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BACKGROUND: Tumor morphology, immune function, inflammatory levels, and nutritional status play critical roles in the progression of intrahepatic cholangiocarcinoma (ICC). This multicenter study aimed to investigate the association between markers related to tumor morphology, immune function, inflammatory levels, and nutritional status with the prognosis of ICC patients. Additionally, a novel tumor morphology immune inflammatory nutritional score (TIIN score), integrating these factors was constructed. METHODS: A retrospective analysis was performed on 418 patients who underwent radical surgical resection and had postoperative pathological confirmation of ICC between January 2016 and January 2020 at three medical centers. The cohort was divided into a training set (n = 272) and a validation set (n = 146). The prognostic significance of 16 relevant markers was assessed, and the TIIN score was derived using LASSO regression. Subsequently, the TIIN-nomogram models for OS and RFS were developed based on the TIIN score and the results of multivariate analysis. The predictive performance of the TIIN-nomogram models was evaluated using ROC survival curves, calibration curves, and clinical decision curve analysis (DCA). RESULTS: The TIIN score, derived from albumin-to-alkaline phosphatase ratio (AAPR), albumin-globulin ratio (AGR), monocyte-to-lymphocyte ratio (MLR), and tumor burden score (TBS), effectively categorized patients into high-risk and low-risk groups using the optimal cutoff value. Compared to individual metrics, the TIIN score demonstrated superior predictive value for both OS and RFS. Furthermore, the TIIN score exhibited strong associations with clinical indicators including obstructive jaundice, CEA, CA19-9, Child-pugh grade, perineural invasion, and 8th edition AJCC N stage. Univariate and multivariate analysis confirmed the TIIN score as an independent risk factor for postoperative OS and RFS in ICC patients (p < 0.05). Notably, the TIIN-nomogram models for OS and RFS, constructed based on the multivariate analysis and incorporating the TIIN score, demonstrated excellent predictive ability for postoperative survival in ICC patients. CONCLUSION: The development and validation of the TIIN score, a comprehensive composite index incorporating tumor morphology, immune function, inflammatory level, and nutritional status, significantly contribute to the prognostic assessment of ICC patients. Furthermore, the successful application of the TIIN-nomogram prediction model underscores its potential as a valuable tool in guiding individualized treatment strategies for ICC patients. These findings emphasize the importance of personalized approaches in improving the clinical management and outcomes of ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Estado Nutricional , Humanos , Colangiocarcinoma/cirurgia , Colangiocarcinoma/patologia , Masculino , Feminino , Estudos Retrospectivos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Pessoa de Meia-Idade , Prognóstico , Idoso , Nomogramas , Inflamação , Biomarcadores Tumorais , Fosfatase Alcalina/sangue , Carga Tumoral , Avaliação Nutricional , Albumina Sérica/análise , Albumina Sérica/metabolismo , Curva ROC , Monócitos/patologiaRESUMO
The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.
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Diferenciação Celular/genética , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/embriologia , RNA/análise , Análise de Sequência de RNA , Análise de Célula Única , Humanos , Interneurônios/citologia , Interneurônios/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese/genética , Neurônios/classificação , Neurônios/citologia , Neurônios/metabolismo , RNA/genética , Transdução de SinaisRESUMO
INTRODUCTION: Distinguishing between malignant pleural effusion (MPE) and benign pleural effusion (BPE) poses a challenge in clinical practice. We aimed to construct and validate a combined model integrating radiomic features and clinical factors using computerized tomography (CT) images to differentiate between MPE and BPE. METHODS: A retrospective inclusion of 315 patients with pleural effusion (PE) was conducted in this study (training cohort: n = 220; test cohort: n = 95). Radiomic features were extracted from CT images, and the dimensionality reduction and selection processes were carried out to obtain the optimal radiomic features. Logistic regression (LR), support vector machine (SVM), and random forest were employed to construct radiomic models. LR analyses were utilized to identify independent clinical risk factors to develop a clinical model. The combined model was created by integrating the optimal radiomic features with the independent clinical predictive factors. The discriminative ability of each model was assessed by receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA). RESULTS: Out of the total 1,834 radiomic features extracted, 15 optimal radiomic features explicitly related to MPE were picked to develop the radiomic model. Among the radiomic models, the SVM model demonstrated the highest predictive performance [area under the curve (AUC), training cohort: 0.876, test cohort: 0.774]. Six clinically independent predictive factors, including age, effusion laterality, procalcitonin, carcinoembryonic antigen, carbohydrate antigen 125 (CA125), and neuron-specific enolase (NSE), were selected for constructing the clinical model. The combined model (AUC: 0.932, 0.870) exhibited superior discriminative performance in the training and test cohorts compared to the clinical model (AUC: 0.850, 0.820) and the radiomic model (AUC: 0.876, 0.774). The calibration curves and DCA further confirmed the practicality of the combined model. CONCLUSION: This study presented the development and validation of a combined model for distinguishing MPE and BPE. The combined model was a powerful tool for assisting in the clinical diagnosis of PE patients.
