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1.
Nano Lett ; 23(11): 5123-5130, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37272668

RESUMO

Developing cost-effective and highly efficient photocathodes toward polysulfide redox reduction is highly desirable for advanced quantum dot (QD) photovoltaics. Herein, we demonstrate nitrogen doped carbon (N-C) shell-supported iron single atom catalysts (Fe-SACs) capable of catalyzing polysulfide reduction in QD photovoltaics for the first time. Specifically, Fe-SACs with FeN4 active sites feature a power conversion efficiency of 13.7% for ZnCuInSe-QD photovoltaics (AM1.5G, 100 mW/cm2), which is the highest value for ZnCuInSe QD-based photovoltaics, outperforming those of Cu-SACs and N-C catalysts. Compared with N-C, Fe-SACs exhibit suitable energy level matching with polysulfide redox couples, revealed by the Kelvin probe force microscope, which accelerates the charge transferring at the interfaces of catalyst/polysulfide redox couple. Density functional theory calculations demonstrate that the outstanding catalytic activity of Fe-SACs originates from the preferable adsorption of S42- on the FeN4 active sites and the high activation degree of the S-S bonds in S42- initiated by the FeN4 active sites.

2.
Sensors (Basel) ; 23(14)2023 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-37514653

RESUMO

In order to ensure the safe operation of buried polyethylene pipelines adjacent to blasting excavations, controlling the effects of blasting vibration loads on the pipelines is a key concern. Model tests on buried polyethylene pipelines under blasting loads were designed and implemented, the vibration velocity and dynamic strain response of the pipelines were obtained using a TC-4850 blast vibrometer and a UT-3408 dynamic strain tester, and the distribution characteristics of blast vibration velocity and dynamic strain were analyzed based on the experimental data. The results show that the blast load has the greatest effect on the circumferential strain of the polyethylene pipe, and the dynamic strain response is greatest at the section of the pipe nearest to the blast source. Pipe peak vibration velocity (PPVV), ground peak particle velocity (GPPV), and the peak dynamic strain of the pipe were highly positively correlated, which verifies the feasibility of using GPPV to characterize pipeline vibration and strain level. According to the failure criteria and relevant codes, combined with the analysis of experimental results, the safety threshold of additional circumferential stress on the pipeline is 1.52 MPa, and the safety control vibration speed of the ground surface is 21.6 cm/s.

3.
BMC Med ; 20(1): 238, 2022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35897098

RESUMO

BACKGROUND: Behavioral weight loss interventions are frequently hampered by long-term inefficacy. As metabolic improvements and health-related quality of life (HRQoL) are diminished by weight regain, effective long-term strategies are highly desirable. We aimed to analyze whether an additional weight maintenance intervention could delay body weight regain and can induce a long-term improvement of metabolism and HRQoL for up to 48 months in humans. Given the short-term metabolic effects of natriuretic peptides (NP), we also investigated the role of the adipose atrial NP (ANP) system in this long-term context. METHODS: After a successful 12-week weight reduction program 143 subjects (age>18; BMI≥27 kg/m2) were randomized (1:1) to a control group or a 12-month multimodal weight maintenance intervention focusing on nutritional counseling and physical exercises. Secondary trial outcomes including course of BMI, HOMA-IR, glucose response after oGTT (glucoseAUC), and HRQoL (SF-36) were analyzed yearly for 48 months. Adipose ANP receptor mRNA expression was analyzed during weight loss. RESULTS: Initial weight loss (- 4.7±1.5 kg/m2) improved glucoseAUC, HOMA-IR, and HRQoL. Although BMI was still reduced after 48 months (-1.98 [95% CI -2.61, -1.35] kg/m2), benefits on HOMA-IR, glucoseAUC, and mental health disappeared after 36 (-0.49 [-1.00, 0.02]), 18 (0.61 [-9.57, 10.79] mg dl-1 min-1), and 18 months (2.06 [-0.08, 4.20]), respectively, while improved physical health persisted up to months 48 (2.95 [0.49, 5.40]). Weight maintenance intervention inhibited weight regain and delayed impairment of HOMA-IR and glucoseAUC (but not HRQoL) for up to 12 months. However, no metabolic long-term effect was seen beyond the intervention period. Lower adipose NPR-C and higher NPR-A mRNA expression after weight loss predicted smaller regain of weight (r=0.398; p<0.05)/fat mass (FM) (r=0.391; p<0.05) and longer improvement of HOMA-IR (r=-0.422; p<0.05), respectively. CONCLUSIONS: Additional benefits of a behavioral 12-month weight maintenance intervention after weight loss regarding body weight regain and metabolic improvement does not persist beyond the intervention period. However, weight loss-induced modulation of the adipose ANP system is probably involved in the long-term control of body weight regain and insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00850629 . Registered on February 25, 2009.


