Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 188
Filtrar
1.
Aging (Albany NY) ; 16(5): 4282-4298, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38441529

RESUMO

White matter hyperintensities (WMH) and gamma-aminobutyric acid (GABA) are associated with executive function. Multiple studies suggested cortical alterations mediate WMH-related cognitive decline. The aim of this study was to investigate the crucial role of cortical GABA in the WMH patients. In the 87 WMH patients (46 mild and 41 moderate to severe) examined in this study, GABA levels in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) assessed by the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence, WMH volume and executive function were compared between the two groups. Partial correlation and mediation analyses were carried out to examine the GABA levels in mediating the association between WMH volume and executive function. Patients with moderate to severe WMH had lower GABA+/Cr in the ACC (p = 0.034) and worse executive function (p = 0.004) than mild WMH patients. In all WMH cases, the GABA+/Cr levels in the ACC mediated the negative correlation between WMH and executive function (ab: effect = -0.020, BootSE = 0.010, 95% CI: -0.042 to -0.004). This finding suggested GABA+/Cr levels in the ACC might serve as a protective factor or potential target for preventing the occurrence and progression of executive function decline in WMH people.


Assuntos
Disfunção Cognitiva , Substância Branca , Humanos , Função Executiva , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Disfunção Cognitiva/psicologia , Ácido gama-Aminobutírico
3.
NPJ Microgravity ; 9(1): 75, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723136

RESUMO

Microgravity-induced bone loss results in a 1% bone mineral density loss monthly and can be a mission critical factor in long-duration spaceflight. Biomolecular therapies with dual osteogenic and anti-resorptive functions are promising for treating extreme osteoporosis. We previously confirmed that NELL-like molecule-1 (NELL-1) is crucial for bone density maintenance. We further PEGylated NELL-1 (NELL-polyethylene glycol, or NELL-PEG) to increase systemic delivery half-life from 5.5 to 15.5 h. In this study, we used a bio-inert bisphosphonate (BP) moiety to chemically engineer NELL-PEG into BP-NELL-PEG and specifically target bone tissues. We found conjugation with BP improved hydroxyapatite (HA) binding and protein stability of NELL-PEG while preserving NELL-1's osteogenicity in vitro. Furthermore, BP-NELL-PEG showed superior in vivo bone specificity without observable pathology in liver, spleen, lungs, brain, heart, muscles, or ovaries of mice. Finally, we tested BP-NELL-PEG through spaceflight exposure onboard the International Space Station (ISS) at maximal animal capacity (n = 40) in a long-term (9 week) osteoporosis therapeutic study and found that BP-NELL-PEG significantly increased bone formation in flight and ground control mice without obvious adverse health effects. Our results highlight BP-NELL-PEG as a promising therapeutic to mitigate extreme bone loss from long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when resistance training is not possible due to incapacity (e.g., bone fracture, stroke).

4.
Anal Chem ; 95(34): 12768-12775, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37587155

RESUMO

Herein, a surface-enhanced Raman scattering (SERS) biosensor was constructed by gold nanobipyramid (Au NBP) hotspot aggregation-induced SERS (HAI-SERS) for the ultrasensitive detection of microRNA-221 (miRNA-221). Impressively, compared with single Au NBP, the multiple Au NBPs assembled by tetrahedral DNA nanostructures (TDNs) could increase hotspot aggregation to significantly enhance the SERS signal of Raman molecule methylene blue (MB). Meanwhile, in the aid of Exo-III assisted target cycle amplification and TDNs-induced catalytic hairpin assembly (CHA) amplification, the biosensor could achieve the sensitive detection of miRNA-221 with a linear range of 1 fM-10 nM, and the limit of detection (LOD) was 0.59 fM, which could be used for practical application in MHCC-97L and MCF-7 cell lysates. This work provided a method for hotspot aggregation to enhance SERS for the detection of biomarkers and disease diagnosis.


