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1.
J Neurophysiol ; 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39258777

RESUMEN

The central auditory system encompasses two primary functions: identification and localization. Spatial release from masking (SRM) highlights speech recognition in competing noise and improves the listening experience when a spatial cue is introduced between noise and target speech. This assessment focuses on the integrity of auditory function and holds clinical significance. However, infants or pre-lingual subjects sometimes provide less reliable results. This study investigates the value of cortical auditory evoked potentials (CAEPs) onset and acoustic change complex (ACC) as an objective measurement of SRM. Thirty normal-hearing young adults (11 males) were recruited. We found the spatial separation of signals and noise (±90 degrees symmetrically) resulted in a signal-to-noise ratio (SNR) improvement of 9.00 ± 1.71 dB behaviorally. It significantly enhanced cortical processing at all SNR levels, shortened CAEPs latencies, and increased amplitudes, resulting in a greater number of measurable peaks for ACC. SRM showed mild to moderate correlations with the differences between the two conditions in CAEP measures. The regression model combining N1'-P2' amplitude at 5 dB SNR (R2 = 0.26), P1 amplitude at 0 dB SNR (R2 = 0.14), and P1 latency at -5 dB SNR (R2 = 0.15), explained 45.3% of the variance in SRM. Our study demonstrates that introducing spatial cues can improve speech perception and enhance central auditory processing in normal-hearing young adults. CAEPs may contribute to predictions about SRM and hold potential for practical application.

2.
Phys Med ; 124: 104492, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39094213

RESUMEN

PURPOSE: The purpose of the study is to investigate the clinical application of deep learning (DL)-assisted automatic radiotherapy planning for lung cancer. METHODS: A DL model was developed for predicting patient-specific doses, trained and validated on a dataset of 235 patients with diverse target volumes and prescriptions. The model was integrated into clinical workflow with DL-predicted objective functions. The automatic plans were retrospectively designed for additional 50 treated manual volumetric modulated arc therapy (VMAT) plans. A comparison was made between automatic and manual plans in terms of dosimetric indexes, monitor units (MUs) and planning time. Plan quality metric (PQM) encompassing these indexes was evaluated, with higher PQM values indicating superior plan quality. Qualitative evaluations of two plans were conducted by four reviewers. RESULTS: The PQM score was 40.7 ± 13.1 for manual plans and 40.8 ± 13.5 for automatic plans (P = 0.75). Compared to manual plans, the targets coverage and homogeneity of automatic plans demonstrated no significant difference. Manual plans exhibited better sparing for lung in V5 (difference: 1.8 ± 4.2 %, P = 0.02), whereas automatic plans showed enhanced sparing for heart in V30 (difference: 1.4 ± 4.7 %, P = 0.02) and for spinal cord in Dmax (difference: 0.7 ± 4.7 Gy, P = 0.04). The planning time and MUs of automatic plans were significantly reduced by 70.5 ± 20.0 min and 97.4 ± 82.1. Automatic plans were deemed acceptable in 88 % of the reviews (176/200). CONCLUSIONS: The DL-assisted approach for lung cancer notably decreased planning time and MUs, while demonstrating comparable or superior quality relative to manual plans. It has the potential to provide benefit to lung cancer patients.


Asunto(s)
Automatización , Aprendizaje Profundo , Neoplasias Pulmonares , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Neoplasias Pulmonares/radioterapia , Humanos , Planificación de la Radioterapia Asistida por Computador/métodos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Órganos en Riesgo/efectos de la radiación
3.
Int J Audiol ; : 1-10, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39162810

RESUMEN

OBJECTIVE: We have shown that the acoustic change complex (ACC) can be elicited by changing the horizontal sound location in young individuals. In this study, we aimed to evaluate the application of ACC within the elderly and its relationship with behavioural results. DESIGN: The minimum audible angle (MAA), as well as onset cortical auditory evoked potentials (onset-CAEPs) and ACC elicited by the stimuli of location-change white noise (±45 to ±2 degrees) were recorded. Latencies and amplitudes were analysed using repeated-measures ANOVA. Pearson correlation analysis was conducted to examine the relationship between ACC and MAA. STUDY SAMPLE: Ten older adults with normal hearing (NH) and twenty with presbycusis. RESULTS: The ACC was effectively elicited with angular variations in elderly participants. The onset-CAEP N1 latency, ACC N1'-P2' amplitude, and N1' latency were all associated with the angle shifts, with the N1' latency being the most predictive factor for angle discrimination. The consistency between MAA and ACC made them complementary for the clinical evaluation of sound localisation. CONCLUSIONS: The utilisation of ACC, evoked by location-change sounds, presented a promising clinical objective measure for evaluating sound localisation abilities in the elderly.

