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1.
World J Hepatol ; 16(6): 900-911, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38948438

RESUMO

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124742, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38950474

RESUMO

Afterglow materials face limitations in color variety, low luminosity, and stability. Thus, developing materials with adjustable afterglow color, increased photoluminescence (PL) intensity, and enhanced stability is crucial. This paper reports the fabrication of a series of core-shell composites, CPB@SMSO@SiO2, which combine Sr2MgSi2O7: Eu2+, Dy3+ (SMSO) and lead halide perovskite quantum dots (CsPbBr3/CPB PeQDs) through a process involving in-situ growth and hydrolytic coating. The SMSO in the composite can absorb 365 nm UV light and then emit 470 nm light, which can be absorbed by the CsPbBr3 PeQDs, resulting in an overall increase in the PL intensity of the composite. The afterglow color can be turned from green to blue by adjusting the ratio of SMSO and CsPbBr3. Furthermore, the stability of the composites is improved by the SiO2 shell layer formed by hydrolysis of tetramethyl orthosilicate (TMOS). This study presents an opportunity to develop innovative afterglow materials.

3.
Front Oncol ; 14: 1395159, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38957322

RESUMO

Background: The performance of artificial intelligence (AI) in the prediction of lymph node (LN) metastasis in patients with oral squamous cell carcinoma (OSCC) has not been quantitatively evaluated. The purpose of this study was to conduct a systematic review and meta-analysis of published data on the diagnostic performance of CT and MRI based on AI algorithms for predicting LN metastases in patients with OSCC. Methods: We searched the Embase, PubMed (Medline), Web of Science, and Cochrane databases for studies on the use of AI in predicting LN metastasis in OSCC. Binary diagnostic accuracy data were extracted to obtain the outcomes of interest, namely, the area under the curve (AUC), sensitivity, and specificity, and compared the diagnostic performance of AI with that of radiologists. Subgroup analyses were performed with regard to different types of AI algorithms and imaging modalities. Results: Fourteen eligible studies were included in the meta-analysis. The AUC, sensitivity, and specificity of the AI models for the diagnosis of LN metastases were 0.92 (95% CI 0.89-0.94), 0.79 (95% CI 0.72-0.85), and 0.90 (95% CI 0.86-0.93), respectively. Promising diagnostic performance was observed in the subgroup analyses based on algorithm types [machine learning (ML) or deep learning (DL)] and imaging modalities (CT vs. MRI). The pooled diagnostic performance of AI was significantly better than that of experienced radiologists. Discussion: In conclusion, AI based on CT and MRI imaging has good diagnostic accuracy in predicting LN metastasis in patients with OSCC and thus has the potential for clinical application. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, PROSPERO (No. CRD42024506159).

4.
Sci Rep ; 14(1): 15251, 2024 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956182

RESUMO

The early diagnosis and treatment of foreign body aspiration (FBA) can significantly improve the overall prognosis of children. There are significant differences in the epidemiology and clinical characteristics of FBA in different regions. Therefore, we conducted a real-world study in the western region of China with over 4000 patients. The aim of this study was to improve the understanding of FBA in terms of its types, the specific months of its occurrence, and the distribution of primary caregiver characteristics in western China. We collected the clinical and epidemiological data of children who were diagnosed with FBA in our hospital over the past 20 years through a big data centre. We matched the data of healthy children who underwent routine physical examinations at the paediatric health clinic during the same period to analyse the differences in the data of actual guardians. A total of 4227 patients from five provinces were included in this study. Foreign bodies were removed by rigid bronchoscopy in 99.4% (4202/4227) of patients, with a median age of 19 months and a median surgical duration 16 min. January was the most common month of onset for 1725 patients, followed by February, with 1027 patients. The most common types of foreign objects were melon peanuts, seeds and walnuts, accounting for 47.2%, 15.3%, and 10.2%, respectively. In the FBA group, the proportion of grandparents who were primary caregivers was 70.33% (2973/4227), which was significantly greater than the 63.05% in the healthy group (2665/4227) (P < 0.01). FBA most commonly occurs in January and February. More than 60% of FBAs occur between the ages of 1 and 2 years, and the incidence of FBA may be greater in children who are cared for by grandparents. A rigid bronchoscope can be used to remove most aspirated foreign bodies in a median of 16 min.