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Derrame Pleural Maligno , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Derrame Pleural Maligno/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Diagnóstico Diferencial , Derrame Pleural/diagnóstico por imagem , Máquina de Vetores de Suporte , Curva ROC , Modelos Logísticos , Adulto , RadiômicaRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant tumor with a poor prognosis. This study aimed to investigate whether Hemoglobin, Albumin, Lymphocytes, and Platelets (HALP) score and Tumor Burden Score (TBS) serves as independent influencing factors following radical resection in patients with ICC. Furthermore, we sought to evaluate the predictive capacity of the combined HALP and TBS grade, referred to as HTS grade, and to develop a prognostic prediction model. METHODS: Clinical data for ICC patients who underwent radical resection were retrospectively analyzed. Univariate and multivariate Cox regression analyses were first used to find influencing factors of prognosis for ICC. Receiver operating characteristic (ROC) curves were then used to find the optimal cut-off values for HALP score and TBS and to compare the predictive ability of HALP, TBS, and HTS grade using the area under these curves (AUC). Nomogram prediction models were constructed and validated based on the results of the multivariate analysis. RESULTS: Among 423 patients, 234 (55.3%) were male and 202 (47.8) were aged ≥ 60 years. The cut-off value of HALP was found to be 37.1 and for TBS to be 6.3. Our univariate results showed that HALP, TBS, and HTS grade were prognostic factors of ICC patients (all P < 0.05), and ROC results showed that HTS had the best predictive value. The Kaplan-Meier curve showed that the prognosis of ICC patients was worse with increasing HTS grade. Additionally, multivariate regression analysis showed that HTS grade, carbohydrate antigen 19-9 (CA19-9), tumor differentiation, and vascular invasion were independent influencing factors for Overall survival (OS) and that HTS grade, CA19-9, CEA, vascular invasion and lymph node invasion were independent influencing factors for recurrence-free survival (RFS) (all P < 0.05). In the first, second, and third years of the training group, the AUCs for OS were 0.867, 0.902, and 0.881, and the AUCs for RFS were 0.849, 0.841, and 0.899, respectively. In the first, second, and third years of the validation group, the AUCs for OS were 0.727, 0.771, and 0.763, and the AUCs for RFS were 0.733, 0.746, and 0.801, respectively. Through the examination of calibration curves and using decision curve analysis (DCA), nomograms based on HTS grade showed excellent predictive performance. CONCLUSIONS: Our nomograms based on HTS grade had excellent predictive effects and may thus be able to help clinicians provide individualized clinical decision for ICC patients.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Feminino , Humanos , Masculino , Albuminas , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/cirurgia , Antígeno CA-19-9 , China/epidemiologia , Colangiocarcinoma/cirurgia , Estudos Retrospectivos , Pessoa de Meia-Idade , IdosoRESUMO
BACKGROUND: The aim of this study was to investigate the prognostic value of arginase-1 (Arg-1) and glypican-3 (GPC-3) in patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Two hundred and thirty-seven patients with ICC were included in this study. All patients had undergone radical surgery and had complete clinical information. Immunohistochemistry was used to assess the levels of Arg-1 and GPC-3 in ICC tissues. Univariate and multivariate analyses were conducted to identify independent risk factors in ICC. The relationship between Arg-1 and GPC-3 levels and patient survival was determined using the Kaplan-Meier method. RESULTS: High Arg-1 and GPC-3 expression levels were associated with poor prognosis in patients with ICC, and they could be as new prognostic biomarkers in ICC. CONCLUSION: Arg-1 and GPC-3 can serve as independent prognostic biomarkers in ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Arginase , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Glipicanas , Humanos , PrognósticoRESUMO
