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BACKGROUND: Reirradiation in standard fractionation for locally advanced recurrent nasopharyngeal carcinoma after a previous course of high-dose radiotherapy is often associated with substantial late toxicity, negating its overall benefit. We therefore aimed to investigate the efficacy and safety of hyperfractionation compared with standard fractionation in intensity-modulated radiotherapy. METHODS: This multicentre, randomised, open-label, phase 3 trial was done in three centres in Guangzhou, China. Eligible patients were aged 18-65 years with histopathologically confirmed undifferentiated or differentiated, non-keratinising, advanced locally recurrent nasopharyngeal carcinoma. Participants were randomly assigned (1:1) to either receive hyperfractionation (65 Gy in 54 fractions, given twice daily with an interfractional time interval of at least 6 h) or standard fractionation (60 Gy in 27 fractions, given once a day). Intensity-modulated radiotherapy was used in both groups. A computer program generated the assignment sequence and randomisation was stratified by treatment centre, recurrent tumour stage (T2-T3 vs T4), and recurrent nodal stage (N0 vs N1-N2), determined at the time of randomisation. The two primary endpoints were the incidence of severe late complications defined as the incidence of grade 3 or worse late radiation-induced complications occurring 3 months after the completion of radiotherapy until the latest follow-up in the safety population, and overall survival defined as the time interval from randomisation to death due to any cause in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02456506. FINDINGS: Between July 10, 2015, and Dec 23, 2019, 178 patients were screened for eligibility, 144 of whom were enrolled and randomly assigned to hyperfractionation or standard fractionation (n=72 in each group). 35 (24%) participants were women and 109 (76%) were men. After a median follow-up of 45·0 months (IQR 37·3-53·3), there was a significantly lower incidence of grade 3 or worse late radiation-induced toxicity in the hyperfractionation group (23 [34%] of 68 patients) versus the standard fractionation group (39 [57%] of 68 patients; between-group difference -23% [95% CI -39 to -7]; p=0·023). Patients in the hyperfractionation group had better 3-year overall survival than those in the standard fractionation group (74·6% [95% CI 64·4 to 84·8] vs 55·0% [43·4 to 66·6]; hazard ratio for death 0·54 [95% CI 0·33 to 0·88]; p=0·014). There were fewer grade 5 late complications in the hyperfractionation group (five [7%] nasal haemorrhage) than in the standard fractionation group (16 [24%], including two [3%] nasopharyngeal necrosis, 11 [16%] nasal haemorrhage, and three [4%] temporal lobe necrosis). INTERPRETATION: Hyperfractionated intensity-modulated radiotherapy could significantly decrease the rate of severe late complications and improve overall survival among patients with locally advanced recurrent nasopharyngeal carcinoma. Our findings suggest that hyperfractionated intensity-modulated radiotherapy could be used as the standard of care for these patients. FUNDING: Key-Area Research and Development of Guangdong Province, the National Natural Science Foundation of China, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center, the Guangzhou Science and Technology Plan Project, and the National Ten Thousand Talents Program Science and Technology Innovation Leading Talents, Sun Yat-Sen University Clinical Research 5010 Program.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Masculino , Humanos , Feminino , Carcinoma Nasofaríngeo/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Recidiva Local de Neoplasia/radioterapia , Neoplasias Nasofaríngeas/radioterapia , HemorragiaRESUMO
BACKGROUND: Paracetamol induces hepatotoxicity and subsequent liver injury, which may increase the risk of liver cancer, but epidemiological evidence remains unclear. We conducted this study to evaluate the association between paracetamol use and the risk of liver cancer. METHODS: This prospective study included 464,244 participants free of cancer diagnosis from the UK Biobank. Incident liver cancer was identified through linkage to cancer and death registries and the National Health Service Central Register using the International Classification of Diseases (ICD)-10 codes (C22). An overlap-weighted Cox proportional hazards model was utilized to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the risk of liver cancer associated with paracetamol use. The number needed to harm (NNH) was calculated at 10 years of follow-up. RESULTS: During a median of 12.6 years of follow-up, 627 cases of liver cancer were identified. Paracetamol users had a 28% higher risk of liver cancer than nonusers (HR 1.28, 95% CI 1.06-1.54). This association was robust in several sensitivity analyses and subgroup analyses, and the quantitative bias analysis indicated that the result remains sturdy to unmeasured confounding factors (E-value 1.88, lower 95% CI 1.31). The NNH was 1106.4 at the 10 years of follow-up. CONCLUSION: The regular use of paracetamol was associated with a higher risk of liver cancer. Physicians should be cautious when prescribing paracetamol, and it is recommended to assess the potential risk of liver cancer to personalize the use of paracetamol.