Assuntos
Resistência à Insulina , Redução de Peso , Fator Natriurético Atrial , Índice de Massa Corporal , Manutenção do Peso Corporal , Glucose , Humanos , Resistência à Insulina/fisiologia , Obesidade/metabolismo , Qualidade de Vida , RNA Mensageiro , Aumento de Peso , Redução de Peso/fisiologia
4.
Int J Gynecol Cancer ; 32(12): 1549-1554, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36423958

RESUMO

BACKGROUND: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies. OBJECTIVE: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of current published literature from peer-reviewed journals. A well-established methodology (modified Delphi) was used to rate the appropriate use of diagnostic and therapeutic procedures for the management of uterine clear cell and serous carcinomas. RESULTS: The primary treatment for non-metastatic uterine clear cell and serous carcinomas is complete surgical staging, with total hysterectomy, salpingo-oophorectomy, omentectomy, and lymph node staging. Even in early-stage disease, patients with uterine clear cell and serous carcinomas have a worse prognosis than those with type I endometrial cancers, warranting consideration for adjuvant therapy regardless of the stage. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined-modality treatment with systemic chemotherapy and radiotherapy. CONCLUSION: Patients diagnosed with uterine clear cell and serous carcinomas should undergo complete surgical staging. Multimodal adjuvant therapies should be considered in the treatment of both early-stage and advanced-stage disease. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors. Long-term surveillance is indicated due to the high risk of locoregional and distant recurrence.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Rádio (Elemento) , Neoplasias Uterinas , Feminino , Humanos , Rádio (Elemento)/uso terapêutico , Neoplasias Uterinas/patologia , Estudos Prospectivos , Radioterapia Adjuvante , Quimioterapia Adjuvante , Estadiamento de Neoplasias , Neoplasias do Endométrio/patologia , Cistadenocarcinoma Seroso/patologia , Histerectomia , Estudos Retrospectivos
5.
Gynecol Oncol ; 158(2): 460-466, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32475772

RESUMO

OBJECTIVE: Uterine carcinosarcomas (UCS) represent a rare but aggressive subset of endometrial cancers, comprising <5% of uterine malignancies. To date, limited prospective trials exist from which evidence-based management of this rare malignancy can be developed. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines developed by a multidisciplinary expert panel for management of women with UCS. An extensive analysis of current medical literature from peer-reviewed journals was performed. A well-established methodology (modified Delphi) was used to rate the appropriate use of imaging and treatment procedures for the management of UCS. These guidelines are intended for the use of all practitioners who desire information about the management of UCS. RESULTS: The majority of patients with UCS will present with advanced extra uterine disease, with 10% presenting with metastatic disease. They have worse survival outcomes when compared to uterine high-grade endometrioid adenocarcinomas. The primary treatment for non-metastatic UCS is complete surgical staging with total hysterectomy, salpingo-oophorectomy and lymph node staging. Patients with UCS appear to benefit from adjuvant multimodality therapy to reduce the chance of tumor recurrence with the potential to improve overall survival. CONCLUSION: Women diagnosed with uterine UCS should undergo complete surgical staging. Adjuvant multimodality therapies should be considered in the treatment of both early- and advanced stage patients. Long-term surveillance is indicated as many of these women may recur. Prospective clinical studies of women with UCS are necessary for optimal management.