Assuntos
Broncoscopia , Corpos Estranhos , Humanos , Corpos Estranhos/epidemiologia , China/epidemiologia , Masculino , Feminino , Lactente , Pré-Escolar , Broncoscopia/métodos , Criança , Aspiração Respiratória/epidemiologia , Adolescente
5.
Medicine (Baltimore) ; 103(27): e38582, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968509

RESUMO

This study is for exploring the effectiveness and security of Jiedu Xiezhuo Yishen Tang in the treatment of gouty arthritis. This retrospective study collected 100 patients with gouty arthritis between February 2022 and February 2023. According to the different treatment methods, the data of patients were divided into control group and experimental group. The control group received routine treatment with benzbromarone, while the experimental group received additional treatment with Xuedu Xiezhuo Yishen Tang on the basis of the control group. The evaluation indicators for the effectiveness of treatment include serum levels of 8-hydroxydeoxyguanosine, 3-NT, interleukin-6, interleukin-10, interleukin-1ß, tumor necrosis factor-α, C-reactive protein, erythrocyte sedimentation rate, urea nitrogen, creatinine, evaluation of knee joint function and pain level, traditional Chinese medicine syndrome score, and safety evaluation. After treatment, the overall treatment effect of the experimental group reached 98%, while the control group was 78%. After treatment, the differences in various indicators possessed statistical significance (SS) (P < .05). In the Lysholm score, the improvement in the experimental group was markedly more excellent than the control group, and the difference possessed SS (P < .05). In the NRS score, the experimental group's NRS score decreased from 8.39 to 1.08 before and after treatment, while the control group only decreased to 3.61. In addition, both groups of patients showed significant improvement in the joint score in the Traditional Chinese medicine syndrome sub-items. The experimental group was able to effectively improve symptoms such as joint pain, joint redness and swelling, joint fever, and limited joint mobility. After treatment, the incidence of adverse reactions in the experimental group was only 8%, while the incidence of adverse reactions in the control group was 24%. After statistical analysis of the incidence of adverse reactions during treatment among the participants, it was found that the difference possessed SS (P < .001). The combination treatment of Jiedu Xiezhuo Yishen Tang and benbromarone can effectively improve oxidative stress response and significantly reduce blood uric acid levels. Meanwhile, this combination therapy can effectively inhibit inflammatory reactions, significantly alleviate knee joint pain, and promote the recovery of knee joint function. This treatment regimen has lower toxic side effects and higher safety.


Assuntos
Artrite Gotosa , Medicamentos de Ervas Chinesas , Humanos , Artrite Gotosa/tratamento farmacológico , Artrite Gotosa/sangue , Masculino , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Feminino , Resultado do Tratamento , Idoso , Benzobromarona/uso terapêutico , Adulto , Medicina Tradicional Chinesa/métodos
6.
Int J Biol Macromol ; : 133552, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39025747

RESUMO

In this study, a new method for preparing gels suitable for 3D printing of food structures using wheat starch and plasma activated water (PAW) is presented. The investigation focused on the effect of PAW on starch pasting and the final 3D printed product. It was found that the use of PAW for 15 min in the preparation of wheat starch gels optimized carrier stability and improved height retention in the printed constructs, showing significant shape retention even after prolonged storage. This durability can be attributed to the hindrance of polymerization between starch molecules and the promotion of intermolecular starch polymerization when reactive groups and ions are integrated into the starch structure. The incorporation of PAW with soluble reactive groups, ions and acidity not only accelerates the breakdown of the starch molecules but also facilitates additional hydrogen bonding within the double helix, which strengthens the structure of the gel. This interaction accelerates the retrogradation of the starch, thereby enhancing its overall stability. This study provides a new green approach to modify the 3D printing properties of starch gels.

