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1.
J Pediatr Urol ; 2020 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-33246830

RESUMEN

INTRODUCTION: Complications remain the top evaluation priority subsequent to hypospadias repair. Complications vary in further management, and usually require one or more reoperations. Patients and/or their parents concern not only with the success rate of reoperation, but also with the risk of numerous reoperations. OBJECTIVE: To identify the risk factors associated with numerous reoperations following primary hypospadias repair. STUDY DESIGN: Data were collected retrospectively from patients who underwent reoperations for complications following primary hypospadias repair at a single institution from August 2008 to October 2017. RESULTS: A total of 507 patients required reoperations following 2754 primary hypospadias repairs. Eventually, 486 patients were eligibly included with a median age of 2.2 years. The median follow-up period was 6.5 years. Preserved urethral plate urethroplasty for primary repair (including Snodgrass, Onlay and Mathieu techniques) was performed in 307 (63.2%) patients, Duckett technique was performed in 121 (24.9%) patients, and staged urethroplasty (including staged Duckett, Byars and Bracka techniques) was performed in 58 (11.9%) patients. The complications included 302 fistulas, 108 dehiscence, 50 urethral strictures, 18 meatal stenosis, 38 diverticula, 24 mild recurrent ventral curvature and 23 severe recurrent ventral curvature. A total of 363 (74.7%) patients needed 1 reoperation, 87 (17.9%) needed 2 reoperations, 19 (3.9%) needed 3 reoperations, and 17 (3.5%) needed >3 reoperations. Ordinal logistic regression demonstrated that severe recurrent ventral curvature, urethral stricture, dehiscence and primary staged hypospadias repair increased the risk of numerous reoperations, with odds ratios of 75.991-fold, 36.967-fold, 11.765-fold and 3.074-fold, respectively. In contrast, diverticulum decreased the risk, with an odds ratio of 0.443-fold. DISCUSSION: Our data demonstrated significant heterogeneity in the risk of numerous reoperations for each complication. Severe recurrent ventral curvature conferred the highest risk of numerous reoperations, followed by urethral stricture, dehiscence. In additional, our data showed an increased risk of numerous reoperations following primary staged repairs. Identification the risk factors confers advantages in the assessment of postoperative outcomes and anticipation of future reoperations. CONCLUSION: Severe recurrent ventral curvature, urethral stricture, dehiscence and primary staged hypospadias repair were associated with numerous reoperations following primary hypospadias repair.

2.
Transl Androl Urol ; 9(5): 2275-2280, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33209693

RESUMEN

Wilms' tumor is the most common primary renal malignancy in children (80%) and the less common tumors include renal cell carcinoma, rhabdoid tumor, clear cell sarcoma, cellular congenital mesoblastic nephroma and medullary carcinoma, all of which originate from renal parenchyma. The tumors originating from renal pelvis are rare. The immunohistochemistry (IHC) showed INI1 deletion with the WT1 positive which has not been reported as we know. A 3-year-old boy was admitted to hospital for vomiting. An ultrasonography examination revealed a mass in the right kidney, medium echo, as well as hydronephrosis with collecting system separation of 3.5 cm. The computed tomography and the magnetic resonance (MR) radical showed that the tumor occupied the right renal pelvis and extended into the ureter. A radical nephroureterectomy was accomplished through a transabdominal approach. The pathologic diagnosis was malignant renal tumor with INI1 deficiency which was atypical in morphology and immunophenotype, but according to immunophenotype renal rhabdomyoid tumor could not be excluded. The patient was treated with carboplatin, etoposide and cyclophosphamide chemotherapy for 6 months. Follow-up studies of the patient showed no indication of recurrence or metastasis 22 months after nephrectomy. The novel findings may expand the spectrum of pediatric renal tumors to include the special malignancy.

