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OBJECTIVE: This study aimed to develop and validate a predictive model for osteoporotic vertebral fractures (OVFs) risk by integrating demographic, bone mineral density (BMD), CT imaging, and deep learning radiomics features from CT images. METHODS: A total of 169 osteoporosis-diagnosed patients from three hospitals were randomly split into OVFs (n = 77) and Non-OVFs (n = 92) groups for training (n = 135) and test (n = 34). Demographic data, BMD, and CT imaging details were collected. Deep transfer learning (DTL) using ResNet-50 and radiomics features were fused, with the best model chosen via logistic regression. Cox proportional hazards models identified clinical factors. Three models were constructed: clinical, radiomics-DTL, and fusion (clinical-radiomics-DTL). Performance was assessed using AUC, C-index, Kaplan-Meier, and calibration curves. The best model was depicted as a nomogram, and clinical utility was evaluated using decision curve analysis (DCA). RESULTS: BMD, CT values of paravertebral muscles (PVM), and paravertebral muscles' cross-sectional area (CSA) significantly differed between OVFs and Non-OVFs groups (P < 0.05). No significant differences were found between training and test cohort. Multivariate Cox models identified BMD, CT values of PVM, and CSAPS reduction as independent OVFs risk factors (P < 0.05). The fusion model exhibited the highest predictive performance (C-index: 0.839 in training, 0.795 in test). DCA confirmed the nomogram's utility in OVFs risk prediction. CONCLUSION: This study presents a robust predictive model for OVFs risk, integrating BMD, CT data, and radiomics-DTL features, offering high sensitivity and specificity. The model's visualizations can inform OVFs prevention and treatment strategies.
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Densidad Ósea , Osteoporosis , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Tomografía Computarizada por Rayos X , Humanos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Femenino , Masculino , Anciano , Fracturas Osteoporóticas/diagnóstico por imagen , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/complicaciones , Densidad Ósea/fisiología , Medición de Riesgo/métodos , Factores de Riesgo , Anciano de 80 o más Años , Aprendizaje ProfundoRESUMEN
BACKGROUND: Two trials in Chinese population showed that endovascular treatment (EVT) alone was noninferior to alteplase follow by EVT at 90 days. However, results of long-term clinical outcomes remain unknown. We reported the results of prespecified 18-month analysis of the DEVT trail. MATERIALS AND METHODS: We assessed clinical outcomes 18 months after patients were randomly assigned to receive EVT alone or bridging therapy for acute ischemic stroke (AIS). The primary outcome was the proportion of functional independence [modified Rankin scale (mRS), 0-2] at 18 months. Secondary outcomes included all-cause mortality and the quality of life at 18 months as measured by means of a health utility index according to the European Quality of Life 5-Dimension 5-level scale (EQ-5D-5L). Kaplan-Meier event curves were used to investigate the risk of mortality in participants with EVT alone or bridging therapy. RESULTS: Among 234 patients (EVT alone, n = 116; bridging therapy, n = 118) in the DEVT trial, only 231 (98.7%) patients were extended follow-up to 18 months. A total of 60 (51.7%) patients in the EVT alone achieved functional independence vs 56 (47.5%) patients in the bridging therapy (difference, 4.3%; 1-sided 97.5% CI, - 8.4% to ∞, P for noninferiority =0.014). No significant between-group difference was detected in EQ-5D-5L score (0.81 vs 0.73; difference, 0; 95% CI, 0 to 0.005). The cumulative mortality was 27.6% in the EVT alone and 28.8% in the bridging therapy. CONCLUSION: At 18 months follow-up, EVT alone was noninferior to bridging therapy regarding favorable functional outcome in patients with AIS. TRIAL REGISTRATION: Trial was registered on Chinese Clinical Trial Registry (ChiCTR-IOR-17013568) on 27/11/2017.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Estudios de Seguimiento , Calidad de Vida , Accidente Cerebrovascular/cirugía , ArteriasRESUMEN
