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1.
Front Med (Lausanne) ; 8: 679260, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646835

RESUMO

Background: Previous studies have demonstrated that serum N-terminal proB-type natriuretic peptide (NT-proBNP) was a predictor of adverse cardiovascular outcomes after surgery. We performed a prospective study to evaluate if NT-proBNP could be a sensitive marker of overall postoperative outcomes in older patients undergoing major elective non-cardiac surgery when combined with myoglobin (MYO). Methods: Two hundred and three adults aged ≥65 years were enrolled in the study. The American Society of Anesthesiologists (ASA) physical status of patients were I to IV. Blood samples would be taken before and 2 h after the surgery for each patients and NT-proBNP and MYO concentrations (NT-proBNP baseline/ 2 h and MYO baseline/ 2 h) of these samples would be measured immediately. The primary outcome was moderate to severe complications, which were based on the Clavien-Dindo Classification (CDC) scheme (≥CDC grade 3), and the secondary outcomes were major complications within 30 days after surgery. This study was registered at China Clinical Trial Registry (ChiCTR1900026223, http://www.chictr.org.cn/). Results: Overall, moderate to severe complications occurred in 15 patients (7.4%) and major complications occurred in 18 patients (8.9%). Both preoperative and postoperative NT-proBNP values were independent predictors of moderate to severe complications (area under the curve (AUC), 0.820; 95% CI: 0.728, 0.912, P < 0.001; AUC, 0.785; 95% CI: 0.685, 0.885, P < 0.001). When NT-proBNP baseline and MYO-2 h were combined (NT-proBNP baseline × MYO-2 h), the predictive power was improved (AUC 0.841, 95% CI: 0.758, 0.923, P < 0.001). Conclusions: A combination of perioperative NT-proBNP and postoperative MYO concentrations was a good predictor of postoperative complications in elderly patients who underwent major non-cardiac surgery. Using fast and dynamic tests provided by point-to-care-testing, NT-proBNP and MYO concentration measurements provided useful guidance for therapy before or soon after surgery, thus helping to reduce postoperative complications in elderly patients.

2.
Brief Bioinform ; 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34571533

RESUMO

Cancer stem cells (CSCs) actively reprogram their tumor microenvironment (TME) to sustain a supportive niche, which may have a dramatic impact on prognosis and immunotherapy. However, our knowledge of the landscape of the gastric cancer stem-like cell (GCSC) microenvironment needs to be further improved. A multi-step process of machine learning approaches was performed to develop and validate the prognostic and predictive potential of the GCSC-related score (GCScore). The high GCScore subgroup was not only associated with stem cell characteristics, but also with a potential immune escape mechanism. Furthermore, we experimentally demonstrated the upregulated infiltration of CD206+ tumor-associated macrophages (TAMs) in the invasive margin region, which in turn maintained the stem cell properties of tumor cells. Finally, we proposed that the GCScore showed a robust capacity for prediction for immunotherapy, and investigated potential therapeutic targets and compounds for patients with a high GCScore. The results indicate that the proposed GCScore can be a promising predictor of prognosis and responses to immunotherapy, which provides new strategies for the precision treatment of GCSCs.

3.
FASEB J ; 35(9): e21667, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34405442

RESUMO

Long noncoding RNAs (lncRNAs) are central regulators of the inflammatory response and play an important role in inflammatory diseases. PINT has been reported to be involved in embryonic development and tumorigenesis. However, the potential functions of PINT in the innate immune system are largely unknown. Here, we revealed the transcriptional regulation of inflammatory genes by PINT, whose expression is primarily dependent on the NF-κB signaling pathway in human and mouse macrophage and intestinal epithelial cell lines. Functionally, PINT selectively regulates the expression of TNF-α in basal and LPS-stimulated cells. Mechanistically, PINT acts as a modular scaffold of p65 and EZH2 to coordinate their localization and specify their binding to the target genes. Further, a high expression level of PINT was detected in intestinal mucosal tissues from patients with ulcerative colitis (UC). Together, these findings demonstrate that PINT acts as an activator of inflammatory responses, highlighting the importance of this lncRNA as a potential therapeutic target in infectious diseases and inflammatory diseases.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação da Expressão Gênica , RNA Longo não Codificante/genética , Fator de Transcrição RelA/metabolismo , Transcrição Genética , Fator de Necrose Tumoral alfa/genética , Animais , Linhagem Celular , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Citocinas/genética , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Regiões Promotoras Genéticas/genética , Ligação Proteica , Transcrição Genética/genética
4.
Med Phys ; 48(9): 5219-5231, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34287939

