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1.
Zygote ; 32(2): 175-182, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38629180

RESUMEN

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.


Asunto(s)
Criopreservación , Índice de Embarazo , Inyecciones de Esperma Intracitoplasmáticas , Motilidad Espermática , Espermatozoides , Humanos , Inyecciones de Esperma Intracitoplasmáticas/métodos , Femenino , Criopreservación/métodos , Masculino , Embarazo , Adulto , Estudios Retrospectivos , Espermatozoides/fisiología , Preservación de Semen/métodos , Resultado del Embarazo , Transferencia de Embrión/métodos , Fertilización In Vitro/métodos
2.
Mol Cancer ; 22(1): 84, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37189103

RESUMEN

BACKGROUND: Checkpoint blockade immunotherapy, represented by PD-1 or PD-L1 antibody treatment, has been of tremendous success in clinical practice. However, the low clinical response rate and lack of biomarkers for prediction of the immune response limit the clinical application of anti-PD-1 immunotherapy. Our recent work showed that a combination of low-dose decitabine and PD-1-ab significantly improved the complete response (CR) rate of cHL patients from 32 to 71%, which indicates that there is a significant correlation between epigenetic regulation and the clinical response to immunotherapy. METHODS: We recruited two groups of Hodgkin lymphoma patients who were treated with anti-PD-1 and DAC+anti-PD-1. CD8+ T cells were isolated from the patients' peripheral blood, DNA methylation was analyzed by EPIC, the expression profile was analyzed by RNA-seq, and multigroup analysis was performed with IPA and GSEA functional annotations. We explored the effect of DAC on the function of CD8+ T cells in the blood, spleen, tumor and lymph nodes using a mouse model. Furthermore, we explored the function of Tils in the tumor microenvironment. Then, we constructed Runx3-knockout mice to confirm the T-cell-specific function of Runx3 in CD8+ T cells and analyzed various subtypes of T cells and cytokines using mass cytometry (CyTOF). RESULTS: Multiomics analysis identified that DNA methylation reprogramming of Runx3 was a crucial mediator of CD8+ T-cell function. Multiomics data showed that reversal of methylation of the Runx3 promoter promoted the infiltration of CD8+ TILs and mitigated the exhaustion of CD8+ T cells. Furthermore, experiments on tissue-specific Runx3-knockout mice showed that Runx3 deficiency reduced CD8+ T infiltration and the differentiation of effector T and memory T cells. Furthermore, Runx3 deficiency significantly decreased CCR3 and CCR5 levels. Immunotherapy experiments in Runx3 conditional knockout mice showed that DAC could not reverse the resistance of anti-PD-1 in the absence of Runx3. Moreover, both our clinical data and data from TISIDB showed that Runx3 could be a potential biomarker for immunotherapy to predict the clinical response rate. CONCLUSION: We demonstrate that the DNA methylation of Runx3 plays a critical role in CD8+ T-cell infiltration and differentiation during decitabine-primed PD-1-ab immunotherapy, which provides a supporting mechanism for the essential role of epiregulation in immunotherapy.


Asunto(s)
Linfocitos T CD8-positivos , Epigénesis Genética , Animales , Ratones , Decitabina/farmacología , Inmunoterapia , Biomarcadores/metabolismo , Metilación de ADN , Ratones Noqueados , Microambiente Tumoral
3.
Respir Res ; 24(1): 299, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017476

RESUMEN

OBJECTIVES: Parametric response mapping (PRM) enables the evaluation of small airway disease (SAD) at the voxel level, but requires both inspiratory and expiratory chest CT scans. We hypothesize that deep learning PRM from inspiratory chest CT scans can effectively evaluate SAD in individuals with normal spirometry. METHODS: We included 537 participants with normal spirometry, a history of smoking or secondhand smoke exposure, and divided them into training, tuning, and test sets. A cascaded generative adversarial network generated expiratory CT from inspiratory CT, followed by a UNet-like network predicting PRM using real inspiratory CT and generated expiratory CT. The performance of the prediction is evaluated using SSIM, RMSE and dice coefficients. Pearson correlation evaluated the correlation between predicted and ground truth PRM. ROC curves evaluated predicted PRMfSAD (the volume percentage of functional small airway disease, fSAD) performance in stratifying SAD. RESULTS: Our method can generate expiratory CT of good quality (SSIM 0.86, RMSE 80.13 HU). The predicted PRM dice coefficients for normal lung, emphysema, and fSAD regions are 0.85, 0.63, and 0.51, respectively. The volume percentages of emphysema and fSAD showed good correlation between predicted and ground truth PRM (|r| were 0.97 and 0.64, respectively, p < 0.05). Predicted PRMfSAD showed good SAD stratification performance with ground truth PRMfSAD at thresholds of 15%, 20% and 25% (AUCs were 0.84, 0.78, and 0.84, respectively, p < 0.001). CONCLUSION: Our deep learning method generates high-quality PRM using inspiratory chest CT and effectively stratifies SAD in individuals with normal spirometry.


