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OBJECTIVE: To compare the diagnostic performance of CEUS-guided biopsy (CEUS-GB) and ultrasound-guided biopsy (US-GB) in evaluating abdominal and pelvic (abdominopelvic) neoplasms in paediatric patients. METHODS: Patients aged < 18 years with abdominopelvic tumours who underwent either CEUS-GB or US-GB between April 2005 and May 2022 were retrospectively evaluated. Tumours diagnosed as malignancies by pathology were considered true-positive findings. Benign lesions were identified by pathology or clinical follow-up of at least 6 months. The diagnostic performance of the two groups was compared using propensity score matching (PSM). Complications were also analysed. RESULTS: The present study included 764 paediatric patients (437 boys; median age, 24 months; interquartile range, 10-60 months); 151 were in the CEUS-GB group, and 613 were in the US-GB group. The sample adequacy rate was 100% (151 of 151) for the CEUS-GB group, which was greater than the 97.4% (597 of 613) for the US-GB group (p < 0.001). The overall diagnostic accuracy of the CEUS-GB group and US-GB group was 98.7% (149 of 151) versus 97.3% (581 of 597) in the total cohort (p = 0.551) and 98.7% (149 of 151) versus 92.7% (140 of 151) in the PSM cohort (p = 0.020). Two patients (0.3%) in the US-GB group experienced complications (Common Terminology Criteria for Adverse Events (CTCAE), grade 1-2) correlated with the biopsy. No adverse reactions occurred in the CEUS-GB group. CONCLUSION: CEUS-GB of abdominopelvic tumours in paediatric patients is an effective and safe procedure with greater diagnostic accuracy than US-GB, especially for tumours with necrotic areas. CLINICAL RELEVANCE STATEMENT: Contrast-enhanced US-guided biopsy of solid abdominal and pelvic tumours in paediatric patients is an effective and safe procedure with greater diagnostic accuracy than US-guided biopsy, especially for tumours with necrotic areas. KEY POINTS: Contrast-enhanced ultrasound (CEUS) may be superior to conventional ultrasound at guiding biopsy of abdominopelvic masses in paediatric patients. CEUS-guided core needle biopsy of abdominopelvic masses in children was safe and resulted in a diagnostic yield of 98.7%. CEUS guidance should be considered in this population when colour Doppler US is unable to determine a biopsy site.
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OBJECTIVES: To evaluate grayscale US combined with contrast-enhanced ultrasound (CEUS) in the preoperative differentiation between benign and malignant ovarian masses in a pediatric population. MATERIALS AND METHODS: This retrospective study enrolled patients who underwent grayscale US and CEUS before surgery because of ovarian masses between July 2018 and September 2023, with available histopathologic or follow-up results. Two senior radiologists summarized the grayscale US and CEUS characteristics of all ovarian masses, including percentage of solidity, ascites, vascularity, and enhanced vessel morphology. These characteristics were then independently reviewed by radiologists with different experience to assess interobserver agreement. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC), while interobserver agreement was evaluated by intraclass correlation coefficient (ICC). RESULTS: A total of 26 children (median age: 10.1 [7.5, 11.7] years; age range: 0-14 years; benign: 15 patients) were included. The main characteristics of malignant ovarian tumors were abundant blood flow and twisted blood vessels within the mass, enhanced portion of the mass over 50 percent (all p < 0.001). The grayscale US combined with CEUS showed better diagnostic performance than the grayscale US alone (AUC = 0.99 [95% CI: 0.95, 1.00] vs AUC = 0.70 [95% CI: 0.50, 0.90] p < 0.001). A statistically significant AUC before and after CEUS was also shown between two junior radiologists (0.75 vs 0.92 and 0.69 vs 0.86, respectively, both p < 0.05). ICC of CEUS was better than that of grayscale US among radiologists. CONCLUSION: The combination of grayscale US and CEUS might improve the diagnostic accuracy in differentiating benign and malignant pediatric ovarian masses. CLINICAL RELEVANCE STATEMENT: Grayscale ultrasound combined with contrast-enhanced ultrasound can improve the diagnostic performance in the preoperative differentiation of benign and malignant ovarian lesions in a pediatric population. KEY POINTS: Correctly distinguishing benign from malignant ovarian masses in pediatric patients is critical for determining treatments. Grayscale combined with contrast-enhanced ultrasound (CEUS) differentiated benign and malignant pediatric ovarian masses better than grayscale US alone. Junior radiologists' diagnostic performances could be and were significantly improved with the application of CEUS.