RESUMO

PURPOSE: The net uptake rate constant (Ki ) derived from dynamic imaging is considered the gold standard quantification index for FDG PET. In this study, we investigated the feasibility and assessed the clinical usefulness of generating Ki images for FDG PET using only two 5-min scans with population-based input function (PBIF). METHODS: Using a Siemens Biograph mCT, 10 subjects with solid lung nodules underwent a single-bed dynamic FDG PET scan and 13 subjects (five healthy and eight cancer patients) underwent a whole-body dynamic FDG PET scan in continuous-bed-motion mode. For each subject, a standard Ki image was generated using the complete 0-90 min dynamic data with Patlak analysis (t* = 20 min) and individual patient's input function, while a dual-time-point Ki image was generated from two 5-min scans based on the Patlak equations at early and late scans with the PBIF. Different start times for the early (ranging from 20 to 55 min with an increment of 5 min) and late (ranging from 50 to 85 min with an increment of 5 min) scans were investigated with the interval between scans being at least 30 min (36 protocols in total). The optimal dual-time-point protocols were then identified. Regions of interest (ROI) were drawn on nodules for the lung nodule subjects, and on tumors, cerebellum, and bone marrow for the whole-body-imaging subjects. Quantification accuracy was compared using the mean value of each ROI between standard Ki (gold standard) and dual-time-point Ki , as well as between standard Ki and relative standardized uptake value (SUV) change that is currently used in clinical practice. Correlation coefficients and least squares fits were calculated for each dual-time-point protocol and for each ROI. Then, the predefined criteria for identifying a reliable dual-time-point Ki estimation for each ROI were empirically determined as: (1) the squared correlation coefficient (R2 ) between standard Ki and dual-time-point Ki is larger than 0.9; (2) the absolute difference between the slope of the equality line (1.0) and that of the fitted line when plotting standard Ki versus dual-time-point Ki is smaller than 0.1; (3) the absolute value of the intercept of the fitted line when plotting standard Ki versus dual-time-point Ki normalized by the mean of the standard Ki across all subjects for each ROI is smaller than 10%. Using Williams' one-tailed t test, the correlation coefficient (R) between standard Ki and dual-time-point Ki was further compared with that between standard Ki and relative SUV change, for each dual-time-point protocol and for each ROI. RESULTS: Reliable dual-time-point Ki images were obtained for all the subjects using our proposed method. The percentage error introduced by the PBIF on the dual-time-point Ki estimation was smaller than 1% for all 36 protocols. Using the predefined criteria, reliable dual-time-point Ki estimation could be obtained in 25 of 36 protocols for nodules and in 34 of 36 protocols for tumors. A longer time interval between scans provided a more accurate Ki estimation in general. Using the protocol of 20-25 min plus 80-85 or 85-90 min, very high correlations were obtained between standard Ki and dual-time-point Ki (R2  = 0.994, 0.980, 0.971 and 0.925 for nodule, tumor, cerebellum, and bone marrow), with all the slope values with differences ≤0.033 from 1 and all the intercept values with differences ≤0.0006 mL/min/cm3 from 0. The corresponding correlations were much lower between standard Ki and relative SUV change (R2  = 0.673, 0.684, 0.065, 0.246). Dual-time-point Ki showed a significantly higher quantification accuracy with respect to standard Ki than relative SUV change for all the 36 protocols (p < 0.05 using Williams' one-tailed t test). CONCLUSIONS: Our proposed approach can obtain reliable Ki images and accurate Ki quantification from dual-time-point scans (5-min per scan), and provide significantly higher quantification accuracy than relative SUV change that is currently used in clinical practice.


