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Pancreatic cancer is highly lethal, and survival chances improve only with early detection at a precancerous stage. However, there remains a significant gap in developing tools for large-scale, rapid screening. To this end, a high-throughput On-Target Array Extraction Platform (OTAEP) by direct sintering of a series of metal-organic frameworks (MOFs) for dual in situ extraction, encompassing both exosomes and their metabolic profiles, is developed. Based on the principle of geometry-dependent photothermal conversion efficiency and standard testing, the appropriate MOF functional unit is identified. This unit enables exosome enrichment within 10 min and metabolic fingerprint extraction in under 1 s of laser irradiation, with over five reuse. To further accelerate and enhance the quality of metabolic profile analysis, the application of Surrogate Variable Analysis to eliminate hidden confounding factors within the profiles is proposed, and five biomarkers demonstrated by MS/MS experiments are identified. These biomarkers enable early diagnosis, risk stratification, and staging of pancreatic cancer simultaneously, with sensitivity of 94.1%, specificity of 98.8%, and precision of 94.9%. This work represents a breakthrough for overcoming throughput challenges in large-scale testing and for addressing confounding factors in big data analysis.
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The downregulation of Cadm4 (Cell adhesion molecular 4) is a prominent feature in demyelination diseases, yet, the underlying molecular mechanism remains elusive. Here, we reveal that Cadm4 undergoes specific palmitoylation at cysteine-347 (C347), which is crucial for its stable localization on the plasma membrane (PM). Mutation of C347 to alanine (C347A), blocking palmitoylation, causes Cadm4 internalization from the PM and subsequent degradation. In vivo experiments introducing the C347A mutation (Cadm4-KI) lead to severe myelin abnormalities in the central nervous system (CNS), characterized by loss, demyelination, and hypermyelination. We further identify ZDHHC3 (Zinc finger DHHC-type palmitoyltransferase 3) as the enzyme responsible for catalyzing Cadm4 palmitoylation. Depletion of ZDHHC3 reduces Cadm4 palmitoylation and diminishes its PM localization. Remarkably, genetic deletion of ZDHHC3 results in decreased Cadm4 palmitoylation and defects in CNS myelination, phenocopying the Cadm4-KI mouse model. Consequently, altered Cadm4 palmitoylation impairs neuronal transmission and cognitive behaviors in both Cadm4-KI and ZDHHC3 knockout mice. Importantly, attenuated ZDHHC3-Cadm4 signaling significantly influences neuroinflammation in diverse demyelination diseases. Mechanistically, we demonstrate the predominant expression of Cadm4 in the oligodendrocyte lineage and its potential role in modulating cell differentiation via the WNT-ß-Catenin pathway. Together, our findings propose that dysregulated ZDHHC3-Cadm4 signaling contributes to myelin abnormalities, suggesting a common pathological mechanism underlying demyelination diseases associated with neuroinflammation.
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Aciltransferases , Sistema Nervoso Central , Lipoilação , Bainha de Mielina , Lipoilação/genética , Animais , Aciltransferases/genética , Camundongos , Humanos , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Bainha de Mielina/patologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/metabolismo , Camundongos KnockoutRESUMO
Motivation: Circular RNAs (circRNAs) play important roles in gene expression and their involvement in tumorigenesis is emerging. circRNA-related database is a powerful tool for researchers to investigate circRNAs. However, existing databases lack advanced platform integrating comprehensive information and analysis tools of cancer-related circRNAs. Results: We developed a comprehensive platform called CircRNA to Cancer Database (C2CDB), encompassing 318 158 cancer-related circRNAs expressed in tumors and adjacent tissues across 30 types of cancers. C2CDB provides basic details such as sequence and expression levels of circRNAs, as well as crucial insights into biological mechanisms, including miRNA binding, RNA-binding protein interaction, coding potential, base modification, mutation, and secondary structure. Moreover, C2CDB collects an extensive compilation of published literature on cancer circRNAs, extracting and presenting pivotal content encompassing biological functions, underlying mechanisms, and molecular tools in these studies. Additionally, C2CDB offers integrated tools to analyse three potential mechanisms: circRNA-miRNA ceRNA interaction, circRNA encoding, and circRNA biogenesis, facilitating investigators with convenient access to highly reliable information. To enhance clarity and organization, C2CDB has meticulously curated and integrated the previously chaotic nomenclature of circRNAs, addressing the prevailing confusion and ambiguity surrounding their designations. Availability and implementation: C2CDB is freely available at http://pengyonglab.com/c2cdb.
