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BACKGROUND: Although non-invasive radiological techniques are widely applied in kidney renal clear cell carcinoma (KIRC) diagnosis, more than 50% of KIRCs are detected incidentally during the diagnostic procedures to identify renal cell carcinoma (RCC). Thus, sensitive and accurate KIRC diagnostic methods are required. Therefore, in this study, we aimed to identify KIRC-associated microRNAs (miRNAs). METHODS: This three-phase study included 224 participants (112 each of patients with KIRC and healthy controls (NCs)). RT-qPCR was used to evaluate miRNA expression in KIRC and NC samples. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to predict the usefulness of serum miRNAs in KIRC diagnosis. In addition, we performed survival and bioinformatics analyses. RESULTS: We found that miR-1-3p, miR-129-5p, miR-146b-5p, miR-187-3p, and miR-200a-3p were significantly differentially expressed in patients with KIRC. A panel consisting of three miRNAs (miR-1-3p, miR-129-5p, and miR-146b-5p) had an AUC of 0.895, ranging from 0.848 to 0.942. In addition, using the GEPIA database, we found that the miRNAs were associated with CREB5. According to the survival analysis, miR-146b-5p overexpression was indicative of a poorer prognosis in patients with KIRC. CONCLUSIONS: The identified three-miRNA panel could serve as a non-invasive indicator for KIRC and CREB5 as a potential target gene for KIRC treatment.
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Pressure-induced surface-enhanced Raman spectroscopy (PI-SERS) has garnered significant attention as a subfield of SERS detection due to its capacity to regulate the band gap between molecules and substrates through pressure modulation. Currently, SERS detection primarily focuses on single molecules at atmospheric pressure with limited investigations conducted under high pressure conditions. Herein, we employed rose-shaped MoS2 nanoflowers as the SERS substrate and realized selective PI-SERS enhancement of R6G molecules in the binary (MV+R6G) and ternary (MV+R6G+RhB) systems. The MoS2 demonstrated an exceptionally low SERS detection limit of 5 × 10-6 M in binary and ternary systems with equimolar amounts of molecules. High-pressure experimental results indicate that MoS2 displays selective enhancement for R6G molecules, as evidenced by the comparison of the PI-SERS peak intensity ratio between MoS2 and the probe molecules. The proposed enhancement mechanism in binary and ternary SERS systems under high pressure involves pressure-induced changes in both the band structures of the MoS2 substrate and molecules, thereby influencing their charge transfer dynamics. Consequently, this approach holds great promise for practical applications in complex SERS systems operating under extreme conditions.
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BACKGROUND: Bladder cancer (BC) is one of the ten most common cancers worldwide with late detection and early age of diagnosis. There is abundant evidence that early detection and timely intervention can lead to a better prognosis of BC. Substantial evidence has indicated that microRNAs (miRNAs) are specific to different tumour types and are remarkably stable, indicating that serum miRNAs may serve as potential cancer diagnostic markers. This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary BC. METHODS: In this study, 18 miRNAs that were differentially expressed in BC were obtained from the PubMed or Gene Expression Omnibus database. Then, 18 BC-related-miRNAs were verified in screening and validation sets created using 56 (28 primary BC vs. 28 NCs) and 168 (84 primary BC vs. 84 NCs) serum samples, respectively. Quantitative reverse transcription-PCR (qRT-PCR) was performed to verify the identity of the differential miRNAs. A multi-miRNA panel with superior diagnostic performance was constructed. TCGA and KEGG databases were used to conduct the survival analysis and bioinformatics analysis, respectively. RESULTS: Six serum miRNAs (miR-221-5p, miR-181a-5p, miR-98-5p, miR-15a-5p, miR-222-3p, and miR-197-3p) were significantly aberrantly expressed in the BC patients, while four miRNAs from among them (miR-221-5p, miR-181a-5p, miR-15a-5p, miR-222-3p) were assembled into a panel that showed high diagnostic value (AUC = 0.875, 95% CI: 0.815 - 0.921; sensitivity: 82.14%; and specificity: 85.71%) based on the logistic regression analysis. The survival analysis showed that miR-181a-5p was closely associated with BC prognosis (Log-rank p-value < 0.05). CONCLUSION: The combination of the four miRNAs (miR-221-5p, miR-181a-5p, miR-15a-5p and miR-222-3p) may be a novel non-invasive serological biomarker for BC screening.