4.
ISA Trans ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39168768

RESUMEN

In this paper, an adaptive dynamic surface (DSC) guidance law for missile is designed to intercept the maneuvering target with field-of-view (FOV) and terminal angle constraints in three-dimensional(3D) space, and the missile autopilot dynamics is considered. Firstly, the time-varying transformation function related to line of sight (LOS) is used to replace the FOV constraints, transforming the process-constrained control problem into the output-constrained control problem. Meanwhile, the 3D coupled relative kinematics model considering missile autopilot dynamics and maneuvering target acceleration is established. Secondly, a novel time-varying asymmetric barrier Lyapunov function (TABLF) with dead-zone characteristics is introduced to the adaptive dynamic surface guidance law design process to improve the robustness of parameter debugging. Thirdly, with the help of a nonlinear adaptive filter, the 'explosion of complexity' problem can be avoided effectively, which is caused by analytic computation of virtual signal derivatives. Furthermore, aiming at the problem of autopilot dynamic errors, target acceleration disturbances, and unmeasurable parameters in the model, a novel adaptive law is used to evaluate online. Then, the stability of the closed-loop system is rigorously proven using Lyapunov criteria. Ultimately, Numerical simulations with various constraints and comparison studies have been considered to show the feasibility and effectiveness of the proposed missile guidance law.

5.
Front Neurol ; 15: 1414738, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39081341

RESUMEN

Unilateral auditory deprivation (UAD) results in cross-modal reorganization of the auditory cortex (AC), which can impair auditory and cognitive functions and diminish the recovery effect of cochlear implantation. Moreover, the subcortical areas provide extensive ascending projections to the AC. To date, a thorough systematic study of subcortical auditory neural plasticity has not been undertaken. Therefore, this review aims to summarize the current evidence on the bidirectional remodeling of the central auditory system caused by UAD, particularly the changes in subcortical neural plasticity. Lateral changes occur in the cochlear nucleus, lateral superior olive, medial nucleus of the trapezoid body, inferior colliculus, and AC of individuals with UAD. Moreover, asymmetric neural activity becomes less prominent in the higher auditory nuclei, which may be due to cross-projection regulation of the bilateral pathway. As a result, subcortical auditory neural plasticity caused by UAD may contribute to the outcomes of cochlear implantation in patients with single-sided deafness (SSD), and the development of intervention strategies for patients with SSD is crucial. Considering that previous studies have focused predominantly on the neural plasticity of the AC, we believe that bidirectional remodeling of subcortical areas after UAD is also crucial for investigating the mechanisms of interventions.

7.
Bioorg Chem ; 148: 107427, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38728911

RESUMEN

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin-proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC50) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin-proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.


Asunto(s)
Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ubiquitina-Proteína Ligasas , Factores de Transcripción p300-CBP , Humanos , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Factores de Transcripción p300-CBP/metabolismo , Factores de Transcripción p300-CBP/antagonistas & inhibidores , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Relación Estructura-Actividad , Estructura Molecular , Apoptosis/efectos de los fármacos , Línea Celular Tumoral
8.
Health Phys ; 127(3): 386-391, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38683685