Assuntos
MicroRNAs , Análise Espectral Raman , Catálise , Ouro , Limite de Detecção
5.
Front Neurosci ; 17: 1220122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37638325

RESUMO

Background and purpose: Executive function impairment, a slight but noticeable cognitive deficit in mild cognitive impairment (MCI) patients, is influenced by gamma-aminobutyric acid (GABA) levels. Reduced cognitive function is accompanied by thinning of the cerebral cortex, which has higher GABA levels than white matter. However, the relationships among GABA levels, cortical thickness, and executive function in MCI patients have not yet been elucidated. We investigated the relationships among GABA levels, cortical thickness, and executive function in MCI patients. Methods: In this study, a total of 36 MCI patients and 36 sex-, age-, and education-matched healthy controls (HC) were recruited. But 33 MCI patients and 35 HC were included because of head motion or poor data quality for three MCI patients and one HC. The levels of gamma-aminobutyric acid plus relative to creatine (GABA+/Cr) and glutamate-glutamine relative to creatine (Glx/Cr) in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) were measured using the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. Metabolite ratios, cortical thickness, and executive function and their interrelationships were determined in the MCI and HC groups. Results: Patients with MCI showed lower GABA+/Cr levels in the ACC and PCC. Combined levels of GABA+ and Glx in the ACC and GABA+ in the PCC showed good diagnostic efficacy for MCI (AUC: 0.82). But no differences in cortical thickness were found between the two groups. In the MCI group, lower GABA+/Cr level was correlated to worse performance on the digit span test backward, and the shape trail test-B. The cortical thickness was not associated with GABA+ levels and executive function in patients. Conclusion: These results implied that decreased GABA levels in the ACC and PCC had a critical role in the early diagnosis of impaired executive function of MCI. Therefore, GABA in the ACC and PCC could be a potential diagnostic marker of the executive function decline of MCI.

6.
Mol Clin Oncol ; 18(6): 45, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37152713

RESUMO

Accurate imaging-based tumor delineation is crucial for guiding the radiotherapy treatments of various solid tumors. Currently, several imaging procedures, including diffusion-weighted magnetic resonance imaging (DW-MRI), intensified computed tomography and positron emission tomography are routinely used for targeted tumor delineation. However, the performance of these imaging procedures has not yet been comprehensively evaluated. In order to address this matter, the present study was conducted in an aim to assess the use of DW-MRI in guiding radiotherapy treatments, by comparing its performance to that of other imaging procedures. Specifically, the exposure dosages to organs at risk, including the lungs, heart and spinal mencord, were evaluated using various radiotherapy regimes. The findings of the present study demonstrated that DW-MRI is a non-invasive and cost-effective imaging procedure that can be used to reduce lung exposure doses, minimizing the risk of radiation pneumonitis. The data further demonstrate the immense potential of the DW-MRI procedure in the precision radiotherapy of lung cancers.

7.
J Sci Food Agric ; 103(12): 5904-5915, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37185886

RESUMO

BACKGROUND: Soy protein isolate (SPI) can be used as an emulsifier to stabilize emulsions, though SPI is unstable under low acidic conditions. Stable composite particles of SPI and dextran sulfate (DS) can be formed by the electrostatic interaction at the pH 3.5. Furthermore, the SPI/DS composite particles can be used to prepare a high complex concentration emulsion. The stabilization properties of the high complex concentration emulsion were investigated. RESULTS: Compared to uncompounded SPI, the particle size of SPI/DS composite particles was smaller at 1.52 µm, and the absolute value of the potential increased to 19.9 mV when the mass ratio of SPI to DS was 1:1 and the pH was 3.5. With the DS ratio increased, the solubility of the composite particles increased to 14.44 times of the untreated protein at pH 3.5, while the surface hydrophobicity decreased. Electrostatic interactions and hydrogen bonds were the main forces between SPI and DS, and DS was electrostatically adsorbed on the surface of SPI. The emulsion stability significantly enhanced with the increase of complex concentration (38.88 times higher than at 1% concentration), the emulsion average droplet size was the lowest (9.64 µm), and the absolute value of potential was the highest (46.67 mV) when the mass ratio of SPI to DS was 1:1 and the complex concentration of 8%. The stability of the emulsion against freezing was improved. CONCLUSION: The SPI/DS complex has high solubility and stability under low acidic conditions, and the emulsion of the SPI/DS complex has good stability. © 2023 Society of Chemical Industry.