Early detection and timely intervention can lead to a better prognosis of bladder cancer.This study aimed to identify suitable serum miRNAs to create a panel that can be used to diagnose primary bladder cancer.
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Biomarcadores Tumorais , MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/sangue , Neoplasias da Bexiga Urinária/diagnóstico , MicroRNAs/sangue , MicroRNAs/genética , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Feminino , Masculino , Pessoa de Meia-Idade , Prognóstico , Regulação Neoplásica da Expressão Gênica , Idoso , Perfilação da Expressão GênicaRESUMO
Background: Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. Materials & methods: A total of 224 participants were involved in this three-cohort trial. A total of 15 candidate miRNAs were selected, and miRNAs with diagnostic ability were screened out with quantitative reverse transcription PCR. Diagnostic capability was ascertained by the receiver operating characteristic curve and area under the curve. Bioinformatics analysis was constructed for target gene prediction and functional annotation. Results: Six candidate miRNAs showed significantly different expression between bladder cancer patients and normal controls, and the final diagnostic panel comprised miR-181b-5p, miR-183-5p, miR-199-5p and miR-221-3p. Conclusion: This four-miRNA panel could represent a stable biomarker for bladder cancer diagnosis.
Bladder cancer is one of the most prevalent malignancies. Due to the disadvantage of existing bladder cancer diagnostic tools, miRNAs hold promise as new diagnostic markers. After an experiment composed of 224 participants, the authors screened out six candidate miRNAs that may contribute to diagnosing bladder cancer. The authors also repeatedly verified the reliability of candidate miRNAs. Finally, a combination of multiple miRNAs, consisting of miR-181b-5p, miR-183-5p, miR-199-5p, and miR-221-3p, was better and more reliable in predicting bladder cancer occurrence.
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MicroRNAs , Neoplasias da Bexiga Urinária , Humanos , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Curva ROC , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/genéticaRESUMO
In this study, the effects of the Cd-resistant and pyoverdine-producing strain Pseudomonas umsongensis CR14 on Cd stabilization and the mechanisms were investigated. Compared with the control, CR14 markedly reduced the Cd concentration in a Cd-containing solution. The genes pvdA, 4498, 4499, and pchF, which are associated with pyoverdine production, were identified in CR14. Subsequently, CR14 and the CR14ΔpvdA, CR14Δ4498, CR14Δ4499, and CR14ΔpchF mutants were characterized for their effects on Cd stabilization in solution. After 72 h of incubation, the CR14ΔpchF and CR14ΔpvdA mutants significantly decreased Cd concentrations compared with CR14. Notably, the CR14ΔpvdA mutant showed a greater impact on Cd stabilization than the other mutants. Compared with CR14, this mutant brought a lower Cd concentration in the solution, with higher levels of cell surface-adsorbed and intracellular accumulated Cd, content of lipopolysaccharide (LPS), expression of the LPS-producing genes lptD and lpxL, and cell surface particles. Additionally, compared with CR14, the CR14ΔpvdA mutant demonstrated increased interactions between the hydroxyl, carboxyl, amino, or ether groups and Cd. These results suggest that the CR14ΔpvdA mutant immobilized Cd by increasing LPS production and cell surface particle numbers, upregulating the expression of LPS-producing genes, and increasing cell surface adsorption and intracellular accumulation in Cd-polluted solutions.
