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BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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Anticorpos Monoclonais Humanizados , Quimiorradioterapia , Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/tratamento farmacológico , Adulto , China/epidemiologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/terapia , Quimiorradioterapia/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Idoso , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gencitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Adulto Jovem , Adolescente , Intervalo Livre de ProgressãoRESUMO
The attractive interactions between aromatic rings, also known as π-π interactions, have been widely used for decades. However, the origin of π-π interactions remains controversial due to the difficulties in experimentally measuring the weak interactions between π-systems. Here, we construct an elaborate system to accurately compare the strength of the π-π interactions between phenylalanine derivatives via molecular exchange processes inside a protein nanopore. Based on quantitative comparison of binding strength, we find that in most cases, the π-π interaction is primarily driven by dispersive attraction, with the electrostatic interaction playing a secondary role and tending to be repulsive. However, in cases where electronic effects are particularly strong, electrostatic induction may exceed dispersion forces to become the primary driving force for interactions between π-systems. The results of this study not only deepen our understanding of π-stacking but also have potential implications in areas where π-π interactions play a crucial role.
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BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.
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Criopreservação , Transferência Embrionária , Placenta , Criopreservação/métodos , Feminino , Gravidez , Animais , Camundongos , Transferência Embrionária/métodos , Placenta/metabolismo , Embrião de Mamíferos , Implantação do Embrião/genética , Desenvolvimento Fetal/genética , Blastocisto/metabolismoRESUMO
The increasing prevalence of drought events poses a major challenge for upcoming crop production. Melatonin is a tiny indolic tonic substance with fascinating regulatory functions in plants. While plants can respond in several ways to alleviate drought stress, the processes underpinning stress sensing and signaling are poorly understood. Hereafter, the objectives of this investigation were to explore the putative functions of melatonin in the regulation of sugar metabolism and abscisic acid biosynthesis in drought-stressed tomato seedlings. Melatonin (100 µM) and/or water were foliar sprayed, followed by the plants being imposed to drought stress for 14 days. Drought stress significantly decreased biomass accumulation, inhibited photosynthetic activity, and stimulated senescence-associated gene 12 (SAG12) expression. Melatonin treatment effectively reversed drought-induced growth retardation as evidenced by increased leaf pigment and water balance and restricted abscisic acid (ABA) accumulation. Sugar accumulation, particularly sucrose content, was higher in drought-imposed seedlings, possibly owing to higher transcription levels of sucrose non-fermenting 1-related protein kinase 2 (SnKR2.2) and ABA-responsive element binding factors 2 (AREB2). Melatonin addition further uplifted the sucrose content, which coincided with increased activity of sucrose synthase (SS, 130%), sucrose phosphate synthase (SPS, 137%), starch degradation encoding enzyme ß-amylase (BAM, 40%) and α-amylase (AMY, 59%) activity and upregulated their encoding BAM1(10.3 folds) and AMY3 (8.1 folds) genes expression at day 14 relative to the control. Under water deficit conditions, melatonin supplementation decreased the ABA content (24%) and its biosynthesis gene expressions. Additionally, sugar transporter subfamily genes SUT1 and SUT4 expression were upregulated by the addition of melatonin. Collectively, our findings illustrate that melatonin enhances drought tolerance in tomato seedlings by stimulating sugar metabolism and negatively regulating ABA synthesis.