Assuntos
Emulsificantes , Proteínas de Soja , Proteínas de Soja/química , Emulsões/química , Sulfato de Dextrana , Emulsificantes/química , Tamanho da Partícula
8.
Front Psychol ; 14: 971552, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36733660

RESUMO

Introduction: In the construction of emergency engineering, the effective participation of organizations such as government and construction enterprises can improve engineering emergency services to emergency adaptive, which faces the challenge of the enthusiasm of enterprises' emergency participation. This study proposed a new diversified social governance mode for public emergency facility construction. Methods: This paper empirically analyzes the performance of stock market returns before and after construction enterprises' participation in emergency engineering. Results: Against the backdrop of COVID-19, the analysis based on the sample data of 141 listed companies found that both construction enterprises directly involved in emergency hospital construction and non-state-owned enterprises involved in donations have higher excess return rates. In contrast, social concern has a positive mediating effect between emergency donations and stock market returns. The study suggests that stock market returns from donation behavior and reputation capital become incentives for firms to actively participate in emergency donations, providing a behavioral basis for professional donations by construction firms. Discussion: Based on the above assumptions, this paper proposes the organizational model of emergency engineering construction and the "Engineering Community" relationship based on the "Engineering Multi-governance" theory. This paper is the first to study the emergency engineering construction model from the perspective of professional donation behavior.

9.
Radiology ; 307(3): e222061, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36853181

RESUMO

Background Quantitative T1, T2, and T2* measurements of carotid atherosclerotic plaque are important in evaluating plaque vulnerability and monitoring its progression. Purpose To develop a sequence to simultaneously quantify T1, T2, and T2* of carotid plaque. Materials and Methods The simultaneous T1, T2, and T2* mapping of carotid plaque (SIMPLE*) sequence is composed of three modules with different T2 preparation pulses, inversion-recovery pulses, and acquisition schemas. Single-echo data were used for T1 and T2 quantification, while the multiecho (ME) data were used for T2* quantification. The quantitative accuracy of SIMPLE* was tested in a phantom study by comparing its measurements with those of reference standard sequences. In vivo feasibility of the technique was prospectively evaluated between November 2020 and February 2022 in healthy volunteers and participants with carotid atherosclerotic plaque. The Pearson or Spearman correlation test, Student t test, and Wilcoxon rank-sum test were used. Results T1, T2, and T2* estimated with SIMPLE* strongly correlated with inversion-recovery spin-echo (SE) (correlation coefficient [r] = 0.99), ME-SE (r = 0.99), and ME gradient-echo (r = 0.99) sequences in the phantom study. In five healthy volunteers (mean age, 25 years ± 3 [SD]; three women), measurements were similar between SIMPLE* and modified Look-Locker inversion recovery, or MOLLI (1151 msec ± 71 vs 1098 msec ± 64; P = .14), ME turbo SE (31 msec ± 1 vs 31 msec ± 1; P = .32), and ME turbo field echo (24 msec ± 2 vs 25 msec ± 2; P = .19). In 18 participants with carotid plaque (mean age, 65 years ± 9; 16 men), quantitative T1, T2, and T2* of plaque components were consistent with their signal characteristics on multicontrast images. Conclusion A quantitative technique for simultaneous T1, T2, and T2* mapping of carotid plaque with 100-mm3 coverage and 0.8-mm3 resolution was developed using the proposed SIMPLE* sequence and demonstrated high accuracy and in vivo feasibility. © RSNA, 2023 Supplemental material is available for this article.


