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1.
Nanomaterials (Basel) ; 14(9)2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38727392

RESUMO

Lead-cooled fast reactors exhibit strong inherent safety performance and good economic features, while material degradation due to corrosion and irradiation is still challenging. Oxide dispersion-strengthened steels are one of the promising candidates for fuel cladding materials. The effects of both irradiation and corrosion on ODS steel need to be further studied. In this work, MX-ODS steel was irradiated by Fe ions at 500 °C up to 46 dpa. Later, the as-received specimen and the irradiated specimen were used to conduct corrosion tests in oxygen-saturated Pb at 550 °C for 1 h. In the as-received specimen, discontinuous oxides penetrated by Pb and Pb in contact with steel matrix were observed, demonstrating unsatisfactory corrosion resistance of the material. However, in the irradiated specimen after corrosion experiment, a protective oxide layer formed and prevented Pb attack. The oxidation behavior differences between the two specimens can be attributed to the defects produced by irradiation and the structural discrepancy in oxides caused by the formation process. A possible mechanism of irradiation on the corrosion is discussed. In the as-received specimen, Fe atoms loss led to voids in the oxides, and lead penetrated the oxides through these voids. In the irradiated specimen, defects left by previous irradiation helped to form a more uniform oxide layer. The adhesive outer magnetite oxide and the Fe ions generated from where grain boundary oxidation developed retarded the presence of voids and made the oxide layer protective.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38560773

RESUMO

Research on new ingredients that can prevent excessive melanin production in the skin while considering efficacy, safety but also environmental impact is of great importance to significantly improve the profile of existing actives on the market and avoid undesirable side effects. Here, the discovery of an innovative technology for the management of hyperpigmentation is described. High-throughput screening tests on a wide chemical diversity of molecules and in silico predictive methodologies were essential to design an original thiopyridinone backbone and select 2-mercaptonicotinoyl glycine (2-MNG) as exhibiting the most favorable balance between the impact on water footprint, skin penetration potential and performance. The effectiveness of 2-MNG was confirmed by topical application on pigmented reconstructed epidermis and human skin explants. In addition, experiments have shown that unlike most melanogenesis inhibitors on the market, this molecule is not a tyrosinase inhibitor. 2-MNG binds to certain melanin precursors, preventing their integration into growing melanin and leading to inhibition of eumelanin and pheomelanin synthesis, without compromising the integrity of melanocytes.

3.
Europace ; 26(4)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38584395

RESUMO

AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7 ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8 min, and fluoroscopy time was 13.1 ± 7.6 min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Catéteres , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Fenômenos Magnéticos , Recidiva
5.
Scand J Clin Lab Invest ; : 1-9, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683948

RESUMO

Early and differential diagnosis of sepsis is essential to avoid unnecessary antibiotic use and further reduce patient morbidity and mortality. Here, we aimed to identify predictors of sepsis and advance a machine-learning strategy to predict sepsis-induced respiratory tract infection (RTI). Patients with sepsis and RTI were selected via retrospective analysis, and essential population characteristics and laboratory parameters were recorded. To improve the performance of the primary model and avoid over-fitting, a recursive feature elimination with cross-validation (RFECV) strategy was used to screen the optimal subset of biomarkers and construct nine machine-learning models based on this subset; the average accuracy, precision, recall, and F1-score were used for evaluation of the models. We identified 430 patients with sepsis and 686 patients with RTI. A total of 39 features were collected, with 23 features identified for initial model construction. Using the RFECV algorithm, we found that the XGBoost classifier, which only needed to include seven biomarkers, demonstrated the best performance among all prediction models, with an average accuracy of 89.24 ± 2.28, while the Ridge classifier, which included 11 biomarkers, had an average accuracy of only 83.87 ± 4.69. The remaining models had prediction accuracies greater than 88%. We developed nine models for predicting sepsis using a strategy that combined RFECV with machine learning. Among these models, the XGBoost classifier, which included seven biomarkers, showed the best performance and highest accuracy for predicting sepsis and may be a promising tool for the timely identification of sepsis.