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Ácido Abscísico , Secas , Regulação da Expressão Gênica de Plantas , Melatonina , Plântula , Solanum lycopersicum , Sacarose , Ácido Abscísico/metabolismo , Melatonina/farmacologia , Melatonina/metabolismo , Solanum lycopersicum/efeitos dos fármacos , Solanum lycopersicum/genética , Solanum lycopersicum/fisiologia , Solanum lycopersicum/metabolismo , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/fisiologia , Plântula/metabolismo , Sacarose/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico , Folhas de Planta/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Folhas de Planta/genética , Glucosiltransferases/metabolismo , Glucosiltransferases/genéticaRESUMO
OBJECTIVE: To assess electrocardiogram (ECG) for risk stratification in inferior ST-elevation myocardial infarction (STEMI) patients within 24 h. METHODS: Three hundred thirty-four patients were divided into four ECG-based groups: Group A: R V1 <0.3 mV with ST-segment elevation (ST↑) V7-V9, Group B: R V1 <0.3 mV without ST↑ V7-V9, Group C: R V1 ≥0.3 mV with ST↑ V7-V9, and Group D: R V1 ≥0.3 mV without ST↑ V7-V9. RESULTS: Group A demonstrated the longest QRS duration, followed by Groups B, C, and D. ECG signs for right ventricle (RV) infarction were more common in Groups A and B (p < .01). ST elevation in V6, indicative of left ventricle (LV) lateral injury, was more higher in Group C than in Group A, while the ∑ST↑ V3R + V4R + V5R, representing RV infarction, showed the opposite trend (p < .05). The estimated LV infarct size from ECG was similar between Groups A and C, yet Group A had higher creatine kinase MB isoform (CK-MB; p < .05). Cardiac troponin I (cTNI) was higher in Groups A and C than in B and D (p < .05 and p = .16, respectively). NT-proBNP decreased across groups (p = .20), with the highest left ventricular ejection fraction (LVEF) observed in Group D (p < .05). Group A notably demonstrated more cardiac dysfunction within 4 h post-onset. CONCLUSIONS: For inferior STEMI patients, concurrent R V1 <0.3 mV with ST↑ V7-V9 suggests prolonged ventricular activation and notable myocardial damage. RV infarction's dominance over LV lateral injury might explain these observations.
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Infarto Miocárdico de Parede Inferior , Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto Miocárdico de Parede Inferior/complicações , Infarto Miocárdico de Parede Inferior/diagnóstico , Eletrocardiografia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Relevância Clínica , Volume Sistólico , Função Ventricular Esquerda , Arritmias CardíacasRESUMO
BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Naâº, Ca²âº, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²âº, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²âº, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.
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Hipertrigliceridemia , Pancreatite , Humanos , Cálcio , Neutrófilos , Doença Aguda , Estudos Retrospectivos , Hipertrigliceridemia/complicações , Apolipoproteínas , Apolipoproteínas A , Apolipoproteínas BRESUMO
Entomopathogenic nematodes (EPNs) use the chemical cues emitted by insects and insect-damaged plants to locate their hosts. Steinernema carpocapsae, a species of EPN, is an established biocontrol agent used against insect pests. Despite its promising potential, the molecular mechanisms underlying its ability to detect plant volatiles remain poorly understood. In this study, we investigated the response of S. carpocapsae infective juveniles (IJs) to 8 different plant volatiles. Among these, carvone was found to be the most attractive volatile compound. To understand the molecular basis of the response of IJs to carvone, we used RNA-Seq technology to identify gene expression changes in response to carvone treatment. Transcriptome analysis revealed 721 differentially expressed genes (DEGs) between carvone-treated and control groups, with 403 genes being significantly upregulated and 318 genes downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the responsive DEGs to carvone attraction were mainly involved in locomotion, localization, behavior, response to stimulus, and olfactory transduction. We also identified four upregulated genes of chemoreceptor and response to stimulus that were involved in the response of IJs to carvone attraction. Our results provide insights into the potential transcriptional mechanisms underlying the response of S. carpocapsae to carvone, which can be utilized to develop environmentally friendly strategies for attracting EPNs.