3.
Nat Neurosci ; 23(12): 1589-1596, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33139942

RESUMEN

Information processing in the brain depends on specialized organization of neurotransmitter receptors and scaffolding proteins within the postsynaptic density. However, how these molecules are organized in situ remains largely unknown. In this study, template-free classification of oversampled sub-tomograms was used to analyze cryo-electron tomograms of hippocampal synapses. We identified type-A GABA receptors (GABAARs) in inhibitory synapses and determined their in situ structure at 19-Å resolution. These receptors are organized hierarchically: from GABAAR super-complexes with a preferred inter-receptor distance of 11 nm but variable relative angles, through semi-ordered, two-dimensional receptor networks with reduced Voronoi entropy, to mesophasic assembly with a sharp phase boundary. These assemblies likely form via interactions among postsynaptic scaffolding proteins and receptors and align with putative presynaptic vesicle release sites. Such mesophasic self-organization might allow synapses to achieve a 'Goldilocks' state, striking a balance between stability and flexibility and enabling plasticity in information processing.

4.
Artículo en Inglés | MEDLINE | ID: mdl-33153180

RESUMEN

Childhood and adolescence overweight and obesity have implications for both health consequences and economic burden. Although it has been an emerging public health problem for primary school children in rural China and the importance of the diet-health link has been stressed for many years, rigorous analysis of the dietary diversity and obesity among children is rare. To clarify this issue, this study provides a better understanding of the functional linkage between dietary diversity and obesity by analyzing data from nearly 8500 rural primary students (aged from 10 to 13 years old) covering three provinces in China. Our estimation results show that there is a significantly negative correlation between dietary diversity and the probability of being overweight among primary students. In particular, for subgroups with higher dietary diversity, the negative correlation between dietary diversity and the incidence of overweight or obesity is stronger, and the absolute value of the coefficient is greater. The results also suggest that the increase in the consumption frequency of all dietary categories can significantly lead to a lower proportion of overweight. Thus, we conclude that higher dietary diversity can help to lower the risk of overweight and obesity among primary school children, presumably through increasing the daily frequency of food intakes and developing a more diverse dietary pattern.

5.
J Recept Signal Transduct Res ; : 1-10, 2020 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-32985331

RESUMEN

Protection against renal fibrosis is important for the management of obstructive nephropathy. We researched the roles and possible mechanism of miR-155-5p in renal interstitial fibrosis, which may provide a potential endogenous target for renal interstitial fibrosis in obstructive nephropathy. Herein, NRK-49F cells were transfected with miR-155-5p mimic, miR-155-5p inhibitor, SIRT1 plasmid and/or SIRT1 siRNA. The unilateral ureteral obstruction (UUO) model was built with male C57 black mice and administrated with SRT1720 by tail vein injection. Levels of miR-155-5p, SIRT1 and relative proteins (TGF-ß1, α-SMA, Collage I and fibronectin) in NRK-49F cells or mice kidney tissues were measured with quantitative reverse transcription polymerase chain reaction or Western blot. The target gene of miR-155-5p was analyzed through TargetScan and dual-luciferase reporter assay. Mice kidney tissue was stained with Masson trichrome. It was found that miR-155-5p overexpression promoted the expressions of fibroblast related proteins expression and inhibited the SIRT1 expression in NRK-49F cells, while miR-155-5p silencing had an opposite effect. SIRT1 can bind with miR-155-5p. MiR-155-5p inhibited the level of SIRT1. Fibroblast related proteins were up-regulated by miR-155-5p and down-regulated by SIRT1 in NRK-49F cells, while the up-regulatory effect of miR-155-5p was reversed by SIRT1. MiR-155-5p expression was up-regulated and SIRT1 expression was down-regulated in the kidney tissue of UUO mice. SRT1720 attenuated the fiber deposition, up-regulated SIRT1 level and down-regulated the levels of fibroblast related proteins in UUO model mice. To conclude, miR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy via inhibiting SIRT1 signaling pathway.

