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Adenocarcinoma , Neoplasias Pancreáticas , Pancreatitis , Tomografía Computarizada por Rayos X , Humanos , Adenocarcinoma/patología , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/diagnóstico , Diagnóstico Diferencial , Quiste Pancreático/diagnóstico por imagen , Quiste Pancreático/patología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico , Pancreatitis/etiología , Pancreatitis/diagnóstico por imagenRESUMEN
PURPOSE: To compare the consistency between fundus fluorescein angiography (FFA) and optical coherence tomography angiography (OCTA) for the diagnosis of diabetic retinopathy (DR). MATERIALS AND METHODS: Ninety-six diabetic patients (185 eyes) treated from January 2019 to December 2019 underwent OCTA and FFA. The image characteristics of fundus lesions were recorded. Sixty-nine patients (137 eyes) who were diagnosed with DR by both examinations and needed to receive panretinal photocoagulation (PRP) were selected. The retinal nerve fiber layer (RNFL) thickness, macular superficial vascular complex (SVC) and deep vascular complex (DVC) blood flow density, 300µm area surrounding foveal avascular zone (FAZ) (FD300) blood flow density and FAZ parameters were compared. RESULTS: The Kappa coefficient of FFA and OCTA for diagnosing DR was 0.537 (P=0.000). FFA and OCTA had substantial consistency for detecting retinal microaneurysms and macular edema (Kappa coefficient=0.643/0.616, P=0.000), perfect consistency for detecting retinal neovascularization and retinal non-perfusion area (Kappa coefficient=0.809/0.832, P=0.000), and moderate consistency for detecting structural changes in the macular ring (Kappa coefficient=0.423, P=0.000). The RNFL thickness in the peripapillary and the superior temporal, temporal inferior, inferior nasal and superior nasal regions rose 1 week after PRP but declined 1 year after treatment (P<0.05). The macular SVC, DVC and FD300 blood flow density declined 1 week after PRP but rose 1 year after treatment (P<0.05). CONCLUSIONS: OCTA shows consistency with FFA for diagnosing DR, which remedies the deficiency of FFA. The reduction in fundus lesions after PRP can be quantified by OCTA.
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Diabetes Mellitus , Retinopatía Diabética , Humanos , Vasos Retinianos/patología , Retinopatía Diabética/diagnóstico por imagen , Retinopatía Diabética/cirugía , Tomografía de Coherencia Óptica/métodos , Angiografía con Fluoresceína/métodos , Resultado del Tratamiento , Diabetes Mellitus/patologíaRESUMEN
BACKGROUND: Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. OBJECTIVES: We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. METHODS: Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. RESULTS: The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 µg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1ß, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure. CONCLUSIONS: This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.
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Dermatitis Atópica , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Humanos , Preescolar , Estudios de Cohortes , Níquel/efectos adversos , Cohorte de Nacimiento , Inmunoglobulina E , CitocinasRESUMEN
Objective: To establish an intramedullary transplantation model of primary megakaryocytes to evaluate the platelet-producing capacity of megakaryocytes and explore the underlying regulatory mechanisms. Methods: Donor megakaryocytes from GFP-transgenic mice bone marrow were enriched by magnetic beads. The platelet-producing model was established by intramedullary injection to recipient mice that underwent half-lethal dose irradiation 1 week in advance. Donor-derived megakaryocytes and platelets were detected by immunofluorescence staining and flow cytometry. Results: The proportion of megakaryocytes in the enriched sample for transplantation was 40 to 50 times higher than that in conventional bone marrow. After intramedullary transplantation, donor-derived megakaryocytes successfully implanted in the medullary cavity of the recipient and produce platelets, which showed similar expression of surface markers and morphology to recipient-derived platelets. Conclusion: We successfully established an in vivo platelet-producing model of primary megakaryocytes using magnetic-bead enrichment and intramedullary injection, which objectively reflects the platelet-producing capacity of megakaryocytes in the bone marrow.