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The advantages of small extracellular vesicles (sEV) in disease management have become increasingly prominent, with the main challenge lying in meeting the demands of large-scale extraction and high-throughput analysis, a crucial aspect in the realm of precision medicine. To overcome this challenge, an engineered on-plate aptamer array (16×24 spots) is developed for continuous scale-up microextraction of plasma sEV and their in situ metabolic analysis using mass spectrometry. With this integrated array strategy, metabolic profiles of sEV are acquired from the plasma of 274 antenatal or postpartum women, reducing analysis time by half (7.5 h) and sample volume by 95% (only 0.125 µL usage) compared to the traditional suspension method. Moreover, using machine learning algorithms on sEV metabolic profiles, a risk score system is constructed that accurately assesses the need for epidural analgesia during childbirth and the likelihood of post-administration fever. The system, based on admission samples, achieves an impressive 94% accuracy. Furthermore, post-administration fever can be identified from delivery samples, reaching an overall accuracy rate of 88%. This work offers real-time monitoring of the childbirth process that can provide timely guidance for maternal delivery, underscoring the significance of sEV detection in large-scale clinical samples for medicine innovation and advancement.
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Background: Alveolar Rhabdomyosarcoma is a profoundly malignant soft-tissue sarcoma that predominantly affects children and adolescents. However, the medical field lacks consensus regarding the optimal surgical approach to be undertaken in cases where this tumor causes local bone destruction in the upper limb. Case description: A 17-year-old male presented a mass in his left forearm and CT and MRI indicated that the mass had penetrated the ulnar cortex and infiltrating the medulla, resulting in the formation of an eccentric trans-ventricular tumor focus. The sizable tumor affected the volar muscles of the forearm as well as the ulnar bone marrow, exerting pressure on the ulnar artery and vein. It was confirmed by needle biopsy that the mass is alveolar rhabdomyosarcoma. Following two courses of neoadjuvant chemotherapy, the tumor was widely excised en bloc. Autologous fibula with a vascular pedicle was utilized for reconstruction during the procedure. In the postoperative follow-up, no local recurrence of the tumor was observed. Furthermore, the patient retained satisfactory wrist flexion and pronation function in the left forearm. Conclusions: Alveolar rhabdomyosarcoma is an uncommon and highly aggressive form of soft tissue sarcoma. Scientific management necessitates a multidisciplinary approach, combining chemotherapy with surgery. In cases where the tumor invaded into compartment of the bone, careful consideration should be given to the boundaries of tumor resection, the extent of osteotomy, and the approach to musculoskeletal reconstruction when designing the surgical plan. Through reporting our own case and thoroughly reviewing previous clinical experiences, we aim to provide valuable insights for the treatment of this particular disease.
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BACKGROUND: Choledochal cyst with perforation (CC with perforation) rarely occurs, early diagnosis and timely treatment plan are crucial for the treatment of CC with perforation. This study aims to forecast the occurrence of CC with perforation. METHODS: All 1111 patients were conducted, who underwent surgery for choledochal cyst at our hospital from January 2011 to October 2022. We conducted univariate and multivariate logistic regression analysis to screen for independent predictive factors for predicting CC with perforation, upon which established a nomogram. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA) curves. RESULTS: The age of children with choledochal cyst perforation is mainly concentrated between 1 and 3 years old. Logistic regression analysis indicates that age, alanine aminotransferase, glutamyl transpeptidase, C-reactive protein, vomiting, jaundice, abdominal distension, and diarrhea are associated with predicting the occurrence of choledochal cyst perforation. ROC curves, calibration plots, and DCA curve analysis curves demonstrate that the nomogram has great discriminative ability and calibration, as well as significant clinical utility. CONCLUSION: The age of CC with perforation is mainly concentrated between 1 and 3 years old. A nomogram for predicting the perforation of choledochal cyst was established.