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Temporal solitons have been the focus of much research due to their fascinating physical properties. These solitons can form bound states, which are fundamentally crucial modes in fiber laser and present striking analogies with their matter molecules counterparts, which means they have potential applications in large-capacity transmission and all-optical information storage. Although traditionally, second-order dispersion has been the dominant dispersion for conventional solitons, recent experimental and theoretical research has shown that pure-high-even-order dispersion (PHEOD) solitons with energy-width scaling can arise from the interaction of arbitrary negative-even-order dispersion and Kerr nonlinearity. Despite these advancements, research on the bound states of PHEOD solitons is currently non-existent. In this study, we obtained PHEOD bound solitons in a fiber laser using an intra-cavity spectral pulse shaper for high-order dispersion management. Specifically, we experimentally demonstrate the existence of PHEOD solitons and PHEOD bound solitons with pure-quartic, -sextic, -octic, and -decic dispersion. Numerical simulations corroborate these experimental observations. Furthermore, vibrating phase PHEOD bound soliton pairs, sliding phase PHEOD bound soliton pairs, and hybrid phase PHEOD bound tri-soliton are discovered and characterized. These results broaden the fundamental understanding of solitons and show the universality of multi-soliton patterns.
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Background: The differentiation between benign and malignant breast tumors extends beyond morphological structures to encompass functional alterations within the nodules. The combination of photoacoustic (PA) imaging and radiomics unveils functional insights and intricate details that are imperceptible to the naked eye. Purpose: This study aims to assess the efficacy of PA imaging in breast cancer radiomics, focusing on the impact of peritumoral region size on radiomic model accuracy. Materials and methods: From January 2022 to November 2023, data were collected from 358 patients with breast nodules, diagnosed via PA/US examination and classified as BI-RADS 3-5. The study used the largest lesion dimension in PA images to define the region of interest, expanded by 2â¯mm, 5â¯mm, and 8â¯mm, for extracting radiomic features. Techniques from statistics and machine learning were applied for feature selection, and logistic regression classifiers were used to build radiomic models. These models integrated both intratumoral and peritumoral data, with logistic regressions identifying key predictive features. Results: The developed nomogram, combining 5â¯mm peritumoral data with intratumoral and clinical features, showed superior diagnostic performance, achieving an AUC of 0.950 in the training cohort and 0.899 in validation. This model outperformed those based solely on clinical features or other radiomic methods, with the 5â¯mm peritumoral region proving most effective in identifying malignant nodules. Conclusion: This research demonstrates the significant potential of PA imaging in breast cancer radiomics, especially the advantage of integrating 5â¯mm peritumoral with intratumoral features. This approach not only surpasses models based on clinical data but also underscores the importance of comprehensive radiomic analysis in accurately characterizing breast nodules.
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OBJECTIVES: To investigate microvascular changes in juvenile localised scleroderma (JLS) lesions using superb microvascular imaging (SMI) and assess SMI's utility in evaluating disease activity. METHODS: This prospective study enroled 16 children (7 males) with pathologically diagnosed JLS between January 2021 and June 2023. Lesions were assessed using Localised Scleroderma Cutaneous Assessment Tools, including the localised scleroderma skin activity index (LoSAI) and localised scleroderma skin damage index (LoSDI). Lesions with LoSAI scores > 0 were classified as active. The thickness and blood flow of the lesions and healthy skin layers of the contralateral site were evaluated using ultrasound. SMI was used to detect microvascular blood flow in the lesions and healthy skin, and the vascular index (VI) was calculated. The difference in VI between active lesions and healthy skin was correlated with LoSAI and total scores. RESULTS: Of 46 lesions, 23 were active and 23 inactive. The skin thickness of the lesion was 0.094 ± 0.024 cm, and that of the healthy site was 0.108 ± 0.026 cm (p < 0.001). The VI of the active lesions and healthy skin were 7.60 (3.60, 12.80)% and 1.10 (0.50, 2.10)%, respectively (p < 0.001). The VI of the inactive lesions and the healthy skin were 0.85 (0.00, 2.20)% and 1.60 (1.00, 3.10)%, respectively (p = 0.011). VI differences between active lesions and healthy skin positively correlated with the LoSAI clinical score (r = 0.625, p = 0.001) and total score (r = 0.842, p < 0.001). CONCLUSION: SMI can quantitatively detect microvascular blood flow changes in JLS skin, indicating lesion activity and severity. CLINICAL RELEVANCE STATEMENT: SMI is a convenient, non-invasive, technique for detecting active JLS lesions and can provide valuable information to guide treatment options. KEY POINTS: Current grading systems of juvenile localised scleroderma rely on subjective clinical information. Superb Microvascular Imaging identified that vascular indexes between active lesions and healthy skin positively correlated with clinical scores. Superb Microvascular Imaging effectively assesses microvascular blood flow, aiding juvenile localised scleroderma lesion activity evaluation.