BACKGROUND: Jaundice occurs in some pancreatic disease. However, its occurrences and role in pancreatic neuroendocrine neoplasms (PNENs) has not been well studied. In this study we showed the association between jaundice and the risk of high grade and poorly differentiated PNENs. METHODS: Ninety-three patients with head-neck PNENs were included. Poorly differentiated pancreatic neuroendocrine neoplasms were defined by a ki67 index > 55.0%. Logistic regression was used to show the association between demographic information, clinical signs and symptoms and the risk of poorly differentiated tumors. A nomogram model was developed to predict poorly differentiated tumor. RESULTS: Eight of 93 PNEN patients (8.6%) had jaundice. The age and ki67 index in patients with jaundice were significantly higher than those patients without jaundice. All jaundice occurred in patients with grade 3 PNENs. Mutivariable regression analysis showed that age (odds ratio(OR) = 1.10, 95% confidence interval (CI):1.02-1.19), tumor size (OR = 1.42, 95%CI:1.01-2.00) and jaundice (OR = 14.98, 95%CI: 1.22-184.09) were associated with the risk of poorly differentiated PNENs. The age and size combination showed a good performance in predicting poorly differentiated PNENs (area under the curve (AUC) = 0.81, 95% CI: 0.71-0.90). The addition of jaundice further improved the age- and size-based model (AUC = 0.86, 95% CI: 0.78-0.91). A nomogram was developed based on age, tumor size and jaundice. CONCLUSION: Our data showed that jaundice was associated with the risk of high grade PNENs and poorly differentiated PNENs.
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Ictericia , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Antígeno Ki-67 , Páncreas/patología , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/patología , Tumores Neuroendocrinos/complicaciones , Tumores Neuroendocrinos/patología , Ictericia/etiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Congenital absence of the pericardium (CAP) is rare in clinical practice, the symptoms vary among patients, and most doctors do not have enough knowledge of the condition. Most reported CAP cases are incidental findings. Therefore, this case report aimed to present a rare case of left partial CAP that presented with non-specific, possibly cardiac-related symptoms. CASE PRESENTATION: The patient, male, 56 years old, Asian, was admitted on March 2, 2021. The patient complained of occasional dizziness in the past week. The patient was suffering from hyperlipidemia and hypertension (stage 2), both untreated. The patient reported chest pain, palpitations, discomfort in the precordium, and dyspnea in the lateral recumbent position after strenuous activities, all of which started when he was about 15 years old. ECG showed sinus rhythm, 76 bpm, premature ventricular beats, incomplete right bundle branch block, and clockwise rotation of the electrical axis. Most of the ascending aorta could be detected in the parasternal intercostal space 2-4 by transthoracic echocardiography in the left lateral position. Chest computed tomography revealed the absence of pericardium between the aorta and the pulmonary artery, and part of the left lung was extending into the space. No changes in his condition have been reported up to now (March 2023). CONCLUSIONS: CAP should be considered when multiple examinations suggest heart rotation and a large moving range of the heart in the thoracic cavity.
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Cardiopatías Congénitas , Pericardio , Humanos , Masculino , Persona de Mediana Edad , Adolescente , Cardiopatías Congénitas/diagnóstico , Ecocardiografía , Dolor en el Pecho , Bloqueo de RamaRESUMEN
Wireless connectivity delay, disruption, or failure can significantly affect the performance of wireless-enabled medical devices, which in turn causes potential risks to the patient. Notably, the challenges related to connectivity provisioning are exacerbated in the fifth-generation (5G)-enabled healthcare use cases where mobility is utilized. In this article, we describe relevant 5G-enabled healthcare use cases involving mobility and identify the connectivity challenges that they face. We then illustrate practical implementation considerations, tradeoffs, and future research directions for enabling reliable 5G healthcare transmissions. This is done through simulation of connected ambulances as an example use-case.