Assuntos
Fluordesoxiglucose F18 , Tomografia por Emissão de Pósitrons , Algoritmos , Humanos , Compostos Radiofarmacêuticos , Imagem Corporal Total
5.
Med Phys ; 48(9): 5115-5129, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34224153

RESUMO

PURPOSE: Positron emission tomography (PET) imaging with various tracers is increasingly used in Alzheimer's disease (AD) studies. However, access to PET scans using new or less-available tracers with sophisticated synthesis and short half-life isotopes may be very limited. Therefore, it is of great significance and interest in AD research to assess the feasibility of generating synthetic PET images of less-available tracers from the PET image of another common tracer, in particular 18 F-FDG. METHODS: We implemented advanced deep learning methods using the U-Net model to predict 11 C-UCB-J PET images of synaptic vesicle protein 2A (SV2A), a surrogate of synaptic density, from 18 F-FDG PET data. Dynamic 18 F-FDG and 11 C-UCB-J scans were performed in 21 participants with normal cognition (CN) and 33 participants with Alzheimer's disease (AD). Cerebellum was used as the reference region for both tracers. For 11 C-UCB-J image prediction, four network models were trained and tested, which included 1) 18 F-FDG SUV ratio (SUVR) to 11 C-UCB-J SUVR, 2) 18 F-FDG Ki ratio to 11 C-UCB-J SUVR, 3) 18 F-FDG SUVR to 11 C-UCB-J distribution volume ratio (DVR), and 4) 18 F-FDG Ki ratio to 11 C-UCB-J DVR. The normalized root mean square error (NRMSE), structure similarity index (SSIM), and Pearson's correlation coefficient were calculated for evaluating the overall image prediction accuracy. Mean bias of various ROIs in the brain and correlation plots between predicted images and true images were calculated for ROI-based prediction accuracy. Following a similar training and evaluation strategy, 18 F-FDG SUVR to 11 C-PiB SUVR network was also trained and tested for 11 C-PiB static image prediction. RESULTS: The results showed that all four network models obtained satisfactory 11 C-UCB-J static and parametric images. For 11 C-UCB-J SUVR prediction, the mean ROI bias was -0.3% ± 7.4% for the AD group and -0.5% ± 7.3% for the CN group with 18 F-FDG SUVR as the input, -0.7% ± 8.1% for the AD group, and -1.3% ± 7.0% for the CN group with 18 F-FDG Ki ratio as the input. For 11 C-UCB-J DVR prediction, the mean ROI bias was -1.3% ± 7.5% for the AD group and -2.0% ± 6.9% for the CN group with 18 F-FDG SUVR as the input, -0.7% ± 9.0% for the AD group, and -1.7% ± 7.8% for the CN group with 18 F-FDG Ki ratio as the input. For 11 C-PiB SUVR image prediction, which appears to be a more challenging task, the incorporation of additional diagnostic information into the network is needed to control the bias below 5% for most ROIs. CONCLUSIONS: It is feasible to use 3D U-Net-based methods to generate synthetic 11 C-UCB-J PET images from 18 F-FDG images with reasonable prediction accuracy. It is also possible to predict 11 C-PiB SUVR images from 18 F-FDG images, though the incorporation of additional non-imaging information is needed.


Assuntos
Doença de Alzheimer , Aprendizado Profundo , Doença de Alzheimer/diagnóstico por imagem , Compostos de Anilina , Encéfalo , Fluordesoxiglucose F18 , Humanos , Tomografia por Emissão de Pósitrons
6.
Biomaterials ; 276: 120991, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34237506

RESUMO

The development of metal-based anticancer drugs is of considerable interest and significance in inorganic medicine. In contrast to noble metal-based small molecules, the anticancer property of earth abundant metal-based small molecules is much less explored which are usually essential trace element for the human body. Among earth abundant metals, chromium (Cr) in the +3 valent is an essential trace element for the human body to low down the blood lipids and maintain the blood sugar; on the other hand, Cr(VI) are known to be highly toxic due to their oxidation power. To design stable high-valent Cr small molecules to construct Cr(high-valent)-Cr(III) in-situ transition system to achieve low-toxic and highly efficient anti-cancer therapy is a very desirable approach. Herein we report the Cr(V)-Cr(III) in-situ transition system promotes ROS generation to achieve efficient cancer therapy in vivo and in vitro. To the best of our knowledge, these Cr-based small molecules are the first stable Cr(V) compounds with potent anticancer efficacy, especially towards malignant cancers.