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BACKGROUND: A previously trained deep learning-based smartphone app provides an artificial intelligence solution to help diagnose biliary atresia from sonographic gallbladder images, but it might be impractical to launch it in real clinical settings. This study aimed to redevelop a new model using original sonographic images and their derived smartphone photos and then test the new model's performance in assisting radiologists with different experiences to detect biliary atresia in real-world mimic settings. METHODS: A new model was first trained retrospectively using 3659 original sonographic gallbladder images and their derived 51,226 smartphone photos and tested on 11,410 external validation smartphone photos. Afterward, the new model was tested in 333 prospectively collected sonographic gallbladder videos from 207 infants by 14 inexperienced radiologists (9 juniors and 5 seniors) and 4 experienced pediatric radiologists in real-world mimic settings. Diagnostic performance was expressed as the area under the receiver operating characteristic curve (AUC). RESULTS: The new model outperformed the previously published model in diagnosing BA on the external validation set (AUC 0.924 vs 0.908, P = 0.004) with higher consistency (kappa value 0.708 vs 0.609). When tested in real-world mimic settings using 333 sonographic gallbladder videos, the new model performed comparable to experienced pediatric radiologists (average AUC 0.860 vs 0.876) and outperformed junior radiologists (average AUC 0.838 vs 0.773) and senior radiologists (average AUC 0.829 vs 0.749). Furthermore, the new model could aid both junior and senior radiologists to improve their diagnostic performances, with the average AUC increasing from 0.773 to 0.835 for junior radiologists and from 0.749 to 0.805 for senior radiologists. CONCLUSIONS: The interpretable app-based model showed robust and satisfactory performance in diagnosing biliary atresia, and it could aid radiologists with limited experiences to improve their diagnostic performances in real-world mimic settings.
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Atresia Biliar , Aplicaciones Móviles , Lactante , Niño , Humanos , Vesícula Biliar/diagnóstico por imagen , Inteligencia Artificial , Atresia Biliar/diagnóstico por imagen , Estudios Retrospectivos , RadiólogosRESUMEN
PURPOSE: To summarize our single-center experience with percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for pediatric recurrent hepatocellular carcinoma (RHCC). METHODS: From September 2007 to September 2021, patients under 18 who underwent percutaneous US-guided RFA for RHCC were retrospectively enrolled in this study. Local effectiveness, complications, local tumor progression (LTP), progression free survival (PFS), and overall survival (OS) were evaluated. RESULTS: A total of 10 patients (9 male and 1 female; mean age, 11.7 ± 4 years ; age range, 6-17 years) with 15 intrahepatic RHCC lesions were enrolled in this study. Complete ablation (CA) was achieved in 14 out of 15 lesions (93.3%) after the first RFA. During the follow-up (mean, 63.1 ± 18 months; range, 5.3-123.3 months), LTP did not occur. Five patients died including three with tumor progression and one with liver failure. The accumulative one- and three-year PFS rates were 30% and 10%, respectively. The accumulative one- and three-year OS rates were 77.8% and 44.4%, respectively. CONCLUSIONS: Our single-center experience suggests the safety and feasibility of percutaneous US-guided RFA for pediatric RHCC.