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Médula Ósea , Megacariocitos , Animales , Plaquetas , Células de la Médula Ósea , Trasplante de Médula Ósea , Humanos , Megacariocitos/metabolismo , RatonesRESUMEN
According to singular optics, the phase and intensity that characterize structured electromagnetic beams can be understood in terms of concepts that involve subspaces where they or their derivatives exhibit a particular behavior, such as giving rise to extreme values or not being well defined. Caustics are a paradigmatic example of the former, while helical dislocation lines exemplify the latter. In this work the interrelation of the morphology of caustics and the morphology of dislocation lines is theoretically studied. The analysis for highly structured beams requires an efficient methodology that allows the identification of optical vortices, their topological charge, and the helical dislocation lines they belong to. Such a methodology is introduced and applied to paraxial elliptic umbilic beams and nonparaxial Airy symmetric three-dimensional beams. Nonparaxial beams exhibit caustic surfaces that delimit regions with a finite volume and different intensity average. It is shown that in the high intensity region so defined, the dislocation lines play the role of an internal skeleton, i.e., an endoskeleton, of the beam. The exoskeleton created in the low intensity regions shows subtle and interesting features that complement those of the endoskeleton; the caustics that delimit low intensity regions have a strong influence on the morphology of the exoskeleton.
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Gastroenteropancreatic neuroendocrine tumor G3(GEP-NET G3) is a novel subtype of neuroendocrine neoplasms proposed in 2019,which has unique biological behavior characteristics. However,there are still many challenges and controversies in its diagnosis and treatment. There are obvious differences between GEP-NET G3 and neuroendocrine carcinoma (NEC) in genetic alterations and molecular profiles. The most frequently mutated genes in NET G3 are MEN1,DAXX/ATRX,while in NEC,TP53 and Rb are the most frequently mutated genes. Currently,the mainstream view is that NET G3 and NEC are two distinct diseases with different genetic backgrounds,and NET G3 will not develop into NEC. Several clinical and pathological factors should be considered to distinguish GEP-NET G3 and NEC,which including patients' medical history,histopathological morphology of neoplasms,Ki-67 index,immunohistochemical results of TP53,Rb,DAXX/ATRX and other markers. Multidisciplinary treatment,including radical resection,chemotherapy,targeted therapy,peptide receptor radionuclide therapy,immunotherapy should be applied in patients with GEP-NET G3. Overall,given its relatively indolent biological behavior,the therapeutic strategy should be more actively. Although the cure strategy of NET G3 has many similarities with NET G1/2,it is completely different from NEC.
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Depression is a common and recurrent mental disease, with complex etiology, which is mainly affected by genetic, metabolic and social factors. The specific pathogenesis is still unclear. In recent years, the hypothesis of inflammatory factors related to depression has attracted wide attention of researchers. A large number of clinical experimental studies have shown that depression is related to the increase of proinflammatory factors in central and peripheral blood. The inflammatory factors in peripheral blood can spread in the brain through the way of specific transporters across the blood-brain barrier, and activate or participate in the brain inflammatory response, and ultimately affect the neuronal activity and neurotransmitter release in the emotional regulation area of the brain, which in turn leads to depressive symptoms. This paper summarizes the relationship between inflammatory factors and depression and its possible mechanism, which provides reference for further prevention and control, clinical treatment and scientific research of depression.
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Encéfalo , Depresión , Humanos , NeuronasAsunto(s)
Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Profesional/diagnóstico , Dermatosis Facial/diagnóstico , Masaje , Dermatitis Alérgica por Contacto/etiología , Dermatitis Profesional/etiología , Dermatosis Facial/inducido químicamente , Femenino , Preparaciones para el Cabello/efectos adversos , Humanos , Masaje/métodos , Persona de Mediana Edad , Odorantes , Aceites Volátiles/efectos adversos , Aceite de Oliva/efectos adversosRESUMEN
A cross-cultural disadvantage exists when inferring the mental state of others, which may be detrimental for individuals acting in an increasingly globalized world. The dorsomedial prefrontal cortex (dmPFC) is a key hub of the social brain involved in ToM. We explored whether facilitation of dmPFC function by focal high-definition tDCS can improve cross-cultural mind-reading. 52 (26 F/M) Singaporeans performed the Caucasian version of the Reading the Mind in the Eyes Test (RMET) and received HD-tDCS to either the dmPFC or a control site (right temporoparietal junction, rTPJ) in sham-controlled, double-blinded, crossover studies. Contact with Caucasians was determined for the Singaporean cohort as a potential mediator of RMET performance and HD-tDCS response. 52 Caucasians completed the RMET during sham-tDCS and served as a comparison group. A cross-cultural disadvantage on the RMET was confirmed in the Singaporean cohort and this disadvantage was more pronounced in those participants who had less contact with Caucasians. Importantly, HD-tDCS to the dmPFC improved RMET performance in those with less contact. No effect was identified for rTPJ HD-tDCS or for the age/sex control task demonstrating task and site specificity of the stimulation effects. Electrical stimulation of the dmPFC selectively improves the rate of cross-cultural ToM inference from facial cues, effectively removing cross-cultural disadvantage that was found in individuals with lower cross-cultural exposure.