Assuntos
Cromo , Neoplasias , Humanos , Metais , Neoplasias/tratamento farmacológico , Oxirredução , Espécies Reativas de Oxigênio
8.
Sheng Wu Gong Cheng Xue Bao ; 37(6): 2085-2104, 2021 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-34227296

RESUMO

Terpenoids are a group of structurally diverse compounds with good biological activities and versatile functions such as anti-cancer and immunity-enhancing effects, and are widely used in food, healthcare and medical industries. Facilitated by the increasing understandings on the natural biosynthetic pathways of terpenoids in recent years, Saccharomyces cerevisiae has been engineered into high-yield strains for production of a variety of terpenoids, some of which have reached or become close to the level required by industrial production. In this connection, synthetic biology driven biotechnological production of terpenoids has become a promising alternative to chemical synthesis and traditional extraction approaches. This article summarizes the recent process in engineering S. cerevisiae for terpenoids biosynthesis, highlighting the effect of synthetic biology strategies by taking a couple of typical terpenoids as examples.


Assuntos
Engenharia Metabólica , Saccharomyces cerevisiae , Vias Biossintéticas , Saccharomyces cerevisiae/genética , Biologia Sintética , Terpenos
9.
Neuroimage ; 238: 118248, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34119639

RESUMO

PURPOSE: 11C-UCB-J PET imaging, targeting synaptic vesicle glycoprotein 2A (SV2A), has been shown to be a useful indicator of synaptic density in Alzheimer's disease (AD). For SV2A imaging, a decrease in apparent tracer uptake is often due to the combination of gray-matter (GM) atrophy and SV2A decrease in the remaining tissue. Our aim is to reveal the true SV2A change by performing partial volume correction (PVC). METHODS: We performed two PVC algorithms, Müller-Gärtner (MG) and 'iterative Yang' (IY), on 17 AD participants and 11 cognitive normal (CN) participants using the brain-dedicated HRRT scanner. Distribution volume VT, the rate constant K1, binding potential BPND (centrum semiovale as reference region), and tissue volume were compared. RESULTS: In most regions, both PVC algorithms reduced the between-group differences. Alternatively, in hippocampus, IY increased the significance of between-group differences while MG reduced it (VT, BPND and K1 group differences: uncorrected: 20%, 27%, 17%; MG: 18%, 22%, 14%; IY: 22%, 28%, 17%). The group difference in hippocampal volume (10%) was substantially smaller than any PET measures. MG increased GM binding values to a greater extent than IY due to differences in algorithm assumptions. CONCLUSION: 11C-UCB-J binding is significantly reduced in AD hippocampus, but PVC is important to adjust for significant volume reduction. After correction, PET measures are substantially more sensitive to group differences than volumetric MRI measures. Assumptions of each PVC algorithm are important and should be carefully examined and validated. For 11C-UCB-J, the less stringent assumptions of IY support its use as a PVC algorithm over MG.


Assuntos
Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Tomografia por Emissão de Pósitrons/métodos , Circulação Cerebrovascular/fisiologia , Humanos , Compostos Radiofarmacêuticos
10.
Nat Commun ; 12(1): 3800, 2021 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155203

RESUMO

Allylic amines are versatile building blocks in organic synthesis and exist in bioactive compounds, but their synthesis via hydroaminoalkylation of alkynes with amines has been a formidable challenge. Here, we report a late transition metal Ni-catalyzed hydroaminoalkylation of alkynes with N-sulfonyl amines, providing a series of allylic amines in up to 94% yield. Double ligands of N-heterocyclic carbene (IPr) and tricyclohexylphosphine (PCy3) effectively promote the reaction.

11.
J Clin Transl Hepatol ; 9(2): 239-246, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-34007806

RESUMO

With the rapid development of research on coronavirus disease 2019 (COVID-19), more and more attention has been drawn to its damage to extrapulmonary organs. There are increasing lines of evidence showing that liver injury is closely related to the severity of COVID-19, which may have an adverse impact on the progression and prognosis of the patients. What is more, severe acute respiratory syndrome coronavirus-2 infection, cytokine storm, ischemia/hypoxia reperfusion injury, aggravation of the primary liver disease and drug-induced liver injury may all contribute to the hepatic damage in COVID-19 patients; although, the drug-induced liver injury, especially idiosyncratic drug-induced liver injury, requires further causality confirmation by the updated Roussel Uclaf Causality Assessment Method published in 2016. Up to now, there is no specific regimen for COVID-19, and COVID-19-related liver injury is mainly controlled by symptomatic and supportive treatment. Here, we review the clinical features of abnormal liver enzymes in COVID-19 and pathogenesis of COVID-19-related liver injury based on the current evidence, which may provide help for clinicians and researchers in exploring the pathogenesis and developing treatment strategies.

