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Time-to-event endpoints are widely used as measures of patients' well-being and indicators of prognosis. In imaging-based biomarker studies, there are increasingly more studies that focus on examining imaging biomarkers' prognostic or predictive utilities on those endpoints, whether in a trial or an observational study setting. In this educational review article, we briefly introduce some basic concepts of time-to-event endpoints and point out potential pitfalls in the context of imaging biomarker research in hope of improving radiologists' understanding of related subjects. Besides, we have included some review and discussions on the benefits of using time-to-event endpoints and considerations on selecting overall survival or progression-free survival for primary analysis. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.
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Cardiac pacing has become a widely accepted treatment strategy for bradyarrhythmia and heart failure. However, conventional right ventricular pacing (RVP) has been associated with electrical dyssynchrony, which may result in atrial fibrillation and heart failure. To achieve physiological pacing, Deshmukh et al. reported the first case of His bundle pacing (HBP) in 2000. This strategy was reported to have preserved ventricular synchronization by activating the conventional conduction system. Nonetheless, due to the anatomical location of the His bundle (HB), several issues such as high pacing thresholds, lead fixation, and early battery depletion may pose a challenge. Recently, left bundle branch area pacing (LBBAP) has emerged as a novel physiological pacing strategy to achieve conduction system pacing by capturing the left bundle branch through the deep septum. Additionally, several studies have investigated the clinical outcomes of LBBAP. In this paper, we describe the pacing parameters, QRS duration (QRSd), cardiac function, complications, and specific applications of LBBAP in recent years.
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Fibrilação Atrial , Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Humanos , Fibrilação Atrial/terapia , Fascículo Atrioventricular , Bloqueio de Ramo/terapia , Doença do Sistema de Condução Cardíaco , Estimulação Cardíaca Artificial , Eletrocardiografia , Insuficiência Cardíaca/prevenção & controle , Prognóstico , Resultado do Tratamento , Relatos de Casos como AssuntoRESUMO
The electrochemical effect of isotope (EEI) of water is introduced in the Zn-ion batteries (ZIBs) electrolyte to deal with the challenge of severe side reactions and massive gas production. Due to the low diffusion and strong coordination of ions in D2 O, the possibility of side reactions is decreased, resulting in a broader electrochemically stable potential window, less pH change, and less zinc hydroxide sulfate (ZHS) generation during cycling. Moreover, we demonstrate that D2 O eliminates the different ZHS phases generated by the change of bound water during cycling because of the consistently low local ion and molecule concentration, resulting in a stable interface between the electrode and electrolyte. The full cells with D2 O-based electrolyte demonstrated more stable cycling performance which displayed â¼100 % reversible efficiencies after 1,000 cycles with a wide voltage window of 0.8-2.0â V and 3,000 cycles with a normal voltage window of 0.8-1.9â V at a current density of 2â A g-1 .
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AIM: To evaluate the risk factors of miscarriage in patients attempted cervical polypectomy during the first and second trimester pregnancy. METHODS: Pregnant women with singleton infants who underwent cervical polypectomy during the first and second trimester between January 2013 and May 2019 were investigated. The study retrospectively reviewed the clinical features and pregnancy outcomes after cervical polypectomy. A multivariable regression was performed to predict the risk factors of miscarriage. RESULTS: A total of 307 pregnant females were eventually included in our study. Twenty-seven patients (8.8%, 27/307) had a miscarriage before 28 weeks, 37 patients (12.1%, 37/307) had a preterm delivery. After univariate analysis, we found that the presence of decidual polyps and vaginal bleeding after polypectomy were the risk factors for miscarriage. Moreover, the incidence of miscarriage was significantly higher in the patients with decidual polyps than in those with endocervical polyps (14.9% vs. 5.6%, p = 0.010). CONCLUSIONS: The most suitable hemostasis method should be taken in the cervical polypectomy during pregnancy. The risk of miscarriage associated with polypectomy during pregnancy is higher in females with decidual polyps. If decidual polyps are highly suspected and they do not cause excessive vaginal bleeding and can be ruled out the possibility of malignancy, conservative treatment may lead to a better outcome.
