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2.
Artículo en Inglés | MEDLINE | ID: mdl-38744667

RESUMEN

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

3.
Gastrointest Endosc ; 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38636818

RESUMEN

BACKGROUND AND AIMS: Accurate bowel preparation assessment is essential for determining colonoscopy screening intervals. Patients with suboptimal bowel preparation are at a high risk of missing >5 mm adenomas and should undergo an early repeat colonoscopy. In this study, we used artificial intelligence (AI) to evaluate bowel preparation and validated the ability of the system to accurately identify patients who are at high risk of having >5 mm adenomas missed due to inadequate bowel preparation. METHODS: This prospective, single-center, observational study was conducted at the Eighth Affiliated Hospital, Sun Yat-sen University, from October 8, 2021, to November 9, 2022. Eligible patients who underwent screening colonoscopy were consecutively enrolled. The AI assessed bowel preparation using the e-Boston Bowel Preparation Scale (e-BBPS) while endoscopists made evaluations using BBPS. If both BBPS and e-BBPS deemed preparation adequate, the patient immediately underwent a second colonoscopy; otherwise, the patient underwent bowel re-cleansing before the second colonoscopy. RESULTS: Among the 393 patients, 72 adenomas >5 mm in size were detected; 27 adenomas >5 mm in size were missed. In unqualified-AI patients, the >5 mm adenoma miss rate (AMR) was significantly higher than in qualified-AI patients (35.71% vs 13.19% [P = .0056]; odds ratio [OR], .2734 [95% CI, .1139-.6565]), as were the AMR (50.89% vs 20.79% [P < .001]; OR, .2532 [95% CI, .1583-.4052]) and >5 mm polyp miss rate (35.82% vs 19.48% [P = .0152]; OR, .4335 [95% CI, .2288-.8213]). CONCLUSIONS: This study confirmed that patients classified as inadequate by AI exhibited an unacceptable >5 mm AMR, providing key evidence for implementing AI in guiding bowel re-cleansing and potentially standardizing future colonoscopy screening. (Clinical trial registration number: NCT05145712.).

4.
Entropy (Basel) ; 26(4)2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38667880

RESUMEN

A hot NUT-Kerr-Newman black hole is a general stationary axisymmetric black hole. In this black hole spacetime, the dynamical equations of fermions at the horizon are modified by considering Lorentz breaking. The corrections to the Hawking temperature and Bekenstein-Hawking entropy at the horizon of the black hole are studied in depth. Based on the semiclassical theory correction, the Bekenstein-Hawking entropy of this black hole is quantum-corrected by considering the perturbation effect of the Planck constant ℏ. The latter part of this paper presents a detailed discussion of the obtained results and their physical implications.

5.
Cell Mol Life Sci ; 81(1): 92, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363375

RESUMEN

The maintenance of genome integrity in the germline is crucial for mammalian development. Long interspersed element type 1 (LINE-1, L1) is a mobile genetic element that makes up about 17% of the human genome and poses a threat to genome integrity. N6-methyl-adenosine (m6A) plays an essential role in regulating various biological processes. However, the function of m6A modification in L1 retrotransposons and human germline development remains largely unknown. Here we knocked out the m6A methyltransferase METTL3 or the m6A reader YTHDF2 in human embryonic stem cells (hESCs) and discovered that METTL3 and YTHDF2 are crucial for inducing human spermatogonial stem cells (hSSCs) from hESCs in vitro. The removal of METTL3 or YTHDF2 resulted in increased L1 retrotransposition and reduced the efficiency of SSC differentiation in vitro. Further analysis showed that YTHDF2 recognizes the METTL3-catalyzed m6A modification of L1 retrotransposons and degrades L1 mRNA through autophagy, thereby blocking L1 retrotransposition. Moreover, the study confirmed that m6A modification in human fetal germ cells promotes the degradation of L1 retrotransposon RNA, preventing the insertion of new L1 retrotransposons into the genome. Interestingly, L1 retrotransposon RNA was highly expressed while METTL3 was significantly downregulated in the seminal plasma of azoospermic patients with meiotic arrest compared to males with normal fertility. Additionally, we identified some potentially pathogenic variants in m6A-related genes in azoospermic men with meiotic arrest. In summary, our study suggests that m6A modification serves as a guardian of genome stability during human germline development and provides novel insights into the function and regulatory mechanisms of m6A modification in restricting L1 retrotransposition.