6.
Heliyon ; 10(5): e27057, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463868

RESUMO

Objective: This study aimed to analyze the clinical characteristics of birth weight discordant twins (BWDT) who were premature and appropriate-for-gestational-age or large-for-gestational-age. Additionally, it assessed the impact of birth weight discordance on the prognosis of appropriately grown premature twins, and investigated the effect of maternal factors on neonatal outcomes. Study design: This retrospective cohort study included twins who were born alive after preterm labor at the Nanjing Drum Tower Hospital from January 2018 to December 2021, along with their mothers. Twins were arranged into discordant and concordant groups according to intertwin birth weight discordance, followed by the analysis of the clinical characteristics of mothers and the prognosis of neonates. Results: A total of 585 mothers and 1170 neonates were included, with 47 mothers and 94 neonates in the discordant group. The incidence of birth weight discordance was 8.0% (94/1,170) in appropriately grown premature twins. The incidence of complications (43.2% vs. 21.8%) and transfer to the neonatal intensive care unit (NICU) (53.2% vs. 29.2%) was higher in the discordant group than in the concordant group (p < 0.05). Furthermore, the incidence of infectious diseases (36.7% vs. 19.4%), necrotizing enterocolitis (7.6% vs. 1.6%), and oxygen therapy rate (22.8% vs. 12.8%) were statistically significantly higher in the discordant group than in the concordant group (p < 0.05). Conclusion: Birth weight discordance remains a high-risk factor for complications and transfer to the NICU in appropriately grown premature twins. It is important to pay attention to birth weight discordance when the outcomes of twins are assessed.

7.
J Environ Manage ; 357: 120663, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38552509

RESUMO

Wetlands, as core habitats for supporting waterbird diversity, provide a variety of ecosystem services through diverse ecosystem functioning. Wetland degradation and wetland-habitat loss undermine the relationship between biodiversity-ecosystem functioning (BEF), affecting the diversity of habitats and waterbirds. The conservation of waterbird diversity is closely linked to the proper functioning of wetland ecosystems (nutrient cycling, energy storage, and productivity). Waterbirds have complex habitat preferences and sensitivities, which affect biotic interactions. By highlighting the importance of temporal and spatial scales guided by BEF, a habitat-waterbird conservation framework is presented (BEF relationships are described at three levels: habitat, primary producers, and waterbird diversity). We present a novel perspective on habitat conservation for waterbirds by incorporating research on the effects of biodiversity and ecosystem functioning to address the crucial challenges in global waterbird diversity loss, ecosystem degradation, and habitat conservation. Last, it is imperative to prioritize strategies of habitat protection with the incorporation of BEF for future waterbird conservation.


Assuntos
Ecossistema , Áreas Alagadas , Conservação dos Recursos Naturais , Biodiversidade , Ciclismo
8.
J Transl Med ; 22(1): 266, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468254

RESUMO

BACKGROUND: The clinical routine test of HBV-specific T cell reactivity is still limited due to the high polymorphisms of human leukocyte antigens (HLA) in patient cohort and the lack of universal detection kit, thus the clinical implication remains disputed. METHODS: A broad-spectrum peptide library, which consists of 103 functionally validated CD8+ T-cell epitopes spanning overall HBsAg, HBeAg, HBx and HBpol proteins and fits to the HLA polymorphisms of Chinese and Northeast Asian populations, was grouped into eight peptide pools and was used to establish an ELISpot assay for enumerating the reactive HBV-specific T cells in PBMCs. Totally 294 HBV-infected patients including 203 ones with chronic hepatitis B (CHB), 13 ones in acute resolved stage (R), 52 ones with liver cirrhosis (LC) and 26 ones with hepatocellular carcinoma (HCC) were detected, and 33 CHB patients were longitudinally monitored for 3 times with an interval of 3-5 months. RESULTS: The numbers of reactive HBV-specific T cells were significantly correlated with ALT level, HBsAg level, and disease stage (R, CHB, LC and HCC), and R patients displayed the strongest HBV-specific T cell reactivity while CHB patients showed the weakest one. For 203 CHB patients, the numbers of reactive HBV-specific T cells presented a significantly declined trend when the serum viral DNA load, HBsAg, HBeAg or ALT level gradually increased, but only a very low negative correlation coefficient was defined (r = - 0.21, - 0.21, - 0.27, - 0.079, respectively). Different Nucleotide Analogs (NUCs) did not bring difference on HBV-specific T cell reactivity in the same duration of treatment. NUCs/pegIFN-α combination led to much more reactive HBV-specific T cells than NUCs monotherapy. The dynamic numbers of reactive HBV-specific T cells were obviously increasing in most CHB patients undergoing routine treatment, and the longitudinal trend possess a high predictive power for the hepatitis progression 6 or 12 months later. CONCLUSION: The presented method could be developed into an efficient reference method for the clinical evaluation of cellular immunity. The CHB patients presenting low reactivity of HBV-specific T cells have a worse prognosis for hepatitis progression and should be treated using pegIFN-α to improve host T-cell immunity.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Neoplasias Hepáticas , Humanos , Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Antígenos E da Hepatite B , Biblioteca de Peptídeos , Epitopos de Linfócito T/uso terapêutico , Cirrose Hepática , DNA Viral
9.
ACS Appl Mater Interfaces ; 16(13): 15809-15818, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38515315