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Acetaminofen , Neoplasias Hepáticas , Humanos , Acetaminofen/efeitos adversos , Estudos Prospectivos , Medicina Estatal , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/epidemiologia , Fatores de RiscoRESUMO
The prognosis for Cholangiocarcinoma (CCA) is unfavorable, necessitating the development of new therapeutic approach such as magnetic hyperthermia therapy (MHT) which is induced by magnetic nano-particle (MNPs) drug to bridge the treatment gap. Given the deep location of CCA within the abdominal cavity and proximity to vital organs, accurately predict the individualized treatment effects and safety brought by the distribution of MNPs in tumor will be crucial for the advancement of MHT in CCA. The Mimics software was used in this study to conduct three-dimensional reconstruction of abdominal computed tomography (CT) and magnetic reso-nance imaging images from clinical patients, resulting in the generation of a realistic digital geometric model representing the human biliary tract and its adjacent structures. Subsequently, The COMSOL Multiphysics software was utilized for modeling CCA and calculating the heat transfer law resulting from the multi-regional distribution of MNPs in CCA. The temperature within the central region of irregular CCA measured approximately 46°C, and most areas within the tumor displayed temperatures surpassing 41°C. The temperature of the inner edge of CCA is only 39 â¼ 41â, however, it can be ameliorated by adjusting the local drug concentration through simulation system. For CCA with diverse morphologies and anatomical locations, the multi-regional distribution patterns of intratumoral MNPs and a slight overlap of drug distribution areas synergistically enhance intratumoral temperature while ensuring treatment safety. The present study highlights the practicality and imperative of incorporating personalized intratumoral MNPs distribution strategy into clinical practice for MHT, which can be achieved through the development of an integrated simulation system which incorporates medical image data and numerical calculations.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Hipertermia Induzida , Colangiocarcinoma/terapia , Colangiocarcinoma/diagnóstico por imagem , Colangiocarcinoma/tratamento farmacológico , Humanos , Hipertermia Induzida/métodos , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/diagnóstico por imagem , Neoplasias dos Ductos Biliares/tratamento farmacológico , Simulação por Computador , Nanopartículas Magnéticas de Óxido de Ferro/química , Modelos BiológicosRESUMO
OBJECTIVE: Genetic and lifestyles contribute to cholelithiasis, but the impact of adhering to healthy lifestyle on cholelithiasis risk remains uncertain. We aimed to assess combined lifestyle factors and a polygenic risk score on incident cholelithiasis. METHODS: We utilized cholelithiasis genome-wide association study (GWAS) data from FinnGen study, constructing varied polygenic risk score (PRS), and applied them to 317,640 UK Biobank participants. The relative and absolute risk of incident cholelithiasis associated with six well-established lifestyle risk factors, was evaluated and stratified by PRS (low risk [quintile 1], intermediate risk [quintiles 2-4] and high risk [quintile 5]). Lifestyle score was also categorized into favorable, intermediate, and unfavorable groups. RESULTS: The PRS derived from 13 single nucleotide polymorphisms (p ≤ 5 × 10-6, r2 < 0.001) showed the best performance. A significant gradient of increase in risk of cholelithiasis was observed across the quintiles of the polygenic risk score (p < 0.001). Compared to participants with low genetic risk, those with intermediate or high genetic risk had a 10% (95% confidence interval [CI] = 1.05-1.17) and 24% (95% CI = 1.16-1.32) higher risk of cholelithiasis. An unfavorable lifestyle was associated with an approximately 50% higher risk of cholelithiasis than a favorable lifestyle. Participants with high genetic risk and an unfavorable lifestyle had 98% (Hazard ratio [HR]: 1.98; 95% CI: 1.67-2.35) higher risk of cholelithiasis than those with low genetic risk and a favorable lifestyle. CONCLUSIONS: Our study highlights the importance of lifestyle behaviors intervention on cholelithiasis risk regardless of the genetic risk in White European population.