Asunto(s)
Azoospermia , Retroelementos , Masculino , Animales , Humanos , Retroelementos/genética , ARN , Azoospermia/genética , Diferenciación Celular/genética , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN Mensajero/genética , Mamíferos/metabolismo
6.
Gastrointest Endosc ; 99(1): 91-99.e9, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37536635

RESUMEN

BACKGROUND AND AIMS: The efficacy and safety of colonoscopy performed by artificial intelligence (AI)-assisted novices remain unknown. The aim of this study was to compare the lesion detection capability of novices, AI-assisted novices, and experts. METHODS: This multicenter, randomized, noninferiority tandem study was conducted across 3 hospitals in China from May 1, 2022, to November 11, 2022. Eligible patients were randomized into 1 of 3 groups: the CN group (control novice group, withdrawal performed by a novice independently), the AN group (AI-assisted novice group, withdrawal performed by a novice with AI assistance), or the CE group (control expert group, withdrawal performed by an expert independently). Participants underwent a repeat colonoscopy conducted by an AI-assisted expert to evaluate the lesion miss rate and ensure lesion detection. The primary outcome was the adenoma miss rate (AMR). RESULTS: A total of 685 eligible patients were analyzed: 229 in the CN group, 227 in the AN group, and 229 in the CE group. Both AMR and polyp miss rate were lower in the AN group than in the CN group (18.82% vs 43.69% [P < .001] and 21.23% vs 35.38% [P < .001], respectively). The noninferiority margin was met between the AN and CE groups of both AMR and polyp miss rate (18.82% vs 26.97% [P = .202] and 21.23% vs 24.10% [P < .249]). CONCLUSIONS: AI-assisted colonoscopy lowered the AMR of novices, making them noninferior to experts. The withdrawal technique of new endoscopists can be enhanced by AI-assisted colonoscopy. (Clinical trial registration number: NCT05323279.).


Asunto(s)
Adenoma , Pólipos del Colon , Neoplasias Colorrectales , Pólipos , Humanos , Inteligencia Artificial , Estudios Prospectivos , Colonoscopía/métodos , Proyectos de Investigación , Adenoma/diagnóstico , Adenoma/patología , Pólipos del Colon/diagnóstico por imagen , Neoplasias Colorrectales/diagnóstico
7.
Radiat Oncol ; 18(1): 192, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37986008

RESUMEN

PURPOSE: Highly modulated radiotherapy plans aim to achieve target conformality and spare organs at risk, but the high complexity of the plan may increase the uncertainty of treatment. Thus, patient-specific quality assurance (PSQA) plays a crucial role in ensuring treatment accuracy and providing clinical guidance. This study aims to propose a prediction model based on complexity metrics and patient planning dose for PSQA results. MATERIALS AND METHODS: Planning dose, measurement-based reconstructed dose and plan complexity metrics of the 687 radiotherapy plans of patients treated in our institution were collected for model establishing. Global gamma passing rate (GPR, 3%/2mm,10% threshold) of 90% was used as QA criterion. Neural architecture models based on Swin-transformer were adapted to process 3D dose and incorporate 1D metrics to predict QA results. The dataset was divided into training (447), validation (90), and testing (150) sets. Evaluation of predictions was performed using mean absolute error (MAE) for GPR, planning target volume (PTV) HI and PTV CI, mean absolute percentage error (MAPE) for PTV D95, PTV D2 and PTV Dmean, and the area under the receiver operating characteristic (ROC) curve (AUC) for classification. Furthermore, we also compare the prediction results with other models based on either only 1D or 3D inputs. RESULTS: In this dataset, 72.8% (500/687) plans passed the pretreatment QA under the criterion. On the testing set, our model achieves the highest performance, with the 1D model slightly surpassing the 3D model. The performance results are as follows (combine, 1D, and 3D transformer): The AUCs are 0.92, 0.88 and 0.86 for QA classification. The MAEs of prediction are 0.039, 0.046, and 0.040 for 3D GPR, 0.018, 0.021, and 0.019 for PTV HI, and 0.075, 0.078, and 0.084 for PTV CI. Specifically, for cases with 3D GPRs greater than 90%, the MAE could achieve 0.020 (combine). The MAPE of prediction is 1.23%, 1.52%, and 1.66% for PTV D95, 2.36%, 2.67%, and 2.45% for PTV D2, and 1.46%, 1.70%, and 1.71% for PTV Dmean. CONCLUSION: The model based on 1D complexity metrics and 3D planning dose could predict pretreatment PSQA results with high accuracy and the complexity metrics play a leading role in the model. Furthermore, dose-volume metric deviations of PTV could be predicted and more clinically valuable information could be provided.


