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BACKGROUND: For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT). METHODS: We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors. RESULTS: A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months (P = .020), 69.2% vs 49.9% (P = .002), and 85.9% vs 50.5% (P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480). CONCLUSION: This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.
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Estadificación de Neoplasias , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Neoplasias Ováricas/mortalidad , Adulto , Anciano , Carcinoma Epitelial de Ovario/terapia , Carcinoma Epitelial de Ovario/patología , Procedimientos Quirúrgicos de Citorreducción/métodos , Radioterapia de Intensidad Modulada/métodos , Radioterapia Adyuvante/métodosRESUMEN
PURPOSE: Iodine 123 labeled meta-iodobenzylguanidine ([123I]MIBG) scan with SPECT/CT imaging is one of the most commonly used imaging modalities in the evaluation of neuroblastoma. [18F]-meta-fluorobenzylguanidine ([18F]MFBG) is a novel positron emission tomography (PET) tracer which was reported to have a similar biodistribution to [123I]MIBG. However, the experience of using [18F]MFBG PET/CT in the evaluation of patients with neuroblastoma is limited. This preliminary investigation aims to assess the efficacy of [18F]MFBG PET/CT in the evaluation of neuroblastomas in comparison to [123I]MIBG scans with SPECT/CT. MATERIALS AND METHODS: In this prospective, single-center study, 40 participants (mean age 6.0 ± 3.7 years) with history of neuroblastoma were enrolled. All children underwent both [123I]MIBG SPECT/CT and [18F]MFBG PET/CT studies. The number of lesions and the Curie scores revealed by each imaging method were recorded. RESULTS: Six patients had negative findings on both [123I]MIBG and [18F]MFBG studies. Four of the 34 patients (11.8%) were negative on [123I]MIBG but positive on [18F]MFBG, while 30 patients were positive on both [123I]MIBG and [18F]MFBG studies. In these 34 patients, [18F]MFBG PET/CT identified 784 lesions while [123I]MIBG SPECT/CT detected 532 lesions (p < 0.001). The Curie scores obtained from [18F]MFBG PET/CT (11.32 ± 8.18, range 1-27) were statistically higher (p < 0.001) than those from [123I]MIBG SPECT/CT (7.74 ± 7.52, range 0-26). 30 of 34 patients (88.2%) with active disease on imaging had higher Curie scores based on the [18F]MFBG study than on the [123I]MIBG imaging. CONCLUSION: [18F]MFBG PET/CT shows higher lesion detection rate than [123I]MIBG SPECT/CT in the evaluation of pediatric patients with neuroblastoma. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov : NCT05069220 (Registered: 25 September 2021, retrospectively registered); Institute Review Board of Peking Union Medical College Hospital: ZS-2514.
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3-Yodobencilguanidina , Neuroblastoma , Niño , Preescolar , Humanos , Neuroblastoma/diagnóstico por imagen , Neuroblastoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Estudios Prospectivos , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único/métodos , Distribución TisularRESUMEN
A transition-metal-free hydrosilylation of allenes is reported herein by using commercially available lithium triethylborohydride (LiHBEt3) as the catalyst. Both mono- and disubstituted allenes could be hydrosilylated with primary or secondary silanes effectively. This reaction represents an environmental and economic method to prepare (E)-allylsilanes in good yields along with decent selectivities.