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Aborto Espontâneo , Pólipos , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/etiologia , Feminino , Humanos , Recém-Nascido , Pólipos/patologia , Pólipos/cirurgia , Gravidez , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos Retrospectivos , Fatores de Risco , Hemorragia Uterina/complicações , Hemorragia Uterina/cirurgiaRESUMO
BACKGROUND: Human papillomavirus (HPV) infection is the main cause of cervical cancer. Characteristics of HPV infections, including the HPV genotype and duration of infection, determine a patient's risk of high-grade lesions. Risk quantification of cervical lesions caused by different HPV genotypes is an important component of evaluation of cervical lesion. Data and evidence are necessary to gain a deeper understanding of the pathogenicity of different HPV genotypes. The present study investigated the clinical characteristics of patients infected with single human papillomavirus (HPV) 53. METHODS: This retrospective study analyzed the clinical data of patients who underwent cervical colposcopy guided biopsy between October 2015 and January 2021. The clinical outcomes and the follow-up results of the patients with single HPV53 infection were described. RESULTS: 82.3% of the initial histological results of all 419 patients with single HPV53 infection showed negative (Neg). The number of patients with cervical intraepithelial neoplasia (CIN)1, CIN2, CIN3, vaginal intraepithelial neoplasia (VaIN)1, CIN1 + VaIN1, CIN1 + VaIN2, and CIN2 + VaIN2 was 45, 10, 2, 9, 6, 1, and 1, respectively. Cancer was not detected in any patient. When the cytology was negative for intraepithelial lesion or malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesion (LSIL), we observed a significant difference in the distribution of histological results (P < 0.05). 95 patients underwent follow-up with cytology according to the exclusion criteria. No progression of high-grade lesions was observed during the follow-up period of 3-34 months. CONCLUSIONS: The lesion caused by HPV53 infection progressed slowly. The pathogenicity of a single HPV53 infection was low.
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Alphapapillomavirus , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Colposcopia , Feminino , Humanos , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Gravidez , Estudos Retrospectivos , Neoplasias do Colo do Útero/epidemiologia , Esfregaço Vaginal , Displasia do Colo do Útero/epidemiologiaRESUMO
BACKGROUND: This study was aimed to investigate the relationship between 25-hydroxy vitamin D (25(OH)D) level and the occurrence of pre-eclampsia (PE) and also the risk factors of developing early and late onset PE. METHODS: A total of 370 pregnant women were included between January 2015 and December 2016 at our hospital. PE was defined as the presence of maternal blood pressure > 140/90 mmHg and 24-hour proteinuria levels > 300 mg or 2 + in a random sample of urine after the 20th week of pregnancy. Controls were pregnant women without hypertension and proteinuria. Assessment of 25(OH)D was performed at 16 - 20 weeks of gestation. Univariate and multivariate analyses were used to evaluate the association of vitamin D with PE. RESULTS: There were 201 patients with PE while 169 pregnant women were controls. Patients with PE had older maternal age (p < 0.001), earlier gestation age (p < 0.001), and higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) (p < 0.001). The level of 25(OH)D in the PE group (17.26 ± 13.95 µg/L) was significantly lower than that in controls (22.15 ± 12.65 µg/L, p = 0.019). Moreover, the proportion of 25(OH)D deficiency in patients with PE was significantly higher than that of controls (27.6% vs. 0.9%, p < 0.001). Older age, high SBP, and low level of 25(OH)D were independent risk factors of both early and late onset PE during pregnancy. CONCLUSIONS: Low 25(OH)D level was more likely presented in PE patients and was an independent risk factor of both early and late onset PE.
