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BACKGROUND: Jianpi Jiedu Recipe has been used to treat digestive tract tumors in China since ancient times, and its reliability has been proven by clinical research. Currently, the specific biological mechanism of JPJDR in treating tumors is unclear. METHODOLOGY: CCK-8 assay was used to detect cell viability. Clone formation assay and EdU assay were used to detect cell proliferation potential. DCFH-DA probe and JC-1 probe were used to detect total intracellular reactive oxygen species and mitochondrial membrane potential, respectively. Western blotting and immunofluorescence were used to detect protein expression level and subcellular localization of cells. The RFP-GFP-LC3B reporter system was used to observe the type of autophagy in cells. The xenograft tumor model was used to study the therapeutic effect of JPJDR in vivo. RESULTS: JPJDR has an excellent inhibitory effect on various colorectal cancer cells and effectively reduces the proliferation ability of HT29 cells. After treatment with JPJDR, the amount of reactive oxygen species in HT29 cells increased significantly, and the mitochondrial membrane potential decreased. JPJDR induced the accumulation of autophagosomes in HT29 cells and was shown to be incomplete autophagy. At the same time, JPJDR reduced the expression of PD-L1. Meanwhile, JPJDR can exert an excellent therapeutic effect in xenograft tumor mice. CONCLUSION: JPJDR is a low-toxicity and effective anti-tumor agent that can effectively treat colon cancer in vitro and in vivo. Its mechanism may be inducing mitochondrial dysfunction and incomplete autophagy injury to inhibit the proliferation of colon cancer cells.
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Autofagia , Proliferação de Células , Neoplasias do Colo , Medicamentos de Ervas Chinesas , Potencial da Membrana Mitocondrial , Espécies Reativas de Oxigênio , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Espécies Reativas de Oxigênio/metabolismo , Autofagia/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Nus , Linhagem Celular Tumoral , Antígeno B7-H1/metabolismo , Células HT29 , Camundongos Endogâmicos BALB C , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
BACKGROUND: Several studies have shown that the survival outcomes of chemoradiotherapy (CRT) are not inferior to surgery alone in patients with esophageal squamous cell carcinoma (ESCC). This study aimed to compare survival outcomes of ESCC treated with immunochemotherapy (ICT) followed by surgery or definitive CRT and to explore subgroups of patients who could benefit from one treatment strategy. METHODS: Pooled data were obtained from two prospectively registered clinical trials of patients with ESCC at the Affiliated Cancer Hospital of Nanjing Medical University. One trial involved treatment with neoadjuvant ICT followed by surgery, while the other involved induction ICT followed by definitive CRT. To balance potential biases, we conducted an overlap weighting (OW) analysis to compare the rates of 2-year progression-free survival (PFS), locoregional relapse-free survival (LRRFS), distant relapse-free survival (DRFS), and overall survival (OS). Additionally, propensity score matching (PSM) was performed to analyze failure pattern. RESULTS: The median follow-up time of the survivors was 39.3 months. After overlap weighting, the rates of 2-year PFS, LRRFS, DRFS, and OS for patients undergoing surgery and CRT were 61.5 % and 59.7 %, 67.2 % and 69.9 %, 81.3 % and 90.7 %, 84.6 % and 79.1 %, respectively (P>.05 for all). A trend for improved 2-year OS was observed in the surgery group in patients who did not respond to ICT (P=.07). CONCLUSION: The differences in the rates of 2-year PFS, LRRFS, DRFS, and OS between the surgery group and the chemoradiotherapy group did not reach statistical significance.
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RATIONALE AND OBJECTIVES: To assess changes in the central executive network (CEN) of patients with mild cognitive impairment (MCI) associated with end-stage renal disease (ESRD). METHODS: A total of 121 patients with ESRD and 66 healthy controls (HCs) were enrolled. Patients were divided into an MCI group (n = 67) and a cognitively unimpaired group (n = 54). All participants underwent resting-state functional magnetic resonance imaging and were evaluated using the Montreal Cognitive Assessment (MoCA). The functional attributes of the CEN were calculated using three methods of functional connectivity (FC) analysis. Relationships among imaging features, cognitive scale scores, and clinical data were assessed, and a model was constructed to diagnose MCI in patients with ESRD. RESULTS: The comparison of the three groups showed that there were significant differences in the FC values of five connection pairs within the CEN, and the CEN demonstrated significant differences in connectivity to ten brain regions. In patients with MCI associated with ESRD, the information transmission efficiency of the CEN was reduced, which demonstrates the characteristics of a random network to some extent. Significant correlations were observed among imaging parameters, cognitive scale scores, and clinical data. The diagnostic model constructed based on these results demonstrated excellent discrimination and calibration. CONCLUSION: Alterations in the function of the CEN provide relevant bases for revealing the neuropathological mechanism of MCI in patients with ESRD. The diagnostic model developed in this study may help to establish more reliable imaging markers for detecting early cognitive impairment in this patient population.