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Obesity is a growing global health problem and is associated with increased prevalence of many metabolic disorders, including diabetes, hypertension and cardiovascular disease. Pancreatic lipase (PL) has been validated as a key target for developing anti-obesity agents, owing to its crucial role in lipid digestion and absorption. In the past few decades, porcine PL (pPL) is always used as the enzyme source for screening PL inhibitors, which generate numerous pPL inhibitors but the potent inhibitors against human PL (hPL) are rarely reported. Herein, a series of salicylanilide derivatives were designed and synthesized, while their anti-hPL effects were assayed by a fluorescence-based biochemical approach. To investigate the structure-activity relationships of salicylanilide derivatives as hPL inhibitors in detail, structural modifications on three rings (A, B and C) of the salicylanilide skeleton were performed. Among all tested compounds, 2t and 2u were found possessing the most potent anti-PL activity, showing IC50 values of 1.86 µM and 1.63 µM, respectively. Inhibition kinetic analyses suggested that both 2t and 2u could effectively inhibit hPL in a non-competitive manner, with the ki value of 1.67 µM and 1.70 µM, respectively. Fluorescence quenching assays suggested that two inhibitors could quench the fluorescence of hPL via a static quenching procedure. Molecular docking simulations suggested that 2t and 2u could tightly bind on an allosteric site of hPL. Collectively, the structure-activity relationships of salicylanilide derivatives as hPL inhibitors were carefully investigated, while two newly identified reversible hPL inhibitors (2t and 2u) could be used as promising lead compounds to develop novel anti-obesity drugs.
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Lipasa , Salicilanilidas , Humanos , Animales , Porcinos , Simulación del Acoplamiento Molecular , Lipasa/metabolismo , Relación Estructura-Actividad , Inhibidores Enzimáticos/química , PáncreasRESUMEN
The potential application of zinc air batteries to tackle the energy shortage and environmental crisis has proposed new requirements of bifunctional catalysts for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER). Utilizing the special spatial structure of zeolitic imidazolate framework-67 (ZIF-67) as an ideal research platform, the effect of a trace amount of Fe on the composition and structure of as-obtained Fe-CoNC catalysts was investigated. It was revealed that, due to the increased exposed pore structure and metal species located at the near surface, the active sites for the ORR/OER on Fe-CoNC are highly exposed, greatly boosting the activity to the reduction and evolution of oxygen in alkaline media. ZABs with Fe-CoNC have the highest maximum power density of 200 mW cm-2 when operated at current densities as high as 328 mA cm-2, better than not only Fe-free CoNC, but also precious metal-based references with the same catalyst loading.
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BACKGROUND: Digital splints are indispensable in orthognathic surgery. However, the present design process of splints is time-consuming and has low reproducibility. To solve these problems, an algorithm for artificial intelligent splints has been developed in this study, making the automatic design of splints accessible. METHODS: Firstly, the algorithm and program of the artificial intelligence splint were created. Then a total of 54 patients with skeletal class III malocclusion were included in this study from 2018 to 2020. Pre and postoperative radiographic examinations were performed. The cephalometric measurements were recorded and the difference between virtual simulation and postoperative images was measured. The time cost and differences between artificial intelligent splints and digital splints were analyzed through both model surgery and radiographic images. RESULTS: The results showed that the efficiency of designing splints is significantly improved. And the mean difference between artificial intelligent splints and digital splints was <0.15 mm in model surgery. Meanwhile, there was no significant difference between the artificial intelligent splints and digital splints in radiological image analysis. CONCLUSIONS: In conclusion, compared with digital splints, artificial intelligent splints could save time for preoperative design while ensuring accuracy. The authors believed that it is conducive to the presurgical design of orthognathic surgery.
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Maloclusión de Angle Clase III , Cirugía Ortognática , Procedimientos Quirúrgicos Ortognáticos , Cirugía Asistida por Computador , Humanos , Férulas (Fijadores) , Procedimientos Quirúrgicos Ortognáticos/métodos , Inteligencia Artificial , Reproducibilidad de los Resultados , Maloclusión de Angle Clase III/cirugía , Cirugía Asistida por Computador/métodosRESUMEN
A general and efficient palladium catalyzed hydroalkynylation of allenes was developed to produce synthetically versatile (E)-1,3-enyne derivatives with high regio- and stereoselectivity. This catalytic system proceeded under mild conditions and was compatible with a broad range of substrates, especially for allenes without electron-bias groups. This work further broadens the synthetic potential of these scaffolds in organic synthesis and medicinal chemistry.