Assuntos
Placa Aterosclerótica , Masculino , Humanos , Feminino , Adulto , Idoso , Interpretação de Imagem Assistida por Computador/métodos , Artérias Carótidas , Imageamento por Ressonância Magnética/métodos , Imagens de Fantasmas , Reprodutibilidade dos Testes
10.
NPJ Precis Oncol ; 7(1): 2, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36599925

RESUMO

Improved treatment strategies for sarcoma rely on clarification of the molecular mediators of disease progression. Recently, we reported that the secreted glycoprotein NELL-1 modulates osteosarcoma (OS) disease progression in part via altering the sarcomatous extracellular matrix (ECM) and cell-ECM interactions. Of known NELL-1 interactor proteins, Contactin-associated protein-like 4 (Cntnap4) encodes a member of the neurexin superfamily of transmembrane molecules best known for its presynaptic functions in the central nervous system. Here, CRISPR/Cas9 gene deletion of CNTNAP4 reduced OS tumor growth, sarcoma-associated angiogenesis, and pulmonary metastases. CNTNAP4 knockout (KO) in OS tumor cells largely phenocopied the effects of NELL-1 KO, including reductions in sarcoma cell attachment, migration, and invasion. Further, CNTNAP4 KO cells were found to be unresponsive to the effects of NELL-1 treatment. Transcriptomic analysis combined with protein phospho-array demonstrated notable reductions in the MAPK/ERK signaling cascade with CNTNAP4 deletion, and the ERK1/2 agonist isoproterenol restored cell functions among CNTNAP4 KO tumor cells. Finally, human primary cells and tissues in combination with sequencing datasets confirmed the significance of CNTNAP4 signaling in human sarcomas. In summary, our findings demonstrate the biological importance of NELL-1/CNTNAP4 signaling axis in disease progression of human sarcomas and suggest that targeting the NELL-1/CNTNAP4 signaling pathway represents a strategy with potential therapeutic benefit in sarcoma patients.

11.
Eur J Radiol ; 158: 110639, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36463703

RESUMO

BACKGROUND: The histological sub-classes of brain tumors and the Ki-67 labeling index (LI) of tumor cells are major factors in the diagnosis, prognosis, and treatment management of patients. Many existing studies primarily focused on the classification of two classes of brain tumors and the Ki-67LI of gliomas. This study aimed to develop a preoperative non-invasive radiomics pipeline based on multiparametric-MRI to classify-three types of brain tumors, glioblastoma (GBM), metastasis (MET) and primary central nervous system lymphoma (PCNSL), and to predict their corresponding Ki-67LI. METHODS: In this retrospective study, 153 patients with malignant brain tumors were involved. The radiomics features were extracted from three types of MRI (T1-weighted imaging (T1WI), fluid-attenuated inversion recovery (FLAIR), and contrast-enhanced T1-weighted imaging (CE-T1WI)) with three masks (tumor core, edema, and whole tumor masks) and selected by a combination of Pearson correlation coefficient (CORR), LASSO, and Max-Relevance and Min-Redundancy (mRMR) filters. The performance of six classifiers was compared and the top three performing classifiers were used to construct the ensemble learning model (ELM). The proposed ELM was evaluated in the training dataset (108 patients) by 5-fold cross-validation and in the test dataset (45 patients) by hold-out. The accuracy (ACC), sensitivity (SEN), specificity (SPE), F1-Score, and the area under the receiver operating characteristic curve (AUC) indicators evaluated the performance of the models. RESULTS: The best feature sets and ELM with the optimal performance were selected to construct the tri-categorized brain tumor aided diagnosis model (training dataset AUC: 0.96 (95% CI: 0.93, 0.99); test dataset AUC: 0.93) and Ki-67LI prediction model (training dataset AUC: 0.96 (95% CI: 0.94, 0.98); test dataset AUC: 0.91). The CE-T1WI was the best single modality for all classifiers. Meanwhile, the whole tumor was the most vital mask for the tumor classification and the tumor core was the most vital mask for the Ki-67LI prediction. CONCLUSION: The developed radiomics models led to the precise preoperative classification of GBM, MET, and PCNSL and the prediction of Ki-67LI, which could be utilized in clinical practice for the treatment planning for brain tumors.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Antígeno Ki-67 , Estudos Retrospectivos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Glioblastoma/diagnóstico por imagem , Glioblastoma/patologia
12.
Front Public Health ; 10: 973488, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36530662