6.
Mol Ther Methods Clin Dev ; 18: 390-401, 2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32695841

RESUMEN

Development of the CRISPR-Cas9 gene-editing system has given rise to a new era of gene editing with wide applications in biology, medicine, agriculture, and other fields. However, the overexpression of Cas9 nuclease causes off-target effects and may trigger an immune response in vivo. Therefore, we constructed a self-restricting CRISPR-Cas9 system, where the target gene sequence corresponding to the guide RNA (gRNA) is inserted on either end of the Cas9 promoter. When double-strand breaks (DSBs) are induced in the target gene sequence, the Cas9 promoter is cut off and transcription ceases. With this system, expression of Cas9 protein at 60 h after transfection is only 10% that of the wild-type system, with about 70% promoter deletion efficiency. The target site editing efficiency and homologous recombination efficiency of the self-restricting system remain at about 50% and 30%, respectively, while the frequency of off-target indel formation decreased by 76.7%. Further, the number of indel types was also reduced from 13 to 2. Because this system does not include additional gRNA sequences, the possibility of introducing new off-target mutations is decreased. Importantly, this system is composed of a single plasmid, which could potentially be easily introduced in vivo using a viral vector or nanoparticles.

7.
Biomed Res Int ; 2020: 3860936, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32461982

RESUMEN

Background: This study explored the relationship between thyroid-associated antibodies, immune cells, and hypothyroidism to establish a predictive model for the incidence of hypothyroidism in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. Methods: A total of 170 patients with NPC treated at the Cancer Hospital of University of Chinese Academy of Sciences between January 2015 and August 2018 were included. The complete blood count, biochemical, coagulation function, immune cells, and thyroid-associated antibodies tested before radiotherapy were evaluated. A logistic regression model was performed to elucidate which hematological indexes were related to hypothyroidism development. A predictive model for the incidence of hypothyroidism was established. Internal verification of the multifactor model was performed using the tenfold cross-validation method. Results: The univariate analysis showed that immune cells had no statistically significant differences among the patients with and without hypothyroidism. Sex, N-stage, antithyroid peroxidase antibody (TPO-Ab), antithyroglobulin antibody (TG-Ab), thyroglobulin (TG), and fibrinogen (Fb) were associated with hypothyroidism. Males and early N-stage were protective factors of thyroid function, whereas increases in TPO-Ab, TG-Ab, TG, and Fb counts were associated with an increased rate of hypothyroidism incidence. The multivariate analysis showed that TPO-Ab, TG-Ab, TG, and Fb were independent predictors of hypothyroidism. The comprehensive effect of the significant model, including TPO-Ab, TG-Ab, TG, and Fb counts, represented the optimal method of predicting the incidence of radiation-induced hypothyroidism (AUC = 0.796). Tenfold cross-validation methods were applied for internal validation. The AUCs of the training and testing sets were 0.792 and 0.798, respectively. Conclusion: A model combining TPO-Ab, TG-Ab, TG, and Fb can be used to screen populations at a high risk of developing hypothyroidism after radiotherapy.

8.
Radiat Oncol ; 15(1): 68, 2020 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-32293496

RESUMEN

BACKGROUND: We investigated the risk factors of radiation-induced thyroid dysfunction, then combined the clinical factors and optimum thyroid dosimetric parameters to predict the incidence rate of hypothyroidism (HT) and to guide individualized treatment. METHODS: A total of 206 patients with histologically proven nasopharyngeal carcinoma (NPC) treated at the Cancer Hospital of the University of Chinese Academy of Sciences between January 2015 and August 2018 were included. Dose-volume histogram (DVH) data, including mean dose, absolute volume, V20, V25, V30, V35, V40, V45, V50, V55, and V60 were extracted and used as dosimetric parameters. A logistic regression analysis model was built to identify predictors related to HT occurring within 2 years. RESULTS: Sex, N stage, thyroid volume, mean thyroid dose, and thyroid V20 and V50 were significantly different between patients with and without HT. Logistic regression analysis showed that N stage, thyroid volume, and thyroid V50 were independent predictors of HT. The radiosensitivity of the thyroid decreased as the thyroid volume increased. Patients with N stage > 1 had significantly higher HT incidence (37.38%) than patients with N stage ≤1 (13.11%). The incidence of HT was 54.55% in patients with thyroid V50 > 24% and was 34.15% in patients with thyroid V50 ≤ 24%. CONCLUSIONS: The incidence of HT is significantly associated with N stage, thyroid volume, and thyroid V50. More attention should be paid to patients with NPC with thyroid volume ≤ 12.82 cm3 and advanced N stage disease.