12.
Virulence ; 12(1): 1199-1208, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33870852

RESUMO

Background: COVID-19 has rapidly become a major health emergency worldwide. The characteristic, outcome, and risk factor of COVID-19 in patients with decompensated cirrhosis remain unclear.Methods: Medical records were collected from 23 Chinese hospitals. Patients with decompensated cirrhosis and age- and sex-matched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling.Results: There were more comorbidities with higher Chalson Complication Index (p < 0.001), higher proportion of patients having gastrointestinal bleeding, jaundice, ascites, and diarrhea among those patients (p < 0.05) and in decompensated cirrhosis patients. Mortality (p < 0.05) and the proportion of severe ill (p < 0.001) were significantly high among those patients. Patients in severe ill subgroup had higher mortality (p < 0.001), MELD, and CRUB65 score but lower lymphocytes count. Besides, this subgroup had larger proportion of patients with abnormal (PT), activated partial thromboplatin time (APTT), D-Dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) and Creatinine (Cr) (p < 0.05). Multivariate logistic regression for severity shown that MELD and CRUB65 score reached significance. Higher Child-Pugh and CRUB65 scores were found among non-survival cases and multivariate logistic regression further inferred risk factors for adverse outcome. Receiver Operating Characteristic (ROC) curves also provided remarkable demonstrations for the predictive ability of Child-Pugh and CRUB65 scores.Conclusions: COVID-19 patients with cirrhosis had larger proportion of more severely disease and higher mortality. MELD and CRUB65 score at hospital admission may predict COVID-19 severity while Child-Pugh and CRUB65 score were highly associated with non-survival among those patients.


Assuntos
COVID-19/mortalidade , Cirrose Hepática/complicações , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto , Idoso , COVID-19/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 207-215, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829693

RESUMO

Objective: To investigate whether long-term exposure to inhaled sevoflurane, a volatile anesthetic, causes abnormal activities and memory impairment related to attention-deficit/hyperactivity disorder (ADHD) in neonatal rats. Methods: On postnatal day 5 (P5), Sprague-Dawley rats were randomly assigned to two sevoflurane subgroups and two control subgroups and underwent experimental intervention. The two sevoflurane (SEVO) subgroups were exposed to 3% sevoflurane for 2 h and 4 h respectively, while the two control subgroups were given pure oxygen for the same amount and duration. Behavioral tests, including open-field test (OFT), five-choice serial reaction time task (5-CSRTT), fear-conditioning (FC) and Morris water maze (MWM), were applied to evaluate changes in cognition, memory, anxiety and ADHD-related behavioral changes in the rats in adolescence (-P25) and in adulthood (-P65). Results: In OFT, the SEVO 2 h and SEVO 4 h subgroups displayed activity level and exploratory behaviors similar to those of the control subgroups on P21 and P61, with no statistically significant difference identified in the data. 5-CSRTT results on P25 and P65 indicated no statistically significant difference between the SEVO subgroups and the control subgroups in regard to ADHD-related abnormal behaviors, including number of immature reaction, rate of correct response and omission rate. In the FC experiment, SEVO 4 h group had a shorter freezing period and longer period of freezing latency ( P=0.029) in comparison to the control groups. The results of the MWM test showed that the escape latency period of rats in the SEVO 4 h group was significantly prolonged on the second day and the third day, compared to the control groups ( P<0.05). The average swimming speed of SEVO groups did no exhibit any statistically significant difference on P69 or P76. The time the SEVO 4 h group spent in the target quadrant was significantly shorter than that of the control group ( P=0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group ( P=0.048). Conclusion: The findings suggest that four hours of inhaled sevoflurane exposure in neonate rats may cause memory impairment, but does no increase risks for ADHD-related abnormal activities.