Assuntos
Carcinossarcoma/diagnóstico , Carcinossarcoma/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Quimioterapia Adjuvante , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Guias de Prática Clínica como Assunto , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
J Perinat Med ; 46(3): 299-307, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-28672756

RESUMO

BACKGROUND: Trial of labor after cesarean (TOLAC) is a viable option for safe delivery. In some cases cervical ripening and subsequent labor induction is necessary. However, the commonly used prostaglandins are not licensed in this subgroup of patients and are associated with an increased risk of uterine rupture. METHODS: This cohort study compares maternal and neonatal outcomes of TOLAC in women (n=82) requiring cervical ripening agents (osmotic dilator vs. prostaglandins). The initial Bishop scores (BSs) were 2 (0-5) and 3 (0-5) (osmotic dilator and prostaglandin group, respectively). In this retrospective analysis, Fisher's exact test, the Kruskal-Wallis rank sum test and Pearson's chi-squared test were utilized. RESULTS: Vaginal birth rate (including operative delivery) was 55% (18/33) in the osmotic dilator group vs. 51% (25/49) in the dinoprostone group (P 0.886). Between 97% and 92% (32/33 and 45/49) (100%, 100%) of neonates had an Apgar score of >8 after 1 min (5, 10 min, respectively). The time between administration of the agent and onset of labor was 36 and 17.1 h (mean, Dilapan-S® group, dinoprostone group, respectively). Time from onset of labor to delivery was similar in both groups with 4.4 and 4.9 h (mean, Dilapan-S® group, dinoprostone group, respectively). Patients receiving cervical ripening with Dilapan-S® required oxytocin in 97% (32/33) of cases. Some patients presented with spontaneous onset of labor, mostly in the dinoprostone group (24/49, 49%). Amniotomy was performed in 64% and 49% (21/33 and 24/49) of cases (Dilapan-S® group and dinoprostone group, respectively). CONCLUSIONS: This pilot study examines the application of an osmotic dilator for cervical ripening to promote vaginal delivery in women who previously delivered via cesarean section. In our experience, the osmotic dilator gives obstetricians a chance to perform induction of labor in these women.


Assuntos
Maturidade Cervical , Dinoprostona/administração & dosagem , Trabalho de Parto Induzido/métodos , Ocitócicos/administração & dosagem , Polímeros , Nascimento Vaginal Após Cesárea/estatística & dados numéricos , Adolescente , Adulto , Índice de Apgar , Feminino , Humanos , Recém-Nascido , Projetos Piloto , Gravidez , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem
7.
Ann Surg Oncol ; 24(3): 660-668, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27704370

RESUMO

OBJECTIVE: The aim of this study was to determine the impact of the results of the 12-gene DCIS Score assay on (i) radiotherapy recommendations for patients with pure ductal carcinoma in situ (DCIS) following breast-conserving surgery (BCS), and (ii) patient decisional conflict and state anxiety. METHODS: Thirteen sites across the US enrolled patients (March 2014-August 2015) with pure DCIS undergoing BCS. Prospectively collected data included clinicopathologic factors, physician estimates of local recurrence risk, DCIS Score results, and pre-/post-assay radiotherapy recommendations for each patient made by a surgeon and a radiation oncologist. Patients completed pre-/post-assay decisional conflict scale and state-trait anxiety inventory instruments. RESULTS: The analysis cohort included 127 patients: median age 60 years, 80 % postmenopausal, median size 8 mm (39 % ≤5 mm), 70 % grade 1/2, 88 % estrogen receptor-positive, 75 % progesterone receptor-positive, 54 % with comedo necrosis, and 18 % multifocal. Sixty-six percent of patients had low DCIS Score results, 20 % had intermediate DCIS Score results, and 14 % had high DCIS Score results; the median result was 21 (range 0-84). Pre-assay, surgeons and radiation oncologists recommended radiotherapy for 70.9 and 72.4 % of patients, respectively. Post-assay, 26.4 % of overall recommendations changed, including 30.7 and 22.0 % of recommendations by surgeons and radiation oncologists, respectively. Among patients with confirmed completed questionnaires (n = 32), decision conflict (p = 0.004) and state anxiety (p = 0.042) decreased significantly from pre- to post-assay. CONCLUSIONS: Individualized risk estimates from the DCIS Score assay provide valuable information to physicians and patients. Post-assay, in response to DCIS Score results, surgeons changed treatment recommendations more often than radiation oncologists. Further investigation is needed to better understand how such treatment changes may affect clinical outcomes.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/radioterapia , Perfilação da Expressão Gênica , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Tomada de Decisão Clínica , Conflito Psicológico , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Padrões de Prática Médica , Radio-Oncologistas , Radioterapia Adjuvante , Medição de Risco/métodos , Cirurgiões , Inquéritos e Questionários
8.
Exp Eye Res ; 161: 82-88, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28603017

