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1.
Biomed Pharmacother ; 174: 116603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636395

RESUMO

Novel strategies in intratumoral injection and emerging immunotherapies have heralded a new era of precise cancer treatments. The affinity of SARS-CoV-2 to ACE2 receptors, a feature which facilitates virulent human infection, is leveraged in this research. Colon cancer cells, with their high ACE2 expression, provide a potentially strategic target for using this SARS-CoV-2 feature. While the highly expression of ACE2 is observed in several cancer types, the idea of using the viral spike protein for targeting colon cancer cells offers a novel approach in cancer treatment. Intratumoral delivery of nucleic acid-based drugs is a promising alternative to overcoming the limitations of existing therapies. The increasing importance of nucleic acids in this realm, and the use of Lipid Nanoparticles (LNPs) for local delivery of nucleic acid therapeutics, are important breakthroughs. LNPs protect nucleic acid drugs from degradation and enhance cellular uptake, making them a rapidly evolving nano delivery system with high precision and adaptability. Our study leveraged a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combined with a receptor-binding domain from the SARS-CoV-2 spike protein, encapsulated in LNPs, to target colon cancer cells. Our results indicated that the TRAIL fusion-mRNA induced apoptosis in vitro and in vivo. Collectively, our findings highlight LNP-encapsulated TRAIL fusion-mRNA as a potential colon cancer therapy.


Assuntos
Apoptose , Neoplasias do Colo , Lipossomos , Nanopartículas , RNA Mensageiro , Ligante Indutor de Apoptose Relacionado a TNF , Humanos , Apoptose/efeitos dos fármacos , Neoplasias do Colo/terapia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Animais , Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Camundongos , Linhagem Celular Tumoral , SARS-CoV-2 , Camundongos Nus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/genética
2.
Comput Biol Med ; 170: 108035, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325214

RESUMO

Alzheimer's disease (AD) diagnosis utilizing single modality neuroimaging data has limitations. Multimodal fusion of complementary biomarkers may improve diagnostic performance. This study proposes a multimodal machine learning framework integrating magnetic resonance imaging (MRI), positron emission tomography (PET) and cerebrospinal fluid (CSF) assays for enhanced AD characterization. The model incorporates a hybrid algorithm combining enhanced Harris Hawks Optimization (HHO) algorithm referred to as ILHHO, with Kernel Extreme Learning Machine (KELM) classifier for simultaneous feature selection and classification. ILHHO enhances HHO's search efficiency by integrating iterative mapping (IM) to improve population diversity and local escaping operator (LEO) to balance exploration-exploitation. Comparative analysis with other improved HHO algorithms, classic meta-heuristic algorithms (MHAs), and state-of-the-art MHAs on IEEE CEC2014 benchmark functions indicates that ILHHO achieves superior optimization performance compared to other comparative algorithms. The synergistic ILHHO-KELM model is evaluated on 202 AD Neuroimaging Initiative (ADNI) subjects. Results demonstrate superior multimodal classification accuracy over single modalities, validating the importance of fusing heterogeneous biomarkers. MRI + PET + CSF achieves 99.2 % accuracy for AD vs. normal control (NC), outperforming conventional and proposed methods. Discriminative feature analysis provides further insights into differential AD-related neurodegeneration patterns detected by MRI and PET. The differential PET and MRI features demonstrate how the two modalities provide complementary biomarkers. The neuroanatomical relevance of selected features supports ILHHO-KELM's potential for extracting sensitive AD imaging signatures. Overall, the study showcases the advantages of capitalizing on complementary multimodal data through advanced feature learning techniques for improving AD diagnosis.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Aprendizado de Máquina , Imageamento por Ressonância Magnética/métodos , Biomarcadores , Disfunção Cognitiva/diagnóstico
3.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38244549