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Carcinoma Hepatocelular , Ablación por Catéter , Neoplasias Hepáticas , Ablación por Radiofrecuencia , Humanos , Masculino , Femenino , Niño , Adolescente , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/cirugíaRESUMEN
ABSTRACT: The application of intracavity contrast-enhanced ultrasound in the evaluation of biliary disease has been confirmed valuable among pediatric population. This pictorial essay aims to demonstrate the role of percutaneous ultrasound cholangiography (PUSC) with microbubbles in the diagnosis of different pediatric biliary diseases in our center. The biliary system's morphologic characteristics in PUSC mode of neonatal hepatitis, biliary atresia, choledochal cysts, and biliary complications of hepatobiliary surgery are presented.
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Atresia Biliar , Sistema Biliar , Recién Nacido , Niño , Humanos , Lactante , Microburbujas , Colangiografía , Sistema Biliar/diagnóstico por imagen , Atresia Biliar/diagnóstico por imagen , Atresia Biliar/complicaciones , UltrasonografíaRESUMEN
Importance: Immunoglobulin G autoantibodies for aquaporin 4 (AQP4-IgG) serve as diagnostic biomarkers for neuromyelitis optica spectrum disorder (NMOSD), and the most sensitive and specific laboratory tests for their detection are cell-based assays (CBAs). Nevertheless, the limited availability of special instruments limits the widespread use of CBAs in routine laboratories. Objective: To validate an enzyme immunodot assay for simple and rapid detection of AQP4-IgG. Design, Setting, and Participants: This multicenter case-control study, conducted from May 2020 to February 2023, involved 4 medical centers (3 in China and 1 in Korea). The study included patients with AQP4-IgG-positive NMOSD, patients with other immune-related diseases, and healthy control individuals. Participants were excluded if they did not agree to participate or if their serum sample had turbidity. Exposures: Serum AQP4 antibodies measured with immunodot assay. Main Outcomes and Measures: The main outcome was performance of the immunodot assay compared with the gold standard CBA for detecting AQP4-IgG. To examine generalizability, cross-validation in Korea and at a second site in China, validation of patients with other immune-related diseases, and follow-up validation of the original cohort were performed. Results: A total of 836 serum samples were collected; 400 were included in the diagnostic study and 436 in the validation sets. In a head-to-head diagnostic study involving 200 patients with NMOSD with AQP4-IgG (mean [SD] age, 43.1 [13.5] years; 188 [94%] female) and 200 healthy controls, use of an immunodot assay demonstrated antibody detection performance comparable to that of the gold standard (κ = 98.0%). The validation sets included 47 patients with NMOSD and 26 patients with other autoimmune diseases from Korea, 31 patients with NMOSD at a second site in China, 275 patients with other diseases, and 57 patients with NMOSD at follow-up. In the validation study, of 436 cases, 2 (<1%) were false positive and none were false negative. The CBA identified 332 AQP4-IgG-positive samples and 504 negative samples (200 [40%] in controls and 304 [60%] in patients with other diseases); 2 of the positive cases (<1%) were false negative and 4 of the negative cases (<1%) were false positive. The overall sensitivity of the immunodot assay was 99.4% (95% CI, 97.8%-99.9%), and the specificity was 99.2% (95% CI, 98.0%-99.8%). Conclusions and Relevance: This case-control study found that the immunodot assay was comparable to CBA for detecting AQP4-IgG. With its time- and cost-efficient characteristics, the immunodot assay may be a practical option for AQP4-IgG detection.
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Neuromielitis Óptica , Humanos , Femenino , Adulto , Masculino , Estudios de Casos y Controles , Acuaporina 4 , Autoanticuerpos , Inmunoglobulina GRESUMEN
One Chinese herbal combination consisting of Panax notoginseng, Bletilla striata and Dendrobium officinale (PBD) is an effective Traditional Chinese Medicine (TCM) prescription and is widely used in clinics to treat gastric ulcers due to their safety and effectiveness compared with chemical agents, such as aspirin and omeprazole. Herein, an in situ forming gel (ISFG) based on Gellan Gum (GG) and Sodium Alginate (SA) was designed to deliver extracts of PBD prescription (EPBDP). The central composite design optimized prescription dosage was 0.1 % w/v of GG and 0.5 % w/v of SA. Gels prepared with this formulation demonstrated outstanding fluidity and instantaneous gel formation. In vitro release data showed that sustained drug release occurred in the gel, and the gel was pH-sensitive. The rheological tests confirmed the formation of stable gel, which exhibited strong viscosity and elasticity. In vitro adhesion assays revealed that the gel had strong gastric mucosal adhesion, while in vivo residual rate experiments of active ingredients revealed that the gel might greatly improve the gastric retention of active ingredients. Animal studies demonstrated that the gel was effective in treating gastric ulcers. Hence, the results of the study show that EPBDP-ISFG, a highly pH-sensitive sustained-release system, is effective.