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Cádmio , Oligopeptídeos , Pseudomonas , Pseudomonas/metabolismo , Pseudomonas/genética , Oligopeptídeos/metabolismo , Poluentes Químicos da Água/metabolismo , Biodegradação Ambiental , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Lipopolissacarídeos , Deleção de GenesRESUMO
To explore the creep characteristics of geomembrane under different tensile stresses, a series of creep tests were carried out on high-density polyethylene (HDPE) geomembrane specimens. For the interpretation and fitting of the experimental data, refined approximation functions were proposed. Particular attention was paid to the creep failure behavior under high tensile stresses, i.e., 70%, 80%, and 90% of maximum peak stress. To investigate the effects of size on the mechanical response, experiments with two different membrane thicknesses were conducted. The results obtained under high stress levels were compared with creep tests at medium and low stress levels. Depending on load level, different creep characteristics can be distinguished. In the secondary creep state, the creep velocity is higher for higher load levels. In contrast to the medium and low load levels, the geomembrane under high stresses underwent the tertiary creep stage after instantaneous deformation and primary and secondary creep stages. In some tests, it was observed that under very high stress levels, creep velocity does not necessarily follow the expected trend and creep rupture can occur within a short time. For numerical simulation, an improved mathematical model was proposed to reproduce in a unified manner the experimental data of the whole non-linear evolution of creep elongation under different stress levels.
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Background: Renal cell carcinoma (RCC) stands as the most prevalent form of urogenital cancer. However, there is currently no universally accepted method for predicting the prognosis of RCC. MiRNA holds great potential as a prognostic biomarker for RCC. Methods: A total of 100 cases with complete paraffin specimens and over 5-year follow-up data meeting the requirements were collected. Utilizing the clinical information and follow-up data of the specimens, an information model was developed. The expression levels of eight microRNAs were identified using RT-qPCR. Finally, determine and analyze the clinical application value of these microRNAs as prognostic markers for RCC. Results: Significant differences were observed in the expression of two types of miRNAs (miR-378a-5p, miR-23a-5p) in RCC tissue, and three types of miRNAs (miR-378a-5p, miR-642a-5p, miR-23a-5p) were found to be linked to the prognosis of RCC. Establish biomarker combinations of miR-378a-5p, miR-642a-5p, and miR-23a-5p to evaluate RCC prognosis. Conclusion: The combination of three microRNA groups (miR-378a-5p, miR-642a-5p, and miR-23a-5p) identified in paraffin section specimens of RCC in this study holds significant potential as biomarkers for assessing RCC prognosis.
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BACKGROUND: Renal cell carcinoma (RCC) carries significant morbidity and mortality globally with an increasing incidence per year predominantly represented by clear-cell renal cell carcinoma (ccRCC) which accounts for 70-80% of all RCC cases. MicroRNAs(miRNAs) implicate tumor development and progression in epigenetic mechanisms and available profiling of serum miRNAs potentiate them as diagnostic markers for various cancers. MATERIALS AND METHODS: A total of 108 ccRCC patients and 112 normal controls were enrolled. A 3-stage experiment was conducted to identify differentially expressed serum miRNAs in ccRCC and establish a diagnostic miRNAs panel. Additionally, bioinformatic analysis was employed to predict selected miRNAs' target genes, preform functional annotation and explore the roles in ccRCC. RESULTS: MiR-429, miR-10a-5p, miR-154-5p were found to be up-regulated miRNAs. Inversely, miR-27a-3p and miR-221-3p were found to be down-regulated miRNAs. These 5 miRNAs were selected to construct diagnostic panel by backward stepwise logistic regression analysis and ultimately a 3-miRNA panel (miR-429, miR-10a-5p and miR-27a-3p) was established [area under the curve (AUC) = 0.897, sensitivity = 85.0%, specificity = 83.3%]. CONCLUSION: The panel of 3-miRNA holds promise as a novel, convenient, and noninvasive diagnostic method for early detection of ccRCC.