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Objectives: This study aimed to determine the effects of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain management in patients undergoing thoracic surgery. Methods: In the prospective, randomized, controlled study, a total of 84 patients undergoing video-assisted thoracoscopic surgery (VATS) were randomly allocated to the TEAS group (Group T) or control group (Group C). Patients in the Group T received TEAS at Neiguan (PC6) and Hegu (LI4) acupoints for 30 min before anesthesia induction and 30 min after thoracoscopic surgery. Patients in the Group C received the same placement of electrodes but without electrical stimulation. The numeric rating scale (NRS) pain score, remifentanil consumption, demand for rescue analgesics and incidence of postoperative nausea and vomiting (PONV), patient satisfaction, and the levels of plasma ß-endorphin (EP) and IL-6 were recorded. Results: Patients in the Group T had significantly lower NRS pain scores at 6 h, 12 h, 24 h, and 48 h after surgery than those in the Group C. Compared with Group C, patients in Group T had lower remifentanil consumption during operation, lower demand for rescue analgesics and lower rate of PONV within 24 h after surgery. Patients in Group T also had lower IL-6 content, higher ß-EP content and higher satisfaction degree than those in the Group C. Conclusions: Perioperative TEAS significantly decreased postoperative pain and rescued analgesia requirements and the incidence of PONV in patients undergoing thoracoscopic surgery, with a higher patient satisfaction. This trial is registered with ChiCTR2100051841.
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Pontos de Acupuntura , Dor Pós-Operatória , Estimulação Elétrica Nervosa Transcutânea , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/etiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Adulto , Idoso , Medição da Dor , Estudos Prospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , beta-Endorfina/sangueRESUMO
PURPOSE: To assess changes in neurovascular coupling (NVC) by evaluating the relationship between cerebral perfusion and brain connectivity in patients with end-stage renal disease (ESRD) undergoing hemodialysis versus in healthy control participants. And by exploring brain regions with abnormal NVC associated with cognitive deficits in patients, we aim to provide new insights into potential preventive and therapeutic interventions. MATERIALS AND METHODS: A total of 45 patients and 40 matched healthy controls were prospectively enrolled in our study. Montreal Cognitive Assessment (MoCA) was used to assess cognitive function. Arterial spin labeling (ASL) was used to calculate cerebral blood flow (CBF), and graph theory-based analysis of results from resting-state functional magnetic resonance imaging (rs-fMRI) was used to calculate brain network topological parameters (node betweenness centrality [BC], node efficiency [Ne], and node degree centrality [DC]). Three NVC biomarkers (CBF-BC, CBF-Ne, and CBF-DC coefficients) at the whole brain level and 3 NVC biomarkers (CBF/BC, CBF/Ne, and CBF/DC ratios) at the local brain region level were used to assess NVC. Mann-Whitney U tests were used to compare the intergroup differences in NVC parameters. Spearman's correlation analysis was used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment, and clinical characteristics multiple comparisons were corrected using a voxel-wise false-discovery rate (FDR) method (p < .05). RESULTS: Patients showed significantly reduced global coupling coefficients for CBF-Ne (p = .023) and CBF-BC (p = .035) compared to healthy controls. Coupling ratios at the local brain region level were significantly higher in patients in 33 brain regions (all p values < .05). Coupling ratio changes alone or accompanied by changes in CBF, node properties, or both CBF and node properties were identified. In patients, negative correlations were seen between coupling ratios and MoCA scores in many brain regions, including the left dorsolateral superior frontal gyrus, the bilateral median cingulate and paracingulate gyri, and the right superior parietal gyrus. The correlations remained even after adjusting for hemoglobin and hematocrit levels. CONCLUSION: Disrupted NVC may be one mechanism underlying cognitive impairment in dialysis patients.