RESUMO

To investigate the effects of diabetes on the biomechanical behavior of cornea in alloxan-induced diabetic rabbits. Diabetes mellitus (DM) was induced in 20 rabbits using alloxan, while another 20 age- and weight-matched non-diabetic rabbits served as controls. Eyes were enucleated after 8 weeks of inducing diabetes and the whole cornea was removed with a 3 mm wide scleral ring and tested under inflation conditions with an internal pressure range of 2.0-30.0 mmHg to determine their stress-strain behavior using an inverse analysis process. The blood glucose level (BG), advanced glycosylation end products (AGEs), central corneal thickness (CCT) and intraocular pressure (IOP) increased significantly in the DM group. There were statistically significant correlations between BG and AGEs (r = 0.768, p = 0.00), and between AGEs and CCT variation upon induction of DM (r = 0.594, p = 0.00). The tangent modulus (Et) of the cornea at four stress levels (1-4 kPa, equivalent to approximately IOP of 7.5, 15, 22.5 and 30 mmHg, respectively) was significantly higher in diabetic rabbits than in the control group (p < 0.05). Further, Et at stress of 2 kPa (which corresponded to the average IOP for the control group) was significantly correlated with BG (r = 0.378, p < 0.05), AGEs (r = 0.496, p < 0.05) and CCT variation upon induction of DM (r = 0.439, p < 0.05). IOP, as measured by contact tonometry, was also significantly correlated with both CCT (r = 0.315, p < 0.05) and Et at 2 kPa (r = 0.329, p < 0.05), and even after correcting for the effects of CCT and Et, IOP still significantly increased with both AGEs (r = 0.772, p = 0.00) and BG (r = 0.762, p = 0.00). The cornea of diabetic rabbits showed a significant increase in mechanical stiffness as evidenced by increases in corneal thickness and tangent modulus. The Et increase may be explained by a non-enzymatic cross-linking of collagen fibrils mediated by AGEs due to the high blood glucose levels in diabetes. The study also found significant IOP increases with higher blood glucose level even after controlling the effects of both corneal thickness and tangent modulus.


Assuntos
Córnea/fisiologia , Doenças da Córnea/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Elasticidade/fisiologia , Aloxano , Animais , Fenômenos Biomecânicos , Glicemia/metabolismo , Paquimetria Corneana , Produtos Finais de Glicação Avançada/metabolismo , Pressão Intraocular , Masculino , Coelhos , Tonometria Ocular
9.
J Org Chem ; 82(20): 11275-11287, 2017 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-28952306

RESUMO

A concise and practical synthetic method has been developed for 8-azachromones, including 8-azaflavones, which have emerged as a promising class of compounds. Using commercially available nicotinates as the starting material, 8-azachromones were obtained in only three steps. The key intramolecular O-arylation reaction was achieved by nucleophilic attack of enolates to C2 of N-oxides under PyBrop or Ac2O activation conditions. These studies provide the basis for the access to 8-azachromones, enabling future work including the discovery and development of novel chromonoid drugs or other functional materials.

10.
Qual Life Res ; 26(5): 1273-1282, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27796773

RESUMO

PURPOSE: Revealing the relationship between mobility impairment and life satisfaction can help to propose effective interventions to secure mobility and life satisfaction. However, the relationship remains unclear and lacks quantitative evidence in China. This study therefore assesses the association of mobility impairment, social engagement, and life satisfaction among the older population in China. METHODS: Based on the sample of China Health and Retirement Longitudinal Survey database in 2013, a structural equation modeling is established. The sample size is 4245 with 55.9% with mobility impairment. RESULTS: The model shows that the length of suffering from disability is significantly related to mobility impairment (ß = 0.058, p < 0.001). Mobility impairment is inversely related to social engagement (ß = -0.300, p < 0.001) and life satisfaction (ß = -0.311, p < 0.001). Social engagement is positively related to life satisfaction (ß = 0.211, p < 0.001). Moreover, the relationships have some differences for the seniors with different sociodemographic characteristics and living in different residential areas. CONCLUSIONS: As seniors get older, they tend to have more severe mobility impairment and participate less in social activities. Those with higher mobility impairment are more likely to report lower life satisfaction partly because they usually participate less in social activities. Different strategies are suggested to be adopted to improve the life satisfaction of the older population from the aspects of promoting mobility and social engagement, including improving the design of transport facilitates, providing assistive facilities for the seniors with severe mobility impairment, promoting the accessibility of community leisure and healthcare services, and constructing more community senior activity centers.