Neuronal autophagy and inflammatory responses are important in the pathogenesis of traumatic brain injury (TBI), and toll-like receptor 4 (TLR4) may play an important role in the related molecular cascade. The present study investigated the protective effect of apocynin, an inhibitor of NADPH oxidase, in a TBI rat model and further examined neuronal autophagy and the TLR4-mediated pathway. Adult male Sprague-Dawley rats were subjected to controlled cortical impact injury and intraperitoneally injected with apocynin (50 mg/kg) immediately after the trauma. In addition to motor and behavioral studies, brain water content and histology analyses were performed. Expression of autophagy-related proteins as well as TLR4/NF-κB signaling and inflammatory mediators was analyzed. The apocynin treatment significantly attenuated TBI-induced motor and behavioral impairment, brain edema and neuronal damage in rats. Immunohistochemical and Western blot analyses revealed that apocynin treatment significantly reduced the expression of NOX2, LC3 and Beclin1 in the hippocampus at 12-48 h after injury. Double immunolabeling demonstrated that apocynin decreased the co-localization of LC3 or TLR4-positive cells with hippocampal neurons at 24 h following TBI. In addition, CD11b (microglial marker) and GFAP (astrocyte marker)-immunopositive cells were also clearly decreased in hippocampal tissues. Meanwhile, protein levels of TLR4, NF-κB p65, TNF-α and IL-1ß were found to be significantly downregulated by Western blot analysis. In conclusion, our findings indicate that the protective effects of apocynin may be related to modulation of neuronal autophagy and the TLR4/NF-κB signaling pathway.
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Acetofenonas/uso terapêutico , Autofagia/fisiologia , Lesões Encefálicas Traumáticas/metabolismo , NF-kappa B/metabolismo , Neurônios/metabolismo , Receptor 4 Toll-Like/metabolismo , Acetofenonas/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Autofagia/efeitos dos fármacos , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Masculino , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod/métodos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: To study the impact of severe idiopathic pulmonary arterial hypertension (IPAH) on pregnancy outcome and to investigate the effect of multidisciplinary approach during pregnancy on the pregnancy outcome in pregnant woman with severe IPAH. METHODS: Between March 2007 and November 2013, 10 pregnant women with severe IPAH undergoing treatment in Beijing Anzhen Hospital were studied retrospectively.Hemodynamic measurements, medical therapy, manner of delivery, anesthetic administration, multidisciplinary management and outcomes were assessed. RESULTS: All 10 cases were first diagnosed at the mean of (24 ± 3) weeks during the pregnancy. The systolic pulmonary artery pressure (sPAP) estimated by transthoracic echocardiography was (95.6 ± 1.3) mmHg (1 mmHg = 0.133 kPa) .Seven cases of class III and 3 cases of class IV were recorded by World Health Organization functional class.One patient underwent pregnancy termination at gestational age of 21 weeks with no maternal death or complications, nine patients continued pregnancy and all the patients underwent cesarean section. The mean pregnancy length was (31 ± 5) weeks.Nine had cesarean deliveries during continuous epidural anesthesia, and one during general anesthesia. There were three maternal deaths in hospital (5, 2, 3 days postpartum), and seven patients were alive, and the average hospitalization days was (8 ± 4) days.One fetus lost with cesarean section. Two were term delivery, and seven cases were premature delivery. The average weight is (1 948 ± 731) g and nine were alive and no malformation. CONCLUSIONS: Because of maternal mortality in patients with severe IPAH remains prohibitively high, patients should continue to be counseled to avoid pregnancy.Women with severe IPAH who become pregnancy should be followed by multidisciplinary approach, and cesarean deliveries during continuous epidural anesthesia are a relatively safe way for pregnancy termination in patients with severe IPAH.