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Monoterpenos Cicloexânicos , Insetos , Rabditídios , Animais , Rabditídios/fisiologiaRESUMO
Artificial olfaction, also known as an electronic nose, is a gas identification device that replicates the human olfactory organ. This system integrates sensor arrays to detect gases, data acquisition for signal processing, and data analysis for precise identification, enabling it to assess gases both qualitatively and quantitatively in complex settings. This article provides a brief overview of the research progress in electronic nose technology, which is divided into three main elements, focusing on gas-sensitive materials, electronic nose applications, and data analysis methods. Furthermore, the review explores both traditional MOS materials and the newer porous materials like MOFs for gas sensors, summarizing the applications of electronic noses across diverse fields including disease diagnosis, environmental monitoring, food safety, and agricultural production. Additionally, it covers electronic nose pattern recognition and signal drift suppression algorithms. Ultimately, the summary identifies challenges faced by current systems and offers innovative solutions for future advancements. Overall, this endeavor forges a solid foundation and establishes a conceptual framework for ongoing research in the field.
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Nariz Eletrônico , Gases , Gases/análise , Humanos , Algoritmos , Monitoramento Ambiental/métodos , Monitoramento Ambiental/instrumentaçãoRESUMO
BACKGROUND: Laboratory scale experiments have shown that curdlan and gellan gum gelled together as curdlan/gellan gum (CG) hybrid gels showed better gel properties than the individual curdlan and gellan gum. In this study, CG and black wolfberry anthocyanin (BWA), CG and maltitol (ML) hybrid gels were constructed using CG hybrid gel as matrix. The effects of BWA or ML on the gel properties and microstructure of CG hybrid gels were investigated and a confectionery gel was developed. RESULTS: The presence of BWA increased the storage modulus (G') value of CG at 0.1 Hz, whereas ML had little effect on the G' value of CG. The addition of BWA (5 g L-1 ) and ML (0.3 mol L-1 ) increased the melting and gelling temperatures of CG hybrid gels to 42.4 °C and 34.1 °C and 44.2 °C and 33.2 °C, respectively. Meanwhile, the relaxation time T22 in CG-ML and CG-BWA hybrid gels was reduced to 91.96 and 410.27 ms, indicating the strong binding between BWA and CG, ML and CG. The hydrogen bond interaction between BWA or ML and CG was confirmed by the shift in the hydroxyl stretching vibration peak. Moreover, the microstructures of CG-ML and CG-BWA hybrid gels were denser than that of CG. In addition, confectionery gel containing CG-BWA-ML has good chewing properties. CONCLUSION: These results indicated that the incorporation of BWA or ML could improve the structure of CG hybrid gels and assign a sustainability potential for the development of confectionery gels based on CG complex. © 2024 Society of Chemical Industry.
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Lycium , Maltose/análogos & derivados , Álcoois Açúcares , beta-Glucanas , Antocianinas , Polissacarídeos Bacterianos/química , Géis/química , ReologiaAssuntos
Ductos Pancreáticos , Pancreatite , Recidiva , Humanos , Ductos Pancreáticos/diagnóstico por imagem , Pancreatite/etiologia , Pancreatite/complicações , Doença Aguda , Masculino , Colangiopancreatografia Retrógrada Endoscópica , Coristoma/complicações , Coristoma/diagnóstico por imagem , Coristoma/cirurgia , Feminino , Pessoa de Meia-IdadeRESUMO
Ajaniaflavida, a new species from western Sichuan and eastern Xizang, China, is described and illustrated. It is readily assigned to A.sect.Ajania owing to its straw-colored, glossy involucres and marginally whitish scarious phyllaries. Within the section, it is distinct in being a shrub of 1-2 m in height, and in having creamy yellow florets. It is superficially similar to A.ramosa in A.sect.Phaeoscyphus, but can easily be distinguished by, among other characters, the plant height, color of the florets and margins of the phyllaries. In addition, we provide a distribution map of the new species.