7.
Clinics (Sao Paulo) ; 79: 100434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38959634

RESUMO

OBJECTIVES: To retrospectively investigate the impact of pre-treatment Extracellular Volume Fraction (ECV) measured by Computed Tomography (CT) on the response of primary lesions to preoperative chemotherapy in abdominal neuroblastoma. METHODS: A total of seventy-five patients with abdominal neuroblastoma were retrospectively included in the study. The regions of interest for the primary lesion and aorta were determined on unenhanced and equilibrium phase CT images before treatment, and their average CT values were measured. Based on patient hematocrit and average CT values, the ECV was calculated. The correlation between ECV and the reduction in primary lesion volume was examined. A receiver operating characteristic curve was generated to assess the predictive performance of ECV for a very good partial response of the primary lesion. RESULTS: There was a negative correlation between primary lesion volume reduction and ECV (r = -0.351, p = 0.002), and primary lesions with very good partial response had lower ECV (p < 0.001). The area under the curve for ECV in predicting the very good partial response of primary lesion was 0.742 (p < 0.001), with a 95 % Confidence Interval of 0.628 to 0.836. The optimal cut-off value was 0.28, and the sensitivity and specificity were 62.07 % and 84.78 %, respectively. CONCLUSIONS: The measurement of pre-treatment ECV on CT images demonstrates a significant correlation with the response of the primary lesion to preoperative chemotherapy in abdominal neuroblastoma.


Assuntos
Neoplasias Abdominais , Neuroblastoma , Tomografia Computadorizada por Raios X , Humanos , Neuroblastoma/diagnóstico por imagem , Neuroblastoma/tratamento farmacológico , Neuroblastoma/cirurgia , Neuroblastoma/patologia , Masculino , Feminino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Pré-Escolar , Criança , Lactente , Neoplasias Abdominais/diagnóstico por imagem , Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/patologia , Neoplasias Abdominais/cirurgia , Resultado do Tratamento , Curva ROC , Valor Preditivo dos Testes , Adolescente , Carga Tumoral/efeitos dos fármacos , Sensibilidade e Especificidade , Valores de Referência , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Reprodutibilidade dos Testes
8.
Huan Jing Ke Xue ; 45(7): 4082-4089, 2024 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-39022956

RESUMO

The rapid cultivation of partial nitritation/ANAMMOX (PN/A) granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX (AMX) bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors (CSTR) (R1-R3) by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·ï¼ˆm3·d)-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria (AMX) by introducing abundant ammonium-oxidizing bacteria (AOB) and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB (genus Nitrosomonas), AMX (genera Candidatus Kuenenia and Candidatus Brocadia), and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.


Assuntos
Processos Autotróficos , Reatores Biológicos , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos , Reatores Biológicos/microbiologia , Nitrogênio/metabolismo , Nitrogênio/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Esgotos/microbiologia , Bactérias/metabolismo , Bactérias/isolamento & purificação , Bactérias/genética , Águas Residuárias/química , Compostos de Amônio/metabolismo , Compostos de Amônio/isolamento & purificação
10.
Chem Sci ; 15(28): 10963-10968, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39027279

RESUMO

The catalytic asymmetric propargylation of enol(ate) intermediates is a well-established method for the synthesis of α-propargyl-substituted carbonyl compounds. However, the propargylation of homo-enol(ate) or its equivalents for the synthesis of ß-propargyl-substituted carbonyl compounds remains underdeveloped. A catalytic enantioselective decarboxylative intramolecular propargylation of cyclopropanols has been developed using a PyBox-complexed copper catalyst. This reaction offers an effective approach to assemble a cyclopentanone skeleton bearing an all-carbon quaternary stereogenic center and an adjacent quaternary gem-dimethyl carbon center, which is the core scaffold of the naturally occurring cuparenoids. Key to the success of this protocol is the use of a new structurally optimized PyBox ligand. This study represents the first example of catalytic asymmetric intramolecular propargylation of cyclopropanols.