RESUMEN

ABSTRACT: Boron neutron capture therapy (BNCT) is an ideal binary targeted radiotherapy for treating refractory tumors. An accelerator-based BNCT (AB-BNCT) neutron source has attracted more and more attention due to its advantages such as higher neutron yield in the keV energy region, less gamma radiation, and higher safety. In addition to 10 B, neutrons also react with other elements in the treatment room during BNCT to produce many activation products. Due to the long half-life of some activation products, there will be residual radiation after the end of treatment and the shutdown of the accelerator, which has adverse effects on radiation workers. Therefore, the ambient dose equivalent rate in the treatment room needs to be evaluated. The AB-BNCT neutron source model proposed by Li is studied in this paper. Based on the Monte Carlo method, the Geant4 platform was used to simulate the dose induced by radionuclides near the Beam Shaping Assembly (BSA) of the source. It is concluded that the concrete wall contributed the most to the radiation dose. The dose rate of 2.45 µSv h -1 after 13 min of shutdown meets the dose rate limit of 2.5 µSv h -1 , at which point it is safe for workers to enter the treatment room area.


Asunto(s)
Terapia por Captura de Neutrón de Boro , Método de Montecarlo , Terapia por Captura de Neutrón de Boro/métodos , Humanos , Análisis de Activación de Neutrones/métodos , Dosis de Radiación , Neutrones , Aceleradores de Partículas , Exposición Profesional/análisis , Dosificación Radioterapéutica
9.
Ear Nose Throat J ; : 1455613241238829, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38590173

RESUMEN

Cochlear implantation (CI) is the most effective solution for patients with severe-to-profound sensorineural hearing loss, especially in children. However, a major postoperative complication, known as chronic suppurative otitis media (CSOM), poses challenges for both doctors and families of the patients, which can affect post-CI hearing outcomes. We present the case of post-CI CSOM in a 15-year-old girl. She had been utilizing a unilateral cochlear implant for 7 years and had been experiencing intermittent earache and discharge in her only audible ear for the past 15 months. After antibiotic treatment failed to resolve her symptoms, we opted for a tympanomastoidectomy, and removed the receiver-stimulator package while keeping the electrode inside her cochlea. Simultaneously, we inserted an irrigation and drainage tube into the mastoid and middle ear space to discharge the exudate and control infection by applying topical antibiotics. The patient's ear discharge had resolved within 1 month, and her tympanic membrane healed naturally. Our successful experience shows that antibiotic irrigation and draining have effectively controlled infection and accelerated wound healing in this patient with post-CI CSOM, and it further prompted the patient to undergo bilateral CI 9 months later.

10.
Front Hum Neurosci ; 18: 1342931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681742

RESUMEN

Objectives: The auditory spatial processing abilities mature throughout childhood and degenerate in older adults. This study aimed to compare the differences in onset cortical auditory evoked potentials (CAEPs) and location-evoked acoustic change complex (ACC) responses among children, adults, and the elderly and to investigate the impact of aging and development on ACC responses. Design: One hundred and seventeen people were recruited in the study, including 57 typically-developed children, 30 adults, and 30 elderlies. The onset-CAEP evoked by white noise and ACC by sequential changes in azimuths were recorded. Latencies and amplitudes as a function of azimuths were analyzed using the analysis of variance, Pearson correlation analysis, and multiple linear regression model. Results: The ACC N1'-P2' amplitudes and latencies in adults, P1'-N1' amplitudes in children, and N1' amplitudes and latencies in the elderly were correlated with angles of shifts. The N1'-P2' and P2' amplitudes decreased in the elderly compared to adults. In Children, the ACC P1'-N1' responses gradually differentiated into the P1'-N1'-P2' complex. Multiple regression analysis showed that N1'-P2' amplitudes (R2 = 0.33) and P2' latencies (R2 = 0.18) were the two most variable predictors in adults, while in the elderly, N1' latencies (R2 = 0.26) explained most variances. Although the amplitudes of onset-CAEP differed at some angles, it could not predict angle changes as effectively as ACC responses. Conclusion: The location-evoked ACC responses varied among children, adults, and the elderly. The N1'-P2' amplitudes and P2' latencies in adults and N1' latencies in the elderly explained most variances of changes in spatial position. The differentiation of the N1' waveform was observed in children. Further research should be conducted across all age groups, along with behavioral assessments, to confirm the relationship between aging and immaturity in objective ACC responses and poorer subjective spatial performance. Significance: ACCs evoked by location changes were assessed in adults, children, and the elderly to explore the impact of aging and development on these differences.