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Pré-Eclâmpsia , Proteinúria , Deficiência de Vitamina D , Vitamina D/análogos & derivados , Adulto , Fatores Etários , Determinação da Pressão Arterial , China/epidemiologia , Correlação de Dados , Feminino , Humanos , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Gravidez , Trimestres da Gravidez , Proteinúria/diagnóstico , Proteinúria/epidemiologia , Fatores de Risco , Urinálise , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/epidemiologiaRESUMO
A novel chemiluminescence resonance energy transfer (CRET) system was developed and combined with a structure-switching aptamer for the highly sensitive detection of platinum. Platinum was chosen as a model analyte to demonstrate the generality of the new CRET system. This aptameric platform consisted of a streptavidin labeled aptamer against platinum and a streptavidin-coated magnetic bead for the selective separation of platinum-bound aptamer. The platinum-aptamer probe contained several guanine (G) bases bound to the 3,4,5-trimethoxyphenyl-glyoxal (TMPG) donor group at the 5' end, a fluorescent acceptor (6-carboxy-2',4,7,7'-tetrachlorofluorescein, TET) at the 3' end, and a streptavidin aptamer sequence in which several base pairs were replaced by the G-G mismatch to induce the platinum-oligonucleotide coordination. The chemiluminescence (CL) generated by TMPG/G bases is transferred to the acceptor (TET). In the presence of platinum, the platinum-aptamer probe was folded such that the G bases at the 5' end and TET at the 3' were in close proximity. The complex was separated using streptavidin-coated magnetic beads by the addition of TMPG to form the TMPG/G bases complex. The ultraweak CL from the TMPG/G bases was strongly enhanced by TET. This novel CRET-based method can be easily performed with high limit of detection (50 ng·mL-1) and selectivity over other metal ions. This technique provides a novel method for simple, fast, and convenient point-of-care diagnostics for monitoring proteins and metal ions. Graphical abstract Schematic presentation of chemiluminescence resonance energy transfer (CRET) detection of platinum(II) by Pt-base pair coordination to the aptamer. TMPG: 3,4,5-trimethoxyphenyl-glyoxal, fluorophore TET: 6-carboxy-2',4,7,7'-tetrachlorofluorescein.
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Cisplatino/sangue , Medições Luminescentes/métodos , Platina/sangue , Animais , Aptâmeros de Nucleotídeos/química , Transferência de Energia , Fluoresceínas/química , Corantes Fluorescentes/química , Glioxal/análogos & derivados , Guanina/química , Limite de Detecção , Luminescência , Fenômenos Magnéticos , Ratos Sprague-Dawley , Estreptavidina/químicaRESUMO
Adaptive enrichment designs (AEDs) of clinical trials allow investigators to restrict enrollment to a promising subgroup based on an interim analysis. Most of the existing AEDs deal with a small number of predefined subgroups, which are often unknown at the design stage. The newly developed Simon design offers a great deal of flexibility in subgroup selection (without requiring pre-defined subgroups) but does not provide a procedure for estimating and testing treatment efficacy for the selected subgroup. This article proposes a 2-stage AED which does not require predefined subgroups but requires a prespecified algorithm for choosing a subgroup on the basis of baseline covariate information. Having a prespecified algorithm for subgroup selection makes it possible to use cross-validation and bootstrap methods to correct for the resubstitution bias in estimating treatment efficacy for the selected subgroup. The methods are evaluated and compared in a simulation study mimicking actual clinical trials of human immunodeficiency virus infection.
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Ensaios Clínicos como Assunto/métodos , Algoritmos , Bioestatística , Ensaios Clínicos como Assunto/estatística & dados numéricos , Simulação por Computador , Infecções por HIV/tratamento farmacológico , Humanos , Modelos Estatísticos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Análise de Regressão , Projetos de Pesquisa , Estatísticas não Paramétricas , Resultado do TratamentoRESUMO
Gallium oxide is a wide-bandgap compound semiconductor material renowned for its diverse applications spanning gas sensors, liquid crystal displays, transparent electrodes, and ultraviolet detectors. This paper details the aerosol assisted chemical vapor deposition synthesis of tin doped gallium oxide thin films using gallium acetylacetonate and monobutyltin trichloride dissolved in methanol. It was observed that Sn doping resulted in a reduction in the transmittance of Ga2O3 films within the visible spectrum, while preserving the wide bandgap characteristics of 4.8 eV. Furthermore, Hall effect testing revealed a substantial decrease in the resistivity of Sn-doped Ga2O3 films, reducing it from 4.2 × 106 Ω cm to 2 × 105 Ω cm for the 2.5 at. % Sn:Ga2O3 compared to the nominally undoped Ga2O3.