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Background Infectious complications after percutaneous thermal ablation are seldom discussed, but better understanding of risk factors and early prediction is critical. Purpose To estimate the incidence of infectious complications after percutaneous thermal ablation of liver malignancies and to develop prediction models. Materials and Methods This single-center retrospective study reviewed the data of 3167 patients who underwent 7545 percutaneous US-guided thermal ablation procedures of liver malignancies between January 2010 and January 2022. All procedures with infectious complications were included as the case group. For each case, one treatment date-matched control subject without infection was randomly selected following a nested case-control design. Independent factors of overall and hepatobiliary infection were investigated with multivariable logistic regression. Results A total of 80 patients (median age, 59 years; IQR, 51-68 years; 64 men, 16 women) developed infectious complications after 80 ablation procedures; the incidence was 1.1% (80 of 7545 procedures). Of those with infection, 18% (14 of 80 patients) were severe, and 10% (eight of 80 patients) died as a result. Independent risk factors for overall infectious complication included prior biliary intervention (odds ratio [OR], 18.6; 95% CI: 4, 86; P < .001), prior transarterial chemoembolization (TACE) (OR, 2.4; 95% CI: 1.0, 5.8; P = .045), and the largest tumor size (OR, 1.9; 95% CI: 1.3, 2.8; P = .002); on this basis, subcapsular location was an additional risk factor of hepatobiliary infection. Prediction models for overall and hepatobiliary infection had an area under the receiver operating characteristics curve (AUC) of 0.77 and 0.82, respectively, both of which showed better AUC compared with the models, including prior biliary intervention alone (AUC = 0.63 and 0.65, respectively; P = .01 and P = .005, respectively). Conclusion Infectious complications after percutaneous thermal ablation of liver malignancies were uncommon but potentially fatal. Independent predictors were prior biliary intervention, prior transarterial chemoembolization, and the largest tumor size. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Ben-Arie and Sosna in this issue.
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Carcinoma Hepatocelular , Ablación por Catéter , Quimioembolización Terapéutica , Neoplasias Hepáticas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Ablación por Catéter/métodosRESUMEN
Medical text classification, as a fundamental medical natural language processing task, aims to identify the categories to which a short medical text belongs. Current research has focused on performing the medical text classification task using a pre-training language model through fine-tuning. However, this paradigm introduces additional parameters when training extra classifiers. Recent studies have shown that the "prompt-tuning" paradigm induces better performance in many natural language processing tasks because it bridges the gap between pre-training goals and downstream tasks. The main idea of prompt-tuning is to transform binary or multi-classification tasks into mask prediction tasks by fully exploiting the features learned by pre-training language models. This study explores, for the first time, how to classify medical texts using a discriminative pre-training language model called ERNIE-Health through prompt-tuning. Specifically, we attempt to perform prompt-tuning based on the multi-token selection task, which is a pre-training task of ERNIE-Health. The raw text is wrapped into a new sequence with a template in which the category label is replaced by a [UNK] token. The model is then trained to calculate the probability distribution of the candidate categories. Our method is tested on the KUAKE-Question Intention Classification and CHiP-Clinical Trial Criterion datasets and obtains the accuracy values of 0.866 and 0.861. In addition, the loss values of our model decrease faster throughout the training period compared to the fine-tuning. The experimental results provide valuable insights to the community and suggest that prompt-tuning can be a promising approach to improve the performance of pre-training models in domain-specific tasks.