RESUMO

The single-nucleotide polymorphism rs3197999 in the macrophage-stimulating protein 1 gene is a missense variant. Studies have indicated that macrophage-stimulating protein 1 mediates neuronal loss and synaptic plasticity damage, and overexpression of the macrophage-stimulating protein 1 gene leads to the excessive activation of microglial cells, thereby resulting in an elevation of cerebral glucose metabolism. Traditional diagnostic models may be disrupted by neuroinflammation, making it difficult to predict the pathological status of patients solely based on single-modal images. We hypothesize that the macrophage-stimulating protein 1 rs3197999 single-nucleotide polymorphism may lead to imbalances in glucose and oxygen metabolism, thereby influencing cognitive resilience and the progression of Alzheimer's disease. In this study, we found that among 121 patients with mild cognitive impairment, carriers of the macrophage-stimulating protein 1 rs3197999 risk allele showed a significant reduction in the coupling of glucose and oxygen metabolism in the dorsolateral prefrontal cortex region. However, the rs3197999 variant did not induce significant differences in glucose metabolism and neuronal activity signals. Furthermore, the rs3197999 risk allele correlated with a higher rate of increase in clinical dementia score, mediated by the coupling of glucose and oxygen metabolism.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Glucose , Doenças Neuroinflamatórias , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Biomarcadores
4.
Quant Imaging Med Surg ; 14(1): 476-488, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223054

RESUMO

Background: Susceptibility-weighted imaging (SWI) and T1/T2 mapping can be used to detect reperfusion intramyocardial hemorrhage (IMH) in ST-segment elevation myocardial infarction (STEMI) patients. However, the sensitivity and accuracy of the SWI and T1/T2 mapping sequences were not systematically compared. The study aimed to evaluate image quality and diagnostic performance of SWI in patients with IMH, compared with T1/T2 mapping. Methods: A prospective study was conducted on consecutive acute STEMI patients who were recruited from January to July 2022. Within 2-6 days after reperfusion treatment, all patients underwent a 3T cardiac magnetic resonance (CMR) examination, including T2-weighted short-tau inversion recovery (T2W-STIR), T1/T2 mapping, and SWI. A total of 36 patients [age, 56.50±17.25 years; males, 83.33% (30/36)] were enrolled. The relative infarct-remote myocardium signal intensity ratio (SIinfarct-remote) and contrast-to-noise ratio (CNR) were calculated for each patient on T1/T2 mapping and SWI, and the difference between relative signal intensity-to-noise ratio (rSNR) in the IMH (rSNRIMH) was measured for IMH patients on T1/T2 mapping and SWI. SIinfarct-remote, CNR, and rSNRIMH were compared among the three sequences. Receiver operating characteristic (ROC) analyses were used to evaluate the diagnostic performance of three sequences by SIinfarct-remote and visual assessment. Results: A total of 26 (72.22%) patients had IMH. Quantitatively, the SIinfarct-remote of three sequences had excellent diagnostic performance for detecting IMH [SWI area under the curve (AUC) =1.000, 95% confidence interval (CI): 1.000-1.000 vs. T1 mapping AUC =0.954, 95% CI: 0.885-1.000 vs. T2 mapping AUC =0.985, 95% CI: 0.955-1.000; SWI vs. T1 mapping, P=0.300; SWI vs. T2 mapping, P=0.188; T1 mapping vs. T2 mapping, P=0.302). Qualitatively, three sequences had similar performance on detecting IMH (SWI AUC =0.895, 95% CI: 0.784-1.000; T1 mapping AUC =0.835, 95% CI: 0.711-0.958; and T2 mapping AUC =0.855, 95% CI: 0.735-0.974; SWI vs. T1 mapping, P=0.172; SWI vs. T2 mapping, P=0.317; T1 mapping vs. T2 mapping, P=0.710). The rSNRIMH was highest in T1 mapping, followed by T2 mapping and SWI, but SWI had the highest CNR. Conclusions: SWI, as well as T1/T2 mapping, is a feasible and accurate approach for clinical diagnosis of IMH with excellent performance.