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BACKGROUND: The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. METHODS: One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. RESULTS: The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor (P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12-0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12-5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02-0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06-0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79-0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70-0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08-0.99). CONCLUSION: Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Colesterol , Humanos , Antígeno Ki-67 , Lipoproteínas HDL , Metástasis Linfática , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Estudios RetrospectivosRESUMEN
Thrombolytic stroke therapy with tissue plasminogen activator (tPA) is limited by risks of hemorrhagic transformation (HT). We have reported that a new 12/15-lipoxygenase (12/15-LOX) inhibitor ML351 reduced tPA related HT in mice subjected to experimental stroke under anticoagulation. In this study, we asked whether ML351 can ameliorate tPA induced HT in an embolic stroke model. Rats were subjected to embolic middle cerebral artery occlusion with 2 or 3 hr ischemia and tPA infusion, with or without ML351. Regional cerebral blood flow was monitored 2 hr after ischemia and continuously monitored for 1 hr after treatment for determining reperfusion. Hemoglobin was determined in brain homogenates and infarct volume was quantified at 24 hr after stroke.12/15-LOX, cluster of differentiation 68(CD68), immunoglobulin G (IgG), and tight junction proteins expression was detected by immunohistochemistry. ML351 significantly reduced tPA related hemorrhage after stroke without affecting its thrombolytic efficacy. ML351 also reduced blood-brain barrier disruption and improved preservation of junction proteins. ML351 and tPA combination improved neurological deficit of rats even though ML351 did not further reduce the infarct volume compared to tPA alone treated animals. Pro-inflammatory cytokines were suppressed by ML351 both in vivo and in vitro experiments. We further showed that ML351 suppressed the expression of c-Jun-N-terminal kinase (JNK) in brains and microglia cultures, whereas exogenous 12-HETE attenuated this effect in vitro. In conclusion, ML351 and tPA combination therapy is beneficial in ameliorating HT after ischemic stroke. This protective effect is probably because of 12/15-LOX inhibition and suppression of JNK-mediated microglia/macrophage activation.
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Embolia Intracraneal/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isoxazoles/uso terapéutico , Inhibidores de la Lipooxigenasa/uso terapéutico , Naftalenos/uso terapéutico , Activador de Tejido Plasminógeno/uso terapéutico , Animales , Araquidonato 12-Lipooxigenasa/metabolismo , Araquidonato 15-Lipooxigenasa/metabolismo , Infarto Encefálico/patología , Circulación Cerebrovascular , Citocinas/antagonistas & inhibidores , Quimioterapia Combinada , Glucosa/deficiencia , Hipoxia Encefálica/metabolismo , Embolia Intracraneal/complicaciones , Accidente Cerebrovascular Isquémico/etiología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Ratas , Ratas Sprague-Dawley , ReperfusiónRESUMEN
Despite the huge efforts to deploy wireless communications technologies in smart manufacturing scenarios, some manufacturing sectors are still slow to massive adoption. This slowness of widespread adoption of wireless technologies in cyber-physical systems (CPS) is partly due to not fully understanding the detailed impact of wireless deployment on the physical processes especially in the cases that require low latency and high reliability communications. In this paper, we introduce an approach to integrate wireless network traffic data and physical processes data in order to evaluate the impact of wireless communications on the performance of a manufacturing factory work-cell. The proposed approach is introduced through the discussion of an engineering use case. A testbed that emulates a robotic manufacturing factory work-cell is constructed using two collaborative-grade robot arms, machine emulators, and wireless communication devices. All network traffic data is collected and physical process data, including the robots and machines states and various supervisory control commands, is also collected and synchronized to the network data. The data is then integrated where redundant data is removed and correlated activities are connected in a graph database. A data model is proposed, developed, and elaborated; the database is then populated with events from the testbed, and the resulting graph is presented. Query commands are then presented as a means to examine and analyze network performance and relationships within the components of the network. Moreover, we detail the way by which this approach is used to study the impact of wireless communications on the physical processes and illustrate the impact of various wireless network parameters on the performance of the emulated manufacturing work-cell. This approach can be deployed as a building block for various descriptive and predictive wireless analysis tools for CPS.