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Hipertensão Pulmonar Primária Familiar/diagnóstico , Mortalidade Materna , Complicações na Gravidez , Resultado da Gravidez , Artéria Pulmonar/diagnóstico por imagem , Aborto Induzido , Anestesia Epidural , Pressão Arterial/fisiologia , Cesárea , Parto Obstétrico , Ecocardiografia , Hipertensão Pulmonar Primária Familiar/mortalidade , Feminino , Idade Gestacional , Hospitalização/estatística & dados numéricos , Humanos , Gravidez , Nascimento Prematuro , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the optimal management of cardiac surgery during pregnancy, and the maternal and fetal outcomes in pregnant patients undergoing cardiac surgery with the use of cardiopulmonary bypass. METHODS: Nine pregnant women with heart diseases were identified, who underwent cardiac surgery with cardiopulmonary bypass between January 2002 and March 2013. Patient charts were reviewed for pregnant age, types of heart diseases, surgical indication, parameters of cardiopulmonary bypass, and maternal and fetal outcomes. RESULTS: Among 9 patients, there were 4 cases of valvular heart disease (two of rheumatic heart disease complicated with subacute bacterial endocarditis and heart failure, one of mechanical prosthetic valves flap after mitral replacement, one of severe aortic stenosis), one case of aortic dissection, three cases with atrial myxoma, and one case with tetralogy of Fallot. The New York Heart Association (NYHA) functional classification: there were three cases with class I, two with class II, two with class III, and two with class IV. Heart surgeries were performed from 9 to 39 weeks gestation. Five patients underwent heart surgery with cardiopulmonary bypass combined with cesarean section. The other 4 patients terminated pregnancies after heart surgeries, two of whom underwent uterine curettage in first trimester, one induction of labor in second trimester, and one continued to be pregnant until 37 weeks' gestation. Seven patients were alive. Nine fetal outcomes were included two with artificial abortion, one with induction of labor and one with cesarean section in second trimester, two of premature labor and three of full-term labor with cesarean section in third trimester. Five newborns were no malformation, four of whom were alive. CONCLUSION: Cardiopulmonary bypass can be used safely with satisfactory maternal and fetal outcomes in pregnant patients with heart disease undergoing cardiac surgery.
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Ponte Cardiopulmonar , Cardiopatias/cirurgia , Complicações Cardiovasculares na Gravidez/cirurgia , Resultado da Gravidez , Aborto Induzido , Adulto , Procedimentos Cirúrgicos Cardíacos/métodos , Cesárea , Feminino , Cardiopatias/mortalidade , Humanos , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
Automatic medical image segmentation has witnessed significant development with the success of large models on massive datasets. However, acquiring and annotating vast medical image datasets often proves to be impractical due to the time consumption, specialized expertise requirements, and compliance with patient privacy standards, etc. As a result, Few-shot Medical Image Segmentation (FSMIS) has become an increasingly compelling research direction. Conventional FSMIS methods usually learn prototypes from support images and apply nearest-neighbor searching to segment the query images. However, only a single prototype cannot well represent the distribution of each class, thus leading to restricted performance. To address this problem, we propose to Generate Multiple Representative Descriptors (GMRD), which can comprehensively represent the commonality within the corresponding class distribution. In addition, we design a Multiple Affinity Maps based Prediction (MAMP) module to fuse the multiple affinity maps generated by the aforementioned descriptors. Furthermore, to address intra-class variation and enhance the representativeness of descriptors, we introduce two novel losses. Notably, our model is structured as a dual-path design to achieve a balance between foreground and background differences in medical images. Extensive experiments on four publicly available medical image datasets demonstrate that our method outperforms the state-of-the-art methods, and the detailed analysis also verifies the effectiveness of our designed module.