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Encéfalo , Disfunção Cognitiva , Falência Renal Crônica , Imageamento por Ressonância Magnética , Acoplamento Neurovascular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Acoplamento Neurovascular/fisiologia , Falência Renal Crônica/fisiopatologia , Falência Renal Crônica/terapia , Falência Renal Crônica/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Adulto , Circulação Cerebrovascular/fisiologia , Diálise Renal , Neuroimagem/métodos , Idoso , Estudos Prospectivos , Testes de Estado Mental e Demência , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologiaRESUMO
The function and structure of brain networks (BN) may undergo changes in patients with end-stage renal disease (ESRD), particularly in those accompanied by mild cognitive impairment (ESRDaMCI). Many existing methods for fusing BN focus on extracting interaction features between pairs of network nodes from each mode and combining them. This approach overlooks the correlation between different modal features during feature extraction and the potentially valuable information that may exist between more than two brain regions. To address this issue, we propose a model using a multi-head self-attention mechanism to fuse brain functional networks, white matter structural networks, and gray matter structural networks, which results in the construction of brain fusion networks (FBN). Initially, three networks are constructed: the brain function network, the white matter structure network, and the individual-based gray matter structure network. The multi-head self-attention mechanism is then applied to fuse the three types of networks, generating attention weights that are transformed into an optimized model. The optimized model introduces hypergraph popular regular term and L1 norm regular term, leading to the formation of FBN. Finally, FBN is employed in the diagnosis and prediction of ESRDaMCI to evaluate its classification performance and investigate the correlation between discriminative brain regions and cognitive dysfunction. Experimental results demonstrate that the optimal classification accuracy achieved is 92.80%, which is at least 3.63% higher than the accuracy attained using other methods. This outcome confirms the effectiveness of our proposed method. Additionally, the identification of brain regions significantly associated with scores on the Montreal cognitive assessment scale may shed light on the underlying pathogenesis of ESRDaMCI.
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Encéfalo , Disfunção Cognitiva , Falência Renal Crônica , Humanos , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/patologia , Falência Renal Crônica/patologia , Falência Renal Crônica/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Substância Cinzenta/patologia , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/fisiopatologia , Rede Nervosa/fisiopatologia , Rede Nervosa/patologia , Substância Branca/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/fisiopatologia , Imageamento por Ressonância MagnéticaRESUMO
BACKGROUND: This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we report survival outcomes with a median follow-up of 40.1 months. METHODS: From January 2018 to October 2022, we retrospectively recruited patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after receiving PD-1 blockade (immunotherapy) plus chemotherapy at Jiangsu Cancer Hospital. RESULTS: A total of 132 eligible ESCC patients were included, and R0 resection was achieved in 131 cases (99.2 %). A complete pathological response rate (ypT0N0) was observed in 32 patients (24.2 %), and the objective response rate was 59.1 %. The most common grade 3-4 treatment-related adverse events (TRAEs) were leukopenia (18.2 %) and neutropenia (15.9 %). Three cases (2.3 %) of grade 3 immune-related AEs were observed, including increased ALT (0.8 %), rash (0.8 %), and encephalitis (0.8 %). The 1-year disease-free survival (DFS) and overall survival (OS) rates were 68.2 % and 89.4 %, respectively, and the 2-year DFS and OS rates were 55.1 % and 78.6 %, respectively. The pathological responses of 103 cases (94.5 % of 109) of the index lymph node (ILN) were categorized as the worst regression subgroup. In these cases, using the pathological response of the ILN to indicate the status of other lymph nodes would not result to a missed therapeutic lymph node dissection. CONCLUSIONS: Neoadjuvant immunotherapy plus chemotherapy is safe and effective for ESCC, with observable survival benefits. The pathological response of the ILN after neoadjuvant therapy may have important value in guiding therapeutic lymph node dissection.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Terapia Neoadjuvante , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Estudos Retrospectivos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Idoso , Adulto , Imunoterapia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Esofagectomia , Receptor de Morte Celular Programada 1/antagonistas & inibidoresRESUMO
OBJECTIVE: To develop and validate a nomogram combining radiomics and pathology features to distinguish between aldosterone-producing adenomas (APAs) and nonfunctional adrenal adenomas (NF-AAs). METHODS: Consecutive patients diagnosed with adrenal adenomas via computed tomography (CT) or pathologic analysis between January 2011 and November 2022 were eligible for inclusion in this retrospective study. CT images and hematoxylin & eosin-stained slides were used for annotation and feature extraction. The selected radiomics and pathology features were used to develop a risk model using various machine learning models, and the area under the receiver operating characteristic curve (AUC) was determined to evaluate diagnostic performance. The predicted results from radiomics and pathology features were combined and visualized using a nomogram. RESULTS: A total of 211 patients (APAs, n = 59; NF-AAs, n = 152) were included in this study, with patients randomly divided into either the training set or the testing set at a ratio of 8:2. The ExtraTrees model yielded a sensitivity of 0.818, a specificity of 0.733, and an accuracy of 0.756 (AUC = 0.817; 95% confidence interval [CI]: 0.675-0.958) in the radiomics testing set and a sensitivity of 0.999, a specificity of 0.842, and an accuracy of 0.867 (AUC = 0.905, 95% CI: 0.792-1.000) in the pathology testing set. A nomogram combining radiomics and pathology features demonstrated a strong performance (AUC = 0.912; 95% CI: 0.807-1.000). CONCLUSION: A nomogram combining radiomics and pathology features demonstrated strong predictive accuracy and discrimination capability. This model may help clinicians to distinguish between APAs and NF-AAs.