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Encéfalo , Teoría de la Mente , Estimulación Transcraneal de Corriente Directa , Comparación Transcultural , Estimulación Eléctrica , Humanos , ParapsicologíaRESUMEN
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Regulation of mTOR by miR-107 to facilitate glioma cell apoptosis and to enhance cisplatin sensitivity, by P.-F. Su, S.-Q. Song, published in Eur Rev Med Pharmacol Sci 2018; 22 (20): 6864-6872-DOI: 10.26355/eurrev_201810_16155-PMID: 30402851" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/16155.
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Objective: To explore the association between precollege sexual abuse experiences at different periods and adult attachment in college students. Methods: In October 2018,a total of 4 034 college students were selected from 4 colleges in Hefei City by using the stratified cluster sampling method. A self-designed questionnaire was used to investigate the demographic characteristics, sexual abuse experience, and attachment style of participants. Multivariate linear regression analysis was performed to analyze the association between different periods, types of precollege sexual abuse experiences and attachment style in college students. Results: The rate of total precollege sexual abuse, noncontact sexual abuse, and contact sexual abuse was 14.1% (569), 12.7% (512) and 5.4% (219), respectively. Multivariate linear regression analysis showed that secure attachment [ß(95%CI)=-0.205 (-0.292, -0.117)] was negatively correlated with total precollege sexual abuse experiences, whereas anxiety attachment [ß(95%CI)=0.211 (0.110, 0.310)], avoidant attachment [ß(95%CI)=0.117 (0.020, 0.216)] were positively correlated with total precollege sexual abuse experiences. The number of periods of precollege noncontact sexual abuse was negatively correlated with secure attachment [ß(95%CI)=-0.106(-0.171, -0.041)]and positively correlated with anxiety attachment [ß(95%CI)=0.158 (0.084, 0.231)]and avoidant attachment [ß(95%CI)=0.080 (0.008, 0.152)]. The noncontact [ß(95%CI)=0.427 (0.018, 0.775)] and contact sexual abuse [ß(95%CI)=0.468 (0.251, 0.687)] in high school were positively correlated with anxiety attachment (P<0.05). Conclusion: Different periods, types of precollege sexual abuse experiences were all associated with adult attachment in college students.
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Delitos Sexuales , Estudiantes , Adulto , Ansiedad , Humanos , Encuestas y Cuestionarios , UniversidadesRESUMEN
Palmoplantar lichen planus is a rare variant of lichen planus with diverse clinical presentations, making the diagnosis challenging. We present an unusual case of a young patient who presented with asymptomatic non-pruritic flat-topped pigmented plaques on his left sole and no other lesions elsewhere. Histology was consistent with lichen planus. We emphasize a high index of suspicion owing to varied clinical presentation and the necessity of a biopsy for diagnosis.
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Dermatosis del Pie/patología , Hiperpigmentación/patología , Liquen Plano/patología , Humanos , Masculino , Adulto JovenRESUMEN
The effect of the γ-ray total dose radiation on the energy storage density (ESD) and the phase transition of antiferroelectric-like (AFE-like) Al-doped HfO2 (HfAlO) thin films was investigated. The ESD property and wake-up behavior of the phase transition during the field cycling of the AFE-like HfAlO thin films were quantified before and after the radiation. The efficiency of the AFE-like thin films for energy storage slightly decreases as the total dose increases from 200 krad (Si) to 5 Mrad (Si), which is attributed to the radiation-induced trapped defects at the interfaces of HfAlO/TiN. Both the J-E, C-V, and εr-f characteristics of the AFE-like HfAlO thin films were also measured before and after the radiation at the same electrodes. These results further confirm that the ferroelectricity of the thin films can be reduced due to the radiation oxide trapped defects. It is worth noting that an enhanced wake-up behavior of the AFE-like HfAlO thin films can be observed after the radiation, which indicates that the transition from the antiferroelectric phase to the ferroelectric phase could be accelerated by the increased radiation-induced defects.