11.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(4): 643-648, 2024 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-39019794

RESUMO

Amyloidosis is a rare disease. This paper reports a case of localized secondary hypopharyngeal amyloidosis presenting with pulmonary tuberculosis as the initial symptom. The patient lacked specific clinical manifestations and primarily exhibited symptoms such as cough, sputum production, acid reflux, belching, and abdominal pain. Chest CT indicated bronchiectasis with infection and pulmonary tuberculosis. Digestive endoscopy revealed a white mucosal elevation at the right pyriform sinus of the hypopharynx. Pathological diagnosis confirmed amyloid deposits in the hypopharyngeal mucosal tissue. The patient tested positive for anti-amyloid A antibodies, Congo red staining (+), and periodate Schiff staining (+). Amyloidosis commonly affects the digestive system and may have various etiologies, often presenting with symptoms that overlap with other digestive system diseases, leading to frequent misdiagnosis and missed optimal treatment opportunities. The hypopharynx, a highly folded and narrow chamber that serves as a common passage for the digestive and respiratory tracts, can be effectively evaluated for amyloidosis using digestive endoscopy.


Assuntos
Amiloidose , Hipofaringe , Humanos , Amiloidose/diagnóstico , Amiloidose/diagnóstico por imagem , Hipofaringe/patologia , Hipofaringe/diagnóstico por imagem , Masculino , Endoscopia do Sistema Digestório/métodos
12.
Tree Physiol ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38965676

RESUMO

Olive (Olea europaea. L), an economically important oil-producing crop, is sensitive to low temperature, which severely limits its productivity and geographical distribution. However, the underlying mechanism of cold tolerance in olive remains elusive. In this study, a chilling experiment (4 °C) on the living saplings of two olive cultivars revealed that O. europaea cv. Arbequina showed stronger cold tolerance with greater photosynthetic activity compared to O. europaea cv. Leccino. Transcriptome analyses revealed that early light-inducible protein 1 (ELIP1), the main regulator for chlorophyll synthesis, is dramatically induced to protect the photosynthesis at low temperatures. Furthermore, weighted gene co-expression network analysis (WGCNA), yeast one-hybrid (Y1H), and luciferase (LUC) assays demonstrated that transcription factor bHLH66 serves as an important regulator of ELIP1 transcription by binding to the G-box motif in the promoter. Taken together, our research revealed a novel transcriptional module consisting of bHLH66- ELIP1 in the adaptation of olive trees to cold stress.

13.
Adv Sci (Weinh) ; : e2403358, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973351

RESUMO

Conductive polymer hydrogels exhibit unique electrical, electrochemical, and mechanical properties, making them highly competitive electrode materials for stretchable high-capacity energy storage devices for cutting-edge wearable electronics. However, it remains extremely challenging to simultaneously achieve large mechanical stretchability, high electrical conductivity, and excellent electrochemical properties in conductive polymer hydrogels because introducing soft insulating networks for improving stretchability inevitably deteriorates the connectivity of rigid conductive domain and decreases the conductivity and electrochemical activity. This work proposes a distinct confinement self-assembly and multiple crosslinking strategy to develop a new type of organic-inorganic hybrid conductive hydrogels with biphase interpenetrating cross-linked networks. The hydrogels simultaneously exhibit high conductivity (2000 S m-1), large stretchability (200%), and high electrochemical activity, outperforming existing conductive hydrogels. The inherent mechanisms for the unparalleled comprehensive performances are thoroughly investigated. Elastic all-hydrogel supercapacitors are prepared based on the hydrogels, showing high specific capacitance (212.5 mF cm-2), excellent energy density (18.89 µWh cm-2), and large deformability. Moreover, flexible self-powered luminescent integrated systems are constructed based on the supercapacitors, which can spontaneously shine anytime and anywhere without extra power. This work provides new insights and feasible avenues for developing high-performance stretchable electrode materials and energy storage devices for wearable electronics.