5.
Virol Sin ; 38(6): 940-950, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839550

RESUMO

Myocardial injury is one of the most common comorbidity in SARS-CoV-2 infected patients, and has poor prognosis. However, the incidence of myocardial injury in patients with SARS-CoV-2 infection has not been sufficiently investigated during the Omicron wave. We conducted a retrospective study of 2690 patients with confirmed SARS-CoV-2 Omicron infection from Tongji Hospital. The results indicated that the myocardial injury accounted for 30.8% of the total patients with SARS-CoV-2 infection and was associated with higher in-hospital mortality than those without injury before and after propensity score matching (PSM) [adjusted hazard ratio (HR), 10.61; 95% confidence interval (CI), 7.76-14.51; P â€‹< â€‹0.001; adjusted HR, 2.70; 95% CI, 1.86-3.93; P â€‹< â€‹0.001; respectively]. Further, the levels of cytokines (IL-1ß, IL-6, IL-10, and TNF-α) in patients with myocardial injury were higher than those without injury, and the higher levels of cytokines in the myocardial injury group were associated with increased mortality. Administration of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) could significantly reduce the mortality in patients with myocardial injury (adjusted HR, 0.52; 95% CI, 0.38-0.71; P â€‹< â€‹0.001). Additionally, the level of angiotensin II increased in patients with SARS-CoV-2 infection was even higher in myocardial injury group compared to those without injury. Collectively, the study summarized the clinical characteristic and outcome of SARS-CoV-2 infected patients with myocardial injury during the Omicron wave in China, and validated the protective role of ACEI/ARB in improving the survival of those with myocardial injury.


Assuntos
COVID-19 , Humanos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , SARS-CoV-2 , Estudos Retrospectivos , Pandemias , Antagonistas de Receptores de Angiotensina , Citocinas
6.
Comput Biol Med ; 165: 107392, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37669585

RESUMO

In order to stop deterioration and give patients with Alzheimer's disease (AD) early therapy, it is crucial to correctly diagnose AD and its early stage, mild cognitive impairment (MCI). A framework for diagnosing AD is presented in this paper, which includes magnetic resonance imaging (MRI) image preprocessing, feature extraction, and the Fuzzy k-nearest neighbor algorithm (FKNN) model. In particular, the framework's novelty lies in the use of an improved Harris Hawks Optimization (HHO) algorithm named SSFSHHO, which integrates the Sobol sequence and Stochastic Fractal Search (SFS) mechanisms for optimizing the parameters of FKNN. The HHO method improves the quality of the initial population overall by incorporating the Sobol sequence, and the SFS mechanism increases the algorithm's capacity to get out of the local optimum solution. Comparisons with other classical meta-heuristic algorithms, state-of-the-art HHO variants in low and high dimensions, and enhanced meta-heuristic algorithms on 30 typical IEEE CEC2014 benchmark test problems show that the overall performance of SSFSHHO is significantly better than other comparative algorithms. Moreover, the created framework based on the SSFSHHO-FKNN model is employed to classify AD and MCI using MRI scans from the ADNI dataset, achieving high classification performance for 6 representative cases. Experimental findings indicate that the proposed algorithm performs better than a number of high-performance optimization algorithms and classical machine learning algorithms, thus offering a promising approach for AD classification. Additionally, the proposed strategy can successfully identify relevant features and enhance classification performance for AD diagnosis.


Assuntos
Doença de Alzheimer , Falconiformes , Humanos , Animais , Doença de Alzheimer/diagnóstico por imagem , Algoritmos , Benchmarking , Análise por Conglomerados
7.
Cardiol Plus ; 8(2): 144-148, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37539020

RESUMO

Herein, we report the case of a young female patient who suffered from myositis and heart failure due to fulminant myocarditis induced by the 2019 coronavirus disease (COVID-19). After receiving intra-aortic balloon pump (IABP) and immunomodulatory treatment, her vital signs gradually stabilized and the IABP was removed. Cardiac and muscle magnetic resonance imaging confirmed extensive myocardial and skeletal muscle edema. Though it is not uncommon for COVID-19 infection to be complicated by myocarditis and myositis, such serious muscle injury warrants clinical vigilance.