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BACKGROUND AND PURPOSE: Transcranial MR imaging-guided focused ultrasound is a promising novel technique to treat multiple disorders and diseases. Planning for transcranial MR imaging-guided focused ultrasound requires both a CT scan for skull density estimation and treatment-planning simulation and an MR imaging for target identification. It is desirable to simplify the clinical workflow of transcranial MR imaging-guided focused ultrasound treatment planning. The purpose of this study was to examine the feasibility of deep learning techniques to convert MR imaging ultrashort TE images directly to synthetic CT of the skull images for use in transcranial MR imaging-guided focused ultrasound treatment planning. MATERIALS AND METHODS: The U-Net neural network was trained and tested on data obtained from 41 subjects (mean age, 66.4 ± 11.0 years; 15 women). The derived neural network model was evaluated using a k-fold cross-validation method. Derived acoustic properties were verified by comparing the whole skull-density ratio from deep learning synthesized CT of the skull with the reference CT of the skull. In addition, acoustic and temperature simulations were performed using the deep learning CT to predict the target temperature rise during transcranial MR imaging-guided focused ultrasound. RESULTS: The derived deep learning model generates synthetic CT of the skull images that are highly comparable with the true CT of the skull images. Their intensities in Hounsfield units have a spatial correlation coefficient of 0.80 ± 0.08, a mean absolute error of 104.57 ± 21.33 HU, and a subject-wise correlation coefficient of 0.91. Furthermore, deep learning CT of the skull is reliable in the skull-density ratio estimation (r = 0.96). A simulation study showed that both the peak target temperatures and temperature distribution from deep learning CT are comparable with those of the reference CT. CONCLUSIONS: The deep learning method can be used to simplify workflow associated with transcranial MR imaging-guided focused ultrasound.
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Aprendizaje Profundo , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Cráneo/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal/métodos , Anciano , Simulación por Computador , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Objective: To explore the association between maternal bisphenol A (BPA) exposure during pregnancy and neurobehavioral development in infant. Methods: Participants were from the Ma'anshan Birth Cohort, which was established from October 2008 to October 2010 based on four municipal medical and health institutions in Ma'anshan. High-performance liquid chromatography-tandem mass spectrometry was applied for the determination of serum BPA concentration in 1 783 pregnant women sampled at their first filing, and during 2.97 to 28.1 months age of the infants. Neurobehavioral development were assessed by 0-6-year-old pediatric examination table of neuropsychological development. Generalized linear model was used to analyze the association between serum BPA levels during pregnancy and infants' neurobehavioral development. Results: A total of 931 mother-child pairs had complete data on serum BPA detection during pregnancy and assessment of infants' neurobehavioral development status. The age of pregnant women at their first filing was (26.67±3.45) years old, and the M (P25,P75) of serum BPA concentration (ng/ml) was 0.23 (0.11, 0.52), with a detection rate of 84.1% (783/931). The age of infants was (13.18±5.46) months, and 53.5% (498) were boys. The developmental quotient scores of large motor, fine motor, adaptive ability, language ability and social behaviors of infants were (97.88±16.32), (97.16±15.35), (99.64±15.47), (95.3±16.04) and (98.95±14.76) points, respectively. Generalized linear model showed that after adjusting for factors such as delivery mode, feeding mode, family per capita monthly income, preterm delivery, gender, maternal age, residence, pre-pregnancy body mass index and residence time, serum BPA level in pregnancy was negatively associated with infant's development of social behavior [ß (95%CI):-2.42 (-4.71, -0.12)]. The post-stratification analysis by infant age revealed that the serum BPA level in pregnancy was only negatively associated with the development of language and social behavior developmental quotient scores in infants between the ages of 12 and 18 months, with ß (95%CI) about -6.66 (-13.06, -0.25) and -7.401 (-12.97, -1.83), respectively. Conclusion: BPA exposure during pregnancy affects language and social behavior development in infants, and the detection window is between 12 and 18 months old of the infant.