Asunto(s)
Radioterapia de Intensidad Modulada , Humanos , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/métodos , Planificación de la Radioterapia Asistida por Computador/métodos , Rayos gamma
8.
Comp Med ; 73(4): 277-284, 2023 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-37550055

RESUMEN

Tree shrews display obvious reproductive cycles, and sexually mature male tree shrews produce little or no sperm with extremely low motility during the nonreproductive season; the mechanism underlying this phenomenon remains unknown. Because testis-specific serine/threonine kinases (TSSK) are specifically expressed in the testis and male germ cells of mammals, we hypothesized that they may have an important role in spermatogenesis or sperm function regulation in tree shrews. In addition, the expression, distribution, subcellular localization, and dynamic changes of TSSK in tree shrew sperm are unclear. Here we show that during the reproductive season, the seminiferous tubules were significantly larger as compared with the nonreproductive season and contained mature sperm and other germ cells. The mRNA expression of Tssk genes in testis was significantly higher than that in other tissues, and the mRNA level in the testis during the reproductive season was significantly higher than that in nonreproductive season. In addition, the mRNA level of Tssk3 in the testis and sperm was significantly higher than that of other members. Specifically, Tssk1 mRNA was distributed in the acrosome and throughout the flagellum of tree shrew sperm, Tssk2 was present in the acrosome, Tssk3 was localized to postacrosomal region and relocated to the main part of the flagellum after capacitation, and Tssk6 was distributed in the acrosome and postacrosomal region. These results indicate that the TSSK are important regulating reproductive function in tree shrews.


Asunto(s)
Testículo , Tupaia , Masculino , Animales , Testículo/metabolismo , Tupaia/genética , Tupaia/metabolismo , Tupaiidae/genética , Tupaiidae/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Musarañas/genética , Musarañas/metabolismo , Estaciones del Año , Semen/metabolismo , Espermatozoides/metabolismo , Treonina , ARN Mensajero , Serina
9.
Colloids Surf B Biointerfaces ; 229: 113468, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37515961

RESUMEN

Thrombus is one of the culprits for global health problems. However, most current antithrombotic drugs are limited by restricted targeting ability and a high risk of systemic bleeding. A hybrid cell membrane-coated biomimetic nanosystem (PM/RM@PLGA@P/R) was constructed in this paper to fulfil the targeted delivery of ginsenoside (Rg1) and perfluorohexane (PFH). Poly lactic-co-glycolic acid (PLGA) is used as carriers to coat Rg1 and PFH. Thanks to the camouflage of erythrocyte membrane (RM) and platelet membrane (PM), the nanosystem in question possesses remarkable features including immune escape and self-targeting. Therefore, a compact nano-core with PLGA@P/R was formed, with a hybrid membrane covering the surface of the core, forming a "core-shell" structure. With its "core-shell" structure, this nanoparticle fancifully combines the advantages of both PFH (the low-intensity focused ultrasound (LIFU)-responsive phase-change thrombolysis) and Rg1(the antioxidant, anti-inflammatory and anticoagulant abilities). Meanwhile, PM/RM@PLGA@P/R nanoparticles exhibits superior in-vitro performance in terms of ROS scavenging, anticoagulant activity and immune escape compared with those without cell membranes (PLGA@P/R). Furthermore, in the animal experiment in which the tail vein thrombosis model was established by injecting k-carrageenan, the combined treatment of LIFU and PM/RM@PLGA@P/R showed a satisfactory antithrombotic efficiency (88.20 %) and a relatively higher biological safety level. This strategy provides new insights into the development of more effective and safer targeted biomimetic nanomedicines for antithrombotic treatments, possessing potential application in synergistic therapy field.