8.
J Cardiovasc Dev Dis ; 10(7)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37504536

RESUMO

Fulminant myocarditis (FM) is an acute and severe form of myocarditis with rapid progression and poor clinical outcomes in the absence of acute or chronic coronary artery disease. Electrocardiogram (ECG) abnormalities can provide preliminary clues for diagnosis; however, there is a lack of systemic descriptions on ECG changes in FM populations. Thus, a retrospective analysis of 150 consecutive FM patients and 300 healthy controls was performed to determine the characteristic ECG findings in FM. All patients included had markedly abnormal ECG findings. Specifically, 83 (55.33%) patients had significantly lower voltage with remarkably decreased QRS amplitudes in all leads compared with healthy controls (p < 0.01), and 77 (51.33%) patients had a variety of arrhythmias with lethality ventricular tachycardia/ventricular fibrillation in 21 (14.00%) patients and third-degree atrioventricular block in 21 (14.00%) patients, whereas sinus tachycardia was only found in 43 (28.67%) patients with the median heart rate (HR; 88.00 bpm, IQR: 76.00-113.50) higher than that of controls (73.00 bpm, IQR: 68.00-80.00) (p = 0.000). Conduction and repolarization abnormalities were common in patients. A longer QTc interval (452.00 ms, IQR: 419.00-489.50) and QRS duration (94.00 ms, IQR: 84.00-119.00) were observed in patients compared to controls (QTc interval = 399.00 ms, IQR: 386.00-414.00; QRS duration = 90.00 ms, IQR: 86.00-98.00) (p < 0.05). Additionally, HR > 86.50 bpm, QTc > 431.50 ms, and RV5 + SV1 < 1.715 mV can be used to predict FM. Thus, marked and severe ECG abnormalities provide preliminary clues for the diagnosis of FM.

9.
Heliyon ; 9(7): e18121, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37519690

RESUMO

The correlation between functional connectivity (FC) network segregation, glucose metabolism and cognitive decline has been recently identified. The coupling relationship between glucose metabolism and the intensity of neuronal activity obtained using hybrid PET/MRI techniques can provide additional information on the physiological state of the brain in patients with AD and mild cognitive impairment (MCI). It is a valuable task to use the above rules for constructing biomarkers that are closely related to the cognitive ability of individuals to monitor the pathological status of patients. This study proposed the concept of the energy connectivity (EC) network and its construction method. We hypothesized that the dissociation between energy connectivity and functional connectivity of brain regions is a valid indicator of cognitive ability in patients with dementia. The number of EC-attenuated brain regions (EC-AR) and the number of FC-attenuated brain regions (FC-AR) are obtained by comparison with the normal group, and the dissociation between functional connectivity and energy connectivity is indicated using the ratio of FC-AR to EC-AR for individuals in the disease group. The findings suggest that FC-AR/EC-AR values are accurate predictors of cognitive performance, while taking into account the cognitive recovery due to compensatory effects of the brain. The cognitive ability of some patients with cognitive recovery can also be predicted more accurately. This also indicates that lower functional connectivity and higher energy connectivity between network modules may be one of the important features that maintain cognitive performance. The concept of energy connectivity also has potential to help explore the pathological state of AD.

10.
Biomed Pharmacother ; 163: 114799, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37121147

RESUMO

Cardiac hypertrophy is characterized by cardiac structural remodeling, fibrosis, microvascular rarefaction, and chronic inflammation. The heart is structurally organized by different cell types, including cardiomyocytes, fibroblasts, endothelial cells, and immune cells. These cells highly interact with each other by a number of paracrine or autocrine factors. Cell-cell communication is indispensable for cardiac development, but also plays a vital role in regulating cardiac response to damage. Although cardiomyocytes and fibroblasts are deemed as key regulators of hypertrophic stimulation, other cells, including endothelial cells, also exert important effects on cardiac hypertrophy. More particularly, endothelial cells are the most abundant cells in the heart, which make up the basic structure of blood vessels and are widespread around other cells in the heart, implicating the great and inbuilt advantage of intercellular crosstalk. Cardiac microvascular plexuses are essential for transport of liquids, nutrients, molecules and cells within the heart. Meanwhile, endothelial cell-mediated paracrine signals have multiple positive or negative influences on cardiac hypertrophy. However, a comprehensive discussion of these influences and consequences is required. This review aims to summarize the basic function of endothelial cells in angiogenesis, with an emphasis on angiogenic molecules under hypertrophic conditions. The secondary objective of the research is to fully discuss the key molecules involved in the intercellular crosstalk and the endothelial cell-mediated protective or detrimental effects on other cardiac cells. This review provides a more comprehensive understanding of the overall role of endothelial cells in cardiac hypertrophy and guides the therapeutic approaches and drug development of cardiac hypertrophy.