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Neoplasias das Glândulas Suprarrenais , Aldosterona , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Adulto , Aldosterona/metabolismo , Aldosterona/sangue , Diagnóstico Diferencial , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Idoso , Tomografia Computadorizada por Raios X , Adenoma Adrenocortical/diagnóstico por imagem , Adenoma Adrenocortical/metabolismo , Adenoma Adrenocortical/patologia , Nomogramas , Adenoma/diagnóstico por imagem , Adenoma/patologia , Adenoma/metabolismo , Neoplasias do Córtex Suprarrenal/diagnóstico por imagem , Neoplasias do Córtex Suprarrenal/metabolismo , Neoplasias do Córtex Suprarrenal/patologia , Sensibilidade e Especificidade , Imagem Multimodal/métodosRESUMO
Cadmium (Cd) exposure is considered as non-infectious stressor to human and animal health. Recent studies suggest that the immunotoxicity of low dose Cd is not directly apparent, but disrupts the immune responses when infected with some bacteria or virus. But how Cd alters the adaptive immunity organ and cells remains unclear. In this study, we applied lipopolysaccharide (LPS, infectious stressor) to induced inflammation in spleen tissues and T cells, and investigated the effects after Cd exposure and the underlying mechanism. Cd exposure promoted LPS-induced the expressions of the inflammatory factors, induced abnormal initiation of autophagy, but blocked autophagic flux. The effects Cd exposure under LPS activation were reversed by the autophagy promoter Rapamycin. Under LPS activation conditions, Cd also induced oxidative stress by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and reducing total antioxidant capacity (T-AOC) activity. The increased superoxide dismutase (SOD) activity after Cd exposure might be a negative feedback or passive adaptive regulation of oxidative stress. Cd-increased autophagic flux inhibition and TNF-α expression were reversed by ROS scavenger α-tocopherol (TCP). Furthermore, under LPS activation condition, Cd promoted activation of toll-like receptor 4 (TLR4)/IκBα/NFκ-B signaling pathway and increased TLR4 protein stability, which were abolished by the pretreatment of Rapamycin. The present study confirmed that, by increasing ROS-mediated inhibiting autophagic degradation of TLR4, Cd promoted LPS-induced inflammation in spleen T cells. This study identified the mechanism of autophagy in Cd-aggravated immunotoxicity under infectious stress, which could arouse public attention to synergistic toxicity of Cd and bacterial or virus infection.
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Autofagia , Cádmio , Inflamação , Lipopolissacarídeos , NF-kappa B , Estresse Oxidativo , Espécies Reativas de Oxigênio , Transdução de Sinais , Receptor 4 Toll-Like , Cádmio/toxicidade , Autofagia/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Inflamação/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Baço/efeitos dos fármacos , Inibidor de NF-kappaB alfa/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , MasculinoRESUMO
Relapse is a major challenge in the treatment of drug addiction, and exercise has been shown to decrease relapse to drug seeking in animal models. However, the neural circuitry mechanisms by which exercise inhibits morphine relapse remain unclear. In this study, we report that 4-week treadmill training prevented morphine conditioned place preference (CPP) expression during abstinence by acting through the nucleus accumbens (NAc)-ventral pallidum (VP) pathway. We found that neuronal excitability was reduced in D2-dopamine receptor-expressing medium spiny neurons (D2-MSNs) following repeated exposure to morphine and forced abstinence. Enhancing the excitability of NAc D2-MSNs via treadmill training decreased the expression of morphine CPP. We also found that the effects of treadmill training were mediated by decreasing enkephalin levels and that restoring opioid modulation of GABA neurotransmission in the VP, which increased neurotransmitter release from NAc D2-MSNs to VP, decreased morphine CPP. Our findings suggest the inhibitory effect of exercise on morphine CPP is mediated by reversing morphine-induced neuroadaptations in the NAc-to-VP pathway.