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BACKGROUND Pulmonary carcinoid tumorlets (PCT) are incidental histologic or radiologic discoveries that are localized neuroendocrine tumors whose proliferation is associated with chronic pulmonary inflammatory processes. This study assessed the imaging findings and histological appearances of PCT co-existing with chronic pulmonary inflammatory processes. MATERIAL AND METHODS We performed a retrospective study of 14 patients with incidentally-found PCT with co-existing chronic pulmonary inflammatory processes who underwent preoperative X-rays and CT between 1 January 2003 and 31 December 2012. The clinical symptoms, X-rays, CT imaging findings, and histological appearances were retrospectively evaluated. RESULTS Twelve women and 2 men were found to have PCT, with a mean age of 55.29±13.90 years (range 25-74 years) at diagnosis. Among these 14 patients, hemoptysis, cough, chest pain, expectoration, and chest tightness were found in 9 (64.3%), 5 (35.7%), 4 (28.6%), 3 (21.4%), and 1, respectively. For most patients, we could not find any small nodules on the X-ray or CT images. However, indirect imaging findings of bronchiectasis (85.7%, 12/14), atelectasis (57.1%, 8/14), inflammation (92.8%, 13/14), tuberculosis (7.1%, 1/14), and lung cancer (7.1%, 1/14) were found in all 14 patients. CONCLUSIONS PCT occurs most commonly in middle-aged women who have chronic pulmonary inflammatory processes such as bronchiectasis, atelectasis, and inflammation. Although there are no specific symptoms or direct imaging findings in these patients, our results showed that patients who have bronchiectasis, atelectasis, or recurrent pulmonary infection are at increased risk for PCT.
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Tumor Carcinoide/diagnóstico por imagen , Tumor Carcinoide/patología , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Neumonía/complicaciones , Adulto , Anciano , Tumor Carcinoide/complicaciones , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
The synthesis of hierarchical NiCo2O4-CoNiO2 hybrids embedded in partially reduced graphene oxide (represented by NiCo2O4/CoNiO2@pPRGO) is described. They were derived from ultrathin CoNi-based zeolitic imidazolate framework (CoNi-ZIF) nanosheets vertically grew on three-dimensional (3D) pRGO networks by pyrolysis at different temperatures (300, 600, and 900 °C) in N2 atmosphere. Transmission electron microscopy, X-ray diffraction, and X-ray photoemission spectroscopy measurements showed that the metal coordination centers (Co or Ni) were transferred into NiCo2O4 spinel and CoNiO2 nanostructures, along with a small number of metallic states of Co and Ni. In view of good electrochemical conductivity and large specific surface area of pRGO, good catalytic activity of Co- and Ni-contained NPs, and homogeneous distribution of NPs within the pRGO network, the NiCo2O4/CoNiO2@pRGO600 nanohybrid calcined at 600 °C displayed superior electrocatalytic activity toward hydrogen peroxide (H2O2) reduction. A glassy carbon electrode modified with NiCo2O4/CoNiO2@pRGO600 was used for determination of H2O2 by amperometry at an applied potential of - 0.4 V vs. Ag/AgCl. The nonenzymatic amperometric sensor exhibited high sensitivity and low detection limit (0.41 µM) within a wide working range (5 µM-3 mM and 3-12 mM) toward H2O2, as well as good selectivity, reproducibility, and long-term stability. Benefiting from the good biocompatibility and remarkable analytical performances of NiCo2O4/CoNiO2@pRGO600, the assay was used to determine real-time H2O2 released from living cancer cells. Graphical abstract.