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BACKGROUND: The current evidence on the use of laryngeal mask airway (LMA) as an airway management technique for general anesthesia (GA) during atrial fibrillation (AF) catheter ablation (CA) is insufficient. This study aims to compare the feasibility, safety, and clinical benefits of LMA and endotracheal intubation (ETI) for airway management in AF CA. METHODS: One hundred fifty-two consecutive patients with AF who underwent CA under GA were included and divided into two groups based on different airway management methods (66 in the LMA group, 86 in the ETI group). After propensity score matching, a final analysis cohort of 132 patients was obtained to compare procedural parameters, adverse events, and prognosis between the two groups. RESULTS: The LMA group exhibited significantly shorter total procedural time (p = 0.039), anesthesia induction time (p = 0.015), and recovery time (p = 0.006) compared to the ETI group. The mean arterial pressure (MAP) and heart rate were significantly lower in the LMA group during extubation and 1-min post-extubation (p < 0.05). Furthermore, the LMA group demonstrated lower MAP levels during intubation (p = 0.029). The incidences of intraoperative hypotension (p = 0.017) and bradycardia (p = 0.032) were significantly lower in the LMA group. The incidences of delayed recovery or delirium (p = 0.027), laryngeal or airway injury (p = 0.016), cough or bucking (p = 0.001), and sore throat (p < 0.001) were significantly lower in the LMA group. There were no statistically significant differences in catheter stability parameters and sinus rhythm maintenance rates between the two groups (p > 0.05). CONCLUSION: LMA is feasible, safe, and effective in AF CA as an optimized airway management technique for GA.
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Manuseio das Vias Aéreas , Anestesia Geral , Fibrilação Atrial , Ablação por Cateter , Intubação Intratraqueal , Máscaras Laríngeas , Pontuação de Propensão , Humanos , Fibrilação Atrial/cirurgia , Masculino , Feminino , Intubação Intratraqueal/métodos , Ablação por Cateter/métodos , Pessoa de Meia-Idade , Manuseio das Vias Aéreas/métodos , Resultado do Tratamento , Idoso , Estudos Retrospectivos , Estudos de ViabilidadeRESUMO
Introduction: Ovarian cancer (OV) is a highly lethal gynecological malignancy with a poor prognosis. Lactate metabolism is crucial for tumor cell survival, proliferation, and immune evasion. Our study aims to investigate the role of lactate metabolism-related genes (LMRGs) in OV and their potential as biomarkers for prognosis, immune microenvironment, and immunotherapy response. Methods: Ovarian samples were collected from the TCGA cohort. And 12 lactate-related pathways were identified from the MsigDB database. Differentially expressed genes within these pathways were designated as LMRGs, which undergo unsupervised clustering to identify distinct clusters based on LMRGs. Subsequently, we assessed survival outcomes, immune cell infiltration levels, Hallmaker pathway activation patterns, and chemotaxis among different subtypes. After conducting additional unsupervised clustering based on differentially expressed genes (DEGs), significant differences in the expression of LMRGs between the two clusters were observed. The differentially expressed genes were subjected to subsequent functional enrichment analysis. Furthermore, we construct a model incorporating LMRGs. Subsequently, the lactate score for each tumor sample was calculated based on this model, facilitating the classification of samples into high and low groups according to their respective lactate scores. Distinct groups examined disparities in survival prognosis, copy number variation (CNV), single nucleotide variation (SNV), and immune infiltration. The lactate score served as a quantitative measure of OV's lactate metabolism pattern and an independent prognostic factor. Results: This study investigated the potential role of LMRGs in tumor microenvironment diversity and prognosis in OV, suggesting that LMRGs play a crucial role in OV progression and the tumor microenvironment, thus serving as novel indicators for prognosis, immune microenvironment status, and response to immunotherapy.