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Cisto do Colédoco , Nomogramas , Humanos , Cisto do Colédoco/cirurgia , Cisto do Colédoco/complicações , Cisto do Colédoco/diagnóstico , Pré-Escolar , Masculino , Feminino , Lactente , Criança , Estudos Retrospectivos , Curva ROCRESUMO
Bacterial diseases caused substantial yield losses worldwide, with the rise of antibiotic resistance, there is a critical need for alternative antibacterial compounds. Natural products (NPs) from microorganisms have emerged as promising candidates due to their potential as cost-effective and environmentally friendly bactericides. However, the precise mechanisms underlying the antibacterial activity of many NPs, including Guvermectin (GV), remain poorly understood. Here, we sought to explore how GV interacts with Guanosine 5'-monophosphate synthetase (GMPs), an enzyme crucial in bacterial guanine synthesis. We employed a combination of biochemical and genetic approaches, enzyme activity assays, site-directed mutagenesis, bio-layer interferometry, and molecular docking assays to assess GV's antibacterial activity and its mechanism targeting GMPs. The results showed that GV effectively inhibits GMPs, disrupting bacterial guanine synthesis. This was confirmed through drug-resistant assays and direct enzyme inhibition studies. Bio-layer interferometry assays demonstrated specific binding of GV to GMPs, with dependency on Xanthosine 5'-monophosphate. Site-directed mutagenesis identified key residues crucial for the GV-GMP interaction. This study elucidates the antibacterial mechanism of GV, highlighting its potential as a biocontrol agent in agriculture. These findings contribute to the development of novel antibacterial agents and underscore the importance of exploring natural products for agricultural disease management.
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Adenosina/análogos & derivados , Antibacterianos , Ivermectina , Antibacterianos/farmacologia , Antibacterianos/química , Ivermectina/farmacologia , Ivermectina/análogos & derivados , Ivermectina/química , Simulação de Acoplamento Molecular , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Testes de Sensibilidade Microbiana , Carbono-Nitrogênio Ligases/metabolismo , Carbono-Nitrogênio Ligases/química , Carbono-Nitrogênio Ligases/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/química , Mutagênese Sítio-DirigidaRESUMO
Exosome metabolite-based liquid biopsy is a promising strategy for large-scale application in practical clinics toward precise medicine. Given the current challenges in successive isolation and analysis of exosomes and their metabolites in this field, we established a low-cost, high-throughput, and rapid platform for serological exosome metabolic biopsy of hepatocellular carcinoma (HCC) via designed core-shell nanoparticles. It starts with the efficient extraction of high-quality serum exosomes and exosome metabolic features, based on which significantly obvious sample clusters are observed by unsupervised cluster analysis. The following integration of feature selection and supervised machine learning enables the identification of six key metabolites and achieves high-performance prediction between HCC, liver cirrhosis, and healthy controls. Specifically, both sensitivity and accuracy achieve 100% among any pairwise intergroup discrimination in a blind test. The quality and reliability of six key metabolites are further evaluated and validated by using different machine learning algorithms and pathway exploration. Our platform contributes to the future growth of new liquid biopsy technologies for precision diagnosis and real-time monitoring of HCC, among other conditions.
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Exosome metabolite-based noninvasive liquid biopsy is an emerging research hotspot that tends to substitute current means in clinics. Nanostructure-based mass spectrometry enables continuous exosome isolation and metabolic profiling with superior analysis speed and high efficiency. Herein, we construct a heterogeneous MXene hybrid that possesses ternary binding sites for exosome capture and outstanding matrix performance for metabolite analysis. Upon optimizing experimental conditions, the average extraction of exosomes and their metabolic patterns from a 60 mL urine sample is completed within 45 s (40 samples per batch for 30 min). According to the exosomal metabolic patterns and the subsequently established biomarker panel, we distinguish early bladder cancer (BCa) from healthy controls with an area under the curve (AUC) value greater than 0.995 in model training and validation sets. As well, we realize subtype classification of BCa in the blind test on metabolic patterns, with an AUC value of 0.867. We also explore the significant biomarkers that are sensitive to follow-up patients, which indeed present reverse change levels compared with pathological progression. This study has the potential to guide the development of the liquid biopsy approach.