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It has been supposed that the interplay of elasticity and activity plays a key role in triggering the non-equilibrium behaviors in biological systems. However, the experimental model system is missing to investigate the spatiotemporally dynamical phenomena. Here, a model system of an active chain, where active eccentric-disks are linked by a spring, is designed to study the interplay of activity, elasticity, and friction. Individual active chain exhibits longitudinal and transverse motions; however, it starts to self-rotate when pinning one end and self-beat when clamping one end. In addition, our eccentric-disk model can qualitatively reproduce such behaviors and explain the unusual self-rotation of the first disk around its geometric center. Furthermore, the structure and dynamics of long chains were studied via simulations without steric interactions. It was found that a hairpin conformation emerges in free motion, while in the constrained motions, the rotational and beating frequencies scale with the flexure number (the ratio of self-propelling force to bending rigidity), χ, as â¼(χ)4/3. Scaling analysis suggests that it results from the balance between activity and energy dissipation. Our findings show that topological constraints play a vital role in non-equilibrium synergy behaviors.
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OBJECTIVE: This study aimed to assess the effectiveness of exercise therapy for Axial spondyloarthritis (axSpA) patients. DATA SOURCES: From the database inception to March 2024, we searched PubMed (via Medline), Cochrane Library, Embase, Web of Science, Scopus, and SPORTDiscus for all relevant publications without any language restriction. STUDY SELECTION: We included randomized controlled trials (RCTs) for axSpA patients in which at least one group received exercise therapy. DATA EXTRACTION: Two independent reviewers assessed the quality of the literature using the Cochrane Collaboration Risk of Bias Tool 2.0. The outcomes were ankylosing spondylitis (AS) disease activity score (ASDAS), Bath AS disease activity index (BASDAI), Bath AS functional index (BASFI), Bath AS metrology index (BASMI), 6-minute walk distance (6MWT), Chest expansion capacity, Peak oxygen consumption (VO2peak), pain, fatigue, C-reactive protein (CRP), and Eythrocyte sedimentation rate (ESR). DATA SYNTHESIS: A total of 20 RCTs, including 1,670 patients, were included in this study. Compared with the control group, exercise therapy improved BASFI (weighted mean difference [WMD]: -0.49, 95% confidence interval [CI]: -0.65 to -0.32, I2= 3.4%, P=0.414), BASMI (WMD: -0.49, 95% CI: -0.87 to -0.11, I2= 71.9%, P=0.679), BASDAI (WMD: -0.78, 95% CI: -1.08, -0.47, I2=55.9%, P=0.021), ASDAS (WMD: -0.44, 95% CI: -0.64 to -0.24, I2 =0.0%, P=0.424), VO2peak (WMD: 3.16, 95% CI: 1.37 to 4.94, I2=0.0%, P=0.873), 6MWT (WMD: 27.64, 95% CI: 12.04 to 43.24, I2= 0.0%, P=0.922), Pain (standardized mean difference [SMD]: -0.47, 95% CI: -0.74 to -0.21, I2= 66.0%, P=0.046) and Fatigue (SMD: -0.49, 95% CI: -0.71 to -0.27, I2= 0.0%, P=0.446). However, no significant benefit was found in Chest expansion, CRP, and ESR outcomes. CONCLUSIONS: Exercise therapy is an effective strategy for improving disease control and symptom relief in axSpA.