RESUMO

This study explores the preferred behavior of self-management among chronic kidney disease (CKD) patients and offers suggestions for different patients from personalized medicine. According to some related references, a questionnaire was designed in 2020 to collect data from 131 patients with CKD in a general hospital. The Sampling patients showed no difference in their disease progress. The questionnaire covered two aspects of demographic and behavior with 29 items on six dimensions. Statistical methods such as a descriptive analysis of the F test in behavior dimensions on demographic characteristics and Principal component analysis from items have been applied to classify some kinds of self-management behavior into different groups. In the demographic insight, employment status closely relates to self-management behavior, and income is insignificant. In the behavior aspects, according to some key items, we found four types of self-management behavior preferred in the sorting: cognitive-knowledge, Diet-exercise-medical, emotion management, and exercise-medical, which were defined by behavior dimensions. Although patients had the same disease progress, their self-management behavior mainly existed in four types based on critical factors. According to their favorite behavior and personality group, healthcare stakeholders can offer lean support for improving patients' self-management of CKD in China.


Assuntos
Insuficiência Renal Crônica , Autogestão , Humanos , Autocuidado , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/psicologia , Inquéritos e Questionários , Comportamentos Relacionados com a Saúde
13.
Front Psychol ; 13: 1016300, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304866

RESUMO

The declaration of the COVID-19 pandemic forced humanity to rethink how we teach and learn. The metaverse, a 3D digital space mixed with the real world and the virtual world, has been heralded as a trend of future education with great potential. However, as an emerging item, rarely did the existing study discuss the metaverse from the perspective of education. In this paper, we first introduce the visions of the metaverse, including its origin, definitions, and shared features. Then, the metaverse in education is clearly defined, and a detailed framework of the metaverse in education is proposed, along with in-depth discussions of its features. In addition, four potential applications of the metaverse in education are described with reasons and cases: blended learning, language learning, competence-based education, and inclusive education. Moreover, challenges of the metaverse for educational purposes are also presented. Finally, a range of research topics related to the metaverse in education is proposed for future studies. We hope that, via this research paper, researchers with both computer science and educational technology backgrounds could have a clear vision of the metaverse in education and provide a stepping stone for future studies. We also expect more researchers interested in this topic can commence their studies inspired by this paper.

14.
Front Cell Dev Biol ; 10: 982199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147737

RESUMO

There is an unmet need for novel and efficacious therapeutics for regenerating injured articular cartilage in progressive osteoarthritis (OA) and/or trauma. Mesenchymal stem cells (MSCs) are particularly promising for their chondrogenic differentiation, local healing environment modulation, and tissue- and organism-specific activity; however, despite early in vivo success, MSCs require further investigation in highly-translatable models prior to disseminated clinical usage. Large animal models, such as canine, porcine, ruminant, and equine models, are particularly valuable for studying allogenic and xenogenic human MSCs in a human-like osteochondral microenvironment, and thus play a critical role in identifying promising approaches for subsequent clinical investigation. In this mini-review, we focus on [1] considerations for MSC-harnessing studies in each large animal model, [2] source tissues and organisms of MSCs for large animal studies, and [3] tissue engineering strategies for optimizing MSC-based cartilage regeneration in large animal models, with a focus on research published within the last 5 years. We also highlight the dearth of standard assessments and protocols regarding several crucial aspects of MSC-harnessing cartilage regeneration in large animal models, and call for further research to maximize the translatability of future MSC findings.