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Efectos Tardíos de la Exposición Prenatal , Adulto , Compuestos de Bencidrilo , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Fenoles , Embarazo , Adulto JovenRESUMEN
Objective: To examine the prospective association of pubertal timing and tempo with depressive symptoms in adolescents. Methods: Since 2013, 2 084 students in grade 1-3 were selected from two primary schools in Bengbu, Anhui Province were selected by using convenience sampling method to establish the adolescence pubertal development cohort. Followed up for 6 years, physical examination, secondary sexual development evaluation (testicular volume for boys and breast development for girls) and depressive symptoms were evaluated biennially. Non-linear growth model was used to estimate pubertal timing and tempo for boys and girls respectively. Depressive symptoms were interviewed by using the Short Mood & Feeling Questionnaire (SMFQ) at baseline and Mood & Feeling Questionnaire (MFQ) during follow-up for students in grade 1-2. Children Depression Inventory (CDI) was used for students in grade 3 at baseline and during follow-up. Depressive symptom scores were standardized by using the Z-score method. Multivariate linear regression model was used to analyze the predictive effects of modeling pubertal timing and tempo on depressive symptoms of adolescence boys and girls. Results: There were 1 909 students with complete questionnaire and puberty development information, including 1 052 boys (59.19%) and 857 girls (43.81%), with average age about (13.94±0.87) years and 91.60 percent follow-up rate. The average modeling pubertal timing of girls (11.25 years) was earlier than that of boys (12.70 years), and the average pubertal tempo of girls about 1.47 Tanner stage/year was faster than that of boys about 1.28 Tanner stage/year. After controlling for depressive symptoms, maternal education and adverse childhood experiences at baseline and age, body mass index (BMI) classification and sleep time during follow-up, this predictive effect of pubertal timing and tempo on depressive symptoms was only significant among girls. Compared with girls with on time pubertal timing, girls in the delay timing group had a lower level of depressive symptoms (ß=-0.19, 95% CI:-0.34,-0.01). Compared with girls in average pubertal tempo group, the fast tempo group associated with an increasing risk of depressive symptoms (ß=0.23, 95%CI: 0.05, 0.40), while the slow tempo group associated with an decreasing risk of depressive symptoms (ß=-0.21, 95ï¼ CI:-0.39,-0.03). Insignificant effects were found in puberty timing and tempo on depressive symptoms of boys (P>0.05). Conclusion: Fast pubertal tempo increases the risk of development of depressive symptoms of adolescent girls. There is no predictive effect of pubertal timing and tempo on depression symptoms of adolescent boys.
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Pubertad , Maduración Sexual , Adolescente , Niño , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Diabetic foot ulcer (DFU) is a serious chronic complication leading to disability and death in patients suffering from diabetes. Currently, there is no effective marker for its early diagnosis. The aim of this study is to analyze the difference of circRNA expression profiles between DFU and normal human wounds (NHW) and to screen serum biomarkers for the early diagnosis of DFU. MATERIALS AND METHODS: Differentially expressed circRNAs were screened by bioinformatics analysis, using GSE114248 chip data downloaded from GEO database, including 5 pairs of tissue samples from DFU patients and NHW cases. Accordingly, 20 cases of DFU (Wagner grade 0~2), 20 non-DFU diabetes and 20 healthy controls were selected in the screening test, and the total RNAs of serum and serum-derived exosomes were extracted. The screened circRNAs were verified in the third largest cohort, and the ROC curves were drawn to assess the diagnostic efficiency. RESULTS: As discovered by experiment, there were a total of 67 circRNAs presented differential expressions between the two groups, with 28 circRNAs upregulated and 39 circRNAs downregulated in DFU group. Two types of circRNAs, hsa_circ_0000907 and hsa_circ_0057362, were selected as candidate biomarkers in current study and validated in a large cohort. The AUCs of serum hsa_circ_0000907 and hsa_circ_0057362 to diagnose early DFU were 0.9389 and 0.8792, respectively, and the AUCs of exosomal hsa_circ_0000907 and hsa_circ_0057362 to diagnose early DFU were 0.8783 and 0.8481, respectively. Furthermore, the expressions of serum hsa_circ_0000907 and hsa_circ_0057362 were negatively correlated with ankle brachial index (ABI) and transcutaneous oxygen pressure (TcPO2) in DFU patients. CONCLUSIONS: Serum and exosomal hsa_circ_0000907 and hsa_circ_0057362, especially hsa_circ_0000907, have novel diagnostic capabilities in the early diagnosis of DFU.