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BACKGROUND: Short-term personalized vestibular rehabilitation (ST-PVR) can establish stable vestibular compensation. However, there is a lack of a clear definition for clinical indicators that can dynamically reflect the progress of vestibular rehabilitation (VR). OBJECTIVE: To explore the clinical indicators suitable for evaluating the effectiveness of ST-PVR in treating benign recurrent vertigo (BRV). METHODS: In total, 50 patients diagnosed with BRV were enrolled. All patients received the ST-PVR treatment program. At 2 and 4 weeks after rehabilitation, subjective scales, including the visual analogue scale (VAS), dizziness handicap inventory scale (DHI), activities-specific balance confidence scale (ABC) and generalized anxiety disorder (GAD-7) were assessed. Objective vestibular function tests were performed. VR grading was determined. RESULTS: At 2 weeks after rehabilitation, significant enhancements were observed in VAS, DHI, ABC, GAD-7, UW, vHIT results, and VR grading scores (p < 0.05). The sensory organization test (SOT) results demonstrated statistically significant improvements at 2 weeks and 4 weeks after rehabilitation (p < 0.05). CONCLUSION AND SIGNIFICANCE: Both subjective scales and partial examination results in objective assessment can serve as indicators to dynamically monitor the compensatory process of vestibular function in patients with BRV. The VR efficacy grading score, which incorporates the above indicators, allows for quantification of the changes that occur during the vestibular rehabilitation process.
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Vertigem , Testes de Função Vestibular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Vertigem/reabilitação , Vertigem/fisiopatologia , Testes de Função Vestibular/métodos , Resultado do Tratamento , Idoso , Recidiva , Equilíbrio Postural/fisiologiaRESUMO
Photothermal regulation concerning solar harvesting and repelling has recently attracted significant interest due to the fast-growing research focus in the areas of solar heating for evaporation, photocatalysis, motion, and electricity generation, as well as passive cooling for cooling textiles and smart buildings. The parallel development of photothermal regulation strategies through both material and system designs has further improved the overall solar utilization efficiency for heating/cooling. In this review, we will review the latest progress in photothermal regulation, including solar heating and passive cooling, and their manipulating strategies. The underlying mechanisms and criteria of highly efficient photothermal regulation in terms of optical absorption/reflection, thermal conversion, transfer, and emission properties corresponding to the extensive catalog of nanostructured materials are discussed. The rational material and structural designs with spectral selectivity for improving the photothermal regulation performance are then highlighted. We finally present the recent significant developments of applications of photothermal regulation in clean energy and environmental areas and give a brief perspective on the current challenges and future development of controlled solar energy utilization.
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PM2.5 is an important risk factor for the development and progression of cognitive impairment-related diseases. Ferroptosis, a new form of cell death driven by iron overload and lipid peroxidation, is proposed to have significant implications. To verify the possible role of ferroptosis in PM2.5-induced neurotoxicity, we investigated the cytotoxicity, intracellular iron content, iron metabolism-related genes, oxidative stress indices and indicators involving in Nrf2 and ferroptosis signaling pathways. Neurotoxicity biomarkers as well as the ferroptotic cell morphological changes were determined by Western Blot and TEM analysis. Our results revealed that PM2.5 induced cytotoxicity, lipid peroxidation, as indicated by MDA content, and neurotoxicity via Aß deposition in a dose-related manner. Decreased cell viability and excessive iron accumulation in HT-22 cells can be partially blocked by ferroptosis inhibitors. Interestingly, GPX activity, Nrf2, and its regulated ferroptotic-related proteins (i.e. GPX4 and HO-1) were significantly up-regulated by PM2.5. Moreover, gene expression of DMT1, TfR1, IRP2 and FPN1 involved in iron homeostasis and NCOA4-dependent ferritinophagy were activated after PM2.5 exposure. The results demonstrated that PM2.5 triggered ferritinophagy-dependent ferroptotic cell death due to iron overload and redox imbalance. Activation of Nrf2 signaling pathways may confer a protective mechanism for PM2.5-induced oxidative stress and ferroptosis.