9.
Cell Discov ; 6: 8, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32133151

RESUMEN

Excitatory synapses in the mammalian brain exhibit diverse functional properties in transmission and plasticity. Directly visualizing the structural correlates of such functional heterogeneity is often hindered by the diffraction-limited resolution of conventional optical imaging techniques. Here, we used super-resolution stochastic optical reconstruction microscopy (STORM) to resolve structurally distinct excitatory synapses formed on dendritic shafts and spines. The majority of these shaft synapses contained N-methyl-d-aspartate receptors (NMDARs) but not α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), suggesting that they were functionally silent. During development, as more spine synapses formed with increasing sizes and expression of AMPARs and NMDARs, shaft synapses exhibited moderate reduction in density with largely unchanged sizes and receptor expression. Furthermore, upon glycine stimulation to induce chemical long-term potentiation (cLTP), the previously silent shaft synapses became functional shaft synapses by recruiting more AMPARs than did spine synapses. Thus, silent shaft synapse may represent a synaptic state in developing neurons with enhanced capacity of activity-dependent potentiation.

10.
Cell Discov ; 6: 2, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31969988

RESUMEN

Exocytosis is a crucial cellular process involved in the release of neural transmitters or signaling hormones, and disposal of waste or toxic materials. The relationship between structural transition and temporal progression of this process is poorly understood, partly due to lack of adequate tools to resolve such dynamic structures at sufficient resolution in 3D. Exocytosis can be hijacked by some viruses, exemplified by the widely used model α-herpesvirus pseudorabies virus (PRV), which relies on exocytosis for trans-synaptic spread across neurons. Here, we have used cryo electron tomography (cryoET) to capture 199 events of PRV exocytosis from cultured hippocampal neurons. We established cumulative frequency analysis to estimate the relative duration of an exocytosis stage based on the frequency of observed viral particles at that stage. This analysis revealed that PRV exocytosis is biphasic, including a fast, "release phase" driven by fusion proteins and fused membranes, and a slow, "recovery phase" driven by flattening of curved membranes. The biphasic property of exocytosis discovered here appears to be conserved for membrane fusion during viral entry, and our approach of cumulative frequency analysis should have general utility for characterizing other membrane fusion events.

11.
Chin J Dent Res ; 23(4): 265-271, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33491358

RESUMEN

Objective: To evaluate the accuracy of digital models obtained from intraoral scanning of edentulous maxilla and mandible models with and without resin markers. Methods: A pair of standard edentulous models were scanned using a laboratory scanner and saved as reference models. The edentulous models were fixed onto a phantom head and scanned with an intraoral scanner (IOS) five times each. Six resin markers were attached on the maxilla model and two on the mandible model, and another five intraoral scans were taken of each model. The scanning time and number of images were recorded. The digital models obtained using the IOS were superimposed on the reference models using image processing software. The trueness and precision of the models made using the IOS were evaluated, and the scanning time and number of images were also compared. Results: The average trueness and precision of the IOS in the maxilla model with resin markers were 135.50 ± 36.28 µm and 254.55 ± 40.62 µm, respectively, while those in the mandible were 161.40 ± 55.45 µm and 368.75 ± 91.03 µm, respectively. Placing resin markers on the edentulous maxilla and mandible did not improve the trueness of the IOS, but placing resin markers on the edentulous maxilla improved the precision and scanning efficiency. However, placing resin markers on the buccal shelf of the edentulous mandible decreased the precision and increased the scanning time. Conclusion: Resin markers placed on the hard palate of edentulous maxillae could improve the precision of the IOS and improve scanning efficiency. However, they did not affect the trueness of the IOS for edentulous maxillae or mandibles.