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Variações do Número de Cópias de DNA , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Prognóstico , Ácido Láctico , Microambiente Tumoral/genéticaRESUMO
Upconverted UCNPs@mSiO2-NH2 nanoparticles were synthesized via thermal decomposition while employing the energy resonance transfer principle and the excellent near-infrared (NIR) light conversion property of up-conversion. The 808 nm NIR-excited photocontrolled nitric oxide (NO) release platform was successfully developed by electrostatically loading photosensitive NO donor Roussin's black salt (RBS) onto UCNPs@mSiO2-NH2, enabling the temporal, spatial, and dosimetric regulation of NO release for biological applications of NO. The release of NO ranged from 0.015â0.099 mM under the conditions of 2.0 W NIR excitation power, 20 min of irradiation time, and UCNPs@mSiO2-NH2&RBS concentration of 0.25â1.25 mg/mL. Therefore, this NO release platform has an anti-tumor effect. In vitro experiments showed that under the NIR light, at concentrations of 0.3 mg/mL and 0.8 mg/mL of UCNPs@mSiO2-NH2&RBS, the activity of glioma (U87) and chordoma (U-CH1) cells, as measured by CCK8 assay, was reduced to 50 %. Cell flow cytometry and Western Blot experiments showed that NO released from UCNPs@mSiO2-NH2&RBS under NIR light induced apoptosis in brain tumor cells. In vivo experiments employing glioma and chordoma xenograft mouse models revealed significant inhibition of tumor growth in the NIR and UCNPs@mSiO2-NH2&RBS group, with no observed significant side effects in the mice. Therefore, NO released by UCNPs@mSiO2-NH2&RBS under NIR irradiation can be used as a highly effective and safe strategy for brain tumor therapy.
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BACKGROUND: Chordoma is a rare congenital low-grade malignant tumor characterized by infiltrative growth. It often tends to compress important intracranial nerves and blood vessels, making its surgical treatment extremely difficult. Besides, the efficacy of radiotherapy and chemotherapy is limited. The photosensitizer hematoporphyrin derivative (HPD) can emit red fluorescence under 405 nm excitation and produce reactive oxygen species for tumor therapy under 630 nm excitation. Herein, we investigated the effects of the photosensitizer hematoporphyrin derivative (HPD) on different cell lines of chordoma and xenograft tumors under 405 nm and 630 nm excitation. METHODS: The photosensitizer hematoporphyrin derivative (HPD) and Two different chordoma cell lines (U-CH1, JHC7) were used for the test. The in vitro experiments were as follows: (1) the fluorescence intensity emitted by chordoma cells excited by different 405 nm light intensities was observed under a confocal microscope; (2) the Cell Counting Kit-8 (CCK-8) assay was performed to detect the effects of different photosensitizer concentrations and 630 nm light energy densities on the activity of chordoma cells. In the in vivo experiments, (3) Fluorescence visualization of chordoma xenograft tumors injected with photosensitizer via tail vein under 405 nm excitation; (4) Impact of 630 nm excitation of photosensitizer on the growth of chordoma xenograft tumors. RESULTS: (1) The photosensitizers in chordoma cells and chordoma xenografts of nude mice were excited by 405 nm to emit red fluorescence; (2) 630 nm excitation photosensitizer reduces chordoma cell activity and inhibits chordoma xenograft tumor growth in chordoma nude mice. CONCLUSION: Photodynamic techniques mediated by the photosensitizer hematoporphyrin derivatives can be used for the diagnosis and treatment of chordoma.
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Cordoma , Fotoquimioterapia , Fármacos Fotossensibilizantes , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fotoquimioterapia/métodos , Cordoma/tratamento farmacológico , Animais , Camundongos , Linhagem Celular Tumoral , Humanos , Derivado da Hematoporfirina/farmacologia , Camundongos Nus , Hematoporfirinas/farmacologia , Hematoporfirinas/uso terapêuticoRESUMO
Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target and maximizing exploration of chemical space, harnessing these building blocks for carbon-carbon bond-forming reactions is a key goal in organic chemistry. In particular, leveraging a single activation mode to form a new C(sp3)-C(sp3) bond from two alcohol subunits would enable access to an extraordinary level of structural diversity. In this work, we report a nickel radical sorting-mediated cross-alcohol coupling wherein two alcohol fragments are deoxygenated and coupled in one reaction vessel, open to air.