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OBJECTIVE: Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic. METHODS: Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined. RESULTS: Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS. CONCLUSION: Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.
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Córtex Motor , Síndrome das Pernas Inquietas , Humanos , Síndrome das Pernas Inquietas/epidemiologia , Estudos Transversais , Estudos de Casos e Controles , Diálise Renal/efeitos adversos , Circulação Cerebrovascular/fisiologia , Ferro , Imageamento por Ressonância MagnéticaRESUMO
Research on functional changes in the brain of inflammatory bowel disease (IBD) patients is emerging around the world, which brings new perspectives to medical research. In this paper, the methods of canonical correlation analysis (CCA), kernel canonical correlation analysis (KCCA), and sparsity preserving canonical correlation analysis (SPCCA) were applied to the fusion of simultaneous EEG-fMRI data from 25 IBD patients and 15 healthy individuals. The CCA, KCCA and SPCCA fusion methods were used for data processing to compare the results obtained by the three methods. The results clearly show that there is a significant difference in the activation intensity between IBD and healthy control (HC), not only in the frontal lobe (p < 0.01) and temporal lobe (p < 0.01) regions, but also in the posterior cingulate gyrus (p < 0.01), gyrus rectus (p < 0.01), and amygdala (p < 0.01) regions, which are usually neglected. The mean difference in the SPCCA activation intensity was 60.1. However, the mean difference in activation intensity was only 36.9 and 49.8 by using CCA and KCCA. In addition, the correlation of the relevant components selected during the SPCCA calculation was high, with correlation components of up to 0.955; alternatively, the correlations obtained from CCA and KCCA calculations were only 0.917 and 0.926, respectively. It can be seen that SPCCA is indeed superior to CCA and KCCA in processing high-dimensional multimodal data. This work reveals the process of analyzing the brain activation state in IBD disease, provides a further perspective for the study of brain function, and opens up a new avenue for studying the SPCCA method and the change in the intensity of brain activation in IBD disease.
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Análise de Correlação Canônica , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Eletroencefalografia , Mapeamento Encefálico/métodosRESUMO
Brain functional networks derived from functional magnetic resonance imaging (fMRI) provide a promising approach to understanding cognitive processes and predicting cognitive abilities. The topological attribute parameters of global networks are taken as the features from the overall perspective. It is constrained to comprehend the subtleties and variances of brain functional networks, which fell short of thoroughly examining the complex relationships and information transfer mechanisms among various regions. To address this issue, we proposed a framework to predict the cognitive function status in the patients with end-stage renal disease (ESRD) at a functional subnetwork scale (CFSFSS). The nodes from different network indicators were combined to form the functional subnetworks. The area under the curve (AUC) of the topological attribute parameters of functional subnetworks were extracted as features, which were selected by the minimal Redundancy Maximum Relevance (mRMR). The parameter combination with improved fitness was searched by the enhanced whale optimization algorithm (E-WOA), so as to optimize the parameters of support vector regression (SVR) and solve the global optimization problem of the predictive model. Experimental results indicated that CFSFSS achieved superior predictive performance compared to other methods, by which the mean absolute error (MAE), mean absolute percentage error (MAPE), and root mean square error (RMSE) were up to 0.5951, 0.0281 and 0.9994, respectively. The functional subnetwork effectively identified the active brain regions associated with the cognitive function status, which offered more precise features. It not only helps to more accurately predict the cognitive function status, but also provides more references for clinical decision-making and intervention of cognitive impairment in ESRD patients.