15.
J Cloud Comput (Heidelb) ; 11(1): 37, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093281

RESUMO

This study investigates the possibility of supporting tourists in a foreign land intelligently by using the Tourism Cloud Management System (TCMS) to enhance and better their tourism experience. Some technologies allow tourists to highlight popular tourist routes and circuits through the visualisation of data and sensor clustering approaches. With this, a tourist can access the shared data on a specific location to know the sites of famous local attractions, how other tourists feel about them, and how to participate in local festivities through a smart tourism model. This study surveyed the potential of smart tourism among tourists and how such technologies have developed over time while proposing a TCMS. Its goals were to make physical/paper tickets redundant via the introduction of a mobile app with eTickets that can be validated using camera and QR code technologies and to enhance the transport network using Bluetooth and GPS for real-time identification of tourists' presence. The results show that a significant number of participants engage in tourist travels, hence the need for smart tourism and tourist management. It was concluded that smart tourism is very appealing to tourists and can improve the appeal of the destination if smart solutions are implemented. This study gives a first-hand review of the preference of tourists and the potential of smart tourism.

16.
Contrast Media Mol Imaging ; 2022: 2681278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36101799

RESUMO

In order to explore the clinical value of large bone flap craniotomy, the effects of standard large bone flap craniotomy on cerebral hemodynamic indexes, incidence of postoperative intracranial infection, and neurological function in patients with severe craniocerebral trauma are investigated. 89 patients with severe craniocerebral trauma admitted from January 2020 to June 2021 are analyzed retrospectively. All patients are divided into a large craniotomy group (n = 45) and control group (n = 44) according to different surgical methods. The large craniotomy group is treated with large craniotomy decompression, and the control group is treated with traditional craniotomy decompression. The incidence of intracranial infection in each group is recorded, and NIHSS is applied to observe the neurological function recovery of 2 groups before and 1 month after operation. Besides, the patients are followed up after surgery and the Kaplan-Meier survival curve is obtained to compare the survival rate of patients in the two groups. It is clearly evident that the two surgical methods have certain clinical efficacy in the treatment of patients with severe craniocerebral trauma. Comparatively, the large craniotomy can further improve brain blood supply and improve neurological function recovery. Also, it can obtain low incidence of postoperative adverse reactions and intracranial infection.


Assuntos
Traumatismos Craniocerebrais , Craniotomia , Traumatismos Craniocerebrais/cirurgia , Craniotomia/métodos , Hemodinâmica , Humanos , Estudos Retrospectivos , Retalhos Cirúrgicos
17.
Biomaterials ; 287: 121609, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35839586

RESUMO

Recent investigations into mechanisms behind the development of osteoporosis suggest that suppressing PPARγ-mediated adipogenesis can improve bone formation and bone mineral density. In this study, we investigated a co-treatment strategy to enhance bone formation by combining NELL-1, an osteogenic molecule that has been extensively studied for its potential use as a therapeutic for osteoporosis, with two methods of PPARγ suppression. First, we suppressed PPARγ genetically using lentiviral PPARγ-shRNA in immunocompromised mice for a proof of concept. Second, we used a PPARγ antagonist to suppress PPARγ pharmacologically in immunocompetent senile osteopenic mice for clinical transability. We found that the co-treatment strategy significantly increased bone formation, increased the proliferation stage cell population, decreased late apoptosis of primary mouse BMSCs, and increased osteogenic marker mRNA levels in comparison to the single agent treatment groups. The addition of PPARγ suppression to NELL-1 therapy enhanced NELL-1's effects on bone formation by upregulating anabolic processes without altering NELL-1's inhibitory effects on osteoclastic and adipogenic activities. Our findings suggest that combining PPARγ suppression with therapeutic NELL-1 may be a viable method that can be further developed as a novel strategy to reverse bone loss and decrease marrow adiposity in age-related osteoporosis.

18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(7): 763-767, 2022 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-35810438

RESUMO

OBJECTIVE: To explore the genetic basis for a child with mental retardation. METHODS: The child was subjected to chromosomal microarray analysis (CMA) and targeted capture next-generation sequencing for the exons of genes related to genetic and metabolic diseases. Candidate variants were verified by Sanger sequencing of the child and his parents. RESULTS: CMA suggested that the child has a 47,XYY karyotype. Next-generation sequencing revealed that the child has harbored compound heterozygous variants of the AUH gene, including c.677G>A (p.R226H) and c.373C>T (p.R125W), which were respectively inherited from his parents. Based on the American college of Medical Genetics and Genomics (ACMG) standards and guidelines, the c.677G>A (P.r226h) variant was predicted as variant of uncertain significance (PM2+PP4+PP3), whilst the c.373C>T (P.R125W) variant was predicted as likely pathogenic (PM1+PM2+PP3+PP4). CONCLUSION: The child had XYY syndrome in conjunct with 3-methylglutaenedioic aciduria type I due to biallelic pathogenic variants of the AUH gene.