RESUMO

Human amniotic membranes (hAMs) are widely used as wound management biomaterials, especially as grafts for corneal reconstruction due to the structure of the extracellular matrix and excellent biological properties. However, their fragile nature and rapid degradation rate hinder widespread clinical use. In this work, we engineered a novel self-powered electronic dress (E-dress), combining the beneficial properties of an amniotic membrane and a flexible electrical electrode to enhance wound healing. The E-dress displayed a sustained discharge capacity, leading to increased epidermal growth factor (EGF) release from amniotic mesenchymal interstitial stem cells. Live/dead staining, CCK-8, and scratch-wound-closure assays were performed in vitro. Compared with amniotic membrane treatment alone, the E-dress promoted cell proliferation and migration of mouse fibroblast cells and lower cytotoxicity. In a mouse full-skin defect model, the E-dress achieved significantly accelerated wound closure. Histological analysis revealed that E-dress treatment promoted epithelialization and neovascularization in mouse skin. The E-dress exhibited a desirable flexibility that aligned with tissue organization and displayed maximum bioactivity within a short period to overcome rapid degradation, implying great potential for clinical applications.


Assuntos
Âmnio , Cicatrização , Camundongos , Animais , Humanos , Âmnio/metabolismo , Pele , Reepitelização , Matriz Extracelular
10.
Cureus ; 16(2): e54620, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523965

RESUMO

BACKGROUND:  It has already been demonstrated by previous studies that Baduanjin training can improve the body's balance. However, its biomechanical mechanism remains unknown. Center of gravity (COG) trajectory analysis is an essential biomechanical test to explore the balance ability of the human body. Previous studies have not used the COG trajectory analysis technique to research Baduanjin training. The study utilizes COG trajectory analysis to analyze the trajectory of COG during Baduanjin training and compare it with that of walking, which is a common exercise for improving balance and aerobic ability, to determine if Baduanjin exercises affect the COG more than walking. MATERIALS AND METHODS:  Eight healthy female college students performed the walking and the eight forms of Baduanjin, a total of nine motions. The lower body kinematics were captured by the Vicon Motion Capture and Analysis System, while the kinetic data were acquired by the Kistler 3D Force Platform. The data were imported into Visual 3D to process the trajectory of the COG displacement amplitude, velocity, and acceleration of each motion. The COG horizontal envelope areas were calculated by Origin 9.0 Software (Origin Lab, Northampton, Massachusetts, USA) . RESULTS: Specific motions of Baduanjin provided significantly higher COG displacement amplitude, velocities, and acceleration training than walking. The F2 and F5 motions could provide a larger COG horizontal envelope area than walking. On the x-axis, F2 provided a greater COG displacement amplitude than walking, F1, F2, and F5 provided greater velocities, while all the motions provided greater accelerations. On the y-axis, all the motions except F2 provided greater COG displacement velocities and accelerations than walking. On the z-axis, F1-7 provided a greater COG displacement amplitude than walking, all the motions provided greater velocities, while all the motions except F2 provided greater accelerations. CONCLUSION: Baduanjin training provides a more intense COG perturbation than walking, which may be a more challenging balance training than walking.

12.
Materials (Basel) ; 17(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38399195

RESUMO

This study focuses on the Medical Isotope Production Reactor (MIPR), an aqueous homogeneous reactor utilized for synthesizing medical isotopes like 99Mo. A pivotal aspect of MIPR's functionality involves the fuel solution's complex chemical interactions, particularly during reactor operation. These interactions result in the formation of precipitates, notably water filamentous uranium ore and columnar uranium ore, which can impact reactor performance. The research presented here delves into the reactions between liquid fuel uranyl nitrate and key radiolytic products, employing simulation calculations complemented by experimental validation. This approach facilitates the identification of uranium precipitate types and their formation conditions under operational reactor settings. Additionally, the article explores strategies to mitigate the formation of specific uranium precipitates, thereby contributing to the efficient and stable operation of MIPR.