11.
J Med Chem ; 67(5): 3244-3273, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38421819

RESUMEN

Camptothecin (CPT) is a potent anti-cancer agent targeting topoisomerase I (TOP1). However, CPT has poor pharmacokinetic properties, causes toxicities, and leads to drug resistance, which limit its clinical use. In this paper, to review the current state of CPT research. We first briefly explain CPT's TOP1 inhibition mechanism and the key hurdles in CPT drug development. Then we examine strategies to overcome CPT's limitations through structural modifications and advanced delivery systems. Though modifications alone seem insufficient to fully enhance CPT's therapeutic potential, structure-activity relationship analysis provides insights to guide optimization of CPT analogs. In comparison, advanced delivery systems integrating controlled release, imaging capabilities, and combination therapies via stimulus-responsive linkers and targeting moieties show great promise for improving CPT's pharmacological profile. Looking forward, multifaceted approaches combining selective CPT derivatives with advanced delivery systems, informed by emerging biological insights, hold promise for fully unleashing CPT's anti-cancer potential.


Asunto(s)
Antineoplásicos Fitogénicos , Camptotecina , Camptotecina/farmacología , Camptotecina/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos Fitogénicos/química , Inhibidores de Topoisomerasa I/farmacología , Inhibidores de Topoisomerasa I/uso terapéutico , ADN-Topoisomerasas de Tipo I/metabolismo
12.
J Neurosci ; 44(10)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38326037

RESUMEN

The inferior colliculus (IC) represents a crucial relay station in the auditory pathway, located in the midbrain's tectum and primarily projecting to the thalamus. Despite the identification of distinct cell classes based on various biomarkers in the IC, their specific contributions to the organization of auditory tectothalamic pathways have remained poorly understood. In this study, we demonstrate that IC neurons expressing parvalbumin (ICPV+) or somatostatin (ICSOM+) represent two minimally overlapping cell classes throughout the three IC subdivisions in mice of both sexes. Strikingly, regardless of their location within the IC, these neurons predominantly project to the primary and secondary auditory thalamic nuclei, respectively. Cell class-specific input tracing suggested that ICPV+ neurons primarily receive auditory inputs, whereas ICSOM+ neurons receive significantly more inputs from the periaqueductal gray and the superior colliculus (SC), which are sensorimotor regions critically involved in innate behaviors. Furthermore, ICPV+ neurons exhibit significant heterogeneity in both intrinsic electrophysiological properties and presynaptic terminal size compared with ICSOM+ neurons. Notably, approximately one-quarter of ICPV+ neurons are inhibitory neurons, whereas all ICSOM+ neurons are excitatory neurons. Collectively, our findings suggest that parvalbumin and somatostatin expression in the IC can serve as biomarkers for two functionally distinct, parallel tectothalamic pathways. This discovery suggests an alternative way to define tectothalamic pathways and highlights the potential usefulness of Cre mice in understanding the multifaceted roles of the IC at the circuit level.


Asunto(s)
Colículos Inferiores , Parvalbúminas , Femenino , Masculino , Ratones , Animales , Parvalbúminas/metabolismo , Colículos Inferiores/fisiología , Neuronas/fisiología , Vías Auditivas/fisiología , Somatostatina/metabolismo
13.
Eur J Med Chem ; 264: 115943, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38039793

RESUMEN

PARP-1 is a crucial factor in repairing DNA single strand damage and maintaining genomic stability. However, the use of PARP-1 inhibitors is limited to combination with chemotherapy or radiotherapy, or as a single agent for indications carrying HRR defects. The ubiquitin-proteasome system processes the majority of cellular proteins and is the principal manner by which cells regulate protein homeostasis. Proteasome inhibitors can cooperate with PARP-1 inhibitors to inhibit DNA homologous recombination repair function. In this study, we designed and synthesized the first dual PARP-1 and proteasome inhibitor based on Olaparib and Ixazomib. Both compounds 42d and 42i exhibited excellent proliferation inhibition and dual-target synergistic effects on cells that were insensitive to PARP-1 inhibitors. Further mechanistic evaluations revealed that 42d and 42i could inhibit homologous recombination repair function by down-regulating the expression of BRCA1 and RAD51. Additionally, 42i induced more significant apoptosis and showed better inhibitory effect on cell proliferation in clonal formation experiments in breast cancer cells than 42d. In summary, our study presented a new class of dual PARP-1/proteasome inhibitors with significant synergistic effects for the treatment of breast cancer.