Asunto(s)
Asma , Aprendizaje Profundo , Enfisema , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Tomografía Computarizada por Rayos X/métodos , Pulmón/diagnóstico por imagen
4.
Cult Health Sex ; 25(1): 1-17, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-34941479

RESUMEN

Translated questionnaires are increasingly used in population health research. Nevertheless, translation is often not conducted with the same rigour as the process of survey development in the original language. This has serious limitations and may introduce bias in question relevance and meaning. This article describes and reflects on the process of translating a large and complex sexual and reproductive health survey from English into Simplified Chinese. We interrogated assumptions embedded in taken-for-granted translation practice to locate the sociocultural origins of these assumptions. We discuss how terminology and expression related to sexual and reproductive health may lose their conceptual or linguistic significance during translation in three different ways. Firstly, meanings can be lost in the negotiation of meanings associated with linguacultural and geographical variations of terminology. Secondly, meanings can be lost in the clash between everyday and professional sexual and reproductive health discourses. Thirdly, meanings can be lost due to the design of the source questionnaire and the intended mode of survey administration. We discuss ways to help overcome the unavoidable translation challenges that arise in the process of translating English sexual and reproductive health surveys for migrants from non-English speaking backgrounds.


Asunto(s)
Lenguaje , Salud Reproductiva , Humanos , Lingüística , Traducción , Encuestas y Cuestionarios
5.
Qual Health Res ; 31(14): 2757-2769, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34636281

RESUMEN

Videoconferencing focus groups have emerged as a popular method for collecting qualitative data. However, its use in sexual and reproductive health research is still very much in its infancy. Based on participants' feedback and researchers' reflections on using videoconferencing focus groups to collect sexual and reproductive health data with 39 heterosexual and non-heterosexual Chinese im/migrants in Australia, we discuss some of the key lessons learned, and considerations involved in shifting from face-to-face to online focus groups. Overall, videoconferencing focus groups appeared to be a highly feasible and acceptable way to discuss "sensitive" topics with Chinese im/migrants. Importantly, researchers need to be both creative and reflexive during the research process and must not forget that the success of a study lies not only in troubleshooting technical issues but also in cultivating and maintaining a trusting relationship with research participants.


Asunto(s)
Salud Reproductiva , Migrantes , China , Grupos Focales , Humanos , Investigación Cualitativa , Comunicación por Videoconferencia
6.
J Cell Mol Med ; 24(9): 4931-4943, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32277576

RESUMEN

Tumour-induced osteomalacia (TIO) is a very rare paraneoplastic syndrome with bone pain, fractures and muscle weakness, which is mostly caused by phosphaturic mesenchymal tumours (PMTs). Cell-free DNA (cfDNA) has been regarded as a non-invasive liquid biopsy for many malignant tumours. However, it has not been studied in benign tumours, which prompted us to adopt the targeted next-generation sequencing approach to compare cfDNAs of 4 TIO patients, four patients with bone metastasis (BM) and 10 healthy controls. The mutational landscapes of cfDNA in TIO and BM groups were similar in the spectrum of allele frequencies and mutation types. Markedly, deleterious missense mutations in FGFR1 and loss-of-function mutations in MED12 were found in 3/4 TIO patients but none of BM patients. The gene ontology analysis strongly supported that these mutated genes found in TIOs would play a potential role in PMTs' process. The genetic signatures and corresponding change in expression of FGFR1 and FGF23 were further validated in PMT tissues from a test cohort of another three TIO patients. In summary, we reported the first study of the mutational landscape and genetic signatures of cfDNA in TIO/PMTs.