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OBJECTIVE: To investigate the factors influencing preterm birth in patients after ultrasound-indicated cerclage with different cervical lengths (CL), and explore the optimal cut-off value of CL. MATERIALS AND METHODS: The retrospective study included 87 pregnant women with a history of preterm birth and second-trimester loss that received ultrasound-indicated cerclage in our hospital between January 2004 and April 2021. Groups were divided by CL at the demarcation point of 1.0, 1.5 and 2.0 cm respectively. The pregnancy outcomes were compared. Logistic regression analysis was performed to assess the independent influence factors. Receiver-operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was used to compare the prediction capability of the associated factors. RESULTS: Significant difference was found in terms of patients delivered at ≥32 weeks of gestation (19 [55.9%]vs. 41 [77.4%], p < 0.05) and neonatal birth weight (2495 [1138,3185]vs. 2995 [2155,3235] g, p < 0.05), when the CL was categorized at the demarcation point of 1.5 cm. Body mass index (BMI) (odds ratio [OR] = 1.224, p < 0.05), a history of preterm birth and second-trimester loss (OR = 3.153, p < 0.05), and C-reactive protein (CRP) > 5 mg/L (OR = 8.097, p < 0.05) were independent risk factors for gestational age more than 28 weeks. The AUC of joint predictor A included those factors was 0.849 (95% CI: 0.701-0.998, p < 0.05). CRP>5 mg/L was found to be a significant independent risk factor for different gestational age at delivery. CONCLUSIONS: A CL of 1.5 cm was the optimal cut-off value that could help women who underwent serial CL surveillance choose ultrasound-indicated cerclage at an appropriate time. High BMI, more history of preterm birth and second-trimester loss and abnormal CRP could be used as combined predictors to recognize the risk of preterm birth (<28 weeks) post-surgery.
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Cerclagem Cervical , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Lactente , Resultado da Gravidez , Nascimento Prematuro/etiologia , Nascimento Prematuro/cirurgia , Estudos Retrospectivos , Medida do Comprimento Cervical , Colo do Útero/diagnóstico por imagem , Colo do Útero/cirurgiaRESUMO
Objective: The aim of this study was to assess the impact of short-term, hospital-based, supervised multimodal prehabilitation on elderly patients with colorectal cancer. Methods: A single-center, retrospective study was conducted from October 2020 to December 2021, which included a total of 587 CRC patients who were scheduled to undergo radical resection. A propensity score-matching analysis was performed to reduce selection bias. All patients were treated within a standardized enhanced recovery pathway, and patients in the prehabilitation group received an additional supervised, short-term multimodal preoperative prehabilitation intervention. Short-term outcomes were compared between the two groups. Results: Among the participants, 62 patients were excluded; 95 participants were included in the prehabilitation group and 430 in the non-prehabilitation group. After PSM analysis, 95 pairs of well-matched patients were included in the comparative study. Participants in the prehabilitation group had better preoperative functional capacity (402.78 m vs. 390.09 m, P<0.001), preoperative anxiety status (9% vs. 28%, P<0.001), time to first ambulation[25.0(8.0) hours vs. 28.0(12.4) hours, P=0.008], time to first flatus [39.0(22.0) hours vs. 47.7(34.0) hours, P=0.006], duration of the postoperative length of hospital stay [8.0(3.0) days vs. 10.0(5.0) days, P=0.007), and quality of life in terms of psychological dimensions at 1 month postoperatively [53.0(8.0) vs. 49.0(5.0), P<0.001]. Conclusion: The short-term, hospital-based, supervised multimodal prehabilitation is feasible with a high degree of compliance in older CRC patients, which improves their short-term clinical outcomes.
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Developing photostable two-photon dyes with high brightness and negligible photocytotoxicity is of key importance in fluorescence imaging but remains a huge challenge. Here, a two-photon dye with ultrahigh brightness and photostability is demonstrated for high-performance long-term two-photon fluorescence imaging. By terminated donor engineering, the designed DBD shows a higher two-photon absorption cross-section (δ, 418â GM vs 329â GM) and photoluminescence quantum yield (ΦPL , 62.74% vs 54.63%) than its counterpart DBA. As a consequence, two-photon fluorescence brightness (δ×ΦPL ) of DBD exhibits a 10-folded enhancement (262â GM vs 19â GM) in comparison with typical Coumarin 307 dye. More importantly, DBD displays ultrahigh photostability and negligible photobleaching under 10â min femtosecond laser irradiation, which stands in marked contrast to Coumarin 307. Furthermore, femtosecond transient absorption spectroscopy ascribes this ultrahigh photostability and negligible photobleaching to the inefficient intersystem crossing. With these merits, DBD can be used long-term two-photon fluorescence imaging inâ vitro.