14.
Reprod Biol ; 24(3): 100924, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39013209

RESUMO

Gestational Diabetes Mellitus (GDM) presents a significant health concern globally, necessitating a comprehensive understanding of its metabolic intricacies for effective management. MicroRNAs (miRNAs) have emerged as pivotal regulators in GDM pathogenesis, influencing glucose metabolism, insulin signaling, and lipid homeostasis during pregnancy. Dysregulated miRNA expression, both upregulated and downregulated, contributes to GDM-associated metabolic abnormalities. Ethnic and temporal variations in miRNA expression underscore the multifaceted nature of GDM susceptibility. This review examines the dysregulation of miRNAs in GDM and their regulatory functions in metabolic disorders. We discuss the involvement of specific miRNAs in modulating key pathways implicated in GDM pathogenesis, such as glucose metabolism, insulin signaling, and lipid homeostasis. Furthermore, we explore the potential diagnostic and therapeutic implications of miRNAs in GDM management, highlighting the promise of miRNA-based interventions for mitigating the adverse consequences of GDM on maternal and offspring health.

15.
Aging (Albany NY) ; 16(11): 10132-10141, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862253

RESUMO

BACKGROUND: Acute pancreatitis (AP) is a prevalent acute abdominal condition, and AP induced colonic barrier dysfunction is commonly observed. Total flavonoids of Chrysanthemum indicum L (TFC) have exhibited noteworthy anti-inflammatory and anti-apoptotic properties. METHODS: We established AP models, both in animals and cell cultures, employing Cerulein. 16S rRNA gene sequencing was performed to investigate the gut microorganisms changes. RESULTS: In vivo, TFC demonstrated a remarkable capacity to ameliorate AP, as indicated by the inhibition of serum amylase, myeloperoxidase (MPO) levels, and the reduction in pancreatic tissue water content. Furthermore, TFC effectively curtailed the heightened inflammatory response. The dysfunction of colonic barrier induced by AP was suppressed by TFC. At the in vitro level, TFC treatment resulted in attenuation of increased cell apoptosis, and regulation of apoptosis related proteins expression in AR42J cells. The increase of Bacteroides sartorial, Lactobacillus reuteri, Muribaculum intestinale, and Parabacteroides merdae by AP, and decrease of of Helicobacter rodentium, Pasteurellaceae bacterium, Streptococcus hyointestinalis by AP were both reversed by TFC treatment. CONCLUSIONS: TFC can effectively suppress AP progression and AP induced colonic barrier dysfunction by mitigating elevated serum amylase, MPO levels, water content in pancreatic tissue, as well as curtailing inflammation, apoptosis. The findings presented herein shed light on the potential mechanisms by which TFC inhibit the development of AP progression and AP induced colonic barrier dysfunction.


Assuntos
Chrysanthemum , Flavonoides , Microbioma Gastrointestinal , Pancreatite , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Chrysanthemum/química , Pancreatite/metabolismo , Pancreatite/microbiologia , Pancreatite/tratamento farmacológico , Flavonoides/farmacologia , Masculino , Ratos , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/patologia , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Linhagem Celular , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia
16.
Abdom Radiol (NY) ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900321