Asunto(s)
Ácidos Nucleicos Libres de Células , Análisis Mutacional de ADN , Neoplasias/complicaciones , Neoplasias/genética , Osteomalacia/complicaciones , Osteomalacia/genética , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/genética , Adulto , Biomarcadores de Tumor , Neoplasias Óseas/complicaciones , Neoplasias Óseas/genética , Estudios de Casos y Controles , Sistema Libre de Células , Femenino , Factor-23 de Crecimiento de Fibroblastos , Perfilación de la Expresión Génica , Biblioteca de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hipofosfatemia Familiar/metabolismo , Masculino , Complejo Mediador/genética , Persona de Mediana Edad , Mutación , Mutación Missense , Metástasis de la Neoplasia , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/genética
7.
J Vasc Surg ; 72(3): 1035-1042, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-31964575

RESUMEN

OBJECTIVE: The aim of this study was to quantitatively evaluate the changes of the foot's blood supply after endovascular treatment in patients with peripheral artery disease (PAD) using foot computed tomography (CT) perfusion. METHODS: Nineteen patients who underwent endovascular treatment for PAD between January 2018 and November 2018 were included in the study. Perfusion CT scanning was performed before and after intervention with the measurement of ankle-brachial index. Regions of interest were selected from two arteries and four different tissues per foot. Perfusion maps of blood volume, blood flow, permeability surface area product, time to peak (TTP), mean transit time (MTT), mean slope of increase (MSI), Tmax, and impulse response function (IRFt0) were constructed and calculated by the perfusion analysis software. Wilcoxon signed rank test was performed on the eight parameter pairs of the limbs on the treated and untreated sides before and after intervention in the 19 patients. RESULTS: Differences in blood flow, MTT, TTP, Tmax, MSI, and IRFt0 on the treated side of the tissue perfusion group and statistical difference in blood flow, MTT, and MSI on the treated side of the arterial perfusion group were observed (all P < .05). Ankle-brachial index improved from 0.41 ± 0.11 to 0.76 ± 0.10 (P < .001). For the untreated side, TTP of the tissue perfusion group was significantly shortened (by 7.71 seconds) after surgery (P = .006), whereas there were no differences in the other parameters. In addition, no significant differences in parameters were observed on the untreated side of the arterial perfusion group. The average radiation dose per phase of perfusion scan was 0.00097 mSv. Moreover, the hyperperfusion zone in the plantar dermis and periosteum reappeared after revascularization. CONCLUSIONS: Perfusion CT is a feasible and repeatable approach for quantifying blood supply in patients with PAD. The increase of blood flow, MSI, and MTT shortening suggest blood supply improvement after revascularization in both arterial perfusion and tissue perfusion. In addition, TTP may be a sensitive indicator of blood supply changes in tissue perfusion.


Asunto(s)
Angiografía por Tomografía Computarizada , Procedimientos Endovasculares , Pie/irrigación sanguínea , Tomografía Computarizada Multidetector , Imagen de Perfusión , Enfermedad Arterial Periférica/terapia , Anciano , Velocidad del Flujo Sanguíneo , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recuperación de la Función , Flujo Sanguíneo Regional , Resultado del Tratamiento
8.
Eur Radiol ; 30(7): 3650-3659, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32162003

RESUMEN

OBJECTIVES: To investigate the value of radiomics based on CT imaging in predicting invasive adenocarcinoma manifesting as pure ground-glass nodules (pGGNs). METHODS: This study enrolled 395 pGGNs with histopathology-confirmed benign nodules or adenocarcinoma. A total of 396 radiomic features were extracted from each labeled nodule. A Rad-score was constructed with the least absolute shrinkage and selection operator (LASSO) in the training set. Multivariate logistic regression analysis was conducted to establish the radiographic model and the combined radiographic-radiomics model. The predictive performance was validated by receiver operating characteristic (ROC) curve. Based on the multivariate logistic regression analysis, an individual prediction nomogram was developed and the clinical utility was assessed. RESULTS: Five radiomic features and four radiographic features were selected for predicting the invasive lesions. The combined radiographic-radiomics model (AUC 0.77; 95% CI, 0.69-0.86) performed better than the radiographic model (AUC 0.71; 95% CI, 0.62-0.81) and Rad-score (AUC 0.72; 95% CI, 0.63-0.81) in the validation set. The clinical utility of the individualized prediction nomogram developed using the Rad-score, margin, spiculation, and size was confirmed in the validation set. The decision curve analysis (DCA) indicated that using a model with Rad-score to predict the invasive lesion would be more beneficial than that without Rad-score and the clinical model. CONCLUSIONS: The proposed radiomics-based nomogram that incorporated the Rad-score, margin, spiculation, and size may be utilized as a noninvasive biomarker for the assessment of invasive prediction in patients with pGGNs. KEY POINTS: • CT-based radiomics analysis helps invasive prediction manifested as pGGNs. • The combined radiographic-radiomics model may be utilized as a noninvasive biomarker for predicting invasive lesion for pGGNs. • Radiomics-based individual nomogram may serve as a vital decision support tool to identify invasive pGGNs, obviating further workup and blind follow-up.