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Alcadienos , Paladio , Catálisis , EstereoisomerismoRESUMEN
Background: The effect of radiotherapy (RT) for second primary malignancies (SPMs) among prostate cancer survivors is controversial. Methods: Applying logistic regression, competing risk analysis and propensity score matching method, this study analyzed clinical data from the Surveillance, Epidemiology, and End Results program to compare the risk for SPMs between patients receiving RT and non-RT. Results: In this study, prostate cancer patients treated with RT developed more SPMs in the anus, bladder, rectum, liver, lung and bronchus and lymphoma than non-RT groups. Conclusion: More intensive surveillance should be adopted for these cancers among prostate cancer survivors.
Plain language summary Patients with prostate cancer have the highest 5-year survival rate, which increases the risk for developing second primary malignancies (SPMs). The effect of radiotherapy (RT) for SPMs is controversial among prostate cancer survivors. This study analyzed a mass of prostate cancer patients from a public database to compare risk for SPMs between RT and non-RT groups. RT indeed increased certain categories of SPM and intensive surveillance should be considered.
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Neoplasias Inducidas por Radiación/etiología , Neoplasias Primarias Secundarias/etiología , Neoplasias de la Próstata/radioterapia , Anciano , Supervivientes de Cáncer/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/epidemiología , Neoplasias Inducidas por Radiación/patología , Neoplasias Primarias Secundarias/epidemiología , Neoplasias Primarias Secundarias/patología , Puntaje de Propensión , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/patología , Radioterapia/efectos adversos , Radioterapia/estadística & datos numéricos , Medición de Riesgo , Programa de VERF/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Several studies have shown that N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly correlated with the complexity of coronary artery disease and the prognosis of patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS), However, it remains unclear about the prognostic value of NT-proBNP in patients with NSTE-ACS and multivessel coronary artery disease (MCAD) undergoing percutaneous coronary intervention (PCI). Therefore, this study aimed to reveal the relationship between NT-proBNP levels and the prognosis for NSTE-ACS patients with MCAD undergoing successful PCI. METHODS: This study enrolled 1022 consecutive NSTE-ACS patients with MCAD from January 2010 to December 2014. The information of NT-proBNP levels was available from these patients. The primary outcome was in-hospital all-cause death. In addition, the 3-year follow-up all-cause death was also ascertained. RESULTS: A total of 12 (1.2%) deaths were reported during hospitalization. The 4th quartile group of NT-proBNP (> 1287 pg/ml) showed the highest in-hospital all-cause death rate (4.3%) (P < 0.001). Besides, logistic analyses revealed that the increasing NT-proBNP level was robustly associated with an increased risk of in-hospital all-cause death (adjusted odds ratio (OR): 2.86, 95% confidence interval (CI) = 1.16-7.03, P = 0.022). NT-proBNP was able to predict the in-hospital all-cause death (area under the curve (AUC) = 0.888, 95% CI = 0.834-0.941, P < 0.001; cutoff: 1568 pg/ml). Moreover, as revealed by cumulative event analyses, a higher NT-proBNP level was significantly related to a higher long-term all-cause death rate compared with a lower NT-proBNP level (P < 0.0001). CONCLUSIONS: The increasing NT-proBNP level is significantly associated with the increased risks of in-hospital and long-term all-cause deaths among NSTE-ACS patients with MCAD undergoing PCI. Typically, NT-proBN P > 1568 pg/ml is related to the all-cause and in-hospital deaths.