Asunto(s)
Neoplasias de la Mama , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Inhibidores de Proteasoma/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Complejo de la Endopetidasa Proteasomal , Línea Celular Tumoral , ADN , Ftalazinas/farmacología , Ftalazinas/uso terapéutico
14.
Mol Cell Biochem ; 479(4): 831-841, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37199893

RESUMEN

Metastasis is the cause of poor prognosis in ovarian cancer (OC). Enhancer of Zeste homolog 2 (EZH2), a histone-lysine N-methyltransferase enzyme, promotes OC cell migration and invasion by regulating the expression of tissue inhibitor of metalloproteinase-2 (TIMP2) and matrix metalloproteinases-9 (MMP9). Hence, we speculated that EZH2-targeting therapy might suppress OC migration and invasion. In this study, the expression of EZH2, TIMP2, and MMP9 in OC tissues and cell lines was analyzed using The Cancer Genome Atlas (TCGA) database and western blotting, respectively. The effects of SKLB-03220, an EZH2 covalent inhibitor, on OC cell migration and invasion were investigated using wound-healing assays, Transwell assays, and immunohistochemistry. TCGA database analysis confirmed that the EZH2 and MMP9 mRNA expression was significantly higher in OC tissues, whereas TIMP2 expression was significantly lower than that in normal ovarian tissues. Moreover, EZH2 negatively correlated with TIMP2 and positively correlated with MMP9 expression. In addition to the anti-tumor activity of SKLB-03220 in a PA-1 xenograft model, immunohistochemistry results showed that SKLB-03220 markedly increased the expression of TIMP2 and decreased the expression of MMP9. Additionally, wound-healing and Transwell assays showed that SKLB-03220 significantly inhibited the migration and invasion of both A2780 and PA-1 cells in a concentration-dependent manner. SKLB-03220 inhibited H3K27me3 and MMP9 expression and increased TIMP2 expression in PA-1 cells. Taken together, these results indicate that the EZH2 covalent inhibitor SKLB-03220 inhibits metastasis of OC cells by upregulating TIMP2 and downregulating MMP9, and could thus serve as a therapeutic agent for OC.


Asunto(s)
Acrilamidas , Proteína Potenciadora del Homólogo Zeste 2 , Neoplasias Ováricas , Humanos , Femenino , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Neoplasias Ováricas/genética , Línea Celular Tumoral , Inhibidor Tisular de Metaloproteinasa-2/genética , Inhibidor Tisular de Metaloproteinasa-2/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Movimiento Celular/genética , Proliferación Celular , Regulación Neoplásica de la Expresión Génica
15.
Journal of Preventive Medicine ; (12): 562-566,570, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1039404

RESUMEN

Objective@#To explore the influencing factors for depressive symptoms in adolescents in China, so as to provide insights into promoting mental health of adolescents.@*Methods@#The 2020 follow-up survey data of China Family Panel Studies were collected, including demographic information, lifestyle, family factors and academic factors of adolescents aged 10-19 years. Depressive symptoms were evaluated using the 8-item Center for Epidemiological Studies Depression Scale. The influencing factors for depressive symptoms in adolescents were analyzed using a multivariable logistic regression model.@*Results@#A total of 2 777 adolescents were analyzed, including 1 470 males (52.93%) and 1 307 females (47.07%). There were 1 186 adolescents (42.71%) from urban areas and 1 591 adolescents (57.29%) from rural areas, 106 smokers (3.82%), and 459 adolescents (16.53%) with depressive symptoms. Multivariable logistic regression analysis showed that academic stress (OR=1.268, 95%CI: 1.151-1.396), poor self-rated health (OR=1.255, 95%CI: 1.116-1.411), smoking (OR=1.901, 95%CI: 1.127-3.207), low trust in parents (OR=0.780, 95%CI: 0.729-0.835) and large family size (OR=1.095, 95%CI: 1.035-1.158) were associated with an increased risk of depressive symptoms in adolescents.@*Conclusion@#The influencing factors for depressive symptoms in adolescents were academic stress, self-rated health, smoking, trust in parents and family size.