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Pie Diabético/diagnóstico , Pie Diabético/genética , ARN Circular , Biomarcadores/sangre , Pie Diabético/sangre , Diagnóstico Precoz , Exosomas/genética , Humanos , ARN Circular/sangre , ARN Circular/genética , Curva ROCRESUMEN
The quality control of coronary artery bypass grafting (CABG) is an important prerequisite to the graft patency and the long-term outcomes. The evaluation of target vessel is the basis, the choice of surgical types is the means, the high-quality acquisition of graft harvesting is the guarantee, and the anastomotic method and quality is the core. As the most commonly used quality control tool, intraoperative transit time flow measurement can effectively detect the coronary graft failure caused by anastomotic stenosis and guide to repair of the graft. However, some studies showed that the positive predictive value is low, and the evidence is insufficient for the relationship with the long-term patency rate of grafts. Intraoperative instantaneous flow measurement combined with high-resolution epicardial ultrasound can improve the quality, safety and effectiveness of CABG, which should be an important recommendation for CABG quality control. Once the shape of the grafts and anastomotic ports is abnormal and the blood flow is not satisfied, it needs to adjust or re-anastomose immediately. The quality control of CABG requires comprehensive judgment and individualized measures to ensure the safety and long-term outcome of patients.
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Puente de Arteria Coronaria/normas , Enfermedad Coronaria/cirugía , Control de Calidad , Anastomosis Quirúrgica/normas , Puente de Arteria Coronaria/métodos , Humanos , Recolección de Tejidos y Órganos/normas , Grado de Desobstrucción VascularRESUMEN
BACKGROUND & AIMS: Chronic liver inflammation leads to fibrosis and cirrhosis and is associated with an accumulation of intrahepatic TNFα-secreting CD206+ macrophages, which may participate in maintaining chronic liver disease in a GM-CSF-dependent manner. We aimed to elucidate the exact role of GM-CSF in the development and progression of chronic liver disease. METHODS: Liver immunohistochemistry and serum quantification were performed in patients with viral and non-viral-related liver disease to compare CD206+ monocyte/macrophages, fibrosis and GM-CSF. This was followed by functional validations in vitro and in vivo in humanised mice. RESULTS: Using multiplex immunofluorescence and histo-cytometry, we show that highly fibrotic livers had a greater density of CD206+ macrophages that produced more TNFα and GM-CSF in the non-tumour liver regions of patients with hepatocellular carcinoma (n = 47), independent of aetiology. In addition, the absolute number of CD206+ macrophages strongly correlated with the absolute number of GM-CSF-producing macrophages. In non-HCC chronic HCV+ patients (n = 40), circulating GM-CSF levels were also increased in proportion to the degree of liver fibrosis and serum viral titres. We then demonstrated in vitro that monocytes converted to TNFα-producing CD206+ macrophage-like cells in response to bacterial products (lipopolysaccharide) in a GM-CSF-dependent manner, confirming the in vivo normalisation of serum GM-CSF concentration following oral antibiotic treatment observed in HBV-infected humanised mice. Finally, anti-GM-CSF neutralising antibody treatment reduced intrahepatic CD206+ macrophage accumulation and abolished liver fibrosis in HBV-infected humanised mice. CONCLUSIONS: While the direct involvement of CD206+ macrophages in liver fibrosis remains to be demonstrated, these findings show that GM-CSF may play a central role in liver fibrosis and could guide the development of anti-GM-CSF antibody-based therapy for the management of patients with chronic liver disease. LAY SUMMARY: Liver fibrosis is a major driver of liver disease progression. Herein, we have shown that granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the development of liver fibrosis. Our findings support the use of anti-GM-CSF neutralising antibodies for the management of patients with chronic liver disease resulting from both viral and non-viral causes.