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Enfermedad de la Arteria Coronaria/terapia , Péptido Natriurético Encefálico/sangre , Infarto del Miocardio sin Elevación del ST/terapia , Fragmentos de Péptidos/sangre , Intervención Coronaria Percutánea , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Causas de Muerte , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/sangre , Infarto del Miocardio sin Elevación del ST/diagnóstico , Infarto del Miocardio sin Elevación del ST/mortalidad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: Patient-perceived quality of care has become an increasingly important index within the healthcare setting. We examined patient-reported overall quality of care and patient experiences in three specific domains of care (physician communication, nursing care, and care coordination) in a sample of Chinese patients with advanced cancer. METHODS: A cross-sectional study was conducted with stage IV cancer patients (N = 202) who were recruited from a public, tertiary hospital in Beijing. Study participants completed surveys administered by a research assistant. Multivariable regression analysis was conducted to examine the extent to which patient demographic factors (age, gender, socioeconomic status), disease/treatment factors, and domain-specific care were associated with overall quality of care. RESULTS: A majority of patients reported overall quality of care scores that we were either excellent (23%) or very good (41%). Patients reported highest ratings in the domain of nursing care (M = 87.57, SD = 31.05), followed by physician communication (M = 68.93, SD = 32.30), and care coordination (M = 66.79, SD = 25.17). Better perceived physician communication (b = 0.17, p < 0.01), care coordination (b = 0.26, p < 0.01), and higher socioeconomic status (b = 11.30, p < 0.05) were associated with higher overall quality of care. CONCLUSIONS: A majority of patients with advanced cancer in this Chinese hospital reported positive overall quality of care. Physician communication and care coordination are potential areas to focus on to improve patient-reported overall quality of care. Understanding perceptions of care quality will allow opportunities to improve delivery of healthcare.
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Neoplasias/terapia , Calidad de la Atención de Salud/normas , Adulto , Anciano , Anciano de 80 o más Años , Beijing , China , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/psicología , Encuestas y Cuestionarios , Adulto JovenRESUMEN
OBJECTIVE: To analyze the association between posttreatment squamous cell carcinoma antigen (SCC Ag) and treatment failure in patients with cervical SCC treated with concurrent chemoradiotherapy (CCRT). METHODS: We reviewed patients with cervical SCC who were treated with definitive radiotherapy or CCRT between June 2012 and May 2015 at our institute. A receiver operating characteristic (ROC) curve was used to analyze the cutoff value of posttreatment SCC Ag in predicting treatment failure. Log-rank tests and Cox proportional hazards models were used to identify whether posttreatment SCC Ag was significant in predicting disease-free survival (DFS). RESULTS: A total of 559 patients were included in this study. With the ROC curve, the optimal cutoff posttreatment SCC Ag level was 1.8â¯ng/mL (sensitivity 27.1%, specificity 96.6%). A posttreatment SCC Ag levelâ¯≥â¯1.8â¯ng/mL was observed in 47 patients. The multivariate analysis showed that posttreatment SCC Ag (hazard ratio 5.10; 95% confidence interval, 3.31-7.88; pâ¯<â¯0.001) was an independent prognostic factor of DFS. The 3-year overall survival (OS), DFS, local control, and distant control rates of patients with posttreatment SCC Agâ¯<â¯1.8â¯ng/mL and ≥1.8â¯ng/mL were 90.7% and 46.4% (pâ¯<â¯0.001), 84.8% and 31.9% (pâ¯<â¯0.001), 81.4% and 69.5% (pâ¯<â¯0.001), and 90.4% and 54.1% (pâ¯<â¯0.001), respectively. CONCLUSION: Patients with posttreatment SCC Agâ¯≥â¯1.8â¯ng/mL suffer due to a high rate of treatment failure and poor survival.