Asunto(s)
Adenocarcinoma del Pulmón/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Adenocarcinoma del Pulmón/patología , Adulto , Anciano , Femenino , Humanos , Modelos Logísticos , Neoplasias Pulmonares/patología , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Nódulos Pulmonares Múltiples/patología , Análisis Multivariante , Invasividad Neoplásica , Nomogramas , Curva ROC , Tomografía Computarizada por Rayos X/métodos
9.
J Xray Sci Technol ; 28(3): 527-539, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32333574

RESUMEN

BACKGROUND: Diagnostic quality of computed tomography (CT) images depends on numerous factors. Recently, two different modalities were introduced for coronary CT angiography (CCTA). OBJECTIVE: This study aims to compare the performance of 16 cm wide-coverage detector CT (WDCT) using the snapshot freeze technique with a new-generation dual-source CT (DSCT) with 66 ms temporal resolution for CCTA. METHODS: Total 101 patients with suspected coronary heart disease were enrolled. Of these, 50 and 51 patients were examined on WDCT and DSCT, respectively. CT values, image noise, signal-to-noise ratio, and contrast-to-noise ratio were measured. The image processing efficiency was recorded, followed by statistical comparison of diagnostic accuracy and radiation dose. RESULTS: Ninety-nine patients (98.02%) had satisfactory diagnostic image quality. DSCT was significantly better than WDCT in terms of quantitative image quality, image processing efficiency, and qualitative analysis (P < 0.05). However, radiation dose was significantly lower on WDCT (P < 0.05) as compared to DSCT. CONCLUSIONS: Image processing efficiency and image quality of CCTA was higher on DSCT compared to WDCT due to the limitation of maximal tube current of WDCT.


Asunto(s)
Corazón/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Angiografía Coronaria/métodos , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Dosis de Radiación
10.
Med Sci Monit ; 25: 2195-2205, 2019 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-30907379

RESUMEN

BACKGROUND This study aimed to use the LUNGMAN N1 anthropomorphic chest model to evaluate protocols for high-definition computed tomography (HDCT) and standard-definition CT (SDCT) to detect and compare small pulmonary nodules and determine the most appropriate low-dose scanning protocols. MATERIAL AND METHODS HDCT imaging used the Discovery HD750 scanner (80, 100, 120 and 140 kVp; 360, 320, 280, 240, 200, 160, 120, 80, 40, and 20 mA), and SDCT imaging used the Lightspeed VCT scanner (80, 120, and 140 kVp; 360, 320, 280, 240, 200, 160, 120, 80, 40, and 20 mA). The LUNGMAN N1 anthropomorphic chest model contained artificial pulmonary nodules (diameter: 5, 8, 10, and 12 mm). Low-dose scanning protocols were used in image acquisition. Two experienced radiologists evaluated the image quality. The combinations of voltage, tube current, image noise, and radiation dose were recorded. Consistency of the image quality between raters was assessed by kappa statistical analysis. RESULTS Seventy CT scans of pulmonary nodules (diameter, 5-12 mm) were performed. There was a high degree of consistency for image quality between the two observers (K=0.929 for 5 mm nodules; K=0.819 for overall image quality). For 8 mm nodules, 100% were detected on both SDCT and HDCT. HDCT outperformed SDCT by 5%, in terms of effective dose. There was no significant difference in image quality between the SDCT and HDCT scanners. CONCLUSIONS Using an anthropomorphic chest model, the identification and image quality using SDCT was similar to that of HDCT for small pulmonary nodules between 5-12 mm.