Assuntos
Pessoas com Deficiência/psicologia , Qualidade de Vida/psicologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , China , Feminino , Humanos , Masculino , Satisfação Pessoal , Habilidades Sociais
11.
Bioorg Med Chem ; 24(13): 3083-3092, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27238842

RESUMO

Current results identified 4-substituted 2-phenylaminoquinazoline compounds as novel Mer tyrosine kinase (Mer TK) inhibitors with a new scaffold. Twenty-one 2,4-disubstituted quinazolines (series 4-7) were designed, synthesized, and evaluated against Mer TK and a panel of human tumor cell lines aimed at exploring new Mer TK inhibitors as novel potential antitumor agents. A new lead, 4b, was discovered with a good balance between high potency (IC50 0.68µM) in the Mer TK assay and antiproliferative activity against MV4-11 (GI50 8.54µM), as well as other human tumor cell lines (GI50<20µM), and a desirable druglike property profile with low logP value (2.54) and high aqueous solubility (95.6µg/mL). Molecular modeling elucidated an expected binding mode of 4b with Mer TK and necessary interactions between them, thus supporting the hypothesis that Mer TK might be a biologic target of this kind of new active compound.


Assuntos
Proteínas Tirosina Quinases/antagonistas & inibidores , Quinazolinas/síntese química , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fenômenos Químicos , Ativação Enzimática/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Modelos Moleculares , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/química
12.
Oncology (Williston Park) ; 30(9): 816-22, 2016 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-27633412

RESUMO

These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia/normas , Neoplasias do Endométrio/terapia , Oncologia/normas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Braquiterapia/efeitos adversos , Braquiterapia/mortalidade , Quimioterapia Adjuvante/normas , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Medicina Baseada em Evidências/normas , Feminino , Procedimentos Cirúrgicos em Ginecologia/normas , Humanos , Excisão de Linfonodo/normas , Gradação de Tumores , Estadiamento de Neoplasias , Doses de Radiação , Radioterapia (Especialidade)/normas , Radioterapia Adjuvante/normas , Fatores de Risco , Terapia de Salvação/normas , Oncologia Cirúrgica/normas , Resultado do Tratamento
13.
Oncology (Williston Park) ; 29(11): 867-72, 874-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26568534

RESUMO

These American College of Radiology consensus guidelines were formed from an expert panel on the appropriate use of adjuvant therapy in vulvar cancer after primary treatment with surgery. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature in vulvar cancer and voted on three variants to establish appropriate use of imaging, adjuvant radiation, including dose, fields, and technique, as well as adjuvant chemotherapy. This report will aid clinicians in selecting appropriate patients for adjuvant treatment and will provide guidelines for the optimal delivery of adjuvant radiation therapy and chemotherapy.


Assuntos
Neoplasias Vulvares/radioterapia , Idoso , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Guias de Prática Clínica como Assunto , Dosagem Radioterapêutica , Radioterapia Adjuvante , Biópsia de Linfonodo Sentinela , Neoplasias Vulvares/patologia
15.
Anticancer Drugs ; 25(8): 857-67, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24714081

RESUMO

Immune adjuvants have been used in cancer biotherapies to stimulate immune response to tumor cells. Despite their potential as anticancer reagents, there are several impediments to their use in clinical applications. In this study, we aim to modify the existing tuftsin structure and evaluate its antitumor activity in preclinical models. We synthesized a novel tuftsin derivative, namely, the T peptide (TP), by linking four tuftsin peptides, which showed enhanced stability in vivo. We then evaluated its anticancer activity in a postoperative residual tumor model in mice, where we surgically removed most of the primary tumor from the host, a procedure mimicking clinically postoperative patients. Despite the limited effect in intact solid tumors, TP strongly inhibited relapsed growth of residual tumors in postsurgical mice. Surgical resection of tumors accelerated residual tumor growth, but TP slowed down this process significantly. Interestingly, TP showed similar effects in human xenograft residual models. As an immunomodulator, TP could synergize the functions of macrophages, thus inhibiting the growth of cocultured tumor cells in vitro. Furthermore, TP could shift the macrophages to the tumor-suppressive M1 type and mobilize them to produce elevated cytotoxic TNF-α and NO. As a result, TP effectively prolonged the survival time of tumor-resected mice. Using the postoperative residual tumor models, we provide a body of evidence showing the antitumor activity of TP, which causes no obvious toxicity. Our study highlights the potential of TP as a postoperative adjuvant in cancer therapies.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasia Residual/tratamento farmacológico , Tuftsina/análogos & derivados , Tuftsina/uso terapêutico , Adjuvantes Imunológicos/farmacologia , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Humanos , Lisina/química , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Neoplasia Residual/imunologia , Neoplasia Residual/patologia , Tuftsina/química , Fator de Necrose Tumoral alfa/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Cancer Control ; 21(1): 57-62, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24357742