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Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Serpinas/metabolismo , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Carcinoma de Células Escamosas/mortalidad , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia del Tratamiento , Neoplasias del Cuello Uterino/mortalidadRESUMEN
BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for local advanced cervical cancer. However, for elderly patients, studies are limited and the outcomes are controversial. We retrospectively analyzed the efficacy and tolerance of radical radiotherapy (RT) or CCRT in elderly cervical cancer patients and performed comparisons between them. METHODS: We retrospectively analyzed the elderly cervical cancer patients (≥70 years old) treated with radical RT or CCRT between January 2006 and December 2014. For external beam radiotherapy, 50Gy in 25 fractions or 50.4Gy in 28 fractions were delivered via 3-dimensional conformal radiation therapy or intensity modulated radiation therapy. High-dose-rate intracavitary brachytherapy was performed with a dose of 30-36Gy in 5-7 fractions to point A. Concurrent chemotherapy regimens included weekly cisplatin and paclitaxel. RESULTS: Seventy-three patients were eligible for this study. Twenty-one(28.8%) and 52(71.2%) patients suffered with FIGO stage IB-IIA and IIB-IVA disease, respectively. Twenty-four (32.9%) patients received CCRT. The median duration of follow-up was 32.4 months (4.8-118.8 months). The 3-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) were 64.9%, 67.8% and 66.5%, respectively. By multivariate analysis, CCRT was a significant predictive factor of OS(p = 0.023, 95% confidence interval [CI]: 1.172-8.860), CSS(p = 0.031, 95% CI: 1.131-13.908)and DFS(p = 0.045, 95% CI: 1.023 ~ 6.430). The 3-year OS of patients received RT and CCRT were 54.3% and 83.1%, CSS were 56.8% and 87.1%, DFS were 57.6% and 83.3%. There was no treatment related death. Grade 3-4 acute hematological, gastrointestinal and urinary toxicity incidences were 31.5%, 19.1% and 12.3%, respectively. For grade 3-4 chronic gastrointestinal and genitourinary toxicities, the incidences were 4.1% and 2.7%, respectively. Compared with RT, CCRT was related with high grade 3-4 hematological toxicity (16.3% and 62.5% respectively, p < 0.001), respectively. However, acute nonhematological toxicity and chronic toxicity were not significantly different. CONCLUSION: Elderly cervical cancer patients could tolerate radical RT and CCRT very well and get a favored survival. Compared with RT, CCRT could improve the survival of elder cervical cancer patients with similar nonhematological toxicity. CCRT should be considered in elderly cervical cancer patients.
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Carcinoma de Células Escamosas/terapia , Neoplasias del Cuello Uterino/terapia , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia , Carcinoma de Células Escamosas/mortalidad , Quimioradioterapia , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Paclitaxel/administración & dosificación , Pronóstico , Modelos de Riesgos Proporcionales , Radioterapia de Intensidad Modulada , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidadRESUMEN
In this study, crude Cortex Periplocae polysaccharides (CCPPs) were extracted with water. CCPPs were decolored with AB-8 resin and deproteinated using papain-Sevage methods. Then, they were further purified and separated through DEAE-52 anion exchange chromatography and Sephadex G-100 gel filtration chromatography, respectively. Three main fractions-CPP1, CPP2, and CPP3, (CPPs)-were obtained. The average molecular weights, monosaccharide analysis, surface morphology, and chemical compositions of the CPPs were investigated by high-performance gel permeation chromatography (HPGPC), gas chromatography-mass spectrometry (GC/MS), UV-vis spectroscopy, Fourier transform infrared (FT-IR) spectrum, and nuclear magnetic resonance (NMR). In addition, the antioxidant activities of these three polysaccharides were investigated. The results indicated that all of the CPPs were composed of rhamnose, arabinose, mannose, glucose, and galactose. These three polysaccharides exhibited antioxidant activities in four assays including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, 2,2'-azino-bis(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical, reducing power, and total antioxidant activity in vitro. The data indicated that these three polysaccharides could be utilized as potential natural sources of alternative additives in the functional food, cosmetics, and pharmaceutical industries.