Asunto(s)
Ginsenósidos , Nanopartículas , Trombosis , Animales , Fibrinolíticos/farmacología , Fibrinolíticos/química , Membrana Eritrocítica , Ginsenósidos/farmacología , Biomimética , Trombosis/tratamiento farmacológico , Anticoagulantes , Nanopartículas/química
10.
Heliyon ; 9(4): e14716, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37009242

RESUMEN

Sever vibration will be induced due to the high flow velocity in the pipe. When the flow velocity exceeds the critical value, the static equilibrium configuration of the pipe loses its stability, and the vibration properties change accordingly. In this paper, the free vibration characteristics of the pipe with fixed-fixed ends are revealed in the supercritical regime. Based on the Timoshenko beam theory, the governing equations of the nonlinear vibration near the non-trivial static equilibrium configuration are established. The influences of system parameters on equilibrium configuration, critical velocity, and free vibration frequency is analyzed. The effects of supercritical velocity in different ranges on the natural frequencies are revealed. In addition, the comparison with the Euler-Bernoulli pipe model shows that the differences in critical velocity, equilibrium configuration, and frequency are still significant even the length-diameter ratio is large. The increase of the flow velocity reduces the difference of non-trivial static equilibrium configurations, but eventually aggravates the difference of natural frequencies. Within a certain supercritical velocity range, the vibration difference between the two pipe models is small, beyond this range, the vibration difference increases significantly.

11.
Med Phys ; 50(5): 3127-3136, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36960718

RESUMEN

BACKGROUND: Stereotactic radiotherapy (SRT) has been widely used for the treatment of brain metastases and early stage non-small-cell lung cancer (NSCLC). Excellent SRT plans are characterized by steep dose fall-off, making it critical to accurately and comprehensively predict and evaluate dose fall-off. PURPOSE: A novel dose fall-off index was proposed to ensure high-quality SRT planning. METHODS: The novel gradient index (NGI) had two different modes: NGIx V for three-dimensions and NGIx r for one-dimension. NGIx V and NGIx r were defined as the ratios of the decreased percentage dose (x%) to the corresponding isodose volume and equivalent sphere radii, respectively. A total of 243 SRT plans at our institution between April 2020 and March 2022 were enrolled, including 126 brain and 117 lung SRT plans. Measurement-based verifications were performed using SRS MapCHECK. Ten plan complexity indexes were calculated. Dosimetric parameters related to radiation injuries were also extracted, including the normal brain volume exposed to 12 Gy (V12 ) and 18 Gy (V18 ) during single-fraction SRT (SF-SRT) and multi-fraction SRT (MF-SRT), respectively, and the normal lung volume exposed to 12 Gy (V12 ). The performance of NGI and other common dose fall-off indexes, gradient index (GI), R50% and D2cm were evaluated using Spearman correlation analysis to explore their correlations with the PTV size, gamma passing rate (GPR), plan complexity indexes, and dosimetric parameters. RESULTS: There were statistically significant correlations between NGI and PTV size (r = -0.98, P < 0.01 for NGI50 V and r = -0.93, P < 0.01 for NGI50 r), which were the strongest correlations compared with GI (r = 0.11, P = 0.13), R50% (r = -0.08, P = 0.19) and D2cm (r = 0.84, P < 0.01). The fitted formulas of NGI50 V = 23.86V-1.00 and NGI50 r = 113.5r-1.05 were established. The GPRs of enrolled SRT plans were 98.6 ± 1.7%, 94.2 ± 4.7% and 97.1 ± 3.1% using the criteria of 3%/2 mm, 3%/1 mm, and 2%/2 mm, respectively. NGI50 V achieved the strongest correlations with various plan complexity indexes (|r| ranged from 0.67 to 0.91, P < 0.01). NGI50 V also showed the highest r values with V12 (r = -0.93, P < 0.01) and V18 (r = -0.96, P < 0.01) of the normal brain during SF-SRT and MF-SRT, respectively, and V12 (r = -0.86, P < 0.01) of the normal lung during lung SRT. CONCLUSIONS: Compared with GI, R50% and D2cm , the proposed dose fall-off index, NGI, had the strongest correlations with the PTV size, plan complexity and V12 /V18 of the normal tissues. These correlations established on NGI are more helpful and reliable for SRT planning, quality control, and reducing the risk of radiation injuries.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Traumatismos por Radiación , Radiocirugia , Radioterapia de Intensidad Modulada , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirugía , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador/métodos , Radiocirugia/métodos , Pulmón , Encéfalo , Radioterapia de Intensidad Modulada/métodos
12.
Front Pediatr ; 11: 1043442, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36846165