Assuntos
Anestésicos Inalatórios , Transtorno do Deficit de Atenção com Hiperatividade , Anestésicos Inalatórios/toxicidade , Animais , Animais Recém-Nascidos , Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Aprendizagem em Labirinto , Ratos , Ratos Sprague-Dawley , Sevoflurano
14.
J Cereb Blood Flow Metab ; 41(9): 2395-2409, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33757318

RESUMO

[11C]UCB-J PET for synaptic vesicle glycoprotein 2 A (SV2A) has been proposed as a suitable marker for synaptic density in Alzheimer's disease (AD). We compared [11C]UCB-J binding for synaptic density and [18F]FDG uptake for metabolism (correlated with neuronal activity) in 14 AD and 11 cognitively normal (CN) participants. We assessed both absolute and relative outcome measures in brain regions of interest, i.e., K1 or R1 for [11C]UCB-J perfusion, VT (volume of distribution) or DVR to cerebellum for [11C]UCB-J binding to SV2A; and Ki or KiR to cerebellum for [18F]FDG metabolism. [11C]UCB-J binding and [18F]FDG metabolism showed a similar magnitude of reduction in the medial temporal lobe of AD -compared to CN participants. However, the magnitude of reduction of [11C]UCB-J binding in neocortical regions was less than that observed with [18F]FDG metabolism. Inter-tracer correlations were also higher in the medial temporal regions between synaptic density and metabolism, with lower correlations in neocortical regions. [11C]UCB-J perfusion showed a similar pattern to [18F]FDG metabolism, with high inter-tracer regional correlations. In summary, we conducted the first in vivo PET imaging of synaptic density and metabolism in the same AD participants and reported a concordant reduction in medial temporal regions but a discordant reduction in neocortical regions.

15.
Alzheimers Res Ther ; 13(1): 11, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402201

RESUMO

BACKGROUND: Attempts to associate amyloid-ß (Aß) pathogenesis with synaptic loss in Alzheimer's disease (AD) have thus far been limited to small numbers of postmortem studies. Aß plaque burden is not well-correlated with indices of clinical severity or neurodegeneration-at least in the dementia stage-as deposition of Aß reaches a ceiling. In this study, we examined in vivo the association between fibrillar Aß deposition and synaptic density in early AD using positron emission tomography (PET). We hypothesized that global Aß deposition would be more strongly inversely associated with hippocampal synaptic density in participants with amnestic mild cognitive impairment (aMCI; a stage of continued Aß accumulation) compared to those with dementia (a stage of relative Aß plateau). METHODS: We measured SV2A binding ([11C]UCB-J) and Aß deposition ([11C]PiB) in 14 participants with aMCI due to AD and 24 participants with mild AD dementia. Distribution volume ratios (DVR) with a cerebellar reference region were calculated for both tracers to investigate the association between global Aß deposition and SV2A binding in hippocampus. Exploratory analyses examined correlations between both global and regional Aß deposition and SV2A binding across a broad range of brain regions using both ROI- and surface-based approaches. RESULTS: We observed a significant inverse association between global Aß deposition and hippocampal SV2A binding in participants with aMCI (r = - 0.55, P = 0.04), but not mild dementia (r = 0.05, P = 0.82; difference statistically significant by Fisher z = - 1.80, P = 0.04). Exploratory analyses across other ROIs and whole brain analyses demonstrated no broad or consistent associations between global Aß deposition and regional SV2A binding in either diagnostic group. ROI-based analyses of the association between regional Aß deposition and SV2A binding also revealed no consistent pattern but suggested a "paradoxical" positive association between local Aß deposition and SV2A binding in the hippocampus. CONCLUSIONS: Our findings lend support to a model in which fibrillar Aß is still accumulating in the early stages of clinical disease but approaching a relative plateau, a point at which Aß may uncouple from neurodegenerative processes including synaptic loss. Future research should investigate the relationship between Aß deposition and synaptic loss in larger cohorts beginning preclinically and followed longitudinally in conjunction with other biomarkers.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico por imagem , Peptídeos beta-Amiloides/metabolismo , Compostos de Anilina , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Humanos , Tomografia por Emissão de Pósitrons
16.
J Cereb Blood Flow Metab ; 41(5): 1067-1079, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-32757741