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Exossomos , Neoplasias da Bexiga Urinária , Humanos , Exossomos/metabolismo , Seguimentos , Detecção Precoce de Câncer , Neoplasias da Bexiga Urinária/patologia , Biomarcadores/análise , Biomarcadores Tumorais/análiseRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in the digestive system with rapid progression and poor prognosis. Recent studies have shown that RPL27A could be used as a biomarker for a variety of cancers, but its role in HCC is not clear. METHOD: We analyzed the expression of RPL27A in the pan-cancer analysis and analyzed the relationship between the expression of RPL27A and the clinical features and prognosis of patients with HCC. We evaluated the expression difference of RPL27A in HCC tissues and paired normal adjacent tissues using immunohistochemistry. Furthermore, we analyzed the co-expression genes of RPL27A and used them to explore the possible mechanism of RPL27A and screen hub genes effecting HCC. In addition, we studied the role of RPL27A in immune infiltration and mutation. RESULTS: We found that the expression level of RPL27A increased in a variety of cancers, including HCC. In HCC patients, the high expression of RPL27A was related to progression and poor prognosis as an independent predictor. We also constructed a protein interaction network through co-expression gene analysis of RPL27A and screened 9 hub genes. Enrichment analysis showed that co-expression genes were associated with ribosome pathway, viral replication, nuclear-transcribed mRNA catabolic process, and nonsense-mediated decay. We found that the expression level of RPL27A was closely related to TP53 mutation and immune infiltration in HCC. CONCLUSION: RPL27A might become a biomarker in the diagnosis, treatment, and follow-up of patients with HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Expressão Gênica , Neoplasias Hepáticas/genética , Mutação , Prognóstico , Mapas de Interação de ProteínasRESUMO
With limited therapeutic options for hepatocellular carcinoma (HCC), it is of great significance to investigate the underlying mechanisms and identifying tumor drivers. MCM6, a member of minichromosome maintenance proteins (MCMs), was significantly elevated in HCC progression and associated with poor prognosis. Knockdown of MCM6 significantly inhibited the proliferation and migration of HCC cells with the increased apoptosis ratio and cell cycle arrest, whereas overexpression of MCM6 induced adverse effects. Mechanistically, MCM6 could decrease the P53 activity by inducing the degradation of P53 protein. In addition, MCM6 enhanced the ubiquitination of P53 by recruiting UBE3A to form a triple complex. Furthermore, overexpression of UBE3A significantly rescued the P53 activation and suppression of malignant behaviors mediated by MCM6 inhibition. In conclusion, MCM6 facilitated aggressive phenotypes of HCC cells by UBE3A/P53 signaling, providing potential biomarkers and targets for HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Manutenção de Minicromossomo/genética , Proteínas de Manutenção de Minicromossomo/metabolismo , Ubiquitinação , Família , Proliferação de Células , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Introduction: Comminuted fractures are characterized by bones broken in at least two places, destabilizing the bone and requiring surgery. Children whose bones are still developing and maturing tend to have a higher risk of sustaining comminuted fractures as the result of trauma. Trauma is a major cause of death in children and constitutes a major issue in orthopedics because of the unique properties of children's bones compared to adult bones and the associated complications. Methods: This retrospective, cross-sectional study aimed to refine the association between comorbid disease and comminuted fractures in pediatric subjects using a large, national database. All data were extracted from the National Inpatient Sample (NIS) database from 2005 to 2018. Logistic regression analysis was used to evaluate associations between comorbidities and comminuted fracture surgery and between various comorbidities and LOS or unfavorable discharge. Results: A total of 2,356,483 patients diagnosed with comminuted fractures were selected initially, of whom 101,032 patients aged younger than 18 years who underwent surgery for comminuted fractures were included. Study results suggest that patients with any comorbidities undergoing orthopedic surgery for comminuted fracture appear to have longer LOS and a higher proportion of discharge to long-term care facilities. Discussion: Almost all comorbidities were significantly associated with poor in-hospital outcomes and longer LOS. The analysis of comminuted fractures in children may provide useful information to help first responders and medical personnel evaluate and manage comminuted fractures appropriately.