Asunto(s)
Angiografía Coronaria/métodos , Tomografía Computarizada Multidetector/métodos , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Humanos , Modelos Anatómicos , Fantasmas de Imagen , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Cintigrafía/métodos , Reproducibilidad de los Resultados , Tórax/diagnóstico por imagen
11.
Bull Environ Contam Toxicol ; 102(5): 695-700, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31065732

RESUMEN

Coal combustion is a dominant source of Hg in atmosphere and is believed to be responsible for increases of atmospheric Hg since industrial revolution. In this study, we compared characteristics of different Hg species emitted from combustion of different types of coal in air and oxygen-enriched environment. Total Hg emissions from coal combustion increased significantly with increase of combustion temperature and the majority of emitted Hg existed in the form of Hg0. Total Hg emissions were 8.61 (5.38-16.48) ng/g (average and range) at 500 °C, while increased to 18.65 (6.49-40.38) ng/g at 900 °C. After burning at high temperatures, the higher percentage of reactive Hg species was observed in the flue gases, which was probably caused by promotion of Hg0 oxidation due to the higher flue gas temperature. Compared with air environment, more Hg (3.00-17.96 ng/g higher than air at 900 °C) was remained in ashes, and the percentage of reactive Hg in flue gases increased by 193%-826% at 900 °C under O2/CO2, which is beneficial for reduction of Hg emissions from coal combustion.


Asunto(s)
Contaminantes Atmosféricos/análisis , Carbón Mineral/análisis , Gases/análisis , Mercurio/análisis , Calor , Oxidación-Reducción , Oxígeno , Centrales Eléctricas
12.
Biochem Biophys Res Commun ; 493(1): 643-649, 2017 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-28865962

RESUMEN

There is an intimate connection between mitochondrial DNA (mtDNA) methylation and some diseases, such as cancer. MtDNA is almost strictly maternally inherited. However, whether the aberrant mtDNA methylation involved in breast cancer progression and whether mtDNA methylation can be transmitted through maternal line are poorly understood. Here we applied bisulfite sequencing to global mitochondrial DNA and whole genomic DNA methylation array from fifteen members of five three-female-generation families with one breast cancer patient in each family. We found that mtDNA methylation was maternally inherited in D-loop region and eight aberrant mtDNA methylation sites were correlated with breast cancer. Furthermore, conjoint analysis showed that mtDNA methylation sites could be potential biomarkers combined with nuclear DNA methylation sites for breast cancer risk prediction.


Asunto(s)
Neoplasias de la Mama/genética , Metilación de ADN/genética , ADN Mitocondrial/genética , Predisposición Genética a la Enfermedad/genética , Genoma Humano/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , China , Femenino , Humanos , Persona de Mediana Edad
13.
Biochem Biophys Res Commun ; 450(1): 692-6, 2014 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-24937452

RESUMEN

Histone methylation status in different lysine residues has an important role in transcription regulation. The effect of H4K20 monomethylation (H4K20me1) on androgen receptor (AR)-mediated gene transcription remains unclear. Here we show that AR agonist stimulates the enrichment of H4K20me1 and SET8 at the promoter of AR target gene PSA in an AR dependent manner. Furthermore, SET8 is crucial for the transcription activation of PSA. Co-immunoprecipitation analyses demonstrate that SET8 interacts with AR. Therefore, we conclude that SET8 is involved in AR-mediated transcription activation, possibly through its interaction with AR and H4K20me1 modification.


Asunto(s)
N-Metiltransferasa de Histona-Lisina/genética , Regiones Promotoras Genéticas/genética , Neoplasias de la Próstata/genética , Receptores Androgénicos/genética , Activación Transcripcional/genética , Apoptosis/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Masculino
14.
Biochem Biophys Res Commun ; 452(4): 1034-9, 2014 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-25240135