Asunto(s)
Técnica de Impresión Dental , Arcada Edéntula , Diseño Asistido por Computadora , Modelos Dentales , Humanos , Imagenología Tridimensional , Arcada Edéntula/diagnóstico por imagen
12.
Radiology ; 291(3): 677-686, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30912722

RESUMEN

Background Nasopharyngeal carcinoma (NPC) may be cured with radiation therapy. Tumor proximity to critical structures demands accuracy in tumor delineation to avoid toxicities from radiation therapy; however, tumor target contouring for head and neck radiation therapy is labor intensive and highly variable among radiation oncologists. Purpose To construct and validate an artificial intelligence (AI) contouring tool to automate primary gross tumor volume (GTV) contouring in patients with NPC. Materials and Methods In this retrospective study, MRI data sets covering the nasopharynx from 1021 patients (median age, 47 years; 751 male, 270 female) with NPC between September 2016 and September 2017 were collected and divided into training, validation, and testing cohorts of 715, 103, and 203 patients, respectively. GTV contours were delineated for 1021 patients and were defined by consensus of two experts. A three-dimensional convolutional neural network was applied to 818 training and validation MRI data sets to construct the AI tool, which was tested in 203 independent MRI data sets. Next, the AI tool was compared against eight qualified radiation oncologists in a multicenter evaluation by using a random sample of 20 test MRI examinations. The Wilcoxon matched-pairs signed rank test was used to compare the difference of Dice similarity coefficient (DSC) of pre- versus post-AI assistance. Results The AI-generated contours demonstrated a high level of accuracy when compared with ground truth contours at testing in 203 patients (DSC, 0.79; 2.0-mm difference in average surface distance). In multicenter evaluation, AI assistance improved contouring accuracy (five of eight oncologists had a higher median DSC after AI assistance; average median DSC, 0.74 vs 0.78; P < .001), reduced intra- and interobserver variation (by 36.4% and 54.5%, respectively), and reduced contouring time (by 39.4%). Conclusion The AI contouring tool improved primary gross tumor contouring accuracy of nasopharyngeal carcinoma, which could have a positive impact on tumor control and patient survival. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Chang in this issue.


Asunto(s)
Aprendizaje Profundo , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Adolescente , Adulto , Algoritmos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nasofaringe/diagnóstico por imagen , Estudios Retrospectivos , Adulto Joven
13.
Curr Opin Struct Biol ; 54: 152-160, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30904821

RESUMEN

Neuronal synapses are key devices for transmitting and processing information in the nervous system. Synaptic plasticity, generally regarded as the cellular basis of learning and memory, involves changes of subcellular structures that take place at the nanoscale. High-resolution imaging methods, especially electron microscopy (EM), have allowed for quantitative analysis of such nanoscale structures in different types of synapses. In particular, the semi-ordered organization of neurotransmitter receptors and their interacting scaffolds in the postsynaptic density have been characterized for both excitatory and inhibitory synapses by studies using various EM techniques such as immuno-EM, electron tomography of high-pressure freezing and freeze-substituted samples, and cryo electron tomography. These techniques, in combination with new correlative approaches, will further facilitate our understanding of the molecular organization underlying diverse functions of neuronal synapses.


Asunto(s)
Proteínas de la Membrana/metabolismo , Microscopía Electrónica , Sinapsis/metabolismo , Animales , Humanos , Receptores de Neurotransmisores/metabolismo , Ácido gamma-Aminobutírico/metabolismo
14.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(5): 493-498, 2019 Jul 25.
Artículo en Chino | MEDLINE | ID: mdl-31901022

RESUMEN

OBJECTIVE: To assess the value of fetal anteroposterior renal pelvic diameter (APD) in predicting antenatal hydronephrosis requiring surgical treatment after birth. METHODS: A total of 525 cases of antenatal hydronephrosis detected by prenatal ultrasonography (ultrasound index APD ≥ 4 mm in the second trimester and APD ≥ 7 mm in the third trimester) in Zhejiang Prenatal Diagnosis Center from June 2007 to June 2018 were retrospectively analyzed. ROC curve was used to analyze the relationship between these ultrasound indicators and the requirement for surgical treatment after birth. RESULTS: There were 162 cases (30.9%) diagnosed in the second trimester and 363 cases (69.1%) diagnosed in the third trimester; 131 cases were diagnosed pathologically after birth, of which 121 finally underwent surgical treatment. The area under ROC curve (AUC) of APD in middle pregnancy for prediction of requiring surgery 1-12 years after birth was 0.910; the cut-off value of APD was 8.45 mm with a sensitivity of 97.1%, specificity of 70.9%, positive predictive value (PPV) of 47.9%, and negative predictive value (NPV) of 98.9%. The AUC of APD in late pregnancy for prediction of requiring surgery 1-12 years after birth was 0.800; the cut-off value of APD was 12.25 mm with a sensitivity of 66.7%, specificity of 81.2%, PPV of 51.7%, and NPV of 89.1%. CONCLUSIONS: APD in pregnancy can be used to predict whether the fetus with hydronephrosis needs surgical treatment after birth, and the prediction value of APD in the middle pregnancy is better.