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Algoritmos , Processamento de Imagem Assistida por Computador , Humanos , Processamento de Imagem Assistida por Computador/métodos , Bases de Dados FactuaisRESUMO
Increasing research has shown that the abnormal expression of circRNAs is closely related to tumorigenesis, apoptosis, and patient prognosis in cervical cancer. This study aimed to reveal the procancer role of circIL21R in cervical cancer and investigate its related molecular mechanisms. Bioinformatics analysis revealed that circIL21R promotes the progression of cervical cancer via the miR-1205/PTBP1 axis. CircIL21R expression was significantly greater in tumor tissue than in adjacent normal tissue, and higher circIL21R expression indicated shorter survival. We applied MTS assays, EdU assays, and Transwell assays to show that the overexpression of circIL21R promoted cervical cancer cell proliferation and invasion. Mechanistically, circIL21R promoted the expression of PTBP1 by sponging miR-1205. Moreover, rescue assays confirmed that regulating the expression of miR-1205 or PTBP1 could reverse the tumorigenic effect caused by circIL21R overexpression. In addition, circIL21R promoted the tumorigenesis of cervical cancer in vivo. In summary, our study demonstrated that circIL21R was highly expressed in cervical cancer and upregulated PTBP1 expression by acting as a ceRNA for miR-1205, making outstanding contributions to several malignant biological processes in cervical cancers, such as growth, proliferation, and invasion. CircIL21R is a potential biomarker for the diagnosis and treatment of cervical cancer.
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Objective: This study aims to investigate the relationship between serum vitamin D, total IgE levels and chronic spontaneous urticaria (CSU). Methods: We collected data from 101 patients with chronic spontaneous urticaria (experimental group) and 115 healthy normal subjects (control group) in the same period of physical examination. Results: The results showed that the number of deficient and absolute deficient 25-hydroxyvitamin D in the experimental group was significantly lower than in the control group (P < 0.05). Pearson correlation analysis showed that the activity score of CSU patients was negatively correlated with serum vitamin D (r = -0.2278, P = 0.0220) and positively correlated with IgE (r = 0.2078, P = 0.0380). It was observed that serum vitamin D in CSU patients was negatively correlated with their activity (r = -0.2278, P = 0.0220) and positively correlated with age (r = 0.2675, P = 0.0069). The Point-biserial correlation analysis revealed that gender was positively correlated with serum vitamin D (Pearson correlation coefficient = 0.286, P = 0.004) and UAS score (Pearson correlation coefficient = 0.273, P = 0.006). Ordinal logistic regression analysis showed that only serum vitamin D was correlated to activity scores (P = 0.008). In addition to activity scores, age (P = 0.005) and gender (P = 0.04) were correlated to serum vitamin D. Conclusion: The activity score of CSU patients was negatively correlated with serum vitamin D and positively correlated with IgE. Serum vitamin D in CSU patients was negatively correlated with activity score and disease duration and positively correlated with age and gender.
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BACKGROUND: A limited number of studies investigated the association between blood pressure variability (BPV) and cognitive impairment in patients with hypertension. This study aimed to identify the longitudinal association between BPV and cognitive decline and the role of blood pressure (BP) control in this association. METHODS AND RESULTS: Participants with hypertension from the HRS (Health and Retirement Study), the ELSA (English Longitudinal Study of Ageing), and the CHARLS (China Health and Retirement Longitudinal Study) were included. Variation independent of the mean (VIM) was adopted to measure BPV. Cognitive function was measured by standard questionnaires, and a standardized Z score was calculated. Linear mixed-model and restricted cubic splines were adopted to explore the association between BPV and cognitive decline. The study included 4853, 1616, and 1432 eligible patients with hypertension from the HRS, ELSA, and CHARLS, respectively. After adjusting for covariates, per-SD increment of VIM of BP was significantly associated with global cognitive function decline in Z scores in both systolic BP (pooled ß, -0.045 [95% CI, -0.065 to -0.029]) and diastolic BP (pooled ß, -0.022 [95% CI, -0.040 to -0.004]) among hypertensive patients. Similar inverse associations were observed in patients with hypertension taking antihypertensive drugs and in patients with hypertension with well-controlled BP. CONCLUSIONS: High BPV was independently associated with a faster cognitive decline among patients with hypertension, even those with antihypertensive medications or well-controlled BP. Further studies are needed to confirm our results and determine whether reducing BPV can prevent or delay cognitive decline.