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Ferroptose , Sobrecarga de Ferro , Humanos , Fator 2 Relacionado a NF-E2/genética , Oxirredução , Ferro , Material Particulado/toxicidadeRESUMO
Lonicera japonica Flos is a valuable herb in the Lonicerae family. While transcriptomic studies on L. japonica have focused on different tissues (stems, leaves, flowers) or flowering stages, few have investigated the molecular mechanisms underlying chemical composition synthesis influenced by exogenous factors, such as foliar fertilization. Moreover, most transcriptomic studies on L. Japonica have been conducted on chlorogenic acid and luteoloside, and the molecular synthesis mechanism of the overall chemical composition has not been analyzed. Methods: We conducted a single-factor, four-level foliar fertilization experiment using yeast polysaccharides. Different yeast polysaccharides concentrations were sprayed on L. japonica for six consecutive days with dynamic sampling. High-performance liquid chromatography determined the active ingredients in each group. The two groups exhibiting the most significant differences were selected for transcriptomic analysis to identify key synthetic genes responsible for L. japonica's active ingredients. Key results: Principal component analysis conducted on samples collected on September 8 revealed significant differences in the active ingredient amounts between the 0.1 g/L yeast polysaccharides treatment group and the control group. Transcriptome sequencing analysis identified 218 significantly differentially expressed genes, including 60 upregulated and 158 downregulated genes. Twelve differential genes involved in the chemical components synthesis pathway of L. japonica under yeast polysaccharides treatment were identified: PAL1, PAL2, PAL3, 4CL1, 4CL, CHS1, CHS2, CHS, CHI1, CHI2, F3H, and SOH. Conclusions: This study contributes to the theoretical understanding of essential synthetic genes associated with L. japonica's active ingredients. It offers data support for further gene exploration and sheds light on the molecular mechanisms underlying L. japonica quality formation. These findings hold significant implications for enhancing the content of secondary metabolites of L. japonica. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01482-1.
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This study investigated the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules based on metabonomics, network pharmacology, and molecular docking. The aging mice model was induced by intraperitoneal injection of D-galactose(D-gal). Mice were randomly divided into a control group, model group, melatonin group(MT group), and low, medium, and high dose groups of Xiyangshen Sanqi Danshen Granules(XSD-L, XSD-M, and XSD-H). An open-field experiment was conducted, and the expression of cell cycle arrest proteins(p16) and phosphorylated histone family 2A variant(γH2AX) in the brain tissue was detected by immunofluorescence. The expression of interleukin-1ß(IL-1ß) and interleukin-6(IL-6) in the brain tissue was detected by enzyme-linked immunosorbent assay(ELISA). Metabolomics analysis was performed on the serum of mice in control, model, and XSD-H groups to obtain metabolic processes and metabolites. The effective chemical components and potential targets of Xiyangshen Sanqi Danshen Granules were predicted through network pharmacology, and the network diagram of "drug-effective chemical components-key targets" was constructed. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were carried out, and a protein-protein interaction(PPI) network was constructed to clarify the anti-aging mechanism of Xiyangshen Sanqi Danshen Granules. The results showed that the Xiyangshen Sanqi Danshen Granules could significantly improve the aging degree of D-gal mice, significantly improve the total motion distance and the mean motion speed of D-gal mice, and reduce the rest time. In addition, Xiyangshen Sanqi Danshen Granules could significantly reduce the protein levels of IL-6 and IL-1ß and the expression of p16 and γH2AX in D-gal mice. Compared with the model group, 66 differential metabolites(DMs) were significantly up-regulated, and 91 DMs were down-regulated in the XSD-H group. Moreover, four key metabolic pathways(tryptophan metabolism, glycerophospholipid metabolism, pyrimidine metabolism, and lysine degradation) and 16 biomarkers(lysine, tryptophan, indoleacetaldehyde, PCs, LysoPCs, 3-hydroxyanthranilic acid, melatonin, etc) were screened out. 58 main active components and 62 key targets of Xiyangshen Sanqi Danshen Granules were screened by network pharmacology. The GO functional enrichment analysis found the positive regulation of gene expression, drug response, etc. KEGG pathway enrichment screening involved diabetic complications-related AGE-RAGE signaling pathway, hypoxia inducible factor-1 signaling pathway, etc. Through the PPI network and molecular docking, six potential core targets of STAT3, MAPK1, MAPK14, EGFR, FOS, and STAT1 were screened.
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Envelhecimento , Biologia Computacional , Medicamentos de Ervas Chinesas , Metabolômica , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Camundongos , Masculino , Envelhecimento/efeitos dos fármacos , Envelhecimento/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Simulação de Acoplamento Molecular , Salvia miltiorrhiza/química , Interleucina-1beta/genética , Interleucina-1beta/metabolismoRESUMO
This Letter demonstrates a novel, to the best of knowledge, overlapping single-sideband (OSSB) transmission scheme for spectrally efficient multi-service fiber-wireless (FiWi) access in a low-cost direct-detection (DD) THz system. Utilizing the proposed OSSB scheme, user data from different services can share the same spectrum resource yet can be successfully demodulated via one cost-effective DD THz receiver in conjunction with the Kramers-Kronig (KK) based SSB field reconstruction and look-up table (LUT) enabled signal separation algorithms. A proof-of-principle experiment is conducted. Based on an IQ modulator and a single THz zero-bias diode (ZBD), two independent 10-GBd quadrature phase shift keying (QPSK) signals with an overlapped spectrum are successfully demodulated after 20-km fiber and up to 3-m wireless transmission at the 300-GHz band. To the best of our knowledge, this is the first demonstration of multi-service FiWi access with an OSSB format in a 300-GHz DD THz system.