RESUMO

The positron emission tomography radioligand [11C]UCB-J binds to synaptic vesicle glycoprotein 2 A (SV2A), a regulator of vesicle release. Increased neuronal firing could potentially affect tracer concentrations if binding site availability is altered during vesicle exocytosis. This study assessed whether physiological brain activation induces changes in [11C]UCB-J tissue influx (K1), volume of distribution (VT), or binding potential (BPND). Healthy volunteers (n = 7) underwent 60-min [11C]UCB-J PET scans at baseline and during intermittent presentation of 8-Hz checkerboard visual stimulation. Sensitivity to intermittent changes in kinetic parameters was assessed in simulations, and visual stimulation was repeated using functional magnetic resonance imaging to characterize neural responses. VT and K1 were determined using the one-tissue compartment model and BPND using the simplified reference tissue model. In primary visual cortex, K1 increased 34.3 ± 15.5% (p = 0.001) during stimulation, with no change in other regions (ps > 0.12). K1 change was correlated with fMRI BOLD response (r = 0.77, p = 0.043). There was no change in VT (-3.9 ± 8.8%, p = 0.33) or BPND (-0.2 ± 9.6%, p = 0.94) in visual cortex nor other regions (ps > 0.19). Therefore, despite robust increases in regional tracer influx due to blood flow increases, binding measures were unchanged during stimulation. [11C]UCB-J VT and BPND are likely to be stable in vivo measures of synaptic density.

17.
Gastrointest Endosc ; 93(2): 422-432.e3, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32598959

RESUMO

BACKGROUND AND AIMS: Rupture of gastroesophageal varices is the most common fatal adverse event of cirrhosis. EGD is considered the criterion standard for diagnosis and risk stratification of gastroesophageal variceal bleeding. The aim of this study was to train and validate a real-time deep convolutional neural network (DCNN) system, named ENDOANGEL, for diagnosing gastroesophageal varices and predicting the risk of rupture. METHODS: After training with 8566 images of endoscopic gastroesophageal varices from 3021 patients and 6152 images of normal esophagus/stomach from 3168 patients, ENDOANGEL was also tested with independent images and videos. It was also compared with endoscopists in several aspects. RESULTS: ENDOANGEL, in contrast with endoscopists, displayed higher accuracy of 97.00% and 92.00% in terms of detecting esophageal varices (EVs) and gastric varices (GVs) in an image contest (97.00% vs 93.94% , P < .01; 92.00% vs 84.43%, P < .05). It also surpassed endoscopists for red color signs of EVs and red spots of GVs (84.21% vs 73.45%, P < .01; 85.26% vs 77.52%, P < .05). Moreover, ENDOANGEL achieved comparable performance in the determination of size, form, color, and bleeding signs. ENDOANGEL also had good performance in making treatment suggestions. With regard to predicting risk factors in multicenter videos, ENDOANGEL showed great stability. CONCLUSIONS: Our data suggest that DCNNs were precise in detecting both EVs and GVs and performed excellently in uncovering the endoscopic risk factors of gastroesophageal variceal bleeding. Thus, the application of DCNNs will assist endoscopists in evaluating gastroesophageal varices more objectively and precisely. (Clinical trial registration number: ChiCTR1900023970.).


Assuntos
Varizes Esofágicas e Gástricas , Varizes , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Cirrose Hepática/complicações , Redes Neurais de Computação , Estudos Retrospectivos
18.
EJNMMI Phys ; 7(1): 67, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33226522

RESUMO

BACKGROUND: Arterial blood sampling is the gold standard method to obtain the arterial input function (AIF) for quantification of whole body (WB) dynamic 18F-FDG PET imaging. However, this procedure is invasive and not typically available in clinical environments. As an alternative, we compared AIFs to population-based input functions (PBIFs) using two normalization methods: area under the curve (AUC) and extrapolated initial plasma concentration (CP*(0)). To scale the PBIFs, we tested two methods: (1) the AUC of the image-derived input function (IDIF) and (2) the estimated CP*(0). The aim of this study was to validate IDIF and PBIF for FDG oncological WB PET studies by comparing to the gold standard arterial blood sampling. METHODS: The Feng 18F-FDG plasma concentration model was applied to estimate AIF parameters (n = 23). AIF normalization used either AUC(0-60 min) or CP*(0), estimated from an exponential fit. CP*(0) is also described as the ratio of the injected dose (ID) to initial distribution volume (iDV). iDV was modeled using the subject height and weight, with coefficients that were estimated in 23 subjects. In 12 oncological patients, we computed IDIF (from the aorta) and PBIFs with scaling by the AUC of the IDIF from 4 time windows (15-45, 30-60, 45-75, 60-90 min) (PBIFAUC) and estimated CP*(0) (PBIFiDV). The IDIF and PBIFs were compared with the gold standard AIF, using AUC values and Patlak Ki values. RESULTS: The IDIF underestimated the AIF at early times and overestimated it at later times. Thus, based on the AUC and Ki comparison, 30-60 min was the most accurate time window for PBIFAUC; later time windows for scaling underestimated Ki (- 6 ± 8 to - 13 ± 9%). Correlations of AUC between AIF and IDIF, PBIFAUC(30-60), and PBIFiDV were 0.91, 0.94, and 0.90, respectively. The bias of Ki was - 9 ± 10%, - 1 ± 8%, and 3 ± 9%, respectively. CONCLUSIONS: Both PBIF scaling methods provided good mean performance with moderate variation. Improved performance can be obtained by refining IDIF methods and by evaluating PBIFs with test-retest data.