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Ligularialushuiensis, a new species from northwestern Yunnan, China, is described and illustrated. It was tentatively placed in L.sect.Ligulariaser.Ligularia on the basis of the pinnate-palmate leaf venation, racemose synflorescence and pappus which is as long as tubular corolla. Within the series, it appeared somewhat close to both L.lamarum and L.pseudolamarum. However, L.lushuiensis can be easily distinguished from the latter two species by, among other characters, the leaf margin, bract size, involucre shape and size, and number and width of ray florets. Morphologically, L.lushuiensis is also superficially similar to L.secunda but differs readily by having distally shortly yellowish and brownish puberulent stems, palmately-pinnately veined leaves regularly dentate at margin, scarious, brown and larger bracts, and larger ray laminae. In addition, a distribution map and a diagnostic key to Chinese species of L.ser.Ligularia are also provided.
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RATIONALE: Complicated pressure injury in paraplegic patients is common and difficult to manage. Previous case studies have documented short-term management; however, little is known regarding suitable approaches to long-term clearing of extensive pressure injury in the sacrococcygeal area under denervation. PATIENT CONCERNS: A 53-year-old man was bedridden for 1.5 years owing to cervical vertebral fracture-dislocation (C5-C6), resulting in extensive sacrococcygeal pressure injury. DIAGNOSES: On admission, he presented with the injury complicated by infection (stage IV necrosis), and his vital signs were unstable. INTERVENTIONS: The infection was treated with a range of antibiotics, including clindamycin phosphate, metronidazole, cefoperazone sodium, and sulbactam sodium. Debridement of the pressure injury was performed, helping remove the necrotic tissue and stimulate tissue regeneration. OUTCOMES: The patient was discharged after 88 days of hospitalization. The extent of the pressure injury at discharge was reduced compared with that at admission. At 4-month follow-up, the injury was nearly healed, with no signs of any further complications. LESSONS: This case study suggests that wound debridement is a cost-effective and clinically efficacious approach to long-term complicated pressure injury management.
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Lesões por Esmagamento , Luxações Articulares , Úlcera por Pressão , Masculino , Humanos , Pessoa de Meia-Idade , Desbridamento/métodos , Úlcera por Pressão/cirurgia , CicatrizaçãoRESUMO
Understanding the effects of food waste biogas residue composting and chemical amendments on soil aggregates composition of different particle sizes, stability, and organic matter distribution in relocation sites could provide primary data for improving soil quality and land utilization of food waste biogas residue composting. We analyzed the characteristics of soil aggregates distribution, stability of aggregates, and organic matter content in different particle sizes under treatments with different application amounts of food waste biogas residue composting, chemical amendments (ß-cyclodextrin, calcium sulfate and ferric oxide were mixed at a mass ratio of 1:1:1), and control (100% soil). The results showed that 20% (soil: biogas residue composting=8:2) and 30% (soil: biogas residue composting =7:3) biogas residue composting significantly decreased the micro-aggregates content with the particle size of <0.106 mm and increased the large aggregates content with the particle size of 0.5-1.0 mm. All treatments significantly increased large aggregates content with the particle size of ≥2.0 mm, soil aggregate structure content, and mean weight diameter, but reduced the percentage of aggregate destruction. Among all the treatments, the effect of mixes application of 20% biogas residue composting and chemical amendments was the best. Biogas residue composting treatments significantly affected the distribution of organic matter in soil aggregates, with the strongest effect under 30% biogas residue composting treatment. Biogas residue composting treatments significantly increased soil organic matter content in all aggregates, with the maximal increase of organic matter content in soil micro-aggregates with the particle size of 0.106-0.25 mm. In conclusion, biogas residue composting could increase organic matter content of soil aggregates in different particle sizes, promote the formation of large soil aggregates, and improve the stability of aggregation. Specifically, the mixed application of biogas residue composting and chemical amendments performed better on soil improvement in relocation site.