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This Letter demonstrates a real-time 100-GbE fiber-wireless seamless integration system operating at the whole W band (75-110â GHz). Based on a pair of commercial digital coherent optical modules, the real-time transparent transmission of 125-Gb/s dual-polarized quadrature phase-shift keying signal has been successfully achieved over two-spans of 20-km fiber and up to 150-m electromagnetic dual-polarized single-input single-output wireless link. To the best of our knowledge, this is the first real-time demonstration of 100-GbE signal transmission over >100-m wireless distance at the millimeter-wave band based on photonics. We believed this real-time and high-speed fiber-wireless seamless integration system with a wireless coverage up to hundreds of meters can significantly accelerate the progress of upcoming 6G.
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BACKGROUND: Diagnosis and treatment of diffuse malignant peritoneal mesothelioma (DMPM) are still challenging. The aim of the present study was to explore the correlation between CD74, CD10, Ki-67 and clinicopathological parameters, and identify independent prognostic factors of DMPM. METHODS: Seventy patients with pathologically proven DMPM were retrospectively reviewed. The expression of CD74, CD10 and Ki-67 in peritoneal tissues was detected by immunohistochemical analysis using standard avidin biotin complex (ABC) immunostaining technique. Kaplan-Meier survival analysis and multivariate Cox regression analyses were performed to assess prognostic factors. The nomogram based on the Cox hazards regression model was established. C-index and calibration curve were performed to evaluate the accuracy of nomogram models. RESULTS: The median age of DMPM was 62.34 years, and the male-to-female ratio was 1: 1.80. CD74 expression was identified in 52 (74.29%) of 70 specimens, CD10 in 34 (48.57%) specimens, and higher Ki-67 in 33(47.14%) specimens. CD74 was negatively associated with asbestos exposure(r = -0.278), Ki-67(r = -0.251) and TNM stage(r = -0.313). All patients were effectively followed up in the survival analysis. Univariate analysis revealed that PCI, TNM stage, treatment, Ki-67, CD74 and ECOG PS were associated with DMPM prognosis. CD74 (HR = 0.65, 95%Cl:0.46-0.91, P = 0.014), Ki-67(HR = 2.09, 95%Cl:1.18-3.73, P = 0.012),TNM stage (HR = 1.89, 95%Cl:1.16-3.09, P = 0.011), ECOG PS(HR = 2.12, 95%Cl:1.06-4.25, P = 0.034), systemic chemotherapy (HR = 0.41, 95%Cl:0.21-0.82, P = 0.011) and intraperitoneal chemotherapy (HR = 0.34, 95%Cl:0.16-0.71, P = 0.004) were independent predictors by multivariate Cox analysis. The Cindex of the nomogram for predicting overall survival (OS) was 0.81. The OS calibration curve showed good agreement between nomogram-predicted and observed survival. CONCLUSIONS: CD74, Ki-67, TNM stage, ECOG PS and treatment were independent factors affecting prognosis of DMPM. Reasonable chemotherapy treatment might improve the prognosis of patients. The proposed nomogram was a visual tool to effectively predict the OS of DMPM patients.