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Cognição , Falência Renal Crônica , Animais , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Algoritmos , Baleias , Falência Renal Crônica/diagnóstico por imagemRESUMO
Regulated cell death (RCD), also known as programmed cell death (PCD), plays a critical role in various biological processes, such as tissue injury/repair, development, and homeostasis. Dysregulation of RCD pathways can lead to the development of many human diseases, such as cancer, neurodegenerative disorders, and cardiovascular diseases. Maintaining proper metal ion homeostasis is critical for human health. However, imbalances in metal levels within cells can result in cytotoxicity and cell death, leading to a variety of diseases and health problems. In recent years, new types of metal overload-induced cell death have been identified, including ferroptosis, cuproptosis, and calcicoptosis. This has prompted us to examine the three defined metal-dependent cell death types, and discuss other metals-induced ferroptosis, cuproptosis, and disrupted Ca2+ homeostasis, as well as the roles of Zn2+ in metals' homeostasis and related RCD. We have reviewed the connection between metals-induced RCD and various diseases, as well as the underlying mechanisms. We believe that further research in this area will lead to the discovery of novel types of metal-dependent RCD, a better understanding of the underlying mechanisms, and the development of new therapeutic strategies for human diseases.
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Ferroptose , Homeostase , Humanos , Ferroptose/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Animais , Metais/metabolismo , Metais/toxicidade , Cálcio/metabolismo , Morte Celular Regulada/efeitos dos fármacos , Cobre/metabolismo , Cobre/toxicidade , Zinco/metabolismo , Apoptose/efeitos dos fármacos , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologiaRESUMO
The block copolymer micelles and natural biopolymers were utilized to form layer-by-layer (LbL) films via electrostatic interaction, which were able to effectively load and controllably release favipiravir, a potential drug for the treatment of coronavirus epidemic. The LbL films demonstrated reversible swelling/shrinking behavior along with the manipulation of temperature, which could also maintain the integrity in the structure and the morphology. Due to dehydration of environmentally responsive building blocks, the drug release rate from the films was decelerated by elevating environmental temperature and ionic strength. In addition, the pulsed release of favipiravir was observed from the multilayer films under the trigger of temperature, which ensured the precise control in the content of the therapeutic reagents at a desired time point. The nanoparticle-based LbL films could be used for on-demandin vitrorelease of chemotherapeutic reagents.
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Amidas , Micelas , Pirazinas , Liberação Controlada de Fármacos , Temperatura , Concentração OsmolarRESUMO
Objective: The aim of this study was to explore the resting-state functional connectivity (rsFC) of amygdala subregions in healthy controls (HCs) and in patients with Crohn's disease (CD) both with and without anxiety or depression. Materials and Methods: A total of 33 patients with CD and with anxiety or depression (CDad group), 31 patients with CD but without anxiety or depression (CDnad group), and 29 age-, sex-, and education level-matched HCs underwent functional magnetic resonance imaging. rsFC analysis was used to analyze the FC between the amygdala subregions and other areas of the brain. Results: Compared with the HC group, the CDad group demonstrated decreased rsFC between the right laterobasal subregion and the left hippocampus (P < .001) and right middle frontal gyrus (P < .001) and between the left superficial subregion and the left insula (P < .001). Compared with the HC group, the CDnad group demonstrated decreased rsFC between the left centromedial subregion and the left insula (P < .001). Compared with the CDnad group, the CDad group demonstrated decreased rsFC between the left centromedial subregion and the right precuneus (P < .001) and postcentral gyrus (P < .001), between the right laterobasal subregion and the left hippocampus (P < .001), and between the left superficial subregion and the right middle frontal gyrus (P < .001). Conclusions: There are significant FC changes in the amygdala subregions in patients with CD. These changes may be related to the disease itself or to the symptoms of anxiety and depression.
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Doença de Crohn , Depressão , Humanos , Tonsila do Cerebelo , Encéfalo , Ansiedade , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: This review was performed to systematically compare the effectiveness and safety of the first dorsal metacarpal artery flaps (FDMAF) and reverse homodigital dorsal flaps (RHDF) for thumb reconstruction. METHODS: All literatures, which compared FDMAF versus RHDF for thumb reconstruction, were acquired through a comprehensive search in multiple databases from inception until 31st August 2022. A meta-analysis was performed using the Cochrane Collaboration's RevMan 5.4 software. RESULTS: A total of 19 articles were retrieved, comprising 396 patients in the FDMAF group and 423 patients in the RHDF group. The pooled estimates suggested that there were no significant differences in venous congestion, complications about flap necrosis and reduced range of motion (ROM) of thumb, static 2-point discrimination (S-2PD) between the two groups. On the other hand, patients in the RHDF group had less vascular crisis (odds ratio [OR] = 3.15, 95%CI, 1.31-7.56), complications about poor cortical reorientation (OR = 440.02, 95%CI, 91.97-2105.27) and higher satisfaction rate (OR = 0.56, 95% CI, 0.33-0.96) than those in the FDMAF group. CONCLUSIONS: The two surgical procedures were both safe and reliable since no significant differences were found in flap necrosis between the two groups. However, the patients in the RHDF group had less complications about vascular crisis, poor cortical reorientation and higher satisfaction rate. Accordingly, we thought RHDF may be more superior for thumb reconstruction than FDMAF.