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Biocombustíveis , Compostagem , Compostos Orgânicos , Eliminação de Resíduos , Solo , Solo/química , Compostagem/métodos , Biocombustíveis/análise , Compostos Orgânicos/análise , Compostos Orgânicos/química , Eliminação de Resíduos/métodos , Tamanho da Partícula , Alimentos , Perda e Desperdício de AlimentosRESUMO
BACKGROUND: Currently, there is limited understanding regarding the clinical significance of the tumor-stroma ratio (TSR) in giant cell tumor of bone (GCTB). Hence, we aimed to investigate the distribution of TSR in GCTB and explore its correlation with various clinicopathologic factors, immune microenvironment, survival prognosis, and denosumab treatment responsiveness. METHODS: We conducted a multicenter cohort study comprising 426 GCTB patients treated at four centers. TSR was evaluated on hematoxylin and eosin-stained and immunofluorescent sections of tumor specimens. Immunohistochemistry was performed to assess CD3+, CD4+, CD8+, CD20+, PD-1+, PD-L1+, and FoxP3+ TIL subtypes as well as Ki-67 expression levels in 426 tissue specimens. These parameters were then analyzed for their correlations with patient outcomes [local recurrence-free survival (LRFS) and overall survival (OS)], clinicopathological features, and denosumab treatment responsiveness. RESULTS: Low TSR was significantly associated with poor LRFS and OS in both cohorts. Furthermore, TSR was also correlated with multiple clinicopathological features, TIL subtype expression, and denosumab treatment responsiveness. TSR demonstrated similar predictive capabilities as the conventional Campanacci staging system for predicting patients' LRFS and OS. CONCLUSION: The results of this study provide evidence supporting the use of TSR as a reliable prognostic tool in GCTB and as a predictor of denosumab treatment responsiveness. These findings may aid in developing individualized treatment strategies for GCTB patients in the future.
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Neoplasias Ósseas , Denosumab , Tumor de Células Gigantes do Osso , Microambiente Tumoral , Humanos , Denosumab/uso terapêutico , Tumor de Células Gigantes do Osso/tratamento farmacológico , Tumor de Células Gigantes do Osso/patologia , Microambiente Tumoral/imunologia , Feminino , Masculino , Adulto , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/imunologia , Pessoa de Meia-Idade , Estudos de Coortes , Adulto Jovem , Resultado do Tratamento , Prognóstico , Conservadores da Densidade Óssea/uso terapêutico , AdolescenteRESUMO
Resonant exchange of the chiral Majorana fermions (MFs) that is coupled to two parallel Majorana zero modes (MZMs) or two parallel quantum dots (QDs) is investigated. We find that, in the two QDs coupling case, the resonant exchange for the chiral MFs is analogous to that in the MZM coupling case. We further propose a circuit based on topological superconductor, which is formed by the proximity coupling of a quantum anomalous Hall insulator and a s-wave superconductor, to observe the resonant exchange of chiral MFs pairs. The numerical calculations show that the resonant transmission of the chiral MFs can be adjusted by varying the coupling parameters at superconductor phase differenceΔφ=π. It is particularly noteworthy that, by only modulating the coupling strength between the two QDs, the resonant exchange may be switched on or off. By adding another MZM, the non-Abelian braiding like operation can be realized. Therefore, our design scheme may provide another way for non-Abelian braiding operation of MFs and the findings may have potential application value in the realization of topological quantum computers.
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BACKGROUND: Although a survival benefit was observed in patients with metastatic renal cell carcinoma (mRCC) who underwent cytoreductive nephrectomy (CN), there is a lack of effective tools for predicting which individuals are likely to benefit from surgical intervention. Herein, we developed a predictive model using data from the Surveillance, Epidemiology, and End Results (SEER) database. MATERIALS AND METHODS: Patients diagnosed with mRCC were screened from the SEER database (2010-2020), supplemented by patients from East Asia. Patients were categorized into surgical and non-surgical groups, with propensity score matching conducted to balance baseline characteristics. Logistic regression analysis was performed to identify independent factors associated with benefits and a nomogram was constructed based on these factors. RESULTS: This study included 11,044 cases from the SEER database and 50 cases from an external validation cohort. CN was identified as an independent protective factor for OS. A nomogram was established, and it performed well in the training and validation sets. The calibration curves and DCA confirmed that the nomogram model could precisely predict the probability of surgical benefit. We used the nomogram to classify surgical patients into benefit and non-benefit groups. Then, we found that OS was significantly higher in the benefit group than in the non-benefit group. The external validation cohort observed the same result (P=0.035). CONCLUSION: While CN offers potential benefits for patients with mRCC, its applicability varies across the patient population. Our study constructed a nomogram that quantitatively assesses the likelihood of surgical benefit in mRCC patients, facilitating more tailored therapeutic decision-making.