13.
Inorg Chem ; 63(8): 3642-3647, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38346447

RESUMO

Two X-ray scintillators based on organic-inorganic hybrids were constructed by judiciously incorporating lanthanide cations and organic ligands within a single material. The obtained Eu-pba and Tb-pba not only feature excellent radiation, hydrolytic, and thermal stabilities but also exhibit a linear response to the X-ray dose rate with detection limits of 4.92 and 3.17 µGy s-1, respectively. We further present a flexible scintillator film fabricated by embedding Tb-pba in a polydimethylsiloxane (PDMS) polymer. Their incorporation enables X-ray imaging with a spatial resolution of approximately 10 lp mm-1. These results emphasize the potential of lanthanide organic-inorganic hybrids to achieve outstanding performance in X-ray scintillation and imaging.

14.
Zhongguo Zhong Yao Za Zhi ; 49(2): 509-517, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403326

RESUMO

This study investigated the absorption profile of Wuwei Qingzhuo San in different intestinal segments and the absorption characteristics of its alkaloids(piperine, piperanine, piperlonguminine, and dihydropiperlonguminine). The everted gut sac model was established, and the chemical components of Wuwei Qingzhuo San in different intestinal segments were detected by UPLC-Q-TOF-MS. The content of piperine, piperanine, piperlonguminine, and dihydropiperlonguminine in intestinal absorption fluid was determined by UPLC-Q-TRAP-MS and the absorption parameters were calculated. The absorption characteristics in different intestinal segments at different time were analyzed. As a result, 27, 27, 8, and 6 absorbent components from Wuwei Qingzhuo San were detected in the intestinal cyst fluid of jejunum, ileum, duodenum, and colon by UPLC-Q-TOF-MS technology, respectively. It was also found that piperine, piperanine, piperlonguminine, and dihydropiperlonguminine from Wuwei Qingzhuo San showed linear absorption in various intestinal segments, with r values exceeding 0.9. In terms of absorption content, the components were ranked as piperine>piperanine>dihydropiperlonguminine>piperlonguminine in various intestinal segments, but the absorption rate and mechanism of each component varied. The results demonstrate that the absorption of the components of Wuwei Qingzhuo San in different intestinal segments is selective and is not a simple semi-permeable membrane permeation process.


Assuntos
Alcaloides , Piperidinas , Alcamidas Poli-Insaturadas , Benzodioxóis , Absorção Intestinal
15.
Nat Commun ; 15(1): 1116, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321072

RESUMO

Stretchable electronics that prevalently adopt chemically inert metals as sensing layers and interconnect wires have enabled high-fidelity signal acquisition for on-skin applications. However, the weak interfacial interaction between inert metals and elastomers limit the tolerance of the device to external friction interferences. Here, we report an interfacial diffusion-induced cohesion strategy that utilizes hydrophilic polyurethane to wet gold (Au) grains and render them wrapped by strong hydrogen bonding, resulting in a high interfacial binding strength of 1017.6 N/m. By further constructing a nanoscale rough configuration of the polyurethane (RPU), the binding strength of Au-RPU device increases to 1243.4 N/m, which is 100 and 4 times higher than that of conventional polydimethylsiloxane and styrene-ethylene-butylene-styrene-based devices, respectively. The stretchable Au-RPU device can remain good electrical conductivity after 1022 frictions at 130 kPa pressure, and reliably record high-fidelity electrophysiological signals. Furthermore, an anti-friction pressure sensor array is constructed based on Au-RPU interconnect wires, demonstrating a superior mechanical durability for concentrated large pressure acquisition. This chemical modification-free approach of interfacial strengthening for chemically inert metal-based stretchable electronics is promising for three-dimensional integration and on-chip interconnection.