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Pressão Sanguínea , Disfunção Cognitiva , Hipertensão , Humanos , Hipertensão/fisiopatologia , Hipertensão/epidemiologia , Hipertensão/tratamento farmacológico , Hipertensão/psicologia , Feminino , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/diagnóstico , Masculino , Pessoa de Meia-Idade , Idoso , Pressão Sanguínea/fisiologia , Estudos Prospectivos , China/epidemiologia , Anti-Hipertensivos/uso terapêutico , Fatores de Tempo , Cognição , Fatores de Risco , Estudos Longitudinais , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
Vascular restenosis following angioplasty continues to pose a significant challenge. The heterocyclic trioxirane compound [1, 3, 5-tris((oxiran-2-yl)methyl)-1, 3, 5-triazinane-2, 4, 6-trione (TGIC)], known for its anticancer activity, was utilized as the parent ring to conjugate with a non-steroidal anti-inflammatory drug, resulting in the creation of the spliced conjugated compound BY1. We found that BY1 induced ferroptosis in VSMCs as well as in neointima hyperplasia. Furthermore, ferroptosis inducers amplified BY1-induced cell death, while inhibitors mitigated it, indicating the contribution of ferroptosis to BY1-induced cell death. Additionally, we established that ferritin heavy chain1 (FTH1) played a pivotal role in BY1-induced ferroptosis, as evidenced by the fact that FTH1 overexpression abrogated BY1-induced ferroptosis, while FTH1 knockdown exacerbated it. Further study found that BY1 induced ferroptosis by enhancing the NCOA4-FTH1 interaction and increasing the amount of intracellular ferrous. We compared the effectiveness of various administration routes for BY1, including BY1-coated balloons, hydrogel-based BY1 delivery, and nanoparticles targeting OPN loaded with BY1 (TOP@MPDA@BY1) for targeting proliferated VSMCs, for prevention and treatment of the restenosis. Our results indicated that TOP@MPDA@BY1 was the most effective among the three administration routes, positioning BY1 as a highly promising candidate for the development of drug-eluting stents or treatments for restenosis.
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Ferroptose , Músculo Liso Vascular , Nanopartículas , Ferroptose/efeitos dos fármacos , Animais , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/citologia , Humanos , Nanopartículas/química , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oxirredutases/metabolismo , FerritinasRESUMO
OBJECTIVE: To evaluate the clinical effectiveness of laparoscopic management of cesarean scar pregnancy (CSP) by deep implantation. BACKGROUND: A pregnancy implanting within the scar from a previous cesarean delivery is a rare condition of ectopic pregnancy. There are two different types of CSPs. Type I is caused by implantation of the amniotic sac on the scar with progression toward either the cervicoisthmic space or the uterine cavity. Type II (CSP-II) is caused by deep implantation into a previous CS defect with infiltrating growth into the uterine myometrium and bulging from the uterine serosal surface, which may result in uterine rupture and severe bleeding during the first trimester of pregnancy. Thus, timely management with an early and accurate diagnosis of CSP-II is important. However, laparoscopic management in CSP-II has not yet been evaluated. METHODS: Eleven patients with CSP-II underwent conservative laparoscopic surgery or laparoscopy combined with transvaginal bilateral uterine artery ligation and resection of the scar with gestational tissue and wound repair to preserve the uterus from March 2008 to November 2011. Patients with CSP-II were diagnosed using color Doppler sonography, and the diagnosis was confirmed by laparoscopy. The operation time, the blood loss during surgery, the levels of ß-human chorionic gonadotropin (ß-hCG) before surgery, the time taken for serum ß-hCG levels to return to <100 mIU/mL postoperatively, and the time for the uterine body to revert to its original state were retrospectively analyzed. RESULTS: All 11 operations were successfully performed using laparoscopy with preservation of the uterus. One patient underwent a dilation and curettage after laparoscopic bilateral uterine artery ligation. Eight patients were treated solely by laparoscopic bilateral uterine artery ligation and resection of the scar with gestational tissue and wound repair. The remaining two patients underwent laparoscopic bilateral uterine artery ligation and transvaginal resection of the CS with gestational tissue and wound repair because of dense adhesions and heavy bleeding. The average operation time was 85.5 (±17.5) minutes, and the blood loss was 250.0 (±221.4) mL. The blood serum level of ß-hCG returned to <100 mIU/mL in 16.4 (±5.3) days postoperatively. Among the 10 patients who underwent resection of CS and wound repair, the time for the uterus to revert to its original state (judged by ultra-sonography) was 10.8 (±3.0) days postoperatively. CONCLUSIONS: Laparoscopy can remove ectopic gestational tissue and allow subsequent wound repair, as well as provide diagnostic confirmation. Being a minimally invasive procedure, laparoscopic or laparoscopy combined with transvaginal bilateral uterine artery ligation and resection of the scar with gestational tissue and wound repair can become an effective alternative for the treatment of CSP-II.