RESUMEN

The ATM protein kinase, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks, mediates responses to ionizing radiation in mammalian cells. Here we show that ATM is held inactive in unirradiated cells as a dimer and phosphorylates the opposite strand of the dimer in response to DNA damage. Cellular irradiation induces rapid intermolecular autophosphorylation of serine 1981 that causes dimer dissociation and initiates cellular ATM kinase activity. ATM cannot phosphorylate the substrates when it could not undergo dimer monomer transition. After DNA repair, the active monomer will undergo dephosphorylation to form dimer again and dephosphorylation is critical for dimer re-formation. Our work reveals novel function of ATM dimer monomer transition and explains why ATM dimer monomer transition plays such important role for ATM cellular activity during DNA repair.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Reparación del ADN/fisiología , Fibroblastos/fisiología , Línea Celular , Dimerización , Humanos , Transición de Fase , Fosforilación
15.
J Thorac Imaging ; 39(3): 146-156, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-36744945

RESUMEN

PURPOSE: Shortened injection durations are not recommended in step-and-shoot coronary computed tomography angiography (CCTA). We aimed to evaluate the image quality of CCTA performed using bodyweight-adjusted iodinated contrast media (ICM) with different injection durations to generate an optimized ICM administration protocol to acquire convincible image quality in step-and-shoot CCTA. MATERIALS AND METHODS: A total of 200 consecutive patients with suspected coronary artery disease (CAD) were enrolled in group A (N=50, 350 mgI/mL, bodyweight×0.8 mL/kg with a 13-s injection duration), group B (N=50, 350 mgI/mL, bodyweight×0.9 mL/kg with a 13-s injection duration), group C (N=50, 350 mgI/mL, bodyweight×0.8 mL/kg with a 12-s injection duration), and group D (N=50, 320 mgI/mL, bodyweight×0.8 mL/kg with a 13-s injection duration). Patient characteristics, ICM administration protocols, quantitative computed tomography (CT) value measurements, and qualitative image scores were analyzed and compared among the groups. RESULTS: Groups A and D achieved the lowest ICM volume, saline volume, injection flow rate, and total iodine and iodine injection rates among the groups. All the CT values of the coronary arteries in all groups were >300 HU. All the observers' average scores exceeded three points. In group A, the CT values showed significant positive correlation with the iodine injection rate ( r =0.226, P <0.001), whereas the signal-to-noise ratio ( r =-0.004, P =0.927) and contrast-to-noise ratio ( r =-0.006, P =0.893) values were not. CONCLUSIONS: Bodyweight×0.8 mL/kg with a 13-second injection duration is a comprehensive option for step-and-shoot CCTA with improved image quality, and a 350 mgI/mL iodine concentration is preferred.

16.
Acta Pharm Sin B ; 13(3): 903-915, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36970213

RESUMEN

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology.

17.
Biology (Basel) ; 12(3)2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36979029

RESUMEN

We aimed to detect acute aortic syndromes (AAS) on non-contrast computed tomography (NCCT) images using a radiomics-based machine learning model. A total of 325 patients who underwent aortic CT angiography (CTA) were enrolled retrospectively from 2 medical centers in China to form the internal cohort (230 patients, 60 patients with AAS) and the external testing cohort (95 patients with AAS). The internal cohort was divided into the training cohort (n = 135), validation cohort (n = 49), and internal testing cohort (n = 46). The aortic mask was manually delineated on NCCT by a radiologist. Least Absolute Shrinkage and Selection Operator regression (LASSO) was used to filter out nine feature parameters; the Support Vector Machine (SVM) model showed the best performance. In the training and validation cohorts, the SVM model had an area under the curve (AUC) of 0.993 (95% CI, 0.965-1); accuracy (ACC), 0.946 (95% CI, 0.877-1); sensitivity, 0.9 (95% CI, 0.696-1); and specificity, 0.964 (95% CI, 0.903-1). In the internal testing cohort, the SVM model had an AUC of 0.997 (95% CI, 0.992-1); ACC, 0.957 (95% CI, 0.945-0.988); sensitivity, 0.889 (95% CI, 0.888-0.889); and specificity, 0.973 (95% CI, 0.959-1). In the external testing cohort, the ACC was 0.991 (95% CI, 0.937-1). This model can detect AAS on NCCT, reducing misdiagnosis and improving examinations and prognosis.