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Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Humanos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , MicroRNAs/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Globally, prostate cancer is the second most common malignancy in males. Serum microRNAs (miRNAs) may function as non-invasive and innovative biomarkers for various cancers. Our study aimed to determine potential miRNAs for prostate cancer screening. METHODS: A three-stage study was accomplished to ascertain crucial miRNAs as markers. In the screening stage, we searched PubMed for aberrantly expressed miRNAs relevant to prostate cancer and selected them as candidate miRNAs. In training and validation stages, with serum specimens from 112 prostate cancer patients and 112 healthy controls, expressions of candidate miRNAs were identified through quantitative reverse transcription-polymerase chain reaction. The diagnostic capabilities of miRNAs were determined by receiver operating characteristic curves. Bioinformatic analysis was utilized to explore the function of the critical miRNAs. RESULTS: Expression of six serum miRNAs (miR-34b-3p, miR-556-5p, miR-200c-3p, miR-361-5p, miR-369-3p, miR-485-3p) were significantly altered in prostate cancer patients contrasted with healthy controls. The optimal combination of critical miRNAs is a three-miRNA panel (miR-34b-3p, miR-200c-3p, and miR-361-5p) with good diagnostic capability. FLRT2, KIAA1755, LDB3, and NTRK3 were identified as the potential genes targeted by the three-miRNA panel. CONCLUSIONS: The three-miRNA panel may perform as an innovative and promising serum marker for prostate cancer screening.
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MicroRNAs , Neoplasias da Próstata , Masculino , Humanos , MicroRNAs/genética , Detecção Precoce de Câncer , Perfilação da Expressão Gênica , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Antígeno Prostático Específico , Biomarcadores Tumorais/genéticaRESUMO
The rapid growth of the Internet of Things (IoT) has led to the widespread adoption of the IoT networks in numerous digital applications. To counter physical threats in these systems, automatic modulation classification (AMC) has emerged as an effective approach for identifying the modulation format of signals in noisy environments. However, identifying those threats can be particularly challenging due to the scarcity of labeled data, which is a common issue in various IoT applications, such as anomaly detection for unmanned aerial vehicles (UAVs) and intrusion detection in the IoT networks. Few-shot learning (FSL) offers a promising solution by enabling models to grasp the concepts of new classes using only a limited number of labeled samples. However, prevalent FSL techniques are primarily tailored for tasks in the computer vision domain and are not suitable for the wireless signal domain. Instead of designing a new FSL model, this work suggests a novel approach that enhances wireless signals to be more efficiently processed by the existing state-of-the-art (SOTA) FSL models. We present the semantic-consistent signal pretransformation (ScSP), a parameterized transformation architecture that ensures signals with identical semantics exhibit similar representations. ScSP is designed to integrate seamlessly with various SOTA FSL models for signal modulation recognition and supports commonly used deep learning backbones. Our evaluation indicates that ScSP boosts the performance of numerous SOTA FSL models, while preserving flexibility.
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Background: Prostate cancer (PCa) remains a worldwide public health problem that poses a serious threat to the health of men worldwide. Many studies have found that microRNA (miRNA) in serum has the potential to be a biomarker for cancer screening. Our study was conducted to investigate the value of serum miRNAs in PCa screening. Methods: We selected 12 miRNAs from past studies for its association with PCa. We checked the expression levels of these miRNAs in the serum of 112 PCa patients and 112 healthy controls in a two-stage experiment. We plotted the receiver operating characteristic curve of miRNAs in the validation stage and constructed a four-miRNA panel with the highest diagnostic value using stepwise logistic regression. We also predicted the target genes with these four miRNAs through online databases and performed Gene Ontology functional annotation and pathway analysis. Results: The results showed that six miRNAs (miR-429, miR-10a-5p, miR-183-5p, miR-181a-5p, miR-1231, miR-129-5p) were abnormally expressed in the serum of PCa patients. We used four of these miRNAs including miR-1231, miR-10a-5p, miR-429 and miR-129-5p to construct a combination of miRNAs with high specificity and sensitivity in screening PCa (area under the curve =0.878). Bioinformatics analysis showed that the genes targeted by these miRNAs can be linked to the development of PCa. Conclusions: Our study detected and identified a set of miRNAs that serves as screening marker for PCa, which may assist in early diagnosis and treatment of PCa.