RESUMO

PURPOSE: To compare the performance of radiomics from contrast-enhanced computed tomography (CECT) and non-contrast magnetic resonance imaging (MRI) in assessing cellular behavior in pediatric peripheral neuroblastic tumors (PNTs). MATERIALS AND METHODS: A retrospective analysis of 81 PNT patients who underwent venous phase CECT, T1-weighted imaging (T1WI), and T2-weighted imaging (T2WI) scans was conducted. The patients were classified into neuroblastoma and ganglioneuroblastoma/ganglioneuroma based on their pathological subtypes. Additionally, they were categorized into favorable histology and unfavorable histology according to the International Neuroblastoma Pathology Classification (INPC). Tumor regions of interest were segmented on CECT, axial T1WI, and axial T2WI images, and radiomics models were developed based on the selected radiomics features. Following five-fold cross-validation, the performance of the radiomics models derived from CECT and MRI was compared using the area under the receiver operating characteristic curve (AUC) and accuracy. RESULTS: For discriminating pathological subtypes, the AUC for CECT radiomics models ranged from 0.765 to 0.870, with an accuracy range of 0.728 to 0.815. In contrast, the AUC for MRI radiomics models ranged from 0.549 to 0.748, with an accuracy range of 0.531 to 0.778. Regarding the discrimination of INPC subgroups, the AUC for CECT radiomics models ranged from 0.503 to 0.759, with an accuracy range of 0.432 to 0.741. Meanwhile, the AUC for MRI radiomics models ranged from 0.512 to 0.739, with an accuracy range of 0.605 to 0.815. CONCLUSIONS: CECT radiomics outperforms non-contrast MRI radiomics in evaluating pathological subtypes. When assessing INPC subgroups, CECT radiomics demonstrates comparability with non-contrast MRI radiomics.

17.
Cancer Res Commun ; 4(6): 1566-1580, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38837899

RESUMO

Glioblastoma (GBM) is the deadliest adult brain cancer. Under the current standard of care, almost all patients succumb to the disease and novel treatments are urgently needed. Recognizing that GBMs are addicted to cholesterol, past clinical trials have repurposed statins against GBM but failed. The purpose of this study was to test whether treatments that upregulate the cholesterol biosynthesis pathway in GBM would generate a metabolic vulnerability that can be exploited using statins and to determine the underlying mechanisms.Effects of radiotherapy and temozolomide or dopamine receptor antagonists on the mevalonate pathway in GBM were assessed in vitro and in vivo. The impact of statins on self-renewal of glioma stem cells and median survival was studied. Branches of the mevalonate pathway were probed to identify relevant effector proteins.Cells surviving combination treatments that converge in activating the immediate early response, universally upregulated the mevalonate pathway and increased stemness of GBM cells through activation of the Rho-GTPase Rac-1. Activation of the mevalonate pathway and Rac-1 was inhibited by statins, which led to improved survival in mouse models of glioblastoma when combined with radiation and drugs that target the glioma stem cell pool and plasticity of glioma cells.We conclude that a combination of dopamine receptor antagonists and statins could potentially improve radiotherapy outcome and warrants further investigation. SIGNIFICANCE: Combination therapies that activate the mevalonate pathway in GBM cells after sublethal treatment enhance self-renewal and migratory capacity through Rac-1 activation, which creates a metabolic vulnerability that can be further potentially exploited using statins.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Ácido Mevalônico , Temozolomida , Proteínas rac1 de Ligação ao GTP , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Ácido Mevalônico/metabolismo , Humanos , Animais , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia
18.
Comput Biol Med ; 178: 108673, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38905891

RESUMO

Deformable Image registration is a fundamental yet vital task for preoperative planning, intraoperative information fusion, disease diagnosis and follow-ups. It solves the non-rigid deformation field to align an image pair. Latest approaches such as VoxelMorph and TransMorph compute features from a simple concatenation of moving and fixed images. However, this often leads to weak alignment. Moreover, the convolutional neural network (CNN) or the hybrid CNN-Transformer based backbones are constrained to have limited sizes of receptive field and cannot capture long range relations while full Transformer based approaches are computational expensive. In this paper, we propose a novel multi-axis cross grating network (MACG-Net) for deformable medical image registration, which combats these limitations. MACG-Net uses a dual stream multi-axis feature fusion module to capture both long-range and local context relationships from the moving and fixed images. Cross gate blocks are integrated with the dual stream backbone to consider both independent feature extractions in the moving-fixed image pair and the relationship between features from the image pair. We benchmark our method on several different datasets including 3D atlas-based brain MRI, inter-patient brain MRI and 2D cardiac MRI. The results demonstrate that the proposed method has achieved state-of-the-art performance. The source code has been released at https://github.com/Valeyards/MACG.