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Mesotelioma Maligno , Mesotelioma , Intervenção Coronária Percutânea , Neoplasias Peritoneais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Antígeno Ki-67/metabolismo , Mesotelioma/patologia , Biomarcadores Tumorais/metabolismo , Neoplasias Peritoneais/tratamento farmacológicoRESUMO
A target-triggered and exonuclease-â ¢-assisted strand displacement, dual-recycling amplification reaction-based biosensor was developed for the rapid, ultrasensitive and accurate detection of kanamycin. The robust profiling platform was constructed using high conductive MXene/VS2 for the electrode surface modification and high active CeCu2O4 bimetallic nanoparticles as nanozyme to improve the sensitivity as well as the catalytic signal amplification of the biosensor. Using the dual supplementary recycling of primer DNA and hairpin DNA, the electrochemical platform could accurately detect kanamycin to as low as 0.6 pM from the range of 5 pM to 5 µM. By profiling five other antibiotics, this platform exhibited high specificity, enhanced repeatability and reproducibility. Based on these intrinsic characteristics and by utilizing milk and water samples, the as-designed biosensor offers a remarkable strategy for antibiotic detection due to its favorable analytical accuracy and reliability, thereby demonstrating potential application prospect for various antibiotic biosensing in food quality control, water contamination detection and biological safety analysis.
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Técnicas Biossensoriais , Canamicina , Canamicina/análise , Reprodutibilidade dos Testes , Técnicas Eletroquímicas , Antibacterianos/análise , DNA , Técnicas Biossensoriais/métodos , Água , Limite de DetecçãoRESUMO
N6 -methyladenosine (m6 A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B-cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m6 A modification in human NPC biopsies, patient-derived xenograft tissues, and cells at different EBV infection stages. m6 A-modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m6 A-dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post-transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m6 A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV-associated cancers.
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Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Adenosina/análogos & derivados , Proteínas de Transporte , Herpesvirus Humano 4/genética , Humanos , Estabilidade de RNA , Proteínas de Ligação a RNA/genética , Replicação ViralRESUMO
Photothermal therapy (PTT) systems typically do not possess intrinsic tumor-targeting capability, resulting in indiscriminate thermal damage to both cancer and normal cells. Herein, a low-density lipoprotein (LDL)-based nanosystem (denoted as MTTQ@LDL) is reported for targeted photothermal killing of cancer cells. Such a nanosystem is fabricated by reconstituting the lipophilic core of LDL with an organic photothermal agent MTTQ. The reconstitution process improves the supramolecular photothermal effects of MTTQ assemblies, which contributes to the significantly enhanced photothermal conversion efficiency (41.3% vs. 16.2%). MTTQ@LDL can actively target LDL receptor-overexpressed cancer cells via receptor-mediated endocytosis, enabling the selective killing of cancer cells over normal cells (98% vs. 7%) post-NIR irradiation. Reconstituted LDL can serve as a promising platform for targeted delivery of functional materials, holding great promise in tumor eradication in vivo.
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Nanopartículas , Neoplasias , Humanos , Fototerapia , Lipoproteínas LDL , Neoplasias/tratamento farmacológico , Linhagem Celular TumoralRESUMO
The purpose of this study was to evaluate and summarize the technical characteristics and clinical efficacy of using Dyna-computed tomography (CT)-assisted neuroendoscopic hematoma evacuation to treat hypertensive intracerebral hemorrhage (HICH). We treated 42 consecutive patients with HICH who underwent neuroendoscopic hematoma evacuation in our department from March 1, 2020, to May 31, 2022. Patients were divided into two groups: Dyna-CT-assisted neuroendoscopic group (n = 18) and neuroendoscopic group (n = 24). Retrospective data, treatment efficacy, and outcomes were collected and compared between these two groups. The operative time in the Dyna-CT-assisted neuroendoscopic group was significantly shorter than the operative time in the neuroendoscopic group (mean time 131.6 ± 13.51 vs. 156.6 ± 19.25 min, P < 0.001). Dyna-CT-assisted neuroendoscopic group had significantly less intraoperative blood loss than the neuroendoscopic group (46.94 ± 10.42 vs. 106.46 ± 23.25, P = 0.003). Meanwhile, patients who underwent Dyna-CT-assisted neuroendoscopic had a comparable hematoma clearance rate to those who underwent neuroendoscopic (89.36 ± 7.31 vs. 68.87 ± 19.44%, P = 0.006). The incidence of complications in the Dyna-CT-assisted neuroendoscopic group (5.5%) was lower than in the neuroendoscopic group (12.5%), but the difference was not statistically significant (P = 0.129). Patients who underwent Dyna-CT-assisted neuroendoscopic hematoma evacuation had better 6-month functional outcomes, and the difference was significant (P = 0.004). Furthermore, multivariable analysis showed that younger age, smaller hematoma volume, and Dyna-CT-assisted neuroendoscopic were predictors of favorable 6-month outcomes in HICH patients. In the treatment of HICH, Dyna-CT-assisted hematoma evacuation appears to be safer and more effective than neuroendoscopic hematoma evacuation. Dyna-CT-assisted neuroendoscopic hematoma evacuation in hybrid operating rooms may improve the clinical effect and outcomes of patients with HICH.