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Influenza D virus (IDV) plays an important role in the bovine respiratory disease (BRD) complex. Its potential for the zoonotic transmission is of particular concern. In China, IDV has previously been identified in agricultural animals by molecular surveys with no live virus isolates reported. In this study, live IDVs were successfully isolated from cattle in China, which prompted us to further investigate the national prevalence, antigenic property, and infection biology of the virus. IDV RNA was detected in 11.1% (51/460) of cattle throughout the country in 2022-2023. Moreover, we conducted the first IDV serosurveillance in China, revealing a high seroprevalence (91.4%, 393/430) of IDV in cattle during the 2022-2023 winter season. Notably, all the 16 provinces from which cattle originated possessed seropositive animals, and 3 of them displayed the 100% IDV-seropositivity rate. In contrast, a very low seroprevalence of IDV was observed in pigs (3%, 3/100) and goats (1%, 1/100) during the same period of investigation. Furthermore, besides D/Yama2019 lineage-like IDVs, we discovered the D/660 lineage-like IDV in Chinese cattle, which has not been detected to date in Asia. Finally, the Chinese IDVs replicated robustly in diverse cell lines but less efficiently in the swine cell line. Considering the nationwide distribution, high seroprevalence, and appreciably genetic diversity, further studies are required to fully evaluate the risk of Chinese IDVs for both animal and human health in China, which can be evidently facilitated by IDV isolates reported in this study.
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Doenças dos Bovinos , Infecções por Orthomyxoviridae , Filogenia , Thogotovirus , Animais , China/epidemiologia , Bovinos , Thogotovirus/genética , Thogotovirus/classificação , Thogotovirus/isolamento & purificação , Thogotovirus/imunologia , Infecções por Orthomyxoviridae/epidemiologia , Infecções por Orthomyxoviridae/virologia , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/transmissão , Estudos Soroepidemiológicos , Suínos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/virologia , Doenças dos Bovinos/transmissão , Cabras , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Anticorpos Antivirais/sangue , Humanos , DeltainfluenzavirusRESUMO
Background: Prostate cancer (PCa) is one of the most prevalent malignancies affecting the male life cycle. The incidence and mortality of prostate cancer are also increasing every year. Detection of MicroRNA expression in serum to diagnose prostate cancer and determine prognosis is a very promising non-invasive modality. Materials and method: A total of 224 study participants were included in our study, including 112 prostate cancer patients and 112 healthy adults. The experiment consisted of three main phases, namely, the screening phase, the testing phase, and the validation phase. The expression levels of serum miRNAs in patients and healthy adults were detected using quantitative reverse transcription-polymerase chain reaction. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were used to evaluate the diagnostic ability, specificity, and sensitivity of the candidate miRNAs. Result: Eventually, three miRNAs most relevant to prostate cancer diagnosis were selected, namely, miR-106b-5p, miR-129-1-3p and miR-381-3p. We used these three miRNAs to construct a diagnostic panel with very high diagnostic potential for prostate cancer, which had an AUC of 0.912 [95% confidence interval (CI): 0.858 to 0.950; p < 0.001; sensitivity = 91.67%; specificity = 79.76%]. In addition, the three target genes (DTNA, GJB1, and TRPC4) we searched for are also expected to be used for prostate cancer diagnosis and treatment in the future.