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Soybean oil body (SOB) emulsions were prepared using OBs extracted at pH 11.0 and pH 7.0. The pH 11.0-SOB comprised oleosins, whereas pH 7.0-SOB comprised extrinsic proteins and oleosins. All SOB emulsions were heated at 60-100 °C for 15 min. Heating may lead to the release of extrinsic proteins from the surface of pH 7.0-SOB due to heat-induced denaturation. The total proportion of α-helix and ß-sheets gradually decreased from 77 (unheated) to 36.2% (100 °C). During stomach digestion, the extrinsic protein hydrolysis of heated pH 7.0-SOB emulsions was fast between 60 and 80 °C, and it then slowed between 90 and 100 °C; heating inhibited the oleosin hydrolysis of pH 7.0- and 11.0-SOBs. Heat treatment promoted aggregation and coalescence, and it resulted in increased particle sizes for all emulsions. Larger aggregates were found in heated pH 7.0-SOB emulsions, and larger oil droplets were found in heated pH 11.0-SOB emulsions. After intestinal digestion, the droplets of all SOB emulsions gradually dispersed, and particle sizes decreased. Different heating temperatures had lesser effects on particle sizes and microstructures. Lipolysis was affected by the extraction pH and heating. For pH 11.0-SOB emulsions, the FFA release tendency was greatly affected by the heating temperature, and heating to 80 °C resulted in the highest FFA release (74%). However, all pH 7.0-SOB emulsions had similar total FFA releases. In addition, the droplet charges of heated pH 7.0-SOB emulsions were lower than those of unheated pH 7.0-SOB emulsions in both the intestine and stomach phases; however, the charge changes in different pH 11.0-SOB emulsions showed the opposite tendency. This study will offer guidance regarding the application of SOB emulsions in food.
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AIMS: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. METHODS: Differentially expressed gene patterns between liver samples of BA (n = 102) and non-BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C-index. RESULTS: Using the least absolute shrinkage and selection operator model, we generated a nine-gene prognostic classifier. The nomogram based on the nine-gene classifier, age, preoperative 2DSWE, and albumin had the better C-index compared to gene classifier alone in the training cohort (0.83 [0.76-0.90] vs. 0.69 [0.61-0.77], p = 0.003) and the validation cohort (0.74 [0.67-0.82] vs. 0.62 [0.55-0.70], p = 0.001). Using risk scores developed from the nomogram, the 12-month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7-56.3) in the high-risk group and 80.8% (95% CI, 63.4-100.0) in the low-risk group in the validation cohort. CONCLUSIONS: The comprehensive genetic-clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.
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Salt and osmotic stress seriously restrict the growth, development, and productivity of horticultural crops in the greenhouse. The papain-like cysteine proteases (PLCPs) participate in multi-stress responses in plants. We previously demonstrated that salt and osmotic stress affect cysteine protease 15 of pepper (Capsicum annuum L.) (CaCP15); however, the role of CaCP15 in salt and osmotic stress responses is unknown. Here, the function of CaCP15 in regulating pepper salt and osmotic stress resistance was explored. Pepper plants were subjected to abiotic (sodium chloride, mannitol, salicylic acid, ethrel, methyl jasmonate, etc.) and biotic stress (Phytophthora capsici inoculation). The CaCP15 was silenced through the virus-induced gene silencing (VIGS) and transiently overexpressed in pepper plants. The full-length CaCP15 fragment is 1568 bp, with an open reading frame of 1032 bp, encoding a 343 amino acid protein. CaCP15 is a senescence-associated gene 12 (SAG12) subfamily member containing two highly conserved domains, Inhibitor 129 and Peptidase_C1. CaCP15 expression was the highest in the stems of pepper plants. The expression was induced by salicylic acid, ethrel, methyl jasmonate, and was infected by Phytophthora capsici inoculation. Furthermore, CaCP15 was upregulated under salt and osmotic stress, and CaCP15 silencing in pepper enhanced salt and mannitol stress resistance. Conversely, transient overexpression of CaCP15 increased the sensitivity to salt and osmotic stress by reducing the antioxidant enzyme activities and negatively regulating the stress-related genes. This study indicates that CaCP15 negatively regulates salt and osmotic stress resistance in pepper via the ROS-scavenging.