RESUMEN

Carpal tunnel syndrome (CTS) is an upper extremity median nerve entrapment disorder that is rare in children and adolescents. Anatomical variations of the wrist, such as anomalous muscles, persistent median artery (PMA), and bifid median nerves (BMN), are rare etiology of CTS. Coexistence of all three variants combined with CTS in adolescents has been rarely reported. Case description: A 16-year-old right-hand dominant male presented to our clinic with several years of bilateral thenar muscle atrophy and weakness but no paresthesia or pain in his both hands. Ultrasonography showed that the right median nerve become significantly thinner, and the left median nerve was split into two branches by PMA. Magnetic resonance imaging (MRI) revealed that anomalous muscles in the bilateral wrist extending to the carpal tunnel, causing compression of the median nerve. Considering the possibility of CTS clinically, the patient underwent bilateral open carpal tunnel release without resection of anomalous muscles and PMA. The patient has no discomfort after 2 years. This suggests that anatomical variations of the carpal tunnel may contribute to CTS, which can be confirmed by preoperative ultrasonography and MRI, and the possibility of carpal tunnel anatomical variations should be considered when CTS occurs in adolescents. Open carpal tunnel release is an effective treatment for juvenile CTS without the need to resect abnormal muscle and PMA during the operation.

13.
Neurosci Biobehav Rev ; 144: 104976, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36435393

RESUMEN

Mental illness is a significant global health issue with a steady prevalence. High heritability is suspected, but genome-wide association studies only identified a small number of risk genes associated with mental disorders. This 'missing inheritance' can be partially explained by epigenetic heredity. Evidence from numerous animal models and human studies supports the possibility that preconception paternal mental health influences their offspring's mental health via nongenetic means. Here, we review two potential pathways, including sperm epigenetics and seminal plasma components. The current review highlights the role of sperm epigenetics and explores epigenetic message origination and susceptibility to chronic stress. Meanwhile, possible spatiotemporal windows and events that induce sexually dimorphic modes and effects of paternal stress transmission are inferred in this review. Additionally, we discuss emerging interventions that could potentially block the intergenerational transmission of paternal psychiatric disorders and reduce the incidence of mental illness. Understanding the underlying mechanisms by which preconception paternal stress impacts offspring health is critical for identifying strategies supporting healthy development and successfully controlling the prevalence of mental illness.


Asunto(s)
Salud Infantil , Trastornos Mentales , Niño , Animales , Humanos , Masculino , Estudio de Asociación del Genoma Completo , Semen , Padre , Epigénesis Genética , Trastornos Mentales/epidemiología , Trastornos Mentales/genética
14.
Int J Mol Sci ; 23(18)2022 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-36142765

RESUMEN

Much progress has been made in determining that paternal environmental exposures can remodel their spermatozoa small noncoding RNAs (sncRANs) and, in turn, affect the phenotypes of their offspring. Studies have shown that changes in the spermatozoa sncRNAs profile occur during passing through the epididymis. Due to the absence of transcription and translation in the epididymis, spermatozoa remodel their sncRNAs profile through communication with the epididymal microenvironment. Since epididymosomes contribute to the process of spermatozoa maturation by mediating the crosstalk between the epididymis and the passing spermatozoa, they are considered to be the leading candidate to mediate these changes. Previous studies and reviews on the role of epididymal transfer proteins in sperm maturation and function are myriad. This review focuses on the role and mechanisms of epididymosome-mediated transfer of sncRNAs cargoes onembryonic development and offspring health.