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Cesárea , Cicatriz/complicações , Laparoscopia/métodos , Gravidez Ectópica , Adulto , Perda Sanguínea Cirúrgica , Gonadotropina Coriônica Humana Subunidade beta/sangue , Feminino , Humanos , Gravidez , Gravidez Ectópica/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Ultrassonografia Pré-Natal , Artéria Uterina/cirurgia , CicatrizaçãoRESUMO
Native starches and their phosphates with various molecular structures was introduced as the depressant to realize the flotation of quartz from hematite in this study. The present starch phosphates (WSP, NSP, GSP) were modified by the reaction between phosphate and three different corn starches (WS, NS, G50). The synthesis and characterization of starch phosphates found that starch with high amylopectin content was easily modified into starch phosphates. Microflotation tests showed that starch phosphates exhibited stronger depressing abilities of hematite flotation than native starches. Zeta potential measurement showed that both starches and starch phosphates could positively shift the zeta potential of hematite, while starch phosphates had more effects than starches. XPS and MDS indicated that the chemisorption occurred between Fe of hematite surface and CO groups of starch-based depressants. In addition, starch phosphates could adsorb onto the hematite surface through PO groups. MDS also presented that the adsorption strength of starch phosphate was mainly determined by the type and number of generating chelating rings, and the molecular structure of starch significantly affected the formation of chelate rings. The proposed adsorption model insights will significantly promote the development of starch-based depressants for iron ore flotation and other mineral processing applications.
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Radiomics was proposed by Lambin et al. in 2012 and since then there has been an explosion of related research. There has been significant interest in developing high-throughput methods that can automatically extract a large number of quantitative image features from medical images for better diagnostic or predictive performance. There have also been numerous radiomics investigations on intrahepatic cholangiocarcinoma in recent years, but no pertinent review materials are readily available. This work discusses the modeling analysis of radiomics for the prediction of lymph node metastasis, microvascular invasion, and early recurrence of intrahepatic cholangiocarcinoma, as well as the use of deep learning. This paper briefly reviews the current status of radiomics research to provide a reference for future studies.
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Background: The degree of inflammation and immune status is widely recognized to be associated with intrahepatic cholangiocarcinoma (ICC) and is closely linked to poor postoperative survival. The purpose of this study was to evaluate whether the systemic immune-inflammatory index (SII) and the albumin bilirubin (ALBI) grade together exhibit better predictive strength compared to SII and ALBI separately in patients with ICC undergoing curative surgical resection. Methods: A retrospective analysis was performed on a cohort of 374 patients with histologically confirmed ICC who underwent curative surgical resection from January 2016 to January 2020 at three medical centers. The cohort was divided into a training set comprising 258 patients and a validation set consisting of 116 patients. Subsequently, the prognostic predictive abilities of three indicators, namely SII, ALBI, and SII+ALBI grade, were evaluated. Independent risk factors were identified through univariate and multivariate analyses. The identified independent risk factors were then utilized to construct a nomogram prediction model, and the predictive strength of the nomogram prediction model was assessed through Receiver Operating Characteristic (ROC) survival curves and calibration curves. Results: Univariate analysis of the training set, consisting of 258 eligible patients with ICC, revealed that SII, ALBI, and SII+ALBI grade were significant prognostic factors for overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). Multivariate analysis revealed the independent significance of SII+ALBI grade as a risk factor for postoperative OS and RFS (p < 0.05). Furthermore, we conducted an analysis of the correlation between SII, ALBI, SII+ALBI grade, and clinical features, indicating that SII+ALBI grade exhibited stronger associations with clinical and pathological characteristics compared to SII and ALBI. We constructed a predictive model for postoperative survival in ICC based on SII+ALBI grade, as determined by the results of multivariate analysis. Evaluation of the model's predictive strength was performed through ROC survival curves and calibration curves in the training set and validation set, revealing favorable predictive performance. Conclusion: The SII+ALBI grade, a novel classification based on inflammatory and immune status, serves as a reliable prognostic indicator for postoperative OS and RFS in patients with ICC.