18.
MedComm (2020) ; 4(1): e208, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36744219

RESUMEN

The recent pandemic of variants of concern (VOC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need for innovative anti-SARS-CoV-2 approaches in addition to vaccines and antiviral therapeutics. Here, we demonstrate that a CRISPR-Cas13-based strategy against SARS-CoV-2 can effectively degrade viral RNA. First, we conducted a cytological infection experiment, screened CRISPR-associated RNAs (crRNAs) targeting conserved regions of viruses, and used an in vitro system to validate functional crRNAs. Reprogrammed Cas13d effectors targeting NSP13, NSP14, and nucleocapsid transcripts achieved >99% silencing efficiency in human cells which are infected with coronavirus 2, including the emerging variants in the last 2 years, B.1, B.1.1.7 (Alpha), D614G B.1.351 (Beta), and B.1.617 (Delta). Furthermore, we conducted bioinformatics data analysis. We collected the sequence information of COVID-19 and its variants from China, and phylogenetic analysis revealed that these crRNA oligos could target almost 100% of the SARS-CoV family, including the emerging new variant, Omicron. The reprogrammed Cas13d exhibited high specificity, efficiency, and rapid deployment properties; therefore, it is promising for antiviral drug development. This system could possibly be used to protect against unexpected SARS-CoV-2 variants carrying multiple mutations.

19.
Eur J Radiol ; 159: 110684, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36621209

RESUMEN

PURPOSE: Individualized follow-up of pulmonary ground-glass nodules (GGNs) remains challenging in clinical practice. Accurate prediction of the growth or long-term stability of persistent GGNs is essential to optimize the follow-up intervals. METHODS: In this retrospective study, 253 patients with 1115 computed tomography (CT) images were recruited. In total, 1115 CT images were randomized into training (70%) and validation sets (30%). We developed models for the growth or long-term stable prediction of GGNs using radiomics and clinical features. We evaluated the prediction accuracy of the models using receiver operating characteristic (ROC) curve analysis, and the areas under the curve (AUCs) were established. The ROC curves of the models were compared using the DeLong method. RESULTS: The growth and stable groups contained 535 and 580 GGNs, respectively. Traditional radiographic features have limited value in the prediction of growth or long-term stability of GGNs. The prediction nomogram model combining radiomics and clinical features (size, location, and age) yielded the best AUC in both the training and validation sets (AUC = 0.843 and 0.824, respectively). The radiomics model outperformed the clinical model in both sets (AUC: 0.836 vs 0.772 and 0.818 vs 0.735, respectively). The radiomics signature and nomogram model achieved similar AUCs (Delong test, training set: P = 0.09; validation set: P = 0.37). CONCLUSIONS: We developed and validated a nomogram model combining radiomics signature, size, age, and location to predict the growth or long-term stability of GGNs. The model achieved good performance and may provide a basis for the improvement of follow-up management of GGNs.


Asunto(s)
Neoplasias Pulmonares , Nódulos Pulmonares Múltiples , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nomogramas , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
20.
Bioengineering (Basel) ; 10(1)2022 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-36671582

RESUMEN

This retrospective study aimed to predict the injury time of rib fractures in distinguishing fresh (30 days) or old (90 days) rib fractures. We enrolled 111 patients with chest trauma who had been scanned for rib fractures at our hospital between January 2018 and December 2018 using gemstone spectral imaging (GSI). The volume of interest of each broken end of the rib fractures was segmented using calcium-based material decomposition images derived from the GSI scans. The training and testing sets were randomly assigned in a 7:3 ratio. All cases were divided into groups distinguishing the injury time at 30 and 90 days. We constructed radiomics-based models to predict the injury time of rib fractures. The model performance was assessed by the area under the curve (AUC) obtained by the receiver operating characteristic analysis. We included 54 patients with 259 rib fracture segmentations (34 men; mean age, 52 years ± 12.02; and range, 19-72 years). Nine features were excluded by the least absolute shrinkage and selection operator logistic regression to build the radiomics signature. For distinguishing the injury time at 30 days, the Support Vector Machine (SVM) model and human-model collaboration resulted in an accuracy and AUC of 0.85 and 0.871 and 0.91 and 0.912, respectively, and 0.81 and 0.804 and 0.83 and 0.85, respectively, at 90 days in the testing set. The radiomics-based model displayed good accuracy in differentiating between the injury time of rib fractures at 30 and 90 days, and the human-model collaboration generated more accurate outcomes, which may help to add value to clinical practice and distinguish artificial injury in forensic medicine.

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