Assuntos
Cardiomegalia , Células Endoteliais , Humanos , Células Endoteliais/metabolismo , Cardiomegalia/metabolismo , Miócitos Cardíacos/metabolismo , Comunicação Parácrina/fisiologia , Fibroblastos/metabolismo
11.
Comput Intell Neurosci ; 2022: 4902485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36262600

RESUMO

In agricultural production with small farmers as the main body, the service scale operation is one of the ways to obtain scale operation benefits. This paper constructs a tripartite evolutionary game model of agricultural scale service providers (integrators), demand subjects (farmers), and agriculture-related government departments and analyzes the influencing factors, influencing relations, and evolutionary stable equilibrium results of each participant's strategy choice. The results show that improving rewards and punishments and strengthening supervision by agriculture-related government departments will help integrators provide high-quality services and encourage farmers to actively produce and reduce speculation; when the cost difference between high-quality service and low-quality service is large, the probability of high-quality service provided by integrators will be reduced, and the evolution result of low Pareto efficiency may appear in the system; when the speculative cost of farmers is not high, the lobbying efforts of integrators will increase the speculative behavior of farmers. Finally, MATLAB2018a is used to simulate and analyze the validity of the model results, which provides a theoretical reference for the scale operation of agricultural services.


Assuntos
Agricultura , Fazendeiros , Humanos , Políticas , Governo , China
12.
J Inflamm Res ; 15: 4939-4949, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060213

RESUMO

Background: Vasospastic angina (VSA) is caused by severe diffuse or segmental coronary artery spasms. Patients with variant angina have poor clinical outcomes, although nitrates and calcium blockers help improve patient symptoms because there is no understanding of the etiology and causal treatment. The present study investigated whether VSA is associated with inflammation of the heart. Patients and Methods: A total of 109 patients with VSA diagnosed by the presence of recurrent angina pectoris, typical electrocardiography, and coronary angiography were recruited, and 61 normal participants and 61 patients with acute myocardial infarction (AMI) and coronary artery stenosis were recruited as controls. The plasma levels of 24 cytokines were measured using a magnetic Luminex assay, and endothelin-1 and histamine levels tested using enzyme-linked immunosorbent assay and mass-spectrometry, respectively, for all participants. Furthermore, four patients with VSA underwent 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT). Results: The plasma levels of interleukin (IL)-12p70, IL-13, PDL-1, IL-10, IL-6, IL-15, macrophage inflammatory protein (MIP)-1α, and MIP-1ß in patients with VSA were significantly higher than those in both normal controls and patients with AMI (p<0.001) but did not differ between normal controls and patients with AMI. 18F-FDG PET/CT showed that the left ventricle, coronary perivascular tissue volume, and coronary perivascular FDG uptake were significantly increased in all four patients. Conclusion: Our findings demonstrate that VSA patients have significantly elevated plasma cytokine levels and myocardial and pericoronary inflammation, suggesting that VSA is associated with myocarditis. This study provides novel insights into the etiology and treatment of VSA.

14.
J Pers Med ; 12(6)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35743794

RESUMO

Cholesterol homeostasis plays a significant role in cardiovascular disease. Previous studies have indicated that ATP-binding cassette transporter A1 (ABCA1) is one of the most important proteins that maintains cholesterol homeostasis. ABCA1 mediates nascent high-density lipoprotein biogenesis. Upon binding with apolipoprotein A-I, ABCA1 facilitates the efflux of excess intracellular cholesterol and phospholipids and controls the rate-limiting step of reverse cholesterol transport. In addition, ABCA1 interacts with the apolipoprotein receptor and suppresses inflammation through a series of signaling pathways. Thus, ABCA1 may prevent cardiovascular disease by inhibiting inflammation and maintaining lipid homeostasis. Several studies have indicated that post-transcriptional modifications play a critical role in the regulation of ABCA1 transportation and plasma membrane localization, which affects its biological function. Meanwhile, carriers of the loss-of-function ABCA1 gene are often accompanied by decreased expression of ABCA1 and an increased risk of cardiovascular diseases. We summarized the ABCA1 transcription regulation mechanism, mutations, post-translational modifications, and their roles in the development of dyslipidemia, atherosclerosis, ischemia/reperfusion, myocardial infarction, and coronary heart disease.