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It is uncertain whether the power of transformer architectures can complement existing convolutional neural networks. A few recent attempts have combined convolution with transformer design through a range of structures in series, where the main contribution of this paper is to explore a parallel design approach. While previous transformed-based approaches need to segment the image into patch-wise tokens, we observe that the multi-head self-attention conducted on convolutional features is mainly sensitive to global correlations and that the performance degrades when these correlations are not exhibited. We propose two parallel modules along with multi-head self-attention to enhance the transformer. For local information, a dynamic local enhancement module leverages convolution to dynamically and explicitly enhance positive local patches and suppress the response to less informative ones. For mid-level structure, a novel unary co-occurrence excitation module utilizes convolution to actively search the local co-occurrence between patches. The parallel-designed Dynamic Unary Convolution in Transformer (DUCT) blocks are aggregated into a deep architecture, which is comprehensively evaluated across essential computer vision tasks in image-based classification, segmentation, retrieval and density estimation. Both qualitative and quantitative results show our parallel convolutional-transformer approach with dynamic and unary convolution outperforms existing series-designed structures.
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Automatically identifying the structural substrates underlying cardiac abnormalities can potentially provide real-time guidance for interventional procedures. With the knowledge of cardiac tissue substrates, the treatment of complex arrhythmias such as atrial fibrillation and ventricular tachycardia can be further optimized by detecting arrhythmia substrates to target for treatment (i.e., adipose) and identifying critical structures to avoid. Optical coherence tomography (OCT) is a real-time imaging modality that aids in addressing this need. Existing approaches for cardiac image analysis mainly rely on fully supervised learning techniques, which suffer from the drawback of workload on labor-intensive annotation process of pixel-wise labeling. To lessen the need for pixel-wise labeling, we develop a two-stage deep learning framework for cardiac adipose tissue segmentation using image-level annotations on OCT images of human cardiac substrates. In particular, we integrate class activation mapping with superpixel segmentation to solve the sparse tissue seed challenge raised in cardiac tissue segmentation. Our study bridges the gap between the demand on automatic tissue analysis and the lack of high-quality pixel-wise annotations. To the best of our knowledge, this is the first study that attempts to address cardiac tissue segmentation on OCT images via weakly supervised learning techniques. Within an in-vitro human cardiac OCT dataset, we demonstrate that our weakly supervised approach on image-level annotations achieves comparable performance as fully supervised methods trained on pixel-wise annotations.
Assuntos
Fibrilação Atrial , Coração , Humanos , Tecido Adiposo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , ConhecimentoRESUMO
Since the overexpression of folate receptors (FRs) in certain types of cancers, a variety of FR-targeted fluorescent probes for tumor detection have been developed. However, the reported probes almost all have the same targeting ligand of folic acid with various fluorophores and/or linkers. In the present study, a series of novel tumor-targeted near-infrared (NIR) molecular fluorescent probes were designed and synthesized based on previously reported 6-substituted pyrrolo[2,3-d]pyrimidine antifolates. All newly synthesized probes showed specific FR binding in vitro, whereas GT-NIR-4 and GT-NIR-5 with a benzene and a thiophene ring, respectively, on the side chain of pyrrolo[2,3-d]pyrimidine exhibited better FR binding affinity than that of GT-NIR-6 with folic acid as targeting ligand. GT-NIR-4 also showed high tumor uptake in KB tumor-bearing mice with good pharmacokinetic properties and biological safety. This work demonstrates the first attempt to replace folic acid with antifolates as targeting ligands for tumor-targeted NIR probes.