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Antioxidantes/farmacología , Periploca/química , Polisacáridos/química , Polisacáridos/farmacología , Antioxidantes/química , Fraccionamiento Químico , Cromatografía en Gel , Cromatografía por Intercambio Iónico , Evaluación Preclínica de Medicamentos/métodos , Depuradores de Radicales Libres/farmacología , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Peso Molecular , Monosacáridos/análisis , Polisacáridos/aislamiento & purificación , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
Bone repair is intricately correlated with vascular regeneration, especially of type H vessels. Sirtuin 1 (SIRT1) expression is closely associated with endothelial function and vascular regeneration; however, the role of SIRT1 in enhancing the coupling of type H vessel formation with osteogenesis to promote bone repair needs to be investigated. A co-culture system combining human umbilical vein endothelial cells and osteoblasts was constructed, and a SIRT1 agonist was used to evaluate the effects of SIRT1 activity. The angiogenic and osteogenic capacities of the co-culture system were examined using short interfering RNA. Mouse models with bone defects in the femur or mandible were established to explore changes in type H vessel formation and bone repair following modulated SIRT1 activity. SIRT1 activation augmented the angiogenic and osteogenic capacities of the co-culture system by activating the PI3K/AKT/FOXO1 signalling pathway and did not significantly regulate osteoblast differentiation. Inhibition of the PI3K/AKT/FOXO1 pathway attenuated SIRT1-mediated effects. The SIRT1 activity in bone defects was positively correlated with the formation of type H vessels and bone repair in vivo, whereas SIRT1 inhibition substantially weakened vascular and bone formation. Thus, SIRT1 is crucial to the coupling of type H vessels with osteogenesis during bone repair.
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Técnicas de Cocultivo , Células Endoteliales de la Vena Umbilical Humana , Osteoblastos , Osteogénesis , Transducción de Señal , Sirtuina 1 , Sirtuina 1/metabolismo , Sirtuina 1/genética , Osteogénesis/fisiología , Animales , Humanos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Ratones , Osteoblastos/metabolismo , Osteoblastos/citología , Neovascularización Fisiológica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Regeneración Ósea , Proteína Forkhead Box O1/metabolismo , Ratones Endogámicos C57BL , Diferenciación Celular , MasculinoRESUMEN
Background: Parameningeal rhabdomyosarcoma (PM-RMS) accounts for about 20% of all rhabdomyosarcoma (RMS) cases. At present, most research on PM-RMS has been conducted in Europe and the United States of America, and research in China has been very limited. This study sought to analyze the clinical outcomes and prognostic factors of PM-RMS in children and adolescents from two consecutive protocols at Beijing Children's Hospital (BCH). Methods: A total of 80 patients aged up to 18 years with previously untreated PM-RMS who had received treatment under two consecutive protocols [i.e., either the BCH-RMS-2006 protocol or the Chinese Children Cancer Group (CCCG)-RMS-2016 protocol] were included in the statistical analysis. The Kaplan-Meier method was used for the survival analysis, and Cox regression was used for the univariate and multivariate analyses. Results: Of the 80 patients enrolled in the study, 69 (86.2%) had meningeal invasion (MI). Of these 69 MI patients, 18 (22.5%) had cranial nerve palsy (CNP), 64 (80.0%) had cranial base bone erosion (CBBE), 25 (31.3%) had intracranial extension (ICE), and 2 (2.5%) had positive cerebrospinal fluid (CSF) tumor cells. The median follow-up time was 20.5 months (range, 5-100 months). The 5-year overall survival (OS) and progression-free survival (PFS) rates for the entire cohort were 51.7% and 45.6%, respectively. The 5-year OS rates of the patients who received the BCH-RMS-2006 protocol (18/80, 22.5%) and the CCCG-RMS-2016 protocol (62/80, 77.5%) were 33.3% and 57.0%, respectively (P<0.05), while the PFS rates of these patients were 22.2% and 53.6%, respectively (P<0.05). In relation to the PM-RMS patients with MI, the 5-year OS rates were 21.4% and 52.7%, and the 5-year PFS rates were 14.3% and 51.1% for the patients who received the old and new regimens, respectively (P<0.05). The extent of surgical resection had no significant effect on survival. The multivariate analysis showed that the coexistence of CBBE and ICE, no radiotherapy, a poor response to induction chemotherapy, and the BCH-RMS-2006 protocol were risk factors affecting PFS and OS. Conclusions: Of the patients examined in this study, those with PM-RMS with CBBE accompanied by ICE had the worst prognosis. The patients with MI benefited from intensive chemotherapy combined with radiation therapy, but the effect of surgery was very limited.