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Carcinoma de Células Renais , Procedimentos Cirúrgicos de Citorredução , Neoplasias Renais , Nefrectomia , Nomogramas , Programa de SEER , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Nefrectomia/métodos , Masculino , Feminino , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Pessoa de Meia-Idade , Idoso , Seleção de Pacientes , Pontuação de Propensão , PrognósticoRESUMO
The proliferation of neural stem cells (NSCs) is precisely regulated by extracellular environmental factors. In situ hypoxia, one of the key factors involved in the regulation of NSC characteristics, has attracted increasing amounts of attention. Numerous studies have demonstrated that hypoxia can significantly promote the formation of neurospheres and the proliferation of NSCs in vitro and that intermittent hypoxia can promote the proliferation of endogenous NSCs in vivo. In this article, the effects of different concentrations of oxygen on NSC proliferation and differentiation both in vivo and in vitro are reviewed, and the potential applications of hypoxia-preconditioned NSCs, as well as research progress and challenges in the treatment of central nervous system diseases, are further summarized. Here, the critical role of oxygen in the neurogenesis of NSCs is emphasized, and insights into the use of hypoxia to regulate NSC characteristics are provided.
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Hipóxia Celular , Proliferação de Células , Células-Tronco Neurais , Neurogênese , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Humanos , Animais , Diferenciação Celular , Oxigênio/metabolismo , Oxigênio/farmacologiaRESUMO
OBJECTIVE: To analyse the comparative clinical outcomes and clinicopathological significance of vocal fold leukoplakia lesions treated by appearance classification and traditional methods. METHOD: A total of 1442 vocal fold leukoplakia patients were enrolled. Group A patients were treated according to appearance classification and Group B patients were treated according to traditional methods. RESULTS: In Group A, 24.4, 14.9 and 60.6 per cent of patients had grade I, II and III dysplasia, respectively. Grade I dysplasia (63.4 per cent) was more than twice as frequent in Group B patients than in Group A patients, while grade II dysplasia (20.4 per cent) and grade III dysplasia (16.2 per cent) were significantly less frequent in Group B patients than in Group A patients (p = 0.000). There was a significant correlation between vocal fold leukoplakia appearance and the degree of dysplasia (p = 0.000). The recurrence and malignant transformation rates (17.6 and 31 per cent, respectively) in Group B were significantly greater than those in Group A (10.8 and 25.9 per cent, respectively) (p = 0.000). CONCLUSION: Vocal fold leukoplakia appearance classification is useful for guiding treatment decision-making and could help to improve therapeutic accuracy.
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Doenças da Laringe , Prega Vocal , Humanos , Prega Vocal/patologia , Doenças da Laringe/patologia , Leucoplasia/cirurgia , Leucoplasia/patologiaRESUMO
Salidroside (Sal), the main bioactive substance in Rhodiola rosea, is a promising functional food component with a wide range of pharmacological effects, but its biological activity is challenging to sustain due to its short half-life, low oral bioavailability, and susceptibility to environmental factors. The aim of this study was to investigate the effect of sodium alginate (SA) concentration on the construction of W/O/W emulsion in the protection of Sal. With the escalation of SA concentrations, the range of droplet size distribution was smaller and the droplets were more uniform. When the concentration of SA was 2 %, the average droplet size reached 9.1 ± 0.1 µm, and the encapsulation efficiency of Sal was 77.8 ± 1.8 %. Moreover, the double emulsion with 2 % SA was the most stable for 28 days at 4 °C since the oil droplets were embedded in the network structure of SA.