19.
Dig Dis Sci ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180244

RESUMO

BACKGROUND: Early detection is critical in limiting the spread of 2019 novel coronavirus (COVID-19). Although previous data revealed characteristics of GI symptoms in COVID-19, for patients with only GI symptoms onset, their diagnostic process and potential transmission risk are still unclear. METHODS: We retrospectively reviewed 205 COVID-19 cases from January 16 to March 30, 2020, in Renmin Hospital of Wuhan University. All patients were confirmed by virus nuclei acid tests. The clinical features and laboratory and chest tomographic (CT) data were recorded and analyzed. RESULTS: A total of 171 patients with classic symptoms (group A) and 34 patients with only GI symptoms (group B) were included. In patients with classical COVID-19 symptoms, GI symptoms occurred more frequently in severe cases compared to non-severe cases (20/43 vs. 91/128, respectively, p < 0.05). In group B, 91.2% (31/34) patients were non-severe, while 73.5% (25/34) patients had obvious infiltrates in their first CT scans. Compared to group A, group B patients had a prolonged time to clinic services (5.0 days vs. 2.6 days, p < 0.01) and a longer time to a positive viral swab normalized to the time of admission (6.9 days vs. 3.3 days, respectively, p < 0.01). Two patients in group B had family clusters of SARS-CoV-2 infection. CONCLUSION: Patients with only GI symptoms of COVID-19 may take a longer time to present to healthcare services and receive a confirmed diagnosis. In areas where infection is rampant, physicians must remain vigilant of patients presenting with acute gastrointestinal symptoms and should do appropriate personal protective equipment.

20.
Virulence ; 11(1): 1250-1256, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32921249

RESUMO

The cause of some patients with negative RT-PCR results experienced turn-positive after treatment remains unclear. In addition, understanding the correlation between changes in clinical data in the course of COVID-19 and treatment outcomes is of great importance in determining the prognosis of COVID-19. To perform cause analysis of RT-PCR turn-positive and the effective screening factors related to treatment outcome in COVID-19. Clinical data, including clinical manifestations, laboratory tests, radiography results, treatment methods and outcomes, were retrospectively collected and analyzed from January to March 2020 in Renmin Hospitals of Wuhan University. 116 COVID-19 patients (40 in recurrent group, 29 in recovered group and 47 in unrecovered group) were recruited. In the recurrent group, white blood cell, Neutrophils, prothrombin time, activated partial thromboplastin time, CD3, CD4, CD8, ratio of CD4/CD8, IgG and C4 complement were of significant difference among the baseline, negative and turn-positive time points. CD19 and CT scan results were found notable difference between recurrent group and recovered group. Odds from CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT scan results validated associations with clinical outcomes of COVID-19. The so-called recurrence in some COVID-19 patients may be due to the false-negative of nucleic acid test results from nasopharyngeal swabs. Levels of CD3, CD4, CD8, CD19, IgM, C3 complement, C4 complement and CT results were significantly correlated with the outcome of COVID-19. The cellular immunity test could be beneficial to further screen the reliability of RT-PCR test on the basis of CT images.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , COVID-19 , Teste para COVID-19 , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/epidemiologia , Reações Falso-Negativas , Feminino , Humanos , Imunidade Celular , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Virulência
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