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Capsicum , Osmorregulación , Cloruro de Sodio/farmacología , Cloruro de Sodio/metabolismo , Capsicum/genética , Antioxidantes/metabolismo , Ácido Salicílico/farmacología , Ácido Salicílico/metabolismo , Manitol/farmacologíaRESUMEN
BACKGROUND: The pediatric liver contrast-enhanced ultrasound (CEUS) criteria were developed to improve the diagnostic performance of CEUS in differentiating pediatric benign and malignant liver lesions. However, the diagnostic performance of CEUS in the evaluation of multiple focal liver lesions in the pediatric population has not yet been fully evaluated. OBJECTIVE: To evaluate the diagnostic performance of the pediatric liver CEUS criteria in differentiating benign and malignant multifocal liver lesions in children. MATERIALS AND METHODS: From April 2017 to September 2022, the CEUS characteristics of multifocal liver lesions in patients < 18 years were analyzed. Lesions classified as CEUS-1, CEUS-2 or CEUS-3 were considered benign and lesions classified as CEUS-4 or CEUS-5 were considered malignant. The diagnostic performance of the pediatric liver CEUS criteria (i.e. sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV] and accuracy) was assessed. RESULTS: After exclusion, 21 patients (median age, 36.0 months; range, 1.0-204 months; 7 boys) were included. There were significant differences in the serum alpha fetoprotein level (P= 0.039) and the presence of washout (P < 0.001) between children with malignant and benign lesions. The sensitivity, specificity, PPV, NPV and accuracy of the pediatric liver CEUS criteria were 100.0% (10/10), 90.9% (10/11), 90.9% (10/11), 100.0% (10/10) and 95.2% (20/21), respectively. CONCLUSION: The pediatric liver CEUS criteria had excellent diagnostic performance in differentiating benign and malignant multifocal liver lesions in children.
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Medios de Contraste , Neoplasias Hepáticas , Masculino , Humanos , Niño , Preescolar , Sensibilidad y Especificidad , Ultrasonografía , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Estudios RetrospectivosRESUMEN
Erythroblastic islands (EBIs) are the specialized structures for erythropoiesis, but they have never been found functional in tumors. As the most common pediatric liver malignancy, hepatoblastoma (HB) requires more effective and safer therapies to prevent progression and the lifelong impact of complications on young children. However, developing such therapies is impeded by a lack of comprehensive understanding of the tumor microenvironment. By single-cell RNA sequencing of 13 treatment-naive HB patients, we discover an immune landscape characterized by aberrant accumulation of EBIs, formed by VCAM1+ macrophages and erythroid cells, which is inversely correlated with survival of HB. Erythroid cells inhibit the function of dendritic cells (DCs) via the LGALS9/TIM3 axis, leading to impaired anti-tumor T cell immune responses. Encouragingly, TIM3 blockades relieve the inhibitory effect of erythroid cells on DCs. Our study provides an immune evasion mechanism mediated by intratumoral EBIs and proposes TIM3 as a promising therapeutic target for HB.
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Hepatoblastoma , Neoplasias Hepáticas , Niño , Humanos , Preescolar , Eritroblastos/fisiología , Receptor 2 Celular del Virus de la Hepatitis A , Eritropoyesis/genética , Microambiente TumoralRESUMEN
The present study was designed to detect possible biomarkers associated with Type 1 diabetes mellitus (T1DM) incidence in an effort to develop novel treatments for this condition. Three mRNA expression datasets of peripheral blood mononuclear cells (PBMCs) were obtained from the GEO database. Differentially expressed genes (DEGs) between T1DM patients and healthy controls were identified by Limma package in R, and using the DEGs to conduct GO and DO pathway enrichment. The LASSO-SVM were used to screen the hub genes. We performed immune correlation analysis of hub genes and established a T1DM prognosis model. CIBERSORT algorithm was used to identify the different immune cells in distribution between T1DM and normal samples. The correlation of the hub genes and immune cells was analyzed by Spearman. ROC curves were used to assess the diagnostic value of genes in T1DM. A total of 60 immune related DEGs were obtained from the T1DM and normal samples. Then, DEGs were further screened to obtain 3 hub genes, ANP32A-IT1, ESCO2 and NBPF1. CIBERSORT analysis revealed the percentage of immune cells in each sample, indicating that there was significant difference in monocytes, T cells CD8+, gamma delta T cells, naive CD4+ T cells and activated memory CD4+ T cells between T1DM and normal samples. The area under curve (AUC) of ESCO2, ANP32A-IT1 and NBPF1 were all greater than 0.8, indicating that these three genes have high diagnostic value for T1DM. Together, the findings of these bioinformatics analyses thus identified key hub genes associated with T1DM development.