16.
Curr Med Imaging ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38415435

RESUMO

PURPOSE: This study aimed to explore the similarities and differences in clinical presentations, multidetector computed tomographic (MDCT) features, and treatment of three types of adult intussusceptions based on location. METHODS: We retrospectively reviewed 184 adult patients with 192 intussusceptions. Depending on the location, intussusceptions were classified as enteric, ileocolic, and colonic types. The similarities and differences of clinical presentations, MDCT features, and treatment of three types of adult intussusception were compared. Meanwhile, the three types of intussusceptions were further divided into surgical and conservative groups based on the treatment. Uni- and multivariate logistic analyses were used to identify risk factors for intussusception requiring surgery. RESULTS: Enteric and ileocolic intussusceptions were mainly presented with abdominal pain (78.46% and 85.71%). Hematochezia/melena (64.29%) was the main symptom of colonic intussusception. On MDCT, ileocolic intussusceptions were longer in length and had more signs of intestinal necrosis (hypodense layer, fluid collection and no/poor bowel wall enhancement) than enteric and colonic intussusceptions. Moreover, it was found that 93.88% (46/49) of ileocolic intussusception and 98.59% (70/71) of colonic intussusception belonged to the surgical group, whereas only 43.06% (31/72) of enteric intussusception belonged to the surgical group. Intussusception length (OR=1.171, P=0.028) and discernible lead point on MDCT (OR=21.003, P<0.001) were reliable indicators of enteric intussusception requiring surgery. CONCLUSION: Ileocolic intussusception may be more prone to intestinal necrosis than enteric and colonic intussusceptions, requiring more attention from clinicians. Surgery remains the treatment of choice for most ileocolic and colonic intussusceptions. Less than half of enteric intussusceptions require surgery, and MDCT features are effective in identifying them.

17.
Hum Cell ; 37(3): 633-647, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38416276

RESUMO

Lethal graft-versus-host disease (GVHD) is the major complication of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT). Pyruvate kinase M2 (PKM2) is essential for CD4+ T-cell differentiation. Using the well-characterized mouse models of Allo-HSCT, we explored the effects of TEPP-46-induced PKM2 tetramerization on GVHD and graft-versus-leukemia (GVL) activity. TEPP-46 administration significantly improved the survival rate of GVHD. The severity of GVHD and histopathological damage of GVHD-targeted organs were obviously alleviated by PKM2 tetramerization. Additionally, tetramerized PKM2 inhibited the activation of NF-κB pathway and decreased the inflammation level of GVHD mice. PKM2 tetramerization blocked Th1 and Th17 cell differentiation and secretion of pro-inflammatory cytokine (IFN-γ, TNF-α, and IL-17). Meanwhile, differentiation of Treg cells and IL-10 secretion were promoted by tetramerized PKM2. These findings demonstrated that PKM2 enhanced the augment of Th1 and Th17 cells to accelerate the progression of GVHD, and allosteric activation of PKM2 targeted Th1 and Th17 cells attenuated GVHD. Furthermore, we also confirmed that TEPP-46 administration did not compromise GVL activity and resulted in slightly improvement of leukemia-free survive. Thus, targeting Th1 and Th17 cell response with PKM2 allosteric activator may be a promising therapeutic strategy for GVHD prevention while preserving the GVL activity in patients receiving Allo-HSCT.


Assuntos
Doença Enxerto-Hospedeiro , Leucemia , Humanos , Camundongos , Animais , Células Th17 , Piruvato Quinase/metabolismo , Piruvato Quinase/farmacologia , Piruvato Quinase/uso terapêutico , Transplante Homólogo/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Leucemia/metabolismo , Diferenciação Celular
18.
Heliyon ; 10(1): e23526, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38173517

RESUMO

Objective: Despite the widespread use of doxorubicin (DOX) in chemotherapy, it can cause cardiotoxicity, which severely limits its potential clinical use. CYP2J2-derived epoxyeicosatrienoic acids (EETs) exert cardioprotective effects by maintaining cardiac homeostasis. The roles and latent mechanisms of EETs in DOX cardiotoxicity remain uncertain. We investigated these aspects using mouse tissue and cell culture models. Methods: C57BL/6J mice were injected with rAAV9-CYP2J2 or a control vector via the caudal vein. A five-week intraperitoneal course of DOX (5 mg/kg per week) was administered. After pretreatment with 14,15-EET, H9C2 cells were treated for 24-h with DOX, to use as a cell model to verify the role of EETs in cardiotoxicity in vitro. Results: CYP2J2 overexpression mitigated DOX-induced cardiotoxicity, as shown by the diminished cardiac injury marker levels, improved heart function, reduced oxidative stress, and inhibition of myocardial apoptosis in vivo. These protective roles are associated with the enhancement of antioxidant and anti-apoptotic abilities and the activation of the AMPK pathway. 14,15-EET suppresses DOX-induced oxidative stress, mitochondrial dysfunction, and apoptosis in H9C2 cells. AMPK knockdown partially abolished the cardioprotective effects of 14,15-EET against oxidative damage and apoptosis in DOX-treated cells, suggesting that AMPK is responsible for EET-mediated protection against cardiotoxicity. Conclusion: CYP2J2-derived EETs confer myocardial protection against DOX-induced toxicity by activating the AMPK pathway, which reduces oxidative stress, mitochondrial dysfunction, and apoptosis.