Asunto(s)
ARN Pequeño no Traducido , Animales , Desarrollo Embrionario , Epidídimo/metabolismo , Masculino , ARN Pequeño no Traducido/genética , Semen , Maduración del Esperma , Espermatozoides/metabolismo
15.
Cell Prolif ; 55(9): e13278, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35733381

RESUMEN

BACKGROUND: Mesangial cell proliferation is the most basic pathological feature of immunoglobulin A nephropathy (IgAN); however, the specific underlying mechanism and an appropriate therapeutic strategy are yet to be unearthed. This study aimed to investigate the therapeutic effect of triptolide (TP) on IgAN and the mechanism by which TP regulates autophagy and proliferation of mesangial cells through the CARD9/p38 MAPK pathway. METHODS: We established a TP-treated IgAN mouse model and produced IgA1-induced human mesangial cells (HMC) and divided them into control, TP, IgAN, and IgAN+TP groups. The levels of mesangial cell proliferation (PCNA, cyclin D1, cell viability, and cell cycle) and autophagy (P62, LC3 II, and autophagy flux rate) were measured, with the autophagy inhibitor 3-Methyladenine used to explore the relationship between autophagy and proliferation. We observed CARD9 expression in renal biopsies from patients and analyzed its clinical significance. CARD9 siRNA and overexpression plasmids were constructed to investigate the changes in mesangial cell proliferation and autophagy as well as the expression of CARD9 and p-p38 MAPK/p38 MAPK following TP treatment. RESULTS: Administering TP was safe and effectively alleviated mesangial cell proliferation in IgAN mice. Moreover, TP inhibited IgA1-induced HMC proliferation by promoting autophagy. The high expression of CARD9 in IgAN patients was positively correlated with the severity of HMC proliferation. CARD9/p38 MAPK was involved in the regulation of HMC autophagy and proliferation, and TP promoted autophagy to inhibit HMC proliferation by downregulating the CARD9/p38 MAPK pathway in IgAN. CONCLUSION: TP promotes autophagy to inhibit mesangial cell proliferation in IgAN via the CARD9/p38 MAPK pathway.


Asunto(s)
Glomerulonefritis por IGA , Animales , Autofagia , Proteínas Adaptadoras de Señalización CARD/metabolismo , División Celular , Proliferación Celular , Células Cultivadas , Diterpenos , Compuestos Epoxi , Glomerulonefritis por IGA/tratamiento farmacológico , Glomerulonefritis por IGA/metabolismo , Glomerulonefritis por IGA/patología , Humanos , Inmunoglobulina A/metabolismo , Inmunoglobulina A/farmacología , Inmunoglobulina A/uso terapéutico , Ratones , Fenantrenos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
16.
Front Med (Lausanne) ; 9: 834164, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35433764

RESUMEN

IgA nephropathy (IgAN) is a common form of primary glomerulonephritis and its main pathological changes are mesangial cell proliferation and matrix expansion. Autophagy inhibition may result in its mesangial cell proliferation and renal lesions. SUMOylation is a eukaryotic-reversible post-translational modification where SUMO is covalently attached to target proteins to regulate their properties. It is largely unclear whether SUMOylation contributes to the pathogenesis of IgAN. This study was designed to investigate the change of protein SUMO1 in mesangial cells of IgAN and its association with autophagy. We found the expression of SUMO1 was upregulated in IgAN, IgA mouse model, and aIgA1-stimulated mesangial cells. In aIgA1-stimulated mesangial cell model, we tested LC3II/I and p62, the autophagy-related proteins suggested the inhibition of autophagy. Inhibited SUMOylation with ginkgolic acid (GA) or silencing SUMO1 could downregulate SUMO1 and SUMO1-p53, promote autophagy, and lessen cell proliferation. In summary, in the mesangial cells stimulated with aIgA1, SUMO1 may contribute to its cell proliferation through inhibited autophagy, and SUMO1-p53 may play a role in this process.