15.
Sci Rep ; 12(1): 7783, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35546615

RESUMO

The self-calibration parallel imaging (SC-SENSE) method reconstructs the image by estimating the coil sensitivity matrix. In order to obtain the sensitivity matrix, it is necessary to take a small amount of automatic calibration signal lines (ACSL) in the center of k-space. This method uses the data of the central region to obtain the sensitivity matrix, and then the reconstructed image is obtained. This paper proposed the triple cycle optimization (TCO) method to continuously optimize reconstructed images. The proposed TCO method takes the sensitivity matrix obtained by ACSL and substituted the reconstructed image as the initial data generation into the loop, and estimates the k-space data repeatedly. A new sensitivity matrix is obtained by using k-space data and the reconstructed image, and a stable triple cycle is obtained. In the cycle, all data are optimized to a certain extent, including the reconstructed image. Experimental results show that under the same sampling density, images reconstructed by using the triple cycle optimization method have lower noise and artifacts than those of the traditional method. When combined with the variable density sampling method, the effect is remarkable with a much low sampling rate.


Assuntos
Algoritmos , Imageamento por Ressonância Magnética , Artefatos , Encéfalo , Aumento da Imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Razão Sinal-Ruído
16.
J Clin Neurosci ; 100: 155-163, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35487021

RESUMO

Determining the association between genetic variation and phenotype is a key step to study the mechanism of Alzheimer's disease (AD), laying the foundation for studying drug therapies and biomarkers. AD is the most common type of dementia in the aged population. At present, three early-onset AD genes (APP, PSEN1, PSEN2) and one late-onset AD susceptibility gene apolipoprotein E (APOE) have been determined. However, the pathogenesis of AD remains unknown. Imaging genetics, an emerging interdisciplinary field, is able to reveal the complex mechanisms from the genetic level to human cognition and mental disorders via macroscopic intermediates. This paper reviews methods of establishing genotype-phenotype to explore correlations, including sparse canonical correlation analysis, sparse reduced rank regression, sparse partial least squares and so on. We found that most research work did poorly in supervised learning and exploring the nonlinear relationship between SNP-QT.


Assuntos
Doença de Alzheimer , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Apolipoproteínas E/genética , Predisposição Genética para Doença/genética , Humanos
17.
J Assist Reprod Genet ; 39(3): 719-728, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35119551

RESUMO

PURPOSE: Congenital bilateral absence of the vas deferens (CBAVD) is a major cause of obstructive azoospermia and male factor infertility. CBAVD is mainly caused by mutations in the genes encoding CFTR (cystic fibrosis transmembrane conductance regulator) and ADGRG2 (adhesion G protein-coupled receptor G2). This study aimed to describe CFTR and ADGRG2 variations in 46 Chinese CBAVD patients and evaluated sperm retrieval and assisted reproductive technology outcomes. METHODS: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI). RESULTS: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI. CONCLUSION: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI.


Assuntos
Infertilidade Masculina , Doenças Urogenitais Masculinas , Criança , China , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Humanos , Infertilidade Masculina/genética , Masculino , Doenças Urogenitais Masculinas/genética , Mutação/genética , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas , Ducto Deferente/anormalidades
18.
Sci Rep ; 12(1): 2405, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165327

RESUMO

For now, Alzheimer's disease (AD) is incurable. But if it can be diagnosed early, the correct treatment can be used to delay the disease. Most of the existing research methods use single or multi-modal imaging features for prediction, relatively few studies combine brain imaging with genetic features for disease diagnosis. In order to accurately identify AD, healthy control (HC) and the two stages of mild cognitive impairment (MCI: early MCI, late MCI) combined with brain imaging and genetic characteristics, we proposed an integrated Fisher score and multi-modal multi-task feature selection research method. We learned first genetic features with Fisher score to perform dimensionality reduction in order to solve the problem of the large difference between the feature scales of genetic and brain imaging. Then we learned the potential related features of brain imaging and genetic data, and multiplied the selected features with the learned weight coefficients. Through the feature selection program, five imaging and five genetic features were selected to achieve an average classification accuracy of 98% for HC and AD, 82% for HC and EMCI, 86% for HC and LMCI, 80% for EMCI and LMCI, 88% for EMCI and AD, and 72% for LMCI and AD. Compared with only using imaging features, the classification accuracy has been improved to a certain extent, and a set of interrelated features of brain imaging phenotypes and genetic factors were selected.