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Cobalto/química , Grafito/química , Peróxido de Hidrógeno/análisis , Nanocompuestos/química , Níquel/química , Catálisis , Línea Celular Tumoral , Técnicas Electroquímicas/instrumentación , Técnicas Electroquímicas/métodos , Electrodos , Humanos , Límite de Detección , Óxidos/química , Reproducibilidad de los ResultadosRESUMEN
Industrial Internet of Things (IIoT) applications, featured with data-centric innovations, are leveraging the observability, control, and analytics, as well as the safety of industrial operations. In IIoT deployments, wireless links are increasingly used in improving the operational connectivity for industrial data services, such as collecting massive process data, communicating with industrial robots, and tracking machines/parts/products on the factory floor and beyond. The wireless system design for IIoT applications is inherently a joint effort between operational technology (OT) engineers, information technology (IT) system architects, and wireless network planners. In this paper, we propose a new reference framework for the wireless system design in IIoT use cases. The framework presents a generic design process and identifies the key questions and tools of individual procedures. Specifically, we extract impact factors from distinct domains including industrial operations and environments, data service dynamics, and the IT infrastructure. We then map these factors into function clusters and discuss their respective impact on performance metrics and resource utilization strategies. Finally, discussions take place in four exemplary IIoT applications where we use the framework to identify the wireless network issues and deployment features in the continuous process monitoring, discrete system control, mobile applications, and spectrum harmonization, respectively. The goals of this work are twofold: 1) to assist OT engineers to better recognize wireless communication demands and challenges in their plants, 2) to help industrial IT specialists to come up with operative and efficient end-to-end wireless solutions to meet demanding needs in factory environments.
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Both cadmium (Cd) and lead (Pb) exposure can induce kidney damage. However, the effects of combined exposure to Cd and Pb on renal function at environmental levels have not been fully clarified. In this study we investigated the renal function in a Chinese population co-exposed to Cd and Pb. A total of 331 subjects (215 women and 116 men), living in either a control or a polluted area, were included in this study. Cd and Pb in blood and urine (BCd, BPb, UCd, and UPb), and kidney effect markers including urinary N-acetyl-ß-D-glucosaminidase (UNAG) and estimated glomerular filtration rate (eGFR), were determined, and the association between exposure markers and renal effect biomarkers were analyzed. The exposure levels in the polluted area were significantly higher than in the control area (all pâ¯<â¯0.01). The eGFR of subjects in the polluted area was decreased compared with that in the control area (pâ¯<â¯0.01). The subjects with high BCd/BPb (BCd ≥ 2⯵g/L, BPb ≥ 100⯵g/L) or high UCd/UPb (UCd ≥ 3⯵g/g creatinine, UPb ≥ 10⯵g/g creatinine) showed higher UNAG and UALB levels compared with other subgroups (pâ¯<â¯0.01). The probability of having elevated UNAG in subjects with high BCd/BPb was greater than those with low BCd/BPb [odds ratio (OR) =â¯2.6, 95% confidence interval (CI): 1.4-4.7), low BCd/high BPb (OR =3.1, 95% CI: 1.4-6.6), and high BCd/low BPb (OR = 1.7, 95% CI: 0.9-3.2). The OR of subjects with low UCd and high UPb, high UCd and low UPb, and high UCd/UPb were 2.9 (95% CI: 1.4-5.7), 3.3 (95% CI: 1.5-7.2), and 7.7 (95% CI: 4.0-14.7), respectively, compared with those with low UCd/UPb. The risk of decrease in eGFR was also higher in subjects with high UCd/UPb than for those with low UCd/UPb (OR = 7.2, 95% CI: 0.8-62.2). Our data demonstrate that Cd and Pb exposure, alone or in combination, are associated with renal impairment. In addition, co-exposure to Pb and Cd propagates the renal tubular dysfunction compared with Cd or Pb exposure alone.
