g = -0.58, 95 % CI -0.75 to -0.40, p < 0.001) for overall APR impairment in BD and DD patients was obtained. The Beck Depression Inventory score and answer option number were significant moderators. Neuropsychological mechanisms, multi-modal interaction and comorbidity effects have become primary research concerns. LIMITATIONS: Extant statistics were insufficient for disorder-specific analysis. CONCLUSIONS: Current findings demonstrate deficits of overall APR in BD and DD patients at a medium-to-large magnitude. APR can clinically serve for early screening and prognosis, but the depression severity, task complexity and confounding variables influence patients' APR performance. Future studies should incorporate neuroimaging approaches and investigate the effects of tonal language stimuli and clinical interventions.
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Transtorno Bipolar , Transtorno Bipolar/psicologia , Comorbidade , Humanos , Reconhecimento PsicológicoRESUMO
Objective: We attempt to discuss the relationship between family support and willingness to participate in exercise rehabilitation in coronary heart disease patients after PCI to provide effective guidance for improving the quality of life of coronary heart disease patients after PCI. Methods: By convenient sampling, we selected 90 coronary heart disease patients in cardiology department from September 2021 to January 2022, using general information questionnaire, rehabilitation exercise knowledge, attitude, and behavior questionnaire of patients with coronary heart disease, and the social support scale to investigate the subjects. Results: The total score of knowledge, belief, and behavior in patients with coronary heart disease was 33.02 ± 6.28 points, the social support scale score was 39.63 ± 6.07 points, the multiple linear regression revealed that the educational level, history of cardiovascular disease, and the number of coronary stents of coronary heart disease patients after PCI are the main influencing factors that affect the willingness of coronary heart disease patients to participate in exercise rehabilitation. Conclusion: Rehabilitation exercise knowledge, belief, and behavior scores in coronary heart disease patients are low, and social support is negatively correlated with rehabilitation exercise in coronary heart disease patients.
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The worldwide rising trend of autism spectrum disorder (ASD) calls for innovative and efficacious techniques for assessment and treatment. Virtual reality (VR) technology gains theoretical support from rehabilitation and pedagogical theories and offers a variety of capabilities in educational and interventional contexts with affordable products. VR is attracting increasing attention in the medical and healthcare industry, as it provides fully interactive three-dimensional simulations of real-world settings and social situations, which are particularly suitable for cognitive and performance training, including social and interaction skills. This review article offers a summary of current perspectives and evidence-based VR applications for children with ASD, with a primary focus on social communication, including social functioning, emotion recognition, and speech and language. Technology- and design-related limitations, as well as disputes over the application of VR to autism research and therapy, are discussed, and future directions of this emerging field are highlighted with regards to application expansion and improvement, technology enhancement, linguistic diversity, and the development of theoretical models and brain-based research.
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PURPOSE: Numerous studies have identified individuals with autism spectrum disorder (ASD) with deficits in unichannel emotion perception and multisensory integration. However, only limited research is available on multichannel emotion perception in ASD. The purpose of this review was to seek conceptual clarification, identify knowledge gaps, and suggest directions for future research. METHOD: We conducted a scoping review of the literature published between 1989 and 2021, following the 2005 framework of Arksey and O'Malley. Data relating to study characteristics, task characteristics, participant information, and key findings on multichannel processing of emotion in ASD were extracted for the review. RESULTS: Discrepancies were identified regarding multichannel emotion perception deficits, which are related to participant age, developmental level, and task demand. Findings are largely consistent regarding the facilitation and compensation of congruent multichannel emotional cues and the interference and disruption of incongruent signals. Unlike controls, ASD individuals demonstrate an overreliance on semantics rather than prosody to decode multichannel emotion. CONCLUSIONS: The existing literature on multichannel emotion perception in ASD is limited, dispersed, and disassociated, focusing on a variety of topics with a wide range of methodologies. Further research is necessary to quantitatively examine the impact of methodological choice on performance outcomes. An integrated framework of emotion, language, and cognition is needed to examine the mutual influences between emotion and language as well as the cross-linguistic and cross-cultural differences. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19386176.
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Transtorno do Espectro Autista , Transtorno Autístico , Percepção da Fala , Transtorno do Espectro Autista/psicologia , Emoções , Expressão Facial , Gestos , Humanos , FalaRESUMO
This study aimed to analyze the therapeutic effect of Rhein on ulcerative colitis (UC) in mice and its possible mechanism. LPS-induced UC cell model and DSS-induced UC mouse model were used to analyze the antiinflammatory effect of Rhein on UC in vitro and in vivo, respectively. Network pharmacology analysis was conducted to identify potential signaling pathways involved in Rhein treating UC, and the results were further confirmed through western blotting assay. 16sRNA sequencing was performed to study the regulatory effect of Rhein on gut microbiota in UC mice. As indicated by the results, Rhein could significantly inhibit the production of pro-inflammatory cytokines (e.g., TNF-α, IL-6 and IL-1ß) in vivo and in vitro, and alleviate DSS-induced UC-associated symptoms in mice (e.g., colon shortening, weight loss, diarrhea and hematochezia). The PI3K/Akt/mTOR signaling pathway was predicted as the potential interacting protein of Rhein in the treatment of UC through network pharmacology analysis. It was found through western blotting assay that the Rhein treatment could significantly inhibit the PI3K/Akt/mTOR signaling pathway by decreasing the phosphorylated protein levels of PI3K, Akt, mTOR and p70S6K1. By 16sRNA gene sequencing analysis, Rhein administration could partially reverse the gut dysbacteriosis of mice induced by DSS and decrease pathogenic bacteria (e.g., Enterobacteriaceae and Turicibacter). It was positively correlated with the production of pro-inflammatory cytokines above, whereas the increase in probiotics (e.g., Unspecified-S24-7 and Rikenellaceae) was negatively correlated with the production of pro-inflammatory cytokines. In conclusion, Rhine had anti-UC efficacy, which was demonstrated by mitigating the UC symptoms and reducing intestinal inflammation by inhibiting the PI3K/Akt/mTOR signaling pathway and modulating gut microbiota.