17.
Ann Transl Med ; 10(24): 1381, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36660724

RESUMEN

Background: To evaluate the effects of dose to tumors and organs at risk (OARs) on inter-fractional anatomic changes. Methods: We evaluated nine patients with cervical cancer treated with intensity-modulated radiotherapy (IMRT) (45 Gy in 25 fractions) using kV cone-beam computed tomography (CBCT) image guidance once or twice a week before treatment. For each patient, the original plan on the computed tomography (CT) image was copied to merged images, and then the fractional doses were calculated. Subsequently, deformable accumulated doses were obtained by summing the fractional absolute doses into a single dose in MIM Maestro software. The volume changes in the target and OARs were compared between the original CT and merged CBCT images, and the differences in the fractional and accumulated doses were also evaluated. Results: Sixty-nine merged CBCT images were obtained and analyzed in this study. For the target areas, the volume changes in the clinical target volume (CTV) and planning target volume (PTV) reached -18.05% and -24.11% at most, respectively. The fractional D2% of the CTV and PTV was generally higher than the original plans, and the accumulated deviations were 2.27%±0.82% (P<0.01) and 2.42%±1.28% (P<0.01), respectively. The fractional D98% of the PTV was underdosed up to 18.28% for 78% of patients, and the accumulated deviations were -2.06% to -17.29% (P<0.05). For the OARs, the bladder volume changes were the most dramatic, reducing up to 93.60%. The fractional Dmean and D2cc of the bladder were generally higher than the original plans, and there were significant differences in their accumulated values (P<0.05). There was no obvious trend of rectal volume change with -69.65% to 74.20%. The rectum Dmean and D2cc of the accumulated were not significantly different from the planned dose (P>0.05). Conclusions: For patients with cervical cancer, the changes in bladder and rectal volume were greater than in the target volume. Although the volume changes in the bladder and rectum had no significant effect on D98% of the CTV and PTV, they had a significant effect on their own D2cc and the D2% of the CTV and PTV. More attention should be paid to the volume changes in the bladder and rectum in clinical work.

18.
Chem Commun (Camb) ; 57(92): 12203-12217, 2021 Nov 19.
Artículo en Inglés | MEDLINE | ID: mdl-34714301

RESUMEN

The direct employment of polyfluoroarenes and gem-difluoroalkenes as building blocks is regarded as one of the most effective and straightforward strategies for the introduction of fluorine-containing moieties into organic skeletons. Accordingly, radical chemistry has gradually become a mild and powerful method for the activation of their C-F bonds. The radical-based transformations of polyfluoroarenes and gem-difluoroalkenes can be primarily categorized into three types based on the specific intermediates involved: (1) multifluoroaryl radical anions, (2) monofluoroalkenyl radicals and (3) other radicals. Compared with the more established multifluoroaryl radical anion pathway, the monofluoroalkenyl radical-involved cross-coupling reaction can proceed through C-radical cross-coupling, radical addition/elimination or the hydrogen atom transfer process. For the presented examples in this review, the typical reaction modes, substrate scope, radical-involved mechanisms, and late-stage applications in the modification of bioactive molecules are discussed, aiming to provide a comprehensive overview of the recent advances of the radical-based transformations of polyfluoroarenes and gem-difluoroalkenes.