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New therapeutic approaches are needed for metastatic osteosarcoma (OS), as survival rates remain low despite surgery and chemotherapy. Epigenetic changes, such as histone H3 methylation, play key roles in many cancers including OS, although the underlying mechanisms are not clear. In this study, human OS tissue and OS cell lines displayed lower levels of histone H3 lysine trimethylation compared with normal bone tissue and osteoblast cells. Treating OS cells with the histone lysine demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX-1) dose-dependently increased histone H3 methylation and inhibited cellular migratory and invasive capabilities, suppressed matrix metalloproteinase expression, reversed epithelial-to-mesenchymal transition by increasing levels of epithelial markers E-cadherin and ZO-1 and decreasing the expression of mesenchymal markers N-cadherin, vimentin, and TWIST, and also reduced stemness properties. An analysis of cultivated MG63 cisplatin-resistant (MG63-CR) cells revealed lower histone H3 lysine trimethylation levels compared with levels in MG63 cells. Exposing MG63-CR cells to IOX-1 increased histone H3 trimethylation and ATP-binding cassette transporter expression, potentially sensitizing MG63-CR cells to cisplatin. In conclusion, our study suggests that histone H3 lysine trimethylation is associated with metastatic OS and that IOX-1 or other epigenetic modulators present promising strategies to inhibit metastatic OS progression.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Histonas/metabolismo , Lisina/metabolismo , Cisplatino/farmacologia , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológicoRESUMO
Tetrabromobisphenol A (TBBPA), as an emerging endocrine disrupter, has been considered one of the persistent organic contaminants in water. It is urgently necessary to develop an efficient technique for the effective removal of TBBPA from water. Herein, a one-step hydrothermal synthesis route was employed to prepare a novel iron-carbon core-shell nanoparticle (Fe@MC) for effectively activating persulfate (PS) to degrade TBBPA. Morphological and structural characterization indicated that the prepared Fe@MC had a typical core-shell structure composed of a 5 nm thick graphene-like carbon shell and a multi-valence iron core. It can be seen that 94.9% of TBBPA (10 mg/L) could be degraded within 30 min at pH = 7. This excellent catalytic activity was attributed to the synergistic effect of the porous carbon shell and a multi-valence iron core. The porous carbon shell could effectively prevent the leaching of metal ions and facilitate PS activation due to its electron transfer capability. Furthermore, numerous micro-reaction zones could be formed on the surface of Fe@MC during the rapid TBBPA removal process. Radical quenching experiments and electron paramagnetic resonance (EPR) technology indicated that reactive oxygen species (ROS), including OH, SO4-, O2-, and 1O2, were involved in the TBBPA degradation process. Based on density functional theory (DFT) calculation, the carbon atoms linked by phenolic hydroxyl groups would be more vulnerable to attack by electron-rich groups; the central carbon was cracked and hydroxylated to generate short-chain aliphatic acids. The toxicity evaluation provides clear evidence for the promising application potential of our prepared material for the efficient removal of TBBPA from water.
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OBJECTIVE: To analyze the incidence trend and establish a model to predict the prognosis of hepatic malignant tumors in children (CHMTs). METHODS: We analyzed the incidence data of CHMTs from 1975 to 2018 from the Surveillance, Epidemiology, and End Results (SEER) database, and evaluated the incidence trends based on different demographic and pathological features. We also analyzed clinicopathologic data from 2000 to 2018 from the SEER database. Univariate and multivariate Cox regression analyses were performed to explore prognostic factors related to overall survival (OS). Then, we established nomograms based on independent predictors and verified them using receiver operating characteristic curves, calibration plots, and decision curve analysis plots. RESULTS: The incidence of CHMTs increased significantly, from 0.1 per 100,000 in 1975 to 0.4 per 100,000 in 2018. Incidences among different races and genders were increasing and converging. The incidence of hepatoblastoma (HB) increased, while that of hepatocellular carcinoma (HCC) was relatively stable. The 1-, 3-, 5-, and 10-year OS rates were 86.2%, 77.5%, 74.2%, and 70.2%, respectively. Being Spanish-Hispanic-Latino, HB, surgery, and systemic therapy were independent predictors of longer OS, whereas regional and distant stages were independent predictors of shorter OS. Nomograms with good predictive ability and clinical utility were established to evaluate the prognosis of children with HB or HCC. CONCLUSION: The incidence of CHMTs is increasing, especially for HB and in younger children. This study identified independent predictors and developed nomograms that could provide a personalized and accurate prognosis for CHMTs.
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Background: Liver transplantation (LT) is one of the most important treatments for children with liver cancer (CLCa) and has been increasingly used. However, there is a lack of large-scale and multicenter studies on the trend in the application and value of LT for the treatment of CLCa. Methods: We analyzed the clinicopathological data of CLCa from 2000 to 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. We explored the trend in the application of LT for the treatment of CLCa. LASSO Cox regression and the Log-Rank test were used to explore prognostic factors, and we built a nomogram using the screened factors. Propensity score matching was used to balance the baseline data of patients undergoing LT and other surgeries, and then the Log-Rank test was used to evaluate the therapeutic value of LT for CLCa. Results: The 1-year, 3-year, 5-year, and 10-year overall survival (OS) rates of CLCa were 88.7%, 80.6%, 76.8%, and 73.0%, respectively. Then, we established a nomogram using many variables including age of diagnosis, regional lymph node metastasis, summary stage, and therapy. Internally validated and externally verified, our nomogram had good predictive power and clinical applicability. LT was increasingly being used to treat CLCa. There was no statistically significant difference in the OS of CLCa between the LT and other surgeries groups. After LT, the hepatoblastoma group had a better prognosis than the hepatocellular carcinoma group. Conclusion: We built a well-performing nomogram to predict the OS of CLCa. LT could improve the prognosis of CLCa as other surgeries and could be considered an effective treatment choice for CLCa.