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Corantes Fluorescentes , Fótons , Corantes Fluorescentes/química , Imagem ÓpticaRESUMO
Developing organic photothermal materials (OPMs) with high photothermal performance for phototheranostic mainly focus on the manipulation of intramolecular nonradiative (intraNR) decay, which often requires quite complicated and time-consuming molecular engineering. In addition to intraNR decay, intermolecular nonradiative (interNR) decay is equally important and more convenient in governing photothermal performance. However, controlling interNR decay remains challenging due to the limited understanding of their origin and dynamics. Here, systemic investigation of intraNR and interNR decay directs the first demonstration of simple manipulation of interNR decay to produce a giant photothermal performance for optimized phototheranostic. Among three designed polymers with varying fluorine substitution, structure-performance studies reveal a dimer-initiated interNR decay to improve photothermal performance. Dimer is formed by intermolecular CF···H hydrogen bond. This finding inspires a simple aggregation control strategy to form excited dimer, namely, excimer. It initiates an ≈100-fold enhancement in interNR decay rate over conventional intraNR decay to produce ultrahigh photothermal conversion efficiency of 81% for efficient photoacoustic imaging-guided photothermal therapy in vivo. This study provides insights into interNR decay in achieving a giant photothermal effect and paves a convenient way to develop high-performance OPMs.
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The restricted mean survival time measure has gained a lot of interests for designing and analyzing oncology trials with time-to-event endpoints due to its intuitive clinical interpretation and potentially high statistical power. In the non-inferiority trial literature, restricted mean survival time has been used as an alternative measure for reanalyzing a completed trial, which was originally designed and analyzed based on traditional proportional hazard model. However, the reanalysis procedure requires a conversion from the non-inferiority margin measured in hazard ratio to a non-inferiority margin measured by restricted mean survival time difference. An existing conversion method assumes a Weibull distribution for the population survival time of the historical active control group under the proportional hazard assumption using data from a single trial. In this article, we develop a methodology for non-inferiority margin conversion when data from multiple historical active control studies are available, and introduce a Kaplan-Meier estimator-based method for the non-inferiority margin conversion to relax the parametric assumption. We report extensive simulation studies to examine the performances of proposed methods under the Weibull data generative models and a piecewise-exponential data generative model that mimic the tumor recurrence and survival characteristics of advanced colon cancer. This work is motivated to achieve non-inferiority margin conversion, using historical patient-level data from a large colon cancer clinical database, to reanalyze an internationally collaborated non-inferiority study that evaluates 6-month versus 3-month duration of adjuvant chemotherapy in stage III colon cancer patients.
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Neoplasias do Colo , Recidiva Local de Neoplasia , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Humanos , Modelos de Riscos Proporcionais , Taxa de SobrevidaRESUMO
The inhibition of function-specific ß-N-acetyl-D-hexosaminidases, such as OfHex1 from the Asian corn borer (Ostrinia furnacalis), is a promising strategy for the development of green pesticides. Among reported OfHex1 inhibitors, glycosyl inhibitors show especially high inhibitory activity. In this study, a series of novel C-glycosidic oximino carbamate derivatives were designed using the OfHex1 crystal structure and synthesized. Among the C-Glycoside derivatives studied, compound 7k exhibited the best inhibitory activity against OfHex1 (IC50 = 47.47 µM). Compound 7k also exhibited excellent larvicidal activity against Plutella xylostella. The potential inhibitory mechanism of 7k was studied using molecular docking. Notably, compound 7k is the first reported C-glycoside inhibitor of OfHex1. These results provide direction for the rational design of novel OfHex1 inhibitors.