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OBJECTIVES: To summarize the clinical characteristics and prognosis of children with nasolabial fold rhabdomyosarcoma (RMS). METHODS: Retrospective review of children treated for nasolabial fold RMS from January 2014 to September 2019. RESULTS: Of 21 patients with nasolabial fold RMS, 90.48% were alveolar subtype, in which PAX3/7-FOXO1 fusion positive accounted for 87.5%. Ten patients (47.62%) had nodals invasion. Almost all patients received comprehensive treatment (chemotherapy [100%], radiation therapy [100%], and surgery [95.24%]). The median follow-up time was 34.3 months. The 3-year overall survival (OS) and event-free survival (EFS) was 67.7% ± 14.1% and 42.1% ± 13.5%, respectively. Four patients had regional lymph node relapse (NR), all in the ipsilateral submandibular lymph node region. CONCLUSION: Majority of the patients with RMS in the nasolabial fold area were alveolar subtype and had positive PAX3/7-FOXO1 gene fusion. In addition, the nasolabial fold RMS had a high probability of regional lymph node metastasis in the submandibular area. To maintain the facial aesthetics and functions, the surgical area for nasolabial fold RMS is often very conservative and restricted. This could be one of the contributors for the poor prognosis of nasolabial fold RMS beside its worse pathological subtype and gene fusion.
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Surco Nasolabial , Rabdomiosarcoma , Niño , Humanos , Surco Nasolabial/patología , Recurrencia Local de Neoplasia , Rabdomiosarcoma/terapia , Rabdomiosarcoma/patología , Pronóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Most animals begin controlling their posture, or orientation with respect to gravity, at an early stage in life. Posture is vital for locomotor function. Even animals like fish, which are capable of swimming upside-down, must actively control their orientation to coordinate behaviors such as capturing prey near the water's surface. Here we review recent research from multiple laboratories investigating the organization and function of the vestibular circuits underlying postural control in zebrafish. Some findings in zebrafish strongly align with prior observations in mammals, reinforcing our understanding of homologies between systems. In other instances, the unique transparency and accessibility of zebrafish has enabled new analyses of several neural circuit components that remain challenging to study in mammalian systems. These new results demonstrate topographical and circuit features in postural control.
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Vestíbulo del Laberinto , Pez Cebra , Animales , Equilibrio Postural , MamíferosRESUMEN
In this study, the surface of aluminum powder was uniformly coated with in situ reduced graphene oxide (r-GO) sheets (Al/r-GO). The Ni powder, Al2O3 powder, and Al/r-GO powders were mixed uniformly in a mass ratio of 20:6:4. In situ rGO-reinforced Ni-Al intermetallic composite coatings were successfully prepared using low-pressure cold spraying and subsequent heat treatment. The microstructure and phase of the composite coatings were characterized using X-ray diffraction (XRD), Raman spectroscopy, and scanning electron microscopy (SEM). The high-temperature wear test was conducted at 200 °C, 400 °C, and 600 °C to understand the mechanism. The results indicate that the in situ rGO-reinforced Ni-Al intermetallic composite coatings exhibit a 33.3% lower friction coefficient and 26% lower wear rate in comparison to pure Ni-Al intermetallic coatings, which could be attributed to the generation of an easy-shearing transferred film between the coating and grinding ball.
RESUMEN
OBJECTIVES: Skeletal muscle mass and function deteriorate with ageing. Adiponectin receptors (APNrs), mainly activated by adiponectin, participate in various physiological activities and have varying signalling pathways at different ages. This study aimed to explore whether discrepant performance exists in APNr activation regulating young and aged muscle satellite cells (MUSCs) and whether age-related muscle dysfunction could be alleviated upon APNr activation. METHODS: The gastrocnemius muscle phenotype was observed in male mice aged 2 and 18 months. An APNr agonist (AdipoRon) was used in vitro and in vivo to investigate the changes in cell biological behaviours and whether muscle dysfunction could be retarded after APNr activation. RESULTS: Aged mice exhibited decreased muscle mass and increased fat infiltration. APNr activation inhibited C2C12 cells and young MUSCs (YMUSCs) proliferation but showed no obvious effect on aged MUSCs (AMUSCs). Moreover, APNr activation inhibited the migration of both YMUSCs and AMUSCs. Interestingly, APNr activation hampered the myogenic differentiation but advanced the adipogenic differentiation of YMUSCs, yet exact opposite results were presented in AMUSCs. It was demonstrated that Wnt and PI3K signalling pathways may mediate the phenotypic differences. Furthermore, in vivo experiments verified that APNr activation ameliorated age-related muscle atrophy and excessive fat infiltration. CONCLUSIONS: APNr activation exerted dual effects on the regulation of myogenesis and adipogenesis of YMUSCs and AMUSCs and rescued age-related skeletal muscle dysfunction.