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Metal-immobilizing bacteria play a critical role in metal accumulation in vegetables. However, little is known concerning the mechanisms involved in bacteria-induced reduced metal availability and uptake in vegetables. In this study, the impacts of metal-immobilizing Pseudomonas taiwanensis WRS8 on the plant biomass, Cd and Pb availability and uptake in two coriander (Coriandrum sativum L.) cultivars, and bacterial community structure were investigated in the polluted soil. Strain WRS8 increased the biomass of two coriander cultivars by 25-48% and reduced Cd and Pb contents in the edible tissues by 40-59% and available Cd and Pb contents in the rhizosphere soils by 11.1-15.2%, compared with the controls. Strain WRS8 significantly increased the pH values and relative abundances of the dominant populations of Sphingomonas, Pseudomonas, Gaiellales, Streptomyces, Frankiales, Bradyrhizobium, and Luteimonas, while strain WRS8 significantly decreased the relative abundances of the dominant populations of Gemmatimonadaceae, Nitrospira, Haliangium, Paenibacillus, Massilia, Bryobacter, and Rokubacteriales and the rare bacterial populations of Enterorhabdus, Roseburia, Luteibacter, and Planifilum in the rhizosphere soils, compared with the controls. Significantly negative correlations were observed between the available metal concentrations and the abundances of Pseudomonas, Luteimonas, Frankiales, and Planifilum. These results implied that strain WRS8 could affect the abundances of the dominant and rare bacterial populations involved in metal immobilization, resulting in increased pH values and decreased metal availability and uptake in the vegetables in the contaminated soil.
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Actinomycetales , Coriandrum , Metais Pesados , Poluentes do Solo , Cádmio/análise , Chumbo , Poluentes do Solo/análise , Metais Pesados/análise , Pseudomonas , Verduras , Bactérias , Solo/químicaRESUMO
Automatic modulation classification (AMC) is an important technology for the monitoring, management, and control of communication systems. In recent years, machine learning approaches are becoming popular to improve the effectiveness of AMC for radio signals. However, the automatic modulation open-set recognition (AMOSR) scheme that aims to identify the known modulation types and recognize the unknown modulation signals is not well studied. Therefore, in this paper, we propose a novel multi-modal marginal prototype framework for radio frequency (RF) signals (MMPRF) to improve AMOSR performance. First, MMPRF addresses the problem of simultaneous recognition of closed and open sets by partitioning the feature space in the way of one versus other and marginal restrictions. Second, we exploit the wireless signal domain knowledge to extract a series of signal-related features to enhance the AMOSR capability. In addition, we propose a GAN-based unknown sample generation strategy to allow the model to understand the unknown world. Finally, we conduct extensive experiments on several publicly available radio modulation data, and experimental results show that our proposed MMPRF outperforms the state-of-the-art AMOSR methods.
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OBJECTIVE: The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti-PD-1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. METHODS: Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow-up ends in April 2022. The study's main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi-square tests, Kaplan-Meier, and Cox proportional hazards models were utilized to analyze the data. RESULTS: The median follow-up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti-PD-1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child-Pugh grade A (HR: 0.38, p = 0.032). CONCLUSIONS: Combining RFA with anti-PD-1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Masculino , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Feminino , Pessoa de Meia-IdadeRESUMO
Owing to its heterogeneous and highly aggressive nature, hepatocellular carcinoma (HCC) has a high recurrence rate, which is a non-negligible problem despite the increasing number of available treatment options. Recent clinical trials have attempted to reduce the recurrence and develop innovative treatment options for patients with recurrent HCC. In the event of liver remnant recurrence, the currently available treatment options include repeat hepatectomy, salvage liver transplantation, tumor ablation, transcatheter arterial chemoembolization, stereotactic body radiotherapy, systemic therapies, and combination therapy. In this review, we summarize the strategies to reduce the recurrence of high-risk tumors and aggressive therapies for recurrent HCC. Additionally, we discuss methods to prevent HCC recurrence and prognostic models constructed based on predictors of recurrence to develop an appropriate surveillance program.