RESUMO

BACKGROUND: Stage IIIA non-small-cell lung cancer (NSCLC) is highly heterogeneous due to differences in the size of the primary tumor and the extent and location of nodal disease. Although the addition of surgery to chemoradiation did not improve overall survival (OS) for stage IIIA patients in a randomized intergroup trial (INT 0139), subset analyses of the trial suggest that a trimodality approach incorporating lobectomy may be superior to bimodality therapy with chemoradiation alone. METHODS: We analyzed the outcomes of patients with stage IIIA NSCLC (T3N1, T1-3N2) treated at our center between January 2000 and December 2008. We compared OS for those undergoing definitive chemoradiation to those undergoing chemoradiation followed by either lobectomy or pneumonectomy. Demographic variables were balanced by propensity score analysis method. RESULTS: In our analysis of 249 patients, the median age was 65 years, 43% were men, and 96.5% had N2 disease. Chemoradiation followed by lobectomy yielded superior OS compared with chemoradiation (median OS 39 months vs 22 months, P = .038 after propensity score adjustment). There was no significant survival benefit for pneumonectomy over chemoradiation (median survival 28 months vs 22 months, P = .534). CONCLUSIONS: Our data corroborate the findings of the INT 0139 trial. We propose that a formal randomized trial be performed comparing chemoradiation followed by lobectomy vs definitive chemoradiation in patients with stage IIIA disease whose tumors are resectable by lobectomy. Our data do not support the incorporation of pneumonectomy in the management of stage IIIA patients with N2 disease.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estudos Multicêntricos como Assunto , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do Tratamento
17.
J Phys Chem B ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38959208

RESUMO

The i-motif, a secondary structure of a four-helix formed by cytosine-rich DNA (i-DNA) through C-C+ base pairing, is prevalent in human telomeres and promoters. This structure creates steric hindrance, thereby inhibiting both gene expression and protein coding. The conformation of i-DNA is intricately linked to the intracellular ionic environment. Hence, investigating its conformation under various ion conditions holds significant importance. In this study, we explored the impact of cations on the i-motif structure at the single-molecule level using the α-hemolysin (α-HL) nanochannel. Our findings reveal that the ability of i-DNA to fold into the i-motif structure follows the order Cs+ > Na+ > K+ > Li+ for monovalent cations. Furthermore, we observed the interconversion of single-stranded DNA (ss-DNA) and the i-motif structure at high and low concentrations of Mg2+ and Ba2+ electrolyte solutions. This study not only has the potential to extend the application of i-motif-based sensors in complex solution environments but also provides a new idea for the detection of metal ions.

18.
Front Neurol ; 15: 1388544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38974688

RESUMO

Background: The treatment of multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) remains challenging due to the limited availability of effective drugs. Linezolid has emerged as a promising therapeutic option for these cases. However, its long-term use can lead to complications such as peripheral and optic neuropathies. Acupuncture, a cornerstone of traditional Chinese medicine, has been shown to be effective in the treatment of peripheral neuropathy (PN). This study examines the potential benefits of acupuncture in the treatment of linezolid-induced peripheral neuropathy (LIPN). Methods: Four patients, aged 27 to 60 years, diagnosed with LIPN, underwent daily acupuncture treatments. The main endpoint was to assess the efficacy of acupuncture in reducing neuropathic pain associated with LIPN in patients. This was primarily measured using changes in the Short Form McGill Pain Questionnaire (SF-MPQ) scores before and after acupuncture treatment. Results: Three of the patients experienced significant symptom remission, while one experienced marginal improvement. Treatments ranged from 7 to 18 sessions. Specifically, the first patient reported substantial relief with a score reduction from 33 to 13; the second patient observed minimal change; the third patient's score decreased dramatically from 10 to 2 after eight sessions; the last patient had a score reduction from 21 to 12 after five sessions, but did not continue treatment for a second assessment. Conclusion: Acupuncture is a promising therapeutic approach for LIPN. However, larger and more thorough studies are needed to determine its full potential.