Asunto(s)
Hidronefrosis , Ultrasonografía , Femenino , Feto/diagnóstico por imagen , Humanos , Hidronefrosis/diagnóstico por imagen , Hidronefrosis/cirugía , Pelvis Renal/diagnóstico por imagen , Embarazo , Estudios Retrospectivos
15.
PLoS Pathog ; 14(12): e1007452, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30507948

RESUMEN

Human cytomegalovirus (HCMV) enters host by glycoprotein B (gB)-mediated membrane fusion upon receptor-binding to gH/gL-related complexes, causing devastating diseases such as birth defects. Although an X-ray crystal structure of the recombinant gB ectodomain at postfusion conformation is available, the structures of prefusion gB and its complex with gH/gL on the viral envelope remain elusive. Here, we demonstrate the utility of cryo electron tomography (cryoET) with energy filtering and the cutting-edge technologies of Volta phase plate (VPP) and direct electron-counting detection to capture metastable prefusion viral fusion proteins and report the structures of glycoproteins in the native environment of HCMV virions. We established the validity of our approach by obtaining cryoET in situ structures of the vesicular stomatitis virus (VSV) glycoprotein G trimer (171 kD) in prefusion and postfusion conformations, which agree with the known crystal structures of purified G trimers in both conformations. The excellent contrast afforded by these technologies has enabled us to identify gB trimers (303kD) in two distinct conformations in HCMV tomograms and obtain their in situ structures at up to 21 Å resolution through subtomographic averaging. The predominant conformation (79%), which we designate as gB prefusion conformation, fashions a globular endodomain and a Christmas tree-shaped ectodomain, while the minority conformation (21%) has a columnar tree-shaped ectodomain that matches the crystal structure of the "postfusion" gB ectodomain. We also observed prefusion gB in complex with an "L"-shaped density attributed to the gH/gL complex. Integration of these structures of HCMV glycoproteins in multiple functional states and oligomeric forms with existing biochemical data and domain organization of other class III viral fusion proteins suggests that gH/gL receptor-binding triggers conformational changes of gB endodomain, which in turn triggers two essential steps to actuate virus-cell membrane fusion: exposure of gB fusion loops and unfurling of gB ectodomain.


Asunto(s)
Citomegalovirus/fisiología , Tomografía con Microscopio Electrónico/métodos , Proteínas del Envoltorio Viral/ultraestructura , Internalización del Virus , Citomegalovirus/química , Citomegalovirus/ultraestructura , Infecciones por Citomegalovirus/transmisión , Humanos , Conformación Proteica
16.
Front Neuroanat ; 12: 48, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29942253

RESUMEN

The morphology and function of neuronal synapses are regulated by neural activity, as manifested in activity-dependent synapse maturation and various forms of synaptic plasticity. Here we employed cryo-electron tomography (cryo-ET) to visualize synaptic ultrastructure in cultured hippocampal neurons and investigated changes in subcellular features in response to chronic inactivity, a paradigm often used for the induction of homeostatic synaptic plasticity. We observed a more than 2-fold increase in the mean number of dense core vesicles (DCVs) in the presynaptic compartment of excitatory synapses and an almost 20-fold increase in the number of DCVs in the presynaptic compartment of inhibitory synapses after 2 days treatment with the voltage-gated sodium channel blocker tetrodotoxin (TTX). Short-term treatment with TTX and the N-methyl-D-aspartate receptor (NMDAR) antagonist amino-5-phosphonovaleric acid (AP5) caused a 3-fold increase in the number of DCVs within 100 nm of the active zone area in excitatory synapses but had no significant effects on the overall number of DCVs. In contrast, there were very few DCVs in the postsynaptic compartments of both synapse types under all conditions. These results are consistent with a role for presynaptic DCVs in activity-dependent synapse maturation. We speculate that these accumulated DCVs can be released upon reactivation and may contribute to homeostatic metaplasticity.