16.
Microsyst Nanoeng ; 9: 121, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37786899

RESUMEN

Liquid biopsy of cancers, detecting tumor-related information from liquid samples, has attracted wide attentions as an emerging technology. Our previously reported large-area PERFECT (Precise-Efficient-Robust-Flexible-Easy-Controllable-Thin) filter has demonstrated competitive sensitivity in recovering rare tumor cells from clinical samples. However, it is time-consuming and easily biased to manually inspect rare target cells among numerous background cells distributed in a large area (Φ ≥ 13 mm). This puts forward an urgent demand for rapid and bias-free inspection. Hereby, this paper implemented deep learning-based object detection for the inspection of rare tumor cells from large-field images of PERFECT filters with hematoxylin-eosin (HE)-stained cells recovered from bronchoalveolar lavage fluid (BALF). CenterNet, EfficientDet, and YOLOv5 were trained and validated with 240 and 60 image blocks containing tumor and/or background cells, respectively. YOLOv5 was selected as the basic network given the highest mAP@0.5 of 92.1%, compared to those of CenterNet and EfficientDet at 85.2% and 91.6%, respectively. Then, tricks including CIoU loss, image flip, mosaic, HSV augmentation and TTA were applied to enhance the performance of the YOLOv5 network, improving mAP@0.5 to 96.2%. This enhanced YOLOv5 network-based object detection, named as BALFilter Reader, was tested and cross-validated on 24 clinical cases. The overall diagnosis performance (~2 min) with sensitivity@66.7% ± 16.7%, specificity@100.0% ± 0.0% and accuracy@75.0% ± 12.5% was superior to that from two experienced pathologists (10-30 min) with sensitivity@61.1%, specificity@16.7% and accuracy@50.0%, with the histopathological result as the gold standard. The AUC of the BALFilter Reader is 0.84 ± 0.08. Moreover, a customized Web was developed for a user-friendly interface and the promotion of wide applications. The current results revealed that the developed BALFilter Reader is a rapid, bias-free and easily accessible AI-enabled tool to promote the transplantation of the BALFilter technique. This work can easily expand to other cytopathological diagnoses and improve the application value of micro/nanotechnology-based liquid biopsy in the era of intelligent pathology.

17.
Eur J Med Chem ; 258: 115628, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37437349

RESUMEN

Fibroblast growth factor receptor 4 (FGFR4) has been proved to be an effective target for cancer therapy. Aberration in FGF19/FGFR4 signaling is oncogenic driving force in human hepatocellular carcinoma (HCC). FGFR4 gatekeeper mutations induced acquired resistance remains an unmet clinical challenge for HCC treatment. In this study, a series of 1H-indazole derivatives were designed and synthesized as new irreversible inhibitors of wild-type and gatekeeper mutant FGFR4. These new derivatives showed significant FGFR4 inhibitory and antitumor activities, among which compound 27i was demonstrated to be the most potent compound (FGFR4 IC50 = 2.4 nM). Remarkably, compound 27i exhibited no activity against a panel of 381 kinases at 1 µM. Additionally, compound 27i displayed nanomolar IC50s against huh7 (IC50 = 21 nM) and two mutant cell lines, BaF3/ETV6-FGFR4-V550L and BaF3/ETV6-FGFR4-N535K (IC50 = 2.5/171 nM). Meanwhile, compound 27i exhibited potent antitumor potency (TGI: 83.0%, 40 mg/kg, BID) in Huh7 xenograft mouse models with no obvious toxicity observed. Overall, compound 27i was identified as a promising preclinical candidate for overcoming FGFR4 gatekeeper mutations for HCC treatment.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Proliferación Celular
18.
Cell Mol Biol (Noisy-le-grand) ; 69(1): 44-47, 2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-37213158