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Cadmio/toxicidad , Contaminantes Ambientales/toxicidad , Riñón/efectos de los fármacos , Plomo/toxicidad , Acetilglucosaminidasa/orina , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Biomarcadores/orina , Cadmio/sangre , Cadmio/orina , Exposición a Riesgos Ambientales/efectos adversos , Contaminantes Ambientales/sangre , Contaminantes Ambientales/orina , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Humanos , Riñón/fisiología , Plomo/sangre , Plomo/orina , Masculino , Persona de Mediana Edad , Oportunidad RelativaRESUMEN
BACKGROUND/AIMS: Cancer stem cells (CSCs) are largely responsible for tumor relapse and metastatic behavior. Doublecortin-like kinase 1 (DCLK1) was recently reported to be a biomarker for gastrointestinal CSCs and involved in the epithelial-mesenchymal transition (EMT) and tumor progression. B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is a crucial regulator of CSC self-renewal, malignant transformation and EMT, and a previous study from our group showed that Bmi-1 is upregulated in pancreatic cancer progression and participates in EMT. However, it remains unclear whether DCLK1 is involved in pancreatic cancer or whether DCLK1 is associated with the altered level of Bmi-1 expression. METHODS: The correlation of DCLK1 expression and clinical features of pancreatic cancer was analyzed in 210 paraffin-embedded archived pancreatic cancer specimens by immunohistochemical analysis. The biological effects of DCLK1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays, cell migration by wound healing assay and cell invasion by Transwell invasion assay. We further investigated the effect of therapeutic siRNA targeting DCLK1 on pancreatic cancer cell growth in vivo. Moreover, the molecular mechanism by which DCLK1 upregulates Bmi-1 expression was explored using real-time PCR, western blotting and Co-immunoprecipitation assay. RESULTS: DCLK1 is overexpressed in pancreatic cancer and is related to metastasis and prognosis. Knockdown of DCLK1 markedly suppressed cell growth in vitro and in vivo and also inhibited the migration and invasion of pancreatic cancer cells. Furthermore, we found that DCLK1 silencing could inhibit EMT in cancer cells via downregulation of Bmi-1 and the mesenchymal markers Snail and Vimentin and upregulation of the epithelial marker E-cadherin. Moreover, high DCLK1 expression in human pancreatic cancer samples was associated with a mesenchymal phenotype and increased cell proliferation. Further co-immunoprecipitation indicated that DCLK1 did not interact with Bmi-1 directly. CONCLUSION: Our data suggest that upregulation of DCLK1 may contribute to pancreatic cancer metastasis and poor prognosis by increasing Bmi-1 expression indirectly. The findings indicate that inhibiting DCLK1 expression might be a novel strategy for pancreatic cancer therapy.
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Péptidos y Proteínas de Señalización Intracelular/metabolismo , Neoplasias Pancreáticas/patología , Complejo Represivo Polycomb 1/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Quinasas Similares a Doblecortina , Transición Epitelial-Mesenquimal , Regulación de la Expresión Génica , Humanos , Péptidos y Proteínas de Señalización Intracelular/antagonistas & inhibidores , Péptidos y Proteínas de Señalización Intracelular/genética , Estimación de Kaplan-Meier , Ratones , Ratones Desnudos , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/mortalidad , Pronóstico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , ARN Interferente Pequeño/uso terapéutico , Factores de Transcripción de la Familia Snail/metabolismo , Vimentina/metabolismoRESUMEN
Camelid single-domain antibodies (sdAbs, VHHs, or Nanobodies®) are types of antibody fragments that are composed of the heavy-chain variable domain only. These VHHs possess unique structural and functional features, as they are small in size and exhibit thermal stability and high solubility. Compared to conventional antibodies, VHHs can be manufactured in microorganisms to significantly save on cost, labor, and time since VHHs lack the Fc domain with its N-linked oligosaccharide. Until now, VHHs have been expressed in several kinds of production systems, ranging from prokaryotic cells, yeasts, fungi, insect cells, and mammalian cell lines, to plants. In this review, we focus on the recent production of VHHs, introduce different platforms, and summarize the current state of this area and its future trends. Finally, the first potential VHH product, produced in Pichia pastoris, will probably be available on the market in 2018; thus, it is of great importance to give this antibody fragment timely attention. This is the first review concerning the production of VHHs in laboratory settings.