19.
Radiat Oncol ; 16(1): 134, 2021 Jul 21.
Artículo en Inglés | MEDLINE | ID: mdl-34289863

RESUMEN

BACKGROUND: Both patient-specific dose recalculation and γ passing rate analysis are important for the quality assurance (QA) of intensity modulated radiotherapy (IMRT) plans. The aim of this study was to analyse the correlation between the γ passing rates and the volumes of air cavities (Vair) and bony structures (Vbone) in target volume of head and neck cancer. METHODS: Twenty nasopharyngeal carcinoma and twenty nasal natural killer T-cell lymphoma patients were enrolled in this study. Nine-field sliding window IMRT plans were produced and the dose distributions were calculated by anisotropic analytical algorithm (AAA), Acuros XB algorithm (AXB) and SciMoCa based on the Monte Carlo (MC) technique. The dose distributions and γ passing rates of the targets, organs at risk, air cavities and bony structures were compared among the different algorithms. RESULTS: The γ values obtained with AAA and AXB were 95.6 ± 1.9% and 96.2 ± 1.7%, respectively, with 3%/2 mm criteria (p > 0.05). There were significant differences (p < 0.05) in the γ values between AAA and AXB in the air cavities (86.6 ± 9.4% vs. 98.0 ± 1.7%) and bony structures (82.7 ± 13.5% vs. 99.0 ± 1.7%). Using AAA, the γ values were proportional to the natural logarithm of Vair (R2 = 0.674) and inversely proportional to the natural logarithm of Vbone (R2 = 0.816). When the Vair in the targets was smaller than approximately 80 cc or the Vbone in the targets was larger than approximately 6 cc, the γ values of AAA were below 95%. Using AXB, no significant relationship was found between the γ values and Vair or Vbone. CONCLUSION: In clinical head and neck IMRT QA, greater attention should be paid to the effect of Vair and Vbone in the targets on the γ passing rates when using different dose calculation algorithms.


Asunto(s)
Huesos/patología , Neoplasias de Cabeza y Cuello/patología , Linfoma Extranodal de Células NK-T/patología , Carcinoma Nasofaríngeo/patología , Órganos en Riesgo/efectos de la radiación , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Algoritmos , Huesos/efectos de la radiación , Rayos gamma , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Linfoma Extranodal de Células NK-T/radioterapia , Método de Montecarlo , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/radioterapia , Pronóstico , Dosificación Radioterapéutica
20.
Pharmacol Res ; 169: 105612, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33865986

RESUMEN

Inconsistencies exist with regard to influence of tibolone treatment on the lipid profile. The reasons for these inconsistencies might derive from several factors, i.e., differences in baseline variables, intervention duration, participants' health status or baseline body mass index (BMI). To address these inconsistencies, based on a systematic search in Scopus, PubMed/Medline, Web of Science, and Embase for papers published until 21 December 2020, we conducted the current dose-response meta-analysis of randomized controlled trials (RCTs) to determine the impact of tibolone treatment on the lipid profile. The overall findings were derived from 26 RCTs. Tibolone administration decreased total cholesterol (TC) (weighted mean difference, WMD: -18.55 mg/dL, CI: -25.95 to -11.16, P < 0.001), high-density lipoprotein-cholesterol (HDL-C) (WMD: -9.42 mg/dL, CI: -11.83 to -7.01, P < 0.001) and triglyceride (TG) (WMD: -21.43 mg/dL, CI: -27.15 to -15.70, P < 0.001) levels. A significant reduction in LDL-C occurred when tibolone was prescribed for ≤ 26 weeks (WMD: -7.64 mg/dL, 95% CI: -14.58 to -0.70, P = 0.031) versus > 26 weeks (WMD: -8.84 mg/dL, 95% CI: -29.98, 12.29, P = 0.412). The decrease in TG (WMD: -22.64 mg/dL) and TC (-18.55 mg/dL) concentrations was more pronounced in patients with BMI ≥ 25 kg/m2versus BMI < 25 kg/m2. This systematic review and meta-analysis discovered that tibolone decreases TC, HDL-C and TG levels. LDL-C concentrations are significantly reduced when tibolone administration lasts for ≤ 26 weeks.


Asunto(s)
Lípidos/sangre , Norpregnenos/efectos adversos , Relación Dosis-Respuesta a Droga , Terapia de Reemplazo de Estrógeno/efectos adversos , Femenino , Humanos , Norpregnenos/farmacología , Norpregnenos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto
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