RESUMEN

The objective of this research was to analyze the miR-145 function in thyroid papillary carcinoma cells and explore its possible mechanism. For this purpose, the TPC-1 cell line was selected, miR-145 overexpression and rab5c shRNA lentiviral vector were constructed, and transfected into PTC cells. Luciferase reporter gene was performed to determine the relationship between miR-145 and rab5c, Western blot and qPCR were performed to detach the expression of the related genes, CCK-8 cell proliferation assay and Transwell cell invasion assay were used to determine the proliferation and invasion ability of PTC-1 cells. Results showed that MiR-145 overexpression inhibited the wt-rab5c (wild-type rab5c)luciferase activity, decreased the expression of rab5c mRNA and protein levels in the TPC-1 cell line, inhibited the proliferation and invasion of PTC cell line TPC-1(P < 0.05). In TPC-1 cells, both miR-145 overexpression and RNA interference with rab5c could increase the expression of the p-ERK protein (P < 0.05). In conclusion, MiR-145 inhibits the proliferation and invasion of PTC cells by downregulating rab5c and activating MAPK/ERK pathway in vitro.


Asunto(s)
Carcinoma Papilar , MicroARNs , Neoplasias de la Tiroides , Humanos , Sistema de Señalización de MAP Quinasas/genética , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Carcinoma Papilar/genética , Proliferación Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/patología , Transducción de Señal , Regulación Neoplásica de la Expresión Génica , Proteínas de Unión al GTP rab5/genética , Proteínas de Unión al GTP rab5/metabolismo
19.
Ear Nose Throat J ; : 1455613231170595, 2023 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-37041743

RESUMEN

OBJECTIVE: To explore the effect of cold-water irrigation on post-tonsillectomy pain after coblation. METHODS: Data from 61 adult patients who underwent coblation tonsillectomy in our hospital from January 2019 to December 2020 were collected, and the patients were randomly divided into the cold-water irrigation group (Group 1) and the room-temperature irrigation group (Group 2). Group 1 was irrigated with ice water mixed saline with the help of a pressure band, and Group 2 was irrigated with room-temperature saline. During the operation, we monitored the temperature of the operating cavity in real time. We recorded the postoperative pain for 11 consecutive days from the day and the 10th day after the operation. RESULTS: The postoperative pain score was significantly lower than that in Group 2, except on the 2nd, 3rd and 7th and 8th days after the operation. CONCLUSION: The perfusion of cold water during coblation tonsillectomy is helpful to reduce postoperative pain.

20.
J Sci Food Agric ; 103(11): 5422-5431, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37031963

RESUMEN

BACKGROUND: Probiotic food provide health benefits by regulating intestinal floras via live bacteria, but the shelf life is short and the preservation condition is demanding due to the bacteria being fragile. Owing to these problems, we have tried to find a fermented food that is helpful for inflammatory bowel disease treatment but independent of live bacteria. In addition, the mechanisms of fermented food were investigated. Dextran sulfate sodium was used to model inflammatory bowel disease in mice, and Lactobacillus paracasei TK1501 fermented soybeans and their metabolites were used to treat inflammatory bowel disease. RESULTS: In this study, TK1501 fermented soybean alleviated colitis. However, the efficacy was associated with bacterial metabolites but not live or dead bacteria. Compositional analysis of soybean before and after fermentation shows that soy carbohydrates were used for bacteria growth and produced functional substances. Further, we display the main active ingredient was lipoteichoic acid and peptidoglycan, because lipoteichoic acid reduced the colonic macrophage and peptidoglycan may increase the mucin-2 expression. A cell experiment displayed that lipoteichoic acid could enhance the phagocytosis of macrophages. CONCLUSION: In general, TK1501 fermented soybean alleviating colitis is dependent on metabolites of TK1501, particularly lipoteichoic acid and peptidoglycan. The fermented food may have a long shelf life and lax storage condition. © 2023 Society of Chemical Industry.


Asunto(s)
Colitis , Alimentos Fermentados , Enfermedades Inflamatorias del Intestino , Lacticaseibacillus paracasei , Probióticos , Animales , Ratones , Glycine max , Sulfato de Dextran/efectos adversos , Peptidoglicano/efectos adversos , Colitis/inducido químicamente , Colitis/microbiología , Probióticos/metabolismo , Modelos Animales de Enfermedad
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