17.
Int J Urol ; 25(7): 649-653, 2018 07.
Artículo en Inglés | MEDLINE | ID: mdl-29717506

RESUMEN

OBJECTIVES: To find a new appropriate evaluation for urethral plate quality in hypospadias repair, with particular interest in the width proportion of the urethral plate to the glans, serving as an appraisal index. METHODS: Data were prospectively collected from prepubertal boys who underwent primary tubularized incised plate hypospadias repair between January 2014 and April 2016 in one center. Intrinsic parameters of the penis (meatal location, glans width, urethral plate width and curvature degree) were measured during the operation. Urethroplasty complications were recorded during follow up. The correlation between width proportion of the urethral plate to the glans and urethroplasty complications was analyzed. RESULTS: Primary tubularized incised plate repair was carried out in 442 patients (mean age 2.8 years, range 0.5-12 years). At mean follow up of 26 months (range 12-38 months), urethroplasty complications occurred in 59 (13.3%) patients. The width proportion of the urethral plate to the glans was weakly correlated to both the glans width and meatal location. The width proportion of the urethral plate to the glans ranged from 0.18 to 0.73, with a mean of 0.39. The cut-off value of width proportion of the urethral plate to the glans was determined to be 0.36 by the receiver operating characteristic curve. Urethroplasty complications occurred in 17 out of 254 patients (6.7%) with width proportion of the urethral plate to the glans >0.36, and 42 out of 188 patients (22.3%) with width proportion of the urethral plate to the glans ≤0.36. The width proportion of the urethral plate to the glans ≤0.36 showed an increased odds of 4.819-fold (95% confidence interval 2.548-9.112, P < 0.001) risk of urethroplasty complications compared with width proportion of the urethral plate to the glans >0.36. Midshaft and proximal meatal location also increased the risk of urethroplasty complications. CONCLUSIONS: The present study highlights the value of the width proportion of the urethral plate to the glans for objectivity and accuracy in urethral plate evaluation, which in turn serves as an independent factor influencing outcomes in tubularized incised plate repair.


Asunto(s)
Hipospadias/cirugía , Pene/cirugía , Procedimientos Quirúrgicos Reconstructivos/métodos , Uretra/trasplante , Procedimientos Quirúrgicos Urológicos Masculinos/métodos , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Masculino , Pene/anomalías , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Procedimientos Quirúrgicos Reconstructivos/efectos adversos , Colgajos Quirúrgicos/trasplante , Resultado del Tratamiento , Uretra/anomalías , Procedimientos Quirúrgicos Urológicos Masculinos/efectos adversos
18.
J Neurosci ; 38(6): 1493-1510, 2018 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-29311144