19.
AJNR Am J Neuroradiol ; 45(4): 444-452, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38485196

RESUMO

BACKGROUND AND PURPOSE: Accelerating the image acquisition speed of MR imaging without compromising the image quality is challenging. This study aimed to evaluate the feasibility of contrast-enhanced (CE) 3D T1WI and CE 3D-FLAIR sequences reconstructed with compressed sensitivity encoding artificial intelligence (CS-AI) for detecting brain metastases (BM) and explore the optimal acceleration factor (AF) for clinical BM imaging. MATERIALS AND METHODS: Fifty-one patients with cancer with suspected BM were included. Fifty participants underwent different customized CE 3D-T1WI or CE 3D-FLAIR sequence scans. Compressed SENSE encoding acceleration 6 (CS6), a commercially available standard sequence, was used as the reference standard. Quantitative and qualitative methods were used to evaluate image quality. The SNR and contrast-to-noise ratio (CNR) were calculated, and qualitative evaluations were independently conducted by 2 neuroradiologists. After exploring the optimal AF, sample images were obtained from 1 patient by using both optimized sequences. RESULTS: Quantitatively, the CNR of the CS-AI protocol for CE 3D-T1WI and CE 3D-FLAIR sequences was superior to that of the CS protocol under the same AF (P < .05). Compared with reference CS6, the CS-AI groups had higher CNR values (all P < .05), with the CS-AI10 scan having the highest value. The SNR of the CS-AI group was better than that of the reference for both CE 3D-T1WI and CE 3D-FLAIR sequences (all P < .05). Qualitatively, the CS-AI protocol produced higher image quality scores than did the CS protocol with the same AF (all P < .05). In contrast to the reference CS6, the CS-AI group showed good image quality scores until an AF of up to 10 (all P < .05). The CS-AI10 scan provided the optimal images, improving the delineation of normal gray-white matter boundaries and lesion areas (P < .05). Compared with the reference, CS-AI10 showed reductions in scan time of 39.25% and 39.93% for CE 3D-T1WI and CE 3D-FLAIR sequences, respectively. CONCLUSIONS: CE 3D-T1WI and CE 3D-FLAIR sequences reconstructed with CS-AI for the detection of BM may provide a more effective alternative reconstruction approach than CS. CS-AI10 is suitable for clinical applications, providing optimal image quality and a shortened scan time.


Assuntos
Neoplasias Encefálicas , Substância Branca , Humanos , Inteligência Artificial , Neoplasias Encefálicas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Substância Cinzenta , Imageamento Tridimensional
20.
Endocrine ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758293

RESUMO

PURPOSE: The current study investigated the correlation between dietary iron intake and diabetic kidney disease among diabetic adults. METHODS: This cross-sectional study enrolled 8118 participants who suffered from diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Dietary iron intake was obtained from 24 h recall interviews, and diabetic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or albumin creatinine ratio (ACR) ≥ 30 mg/g. Three weighted logistic regression models were utilized to investigate odd ratio (OR) and 95% CIs for diabetic kidney disease. Stratified analyses were performed by gender, age, BMI, HbA1c, hypertension status, and smoking status, and diabetes types. RESULTS: Among 8118 participants (51.6% male, mean age 61.3 years), 40.7% of participants suffered from diabetic kidney disease. With the adjustment of potential covariates, we found that ≥ 12.59 mg of dietary iron was related to a lower risk of diabetic kidney disease (OR = 0.78, 95% CI: 0.63 to 0.96; OR = 0.79, 95% CI: 0.63 to 0.98). In stratified analyses, higher iron intake was negatively related to diabetic kidney disease, especially among those who were male, < 60 years, those with hypertension, those with HbA1c < 7.0%, and those who were ex-smokers. The result remained robust in sensitivity analyses. CONCLUSION: We found that ≥ 12.59 mg of dietary iron is associated with a lower risk of diabetic kidney disease, especially in those who were male, younger, heavier weight, have better blood sugar control, and those who were ex-smokers.

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