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RATIONALE: In clinical practice, foreign bodies (FBs) in the digestive tract are more common in children, but intrahepatic FBs are rare, especially those that can cause infection, bleeding, bile leakage, and other complications. However, there is no consensus on its diagnosis and treatment due to the lack of large-scale cohort studies. PATIENT CONCERNS: Case 1 is a 4-years 8-months-old girl, who at the age of 10 months, showed an X-ray finding of a striped FB in her liver, with no symptoms. However, the patient's parents refused surgery. After nearly 4 years of active surveillance, the patient visited our hospital for surgery. Case 2, a 2-year-old male, reported a sewing needle that completely pierced into the right upper abdomen due to an accidental fall that took place half-a-day before admission. He only had right upper abdominal pain. CT showed a striped FB in the liver. DIAGNOSIS: FB in the liver (sewing needle). INTERVENTIONS: Both the patients were injected with human tetanus immunoglobulin and underwent surgical removal. OUTCOMES: Both patients recovered smoothly and had no complications during follow-up. LESSONS: Active surveillance might be considered for cases with no symptoms or complications and no displacement of the FB, but surgery should be the first choice. If the patient's condition is complicated, it is recommended to use ultrasound or X-ray to help decision-making during the operation. Additionally, tetanus, child safety, and family education are important supportive measures.
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Corpos Estranhos , Tétano , Abdome , Dor Abdominal , Criança , Pré-Escolar , Feminino , Corpos Estranhos/complicações , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Lactente , Fígado/diagnóstico por imagem , Fígado/cirurgia , Masculino , AgulhasRESUMO
The prediction of tumor drug sensitivity plays an important role in clinically guiding patients' medication. In this paper, a multi-omics data-based cancer drug sensitivity prediction model was constructed by Stacking ensemble learning method. The data including gene expression, mutation, copy number variation and drug sensitivity value (IC50) of 198 drugs were downloaded from the GDSC database. Multiple feature selection methods were applied for dimensionality reduction. Six primary learners and one secondary learner were integrated into modeling by Stacking method. The model was validated with 5-fold cross-validation. In the prediction results, 36.4% of drug models' AUCs were greater than 0.9, 49.0% of drug models' AUCs were between 0.8-0.9, and the lowest drug model's AUC was 0.682. The multi-omics model for drug sensitivity prediction based on Stacking method is better than the known single-omics or multi-omics model in terms of accuracy and stability. The model based on multi-omics data is better than the single-omics data in predicting drug sensitivity. Function annotation and enrichment analysis of feature genes revealed the potential resistance mechanism of tumors to sorafenib, providing the model interpretability from a biological perspective, and demonstrated the model's potential applicability in clinical medication guidance.
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Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Variações do Número de Cópias de DNA , Resistência a Medicamentos , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genéticaRESUMO
(1) Background: The Fassier−Duval (FD) nail was developed for the treatment of osteogenesis imperfecta (OI). The aim of this study was to review the results of OI patients treated with the FD nail at our institution and discuss a surgical strategy to decrease the FD nail revision rate; (2) Methods: We retrospectively reviewed OI patients treated at our institution between 2015 and 2020. OI patients treated with FD nail insertion in the long bones of the lower extremities were included, and those with a follow-up duration <1 year or incomplete radiographs were excluded. Data on the type of OI, age, sex, use of bisphosphonate treatment, and nail failure were recorded; (3) Results: The final cohort consisted of seven patients (three females and four males) with ten femurs and ten tibiae involved. Six of the patients had type III OI, and one had type IV OI. An exchange of implant was required in 11 limbs. The average interval between previous FD nail insertion and revision surgery was 2.4 years; (4) Discussion: The main reasons for revision surgery were migration of the male/female component, refracture/nail bending, and delayed union. In the femur, migration of the female component or nail bending were common reasons for failure, while migration of the male component and delayed union were common in the tibia; (5) Conclusions: Surgery for OI patients is challenging, and physicians should aim to minimize complications and the need for revision. Sufficient depth of purchase, center−center nail position, and adequate osteotomy to correct bowing are the key factors when using the FD nail.