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Ingeniería Genética , Anticuerpos de Dominio Único/biosíntesis , Animales , Línea Celular , Escherichia coli/metabolismo , Hongos/metabolismo , Cadenas Pesadas de Inmunoglobulina/biosíntesis , Pichia/metabolismo , Plantas/metabolismoRESUMEN
BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive slow growing soft tissue neoplasm, mostly affecting young individuals with no gender difference. It usually arises in deep soft tissue of the lower limbs and trunk, but few cases of LGFMS located in pelvis have been reported. CASE PRESENTATION: We describe the magnetic resonance imaging(MRI) features of LGFMS located in the anterior pelvic wall of a 21-year-old female and correlate them with clinicopathological features. The tumor was completely resected and there is no recidivism during the follow-up one year. CONCLUSIONS: We report on the radiological findings of LGFMS with histological correlation. Awareness of the imaging features may be useful for the diagnosis of LGFMS and helpful to distinguish among mimics.
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Fibrosarcoma/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neoplasias de los Tejidos Blandos/diagnóstico por imagen , Femenino , Fibrosarcoma/cirugía , Humanos , Clasificación del Tumor/métodos , Neoplasias de los Tejidos Blandos/cirugía , Adulto JovenRESUMEN
OBJECTIVES: To characterize imaging features of renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE gene fusion. METHODS: Twenty-one patients with Xp11.2/TFE RCC were retrospectively evaluated. Tumour location, size, density, cystic or solid appearance, calcification, capsule sign, enhancement pattern and metastases were assessed. RESULTS: Fourteen women and seven men were identified with 12 being 25 years old or younger. Tumours were solitary and cystic-solid (76.2 %) masses with a capsule (76.2 %); 90.5 % were located in the medulla. Calcifications and lymph node metastases were each observed in 24 %. On unenhanced CT, tumour attenuation was greater than in normal renal parenchyma (85.7 %). Tumour enhancement was less than in normal renal cortex on all enhanced phases, greater than in normal renal medulla on cortical and medullary phases, but less than in normal renal medulla on delayed phase. On MR, the tumours were isointense on T1WI, heterogeneously hypointense on T2WI and slightly hyperintense on diffusion-weighted imaging. CONCLUSION: Xp11.2/TFE RCC usually occurs in young women. It is a cystic-solid, hyperdense mass with a capsule. It arises from the renal medulla with enhancement less than in the cortex but greater than in the medulla in all phases except the delayed phase, when it is lower than in the medulla. KEY POINTS: ⢠Xp11.2/TFE RCC was more prevalent in young women. ⢠On unenhanced CT, Xp11.2/TFE RCC attenuation was greater than in renal parenchyma. ⢠Xp111/2TFE RCC arises primarily from the renal medulla. ⢠Xp11.2/TFE RCC enhancement was less than in the cortex on all phases. ⢠Enhancement was greater than in the medulla in arterial and corticomedullary phase.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Carcinoma de Células Renales/diagnóstico por imagen , Cromosomas Humanos Par 11/genética , Fusión Génica/genética , Neoplasias Renales/diagnóstico por imagen , Translocación Genética/genética , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Riñón/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
The prevalence of cholesterol gallstones has increased in recent years. Bacterial infection correlates with the formation of gallstones. We studied the composition and function of bacterial communities in cholesterol gallstones and bile from 22 cholesterol gallstone patients using culture-dependent and culture-independent methods. Altogether fourteen and eight bacterial genera were detected in cholesterol gallstones and bile, respectively. Pseudomonas spp. were the dominant bacteria in both cholesterol gallstones and bile. As judged by diversity indices, hierarchical clustering and principal component analysis, the bacterial communities in gallstones were different from those in bile. The gallstone microbiome was considered more stable than that of bile. The different microbial communities may be partially explained by differences in their habitats. We found that 30% of the culturable strains from cholesterol gallstones secreted ß-glucuronidase and phospholipase A2. Pseudomonas aeruginosa strains showed the highest ß-glucuronidase activity and produced the highest concentration of phospholipase A2, indicating that Ps. aeruginosa may be a major agent in the formation of cholesterol gallstones.