19.
Radiat Oncol ; 19(1): 2, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178254

RESUMO

BACKGROUND: To determine the optimal planning target volume (PTV) margins for adequate coverage by daily iterative cone-beam computed tomography (iCBCT)-guided online adaptive radiotherapy (oART) in postoperative treatment of endometrial and cervical cancer and the benefit of reducing PTV margins. METHODS: Fifteen postoperative endometrial and cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective phase 2 study. Pre- and posttreatment iCBCT images of 125 fractions from 5 patients were obtained as a training cohort, and clinical target volumes (CTV) were contoured separately. Uniform three-dimensional expansions were applied to the PTVpre to assess the minimum margin required to encompass the CTVpost. The dosimetric advantages of the proposed online adaptive margins were compared with conventional margin plans (7-15 mm) using an oART emulator in another cohort of 125 iCBCT scans. A CTV-to-PTV expansion was verified on a validation cohort of 253 fractions from 10 patients, and further margin reduction and acute toxicity were studied. RESULTS: The average time from pretreatment iCBCT to posttreatment iCBCT was 22 min. A uniform PTV margin of 5 mm could encompass nodal CTVpost in 100% of the fractions (175/175) and vaginal CTVpost in 98% of the fractions (172/175). The margin of 5 mm was verified in our validation cohort, and the nodal PTV margin could be further reduced to 4 mm if ≥ 95% CTV coverage was predicted to be achieved. The adapted plan with a 5 mm margin significantly improved pelvic organ-at-risk dosimetry compared with the conventional margin plan. Grade 3 toxicities were observed in only one patient with leukopenia, and no patients experienced acute urinary toxicity. CONCLUSION: In the postoperative treatment of endometrial and cervical cancer, oART could reduce PTV margins to 5 mm, which significantly decrease the dose to critical organs at risk and potentially lead to a lower incidence of acute toxicity.


Assuntos
Radioterapia de Intensidade Modulada , Neoplasias do Colo do Útero , Feminino , Humanos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Estudos Prospectivos , Dosagem Radioterapêutica
20.
Radiat Oncol ; 19(1): 6, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38212767

RESUMO

BACKGROUND: Training senior radiation therapists as "adapters" to manage influencers and target editing is critical in daily online adaptive radiotherapy (oART) for cervical cancer. The purpose of this study was to evaluate the accuracy and dosimetric outcomes of automatic contouring and identify the key areas for modification. METHODS: A total of 125 oART fractions from five postoperative cervical cancer patients and 140 oART fractions from five uterine cervical cancer patients treated with daily iCBCT-guided oART were enrolled in this prospective study. The same adaptive treatments were replanned using the Ethos automatic contours workflow without manual contouring edits. The clinical target volume (CTV) was subdivided into several separate regions, and the average surface distance dice (ASD), centroid deviation, dice similarity coefficient (DSC), and 95% Hausdorff distance (95% HD) were used to evaluate contouring for the above portions. Dosimetric results from automatic oART plans were compared to supervised oART plans to evaluate target volumes and organs at risk (OARs) dose changes. RESULTS: Overall, the paired CTV had high overlap rates, with an average DSC value greater than 0.75. The uterus had the largest consistency differences, with ASD, centroid deviation, and 95% HD being 2.67 ± 1.79 mm, 17.17 ± 12 mm, and 10.45 ± 5.68 mm, respectively. The consistency differences of the lower nodal CTVleft and nodal CTVright were relatively large, with ASD, centroid deviation, and 95% HD being 0.59 ± 0.53 mm, 3.6 ± 2.67 mm, and 5.41 ± 4.08 mm, and 0.59 ± 0.51 mm, 3.6 ± 2.54 mm, and 4.7 ± 1.57 mm, respectively. The automatic online-adapted plan met the clinical requirements of dosimetric coverage for the target volume and improved the OAR dosimetry. CONCLUSIONS: The accuracy of automatic contouring from the Ethos adaptive platform is considered clinically acceptable for cervical cancer, and the uterus, upper vaginal cuff, and lower nodal CTV are the areas that need to be focused on in training.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Prospectivos , Dosagem Radioterapêutica , Fracionamento da Dose de Radiação , Órgãos em Risco
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