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Hemorragia Intracraniana Hipertensiva , Humanos , Hemorragia Intracraniana Hipertensiva/diagnóstico por imagem , Hemorragia Intracraniana Hipertensiva/cirurgia , Estudos Retrospectivos , Neuroendoscópios , Hematoma/diagnóstico por imagem , Hematoma/cirurgia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate the imaging effect of a near-infrared fluorescent targeted probe ICG-NP41 on the neurovascular bundles (NVB) around the prostate in rats. METHODS: A near-infrared fluorescent targeted probe ICG-NP41 was synthesized. An animal model for NVB imaging was established using Sprague-Dawley rats (250-400 g). Experiments were conducted using a custom-built near-infrared windowâ ¡(NIR-â ¡) small animal in vivo imaging system, and images collected were processed using ImageJ and Origin. The fluorescence signal data were statistically analyzed using GraphPad Prism. The signal-to-background ratio (SBR) for NVB was quantitatively calculated to explore the effective dosage and imaging time points. Finally, paraffin pathology sections and HE staining were performed on the imaging structures. RESULTS: Except for rats in the control group (n=2), right-sided NVB of the rats injected with ICG-NP41 (n=2 per group) were all observed in NIR-â ¡ fluorescence mode 2 h and 4 h after administration. At 2 h and 4 h, average SBR of cavernous nerve in 2 mg/kg group in fluorescence mode was 1.651±0.142 and 1.619±0.110, respectively, both higher than that in white light mode (1.111±0.036), with no significant difference (P>0.05); average SBR of 4 mg/kg group in fluorescence mode were 1.168±0.066 and 1.219±0.118, respectively, both higher than that in white light mode (1.081±0.040), with no significant difference (P>0.05). At 2 h and 4 h, the average SBR of 2 mg/kg and 4 mg/kg groups in fluorescence mode were higher than that of the control group (SBR=1), the average SBR of the 2 mg/kg group was higher than that of the 4 mg/kg group, and all the above with no significant difference (P>0.05). The average diameter of the nerve measured by full width at half maxima method was about (178±15) µm. HE staining of paraffin sections showed the right major pelvic ganglion. CONCLUSION: The near-infrared fluorescent targeted probe ICG-NP41 can be used for real-time imaging of the NVB around the prostate in rats, providing a potential feasible solution for localizing NVB in real time during nerve-sparing radical prostatectomy.
Assuntos
Parafina , Próstata , Masculino , Ratos , Animais , Próstata/diagnóstico por imagem , Verde de Indocianina , Ratos Sprague-Dawley , Corantes FluorescentesRESUMO
N6-methyladenosine (m6A) is among the most abundant mRNA modifications, particularly in eukaryotes, and is found in mammals, plants, and even some viruses. Although essential for the regulation of many biological processes, the exact role of m6A modification in virus-host interaction remains largely unknown. Here, using m6A -immunoprecipitation and sequencing, we find that Epstein-Barr virus (EBV) infection decreases the m6A modification of transcriptional factor KLF4 mRNA and subsequently increases its protein level. Mechanistically, EBV immediate-early protein BZLF1 interacts with the promoter of m6A methyltransferase METTL3, inhibiting its expression. Subsequently, the decrease of METTL3 reduces the level of KLF4 mRNA m6A modification, preventing its decay by the m6A reader protein YTHDF2. As a result, KLF4 protein level is upregulated and, in turn, promotes EBV infection of nasopharyngeal epithelial cells. Thus, our results suggest the existence of a positive feedback loop formed between EBV and host molecules via cellular mRNA m6A levels, and this feedback loop acts to facilitate viral infection. This mechanism contains multiple potential targets for controlling viral infectious diseases.