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Adipogénesis , Células Satélite del Músculo Esquelético , Masculino , Ratones , Animales , Adipogénesis/genética , Células Satélite del Músculo Esquelético/metabolismo , Receptores de Adiponectina/metabolismo , Músculo Esquelético/metabolismo , Diferenciación Celular , Desarrollo de Músculos/genéticaRESUMEN
BACKGROUND: Treatment of locally advanced pancreatic cancer (LAPC) has long been calling for advances in technology of radiotherapy. Patients who received radiotherapy still had high risks of local recurrence, while suffering from gastrointestinal side effects. Based on the inherent characteristics of the x-ray and γ-Ray radiation techniques, here we proposed and investigated an unexplored radiation therapy. PURPOSE: To investigate the potential clinical benefit of a novel x-ray and γ-Ray combination radiation technique in patients with LAPC. METHODS: Retrospective intensity-modulated radiotherapy (IMRT) treatment plans of 10 LAPC patients were randomly selected to compare with dual-modality plans. The prescribed dose to PGTV was 60.2 Gy. The PGTV dose was further escalated in dual-modality plan while maintaining clinically tolerable dose to organs at risk (OARs). Dosimetric comparisons were made and analyzed for three treatment plans (tomotherapy, standard dual-modality plan, escalated dual-modality plan) to assess the ability to increase dose to target volume while minimizing dose in adjacent OARs. Finally, radiobiological models were utilized for comparison. RESULTS: All strategies resulted in dosimetrically acceptable plans. Dual-modality plans were present with similar conformity index (CI) and significantly lower gradient index (GI) compared with tomotherapy (3.64 ± 0.37 vs. 4.14 ± 0.61, p = 0.002; 3.64 ± 0.42 vs. 4.14 ± 0.61, p = 0.003). Dmean of PGTV (65.46 ± 3.13 vs. 61.56 ± 1.00, p = 0.009; 77.98 ± 5.86 vs. 61.56 ± 1.00, p < 0.001) and PCTV (55.04 ± 2.14 vs. 53.93 ± 1.67, p = 0.016; 58.24 ± 3.24 vs. 53.93 ± 1.67, p = 0.001) were significantly higher, while Dmean of the stomach was reduced in both dual-modality plans (17.98 ± 10.23 vs. 19.34 ± 9.75, p = 0.024; 17.62 ± 9.92 vs. 19.34 ± 9.75, p = 0.040). The lower V30Gy in the liver (4.83 ± 5.87 vs. 6.23 ± 6.68, p = 0.015; 4.90 ± 5.93 vs. 6.23 ± 6.68, p = 0.016) and lower V45Gy of the small intestine (3.35 ± 3.30 vs. 4.06 ± 3.87, p = 0.052) were found in dual-modality plans. Meanwhile, radiobiological models demonstrated higher probability of tumor control (29.27% ± 9.61% vs. 18.34% ± 4.70%, p < 0.001; 44.67% ± 18.16% vs. 18.34% ± 4.70%, p = 0.001) and lower probability of small intestine complication (2.16% ± 2.30% vs. 1.25% ± 2.72%, p = 0.048) in favor of dual-modality strategy. CONCLUSIONS: A novel dual-modality strategy of x-ray and γ-Ray combination radiation appears reliable for target dose escalation and normal tissue dose reduction. This strategy might be beneficial for local tumor control and the protection of normal organs in patients with LAPC.