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BACKGROUND: Urinary bladder cancer (BCa) is globally the 10th most frequent cancer. As a novel diagnostic tool, miRNA in serum screening is non-invasive. This project aimed to determine particular serum miRNAs as novel biomarkers for diagnosing urinary BCa. METHODS: We designed a three-phase study with 122 healthy controls (HCs) and 132 BCa patients. The 30 miRNAs' expressions in serum from HCs and BCa patients were detected during the screening phase. The miRNAs with the most dysregulation were tested in the training (HCs vs. BCa, 30 each) and validation (80 HCs vs. 82 BCa) phase further. The diagnostic ability of these candidate miRNAs was estimated by the receiver operating characteristic (ROC) curves as well as the area under the ROC curve (AUC). The miRNAs' target genes and their annotations to functions were predicted utilizing bioinformatic assays. RESULTS: Six serum miRNAs (miR-124-3p, miR-182-5p, miR-1-3p, miR-196a-5p, miR-23b-3p and miR-34a-5p) had significantly different expression between BCa patients and HCs in the training and validation phase. The four-microRNA panel improved the diagnostic value, with AUC =0.985. The result of bioinformatic analysis showed that these miRNAs' target genes in the panel may be related to the MAPK signaling pathway in bladder cancer. CONCLUSIONS: Our study identified a four-miRNA panel that is a non-invasive new biomarker for diagnosing BCa.
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A comprehensive investigation of the neoantigen spectrum and immune infiltration in patients with hepatocellular carcinoma (HCC) is lacking. This study aimed to examine the molecular features correlating with better prognoses in HCC patients. 27 paired tumor and normal tissues from 27 HCC patients were collected and performed with whole-exome sequencing. The most frequently mutated gene in 27 HCC patients was TP53 (16/27, 59.26%). Based on the whole median disease-free survival (DFS), all patients were divided into 'long-term' (n = 14, median DFS = 318 weeks) and 'short-term' (n = 13, median DFS = 11 weeks) groups. RNA-seq was performed to compare differentially expressed genes, immune infiltration, and neoantigens. Immunohistochemistry was performed to evaluate the immune infiltration. There were no significant differences in tumor mutation burden, immune score, cytolytic activity score, or neoantigen load between two groups. Compared with the long-term group, significantly increased B lineage (P = 0.0463), myeloid dendritic cells (P = 0.0152), and fibroblast (P = 0.0244) infiltration levels were observed in the short-term group, in which genes involved in ribosome, proteasome, and ECM-receptor interaction pathways were also overexpressed. Additionally, 16 patients with tumor thrombus were explored to identify specific biomarkers for prognosis. We found that patients with tumor thrombus carrying TP53/ARID2 neoantigens had significantly longer DFS. In conclusion, higher B lineage, myeloid dendritic cells, and fibroblast infiltration levels might cause poor prognosis in the short-term group, which also showed higher expression of genes involved in ribosome, proteasome, and ECM-receptor interaction pathways. In patients with tumor thrombus, specific TP53/ARID2 neoantigens may be used as biomarkers toward personalized immunotherapy.
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PURPOSE: This retrospective study evaluated the efficacy, safety, and factors affecting the prognosis of transarterial chemoembolisation with irinotecan-eluting beads with CalliSpheres (DEB-TACE) for intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: We retrospectively collected data on 39 patients with unresectable ICC who received DEB-TACE therapy. We assessed the indicators of tumour response, progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. PFS and OS were analysed using Kaplan-Meier curves, while Cox analysis was used to identify factors affecting the prognosis. RESULTS: The 3-month objective response rate (ORR) and disease control rate (DCR) of the 39 patients with unresectable ICC were 35.9% and 56.4%, respectively, while the 6-month ORR and DCR were 23.0% and 40.9%, respectively. The median OS and PFS were 11.0 months and 8.0 months, respectively. Cox analysis demonstrated that combined therapy (adjuvant sorafenib after DEB-TACE) and a low cancer antigen (CA) 125 level (≤ 35 U/ml) were independent favourable prognostic factors. Transient elevation of the aminotransferase level, nausea, vomiting, abdominal pain, fever, and hyper-bilirubinaemia were common adverse events in patients with unresectable ICC treated with DEB-TACE with CalliSphere beads (CBs). Hepatic abscess was the most serious complication, observed in one patient. CONCLUSIONS: DEB-TACE with CBs is a safe and well-tolerated therapy in patients with unresectable ICC with a low incidence of adverse events and relatively prolonged survival. Combined therapy and low CA125 are prognostic factors associated with longer survival.