Assuntos
Transtornos dos Cromossomos Sexuais , Cariótipo XYY , Criança , Testes Genéticos , Humanos , Masculino , Mutação
19.
Cancer Res ; 82(15): 2734-2747, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35700263

RESUMO

Sarcomas produce an abnormal extracellular matrix (ECM), which in turn provides instructive cues for cell growth and invasion. Neural EGF like-like molecule 1 (NELL1) is a secreted glycoprotein characterized by its nonneoplastic osteoinductive effects, yet it is highly expressed in skeletal sarcomas. Here, we show that genetic deletion of NELL1 markedly reduces invasive behavior across human osteosarcoma (OS) cell lines. NELL1 deletion resulted in reduced OS disease progression, inhibiting metastasis and improving survival in a xenograft mouse model. These observations were recapitulated with Nell1 conditional knockout in mouse models of p53/Rb-driven sarcomagenesis, which reduced tumor frequency and extended tumor-free survival. Transcriptomic and phosphoproteomic analyses demonstrated that NELL1 loss skews the expression of matricellular proteins associated with reduced FAK signaling. Culturing NELL1 knockout sarcoma cells on wild-type OS-enriched matricellular proteins reversed the phenotypic and signaling changes induced by NELL1 deficiency. In sarcoma patients, high expression of NELL1 correlated with decreased overall survival. These findings in mouse and human models suggest that NELL1 expression alters the sarcoma ECM, thereby modulating cellular invasive potential and prognosis. Disruption of NELL1 signaling may represent a novel therapeutic approach to short-circuit sarcoma disease progression. SIGNIFICANCE: NELL1 modulates the sarcoma matrisome to promote tumor growth, invasion, and metastasis, identifying the matrix-associated protein as an orchestrator of cell-ECM interactions in sarcomagenesis and disease progression.


Assuntos
Proteínas de Ligação ao Cálcio , Osteossarcoma , Sarcoma , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Progressão da Doença , Matriz Extracelular/metabolismo , Humanos , Camundongos , Osteossarcoma/genética , Osteossarcoma/metabolismo , Sarcoma/metabolismo
20.
Sci Rep ; 12(1): 5693, 2022 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-35383275

RESUMO

At present, more patients suffer from multiple chronic diseases. However, the hospital's existing chronic disease management is carried out according to the department. This means that a patient needs to go to more than one department for a chronic disease treatment. Therefore, this study proposes 6 dimensions (organizational management, medical service support, medical service, community alliance, self-management support, management information system) and 36 questions, to help evaluate the current chronic disease management system in China's large third-class hospitals. In this study, 143 survey samples from doctors and nurses were collected. A principal component analysis was used to extract three key elements of chronic disease management service delivery system (service management organization, management information system, medical core service). Then, multiple regression was used to establish the relationship model between the overall performance of the system and the main elements. Three key service nodes of the system (medical specialist support, patient tracking management and personalized intervention) were determined according to the weight of the regression model. The regression coefficients of the above three main elements show a similar impact on the overall performance of the system, but the key service nodes under each major element have relative differences, including medical specialist support, patient tracking management and personalized intervention. Finally, to establish a chronic disease management system with multiple departmental continuous care for chronic diseases, it is necessary to improve the chronic disease management system from three aspects of medical specialty support, patient tracking management and personalized intervention. This paper proposes corresponding improvement strategies.


Assuntos
Gerenciamento Clínico , Hospitais , China , Doença Crônica , Pesquisa Empírica , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...