Assuntos
Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Encéfalo/diagnóstico por imagem , Algoritmos
19.
Discov Oncol ; 15(1): 201, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822860

RESUMO

OBJECTIVE: Mitosis karyorrhexis index (MKI) can reflect the proliferation status of neuroblastoma cells. This study aimed to investigate the contrast-enhanced computed tomography (CECT) radiomics features associated with the MKI status in neuroblastoma. MATERIALS AND METHODS: 246 neuroblastoma patients were retrospectively included and divided into three groups: low-MKI, intermediate-MKI, and high-MKI. They were randomly stratified into a training set and a testing set at a ratio of 8:2. Tumor regions of interest were delineated on arterial-phase CECT images, and radiomics features were extracted. After reducing the dimensionality of the radiomics features, a random forest algorithm was employed to establish a three-class classification model to predict MKI status. RESULTS: The classification model consisted of 5 radiomics features. The mean area under the curve (AUC) of the classification model was 0.916 (95% confidence interval (CI) 0.913-0.921) in the training set and 0.858 (95% CI 0.841-0.864) in the testing set. Specifically, the classification model achieved AUCs of 0.928 (95% CI 0.927-0.934), 0.915 (95% CI 0.912-0.919), and 0.901 (95% CI 0.900-0.909) for predicting low-MKI, intermediate-MKI, and high-MKI, respectively, in the training set. In the testing set, the classification model achieved AUCs of 0.873 (95% CI 0.859-0.882), 0.860 (95% CI 0.852-0.872), and 0.820 (95% CI 0.813-0.839) for predicting low-MKI, intermediate-MKI, and high-MKI, respectively. CONCLUSIONS: CECT radiomics features were found to be correlated with MKI status and are helpful for reflecting the proliferation status of neuroblastoma cells.

20.
Transl Pediatr ; 13(5): 716-726, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38840678

RESUMO

Background: Diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) are two completely different pathologic subtypes of lymphoma with distinctly different clinical presentations and treatment options. Thus, accurately differentiating between the two subtypes has important clinical implications. This study aimed to construct a radiomics model capable of distinguishing between DLBCL and HL based on enhanced computed tomography (CT) for the non-invasive diagnosis of lymphoma subtypes. Methods: The clinical and imaging data of 16 patients confirmed to have DLBCL (33 lymphomas), and 50 patients confirmed to have HL (106 lymphomas) were retrospectively analyzed. The patients were completely randomized into a training set (n=107, DLBLC׃HL ratio: 23׃84) and a test set (n=32, DLBCL׃HL ratio: 10׃22). After multiple down-sampling, 2,264 radiomics features were automatically extracted by the application software. Feature selection was performed in the training set using Spearman's rank correlation coefficients, maximum correlation minimum redundancy, and the least absolute shrinkage and selection operator algorithm in that order. The features after selection were used to build radiomics models by logistic regression (LR) and quadratic discriminant analysis (QDA). We evaluated the model ability using receiver operating characteristic (ROC) curves and the DeLong test. Moreover, clinical indicators, such as gender, age, clinical stage, and lactate dehydrogenase (LDH), were collected and analyzed by univariate and multivariate LR analyses. The radiomics characteristics with clinical indicators that had independent influences on predicting the pathological subtypes were used to establish a comprehensive classification model. Results: The analysis of the clinical data revealed that LDH can serve as a clinical indicator that has an independent influence on the prediction of HL and DLBCL. The results of the radiomics models were as follows: Radiomics_LR: area under the curve (AUC) =0.814 [95% confidence interval (CI): 0.628-0.999]; and Radiomics_QDA: AUC =0.841 (95% CI: 0.691-0.991). Following the inclusion of LDH as a clinical indicator in the analysis, the results of the comprehensive models were as follows: Radiomics + LDH_LR: AUC =0.768 (95% CI: 0.580-0.956); and Radiomics + LDH_QDA: AUC was 0.845 (95% CI: 0.695-0.996). Conclusions: The models based on radiomics and clinical features were able to effectively distinguish DLBCL from HL. The model with the best overall performance was the Radiomics_LR model.

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