Asunto(s)
Bacterias/clasificación , Bilis/química , Bilis/microbiología , Biota , Colesterol/metabolismo , Cálculos Biliares/química , Cálculos Biliares/microbiología , Adulto , Anciano , Bacterias/enzimología , Bacterias/aislamiento & purificación , ADN Bacteriano/química , ADN Bacteriano/genética , ADN Ribosómico/química , ADN Ribosómico/genética , Electroforesis en Gel de Gradiente Desnaturalizante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fosfolipasas A2/análisis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADNRESUMEN
PURPOSE: High-density lipoprotein cholesterol (HDL-c) plays an important role in tumorigenesis in several endocrine-related cancers. Few studies have shown the effect of non-HDL-c in malignant tumors. The present study aimed to identify the association between non-HDL-c and high-grade pancreatic neuroendocrine neoplasms (PNENs). METHODS: A total of 197 PNEN patients who underwent surgery were analyzed retrospectively. Clinical and histopathological features, such as patients' age and sex, tumor location and size, tumor grade, the level of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c) and fasting plasma-glucose levels were obtained. Non-HDL-c was calculated as total cholesterol - HDL-c. The relationships between those features and high-grade PNENs were identified using logistic regression analysis. RESULTS: Among the 197 patients with PNENs, a lower HDL-c level was more common seen in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.05). The non-HDL-c/HDL-c ratio was greater in patients with poorly differentiated PNENs than in those with well-differentiated PNENs (P < 0.01). Similarly, a greater proportion of patients with a non-HDL-c/HDL-c ratio larger than 5 was found in patients with poorly differentiated PNENs than in those with well-differentiation PNENs (P < 0.01). Multivariate logistic analysis showed that the non-HDL-c/HDL-c ratio was positively associated with poorly differentiated PNENs (odds ratio (OR) = 1.45, 95% conference interval (CI):1.13-1.87). Similarly, the risk of poorly differentiated PNENs increased significantly in patients with a non-HDL-c/HDL-c greater than 5 (OR = 14.13, 95%CI: 2.98-66.89). The risk of high-grade PNENs increased in patients with a high non-HDL-c/HDL-c ratio (OR = 1.27, 95% CI: 1.04-1.55), and the risk also increased markedly when the ratio was greater than 5 (OR = 5.00, 95%CI: 1.28-19.49). CONCLUSIONS: A high ratio of non-HDL-c/HDL-c was associated with high-grade PNENs or poorly differentiated PNENs.
RESUMEN
This study involved the preparation of natural rubber-based composites incorporating varying proportions of heavy metals and rare earth oxides (Sm2O3, Ta2O5, and Bi2O3). The investigation analyzed several parameters of the samples, including mass attenuation coefficients (general, photoelectric absorption, and scattering), linear attenuation coefficients (µ), half-value layers (HVLs), tenth-value layers (TVLs), mean free paths (MFPs), and radiation protection efficiencies (RPEs), utilizing the Monte Carlo simulation software Geant4 and the WinXCom database across a gamma-ray energy spectrum of 40-150 keV. The study also compared the computational discrepancies among these measurements. Compared to rubber composites doped with single-component fillers, multi-component mixed shielding materials significantly mitigate the shielding deficiencies observed with single-component materials, thereby broadening the γ-ray energy spectrum for which the composites provide effective shielding. Subsequently, the simulation outcomes were juxtaposed with experimental data derived from a 133Ba (80 keV) γ-source. The findings reveal that the simulated results align closely with the experimental observations. When compared to the WinXCom database, the Geant4 software demonstrates superior accuracy in deriving radiation shielding parameters and notably enhances experimental efficiency.
RESUMEN
The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages' phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell-cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m, an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.