Assuntos
Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Encéfalo/diagnóstico por imagem , Aprendizado de Máquina , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Polimorfismo de Nucleotídeo Único
19.
Front Cardiovasc Med ; 8: 762371, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881311

RESUMO

Pheochromocytoma multisystem crisis (PMC) is a potentially lethal emergency due to catecholamine secretion. The condition manifests as severe hypertension to intractable cardiogenic shock and has a high mortality rate. This study explored the efficacy and safety of applying chlorpromazine on PMC patients. The study included seven patients (median age, 42 years; range, 14-57 years) diagnosed with pheochromocytoma. Four consecutive PMC patients were admitted to our critical care unit between 2016 and 2020 due to abdominal or waist pain, nausea, and vomiting. Their blood pressure (BP) fluctuated between 200-330/120-200 and 40-70/30-50 mmHg. Chlorpromazine (25 or 50 mg) was injected intramuscularly, followed by continuous intravenous infusion (2-8 mg/h). The patients' BP decreased to 100-150/60-100 mmHg within 1-3 h and stabilized within 3-5 days. Two weeks later, surgical tumor resection was successfully performed in all four patients. Similar clinical outcomes were also obtained in three patients with sporadic PMC reported in the literature who received chlorpromazine treatment, which reduced their BP readings from >200/100 mmHg to 120/70 mmHg. Our observations, combined with sporadic reports, showed that chlorpromazine efficiently controlled PMC. Thus, future studies on the use of chlorpromazine are warranted.

20.
BMC Cardiovasc Disord ; 21(1): 571, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34847863

RESUMO

BACKGROUND: We sought to describe the tendency and extent of high-sensitivity cardiac troponin I (hs-cTnI) changes in patients with fulminant myocarditis (FM) after admission and to explore the relationship between the in-hospital mortality of FM and the absolute and relative changes in hs-cTnI within 24 h and 48 h after admission. METHODS: In the retrospective study, the object are patients diagnosed with FM in our single centre. The value of cardiac troponin was recorded after patients admitted to hospital in succession. The absolute and relative changes in hs-cTnI within 24 h and 48 h were described as range distributions. Receiver operating characteristic (ROC) curve and Cox analyses were performed to determine the relationship between in-hospital mortality of FM and hs-cTnI changes. RESULTS: A total of 83 FM patients admitted to our centre from January 1, 2010 to December 31, 2019 were included; 69 patients survived and 14 patients died. In the survival group, 78% of patients experienced a decline in hs-cTnI within 24 h, while 36% of the mortality group exhibited a declining tendency in hs-cTnI (P = 0.003). Nearly 60% of survival group had a 0-2000 ng/l reduction in troponin from baseline within 24 h of admission. However, troponin levels of 50% of patients in the mortality group were 0-10,000 ng/ L higher than baseline 24 h after admission. Multivariable logistic analysis revealed that the declining tendency of hs-cTnI within 24 h, in addition to time from onset to admittance to hospital, intravenous immunoglobulin treatment and the abnormal level of creatinine, were associated with the in-hospital mortality of FM (for the declining tendency of hs-cTnI within 24 h, OR = 0.10, 95% CI 0.02-0.68, P = 0.018). The ROC curve revealed optimal cut-off values of - 618 ng/l for absolute change within 24 h (AUC = 0.800, P < 0.01), - 4389 ng/l for absolute change within 48 h (area under the curve = 0.711, P < 0.01), - 28.46% for relative change within 24 h (AUC = 0.810, P < 0.01), and - 52.23% for relative change within 48 h (AUC = 0.795, P < 0.01). Absolute changes and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality by Cox regression analysis after adjustment for sex, time from onset to admission, and occurrence of ventricular tachycardia or ventricular fibrillation. CONCLUSION: Most FM patients who survived experienced a decline in hs-cTnI within 24 h. The absolute and relative changes in hs-cTnI within 24 h and 48 h were strong predictors of in-hospital mortality.


Assuntos
Mortalidade Hospitalar , Miocardite/sangue , Miocardite/mortalidade , Troponina I/sangue , Adulto , Biomarcadores/sangue , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
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