Assuntos
Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Polegar , Humanos , Polegar/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos/irrigação sanguínea , Amplitude de Movimento Articular , Complicações Pós-Operatórias , ArtériasRESUMO
PURPOSE: This study aimed to systematically compare the efficacy and safety of arthroscopic wafer procedure (AWP) versus ulnar shortening osteotomy (USO) for ulnar impaction syndrome (UIS) treatment. METHODS: All the studies included in this meta-analysis compared the efficacy of AWP to USO for UIS and were acquired through a comprehensive search across multiple databases. The meta-analysis was performed by calculating the effect sizes with the Cochrane Collaboration's RevMan 5.4 software. RESULTS: A total of 8 articles were included in this analysis, comprising 148 cases in the AWP group and 163 cases in the USO group. The pooled estimates indicated no significant differences in combined Darrow's Criteria or Modified Mayo Wrist Score, Modified Mayo Wrist Score, DASH scores, grip strength, VAS score, and postoperative ulnar variation. On the other hand, the patients in the AWP group exhibited fewer complications (OR = 0.17, 95%CI 0.05-0.54, P = 0.003) and a lower reoperation rate (OR = 0.12, 95%CI 0.05-0.28, P < 0.00001) than those in the USO group. CONCLUSIONS: The two surgical techniques were both effective in treating UIS but the AWP group showed fewer complications and a lower reoperation rate. Therefore, AWP may present a superior alternative for UIS treatment.
Assuntos
Artroscopia , Osteotomia , Ulna , Humanos , Osteotomia/métodos , Ulna/cirurgia , Artroscopia/métodos , Resultado do Tratamento , Síndrome , Articulação do Punho/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , ReoperaçãoRESUMO
The terahertz structured beams played a significant role in imaging. We utilized the transmitter with 0.1 THz to generate the quasi-Pearcey beam. The beam is produced by combining the self-designed parabola-slit modulated plate and Fourier lens, showing stripe-shaped pattern and self-focusing property. Based on that, introducing it into the testing of ptychography, we discovered there are decent effects in field reconstruction of the probe and sample with this beam by comparisons both in the simulations and the experiments. The beam has good spatial coherence through the analysis of the spatial frequency spectrums. It suggests that the beam with such features can take advantage of rapid reconstruction in full-field imaging.
RESUMO
Background: Our previous study has suggested that blocking stanniocalcin 2 (STC2) could reduce sunitinib resistance in clear cell renal cell carcinoma (ccRCC) under normoxia. The hypoxia is a particularly important environment for RCC occurrence and development, as well as sunitinib resistance. The authors proposed that STC2 also plays important roles in RCC sunitinib resistance under hypoxia conditions. Methods: The ccRCC Caki-1 cells were treated within the hypoxia conditions. Real-time quantitative PCR and Western blotting were applied to detect the STC2 expression in ccRCC Caki-1 cells. STC2-neutralizing antibodies, STC2 siRNA, and the recombinant human STC2 (rhSTC2) were used to identify targeting regulation on STC2 in modulating sunitinib resistance, proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion. In addition, autophagy flux and the lysosomal acidic environment were investigated by Western blotting and fluorescence staining, and the accumulation of sunitinib in cells was observed with the addition of STC2-neutralizing antibodies and autophagy modulators. Results: Under hypoxia conditions, sunitinib disrupted the lysosomal acidic environment and accumulated in Caki-1 cells. Hypoxia-induced the STC2 mRNA and protein levels in Caki-1 cells. STC2-neutralizing antibodies and STC2 siRNA effectively aggravated sunitinib-reduced cell viability and proliferation, which were reversed by rhSTC2. In addition, sunitinib promoted EMT, migration, and invasion, which were reduced by STC2-neutralizing antibodies. Conclusion: Inhibiting STC2 could reduce the sunitinib resistance of ccRCC cells under hypoxia conditions.