RESUMEN

As key functional units in neural circuits, different types of neuronal synapses play distinct roles in brain information processing, learning, and memory. Synaptic abnormalities are believed to underlie various neurological and psychiatric disorders. Here, by combining cryo-electron tomography and cryo-correlative light and electron microscopy, we distinguished intact excitatory and inhibitory synapses of cultured hippocampal neurons, and visualized the in situ 3D organization of synaptic organelles and macromolecules in their native state. Quantitative analyses of >100 synaptic tomograms reveal that excitatory synapses contain a mesh-like postsynaptic density (PSD) with thickness ranging from 20 to 50 nm. In contrast, the PSD in inhibitory synapses assumes a thin sheet-like structure ∼12 nm from the postsynaptic membrane. On the presynaptic side, spherical synaptic vesicles (SVs) of 25-60 nm diameter and discus-shaped ellipsoidal SVs of various sizes coexist in both synaptic types, with more ellipsoidal ones in inhibitory synapses. High-resolution tomograms obtained using a Volta phase plate and electron filtering and counting reveal glutamate receptor-like and GABAA receptor-like structures that interact with putative scaffolding and adhesion molecules, reflecting details of receptor anchoring and PSD organization. These results provide an updated view of the ultrastructure of excitatory and inhibitory synapses, and demonstrate the potential of our approach to gain insight into the organizational principles of cellular architecture underlying distinct synaptic functions.SIGNIFICANCE STATEMENT To understand functional properties of neuronal synapses, it is desirable to analyze their structure at molecular resolution. We have developed an integrative approach combining cryo-electron tomography and correlative fluorescence microscopy to visualize 3D ultrastructural features of intact excitatory and inhibitory synapses in their native state. Our approach shows that inhibitory synapses contain uniform thin sheet-like postsynaptic densities (PSDs), while excitatory synapses contain previously known mesh-like PSDs. We discovered "discus-shaped" ellipsoidal synaptic vesicles, and their distributions along with regular spherical vesicles in synaptic types are characterized. High-resolution tomograms further allowed identification of putative neurotransmitter receptors and their heterogeneous interaction with synaptic scaffolding proteins. The specificity and resolution of our approach enables precise in situ analysis of ultrastructural organization underlying distinct synaptic functions.


Asunto(s)
Microscopía por Crioelectrón/métodos , Potenciales Postsinápticos Excitadores/fisiología , Inhibición Psicológica , Sinapsis/fisiología , Tomografía/métodos , Animales , Moléculas de Adhesión Celular/metabolismo , Femenino , Procesamiento de Imagen Asistido por Computador , Neuronas/fisiología , Neuronas/ultraestructura , Densidad Postsináptica/metabolismo , Embarazo , Ratas , Receptores de GABA-A/metabolismo , Receptores de GABA-A/ultraestructura , Receptores de Glutamato/metabolismo , Receptores de Glutamato/ultraestructura , Sinapsis/ultraestructura , Vesículas Sinápticas/fisiología , Vesículas Sinápticas/ultraestructura
19.
Clin Chim Acta ; 466: 127-132, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28111273

RESUMEN

BACKGROUND: Ureteropelvic junction obstruction (UPJO) is the most common cause of hydronephrosis in children. This study was to assess the relationship between serum thioredoxin (S-Trx) and urinary thioredoxin (U-Trx) concentrations and severity of children hydronephrosis caused by UPJO. METHODS: This study included 156 hydronephrosis children with unilateral UPJO and 80 healthy children. S-Trx and U-Trx concentrations were measured using enzyme-linked immunosorbent assay. U-Trx/creatinine (cr) ratio was calculated. RESULTS: S-Trx and U-Trx concentrations and U-Trx/cr ratio were significantly higher in hydronephrosis children than in healthy children. They were significantly correlated with split renal function, anterior-posterior diameter and Society for Fetal Urology classification, as well as were independently related to the split renal function <39.2%, anterior-posterior diameter>30mm and Society for Fetal Urology grade IV. Under receiver operating characteristic curves, U-Trx/cr ratio showed the higher predictive value compared to S-Trx and U-Trx concentrations. CONCLUSION: Increased S-Trx and U-Trx concentrations, especially U-Trx/cr ratio, are closely associated with the severity of children hydronephrosis, substantializing Trx as a promising biomarker for the progression of children hydronephrosis.


Asunto(s)
Hidronefrosis/diagnóstico , Índice de Severidad de la Enfermedad , Tiorredoxinas/análisis , Biomarcadores/análisis , Estudios de Casos y Controles , Niño , Preescolar , Creatinina/análisis , Progresión de la Enfermedad , Humanos , Hidronefrosis/sangre , Hidronefrosis/etiología , Hidronefrosis/orina , Tiorredoxinas/sangre , Tiorredoxinas/orina , Obstrucción Ureteral/complicaciones
20.
J Cancer ; 7(14): 2005-2011, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27877215

RESUMEN

This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases.

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