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Diabetes Mellitus Tipo 1 , Humanos , Pronóstico , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Leucocitos Mononucleares , Algoritmos , Aprendizaje Automático , Proteínas Nucleares , Proteínas de Unión al ARN , Acetiltransferasas , Proteínas Cromosómicas no HistonaRESUMEN
Immune checkpoint blockade (ICB) has shown great promise in treating various advanced malignancies including triple-negative breast cancer (TNBC). However, only limited number of patients could benefit from it due to the low immune response rate caused by insufficient matured dendritic cells (DCs) and inadequate tumor infiltration of cytotoxic T lymphocytes (CTLs). Here, we report a combination therapeutic strategy which integrates STING pathway activation, hypoxia relief and sonodynamic therapy (SDT) with anti-PD-L1 therapy to improve the therapeutic outcome. The synthesized nanodroplet consisted of a O2-filled Perfluorohexane (PFH) core and a lipid membrane carrying sonosensitizer IR-780 and STING agonist Vadimezan (DMXAAs). It released O2 inside the hypoxic tumor tissue, thereby enhancing SDT which relied on O2 to generate cytotoxic reactive oxygen species (ROS). The co-delivered STING agonist DMXAAs promoted the maturation and tumor antigen cross-presenting of DCs for priming of CTLs. Moreover, SDT induced immunogenic cell death (ICD) of tumor to release abundant tumor-associated antigens, which increased tumor immunogenicity to promote tumor infiltration of CTLs. Consequently, not only a robust adaptive immune response was elicited but also the immunologically "cold" TNBC was turned "hot" to enable a potent anti-PD-L1 therapy. The nanodroplet demonstrated strong efficacy to systemically suppress TNBC growth and mimic distant tumor in vivo. STATEMENT OF SIGNIFICANCE: Only a limited number of triple-negative breast cancer (TNBC) patients can benefit from immune checkpoint blockade therapy due to its low immune response rate caused by insufficient matured DCs and inadequate tumor infiltration of cytotoxic T lymphocytes (CTLs). Interestingly, compelling evidence has shown that sonodynamic therapy (SDT) not only directly kills cancer cells but also elicits immunogenic cell death (ICD), which promotes tumor infiltration of cytotoxic T lymphocytes to transform an immunosuppressive "cold" tumor into a "hot" one. However, the hypoxic tumor microenvironment severely restricts the therapeutic efficiency of SDT, wherein, oxygen is indispensable in the process of ROS generation. Here, we report an O2-filled nanodroplet-enhanced sonodynamic therapy that significantly potentiated immune checkpoint blockade for systemic suppression of TNBC.
Asunto(s)
Inhibidores de Puntos de Control Inmunológico , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Especies Reactivas de Oxígeno , Hipoxia , Oxígeno , Línea Celular Tumoral , Microambiente TumoralRESUMEN
OBJECTIVE: To explored the roles of phosphorylated signal transduction and activator of transcription 3 (p-STAT3) and IL (interleukin) -17 in patients with dermatomyositis (DM). METHODS: A total of 20 DM patients and 12 healthy controls were enrolled. The Flow cytometry combined with counting was used to detect the numbers of Th17 cells. Western blotting and immunohistochemistry was used to examine the muscle levels of p-STAT3 and IL-17, and serum levels of IL-17 were measured by enzyme-linked immunosorbent assays. RESULTS: Muscle p-STAT3 and IL-17 levels, the numbers of Th17 cells, and serum IL-17 levels were markedly increased in DM. p-STAT3 and IL-17 were co-expressed in the muscle of DM patients. The p-STAT3 levels correlated with the number of Th17 cells as well as muscle and serum IL-17 levels. The correlations of the p-STAT3 level with elevated levels of transaminases, myocardial enzymes, and the health assessment questionnaire score were significantly positive, while the correlation with manual muscle testing-8 was significantly negative. A receiver operating characteristic curve indicated good predictive value of p-STAT3 for the occurrence of DM. CONCLUSION: The increased p-STAT3/IL-17 signaling pathway activation in DM patients may induce muscle inflammation and necrosis, and it may be a potential target for DM.